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Aim: The molecular mechanism underlying Alzheimer's disease (AD) pathologies remains unclear. The brain is extremely sensitive to oxygen deprivation, and brief interruptions in oxygen supply may lead to permanent brain damage. The objective here was to access the red blood cell (RBC) physiological alterations and the changes in blood oxygen saturation of an AD model as well as to explore the possible mechanism underlying these pathologies. Methods: We used female APPswe/PS1ΔE9 mice as AD models. Data were collected at the age of 3, 6, and 9 months. In addition to examining classic features of AD, namely cognitive deficiency and Aβ depositions, 24 h blood oxygen saturation was monitored by Plus oximeters in real time. In addition, RBC physiological parameters were measured by blood cell counter using peripheral blood from the epicanthal veins. Furthermore, in the mechanism investigations, the expression of phosphorylated band 3 protein was examined by a series of Western blot analyses, and the levels of soluble Aβ40 and Aβ42 on the membrane of RBCs were determined by ELISA. Results: Our results showed that the blood oxygen saturation in the AD mice was significantly reduced as early as at 3 months of age, preceding the neuropathological changes and cognitive impairments. Meanwhile, the expression of phosphorylated band 3 protein and levels of soluble Aβ40 and Aβ42 were all elevated in the erythrocytes of the AD mice. Conclusion: APPswe/PS1ΔE9 mice exhibited decreased oxygen saturation together with reduced RBC counts and hemoglobin concentrations at the early stage, which may aid in the development of predictive markers for AD diagnosis. The increased expression of band 3 protein and elevated Aβ40 and Aβ42 levels may contribute to the deformation of RBCs and, in turn, cause the subsequent AD development. [ABSTRACT FROM AUTHOR]

Objective: Observational studies have established a connection between gut microbiota and ankylosing spondylitis (AS) risk; however, whether the observed associations are causal remains unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential causal associations of gut microbiota with AS risk.Instrumental variants of gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiome Project (n = 7738). The FinnGen consortium provided genetic association summary statistics for AS, encompassing 2860 cases and 270,964 controls. We used the inverse-variance weighted (IVW) method as the primary analysis, supplemented with the weighted median method, maximum likelihood–based method, MR pleiotropy residual sum and outlier test, and MR-Egger regression. In addition, we conducted a reverse MR analysis to assess the likelihood of reverse causality.After the Bonferroni correction, species Bacteroides vulgatus remained statistically significantly associated with AS risk (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.22–1.95, P = 2.55 × 10−4). Suggestive evidence of associations of eleven bacterial traits with AS risk was also observed (P < 0.05 by IVW). Among them, eight were associated with an elevated AS risk (OR 1.37, 95% CI 1.07–1.74, P = 0.011 for phylum Verrucomicrobia; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for class Verrucomicrobiae; OR 1.17, 95% CI 1.01–1.36, P = 0.035 for order Bacillales; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for order Verrucomicrobiales; OR 1.43, 95% CI 1.13–1.82, P = 0.003 for family Alcaligenaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for family Verrucomicrobiaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for genus Akkermansia; OR 1.55, 95% CI 1.19–2.02, P = 0.001 for species Sutterella wadsworthensis). Three traits exhibited a negative association with AS risk (OR 0.68, 95% CI 0.53–0.88, P = 0.003 for genus Dialister; OR 0.84, 95% CI 0.72–0.97, P = 0.020 for genus Howardella; OR 0.75, 95% CI 0.59–0.97, P = 0.026 for genus Oscillospira). Consistent associations were observed when employing alternate MR methods. In the reverse MR, no statistically significant correlations were detected between AS and these bacterial traits.Our results revealed the associations of several gut bacterial traits with AS risk, suggesting a potential causal role of gut microbiota in AS development. Nevertheless, additional research is required to clarify the mechanisms by which these bacteria influence AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Methods: Observational studies have established a connection between gut microbiota and ankylosing spondylitis (AS) risk; however, whether the observed associations are causal remains unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential causal associations of gut microbiota with AS risk.Instrumental variants of gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiome Project (n = 7738). The FinnGen consortium provided genetic association summary statistics for AS, encompassing 2860 cases and 270,964 controls. We used the inverse-variance weighted (IVW) method as the primary analysis, supplemented with the weighted median method, maximum likelihood–based method, MR pleiotropy residual sum and outlier test, and MR-Egger regression. In addition, we conducted a reverse MR analysis to assess the likelihood of reverse causality.After the Bonferroni correction, species Bacteroides vulgatus remained statistically significantly associated with AS risk (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.22–1.95, P = 2.55 × 10−4). Suggestive evidence of associations of eleven bacterial traits with AS risk was also observed (P < 0.05 by IVW). Among them, eight were associated with an elevated AS risk (OR 1.37, 95% CI 1.07–1.74, P = 0.011 for phylum Verrucomicrobia; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for class Verrucomicrobiae; OR 1.17, 95% CI 1.01–1.36, P = 0.035 for order Bacillales; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for order Verrucomicrobiales; OR 1.43, 95% CI 1.13–1.82, P = 0.003 for family Alcaligenaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for family Verrucomicrobiaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for genus Akkermansia; OR 1.55, 95% CI 1.19–2.02, P = 0.001 for species Sutterella wadsworthensis). Three traits exhibited a negative association with AS risk (OR 0.68, 95% CI 0.53–0.88, P = 0.003 for genus Dialister; OR 0.84, 95% CI 0.72–0.97, P = 0.020 for genus Howardella; OR 0.75, 95% CI 0.59–0.97, P = 0.026 for genus Oscillospira). Consistent associations were observed when employing alternate MR methods. In the reverse MR, no statistically significant correlations were detected between AS and these bacterial traits.Our results revealed the associations of several gut bacterial traits with AS risk, suggesting a potential causal role of gut microbiota in AS development. Nevertheless, additional research is required to clarify the mechanisms by which these bacteria influence AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Results: Observational studies have established a connection between gut microbiota and ankylosing spondylitis (AS) risk; however, whether the observed associations are causal remains unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential causal associations of gut microbiota with AS risk.Instrumental variants of gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiome Project (n = 7738). The FinnGen consortium provided genetic association summary statistics for AS, encompassing 2860 cases and 270,964 controls. We used the inverse-variance weighted (IVW) method as the primary analysis, supplemented with the weighted median method, maximum likelihood–based method, MR pleiotropy residual sum and outlier test, and MR-Egger regression. In addition, we conducted a reverse MR analysis to assess the likelihood of reverse causality.After the Bonferroni correction, species Bacteroides vulgatus remained statistically significantly associated with AS risk (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.22–1.95, P = 2.55 × 10−4). Suggestive evidence of associations of eleven bacterial traits with AS risk was also observed (P < 0.05 by IVW). Among them, eight were associated with an elevated AS risk (OR 1.37, 95% CI 1.07–1.74, P = 0.011 for phylum Verrucomicrobia; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for class Verrucomicrobiae; OR 1.17, 95% CI 1.01–1.36, P = 0.035 for order Bacillales; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for order Verrucomicrobiales; OR 1.43, 95% CI 1.13–1.82, P = 0.003 for family Alcaligenaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for family Verrucomicrobiaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for genus Akkermansia; OR 1.55, 95% CI 1.19–2.02, P = 0.001 for species Sutterella wadsworthensis). Three traits exhibited a negative association with AS risk (OR 0.68, 95% CI 0.53–0.88, P = 0.003 for genus Dialister; OR 0.84, 95% CI 0.72–0.97, P = 0.020 for genus Howardella; OR 0.75, 95% CI 0.59–0.97, P = 0.026 for genus Oscillospira). Consistent associations were observed when employing alternate MR methods. In the reverse MR, no statistically significant correlations were detected between AS and these bacterial traits.Our results revealed the associations of several gut bacterial traits with AS risk, suggesting a potential causal role of gut microbiota in AS development. Nevertheless, additional research is required to clarify the mechanisms by which these bacteria influence AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Conclusion: Observational studies have established a connection between gut microbiota and ankylosing spondylitis (AS) risk; however, whether the observed associations are causal remains unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential causal associations of gut microbiota with AS risk.Instrumental variants of gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiome Project (n = 7738). The FinnGen consortium provided genetic association summary statistics for AS, encompassing 2860 cases and 270,964 controls. We used the inverse-variance weighted (IVW) method as the primary analysis, supplemented with the weighted median method, maximum likelihood–based method, MR pleiotropy residual sum and outlier test, and MR-Egger regression. In addition, we conducted a reverse MR analysis to assess the likelihood of reverse causality.After the Bonferroni correction, species Bacteroides vulgatus remained statistically significantly associated with AS risk (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.22–1.95, P = 2.55 × 10−4). Suggestive evidence of associations of eleven bacterial traits with AS risk was also observed (P < 0.05 by IVW). Among them, eight were associated with an elevated AS risk (OR 1.37, 95% CI 1.07–1.74, P = 0.011 for phylum Verrucomicrobia; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for class Verrucomicrobiae; OR 1.17, 95% CI 1.01–1.36, P = 0.035 for order Bacillales; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for order Verrucomicrobiales; OR 1.43, 95% CI 1.13–1.82, P = 0.003 for family Alcaligenaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for family Verrucomicrobiaceae; OR 1.31, 95% CI 1.03–1.65, P = 0.026 for genus Akkermansia; OR 1.55, 95% CI 1.19–2.02, P = 0.001 for species Sutterella wadsworthensis). Three traits exhibited a negative association with AS risk (OR 0.68, 95% CI 0.53–0.88, P = 0.003 for genus Dialister; OR 0.84, 95% CI 0.72–0.97, P = 0.020 for genus Howardella; OR 0.75, 95% CI 0.59–0.97, P = 0.026 for genus Oscillospira). Consistent associations were observed when employing alternate MR methods. In the reverse MR, no statistically significant correlations were detected between AS and these bacterial traits.Our results revealed the associations of several gut bacterial traits with AS risk, suggesting a potential causal role of gut microbiota in AS development. Nevertheless, additional research is required to clarify the mechanisms by which these bacteria influence AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk.Key Points• The association of gut microbiota with AS risk in observational studies is unclear.• This MR analysis revealed associations of 12 gut bacterial traits with AS risk. [ABSTRACT FROM AUTHOR]

