Beta-endorphin (BEP) producing neuron in the hypothalamus plays a key role in brining the stress axis to a state of homeostasis and maintaining body immune defense system. Long-term delivery of BEP to obtain beneficial effect on chemoprevention is challenging, since the peptide rapidly develop tolerance. Using rats as animal model, we show here that transplantation of beta-endorphin neurons into the hypothalamus suppressed carcinogens- and hormone-induced cancers in various tissues and prevented growth and metastasis of established tumors via activation of innate immune functions. Additionally, we show that intracerebroventricular administration of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) increased the number of BEP neurons in the hypothalamus, reduced the stress response, enhanced the innate immune function and prevented tumor cell growth, progression and metastasis. Beta-endorphin neuronal supplementation did not produce any deleterious effects on general health but was beneficial in suppressing age-induced alterations in physical activity, metabolic and immune functions. We conclude that the neuroimmune system has significant control over cancer growth and progression and that activation of the neuroimmune system via beta-endorphin neuronal supplementation/induction may have therapeutic value for cancer prevention and improvement of general health.
In this work, we explore the existence of multiband localized spoof plasmons (LSPs) in closed textured cavities with multiple groove depths. It is interesting to note that the spoof LSPs in each band resemble those generated by the textured 2D cavities of the same periodicity with the corresponding single groove depth, and the field distributions and confinement characteristics of the plasmon-like modes in such a corrugated cavity are different from the conventional cavity. Hence, these multiple resonance band structures can find potential applications in the microwave and terahertz frequencies.
An imbalance between excitation and inhibition in the developing central nervous system may result in a pathophysiological outcome. We investigated the mechanistic roles of endocrine activity and ?-aminobutyric acid type A receptor (GABAAR)-mediated excitation in electroencephalographic seizures caused by the GABAAR-selective anesthetic propofol in neonatal rats.
High-pressure compression of water contained in nanoporous silica allowed fabrication of novel porous ice phases as a function of pressure. The starting liquid nanoporous H2O transformed to ice VI and VII at 1.7 and 2.5 GPa, respectively, which are 0.6 and 0.4 GPa higher than commonly accepted pressures for bulk H2O. The continuous increase of pressure drives the formation of a tetragonally distorted VII structure with the space group I4mm, rather than a cubic Pn3m phase in bulk ice. The enhanced incompressibility of the tetragonal ice is related to the unique nanoporous configuration, and the distortion ratio c/a gradually increases with increasing pressure. The structural changes and enhanced thermodynamic stability may be interpreted by the two-dimensional distribution of silanol groups on the porous silica surfaces and the associated anisotropic interactions with H2O at the interfaces.
Stimulating bone growth and regeneration, especially in patients with delayed union or non-union of bone, is a challenge for orthopaedic surgeons. Treatments employed for bone regeneration are based on the use of cells, biomaterials and factors. Among these therapies, cell treatment with mesenchymal stem cells (MSCs) has a number of advantages as MSCs: (1) are multipotent cells that can migrate to sites of injury; (2) are capable of suppressing the local immune response; and (3) are available in large quantities from the patients themselves. MSC therapies have been used for stimulating bone regeneration in animal models and in patients. Methods of application range from direct MSC injection, seeding MSCs on synthetic scaffolds, the use of gene-modified MSCs, and hetero-MSCs application. However, only a small number of these cell-based strategies are in clinical use, and none of these treatments has become the gold standard treatment for delayed or non-union of bone.
Abstract Objective: To investigate the association of caveolin-1 (CAV1) genetic variants (C239A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T29107A (rs7804372)) with esophageal squamous cell carcinoma (ESCC) susceptibility. Methods: A total of 427 patients with ESCC and 427 healthy controls were genotyped using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Results: There were significant differences between patients and controls in distributions of their genotypes and allelic frequencies in G14713A and T29107A polymorphisms. Furthermore, haplotype analysis revealed that haplotypes CAAT and CAGT were associated with high risk for ESCC, while haplotype CGGA was protective against ESCC. Stratified analysis showed the associations between the SNPs (G14713A and T29107A) and ESCC risk were noteworthy among female patients and patients who never smoke or drank alcohol. Conclusions: Genetic polymorphisms of CAV1 G14713A and T29107A might affect an individual's susceptibility in developing ESCC, making them efficient potential genetic biomarkers for early detection of ESCC.
Magnetite exhibits unique electronic, magnetic, and structural properties in extreme conditions that are of great research interest. Previous studies have suggested a number of transitional models, although the nature of magnetite at high pressure remains elusive. We have studied a highly stoichiometric magnetite using inelastic X-ray scattering, X-ray diffraction and emission, and Raman spectroscopies in diamond anvil cells up to ~20 GPa, while complementary electrical conductivity measurements were conducted in a cubic anvil cell up to 8.5 GPa. We have observed an elastic softening in the diagonal elastic constants (C11 and C44) and a hardening in the off-diagonal constant (C12) at ~8 GPa where significant elastic anisotropies in longitudinal and transverse acoustic waves occur, especially along the  direction. An additional vibrational Raman band between the A1g and T2g modes was also detected at the transition pressure. These abnormal elastic and vibrational behaviors of magnetite are attributed to the occurrence of the octahedrally-coordinated Fe(2+)-Fe(3+)-Fe(2+) ions charge-ordering along the  direction in the inverse spinel structure. We propose a new phase diagram of magnetite in which the temperature for the metal-insulator and distorted structural transitions decreases with increasing pressure while the charge-ordering transition occurs at ~8 GPa and room temperature.
Few studies have reported on the risk factors of dilated Virchow-Robin Spaces (dVRS) in large samples of ischemic stroke patients. Little evidence exists regarding the relationship between dVRS and etiologic subtype of ischemic stroke or lacune. We aimed to investigate the risk factors associated with the severity of dVRS in a large sample of ischemic stroke patients.
BackgroundDespite advancements in wound healing techniques and devices, new treatments are needed to improve therapeutic outcomes. This study aimed to evaluate the potential use of a new biomaterial engineered from human urine-derived stem cells (USCs) and polycaprolactone/gelatin (PCL/GT) for wound healing.MethodsUSCs were isolated from healthy individuals. To fabricate PCL/GT composite meshes, twin-nozzle electrospinning were used to spin the PCL and gelatin solutions in normal organic solvents. The morphologies and hydrophilicity properties of PCL/GT membranes were investigated. After USCs were seeded onto a PCL/GT, cell adhesion, morphology, proliferation, and cytotoxicity were examined. Then, USCs were seeded on a PCL/GT blend nanofibrous membrane and transplanted into rabbit full-thickness skin defects for wound repair. Finally, the effect of USCs condition medium on proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were performed in vitro.ResultsUSCs were successfully isolated from urine samples and expressed specific mesenchymal stem cells markers and could differentiate into osteoblasts, adipocytes, and chondrocytes. PCL/GT membrane has suitable mechanical properties similar with skin tissue and has good biocompatibility. USCs-PCL/GT significantly enhanced the healing of full-thickness skin wounds in rabbits compared to wounds treated with PCL/GT membrane alone or untreated wounds. USCs-PCL/GT-treated wounds closed much faster, with increased re-epithelialization, collagen formation, and angiogenesis. Moreover, USCs could secrete VEGF and TGF-ß1, and USC-conditioned medium enhanced the migration, proliferation, and tube formation of endothelial cells.ConclusionUSCs in combination with PCL/GT significantly prompted the healing of full-thickness skin wounds in rabbits. USCs based therapy provides a novel strategy for accelerating wound closure and promoting angiogenesis.
