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Abstract Background The attrition rate of Chinese medical students is high. This study utilizes a nomogram technique to develop a predictive model for dropout intention among Chinese medical undergraduates based on 19 individual and work-related characteristics. Method A repeated cross-sectional study was conducted, enrolling 3536 medical undergraduates in T1 (August 2020-April 2021) and 969 participants in T2 (October 2022) through snowball sampling. Demographics (age, sex, study phase, income, relationship status, history of mental illness) and mental health factors (including depression, anxiety, stress, burnout, alcohol use disorder, sleepiness, quality of life, fatigue, history of suicidal attempts (SA), and somatic symptoms), as well as work-related variables (career choice regret and reasons, workplace violence experience, and overall satisfaction with the Chinese healthcare environment), were gathered via questionnaires. Data from T1 was split into a training cohort and an internal validation cohort, while T2 data served as an external validation cohort. The nomogram’s performance was evaluated for discrimination, calibration, clinical applicability, and generalization using receiver operating characteristic curves (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Result From 19 individual and work-related factors, five were identified as significant predictors for the construction of the nomogram: history of SA, career choice regret, experience of workplace violence, depressive symptoms, and burnout. The AUC values for the training, internal validation, and external validation cohorts were 0.762, 0.761, and 0.817, respectively. The nomogram demonstrated reliable prediction and discrimination, with adequate calibration and generalization across both the training and validation cohorts. Conclusion This nomogram exhibits reasonable accuracy in foreseeing dropout intentions among Chinese medical undergraduates. It could guide colleges, hospitals, and policymakers in pinpointing students at risk, thus informing targeted interventions. Addressing underlying factors such as depressive symptoms, burnout, career choice regret, and workplace violence may help reduce the attrition of medical undergraduates. Trial registration This is an observational study. There is no Clinical Trial Number associated with this manuscript.

Abstract Heart disease is the world’s leading cause of death. Diagnostic models based on electrocardiograms (ECGs) are often limited by the scarcity of high-quality data and issues of data imbalance. To address these challenges, we propose a conditional generative adversarial network (CECG-GAN). This strategy enables the generation of samples that closely approximate the distribution of ECG data. Additionally, CECG-GAN addresses waveform jitter, slow processing speeds, and dataset imbalance issues through the integration of a transformer architecture. We evaluated this approach using two datasets: MIT-BIH and CSPC2020. The experimental results demonstrate that CECG-GAN achieves outstanding performance metrics. Notably, the percentage root mean square difference (PRD) reached 55.048, indicating a high degree of similarity between generated and actual ECG waveforms. Additionally, the Fréchet distance (FD) was approximately 1.139, the root mean square error (RMSE) registered at 0.232, and the mean absolute error (MAE) was recorded at 0.166.

Abstract The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction. A pod-shaped vest-pocket analysis device achieves the whole process for reaction execution, signal acquisition, and result interpretation. SCOPE can detect as low as 0.5 copies/µL (2.5 copies/reaction) of MPXV within 15 min from the sample input to the answer. We validate the developed assay on 102 clinical samples from male patients / volunteers, and the testing results are 100% concordant with the real-time PCR. SCOPE achieves a single-molecular level sensitivity in minutes with a simplified procedure performed on a miniaturized wireless device, which is expected to spur substantial progress to enable the practice application of CRISPR-based diagnostics techniques in a point-of-care setting.

Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyl compounds. However, few studies have explored the molecular mechanisms of bibenzyl biosynthesis. This study presents a comprehensive analysis of DsBBS1 and DsBBS2 function in D. sinense. A molecular docking simulation revealed high-resolution three-dimensional structural models with minor domain orientation differences. Expression analyses of DsBBS1 and DsBBS2 across various tissues indicated a consistent pattern, with the highest expression being found in the roots, implying that they play a pivotal role in bibenzyl biosynthesis. Protein expression studies identified optimal conditions for DsBBS2-HisTag expression and purification, resulting in a soluble protein with a molecular weight of approximately 45 kDa. Enzyme activity assays confirmed DsBBS2’s capacity to synthesize resveratrol, exhibiting higher Vmax and lower Km values than DsBBS1. Functional analyses in transgenic Arabidopsis demonstrated that both DsBBS1 and DsBBS2 could complement the Atchs mutant phenotype. The total flavonoid content in the DsBBS1 and DsBBS2 transgenic lines was restored to wild-type levels, while the total bibenzyl content increased. DsBBS1 and DsBBS2 are capable of catalyzing both bibenzyl and flavonoid biosynthesis in Arabidopsis. This study provides valuable insights into the molecular mechanisms underlying the biosynthesis of bibenzyl compounds in D. sinense.

The narrative inquiry investigates the construction and evolution of a female Chinese language teacher’s identity across her pre-service and in-service phases. Utilising data from interviews, class observation and written reflections, the research examines how internal and external aspects shape her identity development. It specifically explores the role of third positions, meta positions, and promoter positions drawing on the dialogical self theory. The findings reaffirm that a teacher’s identity is fluid and influenced by personal and professional factors. Over time, however, strong teaching beliefs and a growth mindset emerge as pivotal drivers for sustained and positive teacher development. The paper concludes by offering implications for pre-service teacher education and female teachers’ continuing professional development.

Abstract Vaccines are used to protect human beings from various diseases. mRNA vaccines simplify the development process and reduce the production cost of conventional vaccines, making it possible to respond rapidly to acute and severe diseases, such as coronavirus disease 2019. In this study, a universal integrated platform for the streamlined and on-demand preparation of mRNA products directly from DNA templates was established. Target DNA templates were amplified in vitro by a polymerase chain reaction module and transcribed into mRNA sequences, which were magnetically purified and encapsulated in lipid nanoparticles. As an initial example, enhanced green fluorescent protein (eGFP) was used to test the platform. The expression capacity and efficiency of the products were evaluated by transfecting them into HEK-293T cells. The batch production rate was estimated to be 200–300 μg of eGFP mRNA in 8 h. Furthermore, an mRNA vaccine encoding the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein was produced by this platform. The proposed integrated platform shows advantages for the universal and on-demand preparation of mRNA products, offering the potential to facilitate broad access to mRNA technology and enable the development of mRNA products, including the rapid supply of new mRNA-based vaccines in pandemic situations and personalized mRNA-based therapies for oncology and chronic infectious diseases, such as viral hepatitis and acquired immune deficiency syndrome.

