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Abstract Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well‐characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A‐driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

ObjectiveDespite the fact that China amounts to one-fifth of the world’s population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.MethodsBuilding upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.ResultsA diet rich in “carnivorous”, “vegetarian”, “dairy, fruit, and egg” was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1–4 (L1–4). Yet, a diet rich in “beverage and fried food” was associated with a lower BMD at the FN and L1–4. High quartiles of the carnivorous diet were associated with 34%–39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.ConclusionsOur study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1–4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

Abstract Background Team-based care is an essential part of primary health care (PHC), and its team service delivery process is a systematic one involving multiple and complex influences. Research on the formation mechanism can help improve the effectiveness of primary health care teams (PHCTs). Methods First, based on the Donabedian model, we explored the theoretical framework of a PHC team’s effectiveness formation mechanism. Semi-structured interviews were conducted with 23primary health care team members in Hangzhou, Zhejiang Province, China. A total of seven factors were then included as conditional variables using the crisp set qualitative comparative analysis (csQCA) to explore the complex influences between them and the outcome variable through univariate necessity analysis and path configuration analysis. Results Univariate necessity analysis showed that only “Clear Goals” in the structural dimension were necessary for team effectiveness perception. Six pathways to good primary health care team perception of effectiveness were identified. Two of these paths were more typical. Conclusion “Clear Goals” was the core variable that should be emphasized when exploring the mechanism of PHCT formation. The results suggest that human resources in the management team should be rationally allocated, goal-oriented, and given good attention. Future studies should explore complex combinations of PHCT factors to improve the effectiveness of PHCTs.

Abstract The α‐amylase inhibition and binding behaviors of shikimic acid and its structural analogues were studied. Uncompetitive inhibition characteristic of shikimic acid was identified through several linear transformation equations of enzymatic data considering the good linearity. Interestingly, the change in concentrations of starch would not decrease the inhibitory effects of shikimic acid with various concentrations used in present study. The inhibitory effect reduced greatly after the ethyl esterification of shikimic acid. Gallic acid was distinguished from shikimic acid by a benzene ring and exhibited lower inhibition than shikimic acid. Shikimic acid affected the α‐amylase structure by binding to the non‐active site but did not quench the α‐amylase fluorescent intensity. However, gallic acid anchored with a subsite containing some fluorescent residues at the entrance of active pocket, quenching the fluorescence intensity of α‐amylase strongly. The difference in shikimic acid and gallic acid made the changes in their binding sites as well as the binding behavior. Conclusively, the carboxyl and hexatomic ring with one double‐bond played an important role in binding of shikimic acid with the non‐active sites of α‐amylase. Shikimic acid has potentials as a functional‐factor in α‐amylase inhibition for controlling the postprandial blood sugar level.

Poultry farming is one of the pillar industries of global animal husbandry. In order to guarantee production, poultry are frequently vaccinated from the moment they are hatched. Even so, the initial immunity of chicks is still very poor as they are in the “window period” of immune protection. In ovo vaccination pushes the initial immunization time forward to the incubation period, thereby providing earlier immune protection for chicks. In ovo vaccination is currently a research hotspot of poultry disease prevention and control, which is in line with the intensification of poultry production. However, the vaccines currently available for in ovo vaccination are limited and cannot meet the needs of industrial development, so how to efficiently activate the adaptive immune response of chicken embryos becomes the key to restrict product development and technological progress of in ovo vaccination. Its breakthrough, to a large extent, depends on systematic illustration of the mechanism underlying the adaptive immune response post immunization. Clarification of this issue will provide us with theoretical support and potential solutions for the development of novel vaccines for in ovo vaccination, the augmentation of efficacy of current vaccines and the optimization of immune programs.

Treatment options for herpesvirus infections that target the interactions between the virus and the host have been identified as promising. Our previous studies have shown that transcription factors p53 and Fos are essential host determinants of gallid alpha herpesvirus 1 (ILTV) infection. The impact of p53 and Fos on ILTV replication has ‘not been fully understood yet. Using the sole ILTV-permissive chicken cell line LMH as a model, we examined the effects of hosts p53 and Fos on all phases of ILTV replication, including viral gene transcription, viral genome replication, and infectious virion generation. We achieved this by manipulating the expression of p53 and Fos in LMH cells. Our results demonstrate that the overexpression of either p53 or Fos can promote viral gene transcription at all stages of the temporal cascade of ILTV gene expression, viral genome replication, and infectious virion production, as assessed through absolute quantitative real-time PCR, ILTV-specific RT-qPCR assays, and TCID50 assays. These findings are consistent with our previous analyses of the effects of Fos and p53 knockdowns on virus production and also suggest that both p53 and Fos may be dispensable for ILTV replication. Based on the synergistic effect of regulating ILTV, we further found that there is an interaction between p53 and Fos. Interestingly, we found that p53 also has targeted sites upstream of ICP4, and these sites are very close to the Fos sites. In conclusion, our research offers an in-depth understanding of how hosts p53 and Fos affect ILTV replication. Understanding the processes by which p53 and Fos regulate ILTV infection will be improved by this knowledge, potentially paving the way for the development of novel therapeutics targeting virus–host interactions as a means of treating herpesvirus infections.