Single subcortical infarction (SSI) may be classified as proximal SSI (pSSI) or distal SSI (dSSI) according to its location within the middle cerebral artery territory. Few studies have examined the differences in clinical outcome between the two. Our study investigated such differences in patients with pSSI or dSSI and examined their baseline characteristics and indicators for small-vessel disease.
Neon hydrate was synthesized and studied by in situ neutron diffraction at 480 MPa and temperatures ranging from 260 to 70 K. For the first time to our knowledge, we demonstrate that neon atoms can be enclathrated in water molecules to form ice II-structured hydrates. The guest Ne atoms occupy the centers of D2O channels and have substantial freedom of movement owing to the lack of direct bonding between guest molecules and host lattices. Molecular dynamics simulation confirms that the resolved structure where Ne dissolved in ice II is thermodynamically stable at 480 MPa and 260 K. The density distributions indicate that the vibration of Ne atoms is mainly in planes perpendicular to D2O channels, whereas their distributions along the channels are further constrained by interactions between adjacent Ne atoms.
Background. Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool. Methods. Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol. Results. IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, ?-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro. Conclusion. Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.
Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well-known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mm lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3? (GSK-3?) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK-3? activity, ?-catenin accumulation and Wnt pathway activation. Utilizing a specific GSK-3? inhibitor SB216763 or siRNA-mediated inhibition of GSK-3? produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the ?-catenin/TCF pathway, or siRNA-mediated knockdown of ?-catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK-3?-dependent ?-catenin/Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from ?-catenin/Wnt pathway suppression.
One of the common features of unconventional superconducting systems such as the heavy-fermion, high transition-temperature cuprate and iron-pnictide superconductors is that the superconductivity emerges in the vicinity of long-range antiferromagnetically ordered state. In addition to doping charge carriers, the application of external pressure is an effective and clean approach to induce unconventional superconductivity near a magnetic quantum critical point. Here we report on the discovery of superconductivity on the verge of antiferromagnetic order in CrAs via the application of external pressure. Bulk superconductivity with Tc?2?K emerges at the critical pressure Pc?8?kbar, where the first-order antiferromagnetic transition at TN?265?K under ambient pressure is completely suppressed. The close proximity of superconductivity to an antiferromagnetic order suggests an unconventional pairing mechanism for CrAs. The present finding opens a new avenue for searching novel superconductors in the Cr and other transition metal-based systems.
This study is aimed to evaluate the effects of Psoraleae fructus (PF) on Th2 responses in a rat model of asthma in vivo and psoralen, a major constituent in PF, on Th2 responses in vitro. A rat model of asthma was established by sensitization and challenged with ovalbumin (OVA). Airway hyperresponsiveness was detected by direct airway resistance analysis. Lung tissues were examined for cell infiltration and mucus hypersecretion. Bronchoalveolar lavage fluid (BALF) was assessed for cytokine levels. In vitro study, Th2 cytokine production was evaluated in the culture supernatant of D10.G4.1 (D10 cells) followed by the determination of cell viability, meanwhile Th2 transcription factor GATA-3 expression in D10 cells was also determined. The oral administration of PF significantly reduced airway hyperresponsiveness (AHR) to aerosolized methacholine and decreased IL-4 and IL-13 levels in the BALF. Histological studies showed that PF markedly inhibited inflammatory infiltration and mucus secretion in the lung tissues. In vitro study, psoralen significantly suppressed Th2 cytokines of IL-4, IL-5 and IL-13 by ConA-stimulated D10 cells without inhibitory effect on cell viability. Furthermore, GATA-3 protein expression was also markedly reduced by psoralen. This study demonstrated that PF exhibited inhibitory effects on hyperresponsiveness and airway inflammation in a rat model of asthma, which was associated with the suppression of Th2 response. Psoralen, a major constituent of PF, has immunomodulatory properties on Th2 response in vitro, which indicated that psoralen might be a critical component of PF for its therapeutic effects.
Carbon monoxide clathrate hydrate is a potentially important constituent in the solar system. In contrast to the well-established relation between the size of gaseous molecule and hydrate structure, previous work showed that carbon monoxide molecules preferentially form structure-I rather than structure-II gas hydrate. Resolving this discrepancy is fundamentally important to understanding clathrate formation, structure stabilization and the role the dipole moment/molecular polarizability plays in these processes. Here we report the synthesis of structure-II carbon monoxide hydrate under moderate high-pressure/low-temperature conditions. We demonstrate that the relative stability between structure-I and structure-II hydrates is primarily determined by kinetically controlled cage filling and associated binding energies. Within hexakaidecahedral cage, molecular dynamic simulations of density distributions reveal eight low-energy wells forming a cubic geometry in favour of the occupancy of carbon monoxide molecules, suggesting that the carbon monoxide-water and carbon monoxide-carbon monoxide interactions with adjacent cages provide a significant source of stability for the structure-II clathrate framework.
Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke.
Early-life ethanol feeding (ELAF) alters the metabolic function of proopiomelanocortin (POMC)-producing neurons and the circadian expression of clock regulatory genes in the hypothalamus. We investigated whether the circadian mechanisms control the action of ELAF on metabolic signaling genes in POMC neurons. Gene expression measurements of Pomc and a selected group of metabolic signaling genes, Stat3, Sirt1, Pgc1-?, and Asb4 in laser-captured microdissected POMC neurons in the hypothalamus of POMC-enhanced green fluorescent protein mice showed circadian oscillations under light/dark and constant darkness conditions. Ethanol programmed these neurons such that the adult expression of Pomc, Stat3, Sirt, and Asb4 gene transcripts became arrhythmic. In addition, ELAF dampened the circadian peak of gene expression of Bmal1, Per1, and Per2 in POMC neurons. We crossed Per2 mutant mice with transgenic POMC-enhanced green fluorescent protein mice to determine the role of circadian mechanism in ELAF-altered metabolic signaling in POMC neurons. We found that ELAF failed to alter arrhythmic expression of most circadian genes, with the exception of the Bmal1 gene and metabolic signaling regulating genes in Per2 mutant mice. Comparison of the ELAF effects on the circadian blood glucose in wild-type and Per2 mutant mice revealed that ELAF dampened the circadian peak of glucose, whereas the Per2 mutation shifted the circadian cycle and prevented the ELAF dampening of the glucose peak. These data suggest the possibility that the Per2 gene mutation may regulate the ethanol actions on Pomc and the metabolic signaling genes in POMC neurons in the hypothalamus by blocking circadian mechanisms.
