Fetal growth restriction exhibits various mTOR signaling in different regions of mouse placentas with altered lipid metabolism.

Fetal growth restriction (FGR) is a common complication of pregnancy and can have significant impact on obstetric and neonatal outcomes. Increasing evidence has shown that the inhibited mechanistic target of rapamycin (mTOR) signaling in placenta is associated with FGR. However, interpretation of existing research is limited due to inconsistent methodologies and varying understanding of the mechanism by which mTOR activity contributes to FGR. Hereby, we have demonstrated that different anatomic regions of human and mouse placentas exhibited different levels of mTOR activity in normal compared to FGR pregnancies. When using the rapamycin-induced FGR mouse model, we found that placentas of FGR pregnancies exhibited abnormal morphological changes and reduced mTOR activity in the decidual-junctional layer. Using transcriptomics and lipidomics, we revealed that lipid and energy metabolism was significantly disrupted in the placentas of FGR mice. Finally, we demonstrated that maternal physical exercise during gestation in our FGR mouse model was associated with increased fetal and placental weight as well as increased placental mTOR activity and lipid metabolism. Collectively, our data indicate that the inhibited placental mTOR signaling contributes to FGR with altered lipid metabolism in mouse placentas, and maternal exercise could be an effective method to reduce the occurrence of FGR or alleviate the adverse outcomes associated with FGR.

MiR-135a-5p regulates window of implantation by suppressing pinopodes development and decidualization of endometrial stromal cells.

PURPOSE: The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity. METHODS: Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored. RESULTS: A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI. CONCLUSION: MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity.

Catalytic polymer self-cleavage for CO2 generation before combustion empowers materials with fire safety.

Polymeric materials, rich in carbon, hydrogen, and oxygen elements, present substantial fire hazards to both human life and property due to their intrinsic flammability. Overcoming this challenge in the absence of any flame-retardant elements is a daunting task. Herein, we introduce an innovative strategy employing catalytic polymer auto-pyrolysis before combustion to proactively release CO2, akin to possessing responsive CO2 fire extinguishing mechanisms. We demonstrate that potassium salts with strong nucleophilicity (such as potassium formate/malate) can transform conventional polyurethane foam into materials with fire safety through rearrangement. This transformation results in the rapid generation of a substantial volume of CO2, occurring before the onset of intense decomposition, effectively extinguishing fires. The inclusion of just 1.05 wt% potassium formate can significantly raise the limiting oxygen index of polyurethane foam to 26.5%, increase the time to ignition by 927%, and tremendously reduce smoke toxicity by 95%. The successful application of various potassium salts, combined with a comprehensive examination of the underlying mechanisms, underscores the viability of this strategy. This pioneering catalytic approach paves the way for the efficient and eco-friendly development of polymeric materials with fire safety.

High estrogen during ovarian stimulation induced loss of maternal imprinted methylation that is essential for placental development via overexpression of TET2 in mouse oocytes.

BACKGROUND: Ovarian stimulation (OS) during assisted reproductive technology (ART) appears to be an independent factor influencing the risk of low birth weight (LBW). Previous studies identified the association between LBW and placenta deterioration, potentially resulting from disturbed genomic DNA methylation in oocytes caused by OS. However, the mechanisms by which OS leads to aberrant DNA methylation patterns in oocytes remains unclear. METHODS: Mouse oocytes and mouse parthenogenetic embryonic stem cells (pESCs) were used to investigate the roles of OS in oocyte DNA methylation. Global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels were evaluated using immunofluorescence or colorimetry. Genome-wide DNA methylation was quantified using an Agilent SureSelectXT mouse Methyl-Seq. The DNA methylation status of mesoderm-specific transcript homologue (Mest) promoter region was analyzed using bisulfite sequencing polymerase chain reaction (BSP). The regulatory network between estrogen receptor alpha (ERα, ESR1) and DNA methylation status of Mest promoter region was further detected following the knockdown of ERα or ten-eleven translocation 2 (Tet2). RESULTS: OS resulted in a significant decrease in global 5mC levels and an increase in global 5hmC levels in oocytes. Further investigation revealed that supraphysiological ß-estradiol (E2) during OS induced a notable decrease in DNA 5mC and an increase in 5hmC in both oocytes and pESCs of mice, whereas inhibition of estrogen signaling abolished such induction. Moreover, Tet2 may be a direct transcriptional target gene of ERα, and through the ERα-TET2 axis, supraphysiological E2 resulted in the reduced global levels of DNA 5mC. Furthermore, we identified that MEST, a maternal imprinted gene essential for placental development, lost its imprinted methylation in parthenogenetic placentas originating from OS, and ERα and TET2 combined together to form a protein complex that may promote Mest demethylation. CONCLUSIONS: In this study, a possible mechanism of loss of DNA methylation in oocyte caused by OS was revealed, which may help increase safety and reduce epigenetic abnormalities in ART procedures.

