The calcium-dependent protein kinase CPK28 is targeted by the ubiquitin ligases ATL31 and ATL6 for proteasome-mediated degradation to fine-tune immune signaling in Arabidopsis.

Immune responses are triggered when pattern recognition receptors recognize microbial molecular patterns. The Arabidopsis (Arabidopsis thaliana) receptor-like cytoplasmic kinase BOTRYTIS-INDUCED KINASE1 (BIK1) acts as a signaling hub of plant immunity. BIK1 homeostasis is maintained by a regulatory module in which CALCIUM-DEPENDENT PROTEIN KINASE28 (CPK28) regulates BIK1 turnover via the activities of two E3 ligases. Immune-induced alternative splicing of CPK28 attenuates CPK28 function. However, it remained unknown whether CPK28 is under proteasomal control. Here, we demonstrate that CPK28 undergoes ubiquitination and 26S proteasome-mediated degradation, which is enhanced by flagellin treatment. Two closely related ubiquitin ligases, ARABIDOPSIS TÓXICOS EN LEVADURA31 (ATL31) and ATL6, specifically interact with CPK28 at the plasma membrane; this association is enhanced by flagellin elicitation. ATL31/6 directly ubiquitinate CPK28, resulting in its proteasomal degradation. Furthermore, ATL31/6 promotes the stability of BIK1 by mediating CPK28 degradation. Consequently, ATL31/6 positively regulate BIK1-mediated immunity. Our findings reveal another mechanism for attenuating CPK28 function to maintain BIK1 homeostasis and enhance immune responses.

Mental health conditions in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVES: The reported prevalence of mental health conditions (MHCs) in people with systemic lupus erythematosus (SLE) ranges widely. Whether MHCs are associated with increased risk of SLE or the outcomes of the disease is unclear. This paper aimed to conduct an umbrella and updated meta-analysis of MHCs in people with SLE and to identify whether MHCs are associated with the risk of SLE or patient outcomes. METHODS: We comprehensively searched PubMed, Web of Science, and Embase databases to identify relevant studies published before June 2023. Random-effect models were used to calculate the pooled prevalence and risk ratios for each MHC. RESULTS: 203 studies with 1485094 individuals were included. The most MHCs observed in patients with SLE were sleep disturbance (59.7% [95% CI, 52.4%-66.8%]) among adults and cognitive dysfunction (63.4% [95% CI, 46.9%-77.9%]) among children. We found that depressive disorders (RR = 2.30, 95% CI = 1.94-2.75) and posttraumatic stress disorder (RR = 1.93, 95% CI = 1.61-2.31) in the general population were significantly associated with an increased likelihood of developing SLE. Furthermore, concurrent MHCs were linked to unfavorable outcomes in patients with SLE, such as decreased quality of life, increased risk of unemployment, and other somatic comorbidities. CONCLUSION: Our study demonstrated a high prevalence of MHCs among patients with SLE. Individuals with pre-existing mental disorders exhibited an elevated susceptibility to developing SLE, and patients presenting with MHCs were at increased risk of experiencing suboptimal health and functional outcomes. Therefore, evaluating and preventing MHCs should be considered as an integral component of the comprehensive treatment strategy for SLE.

Efficient Chemical Synthesis of Multi-Monoubiquitylated and Diubiquitylated Histones by the α-Halogen Ketone-Mediated Strategy.

The chemical synthesis of homogeneously ubiquitylated histones is a powerful approach to decipher histone ubiquitylation-dependent epigenetic regulation. Among the various methods, α-halogen ketone-mediated conjugation chemistry has recently been an attractive strategy to generate single-monoubiquitylated histones for biochemical and structural studies. Herein, we report the use of this strategy to prepare not only dual- and even triple-monoubiquitylated histones but also diubiquitin-modified histones. We were surprised to find that the synthetic efficiencies of multi-monoubiquitylated histones were comparable to those of single-monoubiquitylated ones, suggesting that this strategy is highly tolerant to the number of ubiquitin monomers installed onto histones. The facile generation of a series of single-, dual-, and triple-monoubiquitylated H3 proteins enabled us to evaluate the influence of ubiquitylation patterns on the binding of DNA methyltransferase 1 (DNMT1) to nucleosomes. Our study highlights the potential of site-specific conjugation chemistry to generate chemically defined histones for epigenetic studies.

Organic-Inorganic Hybrid Halide X-ray Scintillator with High Antiwater Stability.