P53, a well-known tumor suppressor, has been confirmed to regulate the infection of various viruses, including chicken viruses. Our previous study observed antiviral effect of p53 inhibitor Pifithrin-α (PFT-α) on the infection of avian infectious laryngotracheitis virus (ILTV), one of the major avian viruses economically significant to the poultry industry globally. However, the potential link between this antiviral effect of PFT-α and p53 remains unclear. Using chicken LMH cell line which is permissive for ILTV infection as model, we explore the effects of p53 on ILTV replication and its underlying molecular mechanism based on genome-wide transcriptome analysis of genes with p53 binding sites. The putative p53 target genes were validated by ChIP-qPCR and RT-qPCR. Results demonstrated that, consistent with the effects of PFT-α on ILTV replication we previously reported, knockdown of p53 repressed viral gene transcription and the genome replication of ILTV effectively. The production of infectious virions was also suppressed significantly by p53 knockdown. Further bioinformatic analysis of genes with p53 binding sites revealed extensive repression of these putative p53 target genes enriched in the metabolic processes, especially nucleotide metabolism and ATP synthesis, upon p53 repression by PFT-α in ILTV infected LMH cells. Among these genes, eighteen were involved in nucleotide metabolism and ATP synthesis. Then eight of the 18 genes were selected randomly for validations, all of which were successfully identified as p53 target genes. Our findings shed light on the mechanisms through which p53 controls ILTV infection, meanwhile expand our knowledge of chicken p53 target genes.

ABSTRACT: The tumor suppressor p53, which acts primarily as a transcription factor, can regulate infections from various viruses in chickens. However, the underlying mechanisms of the antiviral functions of chicken p53 (chp53) remain unclear due to the lack of detailed information on its transcriptional regulation. Here, to gain comprehensive insights into chp53 transcriptional regulatory function in a global and unbiased manner, we determined the genome-wide chromatin occupancy of chp53 by chromatin immunoprecipitation, which was followed by sequencing and chp53-mediated gene expression profile by RNA sequencing using chemically immortalized leghorn male hepatoma (LMH) cells with ectopic expression of chp53 as the model. The integrated parallel genome-wide chromatin occupancy and gene expression analysis characterized chp53 chromatin occupancy and identified 754 direct target genes of chp53. Furthermore, functional annotation and cross-species comparative biological analyses revealed the conserved key biological functions and DNA binding motifs of p53 between chickens and humans, which may be due to the consensus amino acid sequence and structure of p53 DNA-binding domains. The present study, to our knowledge, provides the first comprehensive characterization of the chp53 transcriptional regulatory network, and can possibly help to improve our understanding of p53 transcriptional regulatory mechanisms and their antiviral functions in chickens.

Abstract Background The supracondylar humerus fractures are the most common fracture in children’s elbows. Generally, close reduction and percutaneous pinning can provide satisfactory outcomes after adequate reduction. Baumann angle is commonly used to evaluate reduction quality, however, it may fail to assess reduction well when the elbow is in flexion and/or when the patient is young. We conducted this study to evaluate the potential value of the humerus trochlear angle (HTa) for the reduction evaluation and compare it with the Baumann angle. Methods We retrospectively reviewed supracondylar humerus fractures in our trauma center from 2016 to 2019. Patients were grouped as followed: in the HTa group, an arthrogram was used to evaluate the HTa angle and reduction (HTa, defined by the intersection of the axis of the humerus shaft and the tangent of the articular surface of the trochlear); In the Baumann group, the Baumann angle was used to assess the reduction. Baumann angle ratio (BA of injured side/BA of contralateral side) was calculated to evaluate the reduction quality between groups. Flynn’s grading criteria were utilized to evaluate both function and cosmetic outcomes in two groups during the follow-up. Operation time, fluoroscopy shots, complications and Flynn’s grading scores were compared between groups. Results A total of 57 patients with an average age of 4.62 years and follow-up duration of 21.49 ± 5.40 months were included in the analysis. The gender and age distributions were similar in the two groups. Fluoroscopy shots in the HTa group were significantly less than in Baumann group (16.17 ± 0.73 vs. 21.85 ± 0.78, p