Counting of E. coli DH5? cell suspensions in phosphate buffered saline is performed using a micro-flow cytometer based on a photonic-microfluidic integrated device. Side-scattered light signals are used to count the E. coli cells. A detection efficiency of 92% is achieved when compared with the expected count from a haemocytometer. The detection efficiency is correlated to the ratio of sample to sheath flow rates. It is demonstrated that E. coli can be easily distinguished from beads of similar sizes (2-4?m) as their scattering intensities are different. This article is protected by copyright. All rights reserved.
Vanadium dioxide (VO2) with its unique sharp resistivity change at the metal-insulator transition (MIT) has been extensively considered for the near-future terahertz/infrared devices and energy harvesting systems. Controlling the epitaxial quality and microstructures of vanadium dioxide thin films and understanding the metal-insulator transition behaviors are therefore critical to novel device development. The metal-insulator transition behaviors of the epitaxial vanadium dioxide thin films deposited on Al2O3 (0001) substrates were systematically studied by characterizing the temperature dependency of both Raman spectrum and Fourier transform infrared spectroscopy. Our findings on the correlation between the nucleation dynamics of intermediate monoclinic (M2) phase with microstructures will open a new avenue for the design and integration of advanced heterostructures with controllable multifunctionalities for sensing and imaging system applications.
Proximal humeral fractures are common lesions of the elderly, but there are no established treatment guidelines. A surgical treatment for comminuted and displaced fractures of the proximal humerus was developed and is still evolving. The aim of this study was to perform a quantitative review to evaluate the risk of avascular necrosis (AVN) in patients with proximal humeral fractures who were treated by operative fixation compared with conservative treatment.
Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of the hypothalamic-pituitary-adrenal (HPA) axis, immune functions, and energy homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene expression, a decrement in the levels of its derived peptide ?-endorphin and a dysregulation of the stress response in the adult offspring. The HPA axis is a major neuroendocrine system with pivotal physiological functions and mode of regulation. This system has been shown to be perturbed by prenatal alcohol exposure. It has been demonstrated that the perturbation of the HPA axis by FAE is long-lasting and is linked to molecular, neurophysiological, and behavioral changes in exposed individuals. Recently, we showed that the dysregulation of the POMC system function by FAE is induced by epigenetic mechanisms such as hypermethylation of Pomc gene promoter and an alteration in histone marks in POMC neurons. This developmental programming of the POMC system by FAE altered the transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood. These long-lasting epigenetic changes influenced subsequent generations via the male germline. We also demonstrated that the epigenetic programming of the POMC system by FAE was reversed in adulthood with the application of the inhibitors of DNA methylation or histone modifications. Thus, prenatal environmental influences, such as alcohol exposure, could epigenetically modulate POMC neuronal circuits and function to shape adult behavioral patterns. Identifying specific epigenetic factors in hypothalamic POMC neurons that are modulated by fetal alcohol and target Pomc gene could be potentially useful for the development of new therapeutic approaches to treat stress-related diseases in patients with fetal alcohol spectrum disorders.
The transition from liver fibrosis to hepatocellular carcinoma (HCC) has been suggested to be a continuous and developmental pathological process. MicroRNAs (miRNAs) are recently discovered molecules that regulate the expression of genes involved in liver disease. Many reports demonstrate that miR-483-5p and miR-483-3p, which originate from miR-483, are up-regulated in HCC, and their oncogenic targets have been identified. However, recent studies have suggested that miR-483-5p/3p is partially down-regulated in HCC samples and is down-regulated in rat liver fibrosis. Therefore, the aberrant expression and function of miR-483 in liver fibrosis remains elusive. In this study, we demonstrate that overexpression of miR-483 in vivo inhibits mouse liver fibrosis induced by CCl4 . We demonstrate that miR-483-5p/3p acts together to target two pro-fibrosis factors, platelet-derived growth factor-? and tissue inhibitor of metalloproteinase 2, which suppress the activation of hepatic stellate cells (HSC) LX-2. Our work identifies the pathway that regulates liver fibrosis by inhibiting the activation of HSCs.
Biochemical substances relating to renal and hepatic function are influenced not only by individual factors such as gender, lifestyle, and age but also by ecological factors, such as altitude, climate, and ethnic background. The purpose of the present study was to establish reference intervals for 16 biochemical substances relating to renal and hepatic function in healthy Chinese adults.
This meta-analysis aimed to compare the therapeutic effect of mini-plate versus Kirschner wire (K-wire) internal fixation on the treatment of metacarpal and phalangeal fractures among Chinese Han population.
Platelet-rich plasma (PRP) is an autologous concentrated cocktail of growth factors and inflammatory mediators, and has been considered to be potentially effective for cartilage repair. In addition, the fibrinogen in PRP may be activated to form a fibrin matrix to fill cartilage lesions, fulfilling the initial requirements of physiological wound healing. The anabolic, anti-inflammatory and scaffolding effects of PRP based on laboratory investigations, animal studies, and clinical trials are reviewed here. In vitro, PRP is found to stimulate cell proliferation and cartilaginous matrix production by chondrocytes and adult mesenchymal stem cells (MSCs), enhance matrix secretion by synoviocytes, mitigate IL-1?-induced inflammation, and provide a favorable substrate for MSCs. In preclinical studies, PRP has been used either as a gel to fill cartilage defects with variable results, or to slow the progression of arthritis in animal models with positive outcomes. Findings from current clinical trials suggest that PRP may have the potential to fill cartilage defects to enhance cartilage repair, attenuate symptoms of osteoarthritis and improve joint function, with an acceptable safety profile. Although current evidence appears to favor PRP over hyaluronan for the treatment of osteoarthritis, the efficacy of PRP therapy remains unpredictable owing to the highly heterogeneous nature of reported studies and the variable composition of the PRP preparations. Future studies are critical to elucidate the functional activity of individual PRP components in modulating specific pathogenic mechanisms.