In recent years, low-dimensional organic-inorganic hybrid metal halides have garnered significant attention for optoelectronic applications due to their exceptional photophysical properties, despite their persistent challenge of low stability. Addressing this challenge, our study introduces 1-[5-(trifluoromethyl)pyridin-2-yl]piperazinium (TFPP) as a cation, harvesting a novel one-dimensional hybrid cadmium-based halide semiconductor (TFPP)CdCl4, which exhibits intense blue-light emission upon UV excitation. Additionally, (TFPP)CdCl4 demonstrates a high scintillation performance under X-ray excitation, producing 16600 ± 500 photons MeV-1 and achieving a low detection limit of 0.891 µGyair s-1. Notably, (TFPP)CdCl4 showcases remarkable stability against water, intense light sources, heating, and corrosive environments, positioning it as a promising candidate for optoelectronic applications. Through a blend of experimental techniques and theoretical analyses, including density functional theory calculations, we elucidate the unique photophysical properties and structural stability of (TFPP)CdCl4. These findings significantly contribute to the understanding of low-dimensional hybrid halide semiconductors, offering valuable insights into their potential application in advanced optoelectronic devices and paving the way for further research in this field.

Targeting MuRF1 to Combat Skeletal Muscle Wasting in Cardiac Cachexia: Mechanisms and Therapeutic Prospects.

Cardiac cachexia, the terminal stage of chronic heart failure, is characterized by severe systemic metabolic imbalances and significant weight loss, primarily resulting from skeletal muscle mass depletion. Despite the detrimental consequences, there is no standardized and clinically-approved intervention currently available for cardiac cachexia. In the context of cardiac cachexia, accelerated protein turnover, that is, inhibited protein synthesis and enhanced protein degradation, plays a crucial role in skeletal muscle wasting. This process is primarily mediated by various proteins encoded by atrogenes. Among them, the atrogene Trim63 (tripartite motif family 63) and its encoded protein MuRF1 have been extensively studied. This review article aims to elucidate the pathogenic mechanisms underlying skeletal muscle wasting in cardiac cachexia, describe the biochemical characteristics of MuRF1, and provide an overview of the investigation into MuRF1-targeting inhibitors. The ultimate goal is to offer novel strategies for the clinical treatment for skeletal muscle wasting associated with cardiac cachexia.

Lithium Therapy's Potential to Lower Dementia Risk and the Prevalence of Alzheimer's Disease: A Meta-Analysis.

INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. METHODS: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44-0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.

Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

Taraxasterol attenuates zearalenone-induced kidney damage in mice by modulating oxidative stress and endoplasmic reticulum stress.

Taraxasterol is one of the bioactive ingredients from traditional Chinese herb Taraxacum, which exhibits multiple pharmacological activities and protective effects. However, the underlying influence and mechanism of its use against kidney damage caused from zearalenone (ZEA) remain unexplored. The ZEA-induced kidney damage model of mice was established by feeding diets containing ZEA (2 mg/kg), and taraxasterol (5 and 10 mg/kg) was administered by gavage for 28 days. Results demonstrated taraxasterol increased average daily gain (ADG) and average daily feed intake (ADFI), reduced feed-to-gain ratio (F/G) and kidney index of mice induced by ZEA. Taraxasterol alleviated histopathological changes of kidney, reduced ZEA residue and the levels of blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE). Concurrently, taraxasterol reduced the contents of oxidative stress indicator reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of antioxidant enzymes catalase (CAT), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Further, taraxasterol up-regulated the mRNA and protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2), GSH-Px, NAD(P)H quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), and down-regulated the mRNA and protein expression of KELCH like ECH associated protein (Keap1) in Nrf2/Keap1 pathway. Taraxasterol down-regulated the mRNA and protein expression of immunoglobulin binding protein (Bip), C/EBP homologous protein (CHOP), Bcl-2 associated X (Bax), cysteine protease (Caspase)-12, and Caspase-3, and up-regulated B-cell lymphoma 2 (Bcl-2) expression in endoplasmic reticulum stress pathway. This study suggests that taraxasterol attenuates ZEA-induced mouse kidney damage through the modulation of Nrf2/Keapl pathway to play antioxidant role and endoplasmic reticulum stress pathway to enhance anti-apoptotic ability. It will provide a basis for taraxasterol as a potential drug to prevent and treat ZEA-induced kidney damage.

