A facile base-promoted sulfur-centered radical generation mode and a single-step protocol for the synthesis of thiophene derivatives using 1,3-diynes via the interaction between elemental sulfur and NaOtBu has been reported. EPR experiments revealed that the trisulfur radical anion acts as a key intermediate of this process. A plausible mechanism has been proposed.
To improve the photocatalytic activity of Cu2O for hydrogen production through water splitting, the band edges of Cu2O should be modified to meet the electronic transition of angular momentum selection rules (?l = ±1) and match with the hydrogen or oxygen production levels. Upon analyzing the band structure of Cu2O and the chemical potentials of the dopants, we show that passivated codopants such as (Sn + B) can induce superior modification in the band edges of Cu2O: the conduction band edge is changed from the d band character of Cu atoms to the p band character of the Sn atom and shifted slightly downwards, while the valence band edge keeps the d band character of the Cu atoms and energy unchanged, indicating that the stringent requirements get satisfied. Moreover, the optical absorption spectrum of (Sn + B) codoped Cu2O shows a greatly improved absorption of visible light. The calculated defect formation energy shows that the codoping is energetically more favorable than mono-doping due to the Coulomb interactions and charge compensation effects.
To examine the risks of genital herpes and antiherpes treatment during pregnancy in relation to preterm delivery (PTD), we conducted a multicenter, member-based cohort study within 4 Kaiser Permanente regions: northern and southern California, Colorado, and Georgia. The study included 662,913 mother-newborn pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on genital herpes diagnosis and treatment: genital herpes without treatment, genital herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed controls). After controlling for potential confounders, we found that compared with being unexposed, having untreated genital herpes during first or second trimester was associated with more than double the risk of PTD (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for early PTD (?35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast, undergoing antiherpes treatment during pregnancy was associated with a lower risk of PTD compared with not being treated, and the PTD risk was similar to that observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present study revealed increased risk of PTD associated with genital herpes infection if left untreated and a potential benefit of antiherpes medications in mitigating the effect of genital herpes infection on the risk of PTD.
Identification of polymorphisms associated with economic traits is important for successful marker-assisted selection in cattle breeding. The family of mammalian sirtuin regulates many biological functions, such as life span extension and energy metabolism. SIRT2, a most abundant sirtuin in adipocytes, acts as a crucial regulator of adipogenic differentiation and plays a key role in controlling adipose tissue function and mass. Here we investigated single nucleotide polymorphisms (SNPs) of bovine SIRT2 in 1226 cattle from five breeds and further evaluated the effects of identified SNPs on economically important traits of Nanyang cattle. Our results revealed four novel SNPs in bovine SIRT2, one was located in intronic region and the other three were synonymous mutations. Linkage disequilibrium and haplotype analyses based on the identified SNPs showed obvious difference between crossbred breed and the other four beef breeds. Association analyses demonstrated that SNPs g.17333C > T and g.17578A > G have a significantly effect on 18-months-old body weight of Nanyang population. Animals with combined genotype TTGG at the above two loci exhibited especially higher body weight. Our data for the first time demonstrated that polymorphisms in bovine SIRT2 are associated with economic traits of Nanyang cattle, which will be helpful for future cattle selection practices.
The effect of dietary fiber on intestinal function primarily has been ascribed to its interaction with intestinal bacteria in the hindgut, whereas changes in intestinal bacteria in the host have been considered to depend on fiber composition.
A hybrid passivation strategy is employed to modify the surface of colloidal CdSe quantum dots (QDs) for quantum dot-sensitized solar cells (QDSCs), by using mercaptopropionic acid (MPA) and iodide anions through a ligand exchange reaction in solution. This is found to be an effective way to improve the performance of QDSCs based on colloidal QDs. The results show that MPA can increase the coverage of the QDs on TiO2 electrodes and facilitate the hole extraction from the photoxidized QDs, and simultaneously, that the iodide anions can remedy the surface defects of the CdSe QDs and thus reduce the recombination loss in the device. This hybrid passivation treatment leads to a significant enhancement of the power conversion efficiency of the QDSCs by 41%. Furthermore, an optimal ratio of iodide ions to MPA was determined for favorable hybrid passivation; results show that excessive iodine anions are detrimental to the loading of the QDs. This study demonstrates that the improvement in QDSC performance can be realized by using a combination of different functional ligands to passivate the QDs, and that ligand exchange in solution can be an effective approach to introduce different ligands.
O-glycosylation of podoplanin (PDPN) on lymphatic endothelial cells (LECs) is critical for the separation of blood and lymphatic systems by interacting with platelet C-type lectin-like receptor 2 (CLEC-2) during development. However, how O-glycosylation controls endothelial PDPN function and expression remains unclear. Here we report that core 1 O-glycan-deficient or desialylated PDPN was highly susceptible to proteolytic degradation by various proteases including metalloproteinases MMP-2/9. We found that the lymph contained activated MMP-2/9 and incubation of the lymph reduced surface levels of PDPN on core 1 O-glycan-deficient endothelial cells (ECs), but not on WT ECs. The lymph from mice with sepsis induced by cecal ligation and puncture (CLP), which contained bacteria-derived sialidase, reduced PDPN levels on WT ECs. These reductions were rescued by metalloproteinase inhibitor GM6001. Additionally, GM6001 treatment rescued the reduction of PDPN level on LECs in mice lacking endothelial core 1 O-glycan or CLP-treated mice. Furthermore, core 1 O-glycan-deficient or desialylated PDPN impaired platelet interaction under physiological flow. These data indicate that sialylated O-glycans of PDPN are essential for platelet adhesion and prevent PDPN from proteolytic degradation primarily mediated by metalloproteinases in the lymph.
In our study that explored the current end-of-life care provision for Chinese older people with advanced/terminal cancer, hope emerged as a significant aspect of coping with their condition. Drawing on data from in-depth interviews with a group of older people, their family carers and health professionals, this article explores participants' constructions of hope in terms of what they were hoping for, how their hopes helped them cope with their illness and what sociocultural resources they drew on to build and sustain these hopes. While acknowledging similarities to Western studies of hope in terminal illness, this article identifies significant divergences in terms of the impact of different sociocultural values and their implications for clinical practice in light of an unfavourable health care environment for patients with advanced cancer and a social support system sustained mainly by Chinese families. It argues that hope represents an important resource for coping with terminal illness among these patients.
Valley-dependent propagation of light in an artificial photonic hexagonal lattice, akin to electrons in graphene, is investigated in microwave regime. Both numerical and experimental results show that the valley degeneracy in the photonic graphene is broken when the frequency is away from the Dirac point. The peculiar anisotropic wave transport property due to distinct valleys is analyzed using the equifrequency contours. More interestingly, the valley-dependent self-collimation and beam splitting phenomena are experimentally demonstrated with the armchair and zigzag interfaces, respectively. Our results confirm that there are two inequivalent Dirac points that lead to two distinct valleys in photonic graphene, which could be used to control the flow of light and might be used to carry information in valley polarized beam splitter, collimator or guiding device.