• The excellent tolerance to SO 2 and ORR activity of the PtFe@FeNC/C-10 catalyst was verified. • The introduction of Fe negatively shifts the 4f 7/2 binding energy of Pt by 0.2 eV, weakening the adsorption strength of Pt for O 2. • This dual protection mechanism, involving steric hindrance and electronic effects, ensures excellent resistance to sulfur dioxide. • This stability advantage benefits from the protective carbon shell, inhibiting the dissolution and agglomeration of Pt nanoparticles. SO 2 , one of the considerable air pollutants, exhibits a stronger binding affinity with Pt when compared to O 2 , thereby inducing irreversible degradation of the Oxygen Reduction Reaction (ORR) catalyzed by Pt-based catalysts. Despite this detrimental phenomenon, scarce investigations have delved into the realm of contaminant-tolerant catalysts, and so far, no effective SO 2 -tolerant catalysts have been proposed. To meet this challenge, we designed and synthesized a core–shell structure catalyst equipped with a dual protection mechanism. This was achieved through the in-situ polymerization of aniline monomers, concomitantly reducing Pt2+. The resulting shell effectively hinders the transmission of SO 2 to the active sites of Pt, while permitting the unimpeded transmission of O 2. Simultaneously, the intermetallic core inhibits the adsorption of SO 2. Therefore, this catalyst exhibits exemplary ORR activity coupled with exceptional resistance to SO 2 resistance. In particular, the PtFe@FeNC/C-10 catalyst, optimized in terms of the quantity of added aniline, demonstrates a mass activity 1.84 times greater and a specific activity 4.03 times higher than that of commercial Pt/C catalysts. Following exposure to SO 2 -induced poisoning, the E 1/2 value of the PtFe@FeNC/C-10 catalyst undergoes a decrease of only 51.7 mV, lower than that observed for the commercial Pt/C catalyst (92.0 mV). Moreover, the results of an accelerated durability test affirm the superior stability of PtFe@FeNC/C-10 in comparison to commercial Pt/C. This stability advantage is attributed to the protective carbon shell, which effectively prevents the detachment and agglomeration of Pt nanoparticles. [ABSTRACT FROM AUTHOR]

Summary: The gas diffusion layer (GDL) is a vital constituent of proton exchange membrane fuel cells (PEMFCs), which directly affects the performance and cost of PEMFCs. Also, the GDL integration can simplify the structure of PEMFC. Herein, a novel substrate‐free microporous layer (sfMPL) has been successfully prepared by a dry‐press method, which broadens the usable humidity range of PEMFCs and improves the performance under different humidity conditions. Precisely, the maximum power density of a single‐cell assembled by sfMPL (with optimised 10 wt.% binder content and 1.0 g pore‐forming agent) is 754 mW cm−2 at 40% relative humidity, which is 36.6% higher than that with conventional GDL (552 mW cm−2). Furthermore, the sfMPL shows outstanding stability after high potential oxidation (1.6 V vs RHE). Our results highlight a promising new class of low‐cost, substrate‐free MPL for PEMFCs and provide a basis for future research on substrate‐free MPL. [ABSTRACT FROM AUTHOR]

Background: Convulsive status epilepticus (CSE) is a common neurologic emergency with high morbidity and mortality. This single center study is aimed to assess changes of serum biochemical biomarkers after seizure, and their associations with the development of CSE.Methods: From January 2015 to October 2016, a total of 57 CSE patients, and 30 healthy controls without central nervous system diseases were enrolled in Children's Hospital of Soochow University. CSE patients were further divided into viral encephalitis (VEN, 13 cases), primary generalized epilepsy (PGE, 30 cases), and complex febrile seizures (CFS, 14 cases). The levels of serum biochemical biomarkers were measured using the corresponding commercial ELISA kits. Logistic regression analysis was performed to identify the associations between these biomarkers and diseases.Results: At the 1st and 4th day of CSE, neuron-specific enolase (NSE; 1st day: 20.553 ± 5.360, 4th day: 10.094 ± 3.426) and vascular endothelial growth factor (VEGF; 1st day: 153.504 ± 31.246, 4th day: 138.536 ± 25.221) in the CSE group were increased compared to the control (NSE: 6.138 ± 1.941; VEGF: 119.210 ± 31.681). Both the levels of S-100 calcium binding protein B (S-100B; 1st day: 0.738 ± 0.391) and C-reactive protein (CRP; 1st day: 11.128 ± 12.066) were elevated at 1st day of CSE (S-100B: 0.387 ± 0.040; CRP: 3.915 ± 2.064). For glial fibrillary acidic protein (GFAP), it was remarkably upregulated at 4th day of CSE (3.998 ± 1.211). NSE (P = 0.000), S-100B (P = 0.000), CRP (P = 0.011), and VEGF (P = 0.000) at 1st day of CSE, and NSE (P = 0.000), VEGF (P = 0.005), and GFAP (P = 0.000) at 4th day of CSE were significantly associated with the occurrence of CSE. Besides, NSE (P = 0.002), S-100B (P = 0.001), and VEGF (P = 0.002) at 4th day of CSE were significantly associated with VEN.Conclusions: The levels of serum NSE, S-100B, CRP, VEGF, and GFAP are associated with CSE. [ABSTRACT FROM AUTHOR]

Objectives. To discover a more powerful diagnostic tool for the detection of hepatocellular carcinoma (HCC). Methods. 16 extracellularly located candidates were selected by analyzing the expression array datasets in GEO. 10 of them were validated in clinical samples by ELISA. Differences of each variable were compared by one-way ANOVA or Kruskal-Wallis test. CCL20 and LCN2 were determined in all samples (HCC, 167; liver cirrhosis, 106; and healthy control, 106) and finally chosen for the construction of the combination model by binary logistic regression. The models were first built using a comprehensive control, including both liver cirrhosis (LC) and healthy donors. Then, the models were rebuilt by using the LC group alone as a control. ROC analysis was performed to compare the diagnostic efficiency of each indicator. Results. Levels of CCL20 and LCN2 in HCC sera were significantly higher than those in all controls. Using the comprehensive control, ROC curves showed that the optimum diagnostic cutoff of the CCL20 and LCN2 combination was 0.443 (area under curve (AUC) of 0.927 (95% CI 0.896-0.951), sensitivity of 0.808, specificity of 0.892, and accuracy of 0.859). For detection of HCC from LC control, the optimum diagnostic cutoff was 0.590 (AUC of 0.919 (95% CI 0.880-0.948), sensitivity of 0.814, specificity of 0.868, and accuracy of 0.834). Furthermore, the model maintained diagnostic accuracy for patients with HCC in the early stage, with the sensitivity and specificity of 0.75 and 0.77 from LC control, yet the AFP only reached 0.5 and 0.67, respectively. Conclusion. A combination model composed of CCL20 and LCN2 may serve as a more efficient tool for distinguishing HCC from nonmalignant liver diseases. [ABSTRACT FROM AUTHOR]

