Our objective was to describe the virological and immunological responses of ART with attempt to identify the risk factors for treatment failure, and to examine rates and reasons for initial regimen modification in Yunnan Province. A total of 144 HIV-infected adults who initiated antiretroviral treatment between 2004 and 2006 of Yunnan province were recruited in this longitudinal study. The endpoints were virological failure, immunological failure, and initial regimen modification, according to World Health Organization criteria. Over the 6-year follow-up, 16(11.1%) patients demonstrated virological failure and 34 (23.6%) experienced immunological failure, for overall failure rates of 2.79 per 100 person-years (95% CI: 1.71-4.55) and 6.17 per 100 person-years (95% CI: 4.41-8.64), respectively. Male (p=0.007, HR=5.22, 95%CI of HR: 1.58-17.21) was a risk factor for immunological failure. 37.5% patients modified their initial regimen over the follow-up duration, and the most common reason for modification was adverse events. Our analysis of ART in Yunnan reveals excellent outcomes achieved over the past years. High rate of initial regimen modification should be taken seriously. Given the discordant immunological and virological responses emerged after ART initiation, viral load monitoring is urgently needed for evaluating the treatment outcomes in resource-limited settings comprehensively.
The swelling of the lodicule is responsible for floret opening in many grass species, allowing for pollen dispersal and cross-pollination. In barley, the closed floret habit (cleistogamy) is under the control of cly1, a gene which operates by inhibiting the development of the lodicule. In non-cleistogamous cultivars, cly1 mRNA is degraded by miR172-directed cleavage, allowing the lodicules to swell; however, in cultivars carrying the recessive allele cly1.b, a single nucleotide substitution destroys the miR172 target site preventing mRNA cleavage. Barley cv. SV235 is cleistogamous; its cly1 coding sequence is identical to that of cly1.b, but its lodicules do develop, although insufficiently to produce a non-cleistogamous flower. In this cultivar, the down-regulation of cly1 is unrelated to miR172-directed mRNA degradation, but rather is caused by an epiallele which represses transcription. Allelic relationships between known cly1 alleles were explored by the quantification of lodicule vascularization and an assessment of the response of the spike to the supply of exogenous auxin. The SV235 phenotype can be manipulated by a pre-anthesis application of 2,4-D, a feature which could be of interest in the context of hybrid barley grain production based on cleistogamy.
Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.
Using the single-sided reflection response of an unknown layered medium, one-dimensional single-sided acoustic focusing is a process that constructs a normally incident plane waveform such that the sound field collapses to a point inside this medium at a specified time. A recursive method for finding the incident waveform of the discrete single-sided focusing in the Goupillaud layered model is presented. The method is formulated using the standard Z-transform and provides an intuitive way to understand how single-sided focusing works in an unknown medium. Two numerical scattering experiments, with different layered structures, are simulated to verify the proposed method. In addition, the responses to virtual sources in the examples are reconstructed.
The Tibetan Plateau uplift and Cenozoic global cooling are thought to induce enhanced aridification in the Asian interior. Although the onset of Asian desertification is proposed to have started in the earliest Miocene, prevailing desert environment in the Tarim Basin, currently providing much of the Asian eolian dust sources, is only a geologically recent phenomenon. Here we report episodic occurrences of lacustrine environments during the Late Miocene and investigate how the episodic lakes vanished in the basin. Our oxygen isotopic (?(18)O) record demonstrates that before the prevailing desert environment, episodic changes frequently alternating between lacustrine and fluvial-eolian environments can be linked to orbital variations. Wetter lacustrine phases generally corresponded to periods of high eccentricity and possibly high obliquity, and vice versa, suggesting a temperature control on the regional moisture level on orbital timescales. Boron isotopic (?(11)B) and ?(18)O records, together with other geochemical indicators, consistently show that the episodic lakes finally dried up at ?4.9 million years ago (Ma), permanently and irreversibly. Although the episodic occurrences of lakes appear to be linked to orbitally induced global climatic changes, the plateau (Tibetan, Pamir, and Tianshan) uplift was primarily responsible for the final vanishing of the episodic lakes in the Tarim Basin, occurring at a relatively warm, stable climate period.
Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function. To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-1-antitrypsin deficiency (AATD), Niemann-Pick type C1 disease (NPC1), Alzheimer's disease (AD), and cystic fibrosis (CF). Using distinct models, including patient-derived cell lines and primary epithelium, mouse brain tissue, and Caenorhabditis elegans, we found that chronic expression of misfolded proteins not only triggers the sustained activation of the heat shock response (HSR) pathway, but that this sustained activation is maladaptive. In diseased cells, maladaptation alters protein structure-function relationships, impacts protein folding in the cytosol, and further exacerbates the disease state. We show that down-regulation of this maladaptive stress response (MSR), through silencing of HSF1, the master regulator of the HSR, restores cellular protein folding and improves the disease phenotype. We propose that restoration of a more physiological proteostatic environment will strongly impact the management and progression of loss-of-function and gain-of-toxic-function phenotypes common in human disease.
Ganoderma lucidum (G. lucidum, Reishimax) is an herbal mushroom known to have inhibitory effect on tumor cell growth. However, the molecular mechanisms responsible for its anti-proliferative effects on the ovarian cancer have not been fully elucidated.
Modification of single-walled carbon nanotubes (SWNTs) on the surface of monocrystalline silicon solar cells was investigated. The modification was realized by dropping a well-distributed mixture of SWNTs and ethanol with different dosages on the surface of monocrystalline silicon solar cells in the same effective area. The experimental results showed that the increasing rates of conversion efficiency, short-circuit current, and fill factor were 4.37%, 2.18%, and 2.11%, respectively; the open circuit voltage and series resistance decreased by 0.11% and 9.37% compared with the bare solar cell without an antireflection (AR) layer, when the modification reached the best state by dropping a 0.5 mL mixture solution with a concentration of 0.08??g/L. With the energy-band diagrams of the heterojunction and p-n junction, the principles of the modification of SWNTs on monocrystalline silicon solar cells and the reasons for the change of electrical parameters were analyzed theoretically. Through experiments and theoretical analyses, the modification of SWNTs on solar cells is a potential and effective way to improve the performance of solar cells.
Pancreatic cancer is the sixth leading cause of cancer death with an increasing trend in China. Dietary intake is believed to play an important role in pancreatic cancer carcinogenesis. The aim of this paper was to evaluate associations between some dietary factors and risk of pancreatic cancer in a multi-centre case-control study conducted in China.