Lymphatic valves prevent the backflow of the lymph fluid and ensure proper lymphatic drainage throughout the body. Local accumulation of lymphatic fluid in tissues, a condition called lymphedema, is common in individuals with malformed lymphatic valves. The vascular endothelial growth factor receptor 3 (VEGFR3) is required for the development of lymphatic vascular system. The abundance of VEGFR3 in collecting lymphatic trunks is high before valve formation and, except at valve regions, decreases after valve formation. We found that in mesenteric lymphatics, the abundance of epsin 1 and 2, which are ubiquitin-binding adaptor proteins involved in endocytosis, was low at early stages of development. After lymphatic valve formation, the initiation of steady shear flow was associated with an increase in the abundance of epsin 1 and 2 in collecting lymphatic trunks, but not in valve regions. Epsin 1 and 2 bound to VEGFR3 and mediated the internalization and degradation of VEGFR3, resulting in termination of VEGFR3 signaling. Mice with lymphatic endothelial cell-specific deficiency of epsin 1 and 2 had dilated lymphatic capillaries, abnormally high VEGFR3 abundance in collecting lymphatics, immature lymphatic valves, and defective lymph drainage. Deletion of a single Vegfr3 allele or pharmacological suppression of VEGFR3 signaling restored normal lymphatic valve development and lymph drainage in epsin-deficient mice. Our findings establish a critical role for epsins in the temporal and spatial regulation of VEGFR3 abundance and signaling in collecting lymphatic trunks during lymphatic valve formation.
Embryonic stem cells (ESCs) can be induced to differentiate into nerve cells, endowing them with potential applications in the treatment of neurological diseases and neural repair. In this work, we report for the first time that sulfated chitosan can promote the neural differentiation of ESCs. As a type of sulfated glycosaminoglycan analog, sulfated chitosan with well-defined sulfation sites and a controlled degree of sulfation (DS) were prepared through simple procedures and the influence of sulfated glycosaminoglycan on neural differentiation of ESCs was investigated. Compared with other sulfation sites, 6-O-sulfated chitosan showed the most optimal effects. By monitoring the expression level of neural differentiation markers using immunofluorescence staining and PCR, it was found that neural differentiation was better enhanced by increasing the DS of 6-O-sulfated chitosan. However, increasing the DS by introducing another sulfation site in addition to the 6-O site to chitosan did not promote neural differentiation as much as 6-O-sulfated chitosan, indicating that compared with DS, the sulfation site is more important. Additionally, the optimal concentration and incubation time of 6-O-sulfated chitosan were investigated. Together, our results indicate that the sulfate site and the molecular structure in a sulfated polysaccharide are very important for inducing the differentiation of ESCs. Our findings may help to highlight the role of sulfated polysaccharide in inducing the neural differentiation of ESCs.
Randomized trials and meta-analyses have reached conflicting conclusions regarding the risk benefit ratio of thrombolytic therapy or anticoagulant therapy in patients with moderate pulmonary embolism. To investigate the effect of initial thrombolysis and anticoagulant therapy in patients with moderate pulmonary embolism, we performed an updated meta-analysis.
The mortality rate associated with prostate cancer is mainly due to metastases rather than primary organ?confined disease. Decreasing the incidence of metastasis is important in treating prostate cancer. 4',5,7?trihydroxyflavone (apigenin) has been demonstrated to be effective in inhibiting several types of cancer. The aim of this study was to investigate the effect and mechanism of apigenin on the movement of prostate cancer cells. In the present study, DU145 cells were treated with varying concentrations of apigenin for different time periods. Cell viability was evaluated using an MTT assay. Cell motility and invasiveness were assayed using wound healing assays and a Matrigel migration and invasion assay. Flow cytometric and western blot analyses were performed to examine the cell cycle and signaling pathways. The results demonstrated that apigenin suppressed the proliferation and inhibited the migration and invasive potential of the DU145 prostate cancer cells in a dose? and time?dependent manner, which was associated with epithelial mesenchymal transition. These findings suggested that apigenin may be effective in treating human prostate cancer.
Microtubule-stabilizing agents, such as paclitaxel (Taxol), are effective chemotherapy drugs for treating many cancers, and painful neuropathy is a major dose-limiting adverse effect. Cation-chloride cotransporters, such as Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) and K(+)-Cl(-) cotransporter-2 (KCC2), critically influence spinal synaptic inhibition by regulating intracellular chloride concentrations. Here we show that paclitaxel treatment in rats significantly reduced GABA-induced membrane hyperpolarization and caused a depolarizing shift in GABA reversal potential of dorsal horn neurons. However, paclitaxel had no significant effect on AMPA or NMDA receptor-mediated glutamatergic input from primary afferents to dorsal horn neurons. Paclitaxel treatment significantly increased protein levels, but not mRNA levels, of NKCC1 in spinal cords. Inhibition of NKCC1 with bumetanide reversed the paclitaxel effect on GABA-mediated hyperpolarization and GABA reversal potentials. Also, intrathecal bumetanide significantly attenuated hyperalgesia and allodynia induced by paclitaxel. Co-immunoprecipitation revealed that NKCC1 interacted with ?-tubulin and ?-actin in spinal cords. Remarkably, paclitaxel increased NKCC1 protein levels at the plasma membrane and reduced NKCC1 levels in the cytosol of spinal cords. In contrast, treatment with an actin-stabilizing agent had no significant effect on NKCC1 protein levels in the plasma membrane or cytosolic fractions of spinal cords. In addition, inhibition of the motor protein dynein blocked paclitaxel-induced subcellular redistribution of NKCC1, whereas inhibition of kinesin-5 mimicked the paclitaxel effect. Our findings suggest that increased NKCC1 activity contributes to diminished spinal synaptic inhibition and neuropathic pain caused by paclitaxel. Paclitaxel disrupts intracellular NKCC1 trafficking by interfering with microtubule dynamics and associated motor proteins.
Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.
Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.
Two layered V-B-O contained polyoxometalate (POM) net structures, denoted as SUT-12 and SUT-13, are reported here. SUT-12 was synthesized by the boric acid flux method, and it represents the first 2D structure constructed from the V6B20 vanadoborate cluster. SUT-13 was synthesized by the hydrothermal method and constructed from V12B6P12 vanadium borophosphate clusters. In both structures, the vanadoborate or vanadium borophosphate clusters were linked through in situ formed Zn(DETA)2 or Cu(DETA)2 complexes. Surprisingly, for all DETA molecules in the two metal complexes, there is one dangling amine group when it is coordinated to the metal. The phenomenon of the dangling amine group feature is abnormal and the Cu(DETA)2 complexes in SUT-13 were taken as an example and studied by the density functional theory (DFT) calculations in order to understand this unusual feature.