Electrospun fibers containing levocetirizine, a BCS III drug, were prepared from three water-soluble polymers, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). Fiber-spinning technology was optimized for each polymer separately. The polymers contained 10 wt% of the active component. An amorphous drug was homogeneously distributed within the fibers. The solubility of the drug in the polymers used was limited, with a maximum of 2.0 wt%, but it was very large in most of the solvents used for fiber spinning and in the dissolution media. The thickness of the fibers was uniform and the presence of the drug basically did not influence it at all. The fiber diameters were in the same range, although somewhat thinner fibers could be prepared from PVA than from the other two polymers. The results showed that the drug was amorphous in the fibers. Most of the drug was located within the fibers, probably as a separate phase; the encapsulation efficiency proved to be 80–90%. The kinetics of the drug release were evaluated quantitatively by the Noyes–Whitney model. The released drug was approximately the same for all the polymers under all conditions (pH), and it changed somewhere between 80 and 100%. The release rate depended both on the type of polymer and pH and varied between 0.1 and 0.9 min−1. Consequently, the selection of the carrier polymer allowed for the adjustment of the release rate according to the requirements, thus justifying the use of electrospun fibers as carrier materials for levocetirizine.

Autosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder which is associated with kidney and liver pathology, including liver fibrosis. Here the authors develop and characterize human liver organoids with a ARPKD mutation, and find that they show aspects of the pathology, including fibrosis.

The processes of HTHP well fracturing, oil drive, and gas recovery are accompanied by the non-stationary flow of medium in the tubing, which may lead to periodic vibration and cause the failure and fatigue of the tubing, thread leakage, and bending deformation. In this paper, a fluid–structure interaction model with 4-equation was established, which considered the unsteady flow of fluid and the motion state of tubing during the periodic injection, pump start, and shutdown of fluid in the tubing. Further, the discrete solution of MOC was used to obtain the variation of fluid flow rate and pressure, tubing vibration rate, frequency, and additional stress with time. The resonance construction parameters corresponding to different tubing diameters were analyzed by discussing the effects of different start and shutdown times as well as pressure on the tubing vibration parameters. The results show that under the periodic injection condition, increasing the tubing diameter or start inside pressure would lead to a sharp increase in the axial additional stress of the tubing generated by fluid–structure interaction, which is not conducive to the safety protection of the tubing. When the pump was shutdown, excessively short operation times and high pressure in the tubing would lead to excessive transient loads in addition to resonance, which would cause damage to the pipeline. Finally, corresponding to the above analysis results, this paper proposes the optimal injection parameters to avoid the generation of resonance, which provides a theoretical basis and reference range for the safe service conditions of the tubing.

Abdominal adhesions are a common cause of bowel obstruction, but knowledge regarding adhesion biology and anti-adhesion therapies remains limited. Here the authors report a systematic analysis of mouse and human adhesion tissues demonstrating that visceral fibroblast JUN and associated PDGFRA expression promote adhesions, and JUN suppression can prevent adhesion formation.

Fibroblast contributions to lung fibrosis and in particular their crosstalk with immune cells in the lung are incompletely understood. Here, the authors show an overall immune suppressive environment transcriptionally controlled and maintained by fibroblasts in lung fibrosis with possible therapeutic implications.

PLA/regenerated cellulose (RC) nanocomposites containing 0.5, 1.0, 1.5, 2.0, 3.0 and 5.0 wt% cellulose were prepared by the Pickering emulsion process. The structure and the rheological properties of the composites were characterized by microscopy, the measurement of melt flow rate and oscillatory rheometry. Viscosity was modelled with the modified Carreau-Yasuda and the modified Cross models, and a new model was proposed as well. The results show that RC is a suitable reinforcement for PLA and the Pickering emulsion process produces homogeneous material. Good dispersion and the relatively large aspect ratio of the cellulose nanofiller leads to the formation of a network structure already at small cellulose content. Viscosity increases rapidly with increasing cellulose concentration and a yield stress appears already at 0.5 wt% RC content. Modeling helps the quantitative analysis of the experimental results and offers additional information about the structure and properties of the composites studied. All three models predict yield stress well, but only the new model gives reasonable values for the power law exponent. Other parameters and their composition dependence are difficult to interpret.

Dual-phase high-strength titanium alloy has the properties of high specific strength and good toughness, which have resulted in its gradual use in the fields of oil and gas well engineering. The elevated-temperature service environment of deep strata is its key research direction. In this paper, the strength and fracture mechanism of a new type of α + β-phase titanium alloy tubing material in its service-temperature range are studied. Its fracture mechanism changed at 130 °C to 150 °C, from normal-stress ductile fracture to quasi-cleavage fracture formed by β-phase voids, which induced microshear, which significantly reduced the elongation of the material and accelerated the rate of yield strength decline with temperature. This mechanism provides a new guiding idea for the design of the microstructure and element content of dual-phase high-strength titanium alloy. For titanium alloy materials in service within the temperature range of the fracture mechanism transition, which is between 130 °C and 150 °C, reducing the void-inducing factors in the β-phase or reducing the content of the β-phase to avoid microshear failure should be considered.