Neuroblastoma (NB), the most common extracranial solid tumor, accounts for 10% of childhood cancer. To date, scientists have gained quite a lot of knowledge about microRNAs (miRNAs) and their genes in NB. Discovering inner regulation networks, however, still presents problems. Our study was focused on determining differentially-expressed miRNAs, their target genes and transcription factors (TFs) which exert profound influence on the pathogenesis of NB. Here we constructed three regulatory networks: differentially-expressed, related and global. We compared and analyzed the differences between the three networks to distinguish key pathways and significant nodes. Certain pathways demonstrated specific features. The differentially-expressed network consists of already identified differentially-expressed genes, miRNAs and their host genes. With this network, we can clearly see how pathways of differentially expressed genes, differentially expressed miRNAs and TFs affect on the progression of NB. MYCN, for example, which is a mutated gene of NB, is targeted by hsa-miR-29a and hsa-miR-34a, and regulates another eight differentially-expressed miRNAs that target genes VEGFA, BCL2, REL2 and so on. Further related genes and miRNAs were obtained to construct the related network and it was observed that a miRNA and its target gene exhibit special features. Hsa-miR-34a, for example, targets gene MYC, which regulates hsa-miR-34a in turn. This forms a self-adaption association. TFs like MYC and PTEN having six types of adjacent nodes and other classes of TFs investigated really can help to demonstrate that TFs affect pathways through expressions of significant miRNAs involved in the pathogenesis of NB. The present study providing comprehensive data partially reveals the mechanism of NB and should facilitate future studies to gain more significant and related data results for NB.
Novel constructive and destructive parsimonious extreme learning machines (CP- and DP-ELM) are proposed in this paper. By virtue of the proposed ELMs, parsimonious structure and excellent generalization of multiinput-multioutput single hidden-layer feedforward networks (SLFNs) are obtained. The proposed ELMs are developed by innovative decomposition of the recursive orthogonal least squares procedure into sequential partial orthogonalization (SPO). The salient features of the proposed approaches are as follows: 1) Initial hidden nodes are randomly generated by the ELM methodology and recursively orthogonalized into an upper triangular matrix with dramatic reduction in matrix size; 2) the constructive SPO in the CP-ELM focuses on the partial matrix with the subcolumn of the selected regressor including nonzeros as the first column while the destructive SPO in the DP-ELM operates on the partial matrix including elements determined by the removed regressor; 3) termination criteria for CP- and DP-ELM are simplified by the additional residual error reduction method; and 4) the output weights of the SLFN need not be solved in the model selection procedure and is derived from the final upper triangular equation by backward substitution. Both single- and multi-output real-world regression data sets are used to verify the effectiveness and superiority of the CP- and DP-ELM in terms of parsimonious architecture and generalization accuracy. Innovative applications to nonlinear time-series modeling demonstrate superior identification results.
Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n?=?15), control (n?=?15), and edaravone-treated (n?=?15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1? (HIF-1?) and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p?.05). Treatment with edaravone also decreased apoptosis of NSPCs (p?.01). Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1? and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1? and cleaved caspase-3 after cerebral ischemia.
We demonstrate that a reversible semimetallic-to-metallic transition can be realized in monolayer graphene by iodine doping and dedoping processes. Upon iodine doping, the charge transfer from graphene to iodine creates a high hole density up to 4.75 × 10(13)cm(-2), well beyond that realized by applying gate voltages. Iodine-doped graphene shows metallic behaviour, as evidenced by the resistance variation with temperature and magnetic field. We further introduce an iodine dedoping method to completely remove the iodine anions from graphene surfaces. Transport measurements show that after dedoping treatments, the mobility of graphene is significantly enhanced, much higher than that of pristine graphene. The improvement in graphene electronic properties is attributed to the corrosive characteristic of iodine that it can react with and remove absorbed atoms on graphene surfaces. Our work not only opens a facile and effective way to tune the properties of monolayer graphene reversibly, but also demonstrates a new method to increase the quality of graphene.
This paper presents compact yet comprehensive feature representations for the Electroencephalogram (EEG) signal to achieve efficient epileptic seizure prediction performance. The initial EEG feature vectors are formed by acquiring the dominant amplitude and frequency components on an epoch-by-epoch basis from the EEG signals. These extracted parameters can reveal the intrinsic EEG signal changes as well as the underlying stage transitions. To improve the efficacy of feature extraction, an elimination-based feature selection method has been applied on the initial feature vectors. This diminishes redundant and noisy points, providing each patient with a lower dimensional and independent final feature form. In this context, our work is distinguished from that of others currently prevailing. Usually, these latter approaches adopted feature extraction processes which employed time-consuming high-dimensional parameter sets. Machine learning approaches that are considered as state of the art have been employed to build patient-specific binary classifiers that can divide the extracted feature parameters into preictal and interictal groups. Through out-of-sample evaluation on the intracranial EEG (iEEG) recordings provided by the publicly available Freiburg data set, promising prediction performance has been attained. Specifically, we have achieved 98.8% sensitivity results on the 19 patients included in our experiment, where only one of 83 seizures across all patients was not predicted. To make this investigation more comprehensive, we have conducted extensive comparative studies with other recently published competing approaches, in which the advantages of our method are highlighted.
Steam and air co-injection is a newly developed and promising soil remediation technique for non-aqueous phase liquids (NAPLs) in vadose zone. In this study, in order to investigate the mechanism of the remediation process, trichloroethylene (TCE) removal using steam and air co-injection was carried out in a 2-dimensional sandbox with different layered sand structures. The results showed that co-injection perfectly improved the "tailing" effect compared to soil vapor extraction (SVE), and the remediation process of steam and air co-injection could be divided into SVE stage, steam strengthening stage and heat penetration stage. Removal ratio of the experiment with scattered contaminant area was higher and removal speed was faster. The removal ratios from the two experiments were 93.5% and 88.2%, and the removal periods were 83.9 min and 90.6 min, respectively. Steam strengthened the heat penetration stage. The temperature transition region was wider in the scattered NAPLs distribution experiment, which reduced the accumulation of TCE. Slight downward movement of TCE was observed in the experiment with TCE initially distributed in a fine sand zone. And such downward movement of TCE reduced the TCE removal ratio.
Although many metalloenzymes containing iron play a prominent role in biological C-H activation processes, to date iron-mediated C(sp(3))-H heterolysis has not been reported for synthetic models of Fe/S-metalloenzymes. In contrast, ample precedent has established that nature's design for reversible hydrogen activation by the diiron hydrogenase ([FeFe]-H2ase) active site involves multiple irons, sulfur bridges, a redox switch, and a pendant amine base, in an intricate arrangement to perform H-H heterolytic cleavage. In response to whether this strategy might be extended to C-H activation, we report that a [FeFe]-H2ase model demonstrates iron-mediated intramolecular C-H heterolytic cleavage via an agostic C-H interaction, with proton removal by a nearby pendant amine, affording Fe(II)-[ Fe'(II)-CH- S] three-membered-ring products, which can be reduced back to 1 by Cp2Co in the presence of HBF4. The function of the pendant base as a proton shuttle was confirmed by the crystal structures of the N-protonated intermediate and the final deprotonated product in comparison with that of a similar but pendant-amine-free complex that does not show evidence of C-H activation. The mechanism of the process was backed up by DFT calculations.