The electrocatalytic oxidation of urea combined with wastewater splitting is considered a promising approach for sustainable hydrogen production, characterized by minimal energy consumption. However, its evolution is greatly hindered by the shortage of efficient and easily accessible electrocatalytic materials. Here, a facile electrochemical activation strategy was conceived and proposed to construct a Cu-doped NiOOH nanolayer encapsulated on Cu2O nanodendrites on Cu mesh substrate (Cu-NiOOH/Cu2O/CM) from the electrodeposited Ni/Cu2O/CM heterostructured precatalyst. It was verified that the incorporation of Cu not only facilitates the rapid formation of Ni(III) species but also contributes to the formation of Cu-Ni(III) bifunctional electrocatalytic active sites. Benefiting from the accessible Cu-Ni(III) dual active sites, high active surface area, good hydrophilic and aerophobic surface properties and superior electrical conductivity of the Cu mesh substrate, the as-prepared Cu-NiOOH/Cu2O/CM exhibits enhanced bifunctional electrocatalytic abilities for electrocatalytic urea oxidation reaction (UOR) and hydrogen evolution reaction (HER). Particularly, for the Cu-NiOOH/Cu2O/CM||Cu-NiOOH/Cu2O/CM configuration toward the UOR||HER coupled system, a significantly reduced cell voltage of 1.43 V vs. RHE @ 10 mA·cm−2 was obtained. The observed cell voltage for the conventional overall water splitting is approximately 190 mV higher than that observed for overall urea splitting. This study proposes a viable approach to achieve and optimize the bifunctional UOR/HER performance of NiOOH active species, which holds significant importance for efficient and stable hydrogen generation from urea-contaminated substandard water. [ABSTRACT FROM AUTHOR]

Background: The respiratory infectious diseases (RID) threaten the health and life quality of school students. However, previous related studies were insufficient in research design and method applied. This study aimed to evaluate the effect of health education on the knowledge and behavior of students toward RID through difference-in-difference (DID) analysis in Gansu, China.Methods: In 2015-2016, a one-year health education program in Gansu, China was conducted. The intervention group contained 1064 students before and 1001 students after the health education (2015 and 2016, respectively). The control group contained 1018 and 1001 students, respectively. The health education, including playing promotional cartoons, developing lectures, giving out handbook copies and making hand copy and blackboard newspapers, and publicity columns on RID, were conducted monthly from 2015 to 2016 in intervention group. The data were collected before and after the health education program with a questionnaire on the students' knowledge and preventive behaviors regarding RID. The ×2 and t tests were performed to compare the accuracy rate and scores for RID knowledge and behavior of the two groups. DID estimation was conducted to evaluate the effect of health education on RID knowledge and behavior while controlling the non- equilibrium variables.Results: After the health education program, the accuracy rate and scores of most items in the intervention group were significantly higher than those in the control group (P < 0.05) except for item k9 "What methods can prevent flu?". The DID results wherein the demographics- age, nationality, and household register were controlled showed that health education significantly improved the accuracy rate of RID knowledge by 5.2-63.9% for most items, although the accuracy rates of items k2 "What's the transmission way of the mumps?" and k9 were significantly decreased by 36.8 and 12.0%. The health education significantly improved the score of knowledge by 155.2% (P < 0.001) and the accuracy rate of all items of RID behavior by 2.9-51.5% except for item b3 "If you have phlegm, how do you usually deal with it?". In addition, the health education also significantly improved the score of behavior toward RID of the sampled students by 138.2% (P < 0.001).Conclusion: The results of this study show that health education seemed to increase the RID knowledge and behavior of students. It is recommended that the health education should be enhanced and popularized in schools of China, and RID transmission routes and prevention methods should attract more attention. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence of impaired renal function and its associated factors in Chinese children. Methods: Children aged 7–18 years in China Health and Nutrition Survey (CHNS) 2009 were included as participants, and their anthropometric measurements, blood pressure (BP) and biochemical parameters were taken for analysis. The estimated glomerular filtration rate (eGFR) was calculated by using the Schwartz 'original' formula. Results: The prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min per 1.73 m2 and <75 mL/min per 1.73 m2 was 10.09% (95% CI: 8.03–12.11) and 1.01% (95% CI: 0.38–1.77), respectively. The prevalence of impaired renal function (eGFR <60 mL/min per 1.73 m2) was 0.25%. Age was detected as a negative associated factor whereas hyperuricemia and elevated total cholesterol (TC) were positively associated factors for subjects with eGFR <90 mL/min per 1.73 m2. In the group of eGFR <75 mL/min per 1.73 m2, only elevated TC was related to the increased odds of decreased eGFR. Conclusion: Our findings underscore the need for large‐scale programs to detect and treat the early‐stage impaired renal function in the paediatric population in China. Summary at a Glance: In this study on the prevalence of impaired renal function and its associated factors in Chinese children, the authors found that the prevalence of impaired renal function in general Chinese children was 0.25%, and there was a strong association between elevated total cholesterol and decreased eGFR. [ABSTRACT FROM AUTHOR]

Objectives. Infectious disease knowledge and behaviors are key elements that ensure student health and safety. This study explores the impact of health education on student knowledge and behaviors toward infectious diseases and determines the factors affecting infectious diseases knowledge and behaviors among students in Gansu, China. Methods. A cross-sectional study and three sampling methods were used in two counties, 12 schools, and 32 classes in Gansu, China, from 2012 to 2013. Collected data included the following: (1) sociodemographic characteristics of 2002 students (1001 participants in the intervention group and 1001 in the control group); (2) accuracy of student knowledge and behaviors toward infectious diseases based on comparison of intervention and control groups through X2 test; and (3) mean scores on knowledge and behavior of students with different characteristics toward infectious diseases, as analyzed through analysis of variance (ANOVA). Multiple linear regression was conducted to analyze factors affecting student knowledge and behaviors toward infectious diseases. Results. Statistically significant differences were observed among eight items of infectious disease transmission and treatment knowledge between intervention and control groups (P<0.001). Average accuracies of knowledge and behaviors toward infectious diseases reached 72.23% and 60.03%. Significant differences were observed in six items on student behavior in rural and urban areas (P<0.001). Health education, household register, and county affected scores of student knowledge and behaviors toward infectious diseases (P<0.05). Gender and education level also affected scores of student behaviors toward infectious diseases (P<0.001). Conclusions. Health education contributes to student knowledge and behaviors toward infectious diseases. Students in the control group need intensified health education on infectious diseases. Health education needs to pay particular attention to rural students, all male students, and students at senior high school level living on campus. [ABSTRACT FROM AUTHOR]

This study aims to shed light on the relationship between drug content and adhesive properties in drug-in-adhesive transdermal patch, and to elucidate molecular mechanisms from the perspective of polymer chain mobility. Lidocaine was selected as model drug. Two acrylate pressure sensitive adhesives (PSAs) with different polymer chain mobility were synthesized. Tack adhesion, shear adhesion and peel adhesion of PSAs with 0, 5%, 10%, 15% and 20% w/w lidocaine contents were tested. Polymer chain mobility was determined by rheology and modulated differential scanning calorimetry experiments. Drug-PSA interaction was analyzed by FT-IR. The effect of drug content on free volume of PSA were determined by positron annihilation lifetime spectroscopy and molecular dynamics simulation. It was found that the polymer chain mobility of PSA was increased with increasing drug content. Due to the variation of polymer chain mobility, tack adhesion increased, and shear adhesion decreased. It was proved that interactions between polymer chains were destroyed by drug-PSA interactions, free volume between polymer chains was expanded, resulting in the increase of polymer chain mobility. We can conclude that the effect of drug content on polymer chain mobility should be considered, when designing a transdermal drug delivery system with controlled and satisfactory adhesion. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • The antiperovskite-modified heterostructure were synthesized by time-saving solution combustion method. • The p-n junction increases the reaction kinetics and available active sites. • The electrocatalysts experience the different structural evolution during HER and OER process. • The reconstructed species show an optimal free energy of reactive intermediates. Developing bifunctional electrocatalysts with abundant reserves and efficient performance is significant for alkaline water electrolysis. Herein, the antiperovskite nitride (Fe x Cu 1-x) 4 N particles anchored on the surface of Cu 2 O nanosheets have been synthesized by one-step solution combustion synthesis with the assistance of KCl. The (Fe x Cu 1-x) 4 N interacts with Cu 2 O in the form of p-n junction. Such an assembly effectively promotes the charge transfer under the interval built-in field, which can regulate the electronic densities to greatly increase the reaction kinetics and available active sites. Moreover, the electrocatalysts experience the different structural evolution during HER and OER process. The in-situ reconstructed species possess a proper free energy of adsorbed intermediates for highly efficient bifunctional electrocatalysis via DFT calculation. The optimal (Fe 1-x Cu x) 4 N-Cu 2 O heterostructure couples show a superior bifunctional performance for water electrolysis, with a low cell voltage of 1.57 V at 10 mA cm−2 and nearly 100 % Faraday efficiency, surpassing the benchmark precious metal couples. [ABSTRACT FROM AUTHOR]

Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. We found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice and human MIBCs. Multi-omics analyses showed that cathepsin H (CTSH) is correlated with chemoresistance and semi-squamatization. Cathepsin inhibition by E64 treatment induces full squamous differentiation and pyroptosis, and thus specifically restrains chemoresistant MIBCs. Mechanistically, E64 treatment activates the tumor necrosis factor pathway, which is required for the terminal differentiation and pyroptosis of chemoresistant MIBC cells. Our study revealed that semi-squamatization is a type of lineage plasticity associated with chemoresistance, suggesting that differentiation via targeting of CTSH is a potential therapeutic strategy for the treatment of chemoresistant MIBCs. [Display omitted] • Chemotherapy leads to semi-squamatization in MIBC • Cathepsin H is essential for chemoresistant MIBC • Cathepsin H inhibition induces terminal squamous differentiation • The TNF pathway mediates the function of cathepsin H in MIBC Wang et al. reveal that semi-squamatization is a type of lineage plasticity associated with chemoresistance in muscle-invasive bladder cancer (MIBC). They find that targeting cathepsin H can induce the terminal squamous differentiation and thus specifically restrain the chemoresistant MIBC. [ABSTRACT FROM AUTHOR]

Baculoviruses generally produce two progeny phenotypes—the budded virus (BV) and the occlusion-derived virus (ODV)—and the intricate mechanisms that regulate the temporal synthesis of the two phenotypes are critical for the virus replication cycle, which are far from being clearly understood. FP25K was reported to be responsible for the regulation of BV/ODV, and the mutations within result in a decrease of normal ODVs formation and an increase of BVs production. In this study, we demonstrated that the increase of BV titer in an fp25k knockout recombinant (fp25k-negative) was a result of higher infectivity of BVs rather than an increased production of BVs. The constitution of the major structural proteins and genome of parental and fp25k-negative BVs were analyzed. The results showed that the integrity of the majority of DNA packaged into the fp25k-negative BVs was intact; i.e., the genomic DNA of fp25k-negative BV had better transformation and transfection efficiency than that of the parental virus, indicating more intact genomes in the virions. Although the analysis of proteins associated with BVs revealed that more envelope protein GP64 were incorporated into the fp25k-negative BVs, subsequent experiments suggested that overexpression of GP64 did not improve the titer of BVs. Thus, we conclude that the main reason for higher infectivity of BVs is due to better genome integrity, which benefits from the deletion of fp25k resulting in increased stability of the genome and produce a higher proportion of infectious BVs. FP25K acts as a negative factor for the infectivity of BV. [ABSTRACT FROM AUTHOR]

Two novel surface plasmon resonance immunosensors were fabricated for detection of the Bacillus thuringiensis Cry1Ab protein and to demonstrate their performance in analyzing Cry1Ab protein in crop samples. Sensor 2 was modified by 1,6-hexanedithiol, Au/Ag alloy nanoparticles, 3-mercaptopropionic acid, and protein A (or not [sensor 1]), with Cry1Ab monoclonal antibody. As a result, both of the immunosensors exhibited satisfactory linear responses in the Cry1Ab protein concentration ranges of 10 to 500 ng ml −1 and 8 to 1000 ng ml −1 , and the detection limits were 5.0 and 4.8 ng ml −1 , respectively. The immunosensors possessed good specificity and acceptable reproducibility. In addition, crop samples could be analyzed after a simple treatment. The transgenic crops could be easily identified from the conventional ones by the two immunosensors. [ABSTRACT FROM AUTHOR]

Two novel Fourier transform-surface plasmon resonance immunosensors were fabricated for the determination of the subgroup J avian leukosis virus. The immunosensors were based on a functionalized gold substrate and immobilized gold–silver nanoparticles. For the first immunosensor, the gold substrate was functionalized with a dense self-assembled monolayer of 3-mercaptopropionic acid through gold–sulfur bonds, and then protein A which can combine subgroup J avian leucosis virus antibody on the antigen nonbinding site was modified on the sensor chip surface via covalent bonds formed between the amino groups and the activated carboxyl groups of 3-mercaptopropionic acid. After inactivation by ethanolamine, the sensor chip immobilized the antibody by the combination with protein A to produce a sensor. For the second immunosensor, 1,6- hexanedithiol formed a self-assembled monolayer on the sensor chip surface through gold–sulfur bonds. Then gold–silver nanoparticles were immobilized on the sensor chip by gold–sulfur and silver–sulfur bonds. The modification by various reagents and determination of the subgroup J avian leukosis virus antigen were the same as in the first immunosensor. The immunosensors determined the subgroup J avian leukosis virus antigen to analyte concentrations of 659 TCID50·mL− 1and 1054 TCID50·mL− 1, respectively. The result suggested that introducing gold–silver nanoparticles to the Fourier transform-surface plasmon resonance immunosensor is beneficial to effectively improving the sensitivity of the immunosensor. Moreover, the contrast experiment presented that the immunosensors showed high specificity for the subgroup J avian leucosis virus detection. [ABSTRACT FROM AUTHOR]

The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: The Agrotis segetum granulovirus (AgseGV) F protein was previously identified as the first betabaculovirus F protein with functional homology to Autographa californica nucleopolyhedrovirus (AcMNPV) GP64. In the current study, F proteins from Xestia c-nigrum granulovirus (XecnGV), Cydia pomonella granulovirus (CpGV), Phthorimaea operculella granulovirus (PhopGV), Choristoneura occidentalis granulovirus (ChocGV) and Plutella xylostella GV (PlxyGV) were studied for their ability to rescue the infectivity of gp64-null AcMNPV. Our results showed that most studied betabaculovirus F proteins could replace the function of AcMNPV GP64, however, their efficiencies to rescue the infectivity of gp64-null AcMNPV were substantially different. PlxyF, although fusogenic, was the only protein that failed to substitute the function of AcMNPV GP64. Further studies using Sf90p1D cell line showed that PlxyF appeared to be properly incorporated into AcMNPV virions and underwent correct post-translational cleavage and N-linked glycosylation. However, the gp64-null AcMNPV containing PlxyF could not be propagated in either Sf9 or P. xylostella cells. [Copyright &y& Elsevier]

Abstract: ORF85 of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) encodes a homologue of the per os infectivity factor 4 (PIF-4) of Autographa californica multiple nucleocapsid nucleopolyhedrovirus (AcMNPV). In this paper, the functions of HA85, particularly in relation to oral infection and interactions with other PIFs were investigated. An ha85-disrupted recombinant HearNPV was generated and resulted in a complete loss of oral infectivity. Western blotting and co-immunoprecipitation (Co-IP) analyses suggested PIF1, PIF2, and PIF3 assemble into a PIF complex in HearNPV ODV. Although Western blotting and Co-IP did not show that HA85 is associated with the PIF complex, further analysis revealed the inactivation of ha85 led to the disruption of PIF complex. Yeast two hybridization analyses revealed that HA85 interacts with P74, PIF1, PIF2 and PIF3. In conclusion, HA85 is identified as the PIF4 of HearNPV and is proposed to participate in the formation of HearNPV PIF complex via associations with other PIFs. [Copyright &y& Elsevier]

Sepsis is an infection‐triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)‐induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis‐induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean‐Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm. [ABSTRACT FROM AUTHOR]

Mutation rates are of key importance for understanding evolutionary processes and predicting their outcomes. Empirical mutation rate estimates are available for a number of RNA viruses, but few are available for DNA viruses, which tend to have larger genomes. Whilst some viruses have very high mutation rates, lower mutation rates are expected for viruses with large genomes to ensure genome integrity. Alphabaculoviruses are insect viruses with large genomes and often have high levels of polymorphism, suggesting high mutation rates despite evidence of proofreading activity by the replication machinery. Here, we report an empirical estimate of the mutation rate per base per strand copying (s/n/r) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). To avoid biases due to selection, we analyzed mutations that occurred in a stable, non-functional genomic insert after five serial passages in Spodoptera exigua larvae. Our results highlight that viral demography and the stringency of mutation calling affect mutation rate estimates, and that using a population genetic simulation model to make inferences can mitigate the impact of these processes on estimates of mutation rate. We estimated a mutation rate of μ = 1×10−7 s/n/r when applying the most stringent criteria for mutation calling, and estimates of up to μ = 5×10−7 s/n/r when relaxing these criteria. The rates at which different classes of mutations accumulate provide good evidence for neutrality of mutations occurring within the inserted region. We therefore present a robust approach for mutation rate estimation for viruses with stable genomes, and strong evidence of a much lower alphabaculovirus mutation rate than supposed based on the high levels of polymorphism observed. Author summary: Virus populations can evolve rapidly, driven by the large number of mutations that occur during virus replication. It is challenging to measure mutation rates because selection will affect which mutations are observed: beneficial mutations are overrepresented in virus populations, while deleterious mutations are selected against and therefore underrepresented. Few mutation rates have been estimated for viruses with large DNA genomes, and there are no estimates for any insect virus. Here, we estimate the mutation rate for an alphabaculovirus, a virus that infects caterpillars and has a large, 134 kilobase pair DNA genome. To ensure that selection did not bias our estimate of mutation rate, we studied which mutations occurred in a large artificial region inserted into the virus genome, where mutations did not affect viral fitness. We deep sequenced evolved virus populations, and compared the distribution of observed mutants to predictions from a simulation model to estimate mutation rate. We found evidence for a relatively low mutation rate, of one mutation in every 10 million bases replicated. This estimate is in line with expectations for a DNA virus with self-correcting replication machinery and a large genome. [ABSTRACT FROM AUTHOR]

