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Abstract Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass and microstructural deterioration of bone. Changes in the composition and structure of gut microbiota (GM) are related to changes of bone mass and bone microstructure. However, the relationship between GM and bone mineral density (BMD) is complex, and data are especially scarce for Chinese Han youth. Therefore, 62 Chinese Han youth participants were recruited. Furthermore, according to the T–score evaluation criteria of the World Health Organization (WHO), we divided the BMD levels of participants into three groups: osteoporosis\BDL, osteopenia\BDM, normal bone density\BDH, and the associations between GM community and BMD groups were conducted. According to alpha and beta diversity analysis, significant differences were found in the microbial richness and composition between groups. The dominant phyla of GM in a cohort of Chinese Han youth were Bacteroidota (50.6%) and Firmicutes (41.6%). Anaerobic microorganisms, such as g_Faecalibacterium and g_Megamonas, account for the largest proportion in the gut, which were mainly Firmicutes phylum. The dominant genera and species in the three BMD groups were g_Prevotella, g_Bacteroides, g_Faecalibacterium, g_Megamonas, s_Prevotella copri, s_unclassified_g_Faecalibacterium, s_unclassified_g_Prevotella, s_unclassified_g_Bacteroides and s_Bacteroides plebeius. g_Faecalibacterium, g_Bacteroides and g_Ruminococcus differed between the BDH and BDL groups as well as between the BDH and BDM groups. LEfSe showed three genus communities and eight species communities were enriched in the three BMD groups, respectively. The associations between microbial relative abundance and T–score was not statistically significant by Spearman and regression analysis. In conclusion, the alpha diversity indexes in the BDH group were higher than in the BDL group, and several taxa were identified that may be the targets for diagnosis and therapy of OP.

Abstract Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Study RegionGuangzhou, ChinaStudy FocusOur research, based on the meticulous collection and rigorous statistical analysis of ground monitoring records for the entire year of 2022 in Guangzhou, delves into the spatio-temporal distribution patterns, evolution processes, flood formation mechanisms, and corresponding disaster mitigation strategies of urban surface flooding related to the capacity of drainage system in the region. New Hydrological Insights: The urban surface flooding (USF) in Guangzhou in 2022 provides key insights for flood risk management. The overall spatial distribution of USF risk in Guangzhou is stable, but specific flood locations during rainstorms vary due to factors such as rainfall conditions and drainage efficiency. This complexity highlights the diverse nature of USF challenges. The frequency of USF events varies significantly across months and dates, with a higher occurrence during the flood season. However, there is a noticeable extension of flood risk into the non-flood season, challenging traditional flood season concepts. USFs peak within 50 minutes, demanding urgent action within 25 minutes, underscoring the need for an efficient emergency response. Certain areas, times, and processes contribute more to the overall flood risk, emphasizing the importance of focusing on these high-risk factors for effective management and resource allocation. The study also reveals the prevalence of Surface Runoff-type Floods, challenging existing USF simulation methods and necessitating a reevaluation and improvement in the maintenance and design of urban rainwater inlets. The study suggests vigorously promoting private proactive flood mitigation behavior and proposes a hierarchical, classification-based approach to urban flood risk control. Comprehensive intervention in the urban runoff formation process is emphasized for effective flood risk management.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease all over the world, and no drug is approved for the treatment of NAFLD. Bavachinin (BVC) is proven to possess liver-protecting effect against NAFLD, but its mechanism is still blurry. Objectives: With the use of Click Chemistry-Activity‐Based Protein Profiling (CC-ABPP) technology, this study aims to identify the target of BVC, and investigate the mechanism by which BVC exerts its liver-protecting effect. Methods: The high fat diet induced hamster NAFLD model is introduced to investigate BVC’s lipid-lowering and liver-protecting effects. Then, a small molecular probe of BVC is designed and synthesized based on the CC-ABPP technology, and BVC’s target is fished out. A series of experiments are performed to identify the target, including competitive inhibition assay, surface-plasmon resonance (SPR), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and co-immunoprecipitation (Co-IP). Afterward, the pro-regeneration effects of BVC are validated in vitro and in vivo through flow cytometry, immunofluorescence, and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Result: In the hamster NAFLD model, BVC shows lipid-lowing effect and improvement on the histology. PCNA is identified as the target of BVC with the method mentioned above, and BVC facilitates the interaction between PCNA and DNA polymerase delta. BVC promotes HepG2 cells proliferation which is inhibited by T2AA, an inhibitor suppresses the interaction between PCNA and DNA polymerase delta. In NAFLD hamsters, BVC enhances PCNA expression and liver regeneration, reduces hepatocyte apoptosis. Conclusion: This study suggests that, besides the anti-lipemic effect, BVC binds to the pocket of PCNA facilitating its interaction with DNA polymerase delta and pro-regeneration effect, thereby exerts the protective effect against HFD induced liver injury.

Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats. This finding led us to hypothesize that the administration of exogenous CST is an effective strategy to promote wound healing in patients with DUs. We herein successfully prepared CST-loaded pDMA-pEPEMA nanoparticles (CST@NPs) designed to exhibit localized, acid-responsive behavior for enhanced wound healing. These CST@NPs were sensitive to acidic environments, triggering the rapid release of CST. In vitro experiments showed that CST@NPs effectively alleviated oxidative stress and reduced apoptosis in human umbilical vein endothelial cells (HUVECs). Our findings further demonstrated that CST@NPs accelerated re-epithelialization of the wound, enhanced collagen deposition, and stimulated angiogenesis, while alleviating the local inflammatory response. Both in vivo and in vitro results indicate that CST@NPs possess precise and rapid response capabilities in acidic environments, ensuring effective CST release to promote diabetic wound healing. In summary, this acid-responsive nanoparticle system presents a highly efficient therapeutic strategy for the treatment of chronic diabetic wounds.

The sugar content in watermelon significantly influences its flavor. To understand the sugar accumulation pattern in small-fruited watermelon and identify candidate genes involved in sugar synthesis and conversion, we measured the sugar content (sucrose, fructose, and glucose) at five developmental stages: 10d, 16d, 22d, 28d, and 34d post-pollination. Two watermelon varieties with the largest sugar content difference at 28d post-pollination (high-sugar G38-28 and low-sugar 482276-28) were selected for transcriptome sequencing. Differentially expressed genes (DEGs) were validated using RT-qPCR. Additionally, the sugar contents of three commercial varieties (‘Su Meng NO.5’, ‘Su Meng NO.6’, ‘Su Meng NO.7’) and their parents were compared at five stages. Results showed glucose and fructose levels peaked between 22d and 28d, followed by a decrease, while sucrose content continuously increased. F1 hybrids exhibited glucose and sucrose trends similar to their paternal parent and fructose trends similar to their maternal parent. Transcriptome sequencing identified 9337 DEGs (5072 upregulated and 4265 downregulated). Gene Ontology analysis highlighted overrepresentation in categories such as pectinase and oxidoreductase activity. KEGG analysis identified 12 DEGs involved in sugar synthesis and conversion pathways, including phenylpropanoid biosynthesis and pentose and glucuronate interconversions. RT-qPCR validation corroborated the transcriptome data. These findings explain the distinct sugar accumulation patterns in G38-28 and 482276-28 at the transcriptional level, offering insights for genetic breeding and regulation of key sugar-related genes in watermelon.

