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Abstract The proximity-effect, whereby materials in contact appropriate each other’s electronic-properties, is widely used to induce correlated states, such as superconductivity or magnetism, at heterostructure interfaces. Thus far however, demonstrating the existence of proximity-induced charge-density-waves (PI-CDW) proved challenging. This is due to competing effects, such as screening or co-tunneling into the parent material, that obscured its presence. Here we report the observation of a PI-CDW in a graphene layer contacted by a 1T-TaS2 substrate. Using scanning tunneling microscopy (STM) and spectroscopy (STS) together with theoretical-modeling, we show that the coexistence of a CDW with a Mott–gap in 1T-TaS2 coupled with the Dirac-dispersion of electrons in graphene, makes it possible to unambiguously demonstrate the PI-CDW by ruling out alternative interpretations. Furthermore, we find that the PI-CDW is accompanied by a reduction of the Mott gap in 1T-TaS2 and show that the mechanism underlying the PI-CDW is well-described by short-range exchange-interactions that are distinctly different from previously observed proximity effects.

Abstract In this paper, a combination of theoretical modeling, finite element simulation, and experimental methods is employed to investigate the forming mechanism and evolutionary pattern of the stagnant region during mechanical scratching with a diamond wedge tool. The study is structured as follows: Firstly, a theoretical calculation model for the geometric parameters of the stagnant region on the formed groove surface is established based on the contact friction partition mechanism and slip-line field theory. The model indicates that the geometric parameters l B-sg , l V-sg , and ∆l sg of the stagnant region are determined by the length of the stagnant region l p-sg in the plastic flow plane and the transformation parameters. Secondly, the formation process of the stagnant region in mechanical scratching is investigated using an orthogonal cutting simulation model with a negative rake angle tool. The results reveal that the stagnant region is a plastic deformation region formed due to the geometrical characteristics of the negative front surface of the scratching tool and its excessive extrusion, which leads to the formation of adhesive friction within the material. Thirdly, the characteristics of the stagnant region are determined through scratching experiments. Compared to the material in the plastic flow region, the material within the stagnant region exhibits finer and denser microstructures, reduced surface hardening peaks and hardened layer depths, and significantly improved surface roughness. Finally, the evolutionary pattern of the stagnant region under the influence of scratching processing parameters is examined based on the theoretical calculation model of the geometric parameters and the scratching experiment. The findings indicate that as the wedge angle of the scratching tool decreases, the relief angle increases, the absolute value of the rotation angle around the Y-axis decreases, the scratching speed decreases, and the material’s plastic adherence improves, the P I/k value decreases, the l p-sg value increases, and consequently, the geometric parameters l B-sg , l V-sg , and ∆l sg of the stagnant region on the formed groove surface also increase. The deviation analysis of the geometric parameters of the stagnant region reveals a consistent trend between the theoretical and experimental values of l V-sg and ∆l sg , with maximum deviations of 15 μm and 4.13%, respectively. This study provides theoretical and experimental evidence for the establishment of the theoretical model of the stagnant region in mechanical scratching, the analysis of its forming mechanism, and the control of the stagnant region geometric parameters on the formed groove surface.

UAV imaging technology has become one of the means to quickly monitor water quality parameters in freshwater aquaculture ponds. The change of sunlight during a long flight affects the quality of UAV images, which will reduce the accuracy of monitoring water quality. This study aims to propose a method to correct spectral variation during UAV imaging and apply it to detect dissolved organic matter (DOM) concentration and dissolved oxygen (DO) content in freshwater aquaculture ponds. Firstly, a spectral correction method was used to transform UAV-based multispectral images. The spectral data before and after correction was extracted. Secondly, 18 spectral indices before and after correction were constructed. The optimal combination of indices was identified using correlation analysis algorithm. The estimation models of water quality parameters were then constructed and compared using the Random Forest (RF), Support Vector Regression (SVR), and BP neural network (BP) methods. The results showed that the accuracy of estimating DOM concentration using corrected spectral indices was significantly improved compared to pre-correction models, with the highest improvement of 38 % (SVR), the lowest of 23 % (BP), and an average improvement of 31 %. The RF model performed best, achieving R² = 0.81, RMSE = 3.34 mg/L, and MAE = 2.17 mg/L. For DO content estimation, the accuracy of models using corrected spectral indices was also improved significantly, with the highest improvement of 97 % (RF), the lowest of 39 % (SVR), and an average improvement rate of 67 %. The Random Forest model was again optimal, with R² = 0.69, RMSE = 1.97 mg/L, and MAE = 1.47 mg/L. This study indicates that the proposed spectral correction method helps to map the concentration of DOM and DO in freshwater aquaculture ponds with high accuracy using UAV-based multispectral images.

Abstract The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.

Abstract Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

During the development of eukaryote, faithful inheritance of chromatin states is central to the maintenance of cell fate. DNA replication poses a significant challenge for chromatin state inheritance because every nucleosome in the genome is disrupted as the replication fork passes. It has been found that many factors including DNA polymerases, histone chaperones, as well as, RNA Pol II and histone modifying enzymes coordinate spatially and temporally to maintain the epigenome during this progress. In this review, we provide a summary of the detailed mechanisms of replication-coupled nucleosome assembly and post-replication chromatin maturation, highlight the inheritance of chromatin states and epigenome during these processes, and discuss the future directions and challenges in this field.

Objective The purpose of this study is to evaluate the effectiveness of hospital appraisals, specifically the Performance Appraisal for Tertiary Public Hospitals (PATPH), and to examine its impact on the job satisfaction of healthcare professionals in tertiary public hospitals in China.Design A cross-sectional study using a multistage sampling method. Improvements induced by PATPH in the working environment, job satisfaction and other covariates were measured. A series of weighted linear regressions with weights from the inverse probability-of-treatment weighting method were used to examine the effect of PATPH on job satisfaction.Setting Nine tertiary public hospitals across three economic and geographic regions in China.Participants In August 2020, a total of 13 211 hospital employees were surveyed, and 8417 doctors and nurses fully completed questionnaires forming the primary dataset for analysis. Of these respondents, males comprised 18.64% and doctors constituted 28.15%.Results This study revealed that PATPH had a positive impact on the job satisfaction of healthcare professionals. A ‘more effective’ PATPH working environment resulted in an improvement of 9.57 points (95% CI 8.99 to 10.16) in job satisfaction scores, controlling for all other variables. The finding persisted consistently through a series of sensitivity analyses.Conclusion The findings offered insights and inspiration for improving the job satisfaction of healthcare professionals, especially in the development of macrolevel policies targeted towards organisational enhancement.