Transparent electrodes with a dielectric-metal-dielectric (DMD) structure can be implemented in a simple manufacturing process and have good optical and electrical properties. In this study, nickel oxide (NiO) is introduced into the DMD structure as a more appropriate dielectric material that has a high conduction band for electron blocking and a low valence band for efficient hole transport. The indium-free NiO/Ag/NiO (NAN) transparent electrode exhibits an adjustable high transmittance of ?82% combined with a low sheet resistance of ?7.6 ?·s·q(-1) and a work function of 5.3 eV after UVO treatment. The NAN electrode shows excellent surface morphology and good thermal, humidity, and environmental stabilities. Only a small change in sheet resistance can be found after NAN electrode is preserved in air for 1 year. The power conversion efficiencies of organic photovoltaic cells with NAN electrodes deposited on glass and polyethylene terephthalate (PET) substrates are 6.07 and 5.55%, respectively, which are competitive with those of indium tin oxide (ITO)-based devices. Good photoelectric properties, the low-cost material, and the room-temperature deposition process imply that NAN electrode is a striking candidate for low-cost and flexible transparent electrode for efficient flexible optoelectronic devices.
Currently, the Lateral flow Immunoassays (LFIAs) are not able to perform complex multi-step immunodetection tests because of their inability to introduce multiple reagents in a controlled manner to the detection area autonomously. In this research, a point-of-care (POC) paper-based lateral flow immunosensor was developed incorporating a novel microfluidic valve technology. Layers of paper and tape were used to create a three-dimensional structure to form the fluidic network. Unlike the existing LFIAs, multiple directional valves are embedded in the test strip layers to control the order and the timing of mixing for the sample and multiple reagents. In this paper, we report a four-valve device which autonomously directs three different fluids to flow sequentially over the detection area. As proof of concept, a three-step alkaline phosphatase based Enzyme-Linked ImmunoSorbent Assay (ELISA) protocol with Rabbit IgG as the model analyte was conducted to prove the suitability of the device for immunoassays. The detection limit of about 4.8 fm was obtained.
Rational design of effective antifouling polymers is challenging but important for many fundamental and applied applications. Herein we synthesize and characterize an N-acryloylaminoethoxyethanol (AAEE) monomer, which integrates three hydrophilic groups of hydroxyl, amide, and ethylene glycol in the same material. AAEE monomers were further grafted and polymerized on gold substrates to form polyAAEE brushes with well-controlled thickness via surface-initiated atomic transfer radical polymerization (SI-ATRP), with particular attention to a better understanding of the molecular structure-antifouling property relationship of hydroxyl-acrylic-based polymers. The surface hydrophilicity and antifouling properties of polyAAEE brushes as a function of film thickness are studied by combined experimental and computational methods including surface plasmon resonance (SPR) sensors, atomic force microscopy (AFM), cell adhesion assay, and molecular dynamics (MD) simulations. With the optimal polymer film thicknesses (?10-40 nm), polyAAEE-grafted surfaces can effectively resist protein adsorption from single-protein solutions and undiluted human blood plasma and serum to a nonfouling level (i.e., <0.3 ng/cm(2)). The polyAAEE brushes also highly resist mammalian cell attachment up to 3 days. MD simulations confirm that the integration of three hydrophilic groups induce a stronger and closer hydration layer around polyAAEE, revealing a positive relationship between surface hydration and antifouling properties. The molecular structure-antifouling properties relationship of a series of hydroxyl-acrylic-based polymers is also discussed. This work hopefully provides a promising structural motif for the design of new effective antifouling materials beyond traditional ethylene glycol-based antifouling materials.
?1-Adrenoceptors (ARs; 1A, 1B, and 1D) have been determined to perform different prominent functions in the physiological responses of the sympathetic nervous system. A high-throughput screening assay (HTS) was set up to detect ?1-AR subtype-selective agonists by a dual-luciferase reporter assay in HEK293 cells. Using the HTS assay, two novel compounds, CHE3 and CHK3, were discovered as ?1-ARs agonists in ?1-ARs expressed in HEK293 cells. These compounds also showed moderate/weak anti-proliferative activities against tested cancer cell lines. The HTS assay proposed in this study represents a potential method for discovering more ?1-AR subtype-selective ligands.
Temperature-dependent photoluminescence (TDPL), one of the most effective and powerful optical characterisation methods, is widely used to investigate carrier transport and localized states in semiconductor materials. Resonant excitation and non-resonant excitation are the two primary methods of researching this issue. In this study, the application ranges of the different excitation modes are confirmed by analysing the TDPL characteristics of GaN-based light-emitting diodes. For resonant excitation, the carriers are generated only in the quantum wells, and the TDPL features effectively reflect the intrinsic photoluminescence characteristics within the wells and offer certain advantages in characterising localized states and the quality of the wells. For non-resonant excitation, both the wells and barriers are excited, and the carriers that drift from the barriers can contribute to the luminescence under the driving force of the built-in field, which causes the existing equations to become inapplicable. Thus, non-resonant excitation is more suitable than resonant excitation for studying carrier transport dynamics and evaluating the internal quantum efficiency. The experimental technique described herein provides fundamental new insights into the selection of the most appropriate excitation mode for the experimental analysis of carrier transport and localized states in p-n junction devices.
The stabilities and electronic properties of SrZrO3 (1?1?0) (1? × ?1) polar terminations were investigated systematically by the first-principles density functional theory method. Five possible polar surfaces, i.e. O-deficient, O-rich, stoichiometric, SrO-rich and SrO-deficient ones, were considered. The calculated results indicated that the charge neutralization and polarity compensation condition could be achieved by charge redistributions of surface atoms. For the O-deficient (1?1?0) termination, some filled electronic states were separated from the original conduction bands, while a surface reconstruction was found for the O-rich (1?1?0) surface. The remaining three (1?1?0) terminations remained insulated. Furthermore, a stability diagram involving seven different terminations was constructed using the surface grand potential technique, in which the effect of the chemical environment was included. The calculated results indicated that three (1?1?0) (O-rich, SrO-rich and stoichiometric) and 2 (0?0?1) (ZrO2 and SrO) terminations could be stabilized in distinct areas, whereas the O-deficient surface was unstable within the whole region. Finally, we drew a comparison of stability behaviors between SrZrO3 (1?1?0) (1? × ?1) polar surfaces and the counterparts of ATiO3 (A = Ba, Pb, Sr) and BaZrO3 materials.