• Porous iron oxide with tunable structural colors is prepared by electrochemical anodization in an ethylene glycol solution including 0.1 M NH 4 F and 1 M H 2 O. • The microstructure and optical characteristics of the films are characterized. • The relationship between the refractive index and dielectric constant of porous materials is discussed. Porous iron oxide with tunable structural colors in the entire visible range has been prepared by anodizing pure iron foils at 40 V in an ethylene glycol solution. The relationship between the structural color and the anodization time and the electrolyte temperature was discussed. The results showed that the maxima of the reflected wavelengths in the UV–Vis reflectance spectra were consistent with the observed colors, and the refractive index n of the films was obtained. It was found that the n2 was about equal to the effective dielectric constant ɛ of the films, which means that the carriers in the dielectric material of the films are mainly electrons. These results provide a simple and effective method for determining the carrier type of porous materials. [ABSTRACT FROM AUTHOR]

The electrochemiluminescence (ECL) efficiency of porphyrins is limited by the quenching of π–π stacking due to their poor water solubility and inherent instability. Therefore, there is an urgent need to design and explore novel porphyrin luminophores with high ECL efficiency, which presents a significant challenge. In this work, a facile one-pot strategy was developed to synthesize a self-promoter-doped porphyrin-based ECL luminophore with high ECL efficiency for the first time. The silver nanoparticle (AgNPs)-doped meso-tetra(4-carboxyphenyl) porphyrin (TCPP) (AgNPs@TCPP) nanoassembly was prepared by inducing TCPP assembly using Ag nanoseeds produced by the reduction of silver nitrate with N,N-dimethylformamide. In this process, AgNPs could coordinate with the carboxyphenyl groups at the terminus of TCPP and the pyrrole nitrogen of TCPP. The resulting AgNPs@TCPP nanoassembly demonstrated superior ECL performance using K2S2O8 as a co-reactant, with an ECL efficiency of 217%, significantly higher than that of previously reported sodium dodecyl sulfate-assisted TCPP aggregate (92.3%) and cetyltrimethylammonium bromide-assisted TCPP aggregate (57.5%). The self-promoted and highly efficient ECL of the AgNPs@TCPP nanoassembly was attributed to overcoming the ECL quenching due to bad TCPP aggregation by virtue of Ag nanoseeds induced TCPP assembly and the self-promoted ECL amplification by doping AgNPs with excellent conductivity. These findings offer a new approach for exploring highly efficient porphyrin-based ECL luminophores, thereby expanding the applications of porphyrins in ECL. [ABSTRACT FROM AUTHOR]

Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc‐HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc‐HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc‐HZ10 transcription. Meanwhile, lnc‐HZ10 also increases AhR levels by suppressing its CUL4B‐mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc‐HZ10 (mainly 1‐447 nt) interacts with γ‐H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc‐HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage. [ABSTRACT FROM AUTHOR]

Baculoviruses are natural enemies of agricultural and forest insect pests and play an important role in biological pest control. Oral infection by baculovirus in the insect midgut is necessary for establishing systemic infection and eventually killing the insect. Since the insect midgut continuously encounters microbiota, the gut microbiota could affect baculovirus infection. Here, we demonstrated that gut microbiota modulates immune responses and promotes baculovirus infection in the cotton bollworm, Helicoverpa armigera. After oral infection, numerous host immunity‐related genes including genes encoding Toll and immune deficiency (IMD) pathway components were upregulated in the midgut. Elimination of the gut microbiota significantly increased the resistance to viral infection in H. armigera. Quantitative real‐time reverse transcription polymerase chain reaction and proteomic analysis showed that downregulation of the antiviral factor prophenoloxidase (PPO) could be mediated by microbiota during infection. It implied that midgut microbiota diminishes the expression of PPO to facilitate viral infection in H. armigera. Our findings revealed that the microbiota plays an important role in modulating the resistance of H. armigera to baculovirus infection, providing new insights in applying biopesticide. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus, prevalent in more than 30 countries worldwide. Human infection by this virus leads to severe illness, with an average case fatality of 40%. There is currently no approved vaccine or drug to treat the disease. Neutralizing antibodies are a promising approach to treat virus infectious diseases. This study generated 37 mouse-derived specific monoclonal antibodies against CCHFV Gc subunit. Neutralization assays using pseudotyped virus and authentic CCHFV identified Gc8, Gc13, and Gc35 as neutralizing antibodies. Among them, Gc13 had the highest neutralizing activity and binding affinity with CCHFV Gc. Consistently, Gc13, but not Gc8 or Gc35, showed in vivo protective efficacy (62.5% survival rate) against CCHFV infection in a lethal mouse infection model. Further characterization studies suggested that Gc8 and Gc13 may recognize a similar, linear epitope in domain II of CCHFV Gc, while Gc35 may recognize a different epitope in Gc. Cryo-electron microscopy of Gc-Fab complexes indicated that both Gc8 and Gc13 bind to the conserved fusion loop region and Gc13 had stronger interactions with sGc-trimers. This was supported by the ability of Gc13 to block CCHFV GP-mediated membrane fusion. Overall, this study provides new therapeutic strategies to treat CCHF and new insights into the interaction between antibodies with CCHFV Gc proteins. Author summary: Crimean-Congo hemorrhagic fever (CCHF) is a priority disease by the World Health Organization (WHO). It is a deadly viral infectious disease with case fatalities up to 40%, and no approved vaccine or treatment. Neutralizing antibodies are a promising approach toward treating viral infections, as exemplified in other hemorrhagic fevers such as Ebola. Currently, there are few reports of efficient neutralizing antibodies against CCHF virus (CCHFV). This study successfully screened mouse-derived monoclonal antibodies with high in vitro neutralizing activity and in vivo protective efficacy against CCHFV infection. Among those, mAb Gc13 was the most efficient because it strongly bound to the highly conserved fusion loop regions of the CCHFV Gc subunit, thus blocking the crucial virus membrane fusion process. This study highlights the potential of neutralizing antibody-based strategies for CCHF treatment. [ABSTRACT FROM AUTHOR]

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on our societies. Moreover, the disease's extensive and sustained symptoms are now becoming a nonnegligible medical challenge. In this respect, data indicate that heart failure is one of the most common readmission diagnoses among COVID-19 patients. Methods: In this study, we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to develop an in vitro model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and studied the dynamic changes occurring in cardiomyocytes after SARS-CoV-2 infection. Results: To this end, we have created an effective time series SARS-CoV-2 infection model exhibiting different functional patterns of up- and downregulated proteins, and demonstrating that SARS-CoV-2 mainly affects (i) the lipid and the energy metabolism of hiPSC-derived cardiomyocytes during the early infection stage, and (ii) the DNA repair ability of cardiomyocytes during the late infection stage. By analyzing the proteome changes occurring at different infection timepoints, we were able to observe that the simulated disease (COVID-19) course developed rapidly, and that each of the studied timepoints was characterized by a distinct protein expression pattern. Conclusions: Our findings highlight the importance of early detection and personalized treatment based on the disease stage. Finally, by combing the proteomics data with virus-host interaction network analysis, we were able to identify several potential drug targets for the disease. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most common female reproductive tract cancer and its incidence has been continuously increasing in recent years. The underlying mechanisms of EC tumorigenesis remain unclear, and efficient target therapies are lacking, for both of which feasible endometrial cancer animal models are essential but currently limited. Here, an organoid and genome editing‐based strategy to generate primary, orthotopic, and driver‐defined ECs in mice is reported. These models faithfully recapitulate the molecular and pathohistological characteristics of human diseases. The authors names these models and similar models for other cancers as organoid‐initiated precision cancer models (OPCMs). Importantly, this approach can conveniently introduce any driver mutation or a combination of driver mutations. Using these models,it is shown that the mutations in Pik3ca and Pik3r1 cooperate with Pten loss to promote endometrial adenocarcinoma in mice. In contrast, the Kras G12D mutati led to endometrial squamous cell carcinoma. Then, tumor organoids are derived from these mouse EC models and performed high‐throughput drug screening and validation. The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy. [ABSTRACT FROM AUTHOR]