L-F001, a multifunctional fasudil-lipoic acid dimer, antagonizes hypoxic-ischemic brain damage by inhibiting the TLR4/MyD88 signaling pathway.

INTRODUCTION: Neonatal hypoxic-ischemic brain damage (HIBD) is a serious inflammatory injury. At present, the standard treatment for this disease is hypothermia therapy, and the effect of drug intervention is still limited. L-F001 is a compound of fasudil and lipoic acid. Previous in vitro experiments have confirmed that L-F001 has anti-inflammatory neuroprotective functions. However, its therapeutic effect on neonates with HIBD remains unknown. This study was aimed at exploring the therapeutic effect of L-F001 on HIBD rats. METHODS: The newborn rats were divided into three groups: Sham operation group, HIBD group, and HIBD + L-F001 group. HE staining, Nissil staining, the immunofluorescence of iNOS and COX-2, ELISA (IL-1ß, IL-6, TNF-α, and IL-10), and western blotting analyses were performed to determine the therapeutic effect of L-F001. Finally, we evaluated the growth and development of each group by measuring body weight. RESULTS: The hippocampal structure of HIBD rats was disordered, and the Nissil body was small and shallow. The expressions of iNOS and COX-2 in HIBD rats were increased, whereas the expressions of IL-1ß, IL-6, and TNF-α in plasma were upregulated, and the expression of IL-10 was decreased. L-F001 could improve the tissue structure and reduce the expression of iNOS and COX-2 in HIBD rats. Meanwhile, L-F001 could also reduce the expression of pro-inflammatory cytokines and restore the content of anti-inflammatory cytokines in plasma. We further found that the TLR4 pathway was activated after hypoxic-ischemia in neonatal rats. L-F001 could inhibit the activation of TLR4 pathway. Finally, we found that after L-F001 treatment, the body weight of HIBD rats increased significantly compared with the untreated group. CONCLUSIONS: L-F001 antagonizes the inflammatory response after hypoxic-ischemia by inhibiting the activation of the TLR4 signaling pathway, thus playing a neuroprotective role. L-F001 may be a potential therapeutic agent for neonatal HIBD.

Caproic acid production from food waste using indigenous microbiota: Performance and mechanisms.

Caproic acid (CA) production from food waste (FW) is a promising way for waste recycling, while the fermentation processes need further exploration. In this study, FW acidogenic fermentation under different pH (uncontrolled, 4, 5, 6) using indigenous microbiota was investigated. Result showed that substrate hydrolysis, carbohydrate degradation and acidogenesis increased with the increase of pH. Although various microbial communities were observed in FW, lactic acid bacteria (Lactobacillus and Limosilactobacillus) were enriched at pH lower than 6, resulting in lactic acid accumulation. CA (88.24 mM) was produced at pH 6 accounting for 31.23% of the total product carbon. The enriched lactic acid bacteria were directionally replaced by chain elongators (Caproicibacter, Clostridium_sensu_stricto, unclassified_Ruminococcaceae) at pH 6, and carbohydrates in FW were firstly transformed into lactic acid, then to butyrate and CA through lactate-based chain elongation processes. This work provided a novel CA fermentation pathway and further enriched the FW valorization.