Abstract Objective Transcutaneous oxygen pressure (TcPO2) is used to assess microcirculation clinically; however, it is not widely available especially in rural hospital. The study was designed to explore potential alternatively biomarkers to assess microcirculation in diabetic kidney disease (DKD). Methods A total of 404 patients from Xuzhou first hospital were recruited according to the case records system. Patients were grouped via the ratio of albuminuria and creatinine (ACR; 300 mg/g). Biomarkers in different ACR groups were compared by analysis of variance. Correlation analysis was determined by Pearson or Spearman analysis and binary logistic regression. The receiver operating characteristics (ROC) curve was performed to elucidate the prediction effect of ACR on TcPO2. Results A total of 404 diabetic patients were recruited with 248 patients diagnosed as DKD and 156 non‐DKDs. Age and cystatin C were significantly higher in the ACR3 group compared with those in the ACR1 group, whereas glomerular filtration rate, low‐density lipoprotein cholesterol, and TcPO2 were markedly decreased in the ACR3 group (p

【Objective】The light condition is one of the key factors that affect the tissue culture efficiency of Anthurium andraeanum. The effects of different LED light quality ratio and light intensity on different stages of A. andraeanum tissue culture were studied to explore these light conditions suitable for each stage of tissue culture of A. andraeanum and provide an important technical reference for efficient tissue culture of A. andraeanum.【Method】The new A. andraeanum cultivar Fuxing was used as the experimental material, and the effects of different proportions of red and blue LED light ratio and light intensity on callus induction, proliferation culture and strong seedling culture of A. andraeanum Fuxing were analyzed.【Result】The LED red light quality was more suitable for the callus induction of A. andraeanum Fuxing, the 10% R light quality condition with light intensity of 100 lx had the highest callus induction rate of 79.58%, and the callus mass was yellow-green, compact, large in volume and good in state, which was suitable for the callus induction of A. andraeanum Fuxing leaves. The light quality ratio of R ∶ B = 3 ∶ 1 was suitable for callus proliferation culture of A. andraeanum Fuxing, and the proliferation coefficient was the highest (6.44) when the light intensity was 600 lx. Compared with WL light conditions, R ∶ B = 4 ∶ 1 light quality ratio was more suitable for the callus bud differentiation culture of A. andraeanum Fuxing, when the light intensity was 1 000 lx, the number of callus proliferation and differentiation was 19.44, and the buds were short and strong with good growth potential, without yellow leaf phenomenon. The light quality ratio suitable for the tissue culture seedling culture of A. andraeanum Fuxing at the strong seedling stage was R∶B = 4∶1, the light intensity was 900 lx, the number of roots of the strong seedlings of was more, with an average of 5.67, the plant height was 2.88 cm, the stem diameter was 1.44 mm, the leaf length was 11.69 mm, the leaf width was 8.54 mm, the plant leaf was large, the SPAD value was 39.23, the chlorophyll content of the leaf was higher, and the overall growth of the plant was robust without yellow leaf phenomenon.【Conclusion】LED light conditions have an impact on callus induction, proliferation culture, and strong seedling culture of A. andraeanum Fuxing in tissue culture. According to the lighting requirements at different stages of A. andraeanum tissue culture, selecting appropriate LED light quality ratio and light intensity conditions can effectively improve the callus induction rate, proliferation rate and tissue culture seedling production quality of A. andraeanum in tissue culture, and provide technical support for the efficient and standardized production of new A. andraeanum cultivar Fuxing.

Abstract Background Antiviral intervention in hepatitis B virus (HBV)-infected pregnant women can effectively reduce mother-to-child transmission. However, the immunological characteristics of pregnant women with chronic HBV infection and the effects of antiviral intervention during pregnancy on maternal immune response remain unknown. We aimed to investigate these effects by comparing mothers who received antiviral intervention during pregnancy with those who did not. Methods Pregnant women positive for hepatitis B surface antigen and hepatitis B e-antigen (HBsAg+ HBeAg+) were enrolled at delivery, including 34 received prophylactic antiviral intervention during pregnancy (AVI mothers) and 15 did not (NAVI mothers). T lymphocyte phenotypes and functions were analysed using flow cytometry. Results At delivery, maternal regulatory T cell (Treg) frequency in AVI mothers was significantly higher than that in NAVI mothers (P

Abstract Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the β-CASP and the β-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.

NF-κB inhibitor alpha (IKBA) signaling in mature sperm drives sperm motility and controls fatty acid b-oxidation metabolism.

Abstract Extreme climate and urbanization lead to frequent urban floods, and urban water system dispatching is an important means of urban flood control. A coupled model is proposed to simulate urban floods in real‐time and achieve comprehensive water system control for urban floods. First, the systematical description of coordinated drainage and regulation model of urban water systems in China is introduced, then the practice of Fuzhou city was taken as an example to introduce the prediction and forecast systems, as well as water system regulation for urban flood and waterlogging disaster in detail. Results show that the root‐mean‐square error of river flood prediction is less than 0.3 and that the calculation time of waterlogging simulation is less than 10 min; the optimization regulation reduces the peak river water level by 31 cm. This study will establish a novel urban water system management model to help urban managers better reduce the loss caused by urban floods.

Abstract Background The incidence and mortality rate of gastrointestinal cancers are high worldwide. Increasing studies have illustrated that the occurrence, progression, metastasis and prognosis of cancers are intimately linked to the immune system. Mitochondria, as the main source of cellular energy, play an important role in maintaining the physiological function of immune cells. However, the relationship between mitochondrial function of immune cells and tumorigenesis has not yet been systematically investigated. Methods A total of 150 cases, including 60 healthy donors and 90 primary gastrointestinal cancer patients without anti-tumor treatments (30 with gastric cancer, 30 with liver cancer and 30 with colorectal cancer) were involved in our study. The oxidant/antioxidant and cytokine levels in plasma, the ROS level, mitochondrial function and apoptosis ratio of peripheral blood mononuclear cells (PBMCs) were evaluated. Results The imbalance between oxidant and antioxidant in plasma was discovered in the primary gastrointestinal cancer patients. The levels of cell reactive oxygen species (ROS) and mitochondrial ROS in PBMCs of primary gastrointestinal cancers were significantly increased compared with that in healthy donors. Meanwhile, the ATP content, the mtDNA copy number and the mitochondrial membrane potential (MMP) in PBMCs of patients with primary gastrointestinal cancers were lower than those in control group. The decreased MMP also occurred in immune cells of gastrointestinal cancers, including T cell, B cell, NK cell and monocyte. Furthermore, the PBMCs apoptosis ratio of primary gastrointestinal cancer patients was significantly higher than that of control group. Importantly, an increase of IL-2 and IL-6 and a decrease of IgG in plasma were found in the patients with primary gastrointestinal cancers. These changes of mitochondrial function in immune cells were consistent among primary gastrointestinal cancers without anti-tumor treatments, such as liver cancer, gastric cancer and colorectal cancer. Conclusion Our study demonstrated that the imbalance of oxidation/antioxidation in primary gastrointestinal cancer patients without anti-tumor treatments results in excessive ROS. The oxidative stress was associated to the mitochondrial dysfunction, the apoptosis of immune cells and eventually the abnormal immune function in primary gastrointestinal cancers. The application of immune cell mitochondrial dysfunction into clinical evaluation is anticipated.

Colorectal cancer (CRC) is a cancer that occurs in the rectum or colon with a high incidence. Sperm-associated antigen 5 (SPAG5), a gene that regulates cell division, has been observed highly expressed in a variety of cancers, but its role in CRC is unclear. This study aimed to investigate the regulatory role of SPAG5 in CRC. The expression of SPAG5 in multiple cancers and normal tissues was predicted by The Cancer Genome Atlas and Tumor Immune Estimation Resource, and the expression of SPAG5 in human normal intestinal epithelial cells NCM460 and human CRC cell lines Caco2, HT29, SW480, and LOVO was verified by western blotting (WB). The effects of silencing SPAG5 on cell viability, proliferation, and apoptosis were then investigated by cell counting kit-8, WB, and flow cytometry. The effects of silencing SPAG5 on cell migration and invasion were investigated by scratch assay and transwell assay. Finally, the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and AKT in cells were detected by WB. The results showed that SPAG5 was highly expressed in CRC and was verified by WB. Silencing of SPAG5 inhibited cell viability and proliferation and increased the cell apoptosis rate. Furthermore, both cell invasion and migration abilities were suppressed by the low expression of SPAG5. Finally, WB results found that the phosphorylation levels of PI3K and AKT were reduced after SPAG5 silencing. In summary, the results showed that SPAG5 can promote the proliferation and invasion of CRC cells by targeting the PI3K/AKT signaling pathway.