Abstract Biosorbents have been extensively studied for heavy metal adsorption due to their advantages of low cost and high efficiency. In the study, the living and non-living biomass of Cupriavidus necator GX_5 previously isolated were evaluated for their adsorption capacity and/or removal efficiency for Cd (II) through batch experiments, SEM and FT-IR investigations. The maximum removal efficiency rates for the live and dead biomass were 60.51% and 78.53%, respectively, at an optimum pH of 6, a dosage of 1 g/L and an initial Cd (II) concentration of 5 mg/L. The pseudo-second-order kinetic model was more suitable for fitting the experimental data, indicating that the rate-limiting step might be chemisorption. The Freundlich isotherm model fit better than the Langmuir isotherm model, implying that the adsorption process of both biosorbents was heterogeneous. FT-IR observation reflected that various functional groups were involved in Cd (II) adsorption: –OH, –NH, C=O, C–O and C–C groups for the living biomass and –OH, –NH, C–H, C = O, C–N and N–H groups for the dead biomass. Our results imply that non-living biosorbents have a higher capacity and stronger strength for absorbing Cd (II) than living biomass. Therefore, we suggest that dead GX_5 is a promising adsorbent and can be used in Cd (II)-contaminated environments.

With the aggravation of environmental pollution and the worldwide epidemic of infectious diseases, there is a higher demand for air filtration materials to intercept fine particulate matter and capture biological pollutants. Polypropylene (PP)/polycarbonate (PC) blends were melt blown and electrospun with polytetrafluoroethylene (PTFE) on their surfaces. The PP/PC/PTFE membranes structure with micro-nanostructure was constructed through the melt-blown layer with micron structure and the electrospun layer with the nanostructure. Carboxymethyl chitosan (CMCS) was loaded onto the surface of the PP/PC melt-blown layer. The synergistic effect of micro-nanostructure and CMCS can effectively capture PM2.5 and make the composite membrane have excellent antibacterial performance. The inhibition rates of PP/PC/PTFE composite membrane loaded with 5% CMCS against Staphylococcus aureus and Escherichia coli reached 81.54% and 86.1%, respectively. The filtration efficiency of PP/PC/PTFE composite membrane loaded with 5% CMCS is close to 100% for 0.25 μm particles, and the average filtration efficiency for 0.200–4.596 μm and 0.200–2.500 μm particles is 97.31% and 97.27%, respectively. After washing and drying five times, the corresponding inhibition rate only lost 16.52% and 4.24%. The micro/nano structure composite membrane prepared in this study has good antibacterial performance, high filtration efficiency, good stability, and is an excellent antibacterial high efficiency air filter. It provides a new idea for the preparation of air filter fiber composites.

Abstract Intrahepatic cholangiocarcinoma (ICC) is the second common primary hepatic malignancy tumor. In this study, an integrative analysis of differentially expressed genes (DEGs) and miRNAs from the ICC onset and adjacent normal tissues were performed to explore the regulatory roles of miRNA–mRNA interaction. A total of 1018 DEGs and 39 miRNAs were likely involved in ICC pathogenesis, suggesting the changes in cell metabolism in ICC development. The built network indicated that 30 DEGs were regulated by 16 differentially expressed miRNA. The screened DEGs and miRNA together were probably considered the biomarkers of ICC, and their important roles in ICC pathogenesis remain to be elucidated. This study could provide a good basis to uncover the regulatory mechanism of miRNA and mRNAs in ICC pathogenesis.

The development of urbanization and the transformation of green lands into impermeable land increase temperature and create urban heat islands (UHIs). Our observations with remote sensing instruments of Landsat platforms show considerable changes in land use types in Beijing city with the shrinking of green lands, expansion of built environments, and a slight increase in the temperature during the recent four decades. Using remote sensing instruments of Landsat platforms and registered data from two meteorological stations in Beijing, this study finds the relationship between land surface temperature (LST) and the increasing conversion of cultivated lands into built-up areas. This article presents innovative research that shows the mutual correlation well and recommends revisions in the land use policies for better weather. The geographically weighted regression model (GWR) with a Gaussian weighting kernel function analyzes the impact of various urban land use types on the LST and the increase UHIs. In Beijing city, green lands show fewer standard deviations (SD) in the average temperatures equal to 0.109, while the industrial spaces exhibit a high SD equal to 0.212. The outcomes of this paper contribute to finding optimal land use policies everywhere in the world with the increasing urbanization through simulating its model for a more comfortable life.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Oxidative stress is one of the main inducers of NAFLD. Atractylodin (ART), a major active ingredient of Atractylodes lancea, possesses potential antioxidant and anti-inflammatory activity in many types of disease. In the current study, the underlying mechanism by which ART alleviates the progression of NAFLD was explored. The function of ART in facilitating NAFLD was investigated in vitro and in vivo. Functionally, ART attenuated high-fat diet (HFD)-induced NAFLD in mice and palmitic acid (PA)-induced oxidative stress in HepG2 cells. Furthermore, our data verified that ART attenuated HFD-induced NAFLD by inhibiting ferroptosis of hepatocyte cells, as evidenced by decreased Fe2+ concentration, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, and increased glutathione (GSH) content. The protective effect of ART on the cell viability of hepatocytes was blocked by a specific ferroptosis inhibitor (ferrostatin-1). Mechanistically, ART treatment promoted the translocation of nuclear factor erythroid 2-related Factor 2 (NFE2L2/NRF2) and thus increased glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) expression. Taken together, ART alleviates NAFLD by regulating Nrf2-mediated ferroptosis.