Novel target and treatment agents for natural killer/T-cell lymphoma.

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

Effectiveness of traditional Chinese medicine formulas combined with acupuncture in the treatment of ovulation dysfunction infertility: A systematic review and meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of traditional Chinese medicine formulas combined with acupuncture for the treatment of ovulation dysfunction infertility (ODI). METHODS: From January 1, 2018 to March 12, 2023, 7 electronic databases, PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang Database, and CBM, were systematically searched to identify eligible randomized controlled trial studies. RESULTS: Meta analysis showed that traditional Chinese medicine combined with acupuncture can more effectively improve sex hormone levels compared to Western medicine alone, including follicle stimulating hormone (FSH) in older patients (standardized mean difference [SMD]: 3.00; 95% confidence interval [CI]: 2.35-3.66; P  = .024, I 2  = 28%), FSH in younger patients (SMD: 0.45; 95% CI: -0.15, 1.05; P  = .03, I 2  = 71%), estradiol (E2) (SMD: 7.50; 95% CI: v0.47, 15.48; P  < .00001, I 2  = 99%), and progesterone (P) (SMD: 2.20; 95% CI: 2.07-2.33; P  < .00001, I 2  = 29%). Compared to Western medicine alone, traditional Chinese medicine combined with acupuncture also had a better effect to increase ovulation rate (risk ratio [RR]: 2.46; 95% CI: 1.72-3.52; P  < .00001, I 2  = 0%), pregnancy rate (RR: 2.50; 95% CI: 1.96-3.18; P  < .00001, I 2  = 0%), maximum follicle diameter (MFD) (SMD: 2.27; 95% CI: 1.37-3.16; P  < .00001, I 2  = 91%), and endometrial thickness (SMD: 1.71; 95% CI: 1.31-2.11; P  < .00001, I 2  = 87%). The combination of traditional Chinese medicine and acupuncture also had better effects on quality of life (RR: 0.19; 95% CI: 0.15-0.23; P  < .00001, I 2  = 0%) and reduced adverse reactions (RR: 0.15; 95% CI: 0.05-0.48; P  = .001, I 2  = 0%), compared to Western medicine alone. CONCLUSION: This study shows evidence that traditional Chinese medicine formulas combined with acupuncture are an effective and safe treatment approach. However, this conclusion requires further confirmation due to the insufficient quality of the included trials.

Ovarian Stimulation in Mice Resulted in Abnormal Placentation through Its Effects on Proliferation and Cytokine Production of Uterine NK Cells.

Ovarian stimulation is associated with an increased incidence of abnormal placentation. Uterine natural killer (uNK) cells are the major subpopulation of decidual immune cells, which are crucial for placentation. In a previous study, we found that ovarian stimulation impairs uNK cell density on gestation day (GD) 8.5 in mice. However, it was not clear how ovarian stimulation led to a reduction in the density of uNK cells. In this study, we constructed two mouse models, an in vitro mouse embryo transfer model and an estrogen-stimulated mouse model. We used HE and PAS glycogen staining, immunohistochemical techniques, q-PCR, Western blot, and flow cytometry to analyze the mouse decidua and placenta, and the results showed that SO resulted in a fetal weight reduction, abnormal placental morphology, decreased placental vascular density, and abnormal density and function of uNK cells. Our results suggest that ovarian stimulation resulted in aberrant estrogen signaling and may contribute to the disorder of uNK cells caused by ovarian stimulation. Together, these results provide new insights into the mechanisms of aberrant maternal endocrine environments and abnormal placentation.

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment.

Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Comparison of two different therapeutic approaches for skeletal Class II patients with temporomandibular degenerative joint disease.