Context Ganoderma lucidum polysaccharides (GLP), from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Ganodermataceae), are reported to have anti-inflammatory effects, including anti-neuroinflammation and anti-colitis. Nevertheless, the role of GLP in acute pneumonia is unknown.Objective To explore the protective role of GLP against LPS-induced acute pneumonia and investigate possible mechanisms.Materials and methods GLP were extracted and used for high-performance liquid chromatography (HPLC) analysis after acid hydrolysis and PMP derivatization. Sixty C57BL/6N male mice were randomly divided into six groups: Sham, Model, LPS + GLP (25, 50 and 100 mg/kg/d administered intragastrically for two weeks) and LPS + dexamethasone (6 mg/kg/d injected intraperitoneally for one week). Acute pneumonia mouse models were established by intratracheal injection of LPS. Haematoxylin and eosin (H&E) staining was examined to evaluate lung lesions. ELISA and quantitative real-time PCR were employed to assess inflammatory factors expression. Western blots were carried out to measure Neuropilin-1 expression and proteins related to apoptosis and autophagy.Results GLP suppressed inflammatory cell infiltration. In BALF, cell counts were 1.1 × 106 (model) and 7.1 × 105 (100 mg/kg). Release of GM-CSF and IL-6 was reduced with GLP (25, 50 and 100 mg/kg) treatment. The expression of genes IL-1β, IL-6, TNF-α and Saa3 was reduced. GLP treatment also suppressed the activation of Neuropilin-1 (NRP1), upregulated the levels of Bcl2/Bax and LC3 and led to downregulation of the ratio C-Caspase 3/Caspase 3 and P62 expression.Discussion and conclusions GLP could protect against LPS-induced acute pneumonia through multiple mechanisms: blocking the infiltration of inflammatory cells, inhibiting cytokine secretion, suppressing NRP1 activation and regulating pneumonocyte apoptosis and autophagy.

Low temperature is one of the bottleneck factors that limits the degradation of straw during rice straw incorporation. Determining strategies to promote the efficient degradation of straw in cold regions has become a highly active research area. This study was to investigate the effect of rice straw incorporation by adding exogenous lignocellulose decomposition microbial consortiums at different soil depths in cold regions. The results showed that the lignocellulose was degraded the most efficiently during straw incorporation, which was in deep soil with the full addition of a high-temperature bacterial system. The composite bacterial systems changed the indigenous soil microbial community structure and diminished the effect of straw incorporation on soil pH, it also significantly increased rice yield and effectively enhanced the functional abundance of soil microorganisms. The predominant bacteria SJA-15, Gemmatimonadaceae, and Bradyrhizobium promoted straw degradation. The concentration of bacterial system and the depth of soil had significantly positive correlations on lignocellulose degradation. These results provide new insights and a theoretical basis for the changes in the soil microbial community and the application of lignocellulose-degrading composite microbial systems with straw incorporation in cold regions.

Summary: Chlorpyrifos (CPF) has been shown to have male reproductive toxicity in mice and rat. However, the association of CPF and male reproduction in pigs remains unknown. Therefore, this study attempts to investigate the damage of CPF on male reproduction in pigs and its potential molecular mechanisms. First, ST cells and porcine sperms were treated with CPF and then cell proliferation, apoptosis, motility of sperm, and oxidative stress levels were examined, respectively. Meanwhile, RNA sequencing was performed on ST cells before and after the treatment of CPF. The results of experiments in vitro showed that CPF had broad-spectrum toxic effects on ST cells and porcine sperms. The RNA-sequencing data and WB results indicated that CPF may regulate cell survival through the PI3K-AKT pathway. In conclusion, this study may lay the foundation for improving male fertility in pigs and provide theoretical information for human infertility.

【Objective】The study aims to screen out the types, concentrations and application methods of plant growth regulators that can effectively promote early flowering and improve flowering uniformity of Gymnocalycium baldianum, and provide technical support for the regulation of flowering period of G. baldianum.【Method】With uniform seed balls of G. baldianum as test materials, the effects of different concentrations (100, 200, 400 and 800 mg/L) of paclobutrazol, uniconazole, indoleacetic acid and gibberellin on its flowering was explored.【Result】Spraying 100-800 mg/L paclobutrazol, uniconazole and indoleacetic acid solutions had no significant difference in the colour of seed balls, seed ball diameter increment, number of flowers and flowering rate. However, these three plant growth regulators could promote the early flowering of G. baldianum within a appropriate concentration range. The treatment of 100 mg/L paclobutrazol had the best result, which bloomed about 9.0 days earlier than that under water treatment. It could reach the full blooming period within 11.7 days, which was about 20.0 days shorter than that under water treatment, and the flowering had better uniformity. While the 100-800 mg/L gibberellin solution had an inhibitory effect on the flowering of G. baldianum, however, it could promote vegetative growth. The ball size, the number of thorns in the thorn seat, the thorn length, and the mass of the thorn seat all increased, and the colour of the seed ball was greener.【Conclusion】The study results can provide technological support for promoting the early flowering of G. baldianum and improving the uniformity of flowering. At the same time, it can improve the ornamental characters of G. baldianum according to individual needs, and improve its ornamental value, which has great significance to increase market share furtherly.

The novel duck reovirus (NDRV) emerged in southeast China in 2005. The virus causes severe liver and spleen hemorrhage and necrosis in various duck species, bringing serious harm to waterfowl farming. In this study, three strains of NDRV designated as NDRV-ZSS-FJ20, NDRV-LRS-GD20, and NDRV-FJ19 were isolated from diseased Muscovy ducks in Guangdong and Fujian provinces. Pairwise sequence comparisons revealed that the three strains were closely related to NDRV, with nucleotide sequence identities for 10 genomic fragments ranging between 84.8 and 99.8%. In contrast, the nucleotide sequences of the three strains were only 38.9–80.9% similar to the chicken-origin reovirus and only 37.6–98.9% similar to the classical waterfowl-origin reovirus. Similarly, phylogenetic analysis revealed that the three strains clustered together with NDRV and were significantly different from classical waterfowl-origin reovirus and chicken-origin reovirus. In addition, the analyses showed that the L1 segment of the NDRV-FJ19 strain was a recombinant of 03G and J18 strains. Experimental reproduction of the disease showed that the NDRV-FJ19 strain was pathogenic to both ducks and chickens and could lead to symptoms of hemorrhage and necrosis in the liver and spleen. This was somewhat different from previous reports that NDRV is less pathogenic to chickens. In conclusion, we speculated that the NDRV-FJ19 causing duck liver and spleen necrosis is a new variant of a duck orthoreovirus that is significantly different in pathogenicity from any previously reported waterfowl-origin orthoreovirus.