The purpose of this study was to evaluate the repair effects of chondrocytes that were cultured in vitro on osteoarthritis (OA). Chondrocytes were isolated from fetal rabbits and cultured in Biosilon microcarriers. Sixty rabbits were randomly divided into three groups equally (blank group, model group, treatment group). The rabbit knee OA model was established by inducing papain. Rabbits in the treatment group were injected with the chondrocytes that were cultured in vitro. Hematoxylin-eosin (HE) staining and gross morphologic observation were conducted. Expression level of cytokines such as IL-1b?, IL-6, and TNF-? in cartilage synovial cells was also analyzed by an ELISA assay. The cultured chondrocyte was validated by a positive stain of type II collagen and vimentin by immunofluorescence. Compared to the model group, the articular cartilage of the rabbit knee in the treatment group showed a normal color, smooth surface, and none of malacia and coloboma. HE staining indicated that the articular surface of the treatment group tended to be smooth and flat; the matrix stained tinge and the cartilage destruction and fiber hyperplasia of the synovia were lightened. The expression levels of IL-1b?, IL-6, and TNF-? also declined in the treatment group. OA symptoms were improved by treating with chondrocytes. In summary, the animal experiment in the present study indicated that chondrocyte injection played an active effect on renovation of OA.
The present study investigated enhancement of apoptosis induction and the mechanisms underlying calcium overload on C6 glioma cells in vitro, stimulated by low-level ultrasound in combination with hematoporphyrin monomethyl ether (HMME). The optimum frequency of ultrasound was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The apoptotic rate, reactive oxygen species concentration and decreased mitochondrial membrane potential (MMP) were analyzed by flow cytometry. Morphological changes were detected by a transmission electron microscope, and the concentration of intracellular Ca(2+), [Ca(2+)]i, was detected by a confocal laser scanning microscope. In addition, the release of cytochrome c (cyt-c) was measured by western blot analysis. The results revealed that an increased apoptotic effect was induced by sonodynamic therapy (SDT), and this was found to correlate with the overloaded [Ca(2+)]i, derived from the intra- and extracellular sources in the early apoptotic process. The results also revealed an increased level of ROS production, a decreased MMP and an increased release of cyt-c. The present study indicated that low-level ultrasound in combination with HMME improved the apoptotic effect in C6 glioma cells. The overloaded [Ca(2+)]i was involved in the mechanism by which apoptosis was stimulated and enhanced by SDT.
Osteomyelitis (bone infection) is often difficult to cure. The commonly-used treatment of surgical debridement to remove the infected bone combined with prolonged systemic and local antibiotic treatment has limitations. In the present study, an injectable borate bioactive glass cement was developed as a carrier for the antibiotic vancomycin, characterized in vitro, and evaluated for its capacity to cure osteomyelitis in a rabbit tibial model. The cement (initial setting time = 5.8 ± 0.6 min; compressive strength = 25.6 ± 0.3 MPa) released vancomycin over ~25 days in phosphate-buffered saline, during which time the borate glass converted to hydroxyapatite (HA). When implanted in rabbit tibial defects infected with methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis, the vancomycin-loaded cement converted to HA and supported new bone formation in the defects within 8 weeks. Osteomyelitis was cured in 87 % of the defects implanted with the vancomycin-loaded borate glass cement, compared to 71 % for the defects implanted with vancomycin-loaded calcium sulfate cement. The injectable borate bioactive glass cement developed in this study is a promising treatment for curing osteomyelitis and for regenerating bone in the defects following cure of the infection.
Rose (Rosa hybrida) is one of the most important ornamental plants worldwide; however, senescence of its petals terminates the ornamental value of the flower, resulting in major economic loss. It is known that the hormones abscisic acid (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the process. However, the molecular mechanisms underlying the antagonistic effects amongst plant hormones during petal senescence are still unclear. Here we isolated RhHB1, a homeodomain-leucine zipper I transcription factor gene, from rose flowers. Quantitative RT-PCR and GUS reporter analyses showed that RhHB1 was strongly expressed in senescing petals, and its expression was induced by ABA or ethylene in petals. ABA or ethylene treatment clearly accelerated rose petal senescence, while application of the gibberellin GA3 delayed the process. However, silencing of RhHB1 delayed the ABA- or ethylene-mediated senescence, and resulted in higher petal anthocyanin levels and lower expression of RhSAG12. Moreover, treatment with paclobutrazol, an inhibitor of GA biosynthesis, repressed these delays. In addition, silencing of RhHB1 blocked the ABA- or ethylene-induced reduction in expression of the GA20 oxidase encoded by RhGA20ox1, a gene in the GA biosynthetic pathway. Furthermore, RhHB1 directly binds to the RhGA20ox1 promoter, and silencing of RhGA20ox1 promoted petal senescence. Eight senescence-related genes showed substantial differences in expression in petals after treatment with GA3 or paclobutrazol. These results suggest that RhHB1 mediates the antagonistic effect of GAs on ABA and ethylene during rose petal senescence, and that the promotion of petal senescence by ABA or ethylene operates through an RhHB1-RhGA20ox1 regulatory checkpoint.
Three-dimensional porous scaffolds of a borosilicate bioactive glass (designated 13-93B1), with the composition 6Na2O-8K2O-8MgO-22CaO-18B2O3-36SiO2-2P2O5 (mol%), were prepared using a foam replication technique and evaluated in vitro and in vivo. Immersion of the scaffolds for 30 days in a simulated body fluid in vitro resulted in partial conversion of the glass to a porous hydroxyapatite composed of fine needle-like particles. The capacity of the scaffolds to support bone formation in vivo was evaluated in non-critical sized defects created in the femoral head of rabbits. Eight weeks post-implantation, the scaffolds were partially converted to hydroxyapatite, and they were well integrated with newly-formed bone. When loaded with platelet-rich plasma (PRP), the scaffolds supported bone regeneration in segmental defects in the diaphysis of rabbit radii. The results indicate that these 13-93B1 scaffolds, loaded with PRP or without PRP, are beneficial for bone repair due to their biocompatibility, conversion to hydroxyapatite, and in vivo bone regenerative properties.
Materials with zero/near zero thermal expansion coefficients are technologically important for applications in thermal management and engineering. To date, this class of materials can only be produced by chemical routes, either by changing chemical compositions or by composting materials with positive and negative thermal expansion. Here, we report for the first time a physical route to achieve near zero thermal expansion through application of pressure. In the stability field of tetragonal PbTiO3 we observed pressure-induced reversals between thermal contraction and expansion between ambient pressure and 0.9 GPa. This hybrid behavior leads to a mathematically infinite number of crossover points in the pressure-volume-temperature space and near-zero thermal expansion coefficients comparable to or even smaller than those attained by chemical routes. The observed pressures for this unusual phenomenon are within a small range of 0.1-0.9 GPa, potentially feasible for designing stress-engineered materials, such as thin films and nano-crystals, for thermal management applications.