Gallotannins (GTs) are a series of hydrolyzable tannins with multiple health-promoting effects. In this study, an integrated liquid chromatography tandem mass spectrometry (LC–MS/MS) strategy was developed for unveiling the spatial distribution pattern of GTs in the emerging oilseed crops Paeonia rockii and P. ostii. According to the fragmentation behavior of the representative GT (1,2,3,4,6-penta-O-galloyl-β-D-glucose, PGG), the diagnostic neutral loss (NL) of 170 Da was chosen for the non-targeted screening of GT precursors. Simultaneously, the tandem mass spectrometry spectrum (MS/MS) information was acquired through an enhanced product ion (EPI) scan. Nine major GTs were identified in tree peony. To quantify the targeted GTs in different tissues of tree peony, we established a multiple reaction monitoring (MRM)–enhanced product ion (EPI)-based pseudo-targeted approach under the information-dependent acquisition (IDA) mode. The quantitative results show that the GT compounds were ubiquitous in tree peony plants with diverse structures. The typical GT PGG was mainly distributed in roots, leaves, and petals. This strategy can also be utilized for metabolite characterization and quantification in other substrates.

Scleroderma is a devastating fibrotic autoimmune disease. Current treatments are partly effective in preventing disease progression but do not remove fibrotic tissue. Here, we evaluated whether scleroderma fibroblasts take advantage of the “don’t-eat-me-signal” CD47 and whether blocking CD47 enables the body’s immune system to get rid of diseased fibroblasts. To test this approach, we used a Jun-inducible scleroderma model. We first demonstrated in patient samples that scleroderma upregulated transcription factor JUN and increased promoter accessibilities of both JUN and CD47. Next, we established our scleroderma model, demonstrating that Jun mediated skin fibrosis through the hedgehog-dependent expansion of CD26+Sca1– fibroblasts in mice. In a niche-independent adaptive transfer model, JUN steered graft survival and conferred increased self-renewal to fibroblasts. In vivo, JUN enhanced the expression of CD47, and inhibiting CD47 eliminated an ectopic fibroblast graft and increased in vitro phagocytosis. In the syngeneic mouse, depleting macrophages ameliorated skin fibrosis. Therapeutically, combined CD47 and IL-6 blockade reversed skin fibrosis in mice and led to the rapid elimination of ectopically transplanted scleroderma cells. Altogether, our study demonstrates the efficiency of combining different immunotherapies in treating scleroderma and provides a rationale for combining CD47 and IL-6 inhibition in clinical trials.

Although therapeutics targeting viral metabolic processes have been considered as promising strategies to treat herpesvirus infection, the metabolic requirements of gallid alphaherpesvirus 1 (ILTV), which is economically important to the poultry industry worldwide, remain largely unknown. Using the ILTV-susceptible but nonpermissive chicken cell line DF-1 and the ILTV-permissive chicken cell line LMH as models, the present study explored the metabolic requirements of ILTV by global transcriptome analysis and metabolome assays of ILTV infected cell lines in combination with a set of functional validations. The extensive metabolic exploration demonstrated that ILTV infection tended to promote a metabolic shift from glycolysis to fatty acid (FA) and nucleotide biosynthesis and utilizes glutamine independently of glutaminolysis, without significant general effect on the TCA cycle. In addition, different metabolic pathways were found to be required for distinct stages of ILTV replication. Glucose and glutamine were required for the transcription of viral immediate early gene ICP4 and subsequent steps of viral replication. However, FA synthesis was essential for assembly but not required for other upstream steps of ILTV replication. Moreover, the metabolic requirements of ILTV infection revealed in chicken cell lines were further validated in chicken primary cells isolated from chicken embryo kidneys and chicken embryo livers. The present study, to the best of our knowledge, provides the first global metabolic profile of animal herpesviruses and illustrates the main characteristics of the metabolic program of ILTV.