BackgroundThe nurse-physician relationship is important for the stability of collaboration. The COVID-19 pandemic has put unprecedented pressure on the health care system and has placed greater demands on nurse-physician collaboration. Nurses and physicians often struggle to share mutual responsibility and communicate effectively. ObjectiveThis study aimed to evaluate the relationship between nurses and physicians during the COVID-19 pandemic and construct a new model combining the attitude and behaviors of the 2 groups to assess various factors’ impacts on job satisfaction and confrontational behavior. MethodsWe conducted this quantitative cross-sectional study to assess the relationship between nurses and physicians based on the attitudes and behaviors toward nurse-physician collaboration. We first investigated the satisfaction of nurses and physicians with their relationship and how they thought the COVID-19 pandemic had affected that relationship. We used an adapted and modified Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration questionnaire that consisted of 17 items under 5 dimensions. Structural equation modeling was used to assess the relationships between domains. Ordinal logistic regression was used to evaluate the relationship between different domains of the questionnaire and the satisfaction of the current nurse-physician relationship. ResultsWe included a total of 176 nurses and 124 physicians in this study. Compared to 7.2% (9/124) of physicians, 22.7% (40/176) of nurses were dissatisfied with the current nurse-physician relationship. Most physicians (101/124, 81.5%) and nurses (131/176, 74.5%) agreed that the nurse-physician relationship had become better because of the COVID-19 pandemic and that the public had greater respect for them. However, significantly fewer nurses (59/176, 33.5% vs 79/124, 63.7%; P

ABSTRACT The success of Mycobacterium tuberculosis (Mtb) as a pathogen is partly attributed to its ability to sense and respond to dynamic host microenvironments. The cyclic AMP (cAMP) receptor protein (CRP) is closely related to the pathogenicity of Mtb and plays an important role in this process. However, the molecular mechanisms guiding the autoregulation and downstream target genes of CRP while Mtb responds to its environment are not fully understood. Here, it is demonstrated that the acetylation of conserved lysine 193 (K193) within the C-terminal DNA-binding domain of CRP reduces its DNA-binding ability and inhibits transcriptional activity. The reversible acetylation status of CRP K193 was shown to significantly affect mycobacterial growth phenotype, alter the stress response, and regulate the expression of biologically relevant genes using a CRP K193 site-specific mutation. Notably, the acetylation level of K193 decreases under CRP-activating conditions, including the presence of cAMP, low pH, high temperature, and oxidative stress, suggesting that microenvironmental signals can directly regulate CRP K193 acetylation. Both cell- and murine-based infection assays confirmed that CRP K193 is critical to the regulation of Mtb virulence. Furthermore, the acetylation of CRP K193 was shown to be dependent on the intracellular metabolic intermediate acetyl phosphate (AcP), and deacetylation was mediated by NAD+-dependent deacetylases. These findings indicate that AcP-mediated acetylation of CRP K193 decreases CRP activity and negatively regulates the pathogenicity of Mtb. We believe that the underlying mechanisms of cross talk between transcription, posttranslational modifications, and metabolites are a common regulatory mechanism for pathogenic bacteria. IMPORTANCE Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, and the ability of Mtb to survive harsh host conditions has been the subject of intensive research. As a result, we explored the molecular mechanisms guiding downstream target genes of CRP when Mtb responds to its environment. Our study makes a contribution to the literature because we describe the role of acetylated K193 in regulating its binding affinity to target DNA and influencing the virulence of mycobacteria. We discovered that mycobacteria can regulate their pathogenicity through the reversible acetylation of CRP K193 and that this reversible acetylation is mediated by AcP and a NAD+-dependent deacetylase. The regulation of CRPMtb by posttranslational modifications, at the transcriptional level, and by metabolic intermediates contribute to a better understanding of its role in the survival and pathogenicity of mycobacteria.

【Objective】Tissue culture is one of the important ways for rapid propagation of Aglaonema commutatum, the factors affecting leaf color in tissue culture were studied and explored to maintain the redness of leaf color, and to provide technical references for further stabilizing efficient tissue culture technology and regulating leaf color of A. commutatum with red leaves.【Method】Taking A. commutatum 'Guanghuahong' with red leaves as experimental material, the effects of proliferation medium, proliferation mode, light intensity and light quality on leaf color of A. commutatum were studied.【Result】The improved MS medium supplemented with 0.5 g/L K2SO4 was used for proliferation culture, and the proliferation and differentiation seedlings were more robust, with brighter leaf color, and the transplanting seedling rate was 90.00%.The leaf color of tissue culture seedlings cultured by the proliferation of clustered buds was more stable than that cultured by the proliferation of callus, and the transplanting seedling rate was higher. In the stages of proliferation and rooting, when the light intensity was 4 000 lx, the red plaque area increased, and the transplanting seedling rate was higher (88.89%). Under the light quality condition of red light : blue light = 3∶7, the lowest total content of chlorophyll in leaves was 0.037 mg/g, and the highest relative content of anthocyanin was 0.399 Units/g, and the leaves were red and brilliant.【Conclusion】Using the improved proliferation medium, adopting the proliferation mode of clustered buds, adjusting the light intensity and changing the red and blue light quality ratio can effectively maintain the redness of leaves and improve the production efficiency of tissue culture.

Abstract Background Pulmonary infection is common yet serious complication in patients with severe traumatic brain injury (STBI). We aimed to evaluate the predicators of pulmonary infection in STBI patients undergoing tracheostomy, to provide evidence for the clinical nursing care of STBI patients. Methods This study was a retrospective cohort design. STBI patients undergoing tracheostomy treatment from January 1, 2019 to August 31, 2021 in our hospital were included. The characteristics of pulmonary infection and no pulmonary infection patients were analyzed. Results A total 216 STBI patients undergoing tracheostomy were included, the incidence of pulmonary infection was 26.85%. Diabetes (r = 0.782), hypoproteinemia (r = 0.804), duration of coma(r = 0.672), duration of mechanical ventilation(r = 0.724) and length of hospital stay (r = 0.655), length of hospital stay post tracheostomy (r = 0.554), mortality (r = 0.598) were all correlated with pulmonary infection (all p

The amorphous polymers present remarkable temperature- and rate-dependent deformation behaviors. Based on a combination of the multiple relaxation viscoelastic-viscoplastic model and the three-element viscoelastic model, a constitutive model was constructed to describe the changes in mechanical properties of amorphous polymers from below to above glass transition temperature (θg). In this model, an exponential evolution equation of volume fraction was constructed to reflect the changes in glassy and rubbery phases at different temperatures. The proposed model was implemented into ABAQUS using the user-defined material subroutine (VUMAT). The strain-softening after yield and rate-dependent behaviors above and below θg were reasonably captured by the present model. Meanwhile, the creep and relaxation behaviors of the material were described. Finally, the processes of the tensile deformation of a dumbbell plate with a circular hole and the rate-dependent pressed film molding were simulated by the VUMAT. The results show that the implemented model can reasonably predict the structural responses of amorphous polymers.

Abstract Tribbles homolog 1 (TRIB1) belongs to the Tribbles family of pseudokinases, which plays a key role in tumorigenesis and inflammation. Although genome-wide analysis shows that TRIB1 expression is highly correlated with blood lipid levels, the relationship between TRIB1 and adipose tissue metabolism remains unclear. Accordingly, the aim of the present study was to explore the role of TRIB1 on mitochondrial function in the brown adipose tissue (BAT). Trib1-knockout mice were established using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. The metabolic function of the BAT was induced by a β3-adrenoceptor agonist and the energy metabolism function of mitochondria in the BAT of mice was evaluated. Trib1-knockout mice exhibited obesity and impaired BAT thermogenesis. In particular, Trib1 knockout reduced the ability of the BAT to maintain body temperature, inhibited β3-adrenoceptor agonist-induced thermogenesis, and accelerated lipid accumulation in the liver and adipose tissues. In addition, Trib1 knockout reduced mitochondrial respiratory chain complex III activity, produced an imbalance between mitochondrial fusion and fission, caused mitochondrial structural damage and dysfunction, and affected heat production and lipid metabolism in the BAT. Conversely, overexpression of Trib1 in 3T3-L1 adipocytes increased the number of mitochondria and improved respiratory function. These findings support the role of Trib1 in regulating the mitochondrial respiratory chain and mitochondrial dynamics by affecting mitochondrial function and thermogenesis in the BAT.