Abstract As a cryptic species complex, the taxonomy of Echinococcus granulosus has long been controversial. The complete mitochondrial (mt) genome of the E. granulosus G3 genotype was sequenced and characterized. The G3 mt genome was 13,607?bp in length, and contained 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and 12 protein-coding genes, with a gene order identical to those of other reported genotypes. The overall nucleotide composition (coding strand) for the mt genome sequence of G3 was 19.1% A, 47.8% T, 25.0% G, and 8.1% C, with T being the most common base and C the least common.
In the present study, high-strength photoresponsive hydrogels were prepared by the photoinitiated copolymerization of acrylamide (AAm, hydrophilic hydrogen bonding monomer), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT, hydrophobic hydrogen bonding monomer), and spiropyran-containing monomer (SPAA) in the presence of cross-linker poly(ethylene glycol) diacrylate (PEG575DA, Mn = 575). The double hydrogen bondings from AAm-AAm and diaminotriazine-diaminotriazine contributed to the considerable enhancement in tensile and compressive properties of the hydrogels, which showed an excellent ability to resist a variety of external forces. Fifteen minutes of UV (365 nm) irradiation led to the detachment of adhered cells due to the increased surface hydrophilicity caused by the isomerization of spiropyran moieties. Furthermore, repeated attachment/detachment of cells was realized by the alternate illumination of visible and UV light. Reverse gene transfection was carried out successfully by anchoring the PVDT/pDNA complex nanoparticles on the gel surface through hydrogen bonding between diaminotriazine motifs prior to cell seeding. Importantly, fibronectin (FN) modification combined with supplementing PVDT/pDNA complex nanoparticles after the first cycle of reverse gene transfection, so-called sandwich gene transfection, further increased the gene transfection level. A short time of UV light exposure could result in the nonharmful detachment of gene-modified cells from the gel surface. This high-strength photosensitive hydrogel holds potential as a reusable soft-wet platform for cell harvesting as well as gene transfection operation at higher efficiency.
Aim of Study. Gegen Qinlian decoction (GQLD) is an ancient Chinese medicine formula for treating diseases with inner heat. The aim of this study is to investigate the antitumor effect of GQLD in human renal carcinoma cell (RCC) and its possible mechanism. Method. High-performance liquid chromatography was used to identify and quantify active compounds in GQLD. Inhibition of tumor growth was determined by xenograft model. Cell viability on treatment with the decoction was determined by MTT assay; quantitative real-time polymerase chain reaction and immunoblotting were used to determine gene and protein expression; matrix metalloproteinase-2 (MMP-2) activity was detected by gelatin zymography and in vitro enzymatic reaction assay. Results. Thirteen major peaks were detected in the decoction, 8 of which were identified as berberine, baicalin and baicalein, pueranin, daizidin, liquiritin, wogonoside, and wogonin. GQLD exhibited potent inhibition on xenografted expansion of RCC cells. Interestingly, GQLD treatment did not induce cell death to RCC cells, but blocked the neoangiogenesis in xenografted RCC tumor. Particularly, we found that GQLD significantly inhibited MMP-2 in RCC cells, which was involved as a critical factor in avascular growth of RCC. GQLD directly suppressed the enzyme activity of MMP-2. Radix Scutellariae was the major herbal component that contributed to the potent inhibition of MMP-2. Conclusion. The findings of this study provide experimental evidence of the inhibition of expansion and neoangiogenesis of renal carcinoma by Chinese medicine formula GQLD with involvement of MMP-2 suppression.
The purpose of the study was to investigate the incidence of HIV and syphilis and their related factors, as well as to examine the predictors associated with seroconversion among migrant men who have sex with men (MSM) in Beijing, China.
Glycine can persistently potentiate or depress AMPA responses through differential actions on two binding sites: NMDA and glycine receptors. Whether glycine can induce long-lasting modifications in NMDA responses, however, remains unknown. Here, we report that glycine induces long-term potentiation (LTP) or long-term depression (LTD) of NMDA responses (Gly-LTPNMDA or Gly-LTDNMDA) in a dose-dependent manner in hippocampal CA1 neurons. These modifications of NMDA responses depend on NMDAR activation. In addition, the induction of Gly-LTPNMDA requires binding of glycine with NMDARs, whereas Gly-LTDNMDA requires that glycine bind with both sites on NMDARs and GlyRs. Moreover, activity-dependent exocytosis and endocytosis of postsynaptic NMDARs underlie glycine-induced bidirectional modification of NMDA excitatory postsynaptic currents. Thus, we conclude that glycine at different levels induces bidirectional plasticity of NMDA responses through differentially regulating NMDA receptor trafficking. Our present findings reveal important functions of the two glycine binding sites in gating the direction of synaptic plasticity in NMDA responses.
The domestication of cultivated barley has been used as a model system for studying the origins and early spread of agrarian culture. Our previous results indicated that the Tibetan Plateau and its vicinity is one of the centers of domestication of cultivated barley. Here we reveal multiple origins of domesticated barley using transcriptome profiling of cultivated and wild-barley genotypes. Approximately 48-Gb of clean transcript sequences in 12 Hordeum spontaneum and 9 Hordeum vulgare accessions were generated. We reported 12,530 de novo assembled transcripts in all of the 21 samples. Population structure analysis showed that Tibetan hulless barley (qingke) might have existed in the early stage of domestication. Based on the large number of unique genomic regions showing the similarity between cultivated and wild-barley groups, we propose that the genomic origin of modern cultivated barley is derived from wild-barley genotypes in the Fertile Crescent (mainly in chromosomes 1H, 2H, and 3H) and Tibet (mainly in chromosomes 4H, 5H, 6H, and 7H). This study indicates that the domestication of barley may have occurred over time in geographically distinct regions.
Blue light is commonly used to kill Propionibacterium acnes in clinic. Furthermore, blue light exhibits a good bactericidal effect against Helicobacter pylori, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and many oral bacteria in laboratory studies. The bactericidal mechanism of blue light as commonly accepted consists photo-excitation of intracellular porphyrins resulting in production of cytotoxic reactive oxygen species which can inactivate bacteria. Blue light can kill bacteria without additional exogenous photosensitizers. In addition, it produces little harm to mammalian cells. Therefore, as the increasing emergence of antibiotic resistant microorganisms, blue light might be a good antibacterial tool.
Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'- deoxy- 2' -?- fluoro -4'- azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with IC50 values of 0.2?M and 0.097?M, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ?-catenin, the glycogen synthase kinase-3 beta (GSK-3?), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ?-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-3? and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/?-catenin signaling pathway.