BackgroundThis study aimed to translate the revised Hospital Survey on Patient Safety Culture (HSOPSC 2.0) to Mandarin, evaluate its psychometric properties, and apply it to a group of private hospitals in China to identify the determinants associated with patient safety culture.MethodsA two-phase study was conducted to translate and evaluate the HSOPSC 2.0. A cross-cultural adaptation of the HSOPSC 2.0 was performed in Mandarin and applied in a cross-sectional study in China. This study was conducted among 3,062 respondents from nine private hospitals and 11 clinics across six cities in China. The HSOPSC 2.0 was used to assess patient safety culture. Primary outcomes were measured by the overall patient safety grade and patient safety events reported.ResultsConfirmatory factor analysis results and internal consistency reliability were acceptable for the translated HOSPSC 2.0. The dimension with the highest positive response was “Organizational learning - Continuous improvement” (89%), and the lowest was “Reporting patient safety event” (51%). Nurses and long working time in the hospital were associated with lower assessments of overall patient safety grades. Respondents who had direct contact with patients, had long working times in the hospital, and had long working hours per week reported more patient safety events. A higher level of patient safety culture implies an increased probability of a high overall patient safety grade and the number of patient safety events reported.ConclusionThe Chinese version of HSOPSC 2.0 is a reliable instrument for measuring patient safety culture in private hospitals in China. Organizational culture is the foundation of patient safety and can promote the development of a positive safety culture in private hospitals in China.

Abstract Whole-genome duplication (WGD), or polyploidy, events are widespread and significant in the evolutionary history of angiosperms. However, empirical evidence for rediploidization, the major process where polyploids give rise to diploid descendants, is still lacking at the genomic level. Here we present chromosome-scale genomes of the mangrove tree Sonneratia alba and the related inland plant Lagerstroemia speciosa. Their common ancestor has experienced a whole-genome triplication (WGT) approximately 64 million years ago coinciding with a period of dramatic global climate change. Sonneratia, adapting mangrove habitats, experienced extensive chromosome rearrangements post-WGT. We observe the WGT retentions display sequence and expression divergence, suggesting potential neo- and sub-functionalization. Strong selection acting on three-copy retentions indicates adaptive value in response to new environments. To elucidate the role of ploidy changes in genome evolution, we improve a model of the polyploidization–rediploidization process based on genomic evidence, contributing to the understanding of adaptive evolution during climate change.

Abstract H9N2 avian influenza viruses (AIVs) are widely distributed, causing continuous outbreaks in poultry and sporadic infections in humans. Vaccination is the primary method used to prevent and control H9N2 AIV infection. However, the ongoing evolution and mutation of AIVs often result in limited protection effects from vaccines. Therapeutic monoclonal antibodies (mAbs) targeting influenza viruses offer a promising alternative. In this study, we immunized mice with inactivated H9N2-W1 virus, and we screened and acquired five mAbs, namely 4D12, F4, 5C8, 2G8 and A11. We showed that all five mAbs specifically targeted the HA protein of various H9N2 AIV strains. In vitro neutralization tests demonstrated that all five mAbs exhibited neutralization activity against H9N2 AIVs, with mAb F4 displaying the most potent neutralization effect. The F4 mAb exhibited dose-dependent preventive and therapeutic effects against lethal H9N2-115 infection, and the administration of F4 at a dose of 3 μg/g provided complete protection in vivo. Our study presents an alternative approach for preventing and controlling H9N2 AIV infection. Furthermore, the identified F4 mAb holds promise as a solution to potential pandemics in humans caused by H9N2 AIVs.

Abstract Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives. A complex immunization schedule, however, may be burdensome to parents and lead to reduced vaccine compliance and completion. Thus, it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule. This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis and Haemophilus influenzae type B conjugate (DTaP-IPV/Hib) vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations. Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023. The study employed a stratified multistage cluster random sampling method. Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire. Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations. Results Of the 4818 valid responses, 95.3% of children were aged 3–4 years, and 2856 (59.3%) held rural hukou. Coverage rates of the DTaP-IPV/Hib vaccine, from 1 to 4 doses, were 24.4%, 20.7%, 18.5%, and 16.0%, respectively. Caregivers who are concerned about vaccine efficacy [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI): 1.30–1.79], the manufacturer (aOR = 2.05, 95% CI: 1.69–2.49), and a simple immunization schedule (aOR = 1.26, 95% CI: 1.04–1.54) are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib. In addition, caregivers in urban areas showed more concern about the vaccine price (P = 0.010) and immunization schedule (P = 0.022) in regard to vaccinating children. Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low. Factors such as lower socioeconomic status, cultural beliefs, concerns about vaccine safety, and cost may hinder caregivers from vaccinating their children. Further measures, such as health education campaigns to raise knowledge and awareness, and encouragement of domestic vaccine innovation, which would reduce out-of-pocket costs, could be implemented to improve the coverage of DTap-IPV/Hib vaccination. Graphical Abstract

Abstract The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.

Abstract Backgound Efforts to measure performance and identify its driving factors among clinicians are needed for building a high-quality clinician workforce. The availability of data is the most challenging thing. This paper presented a summary performance measure for clinicians and its application on examining factors that influence performance using routine patient-based records. Methods Perfomance indicators and difficulty score were extracted from electronic medical records (EMRs). Difficulty adjustment and standardized processing were used to obtain indicators which were comparable between specialties. Principal component analysis (PCA) was used to estimate the summary performance measure. The performance measure was then used to examine the influence of person-job fit and burnout through a mediator effect model and cluster analysis. Results A valid sample of 404 clinicians were included in this study, and 244 of them had valid response in the questionnaire. PCA explained 79.37% of the total variance presented by the four adjusted performance indicators. Non-performance attributes and performance driving factors help distinguish different clusters of clinicians. Burnout mediates the relationship between person-job fit and performance in a specific group of clinicians (β = 0.120, p = 0.008). Conclusions We demonstrated the analytical steps to estimate clinicians’ performance and its practical application using EMRs. Our findings provide insight into personnel classified management. Such practice can be applied in countries where electronic medical record systems are relatively less developed to continuously improve the application of performance management.