Abstract Background Postpartum alanine transaminase (ALT) flares occur frequently in chronic hepatitis B virus (HBV)-infected mothers with antepartum antiviral therapy (AVT). We aimed to characterize the T cell immunity in HBV-infected mothers experiencing postpartum ALT flares. Methods Twenty HBV-infected pregnant women who received AVT at 26–28 weeks of gestation were enrolled and followed up until 15–18 weeks postpartum. Among the 20 HBV-infected pregnant women, 6 experienced postpartum ALT flare (AF mothers), while 14 did not (NAF mothers). T lymphocyte phenotypes and functions were analyzed using flow cytometry. Results Compared to NAF mothers, the quantitative HBsAg levels in AF mothers decreased significantly at 6–8 or 15–18 weeks postpartum. Significant differences in HBeAg levels between these groups were only found at delivery. Regulatory T cell (Treg) numbers in AF mothers were lower than those of NAF mothers before AVT; however, there were no significant differences in Treg numbers at other follow-up points. Expression of other T cell phenotypes were similar between the two groups. T cells in AF mothers produced more pro-inflammatory cytokines (IFN-γ, IL-21, TNF-α, IL-2) or less anti-inflammatory cytokine (IL-10) than those in NAF mothers before, during, or after antiviral treatment. The ratio of IFN-γ to IL-10 producing by CD4+ T cells or CD8+ T cells was higher in AF mothers than that in NAF mothers during pregnancy or after delivery. Conclusions The characteristics of T cell immunity was distinct between mothers with postpartum ALT flare and those without ALT flare from pregnancy to postpartum, which indicated that T cell immunity might get involved in postpartum ALT flare.

The resistive switching (RS) behaviors have been widely studied in a large number of two-dimensional (2D) materials. Bismuth oxyhalides have emerged as a typical ternary 2D layered material recently. However, the studies focusing on the RS behaviors in 2D bismuth oxyhalides are still limited. Herein, the RS behaviors in 2D BiOX (X = Cl, Br and Cl + Br) nanosheets have been systematically studied. 2D BiOX nanosheets are exfoliated from their bulk materials which are synthesized by a hydrothermal method. Vertical memristors with Pt/BiOX/Pt sandwiched structures have been fabricated for RS measurements. Among them, 2D BiOCl nanosheet has no RS behaviors. BiOBr nanosheet demonstrates non-volatile bipolar RS behaviors with a large ON/OFF ratio (∼105), long time retention (104 s) and good endurance (280 cycles) as well as good environmental stability, suggesting potential applications in non-volatile memory. Furthermore, BiOBr0.7Cl0.3 nanosheet shows volatile threshold switching (TS) behaviors with the ON/OFF ratio up to 105. The device with TS behaviors can be utilized to emulate the leaky integrate-and-fire (LIF) functions in biological synapses. This work demonstrates a new material with non-volatile or volatile RS behaviors, providing a new TS device for emulation of LIF activity.

Recently, so-called “vegetative” and “generative” rootstocks have been identified by seed companies as rootstock types that have different impacts on tomato scions. In this experiment of grafted grape tomato production in an organically managed high tunnel system, we characterized the effects of vegetative and generative rootstock cultivars on tomato yield components and fruit mineral contents. Grape tomato scions ‘BHN 1022’ (determinate) and ‘Sweet Hearts’ (indeterminate) were grafted onto ‘DR0141TX’ (vegetative), ‘Estamino’ (generative), and ‘Multifort’ (noncharacterized) rootstocks with self- and nongrafted scions as controls. Experiments were conducted twice with different transplanting dates (Expt. 1: 31 Jan. vs. Expt. 2: 9 Mar.) in 2018. No rootstock by scion interaction effects on whole-season fruit yield components were observed, indicating similar responses of determinate and indeterminate grape tomato scions to all rootstocks tested. For Expt. 1, the three rootstocks increased marketable fruit number, marketable yield, and total yield by 23.3%, 37.9%, and 34.4% on average, respectively, compared with the self- and nongrafted controls, primarily due to improved productivity during the peak and late harvest periods. For Expt. 2, the rootstocks did not significantly benefit any whole-season yield components. ‘DR0141TX’ and ‘Multifort’ increased stem diameter in both experiments, whereas ‘Estamino’ only increased stem diameter in Expt. 2 relative to the nongrafted controls. Consistent increase in aboveground dry biomass of rootstock treatments at crop termination in Expt. 1 corresponded to the greater yield of rootstock-grafted plants in that experiment. All rootstocks in both experiments consistently increased fruit P, K, Ca, Zn, and Fe contents on a dry weight basis at peak harvest regardless of the tomato scion used. Despite a relatively low level of root-knot nematode infestation, plants grafted with ‘DR0141TX’ or ‘Estamino’ tended to have lower root galling index ratings than scion controls and ‘Multifort’-grafted plants, which was more evident in Expt. 1. Given the different environmental conditions during the tomato production period between the two experiments conducted in high tunnels, our findings highlight the important influence of production environment on grafted tomato performance. This study on grafted grape tomatoes in high tunnel organic production systems also demonstrated that so-called “vegetative” and “generative” rootstocks had similar impacts on tomato scion yield components and fruit mineral contents.

Urban roads in China, particularly low-lying areas such as underpasses, tunnels, and culverts, are highly vulnerable to the dangers of urban pluvial flooding. We used spatial interpolation methods and limited measured data to assign elevation values to the road surface. The road network was divided into tiny squares, enabling us to calculate each square’s elevation, slope, and curvature. Statistical analysis was then employed to evaluate the impact of terrain on flood characteristics in urban road systems. Our analysis reveals a strong spatial correspondence between the distribution of flood-prone points and the curvature parameters of the terrain. The spatial coincidence rate can reach 100% when an appropriate sampling scale is chosen. The presence of depressions is necessary but insufficient for forming flood-prone points. In lowland/gentle slope (LL/GS) areas with higher drainage pressure, we observe a significant negative correlation between flood-prone points and terrain curvature (Spearman’s r = 0.205, p < 0.01). However, in highland/steep slope (HL/SS) areas, we find no significant correlation between them. Notably, terrain matters, but effective drainage is more influential in flood-prone areas. The maximum flood depth (MFD), submerged area, and ponding volume during urban pluvial flooding are constrained by depression topography, while the characteristics of the upstream catchment area also play a role in determining the MFD and flood peak lag time(FPLT). Larger upstream catchment areas and longer flow paths normally result in greater MFD and longer emergency response times/FPLT. Additionally, a higher flow path gradient will directly contribute to an increased flood risk (greater MFD and shorter FPLT). These findings have important implications for flood risk identification and the development of effective flood mitigation strategies.

Until now, the molecular mechanisms underlining sperm motility defect causing male infertility are still poorly understood. Safe and effective compounds or drugs that can improve sperm motility are also very limited. Lysophosphatidic acid (LPA) is a naturally occurring phospholipid and a bioactive intermediate with multiple biological activities. It has been detected in various body fluids such as serum, plasma, saliva, tears, blister fluids, hen egg white, and ascites from patients with ovarian cancer. LPA is also abundant in seminal plasma and follicular fluid. It enhances follicle stimulation, improves oocyte fertilization, and promotes early embryonic development and embryo implantation. However, the physiological role of LPA in the male reproductive system remains unknown. Here, our study showed that LPA significantly improved the motility parameters of human sperm hyperactivation in a dose-dependent manner. The LPA-induced elevation of sperm motility is dependent on bovine serum albumin (BSA) but independent of the classical BSA-induced sAC/cAMP/PKA signaling pathway. The enhancement of sperm motility by LPA could not be blocked by CCCP, a respiratory inhibitor suppressing mitochondrial ATP production. Moreover, LPA improved the activity of triosephosphate isomerase in glycolysis. Meanwhile, LPA treatment significantly increased ATP and phosphoenolpyruvate levels and decreased ADP content during sperm glycolysis. Notably, none of known or identified LPA receptors was detected in human sperm. Further investigations showed that LPA promoted sperm motility through L-type calcium channels. In summary, this study revealed the involvement of LPA in the regulation for human sperm motility by enhancing glycolysis and activating L-type calcium channels. The current findings may shed new light on the understanding of causes of asthenozoospermia, and indicate that LPA could be used as a novel therapeutic agent to improve sperm function and fertilizing capacity.