Cardiovascular disease partially originates from poor environmental and nutritional conditions in early life. Lack of micronutrients like 25 hydroxy vitamin D3 (25OHD) during pregnancy may be an important treatable causal factor. The present study explored the effect of maternal 25OHD deficiency on the offspring.
Visual attentional bias has important functions during the appearance social comparisons. However, for the limitations of experimental paradigms or analysis methods in previous studies, the time course of attentional bias to thin and fat body images among women with body dissatisfaction (BD) has still been unclear. In using free reviewing task combined with eye movement tracking, and based on event-related analyses of the critical first eye movement events, as well as epoch-related analyses of gaze durations, the current study investigated different attentional bias components to body shape/part images during 15s presentation time among 34 high BD and 34 non-BD young women. In comparison to the controls, women with BD showed sustained maintenance biases on thin and fat body images during both early automatic and late strategic processing stages. This study highlights a clear need for research on the dynamics of attentional biases related to body image and eating disturbances.
Pneumatic tourniquet use in total knee arthroplasty (TKA) is always a controversial issue. The aim of the present study is to assess the effectiveness and safety of its use in patients receiving primary unilateral TKA, and to explore the most safe and effective protocols.
This research evaluated information-processing biases related to height dissatisfaction among young Chinese men. In Study 1, 32 highly stature dissatisfied (HSD) men and 36 less stature dissatisfied (LSD) men performed a dot probe task featuring height-related words and neutral words. HSD men were significantly slower than LSD men were in responding to probes that followed short stature words, but the groups did not differ in response speeds to probes that followed tall stature or neutral words. In Study 2, 33 HSD men and 34 LSD men completed an implicit learning task followed by a word recognition task. HSD men recognized significantly more short stature words from the initial task, but recognition accuracy for other word types did not differ between groups. Together, these findings suggest that HSD men are more inclined than LSD men to selectively avoid cues that reflect shortness in stature and to selectively recognize such cues later.
We evaluated the structure and validity of the Upward Appearance Comparison Scale (UPACS) and Downward Appearance Comparison Scale (DACS) (O'Brien et al., 2009) in Chinese samples. In Study 1, principal component analysis on an initial sample (427 women, 123 men) and confirmatory factor analysis on another sample (447 women, 121 men) found that a 15-item, two component model had the best overall fit. Derived components had moderate correlations with most conceptually related measures and low correlations with less conceptually related indices. Study 2 participants (310 women, 201 men) completed the UPACS and DACS as well as measures of disordered eating, fatness concern, and negative affect; they were re-assessed one year later. Baseline UPACS scores predicted changes in disordered eating for women and fatness concerns for men, independent of initial disturbances, but DACS responses were not related to outcomes. Findings highlighted the potential utility of derived UPACS and DACS within a Chinese context.
Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate such function(s), we generated embryonic fibroblasts from conditional epsin triple KO mice. Triple KO cells displayed a dramatic cell division defect. Additionally, a robust impairment in clathrin-mediated endocytosis was observed, with an accumulation of early and U-shaped pits. This defect correlated with a perturbation of the coupling between the clathrin coat and the actin cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results indicate that a key evolutionary conserved function of epsin, in addition to other roles that include, as we show here, a low affinity interaction with SNAREs, is to help generate the force that leads to invagination and then fission of clathrin-coated pits.
The indium segregation in InGaN well layer is confirmed by a nondestructive combined method of experiment and numerical simulation, which is beyond the traditional method. The pre-deposited indium atoms before InGaN well layer growth are first carried out to prevent indium atoms exchange between the subsurface layer and the surface layer, which results from the indium segregation. The uniform spatial distribution of indium content is achieved in each InGaN well layer, as long as indium pre-deposition is sufficient. According to the consistency of the experiment and numerical simulation, the indium content increases from 16% along the growth direction and saturates at 19% in the upper interface, which cannot be determined precisely by the traditional method.
A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines (PC-3, LNCaP, and DU145) were evaluated by a CCK-8 assay. Compounds 9 and 15 exhibited strong cytotoxic activities against LNCaP cells (IC50<5 ?M), and compound 8 (IC50=8.25 ?M) possessed the most potent activity against DU145 cells. However, these compounds also exhibited cytotoxicity towards human epithelial prostate normal cells RWPE-1. The structure-activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.
The quality of data in public health information systems can be ensured by effective data quality assessment. In order to conduct effective data quality assessment, measurable data attributes have to be precisely defined. Then reliable and valid measurement methods for data attributes have to be used to measure each attribute. We conducted a systematic review of data quality assessment methods for public health using major databases and well-known institutional websites. 35 studies were eligible for inclusion in the study. A total of 49 attributes of data quality were identified from the literature. Completeness, accuracy and timeliness were the three most frequently assessed attributes of data quality. Most studies directly examined data values. This is complemented by exploring either data users' perception or documentation quality. However, there are limitations of current data quality assessment methods: a lack of consensus on attributes measured; inconsistent definition of the data quality attributes; a lack of mixed methods for assessing data quality; and inadequate attention to reliability and validity. Removal of these limitations is an opportunity for further improvement.
Cancer multidrug resistance (MDR) is a common cause of treatment failure in cancer patients. Increased expression of permeability glycoprotein (P-gp), which is also known as MDR-1, is the main cause of multidrug resistance. Podophyllotoxin derivatives hold great promise in the battle to overcome multidrug resistance, as they can induce cytotoxicity through multiple mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and evaluated their cytotoxicities in human cancer cell lines, HeLa, K562 and K562/A02. Some of these compounds were more potent than etoposide, a clinically relevant inhibitor of DNA repair enzymes. In particular, compound 5p exhibited the most potent activity toward drug-resistant K562/A02 cells, as it robustly inhibited tumor cell proliferation and induced apoptosis. Furthermore, preliminary investigation suggested that 5p inhibited the expression of MDR-1 in K562/A02 cells more effectively than etoposide.
Diabetic retinopathy (DR) is a common chronic microvascular diabetic complication. The presence of DR may indicate microcirculatory dysfunction in other organ systems besides visual morbidity. The objective of this study was to develop a simple diabetic retinopathy risk score to identify DR in Chinese overweight/obese patients with type 2 diabetes mellitus (T2DM).
In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8 % tetracyclines, 66.8 % sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2)?=?0.330, P?0.05), there was no significant correlation between antibiotics and the corresponding resistant bacteria (P?>?0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P?0.05). Tet (A) and tet (B) displayed noticeable relationships with both tetracycline and combined antibiotic-resistant bacteria (P?0.01).