Vanadium dioxide (VO2) films with moth-eye nanostructures have been fabricated to enhance the thermochromic properties with different periodicity (d) to achieve antireflection (AR). It is revealed that the films with smaller d (210 and 440 nm) could increase both the luminous transmission (Tlum) and infrared transmission (TIR) at 25 and 90 °C, as the d is smaller than the given wavelength and the gradient refractive index produces antireflection. The average Tlum and TIR of VO2 increase with decreasing d. Compared with the planar film, the AR sample with periodicity of 210 nm and thickness of 140 nm can offer approximately 10% enhancement of Tlum and 24.5% increase in solar modulation (?Tsol). With the addition of hydrophobic overcoat on the patterned VO2, ?120° contact angle could be achieved. The present approach can tailor the optical transmittance in different wavelengths at high and low temperature together with self-cleaning, opening new avenues for producing hydrophobic VO2 with enhanced thermochromic properties for smart window applications.
The highly efficient preparation of metal nanoparticles embedded in a carbon nanotube remains a considerable challenge. Herein, we report a simple and template-based procedure for the fabrication of carbon nanotubes with Pd nanoparticles uniformly embedded in the inner carbon surfaces. In addition to the novel structure, the sinter-resistance of the as-prepared Pd/C nanocomposite was much better than that of the traditional carbon-nanotube-supported Pd catalysts. The as-prepared Pd/C nanocomposite has a high recyclability in a liquid-phase Suzuki coupling reaction. This strategy may be extended as a general approach to prepare metal nanoparticles supported on carbon-nanotubes.
Previous studies evaluating the association between the XPG Asp1104His polymorphism and melanoma susceptibility remained controversial. To draw a more precise estimation of the relationship, a total of eight published case-control studies containing 5,212 cases and 7,045 controls were included for meta-analysis. Overall, a significant association was found between the XPG Asp1104His polymorphism and melanoma susceptibility for the dominant model (OR = 2.42, 95 % CI = 2.26-2.60). In subgroup analysis by source of control, there was an obvious association was found among Population-based subgroup for the dominant model CC+GC vs GG (OR 2.51, 95 % CI 2.28-2.77), among the Hospital-based subgroup, an obvious association was also found for the dominant model CC+GC vs GG (OR 2.34, 95 % CI 2.12-2.58). This meta-analysis suggested that the XPG Asp1104His polymorphism was a risk factor for melanoma susceptibility.
Objective of the study is to find the association between p21 rs1059234 polymorphisms and endometrial cancer in Han women from Northeast China. Genotyping of rs1059234 in the p21 gene was performed by sequencing and PCR-restriction fragment length polymorphism (PCR-RFLP) of peripheral blood samples in 263 endometrial cancer patients (case group) and 315 healthy subjects (control group). C allele frequency of rs1059234 was significantly increased in patients of the case group when compared with that in the control group (P = 0.039). The CC genotype frequency of rs1059234 was also significantly increased in patients of case group (0.335, vs. 0.219, P = 0.045). CC genotype increased the risk of endometrial cancer (OR = 1.589, 95 %CI: 1.010-2.502). However, after corrected with regression analysis, the CC genotype did not increase the risk of endometrial cancer (OR = 1.623, 95 % CI: 0.720-3.659, P = 0.243). Our study demonstrates that in Han women from Northeast China, there is no association between rs1059234 polymorphism of p21 gene and risk of endometrial cancer.
The aim of the study was to investigate the inhibitory effects of RNA interference on XIAP gene expression of human endometrial carcinoma RL95-2 cell and the cell apoptosis. Specific small interference RNA (siRNA) of XIAP was designed and composed. Transfection of siRNA was conducted in endometrial carcinoma cell line RL95-2. The XIAP gene mRNA was assessed by real-time PCR and the change of XIAP protein was assessed with Western Blotting. The cell proliferation and apoptosis was assessed by MTT and flow cytometry methods. After transfection of siRNA specifically targeting XIAP, the relative fold of mRNA transfection in the specific transfection group was (0.04 ± 0.06) and the relative protein expression was (0.590 ± 0.178), which was significantly decreased when compared with the control group (P < 0.05); the cell growth inhibition rate in the transfection group was (47.86 ± 4.46) %, which was significantly increased when compared to the control group (P < 0.05). In vitro experiment showed that synthetic siRNA could effectively inhibit the transfection and expression of XIAP gene of human endometrial carcinoma RL95-2 cell at the mRNA level and protein level, thus significantly promote the apoptosis of endometrial carcinoma cell. The mechanisms involved in the apoptosis still require further investigation.
Tumor necrosis factor-alpha (TNF-?) participates as a candidate susceptibility factor for immune thrombocytopenia (ITP). This study attempted to investigate the association between five single nucleotide polymorphisms (SNPs) spanning the TNF-? promoter and the susceptibility of primary ITP in Chinese Han adults.
Hydrogen sulphide (H2S) adsorption capacities on recycled rubber media, tyre-derived rubber particle (TDRP), and other rubber material (ORM) have been evaluated. As part of the research, densities, moisture contents, and surface properties of TDRP and ORM have been determined. The research team findings show that TDRP and ORM are more particulate in nature and not highly porous-like activated carbon. The characteristics of surface area, pore size, and moisture content support chemisorption on the macrosurface rather than physical adsorption in micropores. For example, moisture content is essential for H2S adsorption on ORM, and an increase in moisture content results in an increase in adsorption capacity.
A new acceptor-donor-acceptor (A-D-A) small molecule, namely, BDT-PO-DPP, based on the alkoxyphenyl (PO)-substituted benzo[1,2-b:4,5-b']dithiophene (BDT) derivative and the diketopyrrolopyrrole (DPP) unit was synthesized as an electron donor for solution-processed small-molecule organic solar cells (SMOSCs). BDT-PO-DPP exhibited good thermal stability, with a 5?% weight-lost temperature at 401?°C under a nitrogen atmosphere. BDT-PO-DPP exhibited a lower HOMO energy level of -5.25?eV and a weaker aggregation ability than alkoxy-substituted BDT-O-DPP. A bulk heterojunction SMOSC device based on BDT-PO-DPP and [6,6]-phenyl-C61 -butyric acid methyl ester was prepared, and it showed a power conversion efficiency up to 5.63?% with a high open-circuit voltage of 0.83?V, a short circuit current density of 11.23?mA?cm(-2) , and a fill factor of 60.37?% by using 1,2-dichlorobenzene as the co-solvent after thermal annealing at 110?°C. The results indicate that the alkoxyphenyl-substituted BDT derivative is a promising electron-donor building block for constructing highly efficient solution-processed SMOSCs.