An attempt is made in this paper to devise a finite-time adaptive fuzzy back-stepping control scheme for a class of multi-input and multi-output (MIMO) coupled nonlinear systems with immeasurable states. In view of the uncertainty of the system, adaptive fuzzy logic systems (AFLSs) are used to approach the uncertainty of the system, and the unmeasured states of the system are estimated by the finite-time extend state observers (FT-ESOs), where the state of the observer is a sphere around the state of the system. The accuracy and efficiency of the control effect are ensured by combining the back-stepping and finite-time theory. It is proved that all the states of the closed-loop adaptive control system are semi-global practical finite-time stability (SGPFS) by the finite-time Lyapunov stability theorem, and the tracking errors of the system states converge to a tiny neighborhood of the origin in a finite time. The validity of this scheme is demonstrated by a simulation.

Shrub willows are widely planted for landscaping, soil remediation, and biomass production, due to their rapid growth rates. Identification of regulatory genes in wood formation would provide clues for genetic engineering of willows for improved growth traits on marginal lands. Here, we conducted an expression quantitative trait locus (eQTL) analysis, using a full sibling F1 population of Salix suchowensis, to explore the genetic mechanisms underlying wood formation. Based on variants identified from simplified genome sequencing and gene expression data from RNA sequencing, 16,487 eQTL blocks controlling 5505 genes were identified, including 2148 cis-eQTLs and 16,480 trans-eQTLs. eQTL hotspots were identified, based on eQTL frequency in genomic windows, revealing one hotspot controlling genes involved in wood formation regulation. Regulatory networks were further constructed, resulting in the identification of key regulatory genes, including three transcription factors (JAZ1, HAT22, MYB36) and CLV1, BAM1, CYCB2;4, CDKB2;1, associated with the proliferation and differentiation activity of cambium cells. The enrichment of genes in plant hormone pathways indicates their critical roles in the regulation of wood formation. Our analyses provide a significant groundwork for a comprehensive understanding of the regulatory network of wood formation in S. suchowensis.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Dendrobium sinense, a native orchid species of Hainan Island, is cultivated for its ornamental flowers. Recently, this species has gained significant attention due to its medicinal value. This study focuses on the identification of type III polyketide synthase (PKS), which catalyzes the formation of crucial intermediates in secondary metabolites. Through analysis of previous transcriptome data, a total of ten type III DsPKS genes were identified. Phylogenetic analysis categorized the type III PKS proteins into CHS, BBS, and PKS groups. Interestingly, the DsCHS3 gene exhibited alternative first exons, resulting in two splice variants, namely DsCHS3-1 and DsCHS3-2. Full-length cDNA sequencing revealed that DsCHS3-1 was the more prevalent splice variant. Prokaryotic expression and purification of DsCHS3-1 and DsCHS3-2 proteins were successfully achieved. Enzyme activity analysis demonstrated significantly higher catalytic activity in DsCHS3-2 compared to DsCHS3-1, particularly in the conversion of p-coumaryol-CoA and malonyl-CoA to naringin chalcone. Functional complementation assays in Arabidopsis mutants confirmed the higher catalytic activity of DsCHS3-2, as it restored flavonoid biosynthesis to a greater extent compared to DsCHS3-1. Overall, these findings offer valuable insights into the alternative splicing patterns and functional divergence of DsCHS3 genes in D. sinense.

Objectives: During COVID-19 pandemic in 2020, China, some public health measures of forced lockdown, closure of school and public meeting places, staying at home, transportation stop, masks wearing, hands washing, environmental disinfection were taken on to control epidemic transmission, these measures have made indirect affect on the other infectious diseases incidence. Study design: During COVID-19 pandemic in 2020, we retrospectively analyzed and compared reported cases of other infectious diseases,in order to found what impact of measures in controlling COVID-19 pandemic on the other infectious diseases in China. Methods: We retrospectively analyzed and compared reported cases of measles, pertussis, scarlet fever, seasonal influenza, mumps, HFMD each month in 2018, 2019 and 2020 from the National Health Commission, PRC. Results: Cases of measles, pertussis, scarlet fever, seasonal influenza, mumps and HFMD in January 2020 were not declined, or even increased compare to 2018 and 2019, but from February to December 2020, began to drop significantly compare with the cases of 2018 and 2019. However, seasonal influenza cases in 2020 were more than in 2018. Conclusion: It shown that how important scientific measures are taken to cut off COVID-19 pandemic transmission, However, these taken measures have led to indirect impact on the diffusion of other infectious diseases, led to measles, pertussis, scarlet fever, seasonal influenza, mumps, HFMD declined.

Developing learner autonomy has been a critical task in English teaching that requires a clear understanding of the feature of classroom environment. This study aims to examine how senior high school students perceive classroom environment and learner autonomy, and how classroom environment exerts its influence on learner autonomy in Chinese EFL learning context. Participants (N = 565) from 15 classes located in northeast of China were selected to fill in an adapted version of What is Happening in This Class (WIHIC) and English Autonomous Learning Ability scale. Interview was conducted to confirm and illustrate the quantitative findings. The results revealed that senior high students had favorable perceptions of English classroom environment and learner autonomy. Grade differences existed in their perceptions. Moreover, we found that 53.7% of the variance in learner autonomy was accounted for by students’ perceptions of English classroom environment, which indicated that English classroom environment had significantly positive effects on learner autonomy. Specifically, task orientation, student involvement, teacher support and finding references were strong predictors to learner autonomy. The possible reasons for the findings were discussed and recommendations for future research were given.