Ornithine decarboxylase (ODC) is the first rate-limiting enzyme in polyamine biosynthesis, which is essential for cell survival. We hypothesized that the ODC/polyamine system is involved in ischemic preconditioning (IPC)-mediated cardioprotection through the activation of Erk1/2 and Akt and through the inhibition of the mitochondrial permeability transition (mPT). Isolated rat hearts were subjected to 40 min of ischemia either with or without IPC (3 cycles of 5-min global ischemia), and ODC protein expression, polyamine content, and Akt and Erk1/2 phosphorylation were evaluated after 30 min of reperfusion. IPC significantly upregulated the ODC/polyamine pathway, promoted Erk1/2 and Akt phosphorylation, and reduced the infarct size and heart dysfunction after reperfusion. An inhibitor of ODC, ?-difluoromethylornithine (DFMO), abolished the IPC-induced cardioprotection. Moreover, the inhibition of the IPC-induced activation of Erk1/2 and Akt using PD98059 or wortmannin downregulated the ODC/polyamine system. In separate studies, the Ca(2+) load required to open the mPT pore was significantly lower in DFMO-treated cardiac mitochondria than in mitochondria from IPC hearts. Furthermore, spermine or spermidine significantly inhibited the mPT induced by CaCl2. These results suggest that IPC upregulates the ODC/polyamine system and mediates preconditioning cardioprotection, which may depend on the phosphorylation/activation of Erk1/2 and Akt and on the inhibition of the mPT during reperfusion.
In this study, 10 grapevine (Vitis vinifera) SR/CAMTA (Signal Responsive/Calmodulin-binding Transcription Activators) gene models were identified from three grapevine genome protein datasets. They belong to four gene groups: VvCAMTA1, VvCAMTA3, VvCAMTA4 and VvCAMTA5, which were located on chromosome 5, 7_random, 1 and 5, respectively. Alternative splicing could explain the multiple gene models in one gene group. Subcellular localization using the WoLF tool showed that most of the VvCAMTAs were located in the nucleus, except for VvCAMTA3.1, VvCAMTA3.2 and VvCAMTA5.2, which were located in the chloroplast, chloroplast and cytosol, respectively. Subcellular localization using TargetP showed that most of the VvCAMTAs were not located in the chloroplast, mitochondrion and secretory pathway in cells. VvCAMTA1.1 and VvCAMTA1.2 were located in the mitochondria. The digital gene expression profile showed that VvCAMTAs play important roles in Ca2+ signal transduction. The gene expression patterns of VvCAMTAs were different; for example, VvCAMTA1 was expressed mainly in the bud, while VvCAMTA3 was expressed mainly in fruit and inflorescence, with low expression in the bud. The results of this study make a substantial contribution to our knowledge concerning genes, genome annotation, and cell signal transduction in grapevine.
Evidence shows that psychosocial stress exacerbates asthma, but there is little intervention to alleviate negative effects of psychosocial stress on asthma. We investigated the role of icariin in anti-inflammation and anti-anxiety potential in a murine model combined psychosocial stress with allergic exposure. The results indicated that icariin administered remarkable increased activity in the center of the open field, reversed airway hyperresponsivenesss, reduced inflammatory cytokine infiltration to the lung and whole body and also in part recovered glucocorticoid responsiveness. Furthermore, our data also showed that icariin significantly inhibited increases of corticosterone and markedly increased glucocorticoid receptor mRNA and protein expression in the lungs of mice exposed to both stress and allergen. Collectively, we speculate that inducing glucocorticoid receptor modulation might be the potential mechanisms of icariin to facilitate corticosteroid responsiveness of cytokine production.
The physiological and pathological roles of dopamine D2 receptors (DR2) in the regulation of cardiovacular functions have been recognized. DR2 activation protects hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and apoptosis, and ischemic post-conditioning (PC) plays a critical role in cardioprotection as well; however the involvement of the DR2 activation in the PC-induced cardioprotection is unknown. In the present study, we found that the H/R increased the expressions of DR2 mRNA and protein in cardiomyocytes, which were significantly enhanced by PC. Bromocriptine (Bro, a DR2 agonist) further increased DR2 expression, but Haloperidol (Hal, a DR2 antagonist) reversed the Bro-induced DR2 expressions. PC protected against H/R-induced apoptosis, the rise of [Ca(2+)]i, the expressions of cleaved caspase-3 and -9, release of cytochrome c, and mPTP opening. In addition, PC counteracted the reduction of cell viability caused by H/R, increased the phosphorylation of ERK1/2, PI3K, Akt, GSK-3? and mitochondrial membrane potential. PC further increased Bcl-2 expression, promoted PKC-? translocation to cell membrane, and activated the mitochondrial ATP-sensitive K channels (mKATP). Bro further enhanced the cardioprotective roles of PC, but Hal reversed these effects of Bro. Meanwhile, we found that DR2 was expressed in cell membrane and interacted with PKC-? in PC. In conclusion, these results suggest that PC attenuates cardiomyocyte apoptosis via inhibition of mPTP opening by DR2-mediated activation of ERK1/2, PI3K-Akt-GSK-3? and PKC-?-mKATP. These findings provide a novel target for the treatment of ischemic cardiomyopathy.
The purpose of this study was to identify the feature genes that are associated with non-union skeletal fractures using samples of normal union and non-union skeletal fracture microarray data. The gene expression profile GSE494 was downloaded from the Gene Expression Omnibus database and included 12 samples based on three different platforms (GPL92, GPL93 and GPL8300). Each of the platforms had four sets of expression data, two from normal union skeletal fracture samples and two from non-union skeletal fracture samples. The differentially expressed genes within the three platforms of expression data were identified using packages in R language and the differentially expressed genes common to the three platforms were selected. The selected common differentially expressed genes were further analyzed using bioinformatic methods. The software HitPredict was used to search interactions of the common differentially expressed genes and then FuncAssociate was used to conduct a functional analysis of the genes in the interaction network. Further, the associated pathways were identified using the software WebGestalt. Under the three different platforms, GPL92, GPL93 and GPL8300, the numbers of differentially expressed genes identified were 531, 418 and 914, respectively. The common gene CLU and its interacting genes were most significantly associated with the regulation of sterol transport and the osteoclast differentiation pathway. Upregulation of the gene CLU was identified by comparing data for normal union and non-union skeletal fracture samples. According to the function of CLU and its interacting genes, it was concluded that they inhibit the normal healing process following a fracture, and result in non-union skeletal fractures through the regulation of sterol transport and the pathways of differentiation in osteoclasts.
To determine if objective evidence of autonomic dysfunction exists from a group of Gulf War veterans with self-reported post-exertional fatigue, we evaluated 16 Gulf War ill veterans and 12 Gulf War controls. Participants of the ill group had self- reported, unexplained chronic post-exertional fatigue and the illness symptoms had persisted for years until the current clinical study. The controls had no self-reported post-exertional fatigue either at the time of initial survey nor at the time of the current study. We intended to identify clinical autonomic disorders using autonomic and neurophysiologic testing in the clinical context. We compared the autonomic measures between the 2 groups on cardiovascular function at both baseline and head-up tilt, and sudomotor function. We identified 1 participant with orthostatic hypotension, 1 posture orthostatic tachycardia syndrome, 2 distal small fiber neuropathy, and 1 length dependent distal neuropathy affecting both large and small fiber in the ill group; whereas none of above definable diagnoses was noted in the controls. The ill group had a significantly higher baseline heart rate compared to controls. Compound autonomic scoring scale showed a significant higher score (95% CI of mean: 1.72-2.67) among ill group compared to controls (0.58-1.59). We conclude that objective autonomic testing is necessary for the evaluation of self-reported, unexplained post-exertional fatigue among some Gulf War veterans with multi-symptom illnesses. Our observation that ill veterans with self-reported post-exertional fatigue had objective autonomic measures that were worse than controls warrants validation in a larger clinical series.