Protein adsorption on biomaterials strongly mediates the subsequent cell responses. Here adsorption of fibronectin (Fn) on salt-treated PEI(PSS/PDDA)7 multilayers was characterized. The amounts of adsorbed Fn increased linearly along with the increase of thickness of multilayers pretreated with 1 M and 5 M NaCl solutions (Multilayer-1M and 5M), but was independent on the thickness of Multilayer-3M. The normalized relative RGD activity of Fn were significantly higher on the Multilayer-3M than on others. By comparison of cellular behaviors of VSMCs being cultured in the normal and Fn-depleted serum-containing medium, the significant role of Fn on modulating the behaviors of VSMCs was verified. The Fn adsorption model and its role on linking the biomaterials surface to the VSMCs behaviors are proposed.
The kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) participate in the regulation of the NaCl cotransporter NCC and the Na(+),K(+),2Cl(-) cotransporter NKCC2. The kinases are regulated by WNK (with-no-K[Lys]) kinases. Mutations of genes encoding WNK kinases underly Gordon's syndrome, a monogenic disease leading to hypertension and hyperkalemia. WNK kinases further regulate the renal outer medullary K(+) channel ROMK1. The present study explored, whether SPAK and/or OSR1 have similarly the potential to modify the activity of ROMK1.
DNA methylation is a key epigenetic modification in mammals and plays important roles in muscle development. We sampled longissimus dorsi muscle (LDM) from a well-known elite native breed of Chinese Qinchuan cattle living within the same environment but displaying distinct skeletal muscle at the fetal and adult stages. We generated and provided a genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA for fetal and adult muscle studies. Integration analysis revealed a total of 77 and 1,054 negatively correlated genes with methylation in the promoter and gene body regions, respectively, in both the fetal and adult bovine libraries. Furthermore, we identified expression patterns of high-read genes that exhibit a negative correlation between methylation and expression from nine different tissues at multiple developmental stages of bovine muscle-related tissue or organs. In addition, we validated the MeDIP-Seq results by bisulfite sequencing PCR (BSP) in some of the differentially methylated promoters. Together, these results provide valuable data for future biomedical research and genomic and epigenomic studies of bovine skeletal muscle that may help uncover the molecular basis underlying economically valuable traits in cattle. This comprehensive map also provides a solid basis for exploring the epigenetic mechanisms of muscle growth and development.
Thermoelectric (TE) materials have continuously attracted interest worldwide owing to their capability of converting heat into electricity. However, discovery and design of new TE material system remains one of the greatest difficulties. A TE material, TmCuTe2 , has been designed by a substructure approach and successfully synthesized. The structure mainly features CuTe4 -based layers stacking along the c axis that are separated by Tm(3+) cations. Such an intrinsic Cu site vacancy structure undergoes a first-order phase transition at around 606?K driven by the energetically favorable uniform Cu atom re-distribution on the covalent CuTe4 -based layer substructure, as shown by crystal structure simulations and variable-temperature XRD data. Featured with very low thermal conductivity (ca. 0.6?W?m(-1) ?K(-1) ), large Seebeck coefficient (+185??V?K(-1) ), and moderate electrical conductivity (220?S?cm(-1) ), TmCuTe2 has a maximum ZT of 0.81 at 745?K, which is nine times higher than the value of 0.09 for binary Cu2 Te, thus making it a promising candidate for mid-temperature TE applications. Theoretical studies uncover the electronic structure modifications from the metallic Cu2 Te to the narrow gap semiconductor TmCuTe2 that lead to such a remarkable performance enhancement.
FoxM1 is a specific transcription factor that has an important function in aggressive human carcinomas, including cervical cancer. However, the specific function and internal molecular mechanism in cervical cancer remain unclear. In this study, RNAi-mediated FoxM1 knockdown inhibited cell growth. This process also decreased the migration and invasion activities of HeLa cells in vitro. Downregulation of FoxM1 inhibited tumor growth and angiogenesis in vivo. In addition, the expressions of uPA, matrix metalloproteinase (MMP)-2, MMP-9 and VEGF were significantly decreased in vitro and in vivo. These results suggested that the inactivation of FoxM1 could be a novel therapeutic target for cervical cancer treatment.
Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis.
Gangliocytomas occurring in the sellar region are extremely rare. We examined a cohort of these tumors to examine their clinical presentations and prognoses. Between January 2000 and December 2012, 23 patients were diagnosed with sellar region gangliocytomas in Huashan Hospital. These patients were retrospectively reviewed for medical histories, endocrinological examinations, preoperative magnetic resonance imaging (MRI), pathological findings and follow-ups. Endocrinological tests revealed elevated prolactin (PRL) levels in 10 cases (43.5%) and elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in 9 cases (39.1%). Scattered ganglion cells admixed with adenomatous components were observed in 16 cases (69.6%). In the remaining 7 cases (30.4%), only fragments with ganglion cells dispersed in the fibrillar matrix without adenohypophyseal components were detected. Immunohistochemistry revealed PRL-positive adenomas in 6 cases (26.1%) and GH-positive adenomas in 8 cases (34.8%). The average follow-up period was 4.2 years (range: 1-12.7 years). Gross total resection was achieved in 20 cases (87.0%). One patient recurred five years after tumor resection (4.3%). One patient died of acute myocardial infarction six years after operation. Gangliocytomas located in the sellar region may represent a unique immunopathological entity. The surgical results and prognoses of the gangliocytomas were comparable with those of pituitary adenomas.
Understanding the geometry structures of gold clusters, especially with adsorbates, is essential for designing highly active gold nanocatalysts. Here, CO chemisorption onto the Au5 (-) cluster is investigated using the density functional calculations. It is found that chemisorption of CO molecules can induce previously unreported two- to three-dimensions (3D) structural changes. Even a single CO chemisorption induces a major structural change to explain the huge blue-shift in photoelectron spectroscopy (PES). The apex site in the parent Au5 (-) cluster is not always the most preferred site for the chemisorption, and two bridged adsorption CO molecules are observed in the lowest-energy (CO)3Au5 (-) cluster. A clear splitting is observed in the first PES of (CO)4Au5 (-), and calculated planar and 3D geometries are likely coexisting in the cluster beam. The fifth CO adsorption leads to the structural transformation of Au5 skeleton to create more apex sites to accommodate five CO molecules. The structural properties, together with the vertical electron detachment energy (VDE) and binding energies calculations indicate that the chemisorption-saturated number is 5.