KMT2C and KMT2D are the most frequently mutated epigenetic genes in human cancers. While KMT2C is identified as a tumor suppressor in acute myeloid leukemia (AML), the role of KMT2D remains unclear in this disease, though its loss promotes B cell lymphoma and various solid cancers. Here, it is reported that KMT2D is downregulated or mutated in AML and its deficiency, through shRNA knockdown or CRISPR/Cas9 editing, accelerates leukemogenesis in mice. Hematopoietic stem and progenitor cells and AML cells with Kmt2d loss have significantly enhanced ribosome biogenesis and consistently, enlarged nucleolus, increased rRNA and protein synthesis rates. Mechanistically, it is found that KMT2D deficiency leads to the activation of the mTOR pathway in both mouse and human AML cells. Kmt2d directly regulates the expression of Ddit4, a negative regulator of the mTOR pathway. Consistent with the abnormal ribosome biogenesis, it is shown that CX‐5461, an inhibitor of RNA polymerase I, significantly restrains the growth of AML with Kmt2d loss in vivo and extends the survival of leukemic mice. These studies validate KMT2D as a de facto tumor suppressor in AML and reveal an unprecedented vulnerability to ribosome biogenesis inhibition. [ABSTRACT FROM AUTHOR]

In this paper, a selenium polysaccharide (PGP1) was isolated from the radix of Platycodon grandiflorum . We investigated the protective capacity of PGP1 against the hydrogen peroxide (H 2 O 2 )-induced oxidative damage in cultured rat pheochromocytoma (PC12) cells. Cells were pretreated with various doses of PGP1 (50, 100 and 200 μg/mL) for 24 h before exposure to 0.5 mM H 2 O 2 for 12 h. Cell viability, LDH release, apoptotic rates, malondialdehyde (MDA) content, antioxidant enzyme superoxide dismutase (SOD) activity and intracellular accumulation of reactive oxygen species (ROS) were determined. The results showed pretreatment of PC12 cells with PGP1 prior to H 2 O 2 exposure inhibited the decrease of cell viability, decreased the apoptotic rates, prevented membrane damage (LDH release) and attenuated intracellular ROS formation in PC12 cells injured by H 2 O 2 . Meanwhile, PGP1 increased SOD activity, while it decreased the level of MDA and the production of lipid peroxidation, in PC12 cells after H 2 O 2 exposure. These findings suggested that PGP1 may be considered as a potential useful antioxidant agent in reducing neuronal oxidative damage via inhibiting oxidative stress. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic osteopathy characterized by bone metabolism disorders that become more serious with age increases in postmenopausal women. Recent studies have found that antler protein is the main bioactive component of cervus pantotrichum, and it has a positive regulatory effect on bone metabolism and can improve estrogen level. This study aimed to investigate the effect of velvet antler extract (VAE) on the prevention of osteoporosis and the modulation of gut microbiota in ovariectomized (OVX) mice. OVX mice treated with 12 weeks of VAE exhibited higher levels of serum BGP, Ca2+, CT, and HyP (p <.05). Micro‐CT scans showed that VAE significantly elevated bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone connection density (Conn.D), decreased trabecular separation (Tb.Sp), and structural modality index (SMI) than untreated OVX mice. The right tibial retinaculum in the VAE group was clearer, with a clearer reticular structure, smaller gaps, a tighter distribution, and a more orderly arrangement. The gut microbiota of the cecal contents was analyzed by 16 s rDNA amplicon sequencing. The data indicated that VAE modulated the species, numbers, and diversity of the gut microbiota in OVX mice. Ovariectomy caused dysbiosis of the intestinal microbiota by increasing the ratio of Firmicutes to Bacteroidetes in mice, but the ratio decreased after treatment with VAE. These results suggest that VAE has a therapeutic effect on OVX mice via modulate bone‐related biochemical markers in serum and structure of gut microbiota. In this paper, I show that velvet antler extract has a positive effect on osteoporosis model mice. I found that velvet antler extract can improve the serum biochemical indexes, bone microstructure, and intestinal flora of osteoporosis model mice. In addition, I noticed that the antler extract significantly increased the content of Akkermansia bacteria in the intestinal tract of mice, indicating that Akkermansia bacteria may be a new biomarker of osteoporosis. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) caused by a novel bunyavirus (SFTSV) is an emerging infectious disease with up to 30% case fatality. Currently, there are no specific antiviral drugs or vaccines for SFTS. Here, we constructed a reporter SFTSV in which the virulent factor nonstructural protein (NSs) was replaced by eGFP for drug screening. First, we developed a reverse genetics system based on the SFTSV HBMC5 strain. Then, the reporter virus SFTSV-delNSs-eGFP was constructed, rescued, and characterized in vitro. SFTSV-delNSs-eGFP showed similar growth kinetics with the wild-type virus in Vero cells. We further detected the antiviral efficacy of favipiravir and chloroquine against wild-type and recombinant SFTSV by the quantification of viral RNA, and compared the results with that of fluorescent assay using high-content screening. The results showed that SFTSV-delNSs-eGFP could be used as a reporter virus for antiviral drug screening in vitro. In addition, we analyzed the pathogenesis of SFTSV-delNSs-eGFP in interferon receptor-deficient (IFNAR−/−) C57BL/6J mice and found that unlike the fatal infection of the wild-type virus, no obvious pathological change or viral replication were observed in SFTSV-delNSs-eGFP-infected mice. Taken together, the green fluorescence and attenuated pathogenicity make SFTSV-delNSs-eGFP a potent tool for the future high-throughput screening of antiviral drugs. [ABSTRACT FROM AUTHOR]

Melanization, an important insect defense mechanism, is mediated by clip-domain serine protease (cSP) cascades and is regulated by serpins. Here we show that proteolytic activation of prophenoloxidase (PPO) and PO-catalyzed melanization kill the baculovirus in vitro. Our quantitative proteomics and biochemical experiments revealed that baculovirus infection of the cotton bollworm, Helicoverpa armigera, reduced levels of most cascade members in the host hemolymph and PO activity. By contrast, serpin-9 and serpin-5 were sequentially upregulated after the viral infection. The H. armigera serpin-5 and serpin-9 regulate melanization by directly inhibiting their target proteases cSP4 and cSP6, respectively and cSP6 activates PPO purified from hemolymph. Furthermore, serpin-5/9-depleted insects exhibited high PO activities and showed resistance to baculovirus infection. Together, our results characterize a part of the melanization cascade in H. armigera, and suggest that natural insect virus baculovirus has evolved a distinct strategy to suppress the host immune system. [ABSTRACT FROM AUTHOR]

Background: Pterygium is a common chronic ophthalmic condition, which may result in significant visual morbidity or lead to blindness in extreme cases. The prevalence of pterygium in China has not been reported at the sub-national level. Methods: In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of pterygium in China. China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM-SinoMed), PubMed, Embase and Medline were searched before September 2016. We performed a multilevel mixed-effect meta-regression based on the included studies, our results showed that age, gender and latitude were significantly associated with pterygium prevalence. Based on the final model, the age and gender-specific prevalence of pterygium in 31 Chinese provinces (except Hongkong, Macau and Taiwan) and the whole country was generated. Results: In 2010, the overall prevalence of pterygium in Chinese people aged 15–84 years was 9.84% (95% CI: 6.72–14.14), and the number of pterygium cases in China was 108.65 million (95% CI: 74.23–156.13). Conclusions: In conclusion, the prevalence of pterygium in Chinese population in 2010 was estimated at both the national and provincial levels. The higher burden of pterygium across the country calls for efforts to advocate public health education encouraging people to take appropriate protective measures. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic has caused over six million deaths and huge economic burdens worldwide. Antivirals against its causative agent, SARS-CoV-2, are in urgent demand. Previously, we reported that heterocylic compounds, i.e., chloroquine (CQ) and hydroxychloroquine (HCQ), are potent in inhibiting SARS-CoV-2 replication in vitro. In this study, we discussed the syntheses of two novel heterocylic compounds: tert-butyl rel-4-(((3R,4S)-3-(1H-indol-3-yl)-1-oxo-2-propyl-1,2,3,4-tetrahydroisoquinolin-4-yl)methyl)piperazine-1-carboxylate (trans-1) and rel-(3R,4S)-3-(1H-indol-3-yl)-4-(piperazin-1-ylmethyl)-2-propyl-3,4-dihydroisoquinolin-1(2H)-one (trans-2), which effectively suppressed authentic SARS-CoV-2 replication in Vero E6 cells. Compound trans-1 showed higher anti-SARS-CoV-2 activity than trans-2, with a half maximal effective concentration (EC50) of 3.15 μM and a selective index (SI) exceeding 63.49, which demonstrated comparable potency to CQ or HCQ. Additional anti-SARS-CoV-2 tests on Calu-3 human lung cells showed that trans-1 efficiently inhibited viral replication (EC50 = 2.78 μM; SI: > 71.94) and performed better than CQ (EC50 = 44.90 μM; SI = 2.94). The time of an addition assay showed that the action mechanism of trans-1 differed from that of CQ, as it mainly inhibited the post-entry viral replication in both Vero E6 and Calu-3 cells. In addition, the differences between the antiviral mechanisms of these novel compounds and CQ were discussed. [ABSTRACT FROM AUTHOR]