The ATP binding cassette transporter ABCG2 is a physiologically important drug transporter that has a central role in determining the ADMET (absorption, distribution, metabolism, elimination, and toxicity) profile of therapeutics, and contributes to multidrug resistance. Thus, development of predictive in silico models for the identification of ABCG2 inhibitors is of great interest in the early stage of drug discovery. In this work, by exploiting a large public dataset, a number of ligand-based classification models were developed using partial least squares-discriminant analysis (PLS-DA) with molecular interaction field- and fingerprint-based structural description methods, regarding physicochemical and fragmental properties related to ABCG2 inhibition. An in-house dataset compiled from recently experimental studies was used to rigorously validated the model performance. The key molecular properties and fragments favored to inhibitor binding were discussed in detail, which was further explored by docking simulations. A highly informative chemical property was identified as the principal determinant of ABCG2 inhibition, which was utilized to derive a simple rule that had a strong capability for differentiating inhibitors from non-inhibitors. Furthermore, the incorporation of the rule into the best PLS-DA model significantly improved the classification performance, particularly achieving a high prediction accuracy on the independent in-house set. The integrative model is simple and accurate, which could be applied to the evaluation of drug-transporter interactions in drug development. Also, the dominant molecular features derived from the models may help medicinal chemists in the molecular design of novel inhibitors to circumvent ABCG2-mediated drug resistance.

EsxA, secreted by the ESAT-6 secretion system 1 (ESX-1) secretion system, is considered the major Mycobacterium tuberculosis (Mtb) virulence determinant. However, the roles of the individual ESX-1 substrates, such as EspC, remain unclear due to their interdependency for secretion with EsxA. Here, we validated that EspC triggered ER stress-mediated apoptosis in macrophages. The EspC-mediated ER stress was involved in pro-inflammatory cytokines generation, intracellular Ca2+ release, and reactive oxygen species accumulation. Mitochondrial transmembrane potential dissipation and mitochondrial outer membrane permeabilization occurred in EspC-treated macrophages, causing apoptosis. Furthermore, ER stress-mediated apoptosis was effectively induced in EspC-overexpressing Mycobacterium smegmatis-infected macrophages and mice. EspC overexpression caused a significant increase in bacterial survival in the macrophages, spleens, and lungs, and accelerated mouse death was observed. Moreover, the increased viability of bacteria in the macrophages was significantly reduced by pretreatment with the apoptosis inhibitor. Overall, our results revealed that EspC is an essential ESX-1 protein for Mtb–host interactions and EspC-induced ER stress-mediated apoptosis may be employed by Mtb to establish and spread infection. Given the critical roles of the ESX systems in Mtb pathogenesis and immunity, our findings offer new perspectives on the complex host-pathogen interactions and mechanisms underlying ESX-1-mediated pathogenesis.

BackgroundHemoglobin A1c (HbA1c) variability may be a predictor of diabetic complications, but the predictive values of HbA1c trajectories remain unclear. We aimed to classify long-term HbA1c trajectories and to explore their effects on future clinical outcomes in a 10-year cohort with type 2 diabetes mellitus (T2DM).MethodsA total of 2,161 participants with T2DM from the Beijing Community Diabetes Study were included. The 10-year follow-up was divided into two stages for the present data analysis. Stage I (from 2008 to 2014) was used to identify the HbA1c trajectories and to calculate the adjusted SD of HbA1c (HbA1c-adjSD), or the coefficient of variation of HbA1c (HbA1c-CV). Stage II (from 2014 to 2018) was used to collect the records of the new occurrence of diabetes-related clinical outcomes. Latent growth mixture models were used to identify HbA1c trajectories. Cox proportional hazards models were used to explore the relationship between HbA1c trajectories, HbA1c-adjSD, or HbA1c-CV and the future outcomes.ResultsThree HbA1c trajectories were identified, including low stable (88.34%), gradual decreasing (5.83%), and pre-stable and post-increase (5.83%). Either the risk of death or the chronic complications were significantly higher in the latter two groups compared to the low stable group after adjustment for average HbA1c and other traditional risk factors, the adjusted hazard ratios (HRs) for renal events, composite endpoint, and all-cause death for the pre-stable and post-increase group were 2.83 [95%CI: 1.25–6.41, p = 0.013], 1.85 (95%CI: 1.10–3.10, p = 0.020), and 3.01 (95%CI: 1.13–8.07, p = 0.028), respectively, and the adjusted HR for renal events for the gradual decreasing group was 2.37 (95%CI: 1.08–5.21, p = 0.032). In addition, both univariate and multivariate Cox HR models indicated that participants in the fourth and third quartiles of HbA1c-CV or HbA1c-adjSD were at higher risk of renal events compared to participants in the first quartile.ConclusionsHbA1c trajectories, HbA1c-CV, and HbA1c-adjSD could all predict diabetes-related clinical outcomes. HbA1c trajectories could reflect long-term blood glucose fluctuation more intuitively, and non-stable HbA1c trajectories may predict increased risk of renal events, all-cause death, and composite endpoint events, independent of average HbA1c.

BackgroundThe changes of endothelial function in type 2 diabetes mellitus (T2DM) patients are closely associated with the development of cardiovascular disease (CVD). However, it is still unclear whether commonly used antidiabetic drugs can improve endothelial function. Flow-mediated dilation (FMD) is a noninvasive tool for evaluating endothelial function, which typically examines changes in the brachial artery diameter in response to ischemia using ultrasound. We performed a network meta-analysis (NMA) to explore the associations between changes in endothelial function and antidiabetic drugs by evaluating FMD in T2DM patients.MethodsWe systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until January 25, 2022 with no language restriction. The primary outcome was FMD change in all studies, and we performed subgroup analysis in T2DM patients without CVD. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs).ResultsFrom the 1,987 candidate articles identified in the initial search, 30 RCTs were eventually included in the analysis. In all studies, glucagon-like peptide-1 receptor (GLP-1R) agonists [MD = 3.70 (1.39–5.97)], TZD [MD = 1.96 (0.006–3.89)] produced improvement of FMD change compared to lifestyle intervention. GLP-1R agonists [MD = 3.33 (1.36–5.34) and MD = 3.30 (1.21–5.43)] showed significantly greater improvements in FMD change in pairwise comparisons with sulfonylureas and placebo. SGLT-2i also showed efficacy compared to sulfonylureas (MD = 1.89, 95% CI, 0.10, 3.75). In studies of T2DM patients without CVD, GLP-1R agonists [MD = 3.53 (1.24–5.76)], and TZD [MD = 2.30 (0.27–3.24)] produced improvements in FMD change compared to lifestyle treatment. GLP-1R agonists [MD = 3.25 (1.13–5.40), and MD = 3.85 (1.68–6.13)] showed significantly greater improvements in pairwise comparisons with sulfonylureas, and placebo.ConclusionIn T2DM patients, both GLP-1R agonists, SGLT-2i and TZD have favorable effects to improve endothelial function in T2DM patients. In T2DM patients without CVD, GLP-1R agonists had a greater effect to improve endothelial function than sulfonylureas. These suggested that GLP-1R agonists are associated with significantly improved endothelial function in T2DM patients.