Colony-stimulating factor 1 (CSF1) is known to promote osteoclast progenitor survival, but its roles in osteoclast differentiation and mature osteoclast function are less well understood. In a microarray screen, Jun dimerization protein 2 (JDP2) was identified as significantly induced by CSF1. Recent reports indicate that JDP2 is required for normal osteoclastogenesis and skeletal metabolism. Because there are no reports on the transcriptional regulation of this gene, the DNA sequence from -2612 to +682 bp (relative to the transcription start site) of the JDP2 gene was cloned, and promoter activity was analyzed. The T box-binding element (TBE) between -191 and -141 bp was identified as the cis-element responsible for CSF1-dependent JDP2 expression. Using degenerate PCR, Tbx3 was identified as the major isoform binding the TBE. Overexpression of Tbx3 induced JDP2 promoter activity, whereas suppressing Tbx3 expression substantially attenuated CSF1-induced transcription. Suppressing Tbx3 in osteoclast precursors reduced JDP2 expression and significantly impaired RANKL/CSF1-induced osteoclastogenesis. A MEK1/2-specific inhibitor was found to block CSF1-induced JDP2 expression. Consistent with these data, JDP2(-/-) mice were found to have increased bone mass. In summary, CSF1 up-regulates JDP2 expression by inducing Tbx3 binding to the JDP2 promoter. The downstream signaling cascade from activated c-Fms involves the MEK1/2-ERK1/2 pathway. Tbx3 plays an important role in osteoclastogenesis at least in part by regulating CSF1-dependent expression of JDP2.
Molybdenum disulphide is a layered transition metal dichalcogenide that has recently raised considerable interest due to its unique semiconducting and opto-electronic properties. Although several theoretical studies have suggested an electronic phase transition in molybdenum disulphide, there has been a lack of experimental evidence. Here we report comprehensive studies on the pressure-dependent electronic, vibrational, optical and structural properties of multilayered molybdenum disulphide up to 35?GPa. Our experimental results reveal a structural lattice distortion followed by an electronic transition from a semiconducting to metallic state at ~19?GPa, which is confirmed by ab initio calculations. The metallization arises from the overlap of the valance and conduction bands owing to sulphur-sulphur interactions as the interlayer spacing reduces. The electronic transition affords modulation of the opto-electronic gain in molybdenum disulphide. This pressure-tuned behaviour can enable the development of novel devices with multiple phenomena involving the strong coupling of the mechanical, electrical and optical properties of layered nanomaterials.
In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ?170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells' proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration.
The discovery of induced pluripotent stem cells (iPSCs) rendered the reprogramming of terminally differentiated cells to primary stem cells with pluripotency possible and provided potential for the regeneration and restoration of cartilage defect. Chondrogenic differentiation of iPSCs is crucial for their application in cartilage tissue engineering. In this study we investigated the effect of 3D nanofibrous scaffolds on the chondrogenesis of iPSCs and articular cartilage defect restoration. Super-hydrophilic and durable mechanic polycaprolactone (PCL)/gelatin scaffolds were fabricated using two separate electrospinning processes. The morphological structure and mechanical properties of the scaffolds were characterized. The chondrogenesis of the iPSCs in vitro and the restoration of the cartilage defect was investigated using scanning electron microscopy (SEM), the Cell Counting Kit-8 (CCK-8), histological observation, RT-qPCR, and western blot analysis. iPSCs on the scaffolds expressed higher levels of chondrogenic markers than the control group. In an animal model, cartilage defects implanted with the scaffold-cell complex exhibited an enhanced gross appearance and histological improvements, higher cartilage-specific gene expression and protein levels, as well as subchondral bone regeneration. Therefore, we showed scaffolds with a 3D nanofibrous structure enhanced the chondrogenesis of iPSCs and that iPSC-containing scaffolds improved the restoration of cartilage defects to a greater degree than did scaffolds alone in vivo.
Plant transcription factors involved in stress responses are generally classified by their involvement in either the abscisic acid (ABA)-dependent or the ABA-independent regulatory pathways. A stress-associated NAC gene from rose (Rosa hybrida), RhNAC3, was previously found to increase dehydration tolerance in both rose and Arabidopsis. However, the regulatory mechanism involved in RhNAC3 action is still not fully understood. In this study, we isolated and analyzed the upstream regulatory sequence of RhNAC3 and found many stress-related cis-elements to be present in the promoter, with five ABA-responsive element (ABRE) motifs being of particular interest. Characterization of Arabidopsis thaliana plants transformed with the putative RhNAC3 promoter sequence fused to the ?-glucuronidase (GUS) reporter gene revealed that RhNAC3 is expressed at high basal levels in leaf guard cells and in vascular tissues. Moreover, the ABRE motifs in the RhNAC3 promoter were observed to have a cumulative effect on the transcriptional activity of this gene both in the presence and absence of exogenous ABA. Overexpression of RhNAC3 in A. thaliana resulted in ABA hypersensitivity during seed germination and promoted leaf closure after ABA or drought treatments. Additionally, the expression of 11 ABA-responsive genes was induced to a greater degree by dehydration in the transgenic plants overexpressing RhNAC3 than control lines transformed with the vector alone. Further analysis revealed that all these genes contain NAC binding cis-elements in their promoter regions, and RhNAC3 was found to partially bind to these putative NAC recognition sites. We further found that of 219 A. thaliana genes previously shown by microarray analysis to be regulated by heterologous overexpression RhNAC3, 85 are responsive to ABA. In rose, the expression of genes downstream of the ABA-signaling pathways was also repressed in RhNAC3-silenced petals. Taken together, we propose that the rose RhNAC3 protein could mediate ABA signaling both in rose and in A. thaliana.
Platelet-rich plasma (PRP) has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA) concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1? concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1? level in the P-PRP group was lower than in the HA group (p<0.01) and in the control group (p<0.01). The restoration of the defected cartilage as well as the subchondral bone was better in the P-PRP group than in the HA group or the control group (P<0.05). Our data showed that P-PRP is better than HA in promoting the restoration of the cartilage and alleviating the arthritis caused by cartilage damage.
While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%). No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma.