Chitosan is widely used as a natural preservative of fruits and vegetables, but its poor mechanical and water resistances have limited its application. Therefore, in this study, we prepared chitosan composite films by incorporating different amounts of nano-zinc oxide (nano-ZnO) to improve the mechanical properties of chitosan. We also assessed the antibacterial activity of these films against selected microorganisms. The addition of nano-ZnO improved the tensile strength (TS) and elongation at break (EAB) of the chitosan films and reduced their light transmittance. TS and EAB increased from 44.64 ± 1.49 MPa and 5.09 ± 0.38% for pure chitosan film to 46.79 ± 1.65 MPa and 12.26 ± 0.41% for a 0.6% nano-ZnO composite film, respectively. The ultraviolet light transmittance of composite films containing 0.2%, 0.4%, and 0.6% nano-ZnO at 600 nm decreased from 88.2% to 86.0%, 82.7%, and 81.8%, respectively. A disc diffusion test showed that the composite film containing 0.6% nano-ZnO had the strongest antibacterial activity against Alicyclobacillus acidoterrestris, Staphylococcus aureus, Escherichia coli, and Salmonella. In a 15-day preservation study, chitosan composite films containing 0.6% nano-ZnO maintained the soluble solid content of cherry tomatoes, effectively inhibited their respiration, and exhibited good antibacterial properties against the selected microorganisms. Overall, the prepared chitosan nano-ZnO composite film showed a good preservation effect on cherry tomatoes.

Advances in immuno-oncology (IO) are making immunotherapy a powerful tool for cancer treatment. With the discovery of an increasing number of IO targets, many herbs or ingredients from traditional Chinese medicine (TCM) have shown immunomodulatory function and antitumor effects via targeting the immune system. However, knowledge of underlying mechanisms is limited due to the complexity of TCM, which has multiple ingredients acting on multiple targets. To address this issue, we present TCMIO, a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology, which can be used to explore the molecular mechanisms of TCM in modulating the cancer immune microenvironment. Over 120,000 small molecules against 400 IO targets were extracted from public databases and the literature. These ligands were further mapped to the chemical ingredients of TCM to identify herbs that interact with the IO targets. Furthermore, we applied a network inference-based approach to identify the potential IO targets of natural products in TCM. All of these data, along with cheminformatics and bioinformatics tools, were integrated into the publicly accessible database. Chemical structure mining tools are provided to explore the chemical ingredients and ligands against IO targets. Herb–ingredient–target networks can be generated online, and pathway enrichment analysis for TCM or prescription is available. This database is functional for chemical ingredient structure mining and network analysis for TCM. We believe that this database provides a comprehensive resource for further research on the exploration of the mechanisms of TCM in cancer immunity and TCM-inspired identification of novel drug leads for cancer immunotherapy. TCMIO can be publicly accessed at http://tcmio.xielab.net.

The thickness, reinforcement, and concrete strength grade of railway caps in China are generally determined according to the force, yet the method for calculating the force is unclear. To date, there is no desirable calculation method for analyzing the caps. Based on the fifteen-pile thick cap of mixed passenger and freight railway, the influencing factors on cap bearing capacity were analyzed using finite element method (FEM). The variations of load-bearing capacity and mechanical behavior of thick cap were characterized by introducing rigid angle α. Results indicated that ultimate load-bearing value of the cap increased linearly with the increase of concrete strength grade, and an increasing load-bearing capacity of the reinforcement distributed in the pile diameter range was larger than that of the uniform reinforcement; when the reinforcement ratio was 0.15%, it increased by 9.3%. The cap showed punching failure when α

The Qinling Mountains represent the dividing line of the natural landscape of north-south in China. The prediction on vegetation coverage is important for protecting the ecological environment of the Qinling Mountains. In this paper, the data accuracy and reliability of three vegetation index data (GIMMS NDVI, SPOT NDVI, and MODIS NDVI) were compared at first. SPOT, NDVI, and MODIS NDVI were used for calculating the vegetation coverage in the Qinling Mountains. Based on the CA–Markov model, the vegetation coverage grades in 2008, 2010, and 2013 were used to simulate the vegetation coverage grade in 2025. The results show that the grades of vegetation coverage of the Qinling Mountains calculated by SPOT, NDVI, and MODIS NDVI are highly similar. According to the prediction results, the grade of vegetation coverage in the Qinling Mountains has a rising trend under the guidance of the policy, particularly in urban areas. Most of the vegetation coverage transit from low vegetation coverage to middle and low vegetation coverage. The grades of the vegetation coverage, which were predicted by the CA–Markov model using SPOT, NDVI, and MODI NDVI, are consistent in spatial distribution and temporal variation.