Hepatitis C virus now represents a global viral pandemic and is the fourth most commonly reported infectious disease in China. Information on China's national HCV epidemic was limited to cross -sectional seroprevalence studies of special populations, and a national surveillance effort had been launched to inform prevention and control. We analysed novel data from two national databases: (i) China's national medical HCV case report system and (ii) the national disease sentinel surveillance system. Between 1997 and 2012, reporting incidence of medical cases for HCV infection rose from 0.7 to 15.0 cases per 100 000 with the largest burden of disease concentrated among individuals over 35 years of age, rural residents and those tested as part of routine screening. Between 2010 and 2012, disease sentinel surveillance identified the highest HCV seropositive rates among persons who use drugs and haemodialysis patients, with far lower but not negligible rates among sexually active population. The concentration of cases among older age groups is consistent with past studies of age-specific prevalence rates in Asia. Differences across regions and testing modes suggest diverse biological and social forces driving the spread of HCV in China. Surveillance data show ongoing transmission, particularly among persons who use drugs and persons undergoing invasive medical treatments, particularly haemodialysis. Improvements in case detection and data reporting systems will be critical for understanding current drivers of transmission and identifying key areas for prevention.
A new method of measuring the refractive indices of nanoparticles has been proposed based on refractive index matching between nanoparticles and surrounding organic solvents. By finding the most transparent point of the transmittance spectrum, the refractive index of the nanoparticles is equal to that of the solvents at the corresponding wavelength. Utilizing a Rayleigh scattering model, the effects of refractive index mismatching (?n) on the transmittance are investigated under different conditions. Some criteria for getting highly transparent nanoparticle dispersion and accurate refractive index measurements are suggested, which can support practical applications for nanomaterials in optical and optoelectronic applications.
Sumac (Rhus chinensis Mill) is an abundant and widely distributed Chinese native plant. Sumac fruit contains low content of vegetable oil, as an atypical oil plants hardly being processed through traditional vegetable oil production technologies. Based on our own studies on the characteristics of sumac fruit and branches, we established a novel model of sumac biomass refinery, and constructed the sumac biomass refinery technology system and eco-industrial chain integration. Steam explosion was the key technology, and several components fractionation technologies were integrated in the sumac biomass refinery system. The fractionated components were converted into different products depending on their functional features. Eight products including sumac fruit oil, biodiesel, protein feed, flavonoids, unbleached facial tissue, phenolic resin, biomass briquette and biogas were produced in the refinery. The extracted sumac fruit oil by steam explosion pretreatment was applied for the new food resource of Ministry of Health, and the permit was approved. This research provides a new model for the development of atypical wild plant resources.
This study was to investigate the anticancer effects of baicalein (Bai) and its two sulfated derivatives, namely baicalein-7-O-sulfate (BoS) and baicalein-8-sodium sulfonate (BcS). BcS was shown to exhibit stronger growth inhibition against human breast cancer MCF-7 cells, compared with structurally related Bai and BoS, where IC50 values of BoS, Bai and BcS were 97.7, 68.3 and 30.4?M, respectively. BoS, Bai and BcS were further shown to mediate the cell-cycle arrest principally in G0/G1-phase within 12h of treatment with MCF-7 cells, and after 12h, they arrested principally in S-phase. It was also found that 17.7%, 44.9% and 70.5% of MCF-7 cells entered the early phase of apoptosis when treated with 200?M BoS, Bai and BcS for 24h, followed by an intracellular ROS generation. BcS displays strong antitumor effect through ROS-dependent apoptosis pathway in MCF-7 cells, and has promising potential to be developed as an antitumor compound.
Abstract Background: Recently, CELSR1 was identified by genome-wide association studies (GWAS) as a susceptibility gene for ischaemic stroke (IS) in Japanese individuals. Aim: The goal was to examine whether CELSR1 variants are associated with IS in the Chinese Han population. Subjects and methods: This study genotyped two single nucleotide polymorphisms (SNPs) of CELSR1, rs6007897 and rs4044210, in a Chinese sample of 569 IS cases and 581 controls and assessed their genotype and allele associations with IS. Results: The results showed that rs6007897 and rs4044210 variants of CELSR1 were significantly (p?0.01) associated with IS. These associations remained after adjustment for age, gender, smoking status, hypertension, diabetes mellitus and hypercholesterolemia. In addition, a significant association was observed of rs6007897 and rs4044210 of CELSR1 with large artery atherosclerosis (LAA), a sub-type of IS (p?0.01). Conclusion: Taken together, the present study has proven for the first time that CELSR1 is a susceptibility gene for IS in the Chinese Han population, especially for LAA.
We report the observation of a dense triangular network of one-dimensional (1D) metallic modes in a continuous and uniform monolayer of MoSe(2) grown by molecular-beam epitaxy. High-resolution transmission electron microscopy and scanning tunneling microscopy and spectroscopy studies show that these 1D modes are midgap states at inversion domain boundaries. Scanning tunneling microscopy and spectroscopy measurements further reveal intensity undulations of the metallic modes, presumably arising from the superlattice potentials due to the moiré pattern and the quantum confinement effect. A dense network of the metallic modes with a high density of states is of great potential for heterocatalysis applications. The interconnection of such midgap 1D conducting channels may also imply new transport behaviors distinct from the 2D bulk.
Temporal properties of spike firing in the central nervous system (CNS) are critical for neuronal coding and the precision of information storage. Chronic pain has been reported to affect cognitive and emotional functions, in addition to trigger long-term plasticity in sensory synapses and behavioral sensitization. Less is known about the possible changes in temporal precision of cortical neurons in chronic pain conditions. In the present study, we investigated the temporal precision of action potential firing in the anterior cingulate cortex (ACC) by using both in vivo and in vitro electrophysiological approaches. We found that peripheral inflammation caused by complete Freund's adjuvant (CFA) increased the standard deviation (SD) of spikes latency (also called jitter) of ?51% of recorded neurons in the ACC of adult rats in vivo. Similar increases in jitter were found in ACC neurons using in vitro brain slices from adult mice with peripheral inflammation or nerve injury. Bath application of glutamate receptor antagonists CNQX and AP5 abolished the enhancement of jitter induced by CFA injection or nerve injury, suggesting that the increased jitter depends on the glutamatergic synaptic transmission. Activation of adenylyl cyclases (ACs) by bath application of forskolin increased jitter, whereas genetic deletion of AC1 abolished the change of jitter caused by CFA inflammation. Our study provides strong evidence for long-term changes of temporal precision of information coding in cortical neurons after peripheral injuries and explains neuronal mechanism for chronic pain caused cognitive and emotional impairment.