Abstract During cell renewal, epigenetic information needs to be precisely restored to maintain cell identity and genome integrity following DNA replication. The histone mark H3K27me3 is essential for the formation of facultative heterochromatin and the repression of developmental genes in embryonic stem cells. However, how the restoration of H3K27me3 is precisely achieved following DNA replication is still poorly understood. Here we employ ChOR-seq (Chromatin Occupancy after Replication) to monitor the dynamic re-establishment of H3K27me3 on nascent DNA during DNA replication. We find that the restoration rate of H3K27me3 is highly correlated with dense chromatin states. In addition, we reveal that the linker histone H1 facilitates the rapid post-replication restoration of H3K27me3 on repressed genes and the restoration rate of H3K27me3 on nascent DNA is greatly compromised after partial depletion of H1. Finally, our in vitro biochemical experiments demonstrate that H1 facilitates the propagation of H3K27me3 by PRC2 through compacting chromatin. Collectively, our results indicate that H1-mediated chromatin compaction facilitates the propagation and restoration of H3K27me3 after DNA replication.

ABSTRACT: Multiple outbreaks of avian infectious laryngotracheitis (ILT) in chickens, both domestically and internationally, have been directly correlate to widespread vaccine use in affected countries and regions. Phylogenetic and recombination event analyses have demonstrated that avian infectious laryngotracheitis virus (ILTV) field strains are progressively evolving toward the chicken embryo-origin (CEO) vaccine strain. Even with standardized biosecurity measures and effective prevention and control strategies implemented on large-scale farms, continuous ILT outbreaks result in significant economic losses to the poultry industry worldwide. These outbreaks undoubtedly hinder efforts to control and eradicate ILTV in the future. In this study, an ILTV isolate was successfully obtained by laboratory PCR detection and virus isolation from chickens that exhibited dyspnea and depression on a broiler farm in Hubei Province, China. The isolated strain exhibited robust propagation on chorioallantoic membranes of embryonated eggs, but failed to establish effective infection in chicken hepatocellular carcinoma (LMH) cells. Phylogenetic analysis revealed a unique T441P point mutation in the gJ protein of the isolate. Animal experiments confirmed the virulence of this strain, as it induced mortality in 6-wk-old chickens. This study expands current understanding of the epidemiology, genetic variations, and pathogenicity of ILTV isolates circulating domestically, contributing to the elucidate of ILTV molecular basis of pathogenicity and development of vaccine.

Summary: The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly in vitro, and reduced the turnover of FACT on chromatin in vivo. Strikingly, mouse ESCs harboring this mutation showed elevated naive-to-formative transition. Mechanistically, the SSRP1-Q265K mutation enriched FACT at the enhancers of formative-specific genes to increase targeted gene expression. Together, these findings suggest that the turnover of FACT on chromatin is crucial for regulating the enhancers of formative-specific genes, thereby mediating the naive-to-formative transition. This study highlights the significance of FACT in fine-tuning cell fate transition during early development.

Abstract Background Dietary-induced inflammation is potentially associated with sarcopenia. Nevertheless, few studies have investigated the structure of the inflammatory diet and its correlation with muscle function and performance in both the upper and lower limbs. This study was performed to explore the association of the dietary inflammatory index (DII) with sarcopenia and its diagnostic parameters. Methods We conducted a cross-sectional survey on a sample of 515 Chinese community-dwelling older adults selected through multistage cluster sampling from three districts in Shanghai. DII scores were calculated using a validated food frequency questionnaire. Sarcopenia and its diagnostic parameters were determined based on the definition set by the Asian Working Group on Sarcopenia (AWGS). Results The mean age of study participants was 71.31 ± 4.71 years. The prevalence of sarcopenia in the cohort was 12.4%. Older adults in the highest DII quartile had a 3.339 times increased risk of sarcopenia compared to those in the lowest quartile (OR Quartile4vs1:3.339, 95%CI: 1.232, 9.052, p-trend: 0.004) after adjusting for confounding factors. Additionally, a more pro-inflammatory diet was associated with lower appendicular skeletal muscle index (ASMI) (OR Quartile4vs1: 3.005, 95%CI: 1.275, 7.318, p-trend: 0.005), a higher 5-times sit-stand test time score (OR Quartile4vs1: 4.942, 95%CI: 1.745, 13.993, p-trend: 0.005), and lower gait speed (OR Quartile4vs1: 2.392, 95%CI: 1.104, 5.185, p-trend: 0.041) after adjusting for confounding factors. However, there was no significant association between DII, handgrip strength, and Short Physical Performance Battery (SPPB) score in either the unadjusted or adjusted model. Conclusion This study found that the association between consuming a more pro-inflammatory diet and sarcopenia in Chinese community-dwelling older adults was mainly due to underlying low intakes of dietary energy, protein, and anti-inflammatory foods, and not due to the high intake of pro-inflammatory foods. Meanwhile, DII was more highly correlated with lower limb muscle strength and performance compared to upper limb muscle strength.

BackgroundCardiovascular disease (CVD) causes substantial financial burden to patients with the condition, their households, and the healthcare system in China. Health care costs for treating patients with CVD vary significantly, but little is known about the factors associated with the cost variation. This study aims to identify and rank key determinants of health care costs in patients with CVD in China and to assess their effects on health care costs.MethodsData were from a survey of patients with CVD from 14 large tertiary grade-A general hospitals in S City, China, between 2018 and 2020. The survey included information on demographic characteristics, health conditions and comorbidities, medical service utilization, and health care costs. We used re-centered influence function regression to examine health care cost concentration, decomposing and estimating the effects of relevant factors on the distribution of costs. We also applied quantile regression forests—a machine learning approach—to identify the key factors for predicting the 10th (low), 50th (median), and 90th (high) quantiles of health care costs associated with CVD treatment.ResultsOur sample included 28,213 patients with CVD. The 10th, 50th and 90th quantiles of health care cost for patients with CVD were 6,103 CNY, 18,105 CNY, and 98,637 CNY, respectively. Patients with high health care costs were more likely to be older, male, and have a longer length of hospital stay, more comorbidities, more complex medical procedures, and emergency admissions. Higher health care costs were also associated with specific CVD types such as cardiomyopathy, heart failure, and stroke.ConclusionMachine learning methods are useful tools to identify determinants of health care costs for patients with CVD in China. Findings may help improve policymaking to alleviate the financial burden of CVD, particularly among patients with high health care costs.