Fibers were spun from a mixture of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) solution of poly(lactic acid)(PLA) containing various amounts of amoxicillin (Amox) as the active component. Composition changes during spinning, structure, solubility, and the location of the drug were considered during the evaluation of drug release and microbial activity. The results showed that the composition of the material changes during the preparation procedure. The solubility of the drug in the components and that of the components in each other is limited, which results in the formation of several phases and the precipitation of the drug. The technology used results in the partitioning of the drug; some is located inside, while the rest is among the fibers. The wetting of the fibers or disks by the water-based dissolution media is poor, the penetration of the liquid into and the diffusion of the active component out of the device takes considerable time. Drug release takes place in one, burst-like step, only Amox located among the fibers dissolve and diffuse into the surrounding medium. The slow second stage of release claimed in the literature is less probable because the size of the Amox molecule is considerably larger than the holes creating the free volume of the polymer. The prepared device has antimicrobial activity, inhibits the growth of the two bacterial strains studied. The time scale of activity is short and corresponds to that of the release experiments and the burst-like behavior of the device. The results clearly prove that physical–chemical factors play a determining role in the effect and efficiency of medical devices prepared from electrospun fibers containing an active component.

Objectives: The aim of this study was to determine the impact of the Zero Markup drug (ZMD) policy on hospitalization expenses for inpatients in tertiary Chinese hospitals. Methods: Using the administrative data from hospital electronic health records (EHRs) between 2015 and 2017, we implemented the quantile difference-in-differences (QDID) estimators to evaluate the impact of the ZMD policy on hospitalization expenses while controlling for patient-level and hospital-level characteristics. Results: According to the QDID models, the introduction of ZMD policy significantly induced lower drug costs for all inpatients especially at the 50th (-USD 507.84 (SE = USD 90.91), 75th (-USD 844.77 (SE = USD 149.70), and 90th (-USD 1400.00 (SE = USD 209.97)) percentiles of the overall distributions. However, the total hospitalization, diagnostic, treatment, material and services expenses for inpatients were significantly higher for the treated group than the control group. This tendency was more pronounced for inpatients in tertiary hospitals with lower expenses (in the 10th, 25th and 50th percentiles). Conclusion: The implementation of ZMD policy alone may not be enough to change the medical service providers’ profit-driven behavior. The targeted supervision of hospital costs by the Chinese health administration department should be strengthened to avoid unreasonable hospital charges.

Gallid alpha-herpesvirus 1, also known as avian infectious laryngotracheitis virus (ILTV), continues to cause huge economic losses to the poultry industry worldwide. Similar to that of other herpesvirus-encoded proteins, the expression of viral genes encoded by ILTV is regulated by a cascade, and the underlying regulatory mechanism remains largely unclear. The viral immediate-early (IE) gene ICP4 plays a prominent role in the initiation of the transcription of early and late genes during ILTV replication. In this study, we identified AP-1 as the key regulator of the transcription of ILTV genes by bioinformatics analysis of genome-wide transcriptome data. Subsequent functional studies of the key members of the AP-1 family revealed that Fos, but not Jun, regulates ILTV infection through AP-1 since knockdown of Fos, but not Jun, by gene silencing significantly reduced ICP4 transcription and subsequent viral genome replication and virion production. Using several approaches, we identified ICP4 as a bona fide target gene of Fos that regulated Fos and has Fos response elements within its promoter. Neither the physical binding of Jun to the promoter of ICP4 nor the transcriptional activity of Jun was observed. In addition, knockdown of Fos reduced the transcription of MDH1 and ATP5A1, genes encoding two host rate-limiting enzymes essential for the production of the TCA intermediates OAA and ATP. The biological significance of the transcriptional regulation of MDH1 and ATP5A1 by Fos in ILTV infection was supported by the fact that anaplerosis of OAA and ATP rescued both ICP4 transcription and virion production in infected cells under when Fos was silenced. Our study identified the transcription factor Fos as a key regulator of ILTV infection through its transcription factor function on both the virus and host sides, improving the current understanding of both avian herpesvirus–host interactions and the roles of AP-1 in viral infection.

Cracks at notches deserve special consideration in the design of steam turbine components. This work is addressed to investigate the crack initiation behavior a 10%Cr rotor steel with the help of notched specimens under service-type loading. A significant drifting down of the peak-values of axial deformation under constant amplitude load was observed. Crack initiation was evaluated with the help of the relationship between irreversible deformation energy and cycle number. Further, metallographic examinations were employed to characterize the superposition of creep and fatigue damage mechanisms. Both Neuber-hypothesis and von Mises equivalent strain at notch root were applied for lifetime prediction. Finally, the effectiveness of both methods is validated by comparing with experimental results

Moso bamboo has large potential to alleviate global warming through carbon sequestration. Since soil respiration (Rs) is a major source of CO2 emissions, we analyzed the dynamics of soil respiration (Rs) and its relation to environmental factors in a Moso bamboo (Phllostachys heterocycla cv. pubescens) forest to identify the relative importance of biotic and abiotic drivers of respiration. Annual average Rs was 44.07 t CO2 ha−1 a−1. Rs correlated significantly with soil temperature (P