Objectives Assess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia.Design Retrospective cohort study.Setting Large integrated health system with 9 million members in California, USA.Participants 4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV).Interventions Receipt of tocilizumab within 10 days of initiation of IMV.Outcome measures Using a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge.Results Among 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3–10 days after initiation of IMV.Conclusions Among mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse etiologies, morphologies, and clinical outcomes, but our knowledge of its epidemiology and carcinogenesis is very limited.Materials and methods: The expression patterns of circRNAs were explored in iCCA tissues and corresponding adjacent normal ones, denoted by (iCCA) and (iCCAP), respectively, using high-throughput sequencing.Results: A total of 117 differential expressed (DE) circRNAs were identified. Based on the parental transcripts of circRNAs, these DE circRNAs were related to several important GO terms and were enriched in important pathways. Two circRNA-mediated ceRNA networks were constructed and many important metabolic pathways related to mRNAs were regulated by DE circRNAs via miRNAs.Conclusion: Our study revealed the DE circRNAs in the iCCA tissues compared with iCCAP ones, suggesting that circRNAs may play crucial roles in the pathogenesis of iCCA.

Abstract Introduction Melanoma is a highly aggressive malignant skin tumor as well as the primary reason for skin cancer‐specific deaths. We first identified immune‐related long noncoding RNA (lncRNA) prognostic signature and found potential immunotherapeutic targets for melanoma cancer. Methods RNA‐seq data and clinical features of melanoma samples were obtained from The Cancer Genome Atlas. Samples of melanoma were randomly assigned to the training and testing cohort. The immune‐related lncRNA signature was then obtained via using univariate, LASSO, and multivariate Cox analysis of patients in the training cohort. Eight significant immune‐related lncRNA signature was then subsequently obtained through correlation analysis between immune‐related genes and lncRNAs. The association between risk score and immune cell infiltration was finally assessed using TIMER and CIBERSORT. Results Three hundred and fifty‐six immune‐related lncRNAs were obtained. Among them, eight immune‐related lncRNAs were identified to build a prognostic risk signature model. The model's performance was then confirmed using the Kaplan–Meier curves, risk plots, and time‐dependent receiver‐operating characteristic curves in the training cohort. The risk score was identified and confirmed as an independent prognostic factor through univariate and multivariate Cox regression analyses. These results were further verified in the testing and whole cohorts. CIBERSORT algorithm showed that the infiltration levels of T cells CD8, M1 macrophages, plasma cells, T cells CD4 memory activated, T cells gamma delta, and mast cells activated were significantly lower in the high‐risk group while the infiltration level of macrophages M0 was significantly lower in the low‐risk group. Conclusion The immune‐related lncRNA signature offers prognostic markers and potential immunotherapeutic targets for melanoma.

In order to analyze the effect of EV71 vaccination on the incidence of encephalitis in patients with HFMD, 292 cases were vaccinated, and 2,486 cases were not vaccinated which were collected in 2018 and 2019. It shows that the incidence rate of encephalitis in vaccinated patients was significantly lower than that in non-vaccinated (P = .028), which suggests that EV71 vaccine has a protective effect on the occurrence of encephalitis. But some EV71 vaccinated patients still developed into encephalitis showed that they had not produced protection or protection was weak against EV71-related encephalitis; the reasons require further investigation.

Efforts to improve preservice teacher education have recently focused on developing teachers’ adequate pedagogical knowledge (PK), content knowledge (CK), and pedagogical content knowledge (PCK), which are critical elements of teacher’s professional knowledge, and important indicators of preparedness to teach. However, the development of the three knowledge domains of Chinese preservice English as a foreign language (EFL) teachers is surprisingly under-researched. To fill this gap, this study examined the development of the three knowledge domains of a group of Chinese preservice EFL teachers at different stages of a teacher education program. Specifically, it explored the relationship among the three knowledge domains, and the effects of learning opportunities on their development. Findings revealed that preservice EFL teachers at a later stage outperformed those at an earlier stage with regard to PK and PCK. Our findings also suggested that there were positive correlations among PK, CK, and PCK at different stages of the teacher education program. Furthermore, the findings showed that courses on CK, PK, and PCK, and teaching experience significantly influenced preservice EFL teachers’ professional knowledge. However, the role of classroom observation was not significant. Implications for EFL teacher education and future research were also discussed.

Objectives:. To compare hypertension remission and relapse after bariatric surgery compared with usual care. Background:. The effect of Roux-en-Y gastric bypass and sleeve gastrectomy on hypertension remission and relapse has not been studied in large, multicenter studies over long periods and using clinical blood pressure (BP) measurements. Methods:. This retrospective cohort study was set in Kaiser Permanente Washington, Northern California, and Southern California. Participants included 9432 patients with hypertension 21–65 years old who underwent bariatric surgery during 2005–2015 and 66,651 nonsurgical controls matched on an index date on study site, age, sex, race/ethnicity, body mass index, comorbidity burden, diabetes status, diastolic and systolic BP, and number of antihypertensive medications. Results:. At 5 years, the unadjusted cumulative incidence of hypertension remission was 60% (95% confidence interval [CI], 58–61%) among surgery patients and 14% (95% CI, 13–14%) among controls. At 1 year, the adjusted hazard ratio for the association of bariatric surgery with hypertension remission was 10.24 (95% CI, 9.61–10.90). At 5 years, the adjusted hazard ratio was 2.10 (95% CI, 1.57–2.80). Among those who remitted, the unadjusted cumulative incidence of relapse at 5 years after remission was 54% (95% CI, 51–56%) among surgery patients and 78% (95% CI 76–79%) among controls, although the adjusted hazard ratio was not significant (hazard ratio, 0.71; 95% CI, 0.46–1.08). Conclusions:. Bariatric surgery was associated with greater hypertension remission than usual care suggesting that bariatric surgery should be discussed with patients with severe obesity and hypertension. Surgical patients who experience remission should be monitored carefully for hypertension relapse.