Background The incidence and mortality of hepatocellular carcinoma (HCC) had increased globally over the past decades. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib had also shown efficacy in the unresectable HCC. We aimed to evaluate the safety and efficacy of TACE combined with lenvatinib and camrelizumab to treat unresectable multiple nodular and large HCC (>5 cm). Materials and methods Between November 2018 and June 2021, we retrospectively recruited 82 patients with unresectable multiple nodular and large HCC (BCLC stage B or C with a single nodular diameter of >5 cm). Of the patients who had not previously been treated, 33 patients received TACE + lenvatinib + camrelizumab (group A, TLC), and 49 patients treated with TACE + lenvatinib (group B, TLB) as the initial treatment. Related efficacy and safety results were recorded and assessed. Results The median follow-up periods of groups A and B were 14.5 ± 7.9 months (range, 3-36) and 12.5 ± 8.2 months (range, 3-32), respectively (P = 0.799). The progression-free survival (PFS) of groups A and B was 9.4 months and 5.9 months (P 5 cm), TACE combined with target therapy and immunotherapy is safe and effective.

Here the authors investigated the direct collaboration between ubiquitinated histone H2B (ubH2B) with FACT at the nucleosome level. They found ubH2B enhances FACT’s chaperone property, recruits FACT to form a stable altered nucleosome state, and provides a key platform for transcription.

Abstract Phosphoinositide 3-kinase beta (PI3Kβ) plays an important role in platelet activation and thrombosis, but its role in stroke pathology remains unknown. In this study, we investigated whether inhibition of PI3Kβ protects against cerebral ischemia/reperfusion (I/R) injury by preventing circulating platelet activation and downstream microvascular thrombosis. We used a rat intraluminal filament model of transient middle cerebral artery occlusion (tMCAO) because the rapid restoration of cerebral blood flow to the ischemic area in both tMCAO and endovascular thrombectomy provides clinical relevance for this model. The results showed that TGX221, a selective PI3Kβ inhibitor, treatment immediately before the onset of reperfusion dose-dependently reduced infarct volume and improved neurological function. The protective effects were associated with blocking platelet activation and thrombotic response, thereby reducing downstream microvascular thrombosis, and maintaining reperfusion efficiency. These results suggest that PI3Kβ might be a promising target for treating downstream microvascular thrombosis induced by cerebral I/R injury and offer a novel adjunctive treatment to improve reperfusion therapy for acute ischemic stroke.

Prototheca bovis (P. bovis), an alga that has attracted considerable attention over the years as a causative microorganism of mastitis in dairy cows, exhibits limited susceptibility to specific aminoglycosides and antifungal agents, and no effective clinical treatment is currently available, thereby posing challenges for both prevention and treatment. To investigate the infection of P. bovis mastitis and its impact on raw milk production, a total of 348 raw milk samples were collected from August to December 2022 from a dairy farm in central China. P. bovis and other bacteria were detected, and the average infection rate of P. bovis in raw milk was 60.34% (210/348). The total number of colonies and the somatic cell count (SCC) of P. bovis positive samples were significantly higher than those of P. bovis negative samples (p < 0.01). The daily milk yield, 305-day milk yield, peak milk yield, and days to peak milk yield of the P. bovis positive samples were significantly lower than those of P. bovis negative samples (p < 0.01). A correlation analysis showed that P. bovis infection was negatively correlated with daily milk yield, 305-day milk yield, peak milk yield, and days to peak milk yield (p < 0.0001), while being positively correlated with the total number of colonies, SCC, milk loss, and protein percentage (p < 0.0001). These findings may help practitioners in comprehending the occurrence of Prototheca mastitis and developing more effective strategies for the prevention of P. bovis infections.

Rhizosphere microbiota play an important role in regulating soil physical and chemical properties and improving crop production performance. This study analyzed the relationship between the diversity of rhizosphere microbiota and the yield and quality of flue-cured tobacco at different transplant times (D30 group, D60 group and D90 group) and in different regions [Linxiang Boshang (BS) and Linxiang ZhangDuo (ZD)] by high-throughput sequencing technology. The results showed that there were significant differences in the physicochemical properties and rhizosphere microbiota of flue-cured tobacco rhizosphere soil at different transplanting times, and that the relative abundance of Bacillus in the rhizosphere microbiota of the D60 group was significantly increased. RDA and Pearson correlation analysis showed that Bacillus, Streptomyces and Sphingomonas were significantly correlated with soil physical and chemical properties. PIGRUSt2 function prediction results showed that compared with the D30 group, the D60 group had significantly increased metabolic pathways such as the superpathway of pyrimidine deoxyribonucleoside salvage, allantoin degradation to glyoxylate III and pyrimidine deoxyribonucleotides de novo biosynthesis III metabolic pathways. The D90 group had significantly increased metabolic pathways such as ubiquitol-8 biosynthesis (prokaryotic), ubiquitol-7 biosynthesis (prokaryotic) and ubiquitol-10 biosynthesis (prokaryotic) compared with the D60 group. In addition, the yield and quality of flue-cured tobacco in the BS region were significantly higher than those in the ZD region, and the relative abundance of Firmicutes and Bacillus in the rhizosphere microbiota of flue-cured tobacco in the BS region at the D60 transplant stage was significantly higher than that in the ZD region. In addition, the results of the hierarchical sample metabolic pathway abundance map showed that the PWY-6572 metabolic pathway was mainly realized by Paenibacillus, and that the relative abundance of flue-cured tobacco rhizosphere microbiota (Paenibacillus) participating in PWY-6572 in the D60 transplant period in the BS region was significantly higher than that in the ZD region. In conclusion, different transplanting periods of flue-cured tobacco have important effects on soil physical and chemical properties and rhizosphere microbial communities. There were significant differences in the rhizosphere microbiota and function of flue-cured tobacco in different regions, which may affect the performance and quality of this type of tobacco.

BackgroundThe global COVID-19 pandemic has been widely regarded as a catalyst for adopting internet health care technology (IHT) in China. IHT consists of new health care technologies that are shaping health services and medical consultations. Health care professionals play a substantial role in the adoption of any IHT, but the consequences of doing so can often be challenging, particularly when employee burnout is prevalent. Few studies have explored whether employee burnout influences the adoption intention of IHT in health care professionals. ObjectiveThis study aims to explain the determinants influencing the adoption of IHT from the perspective of health care professionals. To do so, the study extends the value-based adoption model (VAM) with consideration for employee burnout as a determining factor. MethodsA cross-sectional web-based survey using a sample of 12,031 health care professionals selected through multistage cluster sampling from 3 provinces in mainland China was conducted. The hypotheses of our research model were developed based on the VAM and employee burnout theory. Structural equation modeling was then used to test the research hypotheses. ResultsThe results indicate that perceived usefulness, perceived enjoyment, and perceived complexity positively correlate with perceived value (β=.131, P=.01; β=.638, P