OBJECTIVES: To compare two different therapeutic approaches for skeletal Class II patients with temporomandibular degenerative joint disease. MATERIALS AND METHODS: A total of 47 patients were included in this study. Group anterior repositioning splint (ARS) was treated with temporomandibular joint (TMJ) disc surgery followed by an ARS and camouflage orthodontic treatment. Group stabilization splint (SS) was treated with an SS followed by orthodontic treatment combined with orthognathic surgery. Cephalometric analysis of lateral radiographs and measurements of condylar height were evaluated before and after splints. RESULTS: In group ARS, mandibular advancement was observed after treatment in 21 of 24 patients (87.5%). The SNB angle increased by an average of 1.40 ± 1.01°. The ANB angle, overjet, Wits, and convexity decreased. Facial angle and soft tissue N Vert to pogonion increased. Vertically, MP-FH, MP-SN, y-axis, and vertical ratio decreased and ANS-Me/N-Me and S-Go/N-Me increased, suggesting a counterclockwise rotation of the mandible. In group SS, 18 of 23 patients (78.3%) showed a backward change tendency. The SNB angle reduced by 0.90 ± 0.93°. The ANB angle, overjet, Wits, convexity, and y-axis increased. The facial angle and soft tissue N Vert to soft tissue pogonion (ST N Vert to ST pogonion) decreased. Magnetic resonance imaging showed condylar height increased by 1.45 ± 3.05 mm (P = .002) in group ARS. In group SS, condylar height change was not consistent. CONCLUSIONS: TMJ disc surgery followed by ARS promoted condylar bone remodeling and regeneration. The SNB angle increased, and the severity of skeletal Class II was improved. The SS enabled the mandible to withdraw backward and revealed a retrognathic but true mandible position.

A Virtual Reality Platform for Context-Dependent Cognitive Research in Rodents.

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.

A Virtual Reality Platform for Context-Dependent Cognitive Research in Rodents / 神经科学通报·英文版

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.

Association and Interacting Factors between Bronchial Asthma and Attention-deficit Hyperactivity Disorder in Children: Meta-analysis and Systematic Review

Background: This study aims to systematically assess the possible link between bronchial asthma usage and attention-deficit hyperactivity disorder (ADHD) in children. Methods: PubMed, Web of Science, ScienceDirect, CNKI, Wanfang, and the China Biological Medicine Database (CBM) were searched for relevant articles published from database inception until September 28, 2023. The statistical analyses were conducted using Stata 15.1 software, followed by a quantitative meta-analysis to synthesize the results of the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results: A total of 10 articles involving 729,375 participants were included in the meta-analysis. The overall analysis revealed a statistically significant association between ADHD and an increased likelihood of having bronchial asthma, as indicated by a pooled odds ratio (OR) of 1.46 and a 95% confidence interval (CI) ranging from 1.41 to 1.51, p < 0.001, I2 = 58%. Potential associated factors linking bronchial asthma and ADHD in children include demographic characteristics, healthcare access, socioeconomic factors, comorbidities, genetic susceptibility, immune dysregulation, chronic conditions, growth and development factors, and parental/environmental influences. Conclusion: This systematic review and meta-analysis presents convincing evidence for a notable link between bronchial asthma and ADHD in children. The results indicate an increased likelihood of bronchial asthma among children with ADHD compared to those without the condition. Additionally, various potential factors can underlie the association between bronchial asthma and ADHD in children, necessitating further research to fully comprehend their complex relationship. These findings have implications for clinical practice, highlighting the need for an integrated approach in managing asthma and ADHD.(AU)

Association and Interacting Factors between Bronchial Asthma and Attention-deficit Hyperactivity Disorder in Children: Meta-analysis and Systematic Review.