Background Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.Methods We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Results Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p

Myricetin (MYR) and myricitrin (MYT) are well recognized for their nutraceutical value, such as antioxidant, hypoglycemic, and hypotensive effects. In this work, fluorescence spectroscopy and molecular modeling were adopted to investigate the conformational and stability changes of proteinase K (PK) in the presence of MYR and MYT. The experimental results showed that both MYR and MYT could quench fluorescence emission via a static quenching mechanism. Further investigation demonstrated that both hydrogen bonding and van der Waals forces play significant roles in the binding of complexes, which is consistent with the conclusions of molecular modeling. Synchronous fluorescence spectroscopy, Förster resonance energy transfer, and site-tagged competition experiments were performed to prove that the binding of MYR or MYT to PK could alter its micro-environment and conformation. Molecular docking results revealed that either MYR or MYT spontaneously interacted with PK at a single binding site via hydrogen bonding and hydrophobic interactions, which is consistent with the results of spectroscopic measurements. A 30 ns molecular dynamics simulation was conducted for both PK-MYR and PK-MYT complexes. The calculation results showed that no large structural distortions or interaction changes occurred during the entire simulation time span. The average RMSD changes of PK in PK-MYR and PK-MYT were 2.06 and 2.15 Å, respectively, indicating excellent stability of both complexes. The molecular simulation results suggested that both MYR and MYT could interact with PK spontaneously, which is in agreement with spectroscopic results. This agreement between experimental and theoretical results indicates that the method herein could be feasible and worthwhile for protein–ligand complex studies.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

Purpose. To investigate the characteristics of anterior chamber angle parameters in congenital ectopia lentis (CEL) patients and to evaluate the sensitivity and specificity of anterior segment parameters in distinguishing CEL from healthy controls. Setting. Zhongshan Ophthalmic Center, Guangzhou, China. Design. Cross-sectional study. Methods. 35 CEL patients and 35 age- and sex-matched healthy controls were recruited. Axial length (AL) and anterior segment parameters including anterior chamber width (ACW), angle open distance (AOD), angle recess area (ARA), trabecular-iris space area (TISA), and trabecular-iris angle (TIA) were measured. All the above parameters and the ratio index of angle parameters, which was defined as the angle parameter value of the narrower side to that of the contralateral side, were compared between CEL and controls. Receiver operating characteristic (ROC) curves were also plotted to evaluate the diagnostic performance of anterior chamber angle parameters in CEL patients. Results. All angle parameters of the contralateral side to the dislocated lens side were significantly smaller than those of the dislocated lens side in CEL (all P

Objective: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. Methods: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9–25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. Results: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1–36.1; p = 0.039). Conclusions: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.

Background: Osteosarcoma is the most general bone malignancy that mostly affects children and adolescents. Numerous stem cell-related genes have been founded in distinct forms of cancer. This study aimed at identifying a stem cell-related gene model for the expected assessment of the prognosis of osteosarcoma patients.Methods: We obtained the genes expression data and relevant clinical materials from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We identified differentially expressed genes (DEGs) from the GEO dataset, whereas prognostic stem cell-related genes were obtained from the TARGET database. Subsequently, univariate, LASSO and multivariate Cox regression analyses were applied to establish the stem cell-related signature. Finally, the prognostic value of the signature was validated in the GEO dataset.Results: Twenty-five genes were prognostic ferroptosis-related DEGs. Consequently, we identified eight stem cell-related genes as a signature of prognosis of osteosarcoma patients. Then, the Kaplan–Meier (K-M) curve, the AUC value of ROC, and Cox regression analysis verified that the eight stem cell-related gene model were a new and substantial prognostic marker independent of other clinical traits. Moreover, the nomogram on the foundation of risk score and other clinical traits was established for predicting the survival rate of osteosarcoma patients. Biological function analyses displayed that tumor related pathways were affluent.Conclusion: The expression level of stem cell-related genes offers novel prognostic markers as well as underlying therapeutic targets for the therapy and prevention of osteosarcoma.

Retinal ganglion cells (RGCs), the projection neurons of the eye, are irreversibly lost once the optic nerve is injured, which is a critical mechanism of glaucoma. Mobile zinc (Zn2+) levels rapidly increase in retinal interneuron amacrine cells and Zn2+ is then transferred to RGCs via the Zn2+ transporter protein ZnT-3, triggering RGC loss in optic nerve injury. Zn2+ chelation and ZnT-3 deletion promote long-term RGC survival. However, the downstream signaling pathways of Zn2+ in RGCs remains unknown. Here, we show that increased levels of Zn2+ upregulate the expression and activity of mitochondrial zinc metallopeptidase OMA1 in the retina, leading to the cleavage of DELE1 and activation of cytosolic eIF2α kinase PKR, triggering the integrated stress response (ISR) in RGCs. Our study identified OMA1 and ISR as the downstream molecular mechanisms of retinal Zn2+ and potential targets for preventing the progression of Zn2+-associated neuronal damage.

Abstract Background Coronavirus disease 2019 (COVID‐19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has extracted devastating tolls. Despite its pervasiveness, robust information on disease characteristics in the emergency department (ED) and how that information predicts clinical course remain limited. Methods We conducted a retrospective cohort study of the first ED visit from SARS‐CoV‐2‐positive patients in our health system, from February 21, 2020 to April 5, 2020. We reviewed each patient's ED visit(s) and included the first visit with symptoms consistent with COVID‐19. We collected demographic, clinical, and treatment variables from electronic health records and structured manual chart review. We used multivariable logistic regression to examine the association between patient characteristics and 2 primary outcomes: a critical outcome and hospitalization from index visit. Our critical outcome was defined as death or advanced respiratory support (high flow nasal cannula or greater) within 21 days. Results Of the first 1030 encounters, 801 met our inclusion criteria: 15% were over age 75 years, 47% were female, and 24% were non‐Hispanic white. We found 161 (20%) had a critical outcome and 393 (49%) were hospitalized. Independent predictors of a critical outcome included a history of hypertension, abnormal chest x‐ray, elevated neutrophil to lymphocyte ratio, elevated blood urea nitrogen (BUN), measured fever, and abnormal respiratory vital signs (respiratory rate, oxygen saturation). Independent predictors of hospitalization included abnormal pulmonary auscultation, elevated BUN, measured fever, and abnormal respiratory vital signs. Conclusions In this large, diverse study of ED patients with COVID‐19, we have identified numerous clinical characteristics that have independent associations with critical illness and hospitalization.