Abstract The therapeutic use of messenger RNA (mRNA) has fueled great hope to combat a wide range of incurable diseases. Recent rapid advances in biotechnology and molecular medicine have enabled the production of almost any functional protein/peptide in the human body by introducing mRNA as a vaccine or therapeutic agent. This represents a rising precision medicine field with great promise for preventing and treating many intractable or genetic diseases. In addition, in vitro transcribed mRNA has achieved programmed production, which is more effective, faster in design and production, as well as more flexible and cost-effective than conventional approaches that may offer. Based on these extraordinary advantages, mRNA vaccines have the characteristics of the swiftest response to large-scale outbreaks of infectious diseases, such as the currently devastating pandemic COVID-19. It has always been the scientists’ desire to improve the stability, immunogenicity, translation efficiency, and delivery system to achieve efficient and safe delivery of mRNA. Excitingly, these scientific dreams have gradually been realized with the rapid, amazing achievements of molecular biology, RNA technology, vaccinology, and nanotechnology. In this review, we comprehensively describe mRNA-based therapeutics, including their principles, manufacture, application, effects, and shortcomings. We also highlight the importance of mRNA optimization and delivery systems in successful mRNA therapeutics and discuss the key challenges and opportunities in developing these tools into powerful and versatile tools to combat many genetic, infectious, cancer, and other refractory diseases.

As a representative nematode-trapping fungus, Dactylellina haptotyla can capture and kill nematodes by producing traps, known as adhesive knobs. In this paper, the strain of D. haptotyla YMF1.03409 was studied by means of medium screening, fermentation, and purification and identification of crude extracts. Eighteen compounds were obtained from D. haptotyla YMF1.03409, including two new metabolites, nosporins C (1) and D (2). The known metabolites were identified to be 3-chloro-4-methoxybenzaldehyde (3), 3-chloro-4-methoxybenzoic acid (4), 2-chloro-1-methoxy-4-(methoxymethyl)benzene (5), 3-hydroxy-3-methyloxindole (6), nicotinic acid (7), succinic acid (8), 3,4-dihydroxybutanoic acid (9), 5′-O-methyladenosine (10), uridine (11), 2′-deoxyuridine (12), thymidine (13), 3-(phenylmethyl)-2,5-morpholinedione (14), methyl-β-D-glucopyranoside (15), 1,2-benzenedicarboxylic acid bis(2-methyl heptyl) ester (16), β-sitosterol (17), and 3β,6α-diol-stigmastane (18). The bioactive assay showed that these compounds had no obvious nematicidal activity against the nematodes Meloidogyne incognita and Panagrellus redivivus.

Rural industrial integration is the key to promoting the development of rural industrial restructuring and modernization, and plays a vital role in improving agricultural economic resilience. Based on the evaluation index system of agricultural economic resilience and the level of rural industrial integration development, respectively, this paper uses panel data from 30 provincial administrative regions in China from 2000 to 2020 to empirically test the impact of rural industrial integration development on agricultural economic resilience by using an individual fixed-effects model and a mediating-effects model. The results show that rural industrial integration significantly contributes to enhancing agricultural economic resilience, and the conclusion still holds after a series of robustness tests. There is dimensional and regional heterogeneity in the impact of rural industrial integration on agricultural economic resilience, and the strength of the promotion effect by dimension is in the order of adaptive adjustment capacity, transformation and innovation capacity, and resilience to recovery capacity. In the eastern and central regions, the promotion effect of rural industrial integration on agricultural economic resilience is more significant. In the main food-producing areas, the promotion effect of rural industrial integration on resilience to recovery is significantly slighter than that of non-food-producing regions. Mechanism analysis indicates that regional industrial structure optimization is an essential channel for rural industrial integration to enhance the resilience of the agricultural economy. On this basis, in order to strengthen agricultural economic resilience, provinces should actively explore differentiated industrial integration policies to enhance industrial structure optimization and upgrading, stimulate agricultural economic vitality, and foster the development of China’s agricultural modernization.

Pioneer transcription factors (TFs) have been proposed to act as protein anchors to orchestrate cell type-specific 3D genome architecture. MyoD is a pioneer TF for myogenic lineage specification. Here the authors provide further support for the role of MyoD in 3D genome architecture in muscle stem cells by comparing MyoD knockout and wild-type mice.

BackgroundStudies have shown that hospitals or physicians with multiple malpractice claims are more likely to be involved in new claims. This finding indicates that medical malpractice may be clustered by institutions. ObjectiveWe aimed to identify the underlying mechanisms of medical malpractice that, in the long term, may contribute to developing interventions to reduce future claims and patient harm. MethodsThis study extracted the semantic network in 6610 medical litigation records (unstructured data) obtained from a public judicial database in China. They represented the most serious cases of malpractice in the country. The medical malpractice network of China was presented as a knowledge graph based on the complex network theory; it uses the International Classification of Patient Safety from the World Health Organization as a reference. ResultsWe found that the medical malpractice network of China was a scale-free network—the occurrence of medical malpractice in litigation cases was not random, but traceable. The results of the hub nodes revealed that orthopedics, obstetrics and gynecology, and the emergency department were the 3 most frequent specialties that incurred malpractice; inadequate informed consent work constituted the most errors. Nontechnical errors (eg, inadequate informed consent) showed a higher centrality than technical errors. ConclusionsHospitals and medical boards could apply our approach to detect hub nodes that are likely to benefit from interventions; doing so could effectively control medical risks.

ABSTRACT The therapeutic use of bacteriophages (phages) provides great promise for treating multidrug-resistant (MDR) bacterial infections. However, an incomplete understanding of the interactions between phages and bacteria has negatively impacted the application of phage therapy. Here, we explored engineered anti-CRISPR (Acr) gene-containing phages (EATPs, eat Pseudomonas) by introducing Type I anti-CRISPR (AcrIF1, AcrIF2, and AcrIF3) genes into the P. aeruginosa bacteriophage DMS3/DMS3m to render the potential for blocking P. aeruginosa replication and infection. In order to achieve effective antibacterial activities along with high safety against clinically isolated MDR P. aeruginosa through an anti-CRISPR immunity mechanism in vitro and in vivo, the inhibitory concentration for EATPs was 1 × 108 PFU/mL with a multiplicity of infection value of 0.2. In addition, the EATPs significantly suppressed the antibiotic resistance caused by a highly antibiotic-resistant PA14 infection. Collectively, these findings provide evidence that engineered phages may be an alternative, viable approach by which to treat patients with an intractable bacterial infection, especially an infection by clinically MDR bacteria that are unresponsive to conventional antibiotic therapy. IMPORTANCE Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic Gram-negative bacterium that causes severe infection in immune-weakened individuals, especially patients with cystic fibrosis, burn wounds, cancer, or chronic obstructive pulmonary disease (COPD). Treating P. aeruginosa infection with conventional antibiotics is difficult due to its intrinsic multidrug resistance. Engineered bacteriophage therapeutics, acting as highly viable alternative treatments of multidrug-resistant (MDR) bacterial infections, have great potential to break through the evolutionary constraints of bacteriophages to create next-generation antimicrobials. Here, we found that engineered anti-CRISPR (Acr) gene-containing phages (EATPs, eat Pseudomonas) display effective antibacterial activities along with high safety against clinically isolated MDR P. aeruginosa through an anti-CRISPR immunity mechanism in vitro and in vivo. EATPs also significantly suppressed the antibiotic resistance caused by a highly antibiotic-resistant PA14 infection, which may provide novel insight toward developing bacteriophages to treat patients with intractable bacterial infections, especially infections by clinically MDR bacteria that are unresponsive to conventional antibiotic therapy.