Identifying disease genes is one of the most important topics in biomedicine and may facilitate studies on the mechanisms underlying disease. Age-related macular degeneration (AMD) is a serious eye disease; it typically affects older adults and results in a loss of vision due to retina damage. In this study, we attempt to develop an effective method for distinguishing AMD-related genes. Gene ontology and KEGG enrichment analyses of known AMD-related genes were performed, and a classification system was established. In detail, each gene was encoded into a vector by extracting enrichment scores of the gene set, including it and its direct neighbors in STRING, and gene ontology terms or KEGG pathways. Then certain feature-selection methods, including minimum redundancy maximum relevance and incremental feature selection, were adopted to extract key features for the classification system. As a result, 720 GO terms and 11 KEGG pathways were deemed the most important factors for predicting AMD-related genes.
Molecular biologists have collected considerable data regarding the involvement of genes and microRNAs (miRNAs) in cancer. However the underlying mechanisms of cancer with regard to genes and miRNAs remain unclear. The aim of the present study was to evaluate diffuse large B-cell lymphoma (DLBCL) and construct regulatory networks of genes and miRNAs to gradually reveal the underlying mechanisms of DLBCL development. The first differential expression network that is presented is an experimentally validated network of miRNAs and genes. This network presents known biological regulatory associations among miRNAs and genes in the human body. The second network is a DLBCL differential expression network. Differentially expressed gene and miRNA data regarding DLBCL were collected and, based on the first network and the differentially expressed data, the second network was inferred, which demonstrates the irregular regulatory associations that may lead to the occurrence of DLBCL. The third network is a DLBCL-associated network. This network is comprised of non-differentially expressed genes and miRNAs that contribute to numerous DLBCL processes. The similarities and differences among the three networks were extracted and compared to distinguish key regulatory associations; furthermore, important signaling pathways in DLBCL were identified. The present study partially clarified the pathogenesis of DLBCL and provided an improved understanding of the underlying molecular mechanisms, as well as a potential treatment for DLBCL.
This paper developed a rapid and nondestructive method for quantitative analysis of a cheaper adulterant (wheat flour) in oat flour by NIR spectroscopy and chemometrics. Reflectance FT-NIR spectra in the range of 4000 to 12000?cm(-1) of 300 oat flour objects adulterated with wheat flour were measured. The doping levels of wheat flour ranged from 5% to 50% (w/w). To ensure the generalization performance of the method, both the oat and the wheat flour samples were collected from different producing areas and an incomplete unbalanced randomized block (IURB) design was performed to include the significant variations that may be encountered in future samples. Partial least squares regression (PLSR) was used to develop calibration models for predicting the levels of wheat flour. Different preprocessing methods including smoothing, taking second-order derivative (D2), and standard normal variate (SNV) transformation were investigated to improve the model accuracy of PLS. The root mean squared error of Monte Carlo cross-validation (RMSEMCCV) and root mean squared error of prediction (RMSEP) were 1.921 and 1.975 (%, w/w) by D2-PLS, respectively. The results indicate that NIR and chemometrics can provide a rapid method for quantitative analysis of wheat flour in oat flour.
A novel bactericidal material comprising rod-shaped core-shell-shell Au-Ag-Au nanorods is constructed as a nanoheater in the near-infrared (NIR) region. The outer Au shell melts under laser irradiation and results in exposure of the inner Ag shell, facilitating the controlled release of the antibacterial Ag shell/layer or Ag(+). This results in the Au-Ag-Au nanorods having a favorable bactericidal ability as it combines the features of physical photothermal ablation sterilization of the outer Au shell and the antibacterial effect of the inner Ag shell or Ag(+) to the surrounding bacteria. The sterilizing ability of Au-Ag-Au nanorods is investigated with Escherichia coli O157:H7 as a model bacterial strain. Under low-power NIR laser irradiation (785nm, 50mWcm(-2)), the Au-Ag-Au nanoheater exhibits a higher photothermal conversion efficiency (with a solution temperature of 44°C) with respect to that for the Au-Ag nanorods (39°C). Meanwhile, a much improved stability with respect to Au-Ag nanorods is observed, i.e., 16 successive days of monitoring reveal virtually no change in the ultraviolet-visible spectrum of Au-Ag-Au nanorods, while a significant drop in absorption along with a 92nm red shift of Localized Surface Plasmon Resonance is recorded for the Au-Ag nanorods. This brings an increasing bactericidal efficiency and long-term stability for the Au-Ag-Au nanorods. At a dosage of 10?gml(-1), a killing rate of 100% is reached for the E. coli O157:H7 cells under 20min of irradiation. The use of Au-Ag-Au nanorods avoids the abuse of broad-spectrum antibiotics and reduces the damage of tissues by alleviating the toxicity of silver under controlled release and by the use of low-power laser irradiation. These features could make the bimetallic core-shell-shell nanorods a favorable nanoheater for in vivo biomedical applications.
The present work is a first trial to introduce activated carbon fibers (ACF) with high adsorption capacity into poly(lactic-co-glycolic) acid (PLGA), resulting in a novel kind of scaffolds for tissue engineering applications. ACF, prepared via high-temperature processing of carbon fibers, are considered to possess bioactivity and biocompatibility. The ACF/PLGA composite scaffolds are prepared by solvent casting/particulate leaching method. Increments in both pore quantity and quality over the surface of ACF as well as a robust combination between ACF and PLGA matrix are observed via scanning electron microscopy (SEM). The high adsorption capacity of ACF is confirmed by methylene blue solution absorbency test. The surfaces of ACF are affiliated with many hydrophilic groups and characterized by Fourier transform infrared spectroscopy. Furthermore, the SEM images show that cells possess a favorable spreading morphology on the ACF/PLGA scaffolds. Besides, vivo experiments are also carried out to evaluate the histocompatibility of the composite scaffolds. The results show that ACF have the potential to become one of the most promising materials in biological fields.
The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-?1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-?1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-?1 level, tumor differentiation, lymph node metastasis, and clinical stage (p?0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor.
This study investigated genome-wide gene expressions and the cardioprotective effects of electro-acupuncture pretreatment at the PC6 Neiguan acupoint on myocardial ischemia reperfusion (I/R) injury. Male SD rats were randomly divided into four groups: sham operation (SO), I/R, electro-acupuncture at the PC6 Neiguan acupoint pretreatment (EA) and electro-acupuncture at non-acupoint pretreatment (NA). Compared with the I/R group, the survival rate of the EA group was significantly increased, the arrhythmia score, infarction area, serum concentrations of CK, LDH and CK-Mb and plasma level of cTnT were significantly decreased. RNA-seq results showed that 725 genes were up-regulated and 861 genes were down-regulated under I/R conditions compared to the SO group; both EA and NA reversed some of these gene expression levels (592 in EA and 238 in NA group). KEGG pathway analysis indicated that these genes were involved in multiple pathways, including ECM, MAPK signaling, apoptosis, cytokine and leukocyte pathways. In addition, some pathways were uniquely regulated by EA, but not NA pretreatment, such as oxidative stress, cardiac muscle contraction, gap junction, vascular smooth muscle contraction, hypertrophic, NOD-like receptor, and P53 and B-cell receptor pathways. This study was first to reveal the gene expression signatures of acute myocardial I/R injury and electro-acupuncture pretreatment in rats.