Wulungu Lake is the second largest lake and the second largest fishery base in Xinjiang, but there are few studies on heavy metal pollution in water environment. In order to explore the characteristics and sources of heavy metal pollution in the water environment of Wulungu Lake, the distribution characteristics, ecological risks and pollution sources of 8 heavy metals (Cr, Cu, Cd, Zn, Ni, Pb, Hg and As) in water and sediments of 13 sampling points of Wulungu Lake were analyzed. Geological accumulation index method and potential ecological hazard index method show that Hg has a strong potential ecological risk, which leads to a high potential ecological risk in Wulungu Lake. The water quality of Wulungu Lake is good, but we need to pay attention to the health risk of as. Multivariate statistical analysis shows that Cu, Cd, Zn, Ni and Pb in the water body of Wulungu Lake are affected by the discharge of mining or enterprise wastewater. Hg and Cr may come from the use of fertilizer in farmland. Cr, Cu, Zn, Ni and As in surface sediments are mainly affected by regional geochemical characteristics, while Cd, Pb and Hg are also affected by human activities. The distribution of heavy metals in sediments is different from that in water, which should also be affected by the hydrological conditions of lakes. [ABSTRACT FROM AUTHOR]

Baculoviruses have been widely used as expression vectors. However, numerous genes in the baculoviral genome are non-essential for cellular infection and protein expression, making the optimisation of baculovirus expression vectors possible. We used a synthetic biological method to reduce the number of genes in a partial region of the autograph californica multiple nucleopolyhedrovirus (AcMNPV), the most widely used baculovirus expression vector. The C1 region of the AcMNPV is 46.4 kb and is subdivided into B1, B2, and B3 fragments. We first designed modified B1, B2, and B3 fragments by deleting the non-essential genes, and then synthesised complete viral genomes containing either individual modified B fragments or joint modified B fragments through transformation-related recombination in yeast. The synthetic genomes were then transfected into Sf9 cells to rescue the progeny viruses and test their infectivity. The design-build-test cycle was repeated until the ultimately rescued virus could produce progeny viruses efficiently. Finally, AcMNPV-Syn-mC1-1.1 by deleting approximately 17.2 kb, including 20 ORFs, in the C1 region, was obtained. This is essential to the synthesis of a minimal AcMNPV genome that can generate infectious progeny viruses and can be further used to optimise the foundation of baculovirus expression vectors. [ABSTRACT FROM AUTHOR]

Background: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment.Methods: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis.Results: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1.Conclusions: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases. [ABSTRACT FROM AUTHOR]

A recent article in Advanced Science discusses a novel drug candidate for sepsis, a condition that currently lacks specific clinical treatment. The drug targets Heparanase, which is responsible for increased vascular permeability and endothelial damage in sepsis. In mouse models, the drug protected the vascular endothelial glycocalyx and significantly improved survival rates from 0 to 80%. This research shows promise for the development of a treatment for sepsis. [Extracted from the article]

Crimean–Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called "cap-snatching" is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the "cap-snatching" mechanism) could inhibit CCHFV infection. In cell culture, baloxavir acid effectively inhibited CCHFV infection and targeted CCHFV RNA transcription/replication. However, it has weak oral bioavailability. Baloxavir marboxil (the oral prodrug of baloxavir) failed to protect mice against a lethal dose challenge of CCHFV. To solve this problem, baloxavir sodium was synthesized owing to its enhanced aqueous solubility and pharmacokinetic properties. It consistently and significantly improved survival rates and decreased tissue viral loads. This study identified baloxavir sodium as a novel scaffold structure and mechanism of anti-CCHF compound, providing a promising new strategy for clinical treatment of CCHF after further optimization. [Display omitted] • Baloxavir acid effectively inhibits Crimean–Congo hemorrhagic fever virus (CCHFV) infection in vitro. • Baloxavir acid inhibits CCHFV infection during viral transcription and replication. • Baloxavir marboxil failed to protect mice from lethal CCHFV infection after oral administration. • Baloxavir sodium with enhanced pharmacokinetic properties significantly improves the survival rate of CCHFV-infected mice. [ABSTRACT FROM AUTHOR]

Bombyx mori nucleopolyhedrovirus (BmNPV) is a pathogen that causes severe disease in silkworms. In a previous study, we demonstrated that by using the CRISPR/Cas9 system to disrupt the BmNPV ie-1 and me53 genes, transgenic silkworms showed resistance to BmNPV infection. Here, we used the same strategy to simultaneously target lef8 and lef9, which are essential for BmNPV replication. A PCR assay confirmed that double-stranded breaks were induced in viral DNA at targeted sequences in BmNPV-infected transgenic silkworms that expressed small guide RNAs (sgRNAs) and Cas9. Bioassays and qPCR showed that replication of BmNPV and mortality were significantly reduced in the transgenic silkworms in comparison with the control groups. Microscopy showed degradation of midgut cells in the BmNPV-infected wild type silkworms, but not in the transgenic silkworms. These results demonstrated that transgenic silkworms using the CRISPR/Cas9 system to disrupt BmNPV lef8 and lef9 genes could successfully prevent BmNPV infection. Our research not only provides more alternative targets for the CRISPR antiviral system, but also aims to provide new ideas for the application of virus infection research and the control of insect pests. [ABSTRACT FROM AUTHOR]

Simulating bus and stationary protocols are designed to study the durability and degradation mechanisms of proton exchange membrane fuel cells. A quantitative method combined with characterization techniques, including electrochemical impedance spectroscopy, X-ray fluorescence spectroscopy and X-ray diffraction spectroscopy, is applied to distinguish performance degradation. Experimental results show that, for proton exchange membrane attenuation, chemical attenuation due to high cathode potential with long duration is more severe than mechanism attenuation due to dynamic load. For cathode catalyst layer decay, the principal reason under bus condition is particles growth (∼35%), followed by Pt dissolution (∼34%). In contrast,∼43% ECSA loss results from ionomer/catalyst interface loss under stationary condition. Such information indicates that the bus condition results in particles growth and Pt dissolution while the stationary condition induces ionomer/catalyst interface loss in the cathode catalyst layer. Combining more realistic protocols and quantitative analysis method can reveal the relationship between operating conditions of fuel cell in realistic road and MEA degradation. • Simulating stationary and bus protocols are used to study MEA degradation. • The attenuation mechanisms of MEA under these two protocols is proposed. • Chemical decay by durable high-potential affects severely PEM durability. • Particle growth and Pt dissolution cease CL decay under bus protocol. • Ionomer loss ceases CL degradation under stationary protocol. [ABSTRACT FROM AUTHOR]

In response to the problem of unclear texture structure in steel wire rope images caused by complex and uncertain lighting conditions, resulting in inconsistent LBP feature values for the same structure, this paper proposes a steel wire surface damage recognition method based on exponential weighted guided filtering and complementary binary equivalent patterns. Leveraging the phenomenon of Mach bands in vision, we introduce a guided filtering method based on local exponential weighting to enhance texture details by applying exponential mapping to evaluate pixel differences within local window regions during image filtering. Additionally, we propose complementary binary equivalent pattern descriptors as neighborhood difference symbol information representation operators to reduce feature dimensionality while enhancing the robustness of binary encoding against interference. Experimental results demonstrate that compared to classical guided filtering algorithms, our image enhancement method achieves improvements in PSNR and SSIM mean values by more than 32.5% and 18.5%, respectively, effectively removing noise while preserving image edge structures. Moreover, our algorithm achieves a classification accuracy of 99.3% on the steel wire dataset, with a processing time of only 0.606 s per image. [ABSTRACT FROM AUTHOR]