Different effects of vitamin supplementation on arsenic bioaccessibility in contaminated soils using multiple in vitro methods and their relevant mechanisms.

Exposure to arsenic (As) induces adverse effects on human health. Vitamins B1, B6, and C, as indispensable micronutrients for humans, have been proven to influence the metabolism and toxicity of ingested As. To determine the effect of vitamins on health risks associated with soil exposure, As bioaccessibility in 14 soil samples using four in vitro methods of IVG, PBET, SBRC, and UBM was measured with the addition of vitamins B1, B6, and C. With vitamins B1 and B6 addition, the gastric As bioaccessibility in 14 soil samples was reduced by 1.14-3.52 and 1.14-5.02 fold, respectively, and instead an increase in the intestinal bioaccessibility was presented in some cases. Vitamin C supplementation yielded higher As bioaccessibility in the gastric (1.13-13.02 fold) and small intestinal (1.21-33.35 fold) phases, respectively. As evidenced by the X-ray absorption near-edge spectroscopy (XANES) and Fourier transform infrared spectroscopy (FTIR) analysis, arsenic dissolution was promoted by Fe-As and hindered by the formation of Al-As fractions. Soil As dissolution in the simulated gastrointestinal tract was strongly influenced by soil minerals and ingested vitamins, due to the chelation of arsenic with vitamins and soil minerals such as Fe (hydr)oxides, and Fe(III) reductive dissolution to enhance As release by vitamin C as an iron reducer. These findings will expand the knowledge of health risks of exposure to As-contaminated soils and nutritional interventions aiming at the mitigation of As toxicity.

Regulatory Role of Meox1 in Muscle Growth of Sebastes schlegelii.

Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost fish, Sebastes schlegelii. Through in situ hybridization and histological analysis, we discovered that SsMeox1 can be employed as a specific marker of growth-specific muscle stem cells, which originate from the somite stage and are primarily situated in the external cell layer (ECL) and myosepta, with a minor population distributed among muscle fibers. The knockdown of SsMeox1 resulted in a significant increase in Ccnb1 expression, subsequently promoting cell cycle progression and potentially accelerating the depletion of the stem cell pool, which ultimately led to significant growth retardation. These findings suggest that SsMeox1 arrests the cell cycle of growth-specific muscle stem cells in the G2 phase by suppressing Ccnb1 expression, which is essential for maintaining the stability of the growth-specific muscle stem cell pool. Our study provides significant insights into the molecular mechanisms underlying the indeterminate growth of large teleosts.

An Overview of Bioactive Compounds' Role in Modulating the Nrf2/Keap1/NF-κB Pathway to Alleviate Lipopolysaccharide-Induced Endometritis.

Endometritis is a common inflammatory condition of the uterine endometrial lining that primarily affects perinatal dairy animals and causes significant economic losses in agriculture. It is usually triggered by pathogenic bacteria and is associated with chronic postpartum reproductive tract infections. Bacterial lipopolysaccharides (LPSs) are known to increase levels of reactive oxygen species (ROS), leading to oxidative stress and inflammation through the activation of the NF-κB signaling pathway and the inhibition of Nrf2 nuclear translocation, which regulates antioxidant response elements (AREs). The effectiveness of the conventional management strategy involving antibiotics is decreasing due to resistance and residual concerns. This review explores the potential therapeutic benefits of targeting the Nrf2/Kelch-like ECH-associated protein 1 (Keap1)/NF-κB signaling pathway to alleviate LPS-induced endometritis. We discuss recent advancements in veterinary medicine that utilize exogenous antioxidants to modulate these pathways, thereby reducing oxidative stress and inflammatory responses in endometrial cells. This review highlights the efficacy of several bioactive compounds that enhance Nrf2 signaling and suppress NF-κB activation, offering protective effects against oxidative damage and inflammation. By examining various in vitro studies, this review emphasizes the emerging role of these signaling pathways in developing new therapeutic strategies that could potentially replace or supplement traditional treatments and mitigate the economic impacts of endometritis in livestock.

Sources, fate and influencing factors of nitrate in farmland drainage ditches of the irrigation area.