Grapes are one of the world’s oldest and most important fruit crops. They are of high economic value in many countries, but the susceptibility of the dominant winegrape species Vitis vinifera to fungal disease is a significant problem. The Chinese wild grape species are a rich source of disease-resistance genes and these can be used to discover how disease resistance in V. vinifera grapevines might be enhanced. Pathogenesis-related (PR) 10 proteins are involved in the disease-response. Here, we use the genomic DNA of the Chinese wild species Vitis pseudoreticulata accession “Baihe-35-1” as the template to design specific primers based on VvPR10s sequences. We used overlap extension PCR to obtain the sequences: VpPR10.4, VpPR10.6, VpPR10.7 and VpPR10.9. The coding sequences of the VpPR10s were then cloned into the pGEX-4T-1 vector. The purified proteins VpPR10.4, VpPR10.6, VpPR10.7 and VpPR10.9 were used to analyse nuclease activity. Meanwhile, functional analysis of VpPR10s under different biotic and abiotic stresses was carried out to further clarify the disease-resistance mechanisms of the Chinese wild grapevine VpPR10 genes. The analysis of protein structure indicates that VpPR10.4 and VpPR10.7 had the P-loop domain and the Bet v 1 motif, which are a consistent feature of plant PR10. However, there was no P-loop domain or Bet v 1 motif in VpPR10.9 and we could not find the Bet v 1 motif in VpPR10.6. The results of the nuclease activity assay and of the functional analyses of VpPR10s under different biotic and abiotic stresses also confirm that VpPR10.4 and VpPR10.7 proteins have marked RNase, DNase, anti-fungal activities and respond to abiotic stresses. The VpPR10.6 and VpPR10.9 proteins do not have these activities and functions.

Association mapping has been widely used to map the significant associated loci responsible for natural variation in complex traits and are valuable for crop improvement. Sugars and organic acids are the most important metabolites in tomato fruits. We used a collection of 174 tomato accessions composed of S. lycopersicum (123 accessions) and S. lycopersicum var cerasiforme (51 accessions) to detect significantly associated loci controlling the variation of main sugars and organic acids. The accessions were genotyped with 182 SSRs spreading over the tomato genome. Association mapping was conducted on the main sugars and organic acids detected by gas chromatography-mass spectrometer (GC-MS) over two years using the mixed linear model (MLM). We detected a total of 58 significantly associated loci (P

To study the erosion⁻corrosion characteristics of TP140 casing steel and 13Cr tubing steel in oil fields, we performed gas⁻solid and liquid⁻solid jet flow experiments to control particle addition, jet angle, and flow velocity and measure erosion and corrosion components. Meanwhile, we used a standard three-electrode system to study the changes in electrochemical parameters on a metal surface in a two-phase flow containing 2 wt % NaCl. Results showed that erosion is mainly dominated by the flow velocities and impact angles of particles, and corrosion rate is mainly affected by liquid flow rate. The erosion rates of the two materials increase with flow velocity, and the critical angle of maximum erosion rate exists. Meanwhile, flow velocity growth increases the current density on the TP140 surface while reducing the corrosion potential of 13Cr, but the effect of the angle on the two parameters is relatively small. The uniform corrosion of TP140 increases the erosion rate in the range of 10⁻20%, and the pitting of 13Cr increases the erosion rate in the range of 30⁻90%, indicating that the interaction between the erosion and corrosion of stainless steel is obvious.

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.

China is one of the countries with the most abundant bamboo forest resources in the world, and Zhejiang province is among the top-3 Chinese provinces with richest bamboo forests. For rational bamboo forests management, it is of great significance to study the spatiotemporal dynamic changes of Aboveground Carbon (AGC) stocks of bamboo forest in Zhejiang. In this study, remote sensing variables, such as spectral, vegetation indices and texture features of bamboo forest in Zhejiang, were extracted from 32 Landsat TM and OLI images got from four different years (2000, 2004, 2008 and 2014). These variables were subsequently selected with stepwise regression method to build an estimation model of AGC of the bamboo forests. The results showed that (1) the accuracy of bamboo forest remote sensing information extracted from the four different years was high with a classification accuracy of >76.26% and an accuracy of users of >91.62%. The classification area of bamboo forest was highly consistent with the area from forest resource inventory, and the area accuracy was over 96.50%; (2) the estimation model performed well in predicting the AGC in Zhejiang for different years. The correlation coefficient for estimated and measured AGC was between 63% and 72% with low root mean square error; (3) the derived AGC of the bamboo forests in Zhejiang province increased gradually from 2000 to 2014, with the AGC density of 6.75 Mg·ha−1, 10.95 Mg·ha−1, 15.25 Mg·ha−1 and 19.07 Mg·ha−1 respectively, and the average annual growth of 0.88 Mg·ha−1. The spatiotemporal evolution of bamboo forest AGC in Zhejiang province had a close relationship with the gradual expansion of bamboo forest in the province and the differentiation of management levels in different regions.