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.

Neurodevelopmental disorders are psychiatric diseases that are usually first diagnosed in infancy, childhood and adolescence. Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by core symptoms including impaired social communication, cognitive rigidity and repetitive behavior, accompanied by a wide range of comorbidities such as intellectual disability (ID) and dysmorphisms. While the cause remains largely unknown, genetic, epigenetic, and environmental factors are believed to contribute toward the onset of the disease. Autism Susceptibility Candidate 2 (Auts2) is a gene highly associated with ID and ASD. Therefore, understanding the function of Auts2 gene can provide a unique entry point to untangle the complex neuronal phenotypes of neurodevelpmental disorders. In this review, we discuss the recent discoveries regarding the molecular and cellular functions of Auts2. Auts2 was shown to be a key-regulator of transcriptional network and a mediator of epigenetic regulation in neurodevelopment, the latter potentially providing a link for the neuronal changes of ASD upon environmental risk-factor exposure. In addition, Auts2 could synchronize the balance between excitation and inhibition through regulating the number of excitatory synapses. Cytoplasmic Auts2 could join the fine-tuning of actin dynamics during neuronal migration and neuritogenesis. Furthermore, Auts2 was expressed in developing mouse and human brain regions such as the frontal cortex, dorsal thalamus, and hippocampus, which have been implicated in the impaired cognitive and social function of ASD. Taken together, a comprehensive understanding of Auts2 functions can give deep insights into the cause of the heterogenous manifestation of neurodevelopmental disorders such as ASD.

Human papillomavirus (HPV) infection is a major cause of cervical cancer. HPV vaccine has been shown to be highly effective in preventing HPV infection, and understanding the genotypes of HPV infection can guide the utilization of HPV vaccine. This epidemiological study aimed to investigate the genotype distribution of HPV in HPV-positive female patients in Changzhou. This study enrolled HPV-positive female patients admitted at the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University were enrolled in this study. HPV genotypes were identified via standard HPV DNA testing. The cohort comprised 5738 patients, that the predominant genotypes were HPV52 (13.4%), HPV16 (9.6%), HPV58 (8.8%), HPV81 (8.6%), and HPV53 (7.7%). HPV infection prevalence was the highest among those aged 41–45 y (16.6%), followed by those aged 31–35 y (15.1%) and 36–40 y (15.1%). In total, 46.8% of infections were found in women aged 31–45 y. The main genotypes of HPV infection upon physical examination or diagnosis of cervicitis and cervical cancer were HPV52, 16, 58, 81, and 53. HPV52, 16, 58, 81, and 53 are the most predominant genotypes of HPV infection. Further, HPV infection is most prevalent among women aged 31–45 y. Our findings provide experimental evidence for guiding HPV vaccination policy.

With the rapid development of high-speed and large-scale complex network, network vulnerability data presents the characteristics of massive, multi-source and heterogeneous, which makes data fusion become more complex. Although existing data fusion methods can fuse multi-source data, they do not consider that the multisource data may affect the accuracy of fusion result. To solve this problem, we propose an ontology and weighted D-S evidence theory-based vulnerability data fusion method. In our method, we utilize ontology to describe the network vulnerability semantically and construct the network vulnerability ontology hierarchically. Then we use weighted D-S evidence theory to perform the operation of probability distribution and fusion processing. Besides, we simulate our method on MapReduce parallel computing platform. The experiment results show that our method is more effective and accurate compared with existing fusion approaches using single detection tool and traditional D-S evidence theory.

Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyls. However, the key rate-limited enzyme involved in bibenzyl biosynthesis has yet to be identified in D. sinense. In this study, to explore whether there is a significant difference between the D. sinense tissues, the total contents of bibenzyls were determined in roots, pseudobulbs, and leaves. The results indicated that roots had higher bibenzyl content than pseudobulbs and leaves. Subsequently, transcriptomic sequencings were conducted to excavate the genes encoding type III polyketide synthase (PKS). A total of six D. sinense PKS (DsPKS) genes were identified according to gene function annotation. Phylogenetic analysis classified the type III DsPKS genes into three groups. Importantly, the c93636.graph_c0 was clustered into bibenzyl synthase (BBS) group, named as D. sinense BBS (DsBBS). The expression analysis by FPKM and RT-qPCR indicated that DsBBS showed the highest expression levels in roots, displaying a positive correlation with bibenzyl contents in different tissues. Thus, the recombinant DsBBS-HisTag protein was constructed and expressed to study its catalytic activity. The molecular weight of the recombinant protein was verified to be approximately 45 kDa. Enzyme activity analysis indicated that the recombinant DsBBS-HisTag protein could use 4-coumaryol-CoA and malonyl-CoA as substrates for resveratrol production in vitro. The Vmax of the recombinant protein for the resveratrol production was 0.88 ± 0.07 pmol s−1 mg−1. These results improve our understanding with respect to the process of bibenzyl biosynthesis in D. sinense.

Efforts to improve student–teacher education have recently focused on developing adequate Pedagogical Content Knowledge (PCK) as a critical element for effective preparation. Despite many initiatives implemented in teacher education programs, however, their effectiveness in developing student–teachers’ PCK and factors affecting the PCK development are under-researched and evidenced. Drawing upon theories about and research on PCK, this study examined whether a recently updated 2-year teacher education program could develop student–teachers’ PCK effectively and explored what factors influencing the PCK development of student–teachers with different developmental trajectories. Forty English-as-foreign-language (EFL) student–teachers on the program were involved as participants. This study employed a longitudinal research design. Data were collected at four different stages along with the program through the content representation matrix, interviews with all the participants, and focus group interviews with four particularly sampled participants. Findings revealed that the current teacher education program successfully enhanced student–teachers’ PCK and the factors influencing different PCK developmental trajectories were varied and personalized. Implications for teacher education are also discussed.