The control based on dynamic model could improve the dynamic performance of manipulators and obtain better control effects than the control based on kinematic model. As manipulators are complex online multivariable systems, there are various uncertainties in different environments and working conditions. Accurate dynamic parameters are difficult to obtain in practical engineering applications. In this article, a controller is designed by combining the precise control torques obtained by the analytical dynamics method with the compensation control torques obtained by sliding mode method for trajectory tracking of the manipulator with bounded uncertainty. Precise control torques obtained from the Udwadia–Kalaba modeling method could be applied for the control of the ideal manipulator tracking the desired trajectory. Compensation control torques obtained from the sliding mode concept and the Lyapunov stability theory could be applied to compensate the uncertainties of parameters and external disturbances, thus enhancing the robustness of the system. By combining precise control torques with compensation control torques, the end point of the manipulator with uncertainty could track the end of the ideal manipulator and then track the desired trajectory. The simulation results of the three-link manipulator with uncertainty show that the control method can make the controlled target approach the desired trajectory in relatively small torque ranges and obtain high stability accuracy, and the chattering is effectively reduced at the stage of approaching the sliding mode surface.

Abstract Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

Brevundimonas diminuta is broadly distributed in terrestrial and aquatic environments and has various biological activities. In this study, we found that B. diminuta exhibited nematicidal activity against the plant root-knot nematode, Meloidogyne javanica. A total of 42 volatile organic compounds (VOCs) from B. diminuta were identified using gas chromatography–mass spectrometry (GC-MS). The nematicidal activity of the 10 main VOCs was tested against M. javanica. Butyl butanoate (4 µL) caused the mortality of 80.13% of M. javanica after 4 h. The nematicidal activity of an additional 38 butyl-butyrate-like volatile esters was also investigated. Of these, seven had strong nematicidal activity against M. javanica, five of which showed egg-hatching inhibitory activity. This study is the first to report that butyl butanoate, ethyl 2-methylbutanoate, ethyl 4-methylpentanoate, ethyl pent-4-enoate, and methyl undecanoate have nematicidal activity against M. javanica. The results indicated that B. diminuta could serve as a candidate microorganism for the biocontrol of plant root-knot nematodes, showing that volatile esters have great potential as nematicides.

Background and purposeJ147, a novel neurotrophic compound, was originally developed to treat aging-associated neurological diseases. Based on the broad spectrum of cytoprotective effects exhibited by this compound, we investigated whether J147 has cerebroprotection for acute ischemic stroke and whether it can enhance the effectiveness of thrombolytic therapy with tissue plasminogen activator (tPA).MethodsRats were subjected to transient occlusion of the middle cerebral artery (tMCAO) by insertion of an intraluminal suture or embolic middle cerebral artery occlusion (eMCAO), and treated intravenously with J147 alone or in combination with tPA.ResultsWe found that J147 treatment significantly reduced infarct volume when administered at 2 h after stroke onset in the tMCAO model, but had no effect in eMCAO without tPA. However, combination treatment with J147 plus tPA at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 72 h after stroke compared with saline or tPA alone groups in the eMCAO model. Importantly, the combination treatment significantly reduced delayed tPA-associated brain hemorrhage and secondary microvascular thrombosis. These protective effects were associated with J147-mediated inhibition of matrix metalloproteinase-9 (MMP9), 15-lipoxygenase-1, and plasminogen activator inhibitor (PAI) expression in the ischemic hemispheres (predominantly in ischemic cerebral endothelium). Moreover, the combination treatment significantly reduced circulating platelet activation and platelet-leukocyte aggregation compared with saline or tPA alone groups at 24 h after stroke, which might also contribute to reduced microvascular thrombosis and neuroinflammation (as demonstrated by reduced neutrophil brain infiltration and microglial activation).ConclusionOur results demonstrate that J147 treatment alone exerts cerebral cytoprotective effects in a suture model of acute ischemic stroke, while in an embolic stroke model co-administration of J147 with tPA reduces delayed tPA-induced intracerebral hemorrhage and confers cerebroprotection. These findings suggest that J147-tPA combination therapy could be a promising approach to improving the treatment of ischemic stroke.

BackgroundThe measures put in place by health authorities to ensure the professionalism of doctors are important. Hospitals in China have included academic outputs in the promotion criteria to incentive medical clinicians to engage in scientific research so that to improve job performance (JP). However, such practice disproportionally focuses on academic outputs but ignores the force of needs fulfilled brought by intrinsic incentive. This study aims to discuss the realistic problem regarding the promotion mechanism and the potential drivers to clinical JP.MethodsThis study was based on multi-source data collection on clinical performance from electric medical record (EMR), person-environment (P–E) fit from the survey, and academic output from personnel files of ward clinicians (n = 244) of general public hospitals who sought for career progression in Shanghai in 2020. Independent-Sample t-test and chi-square test were used for comparison of two sample means or constituent ratio between promoted and not promoted clinicians. Linear multilevel regression was conducted to examine the relationship between clinical performance and academic outputs and P–E fit.ResultsClinicians who were promoted were more productive in producing academic outputs than those who were not (t = −5.075, p < 0.001). However, there was no difference in clinical performance between the two groups (t = −1.728 to 0.167, p > 0.05). The regression showed that academic outputs were not related to clinical performance, while higher P–E fit was associated with the improvement of various clinical performances.ConclusionThis study shows that P–E fit plays a more important role in facilitating clinical performance than academic performance and highlights the importance of intrinsic motivation of clinicians in achieving clinical performance.