[Display omitted] • The innovative application of the semi-IPN pressure-sensitive adhesive for transdermal drug delivery system. • Pressure-sensitive adhesive with excellent mechanical properties, effective adhesion to the skin, and high drug release. • A simple but effective method to synthesize the semi-IPN pressure-sensitive adhesive with high cohesion and adhesion. The application of pressure-sensitive adhesives (PSAs) in transdermal drug delivery systems (TDDSs) is limited. Insufficient cohesion in TDDS can lead to cold flow, patch displacement, dose inaccuracies, and the 'dark ring' phenomenon. To address these issues, we developed a semi-interpenetrating network (semi-IPN) PSA using a 2-hydroxyethylacrylate-modified acrylic copolymer as the linear polymer and poly[tri(propylene glycol) diacrylate] as the cross-linked network. Semi-IPN PSAs have better mechanical properties compared to traditional PSAs. The cohesion of the semi-IPN PSA was 31 times and 1.6 times that of commercially available DURO-TAK®87-2287 and DURO-TAK® 87–4098, respectively, and the cold flow of the semi-IPN PSA was significantly reduced. Furthermore, the semi-IPN PSA adhered to the human forearm for longer time and did not exhibit the 'dark ring' phenomenon after removal. When loaded with flurbiprofen, the semi-IPN PSA was found to maintain high levels of drug release and skin permeation amount, and flurbiprofen loading did not affect its superior cohesive performance. In conclusion, the innovative application of the semi-IPN PSA for TDDS showed excellent mechanical properties, effective adhesion to the skin without irritation, and highly effective drug release. These findings indicate that the use of the semi-IPN is both simple and highly effective for TDDS. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) patients with impact on skin and hair loss are reported. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is detected in the skin of some patients; however, the detailed pathological features of skin tissues from patients infected with SARS‐CoV‐2 at a molecular level are limited. Especially, the ability of SARS‐CoV‐2 to infect skin cells and impact their function is not well understood. A proteome map of COVID‐19 skin is established here and the susceptibility of human‐induced pluripotent stem cell (hiPSC)‐derived skin organoids with hair follicles and nervous system is investigated, to SARS‐CoV‐2 infection. It is shown that KRT17+ hair follicles can be infected by SARS‐CoV‐2 and are associated with the impaired development of hair follicles and epidermis. Different types of nervous system cells are also found to be infected, which can lead to neuron death. Findings from the present work provide evidence for the association between COVID‐19 and hair loss. hiPSC‐derived skin organoids are also presented as an experimental model which can be used to investigate the susceptibility of skin cells to SARS‐CoV‐2 infection and can help identify various pathological mechanisms and drug screening strategies. [ABSTRACT FROM AUTHOR]

In recent years, antibiotics have become widely used in animal breeding. The application of antibiotics in livestock may lead to the presence of antibiotic residues in animal‐derived foods, especially meat, that may pose a threat to human health. In this study, 26 common antibiotics (eight sulfonamides, nine fluoroquinolones, four tetracyclines, and five macrolides) were screened in 88 meat samples (cattle muscles and sheep muscles, kidneys, and livers) obtained from southern Xinjiang. The antibiotics were screened via the clean‐up step based on solid‐phase extraction and determined through ultraperformance liquid chromatography–tandem mass spectrometry. Moreover, their risk to human health was analyzed. Overall, 16 antibiotics were detected with a total detection rate of 95.46%. The percentage of noncompliant samples was 28.41% with an exceedance maximum residue limit of 1.14%. The illegal use rate of the antibiotic norfloxacin was 27.27%. The estimated daily exposure doses of all compounds in adults were <102.218 ng/kg bw/day even after applying the worst‐case scenario approach. This result demonstrated that the antibiotic residues in the tested samples imposed negligible harm to people's health and had an acceptable level of food safety risk. However, the high detection frequencies found in this work indicated that the risk of antibiotic residues could not be ignored given the cumulative risk of antibiotics, particularly the emergence of bacterial resistance, to the human body. The need for effective strategies and publicity for the judicious use of antibiotics to safeguard residents' health is immediate. [ABSTRACT FROM AUTHOR]

The preventive and therapeutic mechanisms of CDBE on osteoporosis were studied by observing the serum bone‐related biochemical indicators, bone trabecular micro‐structure and intestinal flora in ovariectomized osteoporosis model mice, in order to provide a scientific theoretical basis for the further study on the effect of CDBE on osteoporosis, and the prevention and treatment of osteoporosis with clinical traditional Chinese medicines. The components in CDBE were detected by UHPLC‐MS. A mouse osteoporosis model was established by the bilateral ovariectomy in female ICR mice. The biochemical indicators related to osteoporosis were detected, the right proximal tibia was scanned by Micro‐CT, the intestinal microflora in the colon contents were examined, and the changes of microflora were taken as the main target to evaluate the effect of CDBE on the intestinal microflora in the model mice. A total of 16 compounds were obtained by the combined application of UHPLC‐MS. CDBE could significantly increase the contents of E2, Ca2+, CT, HyP, OCN, FOXP3, P1NP and CTX‐II, in the model mice. CDBE could significantly improve the trabecular micro‐structure, Tb.N, Tb.Sp, SMI and Conn.D. CDBE could make the intestinal flora of osteoporosis model mice tend to healthy mice in species and quantity. CDBE can improve the symptoms of postmenopausal osteoporosis in mice, with a positive effect on the intestinal flora of postmenopausal mice. Its mechanism of regulating the symptoms of osteoporosis may be related to the regulation of bone‐related biochemical indicators in the serum of mice. Practical applications: This research has a positive impact on the development of functional food with anti‐osteoporosis in the future. [ABSTRACT FROM AUTHOR]

Background: ATP1A2 gene mutation has been indicated to cause alternating hemiplegia of childhood (AHC); however, limited evidence supports this relationship so far. Case presentation: We reported two Chinese patients with de novo ATP1A2 variants (c.970G>A and c.889G>A). Both patients presented with episodes of alternating hemiplegia, seizures and mild developmental delay. Brain magnetic resonance imaging revealed abnormal signals in both patients. Conclusions: The new genetic evidence we reported here strengthened the gene–disease relationship, and the gene curation level between ATP1A2 and AHC became "Moderate" following the ClinGen Standard Operation Procedure. Consequently, the two variants can be reclassified as likely pathogenic. [ABSTRACT FROM AUTHOR]

Only a few studies investigated the impact of quarantine on anxiety of general population during a second wave of COVID-19 breakout. We aimed to compare anxiety levels of quarantined and non-quarantined people and investigate factors affecting anxiety during the second COVID-19 pandemic. A total of 1837 participants were included in this cross-sectional study. Anxiety was measured by the State-Trait Anxiety Inventory (STAI). Participants were divided into the quarantined group (QG) and non-quarantined group (Non-QG). The mean STAI-S score in the QG was significantly higher than Non-QG (41.8 ± 11.2 vs 40.01 ± 9.9), so was the proportion of severe state anxiety (11.6% vs 5.5%). Males in the QG were significantly more anxious than females evaluated by both STAI-S and STAI-T. High income was independent protective factors while moderate or bad health status and high trait anxiety level were independent risk factors for severe state anxiety. In conclusion, the COVID-19 confinement could significantly increase anxiety of quarantined people. Males were more vulnerable to the quarantine of COVID-19 with significantly increased anxiety level than females. The results suggest that attention should be paid to anxiety during a second round of quarantine due to COVID-19 and are of help in planning psychological interventions. • The COVID-19 confinement could significantly increase anxiety of quarantined people. • Males were more vulnerable to the quarantine of COVID-19 with significantly increased anxiety level than females. • Attention should be paid to anxiety during a second round of quarantine due to COVID-19. [ABSTRACT FROM AUTHOR]

To identify potential pathogens responsible for a disease outbreak of cultured peafowls in China in 2013, metagenomic sequencing was conducted. The genomes of two closely related parvoviruses, namely peafowl parvovirus 1 (PePV1) and PePV2, were identified with size of 4428 bp and 4348 bp, respectively. Phylogenetic analysis revealed that both viruses are novel parvoviruses, belonging to the proposed genus Chapparvovirus of Parvoviridae. The transcriptional profile of PePV1 was analyzed by transfecting a nearly complete PePV1 genome into HEK-293T cells. Results revealed that PePV1 employs one promoter and two polyadenylation sites to start and terminate its transcriptions, with one donor site and two acceptor sites for pre-mRNA splicing. PePV1 DNA and structural protein were detected in several tissues of a dead peafowl, which appeared to have suffered enteritis, pneumonia and viremia. These results provide novel information of chapparvoviruses, and call for attention to the potential pathogens. • PePV1 and PePV2 were likely the etiological agents for the peafowl outbreak in 2013. • PePV1 and PePV2 belong to the proposed genus Chapparvovirus of Parvoviridae. • Genome organization of chapparvoviruses are highly similar. • The transcription profile of PePV1 was identified. • DNA and structural protein of PePV1 were detected in several tissues. [ABSTRACT FROM AUTHOR]