The pattern, process, and mechanism of residential heterogeneity vary significantly with different geographical scales. However, most traditional methods ignore the checkboard and modifiable areal unit problem (MAUP), which may cover up the complexity and hierarchy of social space. Taking Hangzhou city as an example, a multiscalar method was proposed based on the information entropy theory to estimate residential heterogeneity and its scale sensitivity. Based on the sixth population census of Hangzhou and the housing price database of 6,536 residential districts from 2008 to 2018, we explore the scale effect and dynamic characteristics of residential heterogeneity. The results of spatial simulation and geostatistical analysis based on Python Spatial Analysis Library (PySAL) module show that the multiscalar algorithm better presents the real segregation pattern than traditional method, which is one of the new models and technologies in urban geography complex system. Exploring residential heterogeneity through multiscalar lens provides an important basis for the gradual and refined urban renewal.

Osteosarcoma is the most common malignant bone tumor in children and adolescence. Multiple immune-related genes have been reported in different cancers. The aim is to identify an immune-related gene signature for the prospective evaluation of prognosis for osteosarcoma patients. In this study, we evaluated the infiltration of immune cells in 101 osteosarcoma patients downloaded from TARGET using the ssGSEA to the RNA-sequencing of these patients, thus, high immune cell infiltration cluster, middle immune cell infiltration cluster and low immune cell infiltration cluster were generated. On the foundation of high immune cell infiltration cluster vs. low immune cell infiltration cluster and normal vs. osteosarcoma, we found 108 common differentially expressed genes which were sequentially submitted to univariate Cox and LASSO regression analysis. Furthermore, GSEA indicated some pathways with notable enrichment in the high- and low-immune cell infiltration cluster that may be helpful in understanding the potential mechanisms. Finally, we identified seven immune-related genes as prognostic signature for osteosarcoma. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that the seven immune-related genes signature was an innovative and significant prognostic factor independent of clinical features. These results of this study offer a means to predict the prognosis and survival of osteosarcoma patients with uncovered seven-gene signature as potential biomarkers.

Clonorchiasis is an important zoonotic parasitic disease worldwide. In view of the fact that parasite infection affects host metabolism, and there is an intricate relationship between metabolism and immunity. Metabolic analysis of the spleen could be helpful for understanding the pathophysiological mechanisms in clonorchiasis. A non-targeted ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF MS) approach was employed to investigate the metabolic profiles of spleen in rats at 4 and 8 weeks post infection with Clonorchis sinensis (C. sinensis). Then a targeted ultra-high performance liquid chromatography multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS) approach was used to further quantify amino acid metabolism. Multivariate data analysis methods, such as principal components analysis and orthogonal partial least squares discriminant analysis, were used to identify differential metabolites. Finally, a total of 396 and 242 significant differential metabolites were identified in ESI+ and ESI− modes, respectively. These metabolites included amino acids, nucleotides, carboxylic acids, lipids and carbohydrates. There were 38 significantly different metabolites shared in the two infected groups compared with the control group through the Venn diagram. The metabolic pathways analysis revealed that pyrimidine metabolism, aminoacyl-tRNA biosynthesis, purine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis were significantly enriched in differential metabolites, which was speculated to be related to the disease progression of clonorchiasis. Furthermore, 15 amino acids screened using untargeted profiling can be accurately quantified and identifed by targeted metabolomics during clonrochiasis. These results preliminarily revealed the perturbations of spleen metabolism in clonorchiasis. Meanwhile, this present study supplied new insights into the molecular mechanisms of host-parasite interactions.

Autism spectrum disorders (ASD) have been found to be associated with immune dysfunction and elevated cytokines, although the detailed mechanism remains unknown. In this study, we aim to investigate the potential mechanisms through a maternal diabetes-induced autistic mouse model. We found that maternal diabetes-induced autistic offspring have epigenetic changes on the superoxide dismutase 2 (SOD2) promoter with subsequent SOD2 suppression in both hematopoietic stem cells (HSC) and peripheral blood mononuclear cells (PBMC). Bone marrow transplantation of normal HSC to maternal diabetes-induced autistic offspring transferred epigenetic modifications to PBMC and significantly reversed SOD2 suppression and oxidative stress and elevated inflammatory cytokine levels. Further, in vivo human study showed that SOD2 mRNA expression from PBMC in the ASD group was reduced to ~12% compared to typically developing group, and the SOD2 mRNA level-based ROC (Receiver Operating Characteristic) curve shows a very high sensitivity and specificity for ASD patients. We conclude that maternal diabetes induces immune dysfunction in autistic offspring through SOD2 suppression and oxidative stress in HSC. SOD2 mRNA expression in PBMC may be a good biomarker for ASD diagnosis.

Doxorubicin (DOX), a wide-spectrum chemotherapeutic agent, is recognized to have cardiotoxic side effects when it is applied in hematological diseases and solid tumor management. However, the mechanisms behind the DOX-induced anomaly of vascular homeostasis remain mostly elusive. qRT-PCR and immumohistochemical staining indicated cardiac increase of miR-526b-3p, and decrease of CD31 and CD34 in DOX-treated mice. The regulatory function of miR-526b-3p on cardiac function and cardiac microvessel density was detected via the transfection of miR-526b-3p mimics or inhibitor into Human Umbilical Vein Endothelial Cells (HUVECs) and the administration of rAAV in mice. HUVECs proliferation, apoptosis, tube formation, and migration were inspected by EdU, flow cytometry, tube formation and transwell assays. MiR-526b-3p was anti-proliferative but apoptosis-initiating in HUVECs, and aggravated cardiac abnormalities caused by DOX. Mechanically, the relationship between miR-526b-3p and VEGFA was disclosed by qRT-PCR. VEGFA and STAT3 interaction was confirmed by ChIP and luciferase reporter assay. MiR-526b-3p targeted STAT3 to reduce VEGFA transcription. We designed rescue assays and presented that the negative effects of miR-526b-3p on cardiac dysfunction and HUVECs were rescued by VEGFA reintroduction in DOX-affected mice. Overall, miR-526b-3p accelerated doxorubicin-induced cardiotoxicity through modulating STAT3/VEGFA, highlighting that targeting miR-526b-3p as a potential method to protect against DOX-induced cardiac dysfunction.