The Chinese Wenchuan earthquake, which happened on the 28th of May in 2008, may leave deep invisible scars in individuals. China has a large number of children and adolescents, who tend to be most vulnerable because they are in an early stage of human development and possible post-traumatic psychological distress may have a life-long consequence. Trauma survivors without post-traumatic stress disorder (PTSD) have received little attention in previous studies, especially in event-related potential (ERP) studies. We compared the attention bias to threat stimuli between the earthquake-exposed group and the control group in a masked version of the dot probe task. The target probe presented at the same space location consistent with earthquake-related words was the congruent trial, while in the space location of neutral words was the incongruent trial. Thirteen earthquake-exposed middle school students without PTSD and 13 matched controls were included in this investigation. The earthquake-exposed group showed significantly faster RTs to congruent trials than to incongruent trials. The earthquake-exposed group produced significantly shorter C1 and P1 latencies and larger C1, P1 and P2 amplitudes than the control group. In particular, enhanced P1 amplitude to threat stimuli was observed in the earthquake-exposed group. These findings are in agreement with the prediction that earthquake-exposed survivors have an attention bias to threat stimuli. The traumatic event had a much greater effect on earthquake-exposed survivors even if they showed no PTSD symptoms than individuals in the controls. These results will provide neurobiological evidences for effective intervention and prevention to post-traumatic mental problems.
Hematoxylin and eosin (H&E) staining of tissue samples is the standard approach in histopathology for imaging and diagnosing cancer. Recent reports have shown that multiphoton microscopy (MPM) provides better sample interface with single-cell resolution, which enhances traditional H&E staining and offers a powerful diagnostic tool with potential applications in oncology. The purpose of this study was to further expand the versatility of MPM by establishing the optical parameters required for imaging unstained histological sections of pancreatic neoplasms, thereby providing an efficient and environmentally sustainable alternative to H&E staining while improving the accuracy of pancreatic cancer diagnoses. We found that the high-resolution MPM images clearly distinguish between the structure of normal pancreatic tissues compared with pancreatic neoplasms in unstained histological sections, and discernable differences in tissue architecture and cell morphology between normal versus tumorigenic cells led to enhanced optical diagnosis of cancerous tissue. Moreover, quantitative assessment of the cytomorphological features visualized from MPM images showed significant differences in the nuclear–cytoplasmic ratios of pancreatic neoplasms compared with normal pancreas, as well as further distinguished pancreatic malignant tumors from benign tumors. These results indicate that the MPM could potentially serve as an optical tool for the diagnosis of pancreatic neoplasms in unstained histological sections.
An efficient and green strategy, i.e. adding nano zero-valent iron into anaerobic fermentation systems to remarkably stimulate the accumulation of short-chain fatty acids from waste activated sludge via accelerating the solubilization and hydrolysis processes has been developed. In the presence of nano zero-valent iron, not only the short-chain fatty acids production was significantly improved, but also the fermentation time for maximal short-chain fatty acids was shortened compared with those in the absence of nano zero-valent iron. Mechanism investigations showed that the solubilization of sludge, hydrolysis of solubilized substances and acidification of hydrolyzed products were all enhanced by addition of nano zero-valent iron. Also, the general microbial activity of anaerobes and relative activities of key enzymes with hydrolysis and acidification of organic matters were improved than those in the control. 454 high-throughput pyrosequencing analysis suggested that the abundance of bacteria responsible for waste activated sludge hydrolysis and short-chain fatty acids production was greatly enhanced due to nano zero-valent iron addition.
Metal ion homeostasis and heavy metal detoxification systems are regulated by certain genes associated with metal ion transport. Metallothionein (MT) and metal response element binding transcription factor 1 (MTF?1) are important regulatory proteins involved in the mediation of intracellular metal ion balance. Differences in the zinc?binding affinities of the zinc fingers of MTF?1 and the ?? and ??domains of MT facilitate their regulation of Zn2+ concentration. Alterations in the intracellular concentration of Zn2+ influence the MTF?1 zinc finger number, and MTF?1 containing certain zinc finger numbers regulates the expression of corresponding target genes. The present review evaluates the association between zinc finger number in MTF?1 protein, MTF?1 target genes and the mechanism underlying MT regulation of the zinc finger number in MTF?1.
Two-photon excited fluorescence (TPEF) microscopy, based on signal from cells, can provide detailed information on tissue architecture and cellular morphology in unstained histological sections to generate subcellular-resolution images from tissue directly. In this paper, we used TPEF microscopy to image microstructure of human normal gallbladder and three types of differentiated carcinomas in order to investigate the morphological changes of tissue structure, cell, cytoplasm, and nucleus without hematoxylin and eosin (H&E) staining. It displayed that TPEF microscopy can well image the stratified normal gallbladder tissue, including the mucosa, the muscularis, and the serosa. The typical cancer cell, characterized by cellular and nuclear pleomorphism, enlarged nuclei, and augmented nucleolus, can be identified in histological sections without H-E staining as well. The quantitative results showed that the areas of the nucleus and the nucleolus in three types of cancerous cells were all significantly greater than those in normal gallbladder columnar epithelial cells derived from TPEF microscopic images. The studies demonstrated that TPEF microscopy has the ability to characterize tissue structures and cell morphology of gallbladder cancers differentiated from a normal gallbladder in a manner similar to traditional histological analysis. As a novel tool, it has the potential for future retrospective studies of tumor staging and migration by utilizing histological section specimens without H-E staining.
The transcription factor T-bet controls the Th1 genetic program in T cells for effective antitumor responses. Anti-CTLA-4 immunotherapy elicits dramatic antitumor responses in mice and in human patients; however, factors that regulate T-bet expression during an antitumor response mediated by anti-CTLA-4 remain to be elucidated. We were the first to report that treatment with anti-CTLA-4 led to an increase in the frequency of T cells expressing inducible costimulator (ICOS). In both treated patients and mice, our data revealed that CD4(+)ICOS(hi) T cells can act as effector T cells, which produce the Th1 cytokine IFN-?. We also showed in a small retrospective analysis that an increased frequency of CD4(+)ICOS(hi) T cells correlated with better clinical outcome and the absence of ICOS or its ligand (ICOSL) in mouse models led to impaired tumor rejection. Here, we show that CD4(+)ICOS(hi) T cells from anti-CTLA-4-treated patients had an increase in signaling via the phospoinositide-3-kinase (PI3K) pathway and an increase in expression of T-bet. An ICOS-specific siRNA transfected into human T cells led to diminished PI3K signaling and T-bet expression. Therefore, we hypothesized that ICOS, and specifically ICOS-mediated PI3K signaling, was required for T-bet expression. We conducted studies in ICOS-deficient and ICOS-YF mice, which have a single amino acid change that abrogates PI3K signaling by ICOS. We found that ICOS-mediated PI3K signaling is required for T-bet expression during an antitumor response elicited by anti-CTLA-4 therapy. Our data provide new insight into the regulation of T-bet expression and suggest that ICOS can be targeted to improve Th1 antitumor responses.