BACKGROUND: This study aims to systematically assess the possible link between bronchial asthma usage and attention-deficit hyperactivity disorder (ADHD) in children. METHODS: PubMed, Web of Science, ScienceDirect, CNKI, Wanfang, and the China Biological Medicine Database (CBM) were searched for relevant articles published from database inception until September 28, 2023. The statistical analyses were conducted using Stata 15.1 software, followed by a quantitative meta-analysis to synthesize the results of the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: A total of 10 articles involving 729,375 participants were included in the meta-analysis. The overall analysis revealed a statistically significant association between ADHD and an increased likelihood of having bronchial asthma, as indicated by a pooled odds ratio (OR) of 1.46 and a 95% confidence interval (CI) ranging from 1.41 to 1.51, p < 0.001, I2 = 58%. Potential associated factors linking bronchial asthma and ADHD in children include demographic characteristics, healthcare access, socioeconomic factors, comorbidities, genetic susceptibility, immune dysregulation, chronic conditions, growth and development factors, and parental/environmental influences. CONCLUSION: This systematic review and meta-analysis presents convincing evidence for a notable link between bronchial asthma and ADHD in children. The results indicate an increased likelihood of bronchial asthma among children with ADHD compared to those without the condition. Additionally, various potential factors can underlie the association between bronchial asthma and ADHD in children, necessitating further research to fully comprehend their complex relationship. These findings have implications for clinical practice, highlighting the need for an integrated approach in managing asthma and ADHD.

Study of liver cirrhosis over twenty consecutive years in adults in Southern China.

BACKGROUND: Liver cirrhosis (LC) is a prevalent and severe disease in China. The burden of LC is changing with widespread vaccination of hepatitis B virus (HBV) and antiviral therapy. However, the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear. AIM: To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China. METHODS: In this retrospective, cross-sectional study we included LC inpatients admitted between January 2001 and December 2020. Medical data indicating etiological diagnosis and LC complications, and demographic, laboratory, and imaging data were collected from our hospital-based dataset. The etiologies of LC were mainly determined according to the discharge diagnosis, and upper gastrointestinal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma (HCC), portal vein thrombosis, hepatorenal syndrome, and acute-on-chronic liver failure (ACLF) were considered LC-related complications in our study. Changing trends in the etiologies and clinical characteristics were investigated using logistic regression, and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test. In-hospital prognosis and risk factors associated with in-hospital mortality were also investigated. RESULTS: A total of 33143 patients were included in the study [mean (SD) age, 51.7 (11.9) years], and 82.2% were males. The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020 (P < 0.001), and the proportion of female patients increased from 16.7% in 2001-2010 to 18.2% in 2011-2020 (P = 0.003). LC patients in the decompensated stage at diagnosis decreased from 68.1% in 2001-2010 to 64.6% in 2011-2020 (P < 0.001), and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0 (P < 0.001). HBV remained the major etiology of LC (75.0%) and the dominant cause of viral hepatitis-LC (94.5%) during the study period. However, the proportion of HBV-LC decreased from 82.4% in 2001-2005 to 74.2% in 2016-2020, and the proportion of viral hepatitis-LC decreased from 85.2% in 2001-2005 to 78.1% in 2016-2020 (both P for trend < 0.001). Meanwhile, the proportions of LC caused by alcoholic liver disease, autoimmune hepatitis and mixed etiology increased by 2.5%, 0.8% and 4.5%, respectively (all P for trend < 0.001). In-hospital mortality was stable at 1.0% in 2011-2020, whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications (35.8% to 41.0% and 5.7% to 12.4%, respectively) and were associated with 6-fold and 4-fold increased risks of mortality (odds ratios: 6.03 and 4.22, respectively). CONCLUSION: LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China. HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.

Polyelectrolyte Complex with Controllable Viscosity by Doping Cu2+ Protects Nylon-Cotton Fabric against Fire.

Nylon-cotton (NC) blend fabrics are widely used in military and industrial applications, but their high flammability still remains a serious problem. In an effort to effectively and quickly impart flame retardancy to the NC fabric, it was treated by simply blade coating with a Cu2+-doped polyelectrolyte complex (CPEC) that consists of ammonium polyphosphate (APP), polyethylenimine (PEI), and copper sulfate. The viscosity of the CPEC can be adjusted by altering the content of CuSO4, which controls the amount of extrinsic and intrinsic ion pairs. By adjusting the proportion and content of PEI, APP, and CuSO4, CPEC suitable for treating the NC fabric was obtained. Only 0.067 wt % Cu2+ was needed to adjust the viscosity and impart self-extinguishing behavior in a vertical burning test. This simple two-step treatment provides a promising technology to protect flammable polymeric substrates with ultralow metal-doped polyelectrolyte complexes.