In plants, many trans-acting small interfering RNA (ta-siRNA) regulatory pathways have been identified as significant components of the gene networks involved in development, metabolism, responses to biotic and abiotic stresses, and DNA methylation at the TAS locus. To obtain a more comprehensive understanding on the nature of ta-siRNA regulatory pathways, we developed a freely accessible resource, tasiRNAdb, to serve as a repository for the sequences of ta-siRNA regulatory pathway-related microRNAs, TASs, ta-siRNAs, and ta-siRNA targets, and for the cascading relations among them. With 583 pathways from 18 species, tasiRNAdb is the largest resource for known ta-siRNA regulatory pathways currently available. tasiRNAdb also provides a tool named TasExpAnalysis that was developed to map user-submitted small RNA and degradome libraries to a stored/input TAS and to perform sRNA phasing analysis and TAS cleavage analysis.
Perovskite oxides ABO3 are important materials used as components in electronic devices. The highly compact crystal structure consists of a framework of corner-shared BO6 octahedra enclosing the A-site cations. Because of these structural features, forming a strong bond between A and B cations is highly unlikely and has not been reported in the literature. Here we report a pressure-induced first-order transition in PbRuO3 from a common orthorhombic phase (Pbnm) to an orthorhombic phase (Pbn21) at 32 GPa by using synchrotron X-ray diffraction. This transition has been further verified with resistivity measurements and Raman spectra under high pressure. In contrast to most well-studied perovskites under high pressure, the Pbn21 phase of PbRuO3 stabilized at high pressure is a polar perovskite. More interestingly, the Pbn21 phase has the most distorted octahedra and a shortest Pb-Ru bond length relative to the average Pb-Ru bond length that has ever been reported in a perovskite structure. We have also simulated the behavior of the PbRuO3 perovskite under high pressure by first principles calculations. The calculated critical pressure for the phase transition and evolution of lattice parameters under pressure match the experimental results quantitatively. Our calculations also reveal that the hybridization between a Ru:t2g orbital and an sp hybrid on Pb increases dramatically in the Pbnm phase under pressure. This pressure-induced change destabilizes the Pbnm phase to give a phase transition to the Pbn21 phase where electrons in the overlapping orbitals form bonding and antibonding states along the shortest Ru-Pb direction at P > Pc.
The recent discovery of iron ferropnictide superconductors has received intensive concern in connection with magnetically involved superconductors. Prominent features of ferropnictide superconductors are becoming apparent: the parent compounds exhibit an antiferromagnetic ordered spin density wave (SDW) state, the magnetic-phase transition is always accompanied by a crystal structural transition, and superconductivity can be induced by suppressing the SDW phase via either chemical doping or applied external pressure to the parent state. These features generated considerable interest in the interplay between magnetism and structure in chemically doped samples, showing crystal structure transitions always precede or coincide with magnetic transition. Pressure-tuned transition, on the other hand, would be more straightforward to superconducting mechanism studies because there are no disorder effects caused by chemical doping; however, remarkably little is known about the interplay in the parent compounds under controlled pressure due to the experimental challenge of in situ measuring both of magnetic and crystal structure evolution at high pressure and low temperatures. Here we show from combined synchrotron Mössbauer and X-ray diffraction at high pressures that the magnetic ordering surprisingly precedes the structural transition at high pressures in the parent compound BaFe2As2, in sharp contrast to the chemical-doping case. The results can be well understood in terms of the spin fluctuations in the emerging nematic phase before the long-range magnetic order that sheds light on understanding how the parent compound evolves from a SDW state to a superconducting phase, a key scientific inquiry of iron-based superconductors.
A flash lamp pumped Cr,Er:YSGG laser utilizing a langasite (LGS) crystal as an electro-optic Q-switch is proposed and demonstrated. It is proved that a LGS crystal with relatively high damage threshold can be used as the electro-optic Q-switch at 2.79 ?m, and 216 mJ pulse energy with 14.36 ns pulse width is achieved. Its corresponding peak power of pulse can reach 15 MW, to our knowledge the best result at a 2.79 ?m wavelength.
Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.
There are several studies published to assess the associations of murine double minute 2 (MDM2) genetic polymorphisms with risk of malignant bone tumors, but they reported contradictory results and failed to confirm a strong and consistent association. To assess the evidence regarding the associations of MDM2 genetic polymorphisms with the risk of malignant bone tumors, we conducted a meta-analysis of epidemiological studies. The pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) was used to assess these possible associations. Four studies with a total of 3,958 individuals were finally included the meta-analysis. Meta-analysis of two studies on MDM2 SNP309 polymorphism showed that MDM2 SNP309 polymorphism was associated with an increased risk of malignant bone tumors (G versus T: OR?=?1.72, 95 % CI 1.35-2.20, P?0.001; GG versus TT: OR?=?2.64, 95 % CI 1.59-4.39, P?0.001; GG/GT versus TT: OR?=?1.87, 95 % CI 1.33-2.62, P?0.001; GG versus TT/GT: OR?=?2.20, 95 % CI 1.38-3.51, P?=?0.001). Meta-analysis of those two studies on MDM2 rs1690916 polymorphism showed that MDM2 rs1690916 minor allele A was associated with decreased risk of malignant bone tumors (OR?=?0.60, 95 % CI 0.46-0.77, P?0.001). Meta-analyses of available data show that there are significant associations of MDM2 SNP309 polymorphism and MDM2 rs1690916 polymorphism with malignant bone tumors.
Body and mind interact extensively with each other to control health. Emerging evidence suggests that chronic neurobehavioral stress can promote various tumor growth and progression. The biological reaction to stress involves a chemical cascade initiated within the central nervous system and extends to the periphery, encompassing the immune, endocrine, and autonomic systems. Activation of sympathetic nervous system, such as what happens in the "fight or flight" response, downregulates tumor-suppressive genes, inhibits immune function, and promotes tumor growth. On the other hand, an optimistic attitude or psychological intervention helps cancer patients to survive longer via increase in ?-endorphin neuronal suppression of stress hormone levels and sympathetic outflows and activation of parasympathetic control of tumor suppressor gene and innate immune cells to destroy and clear tumor cells.
High-pressure angle-dispersive X-ray diffraction experiments on iron-based superconductor Ce(O(0.84)F(0.16))FeAs were performed up to 54.9 GPa at room temperature. A tetragonal to tetragonal isostructural phase transition starts at about 13.9 GPa, and a new high-pressure phase has been found above 33.8 GPa. At pressures above 19.9 GPa, Ce(O(0.84)F(0.16))FeAs completely transforms to a high-pressure tetragonal phase, which remains in the same tetragonal structure with a larger a-axis and smaller c-axis than those of the low-pressure tetragonal phase. The structure analysis shows a discontinuity in the pressure dependences of the Fe-As and Ce-(O, F) bond distances, as well as the As-Fe-As and Ce-(O, F)-Ce bond angles in the transition region, which correlates with the change in T(c) of this compound upon compression. The isostructural phase transition in Ce(O(0.84)F(0.16))FeAs leads to a drastic drop in the superconducting transition temperature T(c) and restricts the superconductivity at low temperature. For the 1111-type iron-based superconductors, the structure evolution and following superconductivity changes under compression are related to the radius of lanthanide cations in the charge reservoir layer.