Myocardial injury after noncardiac surgery (MINS) is a newly proposed concept that is common among adults undergoing noncardiac surgery and associated with substantial mortality. We analyzed whether MINS was a risk factor for weaning failure in critical patients who underwent major abdominal surgery.
The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-? spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.
1: This study investigated 15 coexisting dominant species in a humid subtropical evergreen broad-leaved forest in southwest China, consisting of long-lived pioneers and climax species occurring in natural and disturbed regimes. The authors hypothesized that there would be non-tradeoff scaling relationships between sprouting and seed size among species, with the aim of uncovering the ecological relationship between plant sprouting and seed characteristics in the two functional groups. 2: The sprouting variations of the species were initially examined using pairwise comparisons between natural and disturbed habitats within and across species and were noted to show a continuum in persistence niches across the forest dominants, which may underlie the maintenance of plant diversity. Second, a significantly positive, rather than tradeoff, relationship between sprout number and seed size across species within each of the two functional groups was observed, and an obvious elevational shift with a common slope among the two groups in their natural habitat was examined. The results indicate the following: 1) the relationship of seed size vs. sprouts in the natural habitat is more likely to be bet-hedging among species within a guild in a forest; 2) climax species tend to choose seeding rather than sprouting regeneration, and vice versa for the long-lived pioneers; and 3) the negative correlation between sprouting and seed dispersal under disturbed conditions may imply a tradeoff between dispersal and persistence in situ during the process of plant regeneration. 3: These findings may be of potential significance for urban greening using native species.
Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway.
Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (IN) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+IN) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After IN administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (IV) drug injection is employed, FUS was also applied after IV injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+IN enhanced drug delivery within the targeted region compared with that achieved by IN only. Despite the fact that the IN route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+IN was not significantly different from that of FUS+IV. As a new drug delivery platform, the FUS+IN technique is potentially useful for treating CNS diseases.
FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84% anaplastic large cell lymphoma and 65% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.
Fractalkine (FKN) is involved in the immunopathogenesis of inflammatory diseases, including endometriosis. Our objective was to investigate the role of FKN in the cross-talking between endometrial stromal cells (ESCs) and U937 (macrophage line) in the endometriotic milieu. We have found that FKN levels in peritoneal fluid and ESCs positively correlate with the progress of endometriosis. The expression of CX3CR1 in the normal ESCs were significantly lower than that in eutopic and ectopic ESCs from women with endometriosis. CX3CR1 expression in U937 was higher than that in ectopic ESCs. FKN secreted by eutopic ESCs could change the balance between the release of IL10 and IL12 of macrophages with the upregulation of IL10 production and downregulation of IL12 production. Moreover, FKN could induce M2 polarization of macrophage with decreased expression of CD86. FKN could increase the expression of matrix metalloproteinase 9 and decrease the expression of tissue inhibitor of metalloproteinase1 and 2, and promote the invasiveness of ESCs by activating p38MAPK and integrin?1 signal pathway. In conclusion, the higher levels of FKN secreted by eutopic ESCs facilitate the onset and progression of endometriosis by inducing M2 polarization of macrophage which in turn enhances invasiveness of ESCs.
Recent studies have shown that the tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway-induced lymphangiogenesis provides a buffering mechanism for high salt (HS) intake-induced elevation of blood pressure (BP). Moreover, blocking of TonEBP/VEGF-C signaling by mononuclear phagocyte depletion can induce salt-sensitive hypertension in rats. We hypothesized that HS intake could have an impact on cardiac lymphangiogenesis, and regulation of VEGF-C bioactivity, which is largely through the main receptor for VEGFR-3, may modulate HS intake-induced left ventricular remodeling. We demonstrated upregulation of TonEBP, increased macrophage infiltration and enhanced lymphangiogenesis in the left ventricles of spontaneously hypertensive rats (SHR) that were fed a HS diet (8.0% NaCl). Then, retrovirus vectors capable of overexpression (?N?C/VEGF-C/Cys152Ser, used for overexpressing VEGF-C) and blocking (VEGFR-3-Rg, used for trapping of bioactive VEGF-C) of VEGF-C and control vector (pLPCX) were intravenously administered to SHR from the 9(th) week of a 12-week HS loading period. At the end of the HS challenge, overexpression of VEGF-C led to enhanced cardiac lymphangiogenesis, decreased myocardial fibrosis and macrophage infiltration, preserved left ventricular functions as well as decreased BP level compared with the HS group and the control vector-treated HS group. In contrast, systemic blocking of VEGF-C was associated with elevation of BP level and an exacerbation of hypertensive LV remodeling, as indicated by increased fibrosis and macrophage infiltration, and diminished lymphangiogenesis. Hence, our findings highlight VEGF-C/VEGFR-3 is a promising therapeutic target to attenuate hypertensive left ventricular remodeling induced by HS intake, presumably via BP-dependent and -independent mechanisms.
To compare morphological differences of three drug-resistant hepatocellular carcinoma (HCC) cell subclones (Huh-7/ADM, Huh-7/CBP, Huh-7/MMC) and their parental Huh-7 cell line, to analyze differential microRNA (miRNA) expression profiles in these cells and, finally to screen for the abnormal expressed miRNAs in drug-resistant HCC cells.
We previously showed that endothelial epsin deficiency causes elevated vascular endothelial growth factor receptor 2 (VEGFR2) and enhanced VEGF signaling, resulting in aberrant tumor angiogenesis and tumor growth in adult mice. However, direct evidence demonstrating that endothelial epsins regulate angiogenesis specifically through VEGFR2 downregulation is still lacking. In addition, whether the lack of epsins causes abnormal angiogenesis during embryonic development remains unclear.
Few studies have investigated associations between nonoccupational exposure to ambient volatile organic compounds and lung cancer. We conducted a case-control study of 445 incident lung cancers and 948 controls (523 hospital, 425 general population) in Toronto, Ontario, Canada, between 1997 and 2002. Participants provided information on several risk factors, including tobacco use, secondhand exposure to cigarette smoke, obesity, and family history of cancer. Exposure to benzene, hydrocarbons, and nitrogen dioxide was estimated using land-use regression models. Exposures were linked to residential addresses to estimate exposure at the time of interview, 10 years before interview, and across past residences (time-weighted average). Logistic regression was used to estimate adjusted odds ratios. Analyses involving the population-based controls found that an interquartile-range increase in the time-weighted average benzene concentration (0.15 µg/m(3)) across previous residences was associated with lung cancer (odds ratio = 1.84, 95% confidence interval: 1.26, 2.68). Similarly, an interquartile-range increase in the time-weighted average nitrogen dioxide concentration (4.8 ppb) yielded an odds ratio of 1.59 (95% confidence interval: 1.19, 2.12). Our study suggests that long-term exposure to ambient volatile organic compounds and nitrogen dioxide at relatively low concentrations is associated with lung cancer. Further work is needed to evaluate joint relationships between these pollutants, smoking, and lung cancer.