This paper presents an experimental study of the basic properties of the main materials found in reinforced concrete (RC) structures strengthened by fibre reinforced polymer (FRP) sheets with scope to investigate the effect of ultraviolet (UV) exposure on the degradation of FRP, resin adhesive materials and concrete. The comparison studies focused on the physical change and mechanical properties of FRP sheet, and resin adhesive materials and concrete before and after UV exposure. However, the degradation mechanisms of the materials under UV exposure were not analyzed. The results show that the ultimate tensile strength and modulus of FRP sheets decrease with UV exposure time and the main degradation of FRP-strengthened RC structures is dependent on the degradation of resin adhesive materials. The increase in the number of FRP layers cannot help to reduce the effect of UV exposure on the performance of these materials. However, it was verified that carbon FRP materials have a relatively stable strength and elastic modulus, and the improvement of the compression strength of concrete was also observed after UV exposure.

Bamboo forests, especially the Moso bamboo forest (MBF) and the Lei bamboo forest (LBF), have a strong carbon sequestration capability and play an important role in the global forest carbon cycle. The leaf area index (LAI) is an important structural parameter for simulating the spatiotemporal pattern of the carbon cycle in bamboo forests. However, current LAI products suffer from substantial noise and errors, and data assimilation methods are the most appropriate way to improve the accuracy of LAI data. In this study, two data assimilation methods (the Dual Ensemble Kalman filter (DEnKF) and Particle filter (PF) methods) were applied to improve the quality of MODIS LAI time-series data, which removed noises and smoothed the results using a locally adjusted cubic-spline capping method for the MBF and LBF during 2014–2015. The method with the highest correlation coefficient (r) and lowest root-mean-square error (RMSE) was used to generate highly accurate LAI products of bamboo forests in Zhejiang Province. The results show that the LAI assimilated using two methods saw greatly reduced fluctuations in the MODIS LAI product for both the MBF and the LBF. The LAI assimilated using DEnKF significantly correlated with the observed LAI, with an r value of 0.90 and 0.95, and an RMSE value of 0.42 and 0.42, for the MBF and the LBF, respectively. The PF algorithm achieved a better accuracy than the DEnKF algorithm, with an average increase in r of 8.78% and an average decrease in the RMSE of 33.33%. Therefore, the PF method was applied for LAI assimilation in Zhejiang Province, and the assimilated LAI of bamboo forests achieved a reasonable spatiotemporal pattern in Zhejiang Province. The PF algorithm greatly improves the accuracy of MODIS LAI products and provides a reliable structural parameter for the large-scale simulation of the carbon cycle in bamboo forest ecosystems.

We present a review on manipulations of electromagnetic scattering features by using metamaterials or metasurfaces. Several approaches in controlling the scattered fields of objects are presented, including invisibility cloaks and radar illusions based on transformation optics, carpet cloak using gradient metamaterials, dc cloaks, mantle cloaks based on scattering cancellation, “skin” cloaks using phase compensation, scattering controls with coding/programmable metasurfaces, and scattering reductions by multilayered structures. Finally, the future development of metamaterials on scattering manipulation is predicted.

Abstract Background Heat shock proteins (Hsps) are a set of highly conserved proteins, Hsp105, has been suggested to play a role in reproduction. Methods Spatio-temporal expression of Hsp105 in rat uterus during peri-implantation period was examined by immunohistochemistry and Western blot, pseudopregnant uterus was used as control. Injection of antisense oligodeoxynucleotides to Hsp105 into pregnant rat uteri was carried out to look at effect of Hsp105 on embryo implantation. Results Expression of Hsp105 was mainly in the luminal epithelium on day 1 of pregnancy, and reached a peak level on day 5, whereas in stroma cells, adjacent to the implanting embryo, the strongest expression of Hsp105 was observed on day 6. The immunostaining profile in the uterus was consistent with that obtained by Western blot in the early pregnancy. In contrast, no obvious peak level of Hsp105 was observed in the uterus of pseudopregnant rat on day 5 or day 6. Furthermore, injection of antisense oligodeoxynucleotides to Hsp105 into the rat uterine horn on day 3 of pregnancy obviously suppressed the protein expression as expected and reduced number of the implanted embryos as compared with the control. Conclusion Temporal and spatial changes in Hsp105 expression in pregnant rat uterus may play a physiological role in regulating embryo implantation.