Fault identification under variable operating conditions is a task of great importance and challenge for equipment health management. However, when dealing with this kind of issue, traditional fault diagnosis methods based on the assumption of the distribution coherence of the training and testing set are no longer applicable. In this paper, a novel state identification method integrated by time-frequency decomposition, multi-information entropies, and joint distribution adaptation is proposed for rolling element bearings. At first, fast ensemble empirical mode decomposition was employed to decompose the vibration signals into a collection of intrinsic mode functions, aiming at obtaining the multiscale description of the original signals. Then, hybrid entropy features that can characterize the dynamic and complexity of time series in the local space, global space, and frequency domain were extracted from each intrinsic mode function. As for the training and testing set under different load conditions, all data was mapped into a reproducing space by joint distribution adaptation to reduce the distribution discrepancies between datasets, where the pseudolabels of the testing set and the final diagnostic results were obtained by the k-nearest neighbor algorithm. Finally, five cases with the training and testing set under variable load conditions were used to demonstrate the performance of the proposed method, and comparisons with some other diagnosis models combined with the same features and other dimensionality reduction methods were also discussed. The analysis results show that the proposed method can effectively recognize the multifaults of rolling element bearings under variable load conditions with higher accuracies and has sound practicability.

Fluorophores with aggregation-induced emission enhancement (AIEE) properties have attracted increasing interest in recent years. On the basis of our previous research, we successfully designed and synthesized eleven chalcones. Through an optical performance experiment, we confirmed that compounds 1–6 had obvious AIEE properties. As these AIEE molecules had excellent fluorescence properties and a large Stokes shift, we studied their application in living cell imaging, and the results showed that these compounds had low cytotoxicity and good biocompatibility at the experimental concentrations. More importantly, they could specifically label mitochondria. Subsequently, we selected zebrafish as experimental animals to explore the possibilities of these compounds in animal imaging. The fluorescence imaging of zebrafish showed that these AIEE molecules can enter the embryo and can be targeted to aggregate in the digestive tract, which provides a strong foundation for their practical application in the field of biological imaging. Compared with traditional fluorophores, these AIEE molecules have the advantages of possessing a small molecular weight and high flexibility. Therefore, they have excellent application prospects in the field of biological imaging. In addition, the findings of this study have very positive practical significance for the discovery of more AIEE molecules.

Abstract The present study investigated the environmental distribution and fate of low molecular weight (LMW) polychlorinated biphenyls (PCBs) in China using the ChnGIPERM (Chinese Gridded Industrial Pollutants Emission and Residue Model), in which the air-soil exchange, spatial-temporal variations and the heterogeneity of secondary emission and residue in the non-source areas were studied. The model simulated the temporal and spatial variations of the PCB28 concentration in soils and air which agreed well with historical monitoring data across China. The long-range atmospheric transport (LRAT) and temperature was identified as the major factor affecting the distribution patterns of the secondary emissions and residues. Soil residue was considered as important environmental fate of PCB28. However, the intensity of an emissions source and the distance with non-source area strongly affected the spatial and temporal variations of PCB28 residues in soil. Several factors strongly impacted the distribution characteristics and air-soil exchange of PCB28, including emission patterns, atmospheric transport, soil organic carbon (SOC), soil vertical transfer, ambient temperature, and precipitation.

Abstract The inhibition of microbial biofilms is a significant concern in food safety. In the present study, the inhibitory effect of sodium citrate and cinnamic aldehyde on biofilm formation at minimum inhibitory concentrations (MICs) and sub‐MICs was investigated for Escherichia coli O157:H7 and Staphylococcus aureus. The biofilm inhibition rate was measured to evaluate the effect of sodium citrate on S. aureus biofilms at 24, 48, 72, and 96 hr. According to the results, an antibiofilm effect was shown by both food additives, with 10 mg/ml of sodium citrate exhibiting the greatest inhibition of S. aureus biofilms at 24 hr (inhibition rate as high as 77.51%). These findings strongly suggest that sodium citrate exhibits a pronounced inhibitory effect on biofilm formation with great potential in the extension of food preservation and storage.

We previously reported that acute necrotizing pancreatitis (ANP) after normal or high-fat diet is associated with a decreased number of Paneth cells in ileal crypts. Here, we ablated Paneth cells in a rat model of ANP after normal and high-fat diet to investigate the effects on disease symptoms. Adult male Sprague-Dawley rats received standard rat chow or a high-fat diet for 2 weeks, after which they were treated with dithizone to deplete Paneth cells. Six hours later, ANP was established by retrograde injection of sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at 6, 12, and 24 h for assessment. We found dithizone aggravated ANP-associated pathological injuries to the pancreas and ileum in rats on high-fat or standard diets. Lysozyme expression in ileal crypts was decreased, while serum inflammatory cytokines (TNFα, IL-1β, and IL-17A) and intestinal permeability (serum DAO activity and D-lactate) were increased. Expression of tight junction proteins (claudin-1, zo-1, and occludin) was decreased. Using high-throughput 16S rRNA sequencing, we found dithizone reduced microbiota diversity and altered microbiota composition in rats on high-fat or standard diets. Dithizone decreased fecal short-chain fatty acids (SCFAs) in rats on high-fat or standard diets. Changes in intestinal microbiota correlated significantly with SCFAs, lysozyme, DAO activity, D-lactate, inflammatory cytokines, and pathological injury to the pancreas and ileum in rats on high-fat or standard diets. In conclusion, ablation of Paneth cells exacerbates pancreatic and intestinal injuries in ANP after normal and high-fat diet. These symptoms may be related to changes in the intestinal microbiota.