Millions of museum specimens are integral to biodiversity studies; however, DNA degradation may limit the ability to obtain DNA sequences. In this study, a degradation analysis model for Lepidoptera specimens was established. Based on this model, we revealed the characteristics of DNA fragment distribution caused by external DNA damage factors during specimen preservation. We found that the degree of DNA degradation increased over time; DNA degradation of spread and dried adult specimens was significantly higher than that in the folded and formalin-fixed larval specimens. However, the effects of folding wings on DNA degradation and the effects of the preservation method/stage (formalin-fixed larval vs air-dried adult specimens) were different for different species.

Abstract Background Cesarean section (CS) rate has risen dramatically and stayed at a very high level in China over the past two to three decades. Given the short- and long-term adverse effects of CS, effective strategies are needed to reduce unnecessary CS. We aimed to evaluate whether a multifaceted intervention would decrease the CS rate in China. Methods We carried out a cluster-randomized field trial with a multifaceted intervention in Shanghai, China, from 2015 to 2017. A total of 20 hospitals were randomly allocated into an intervention or a control group. The intervention consisted of more targeted health education to pregnant women, improved hospital CS policy, and training of midwives/doulas for 8 months. The study included a baseline survey, the intervention, and an evaluation survey. The primary outcome was the changes of overall CS rate from the pre-intervention to the post-intervention period. A subgroup analysis stratified by the Robson classification was also conducted to examine the CS change among women with various obstetric characteristics. Results A total of 10,752 deliveries were randomly selected from the pre-intervention period and 10,521 from the post-intervention period. The baseline CS rates were 42.5% and 41.5% in the intervention and control groups, respectively, while the post-intervention CS rates were 43.4% and 42.4%, respectively. Compared with the control group, the intervention did not significantly reduce the CS rate (adjusted OR = 0.92; 95% CI 0.73, 1.15). Similar results were obtained in subgroup analyses stratified by the risk level of pregnancy, maternal age, number of previous CS, or parity. Scarred uterus and maternal request remained the primary reasons for CS after the interventions in both groups. The intervention did not alter the perinatal outcomes (adjusted change of risk score = − 0.06; 95%CI − 0.43, 0.31). Conclusions A multifaceted intervention including more targeted prenatal health education, improved hospital CS policy, and training of midwives/doulas, did not significantly reduce the CS rate in Shanghai, China. However, our experience in implementing a multifaceted intervention may provide useful information to other similar areas with high CS use. Trial registration This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (ChiCTR-IOR-16009041) on 17 August 2016.

Arrestins are a family of scaffold proteins that play a crucial role in regulating numerous cellular processes, such as GPCR signaling. The Arthrobotrys oligospora arrestin family contains 12 members, which have highly conserved N-terminal and C-terminal domains. In the presence of ammonia, A. oligospora can change its lifestyle from saprotrophic to carnivorous. During this transition, the expression pattern of arrestin-coding (AoArc) genes was markedly upregulated. Therefore, we disrupted seven AoArc genes from A. oligospora to identify their functions. Although individual arrestin mutant strains display similar pathogenesis, phenotypes, and stress resistance, the fundamental data on the roles of AoArc genes in A. oligospora are obtained in this study. Membrane endocytosis in AoArc mutants was significantly reduced. Meanwhile, the capacity of trap device formation against nematodes and ammonia was impaired due to AoArc deletions. We also found that AoArc genes could regulate conidial phenotypes, cell nuclear distribution, pH response, and stress resistance. Results of qRT-PCR assays revealed that sporulation-regulated genes were affected after the deletion of AoArc genes. In particular, among the 12 arrestins, AoArc2 mediates pH signaling in the fungus A. oligospora. Notably, combined with the classical paradigm of arrestin–GPCR signal transduction, we suggest that arrestin-regulated trap formation in A. oligospora may be directly linked to the receptor endocytosis pathway.

Target of rapamycin complex 1 (TORC1) is an important regulator of various signaling pathways. It can control cell growth and development by integrating multiple signals from amino acids, glucose, phosphate, growth factors, pressure, oxidation, and so on. In recent years, it has been reported that TORC1 is of great significance in regulating cytotoxicity, morphology, protein synthesis and degradation, nutrient absorption, and metabolism. In this review, we mainly discuss the upstream and downstream signaling pathways of TORC1 to reveal its role in fungi.

MicroRNAs (miRNAs or miRs) are a class of small non-coding RNAs that negatively regulate the expression of target genes by interacting with 3′ untranslated regions of target mRNAs to induce mRNA degradation and translational repression. The miR-30 family members are involved in the development of many tissues and organs and participate in the pathogenesis of human diseases. As a key member of the miR-30 family, miR-30c has been implicated in neurological disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and stroke. Mechanistically, miR-30c may act as a multi-functional regulator of different pathogenic processes such as autophagy, apoptosis, endoplasmic reticulum stress, inflammation, oxidative stress, thrombosis, and neurovascular function, thereby contributing to different disease states. Here, we review and discuss the biogenesis, gene regulation, and the role and mechanisms of action of miR-30c in several neurological disorders and therapeutic potential in clinics.

Background: The promotion of a healthy diet via health education is a component of the “Healthy China 2030” plan. However, few studies have reported whether health knowledge about nutrition and diet has gained public attention, and whether it is needed by the public.Methods: The numbers of views, shares, and reads of articles published by the official WeChat account of a hospital in China were accessed. The influence index was obtained via the entropy analysis of these three indices. A questionnaire survey was developed based on the purpose of the study and the conclusion of the content analysis, which conducted to analyze users' requirements for health knowledge and their influencing factors. Moreover, risk factors were explored by logistic regression models.Results: Of the 103 articles considered in this study, four articles in the Top 10 were related to nutrition and diet. The influence index of nutrition and diet knowledge was found to be the highest in the content analysis (p < 0.05). The higher degrees of humor (β = 0.224, p = 0.027), nutrition and diet articles (β = 0.776, p = 0.034), and cover articles (β = 0.312, p = 0.021) have significant influences on the influence index. In total, 581 questionnaires were obtained, and 78.1% of the respondents reported believing that the health knowledge of greatest concern was that related to nutrition and diet. Multivariate logistic regression analyses were conducted to explore the associations between the features of the articles and users reading nutrition and diet knowledge; it was found that gender (female, OR: 4.651, 95%Cl: 2.598, 8.325, and p < 0.001), age (young adult, OR: 0.358, 95%Cl: 0.266, 0.481, and p < 0.001), cancer precaution knowledge (OR: 4.333, 95%Cl: 2.262, 8.299, and p < 0.001), traditional Chinese medicine (OR: 2.121, 95%Cl: 1.064, 4.230, and p = 0.033), the knowledge acquisition approach [circle of friends (OR: 2.586, 95%Cl: 1.373, 4.868, and p = 0.003), social media (OR: 2.183, 95%Cl: 1.204, 3.960, and p = 0.010)), hospitals (OR: 3.194, 95%Cl: 1.793, 5.692, and p < 0.001), television media (OR: 4.348, 95%Cl: 2.341, 8.077, and p < 0.001)], and social media strategies [professionalism and authority (OR: 2.354, 95%Cl: 1.231, 4.505, and p = 0.006)] have statistically significant relationships with users reading nutrition and diet knowledge.Conclusion: Nutrition and diet knowledge could contribute to WeChat user engagement of health information dissemination. Nutrition professionals should improve the scientific popularization ability and effectively use social media for health promotion.