Cyclin D1b is one of two proteins translated from cyclin D1 transcripts (isoforms a and b) that are generated due to gene polymorphism. Our previous study has reported low cyclin D1b expression in cervical cancer tissue, with an expression level in moderately or poorly differentiated tissues that was significantly lower than that in well-differentiated tissues. However, the functional role of cyclin D1b in cervical cancer remains to be elucidated. In this study, using a cervical cancer cell line with stable expression of cyclin D1b, we found that upregulation of cyclin D1b initiated cell cycle arrest at the G0/G1 phase and induced apoptosis, thereby inhibiting cell proliferation and colony formation. Furthermore, xenograft transplantation experiments in nude mice demonstrated that cyclin D1b upregulation inhibited cancer growth and induce apoptosis in vivo. In conclusion, the present study indicates anti-tumor effects of cyclin D1b in cervical cancer, suggesting that cyclin D1b may represent a potential therapeutic target for cervical cancer.
Hirschsprung's disease (HSCR) is characterized by the absence of enteric ganglion cells along variable regions of the colon. Established theory demonstrates that HSCR is the consequence caused by the abnormal arrest of the migration and differentiation of neural crest-derived stem cells (NCSCs). And retinoid signaling was considered to be involved. We speculated that, HA117, a retinoid-related transcript of a long noncoding RNA (LncRNA), may be involved in the genesis of HSCR. In current research, colon specimens were collected from 25 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Real-Time PCR was used to analyze the expression profiles of HA117 and its neighboring gene DPF3 in different colon segments. Fluorescence in situ hybridization (FISH) was employed to detect the distribution of HA117 in the gut wall. Immunohistochemistry was performed to analyze the protein expression of DPF3 in different colon segments. HA117 expression in stenotic segment was higher compared to proximal anastomosis and dilated segment (p < 0.05). Whereas DPF3b mRNA was lower in stenotic segment than that in two other segments (p < 0.05). FISH detected HA117 was distributed in mucosa and muscle layer, mainly present in stenotic segment. Immunohistochemical staining showed that intensive DPF3 staining occurred in proximal anastomosis and the positive staining was hardly observed in stenotic segment. The results suggested that HA117 may be a factor exerting an anti-differentiation or or anti-maturation role in the genesis of HSCR. This gave us a novel cue for better understanding the etiology of HSCR.
The apurinic/apyrimidinic endonuclease 1 (APE1) plays important roles in the repair of DNA damage and adducts. However, previous case-control studies on the association between the APE1 Asp148Glu polymorphism and prostate cancer susceptibility have shown contradictory results, this meta-analysis was performed to draw a more precise estimation of the relationship. A total of seven case-control studies including 1,294 cases and 1,762 controls were included for analysis. In overall, no significant associations were found in all genetic models (GG vs. TT: OR = 1.16, 95 % CI 0.89-1.52; TG vs. TT: OR = 1.04, 95 % CI 0.81-1.35; the dominant model GG + TG vs. TT: OR = 1.12, 95 % CI 0.96-1.30; the recessive model GG vs. TG + TT: OR = 0.90, 95 % CI 0.77-1.04); in the subgroup by source of control, we found a significant association for the dominant model in Hospital-based subgroup (OR = 1.34, 95 % CI 1.08-1.68), no significant associations were found in other models in the subgroups. This meta-analysis suggested that the APE1 Asp148Glu polymorphism was a risk factor for prostate cancer susceptibility in Hospital-based population.
The purpose of the study was to determine the signal transduction mechanism of cepharanthine hydrochloride (CH) on reversing tumor multidrug resistance. RT-PCR and Western blot analysis were used to determine the effects of CH on the expression of MDR1 mRNA and P-glycoprotein in K562/ADR cells when CH was used alone and combined with SP600125, a JNK inhibitor, to explore the effects of CH on JNK pathway. Western blot analysis was used to determine the effects of CH on c-Jun protein expression and phosphorylation, to explore the regulating effects of CH on c-Jun and phosphorylated c-Jun (p-c-Jun) proteins. Our results showed that the inhibitory effect of CH on MDR1 mRNA increased with the concentrations of CH (5.0, 10.0, and 20.0??M) and the inhibitory effects of CH on MDR1 mRNA and P-glycoprotein increased with the incubation time of CH (0, 12, 24, 36, and 48 hours). The inhibitory effect was weakened after CH combined with SP600125. The expressions of c-Jun and p-c-Jun proteins increased with the incubation time of CH (0, 6, 12, and 24 hours). These findings suggest that CH downregulated the expressions of MDR1 mRNA and P-glycoprotein in a time and concentration manner; the mechanism may be mediated via activating c-Jun/JNK pathway.
Limited population-based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population-based cancer registries, data from 17 registries (n?=?138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003-2005 and followed until the end of 2010. Age-standardized relative survival was calculated using region-specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age-standardized 5-year relative survival for all cancers was 30.9% (95% confidence intervals: 30.6%-31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban-rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health-care to the disadvantaged populations will be essential for reducing this disparity in the future.
Tumour-repopulating cells (TRCs) are a self-renewing, tumorigenic subpopulation of cancer cells critical in cancer progression. However, the underlying mechanisms of how TRCs maintain their self-renewing capability remain elusive. Here we show that relatively undifferentiated melanoma TRCs exhibit plasticity in Cdc42-mediated mechanical stiffening, histone 3 lysine residue 9 (H3K9) methylation, Sox2 expression and self-renewal capability. In contrast to differentiated melanoma cells, TRCs have a low level of H3K9 methylation that is unresponsive to matrix stiffness or applied forces. Silencing H3K9 methyltransferase G9a or SUV39h1 elevates the self-renewal capability of differentiated melanoma cells in a Sox2-dependent manner. Mechanistically, H3K9 methylation at the Sox2 promoter region inhibits Sox2 expression that is essential in maintaining self-renewal and tumorigenicity of TRCs both in vitro and in vivo. Taken together, our data suggest that 3D soft-fibrin-matrix-mediated cell softening, H3K9 demethylation and Sox2 gene expression are essential in regulating TRC self-renewal.
Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals) were used in the study. The key words including "cancer", "cell death", "apoptosis", "autophagy," "necrosis," and "Chinese medicine" were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future.
This paper proposes a sensorless speed control strategy for ship propulsion interior permanent magnet synchronous motor (IPMSM) based on a new sliding-mode observer (SMO). In the SMO the low-pass filter and the method of arc-tangent calculation of extended electromotive force (EMF) or phase-locked loop (PLL) technique are not used. The calculation of the rotor speed is deduced from the Lyapunov function stability analysis. In order to reduce system chattering, sigmoid functions with switching gains being adaptively updated by fuzzy logic systems are innovatively incorporated into the SMO. Finally, simulation results for a 4.088MW ship propulsion IPMSM and experimental results from a 7.5kW IPMSM drive are provided to verify the effectiveness of the proposed SMO method.