A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.

The lens is a relatively special and simple organ. It has become an ideal model to study the common developmental characteristics among different organic systems. Lens development is a complex process influenced by numerous factors, including signals from the intracellular and extracellular environment. Reactive oxygen species (ROS) are a group of highly reactive and oxygen-containing molecules that can cause endoplasmic reticulum stress in lens cells. As an adaptive response to ER stress, lens cells initiate the unfolded protein response (UPR) to maintain normal protein synthesis by selectively increasing/decreasing protein synthesis and increasing the degradation of misfolded proteins. Generally, the UPR signaling pathways have been well characterized in the context of many pathological conditions. However, recent studies have also confirmed that all three UPR signaling pathways participate in a variety of developmental processes, including those of the lens. In this review, we first briefly summarize the three stages of lens development and present the basic profiles of ROS and the UPR. We then discuss the interconnections between lens development and these two mechanisms. Additionally, the potential adoption of human pluripotent stem-cell-based lentoids in lens development research is proposed to provide a novel perspective on future developmental studies.

Exploring the Underlying Mechanism of Ren-Shen-Bai-Du Powder for Treating Inflammatory Bowel Disease Based on Network Pharmacology and Molecular Docking.

Ren-Shen-Bai-Du Powder (RSBDP) is currently used for inflammatory bowel disease (IBD) therapy in China. However, its potential mechanism against IBD remains unknown. In this study, we initially identified potential targets of RSBDP against IBD through network pharmacology analysis and molecular docking. Afterwards, the DSS-induced colitis mice model was employed to assess the effects of RSBDP. The results of network pharmacology indicated that a total of 39 main active ingredients in RSBDP generated 309 pairs of drug-ingredient and ingredient-target correspondences through 115 highly relevant targets of IBD. The primary ingredients (quercetin, kaempferol, luteolin, naringenin, and sitosterol) exerted functions through multiple targets that include CYP1B1, CA4/7, and ESR1/2, etc. GO functional enrichment analysis revealed that the targets related to IBD were significantly enriched in the oxidation-reduction process, protein binding, and cytosol. Per the KEGG pathway analysis, pathways in cancer, adherens junction, and nitrogen metabolism were pivotal in the RSBDP's treatment of IBD. Additionally, molecular docking demonstrated that a set of active ingredients and their targets displayed good bonding capabilities (e.g., kaempferol and AhR with combined energy < 5 kcal/mol). For the animal experiment, oral RSBDP promoted weight recovery, reduced intestinal inflammation, and decreased serum IL-1, IL-6, and IL-8 concentrations in the DSS + RSBDP group. Meanwhile, oral RSBDP significantly up-regulated the mRNA levels of CA7, CPY1B1, and PTPN11; in particular, the expression level of CYP1B1 in the DSS + RSBDP group was up-regulated by as high as 9-fold compared to the DSS group. Western blot results indicated that the protein levels of AKR1C1, PI3K, AKT, p-AKT, and Bcl-2 were significantly down-regulated, and Bax was significantly up-regulated in the DSS + RSBDP group. Compared to the DSS and control groups, the Bax/Bcl-2 value in the DSS + RSBDP group increased 4-fold and 8-fold, respectively, which suggested that oral RSBDP promotes apoptosis of intestinal epithelial cells. In short, this study established quercetin, kaempferol, luteolin, naringenin, and sitosterol as the primary key active ingredients of RSBDP that exert synergistic therapeutic effects against IBD through modulating the AhR/CYP1B1 and AKR1C1/PI3K/AKT pathways.