Topological vortices with swirling ferroelectric, magnetic and structural anti-phase relationship in hexagonal RMnO3 (R = Ho to Lu, Y, and Sc) have attracted much attention because of their intriguing behaviors. Herein, we report the structure of multiferroic vortex domains in YMnO3 at atomic scale using state-of-the-art aberration-corrected scanning transmission electron microscopy (STEM). Two types of displacements were identified among six domain walls (DWs); six translation-ferroelectric domains denoted by ?+, ?-, ?+, ?-, ?+ and ?-, respectively, were recognized, demonstrating the interlocking nature of the anti-vortex domain. We found that the anti-vortex core is about four unit cells wide. In addition, we reconstructed the vortex model with three swirling pairs of DWs along the  direction. These results are very critical for the understanding of topological behaviors and unusual properties of the multiferroic vortex.
The production of small RNAs (sRNAs) from phased positions set by microRNA-directed cleavage of trans-acting-siRNA-producing locus (TAS) transcript has been characterized extensively; however, the production of sRNAs from non-phased positions remains unknown. We report three cis-cleavages that occurred in TAS3 transcripts in Vitis vinifera, by combining high-throughput sRNA deep sequencing information with evolutional conservation and genome-wide RNA degradome analysis. The three cis-cleavages can be deciphered to generate an orderly cleavage cascade, and can also produce distinct phasing patterns. Each of the patterns, either upstream or downstream of the cis-cleaved position, had a set of sRNAs arranged in 21-nucleotide increments. Part of the cascading cis-cleavages was also conserved in Arabidopsis thaliana. Our results will enhance the understanding of the production of sRNAs from non-phased positions that are not set by microRNA-directed cleavage.
The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.
We present a case of spinal tumor, with fibrohistiocytoma combined with aneurysmal bone cyst (ABC) at the pedicle and transverse process of T7 in a 63-year-old female. ABC is a rare skeletal tumor and spinal ABC is extremely rare. Fibrohistiocytoma is a type of primary benign bone tumor. ABC is also a rare bone tumor that most often occurs in the pelvis. The combined lesion of two primary bone benign tumors is relatively rare in clinic. In addition, fibrohistiocytoma and ABC are widely confused with other giant cell containing tumors of the bone. X-rays, magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) scans were performed and assessed. Finally, the diagnosis was confirmed by pathological tests. The patient underwent surgery and had an extremely good recovery. The correct diagnosis of a spine tumor is important when determining the surgical procedure.
There is no consensus on the difference in effects of internal fixation (IF) and external fixation (EF) on outcomes for the treatment of distal radius fractures. We performed a meta-analysis of randomized clinical studies.
A life cycle assessment was conducted to evaluate the environmental and economic effects of sewage sludge co-incineration in a coal-fired power plant. The general approach employed by a coal-fired power plant was also assessed as control. Sewage sludge co-incineration technology causes greater environmental burden than does coal-based energy production technology because of the additional electricity consumption and wastewater treatment required for the pretreatment of sewage sludge, direct emissions from sludge incineration, and incinerated ash disposal processes. However, sewage sludge co-incineration presents higher economic benefits because of electricity subsidies and the income generating potential of sludge. Environmental assessment results indicate that sewage sludge co-incineration is unsuitable for mitigating the increasing pressure brought on by sewage sludge pollution. Reducing the overall environmental effect of sludge co-incineration power stations necessitates increasing net coal consumption efficiency, incinerated ash reuse rate, dedust system efficiency, and sludge water content rate.
Petal cell expansion depends on cell wall metabolism, changes in cell turgor pressure and restructuring of the cytoskeleton, and recovery ability of petal cell expansion is defined as an indicator of dehydration tolerance in flowers. We previously reported that RhNAC2, a development-related NAC domain transcription factor, confers dehydration tolerance through regulating cell wall-related genes in rose petals. Here, we identify RhNAC3, a novel rose SNAC gene, and its expression in petals induced by dehydration, wounding, exogenous ethylene and abscisic acid (ABA). Expression studies in Arabidopsis protoplasts and yeast show that RhNAC3 has transactivation activity along its full length and in the carboxyl-terminal domain. Silencing RhNAC3 in rose petals by virus-induced gene silencing (VIGS) significantly decreased the cell expansion of rose petals under rehydration conditions. In total, 24 of 27 osmotic stress-related genes were down-regulated in RhNAC3-silenced rose petals, while only 4 of 22 cell expansion-related genes were down-regulated. Overexpression of RhNAC3 in Arabidopsis gave improved drought tolerance, with lower water loss of leaves in transgenic plants. Arabidopsis ATH1 microarray analysis showed that RhNAC3 regulated the expression of stress-responsive genes in overexpressing lines, and further analysis revealed that most of the RhNAC3-up-regulated genes were involved in the response to osmotic stress. Comparative analysis revealed that different transcription regulation existed between RhNAC3 and RhNAC2. Taken together, these data indicate that RhNAC3, as a positive regulator, confers dehydration tolerance of rose petals mainly through regulating osmotic adjustment-associated genes.
Prenatal alcohol exposure has been shown to increase offspring susceptibility to some chemical carcinogens. Whether prenatal exposure to alcohol makes the offspring more susceptible to the development of prostate cancer is not known. Therefore, we determined whether any functional abnormalities and increased cancer susceptibility exist in the prostate of fetal alcohol-exposed male rats during the adult period.
Protein kinase C (PKC) ? and ? activation has been implicated in synaptogenesis. We used aged rats to test whether the PKC?/? activator bryostatin and PKC?-specific activator DCP-LA combined with spatial memory training could restore mushroom dendritic spinogenesis and synaptogenesis. Compared with young rats, aged, learning-impaired rats had lower memory retention; lower densities of mushroom spines and synapses in the apical dendrites of CA1 pyramidal neurons; fewer PKC?-containing presynaptic axonal boutons; and lower activation and expression of two PKC?/? substrates, the mRNA-stabilizing protein HuD and brain-derived neurotrophic factor (BDNF). PKC activator treatment combined with spatial memory training restored mushroom spines and mushroom spine synapses; rescued PKC?/? expression and PKC/HuD/BDNF signaling; and normalized memory to the levels seen in young rats. These effects were produced by treatment with either bryostatin or the PKC?-specific activator, DCP-LA. Bryostatin also reversed alterations in GABAergic inhibitory postsynaptic currents (IPSPs) in aged, learning-impaired rats. Thus, our results support the therapeutic potential of PKC activators when added to cognitive rehabilitation for inducing mushroom spine synaptogenesis and reversing memory decline associated with aging.
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