Background People with diabetes are more likely to develop cardiovascular diseases. Lipotoxicity plays a key role in the development of diabetic cardiomyopathy. Panax notoginseng saponin (PNS) has been used to treat diabetes and obesity. However, the role of PNS in diabetic cardiomyopathy remains unclear. Methods and Results Diabetic db/db mice received high‐dose (200 mg/kg per day) or medium‐dose (100 mg/kg per day) PNS by gavage for 12 weeks until week 36. Lipid accumulation and cardiac function in diabetic mice were detected and possible mechanisms involved were explored. PNS significantly improved body weight, body fat content, serum lipids, adipocytokines, and antioxidative function in db/db mice. Lipid accumulation in adipose tissue, liver, and heart were also alleviated by PNS treatment. Cardiac function and mitochondrial structure were also improved by PNS. H9c2 cells were treated with palmitate acid, and PNS pretreatment reduced lipid accumulation, mitochondrial reactive oxygen species, as well as improved mitochondrial membrane potential and mitochondrial oxygen consumption rate. Levels of proteins and expression of genes related to glucose and lipid metabolism, antioxidative function, and mitochondrial dynamics were also improved by PNS administration. Conclusions PNS attenuated heart dysfunction in diabetic mice by reducing lipotoxicity as well as modulating oxidative stress and improving mitochondrial function.

BackgroundFacial paralysis is a common clinical disease, it was named intractable facial paralysis when the clinical course more than 2 months. Intractable facial paralysis will produce anxiety and depression, which will seriously affect patients' life and work. Electric acupuncture has been widely used in the treatment of intractable facial paralysis. However, the results of clinical studies on the efficacy and safety have been inconsistent. This study aims to evaluate the efficacy and safety of electric acupuncture for intractable facial paralysis patients by systematic review and meta-analysis, so as to provide clinical decision-making based on evidence-based medicine.MethodsThe following databases will be searched by electronic methods: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, VIP Database, Wan-fang Data and Chinese Biomedical Database. All of them will be retrieved from the establishment date of the electronic database to March 2022, all included studies will be evaluated risk of bias by the Cochrane Handbook. The total effective rate will be the primary outcome. The systematic review will be conducted with the use of the RevMan5.3 software in this study.ResultsThis study will obtain efficacy and safety of electric acupuncture for the treatment of intractable facial paralysis.DiscussionThis study will provide clinical decision-making based on evidence-based medicine that whether electric acupuncture could be used to treat intractable facial paralysis, and when and how it might be more effective and safety. It will help standardize electric acupuncture treatment strategies for intractable facial paralysis.Prospero registration numberCRD42021278541.

Abstract Background High-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method. Methods We retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China). Results Of the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9–72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0–75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0–94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002). Conclusions Both cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method.

Background: Wolf-Hirschhorn syndrome, a well-known contiguous microdeletion syndrome, is caused by deletions on chromosome 4p. While the clinical symptoms and the critical region for this disorder have been identified based on genotype-phenotype correlations, duplications in this region have been infrequently reported.Conclusion: Our case report shows that both deletions and duplications of the Wolf-Hirshhorn critical region cause intellectual disability/developmental delay and multiple congenital anomalies.

The PE/PPE protein family commonly exists in pathogenic species, such as Mycobacterium tuberculosis, suggesting a role in virulence and its maintenance. However, the exact role of most PE/PPE proteins in host–pathogen interactions remains unknown. Here, we constructed a recombinant Mycobacterium smegmatis expressing M. tuberculosis PE_PGRS19 (Ms_PE_PGRS19) and found that PE_PGRS19 overexpression resulted in accelerated bacterial growth in vitro, increased bacterial survival in macrophages, and enhanced cell damage capacity. Ms_PE_PGRS19 also induced the expression of pro-inflammatory cytokines, such as IL-6, TNF-α, IL-1β, and IL-18. Furthermore, we demonstrated that Ms_PE_PGRS19 induced cell pyroptosis by cleaving caspase-11 via a non-classical pathway rather than caspase-1 activation and further inducing the cleavage of gasdermin D, which led to the release of IL-1β and IL-18. To the best of our current knowledge, this is the first report of a PE/PPE family protein activating cell pyroptosis via a non-classical pathway, which expands the knowledge on PE/PPE protein functions, and these pathogenic factors involved in bacterial survival and spread could be potential drug targets for anti-tuberculosis therapy.

Diabetic retinopathy (DR) is the most common complication of diabetes. It is also the main cause of blindness caused by multicellular damage involving retinal endothelial cells, ganglial cells, and pigment epithelial cells in adults worldwide. Currently available drugs for DR do not meet the clinical needs; thus, new therapeutic targets are warranted. Noncoding RNAs (ncRNAs), a new type of biomarkers, have attracted increased attention in recent years owing to their crucial role in the occurrence and development of DR. NcRNAs mainly include microRNAs, long noncoding RNAs, and circular RNAs, all of which regulate gene and protein expression, as well as multiple biological processes in DR. NcRNAs, can regulate the damage caused by various retinal cells; abnormal changes in the aqueous humor, exosomes, blood, tears, and the formation of new blood vessels. This study reviews the different sources of the three ncRNAs—microRNAs, long noncoding RNAs, and circular RNAs—involved in the pathogenesis of DR and the related drug development progress. Overall, this review improves our understanding of the role of ncRNAs in various retinal cells and offers therapeutic directions and targets for DR treatment.

As a widely existing traditional Chinese medicine component, TP (triptolide) has serious reproductive toxicity which causes severe damage to the reproductive system and limits its application prospect. TP and MET (metformin) have shown great potential in combined with each other in anticancer and anti-inflammatory. Whether metformin can resist the reproductive toxicity caused by triptolide, the effects of MET on TP-induced reproductive capacity has not been reported. In this study, metformin was used to investigate the therapeutic effect on reproductive toxicity induced by TP in rat. The results showed that metformin had significant therapeutic effects on oxidative stress damage, destruction of the blood-testosterone barrier and apoptosis. And it proved that its therapeutic effect is mainly to restore the structural and functional stability of testis through antioxidant stress. It will provide guidance for the treatment of reproductive toxicity caused by TP and the adjuvant detoxification of TP application.

Diabetic cardiomyopathy (DCM), one severe complication in the diabetes, leads to high mortality in the diabetic patients. However, the understanding of molecular mechanisms underlying DCM is far from completion. Herein, we investigated the disease-related differences in the proteomes of DCM based on db/db mice and verified the protective roles of peroxiredoxin-4 (Prdx4) in H9c2 cardiomyocytes treated by palmitic acid (PA). Fasting blood glucose (FBG) and cardiac function was detected in the 6-month-old control and diabetic mice. The hearts were then collected and analyzed by a coupled label-free and mass spectrometry approach. In vivo investigation indicated that body weight and FBG of db/db mice markedly increased, and diabetic heart exhibited obvious cardiac hypertrophy and lipid droplet accumulation, and cardiac dysfunction as is indicated by the increases of left ventricle posterior wall thickness in systole (LVPWd) and diastole (LVPWs), and reduction of fractional shortening (FS). We used proteomic analysis and then detected a grand total of 2636 proteins. 175 differentially expressed proteins (DEPs) were markedly detected in the diabetic heart. Thereinto, Prdx4 was markedly down-regulated in the diabetic heart. In vitro experiments revealed that 250 μM PA significantly inhibited viability of H9c2 cell. PA induced much accumulation of lipid droplet in cardiomyocytes and resulted in an increase of mRNA expressions of lipogenic genes (FASN and SCD1) and cardiac hypertrophic genes. Additionally, protein level of Prdx4 evidently reduced in the PA-treated H9c2 cell. It was further found that shRNA-mediated Prdx4 knockdown exacerbated PA-induced oxidative stress and cardiomyocyte apoptosis, whereas overexpressing Prdx4 in the H9c2 cells noteworthily limited PA-induced ROS generation and cardiomyocytes apoptosis. These data collectively reveal the essential role of abnormal Prdx4 in pathological alteration of DCM, and provide potentially therapeutic target for the prevention of DCM.