Methicillin-resistant Staphylococci (MRS), methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) have become a challenging problem in nosocomial infections and are connected with high morbidity and mortality rates. This is due to the increasing incidence of resistance to virtually all ?-lactams and a wide variety of antimicrobials. The spread of MRS severely limits therapeutic options and generates the need for novel antibiotics that are able to combat MRS infections. One method of inhibiting bacterial growth is by blocking the expression of conserved bacterial genes and provides potential new avenues for generating a new generation of antimicrobials. The mecA gene is highly conserved among Staphylococcal species, and this makes it an ideal target for antisense inhibition. We had identified a target sequence (854-871?nt) within the mecA mRNA coding region that is particularly sensitive to antisense inhibition. The anti-mecA PS-ODN04 oligonucleotide was encapsulated into an anionic liposome. MRSA01 and MRSE01 clinical strains treated with this antisense sequence became susceptible to existing ?-lactam antibiotics, and their growth was inhibited by oxacillin in vitro and in vivo. PS-ODN04 reduced the bacterial titers in the blood of mice infected with MRSA01 and MRSE01 and significantly improved their survival rate. Our data offer a possible new strategy for treating MRS infections.The Journal of Antibiotics advance online publication, 1 October 2014; doi:10.1038/ja.2014.132.
The diagnostic accuracy of cardiovascular magnetic resonance (CMR) for pulmonary hypertension (PH) compared with right heart catheterization were assessed. The purpose of this systematic review was to comprehensively evaluate the diagnostic accuracy of CMR in evaluating PH.
Large epidemiologic studies about the relationship between benzo[a]pyrene (B[a]P) and hepatocellular carcinoma (HCC) have been limited. B[a]P diol epoxide (BPDE) is a highly reactive metabolite of B[a]P that binds covalently to form DNA adducts. We evaluated the interaction between B[a]P exposure with other risk factors in HCC, in a case-control study of 345 HCC and 961 healthy controls.
Dopamine D1 receptors (D1Rs) play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphorylates the D1R at S421 and promotes its membrane localization. Moreover, this phosphorylation of S421 is required for cocaineinduced behaviors in rats. In the present study, we generated transgenic mice over-expressing S421A-D1R in the forebrain. These transgenic mice showed reduced phospho-D1R (S421) and its membrane localization, and reduced downstream ERK1/2 activation in the striatum. Importantly, acute and chronic cocaine-induced locomotor hyperactivity and conditioned place preference were significantly attenuated in these mice. These findings provide in vivo evidence for the critical role of S421 phosphorylation of the D1R in its membrane localization and in cocaine-induced behaviors. Thus, S421 on the D1R represents a potential pharmacotherapeutic target for cocaine addiction and other drug-abuse disorders.
Mitotic centromere-associated kinesin (MCAK) is a microtubule depolymerase indispensable for microtubule binding during spindle formation. The purpose of this study was to investigate the association of MCAK expression with squamous cell carcinoma of the oral tongue (SCCOT).
Assisted reproduction technology (ART) has become an attractive option for infertility treatment and holds tremendous promise. However, at present, there is still room for improvement in its success rates. Oocyte maturation is a process by which the oocyte becomes competent for fertilization and subsequent embryo development. To better understand the mechanism underlying oocyte maturation and for the future improvement of assisted reproduction technology, this review focuses on the complex processes of cytoplasmic organelles and the dynamic alterations of the cytoskeleton that occur during oocyte maturation. Ovarian stimulation and in-vitro maturation are the major techniques used in assisted reproduction technology and their influence on the organelles of oocytes is also discussed. Since the first birth by assisted reproduction treatment was achieved in 1978, numerous techniques involved in assisted reproduction have been developed and have become attractive options for infertility treatment. However, the unsatisfactory success rate remains as a main challenge. Oocyte maturation is a process by which the oocyte becomes competent for fertilization and subsequent embryo development. Oocyte maturation includes both nuclear and cytoplasmic maturation. Nuclear maturation primarily involves chromosomal segregation, which has been well studied, whereas cytoplasmic maturation involves a series of complicated processes, and there are still many parts of this process that remain controversial. Ovarian stimulation and in-vitro maturation (IVM) are the major techniques of assisted reproduction. The effect of ovarian stimulation or IVM on the behaviour of cell organelles of the oocyte has been postulated as the reason for the reduced developmental potential of in-vitro-produced embryos. To further understanding of the mechanism of oocyte maturation and future improvement of assisted reproduction treatment, the complex events of cytoplasmic organelles and the cytoskeleton that occur during oocyte maturation and the influence of ovarian stimulation and IVM on these organelles are described in this review.
Rearranged during transfection (RET) is widely expressed in neuroblastoma (NB) and partly contributes to high metastatic potential and survival of NB. The aim of the present study was to investigate whether vandetanib (a RET inhibitor) inhibits proliferation, migration and invasion of NB cells in vitro. The effects of vandetanib on the proliferation, apoptosis and cell cycle and on RET phosphorylation of SK-N-SH and SH-SY5Y cells were evaluated in vitro. The migration and invasion potential of vandetanib-treated NB cells were analyzed using Transwell cell migration and invasion assays, respectively. qPCR, western blotting and immunofluorescence were used to detect mRNA and protein levels in NB cells treated with vandetanib. Our data demonstrated that vandetanib inhibits the proliferation of SK-N-SH and SH-SY5Y cells and that this inhibition is mediated by the induction of G1 phase cell cycle arrest at lower concentrations and by apoptosis at higher concentrations. In the presence of vandetanib, the migration and invasion of two NB cell lines were markedly decreased compared with the control group (p<0.01). In addition, our data showed that the levels of C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase 14 (MMP14) mRNA expression in NB cell lines treated with vandetanib were significantly lower than those in the cells that were treated with vehicle (p<0.01) and similar results were obtained for protein levels as determined by western blotting and immunofluorescence analysis. Vandetanib may inhibit the proliferation, migration and invasion of NB cells in vitro. The potential mechanisms for the inhibition of NB migration and invasion by vandetanib may partly be attributed to the ability of vandetanib to suppress the expression of CXCR4 and MMP14 in human NB cells.
Consistent and correct condom use and suppressive antiretroviral therapy for the infected partner are two of the primary strategies recommended for prevention of heterosexual HIV transmission in serodiscordant couples today. The applied effectiveness of treatment as a prevention strategy in China is still under investigation, and much less is known about its effects in the presence of other prevention strategies such as consistent condom use.
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