A nematicidal actinomycete strain WH06 was isolated from soil samples and was identified using 16S rRNA as Micromonospora sp. Through medium screening and fermentation, 10 metabolites were isolated from the ethyl acetate extract of its fermentation broth using Sephadex LH-20 and silica gel column chromatography. These compounds were identified as N-acetyltyramine (1), N-acetyltryptamine (2), 1-methylhydantoin (3), benzenepropanoic acid (4), cyclo-(L-Pro-L-Tyr) (5), cyclo(L-Phe-Gly) (6), catechol (7), methyl (4-hydroxyphenyl)acetate (8), 3-hydroxybenzoic acid (9), and 4-hydroxybenzoic acid (10). In an in vitro assay against Meloidogyne incognita, a root-knot nematode, compounds 1, 4, 9, and 10 show nematicidal activity. Among them, benzenepropanoic acid (4) causes 99.02% mortality of nematode at 200 μg mL−1 after 72 h. Moreover, compound 4 also displays activity in inhibiting egg hatching of M. incognita. This suggests that Micromonospora sp. WH06 is a promising candidate for biocontrol of M. incognita.

BackgroundIn China, significant emphasis and investment in health care reform since 2009 has brought with it increasing scrutiny of its public hospitals. Calls for greater accountability in the quality of hospital care have led to increasing attention toward performance measurement and the development of hospital ratings. Despite such interest, there has yet to be a comprehensive analysis of what performance information is publicly available to understand the performance of hospitals in China. ObjectiveThis study aims to review the publicly available performance information about hospitals in China to assess options for ranking hospital performance. MethodsA review was undertaken to identify performance measures based on publicly available data. Following several rounds of expert consultation regarding the utility of these measures, we clustered the available options into three key areas: research and development, academic reputation, and quality and safety. Following the identification and clustering of the available performance measures, we set out to translate these into a practical performance ranking system to assess variation in hospital performance. ResultsA new hospital ranking system termed the China Hospital Development Index (CHDI) is thus presented. Furthermore, we used CHDI for ranking well-known tertiary hospitals in China. ConclusionsDespite notable limitations, our assessment of available measures and the development of a new ranking system break new ground in understanding hospital performance in China. In doing so, CHDI has the potential to contribute to wider discussions and debates about assessing hospital performance across global health care systems.

Abstract Background The splenic inflammatory response after cerebral ischemia has been implicated in secondary brain injury. We have recently reported that CD147 plays an important role in driving brain inflammation after ischemic stroke. In this study, we hypothesized that CD147 may play a role in the splenic inflammatory response after cerebral ischemia. Methods Transient (60 min) middle cerebral artery occlusion was induced in wild-type mice treated with an anti-CD147 antibody (αCD147) 1 h before ischemia onset. The splenic inflammatory response was evaluated at 4 and 24 h, representing the peak and early stage of splenic inflammatory activation in this model. Changes in mRNA and protein expression of CD147 and inflammatory markers were measured using RT-qPCR and western blot, respectively. Immune cells in the spleen and brain were measured using flow cytometry. Results CD147 expression was rapidly upregulated in the spleen at 4 and 24 h after ischemia onset. The splenic inflammatory response induced by cerebral ischemia was inhibited by αCD147 treatment as demonstrated by the reduced expression of cytokines (TNFα, IL-6, IL-1β) and monocyte chemoattractant protein-1 (MCP-1) in the spleen at 4 and 24 h after ischemia onset. Furthermore, reduced expression of Ly-6C and CCR2 coincided with a decrease in the number of Ly-6Chigh MMs subset in the spleen at 4 h after ischemia onset. This suggests αCD147 treatment abrogates cerebral ischemia-induced inflammatory activation of splenic monocytes/macrophages (MMs). In addition, the experiment in splenectomized mice showed the spleen as the major source of infiltrated Ly-6Chigh MMs subset in the ischemic brain and that brain infiltration of Ly-6Chigh MMs was reduced by αCD147 treatment. These results reveal CD147 as a key mediator of the spleen’s inflammatory activation in response to cerebral ischemia.

Abstract Background To investigate any associations between blood glucose (BG) and lipid levels in patients with different glucose tolerance statuses, including type 2 diabetes (T2DM) and impaired glucose regulation (IGR) cases as well as normal glucose tolerance (NGT) individuals. Methods A total of 354 participants were recruited to this study including 174 in the T2DM group, 112 in the IGR group and 68 in the NGT group. We compared BG, insulin and C-peptide (CP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) serum levels during a 3 h oral glucose tolerance test (OGTT) in the 3 groups. Results Basic overall HbA1c serum concentration percentages were 5.52, 6.33 and 9.76% for the NTG, IGR and T2DM cases. During the OGTT, insulin secretion in the IGR group was almost double that of the T2DM group. CP levels were highest in the IGR patients and OGTT related BG concentrations were highest in the T2DM group followed by IGR, but in the IGR group hyperglycemia was less pronounced than in T2DM patients (P

Abstract Shear and membrane locking phenomena are fundamental issues of shell finite element models. A family of refined shell elements for laminated structures has been developed in the framework of Carrera Unified Formulation, including hierarchical elements based on higher-order Legendre polynomial expansions. These hierarchical elements were reported to be relatively less prone to locking phenomena, yet an exhaustive evaluation of them regarding the mitigation of shear and membrane locking on laminated shells is still essential. In the present article, numerically efficient integration schemes for hierarchical elements, including also reduced and selective integration procedures, are discussed and evaluated through single-element p-version finite element models. Both shear and membrane locking are assessed quantitatively through the estimation of strain energy components. The numerical results show that the fully integrated hierarchical shell elements can overcome the shear and membrane locking effectively when a sufficiently high polynomial degree is reached. Reduced and selective integration schemes can help with the mitigation of locking on lower-order hierarchical shell elements.