Recent studies have confirmed that chlorophyllase (CLH), a long-found chlorophyll (Chl) dephytylation enzyme for initiating Chl catabolism, has no function in leaf senescence-related Chl breakdown. Yet, CLH is considered to be involved in fruit degreening and responds to external and hormonal stimuli. The purpose of this work was to elucidate in detail the biochemical, structural properties, and gene expression of four CLHs from the Solanum lycopersicum genome so as to understand the roles of Solanum lycopersicum chlorophyllases (SlCLHs). SlCLH1/4 were the predominantly expressed CLH genes during leaf and fruit development/ripening stages, and SlCLH1 in mature green fruit was modulated by light. SlCLH1/2/3/4 contained a highly conserved GHSXG lipase motif and a Ser-Asp-His catalytic triad. We identified Ser159, Asp226, and His258 as the essential catalytic triad by site-directed mutagenesis in recombinant SlCLH1. Kinetic analysis of the recombinant enzymes revealed that SlCLH1 had high hydrolysis activities against Chl a, Chl b, and pheophytin a (Phein a), but preferred Chl a and Chl b over Phein a; SlCLH2/3 only showed very low activity to Chl a and Chl b, while SlCLH4 showed no Chl dephytylation activity. The recombinant SlCLH1/2/3 had different pH stability and temperature optimum. Removal of the predicted N-terminal processing peptide caused a partial loss of activity in recombinant SlCLH1/2 but did not compromise SlCLH3 activity. These different characteristics among SlCLHs imply that they may have different physiological functions in tomato.

Charcot-Marie-Tooth (CMT) disease is the most common inherited neurodegenerative disorder with selective degeneration of peripheral nerves. Despite advances in identifying CMT-causing genes, the underlying molecular mechanism, particularly of selective degeneration of peripheral neurons remains to be elucidated. Since peripheral neurons are sensitive to multiple stresses, we hypothesized that daily repeated stress might be an essential contributor to the selective degeneration of peripheral neurons induced by CMT-causing mutations. Here, we mainly focused on the biological effects of the dominant missense mutation (S135F) in the 27-kDa small heat-shock protein HSPB1 under repeated heat shock. HSPB1S135F presented hyperactive binding to both α-tubulin and acetylated α-tubulin during repeated heat shock when compared with the wild type. The aberrant interactions with tubulin prevented microtubule-based transport of heat shock-induced misfolded proteins for the formation of perinuclear aggresomes. Furthermore, the transport of autophagosomes along microtubules was also blocked. These results indicate that the autophagy pathway was disrupted, leading to an accumulation of ubiquitinated protein aggregates and a significant decrease in cell adaptation to repeated stress. Our findings provide novel insights into the molecular mechanisms of HSPB1S135F-induced selective degeneration of peripheral neurons and perspectives for targeting autophagy as a promising therapeutic strategy for CMT neuropathy.

Abstract Background Abaxially anthocyanic leaves of deeply-shaded understorey plants play important ecological significance for the environmental adaption. In contrast to the transient pigmentation in other plants, anthocyanins are permanently presented in these abaxially red leaves, however, the mechanism for the pigment maintenance remains unclear. In the present study, we investigated phenolic metabolites that may affect pigment stability and degradation in Excoecaria cochinchinensis (a bush of permanently abaxial-red leaves), via a comparison with Osmanthus fragrans (a bush of transiently red leaves). Results High levels of galloylated anthocyanins were identified in the Excoecaria but not in the Osmanthus plants. The galloylated anthocyanin showed slightly higher stability than two non-galloylated anthocyanins, while all the 3 pigments were rapidly degraded by peroxidase (POD) in vitro. High levels of hydrolysable tannins [mainly galloylglucoses/ellagitannins (GGs/ETs)] were identified in Excoecaria but none in Osmanthus. GGs/ETs showed inhibition effect on POD, with IC50 ranged from 35.55 to 83.27 μM, correlated to the markedly lower POD activities detected in Excoecaria than in Osmanthus. Strong copigmentation was observed for GGs/ETs and anthocyanins, with more than 30% increase in the red intensity of non-galloylated anthocyanin solutions. In the leaf tissue, the hydrolysable tannins were observed to be co-localized with anthocyanins at the abaxial layer of the Excoecaria leaves, correlated to the low POD activity, more acidity and increased red intensity of the tissue. Conclusion The results suggest that the Excoecaria leaves accumulate a distinct group of phenolic metabolites, mainly GGs/ETs, at the abaxial layer, which prevent anthocyanin degradation and increase the pigment stability, and consequently lead to the permanent maintenance of the red leaves.

Background: Obesity is more prevalent in men than in women in China, especially within the middle-aged population. Objectives: The present study aims to determine the contribution of sexual dimorphisms to obesity and related traits in terms of the mechanisms involving the obesity-related genetic variants among patients of Chinese Han ancestry with type 2 diabetes. Method: In the Chinese National Diabetes and Metabolic Disorders Study, 2,555 out of 4,036 patients with type 2 diabetes were treatment naive, including 1,142 men and 1,413 women. Single-nucleotide polymorphisms (SNP) from 18 genomic loci previously found to be associated with obesity-related traits were successfully genotyped, and a genetic risk score (GRS) was constructed by summing the risk alleles for obesity. Results: Single SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05). Interactions between sex and SNP in PRL, MTCH2,and FTO were detected (p < 0.05). In the untreated patients with diabetes, the GRS was nominally associated with WC (β = 0.0032, SE = 0.0011; p = 0.003), BMI (β = 0.0030, SE = 0.0013; p = 0.027), and increased risk for abdominal (OR = 1.08; 95% CI 1.02–1.13; p = 0.004) or general obesity (OR = 1.07; 95% CI 1.02–1.13; p = 0.011) in men but not in women. GRS-sex interactions were detected in the determinant of WC (p = 0.019) and abdominal obesity (p = 0.016). Among patients aged 30–60 years, GRS was found to be significantly associated with WC (β = 0.0050, SE = 0.0016; p = 0.002) and abdominal obesity (OR = 1.10; 95% CI 1.04–1.17; p = 0.001) and nominally associated with BMI (β = 0.0057, SE = 0.0020; p = 0.005) and general obesity (OR = 1.07; 95% CI 1.01–1.14; p = 0.027) in men, whereas in women none of the associations were detected. GRS-sex interactions were present in the determinant of WC (p = 0.015), BMI (p = 0.032), and abdominal obesity (p = 0.012). Among patients aged 60 years or older, neither an association of GRS with obesity-related traits nor GRS-sex interactions were detected. Conclusions: Genetic factors contribute to obesity-related traits in a sex-dependent pattern among middle-aged Chinese, and men tend to be more susceptible to the genetic risk of obesity.

This paper proposes a compact, physics-based current model for fully depleted silicon-on-insulator (FDSOI) MOSFETs and applies it to delay variability analysis. An analytical method is applied to avoid the numerical iterations required in the evaluation of surface potential, which directly improves the computational efficiency. The accuracy of the explicit surface potential approximation is 190.3 nV, which allows for fast convergence. Surface potential and current calculations achieve 1.8× and 1.4× acceleration compared with BSIM-IMG, respectively. To establish the relationship between delay and underlying process parameters, we introduce the effective current and propose a process variation-aware delay prediction model. Higher-order derivatives are calculated to compensate the nonlinearity of delay variations with respect to process parameters. Experiments show a significant improvement in the prediction accuracy with higher-order derivatives, which are proved to be able to handle nonlinearity under process variations. The front gate work function contributes the most to the nonlinearity of the delay variation and the accuracy of the third-order prediction is 4.07%. Under the variation in the channel length and width, front and back gate oxide thickness and body thickness, delay variations have similar characteristics and the second-order prediction is found to be sufficient to model the nonlinearity with a maximum relative error of 1.22%. The delay prediction model only requires a single-point HSPICE DC or transient simulation and is universal for different voltages and different cells. Compared with the Monte Carlo (MC) simulation, the accuracy of the first-order prediction in the above-threshold region (0.8 V) is 0.94%. In the sub-threshold region (0.3 V), a prediction accuracy of 2.01% can be obtained while achieving a 21× reduction in computational time.