The majority of studies that assessed population-level exposure to traffic-related noise were conducted in European countries and less is known about the exposure to traffic noise in North America, particularly in Canadian cities. This study explored the temporal and spatial variability of traffic noise in the City of Toronto, the largest city in Canada. We conducted two cycles of intensive field measurement campaign to collect real-time measurements of traffic noise at 554 locations across Toronto between June 2012 and January 2013. At each site, we collected measurements for a period of 30min during daytime. Repeated measurements were made in cycle two at 62 locations randomly selected from cycle one, which exhibited high correlation (Pearsons correlation coefficient (r): 0.79). In addition, continuous measurements of noise were recorded for seven days at ten sites. We observed that noise variability was predominantly spatial in nature, rather than temporal: spatial variability accounted for 60% of the total observed variations in traffic noise. Traffic volume, length of arterial road, and industrial area were three most important variables, explaining the majority of the spatial variability of noise (R(2)=0.68 to 0.74, depending on the cycle). In comparison to the 16-h equivalent sound level guideline for outdoor locations set out by the Ministry of the Environment of the Province of Ontario, 80% of our sampled locations exceeded this guideline (i.e. 55 dBA,16h). These findings suggested ubiquitous traffic noise exposure across Toronto and that noise variability was explained mostly by spatial characteristics.
The myostatin gene (MSTN) is a genetic determinant of skeletal muscle growth. Single nucleotide polymorphisms (SNP) in MSTN are of importance due to their strong associations with horse racing performances. In this study, we screened the SNPs in MSTN gene in 514 horses from 15 Chinese horse breeds. Six SNPs (g.26T>C, g.156T>C, g.587A>G, g.598C>T, g.1485C>T, g.2115A>G) in MSTN gene were detected by sequencing and genotyped using PCR-RFLP method. The g.587A>G and g.598C>T residing in the 5UTR region were novel SNPs identified by this study. The g.2115A>G which have previously been associated with racing performances were present in Chinese horse breeds, providing valuable genetic information for evaluating the potential racing performances in Chinese domestic breeds. The six SNPs together defined thirteen haplotypes, demonstrating abundant haplotype diversities in Chinese horses. Most of the haplotypes were shared among different breeds with no haplotype restricted to a specific region or a single horse breed. AMOVA analysis indicated that most of the genetic variance was attributable to differences among individuals without any significant contribution by the four geographical groups. This study will provide fundamental and instrumental genetic information for evaluating the potential racing performances of Chinese horse breeds.
Forkhead box A2 (Foxa2) has been recognized as one of the most potent transcriptional activators that is implicated in the control of feeding behavior and energy homeostasis. However, similar researches about the effects of genetic variations of Foxa2 gene on growth traits are lacking. Therefore, this study detected Foxa2 gene polymorphisms by DNA pool sequencing, PCR-RFLP and PCR-ACRS methods in 822 individuals from three Chinese cattle breeds. The results showed that four sequence variants (SVs) were screened, including two mutations (SV1, g. 7005 C>T and SV2, g. 7044 C>G) in intron 4, one mutation (SV3, g. 8449 A>G) in exon 5 and one mutation (SV4, g. 8537 T>C) in the 3UTR. Notably, association analysis of the single mutations with growth traits in total individuals (at 24months) revealed that significant statistical difference was found in four SVs, and SV4 locus was highly significantly associated with growth traits throughout all three breeds (P<0.05 or P<0.01). Meanwhile, haplotype combination CCCCAGTC also indicated remarkably associated to better chest girth and body weight in Jiaxian Red cattle (P<0.05). We herein described a comprehensive study on the variability of bovine Foxa2 gene that was predictive of molecular markers in cattle breeding for the first time.
Copy number variations (CNVs) have been recently recognized as another important genetic variability complementary to single nucleotide polymorphisms (SNPs). Compelling evidence has indicated that CNVs are responsible for phenotypic traits by changing the copy numbers of functional genes. Myosin heavy chain 3 (MYH3) gene is a critical regulatory factor in skeletal muscle development, and has been detected in the CNVs region by comparative genomic hybridization (CGH) array. This study was conducted to validate and detect the distribution of MYH3 copy numbers (relative to Angus cattle) in four Chinese cattle breeds (NY, QC, LX, and CY), and further to investigate the associations of the copy number changes with its transcriptional expression and cattle growth traits. Substantial genetic differences of MYH3 copy numbers were identified between NY and the other three breeds (P<0.01). The copy numbers of MYH3 gene presented the positive correlations with the transcript level of MYH3 gene in both fetal and adult skeletal muscles (P<0.05). Statistical analysis revealed that CNVs of MYH3 gene were significantly associated with growth traits of NY cattle, and the individuals with copy number gain showed better phenotypes than the loss and/or median groups (P<0.05). This study firstly attempted to establish the correlations between CNVs of candidate genes and growth traits, and our results suggested that the CNVs of MYH3 gene may be utilized as the potential markers for economic traits in selection breeding programs of Chinese cattle.
An ultrasensitive label-free electrochemiluminescence (ECL) aptasensor for the detection of thrombin was developed based on the specific recognition between tris(bipyridine)ruthenium(II)-?-cyclodextrin (tris(bpyRu)-?-CD) and the anti-thrombin aptamer (aptamer). The NH2-aptamer was first immobilized on the activated glassy carbon electrode (GCE) by coupling interaction. By use of the specific recognition between tris(bpyRu)-?-CD and aptamer, tris(bpyRu)-?-CD was then attached on the surface of GCE. Resulting from the outstanding photoactive properties of tris(bpyRu)-?-CD, the fabricated GCE performed strong ECL signal with the coreactant of 2-(dibutylamino)ethanol (DBAE). However, in the presence of thrombin, aptamer-thrombin bioaffinity complexes were formed, which restricted the recognition activities between aptamer and tris(bpyRu)-?-CD. Thus, fewer tris(bpyRu)-?-CD could be attached on the surface of GCE and led to an obvious decrease of ECL signal. Fortunately, the difference of ECL intensity before and after combination with thrombin was logarithmically linear with the concentration of thrombin in a wide range of 10nM-1pM. Meantime, a detection limit of 0.1pM without any other signal labeling or amplifying procedures indicated that the biosensor performed excellent sensitivity, operability and simplicity.
To analyze the development and innervation of bladder smooth muscle and lesions of the spinal cord in fetal rats with meningomyelocele (MMC) at different gestational ages and to investigate interactions between spinal cord lesions and bladder.
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