Global irrigation areas face the contradictory challenges of controlling nitrate inputs and ensuring food-safe production. To prevent and control nitrate pollution in irrigation areas, the study using the Yellow River basin (Ningxia section) of China as a case study, employed nitrogen and oxygen dual isotope tracing and extensive field investigations to analyze the sources, fate, and influencing factors of nitrate in agricultural drainage ditches. The results of source tracing of nitrate showed that annual proportions of nitrate sources entering the Yellow River in the ditches are as follows: for manure & sewage, fertilizer, and natural sources, the ratios are 33%, 35%, and 32% overall. The results of nitrate fate showed that nitrates derived from nitrate fertilizer exhibit a lower residual rate in drainage ditches (ecological ditches) compared to ammonium fertilizer, which can undergo self-ecological restoration within one year. The results of influencing factors showed that crops with high water and nutrient requirements, such as vegetables, the nitrate pollution and environmental harm resulting from "exploitative cultivation" are five times more than normal cultivation practices in dryland and paddy fields, especially winter irrigation without crop interception exacerbates the leaching of nitrate from the soil. Therefore, nitrate management in irrigation areas should focus on preventing and controlling "exploitative cultivation" and losses during winter irrigation, while appropriately adjusting the application ratio of ammonium nitrogen fertilizers. The results of the study can guide strategies to mitigate nitrate pollution in irrigated areas such as livestock farming, fertilizer application, irrigation management, ditch optimization, and crop cultivation.

The present situation of the nursing practice environment and its influence on nursing quality in a post-epidemic era: a cross-sectional study.

BACKGROUND: Nursing Practice Environment is an important index to improve nursing quality and patient outcome. To explore the nursing practice environment in the COVID-19 ward during the period of COVID-19 and its impact on nursing quality to provide reference for setting up supporting nursing team in epidemic area in the future. METHODS: A cross-sectional survey was conducted among 251 nurses working in COVID-19 ward in Shanghai, Hainan and Hunan in December 2022 through stratified proportional sampling. Structured questionnaires, including general information questionnaire, professional practice environment scale and nursing quality questionnaire, were used to investigate the patients. Pearson correlation was used to analyze the correlation between nursing practice environment and nursing quality, and multiple linear regression analysis was used to analyze the influencing factors of nursing quality in the COVID-19 ward. RESULTS: The professional practice environment scale score was (3.34 ± 0.40), the nursing quality questionnaire score was (9.47 ± 0.81), both at a high level. Single factor analysis showed that nursing quality was related to educational background, physical condition, professional title, grade of the original hospital and composition of nursing staff in supported departments. Nursing quality were positively correlated with each nursing practice environment dimensions (in addition to teamwork). The results of regression analysis showed that the nursing practice environment in the COVID-19 ward had a positive impact on nursing quality. CONCLUSIONS: The nursing practice environment and nursing quality of nurses in the COVID-19ward is generally very high. The education, working hospital level and nursing practice environment of nurses are the important factors influencing nursing quality. The relationship between nursing practice environment (include leadership and autonomy in clinical practice, staff relationships with physicians, control over practice, communication about patients, handling disagreement and conflict, internal work motivation and cultural sensitivity) and nursing quality is positive. It is suggested that the hospital should pay special attention to and improve nursing practice environment in order to improve nursing quality when setting up temporary ward in the future epidemic period of infectious diseases, ensure patient safety. IMPACT ON CLINICAL PRACTICE: Research shows that an active nursing practice environment can improve the quality of care, and nursing managers create and maintain an active practice environment to improve the quality of care and ensure patient safety.

The Arabidopsis ubiquitin ligases ATL31 and ATL6 regulate plant response to salt stress in an ABA-independent manner.

E3 ubiquitin ligases play critical roles in regulating plant response to salt stress. Arabidopsis Tóxicos En Levadura (ATL) is a subfamily of RING-type E3 ubiquitin ligases widely conserved in plant species. ATL genes have been shown to be involved in regulating plant response to biotic or abiotic stresses. We previously found that a pair of ATL genes, ATL31 and ATL6 positively regulated plant innate immunity. However, whether ATL31/6 are also involved in salt stress response remains to be investigated. Here, we demonstrate that ATL31/6 are induced by salt stress. The atl31 atl6 double mutant exhibits increased salt tolerance compared to the wild-type plants, while transgenic plants overexpressing ATL31 are more salt-sensitive. Notably, ATL31 and ATL6 do not participate in the abscisic acid (ABA) response. Furthermore, NaCl treatment induces the proteasomal degradation of ATL31 proteins. Together, we demonstrate that ATL31/6 positively regulate plant tolerance to salt stress, which is independent of ABA, and our work reveals that ATL31/6 are involved in regulating plant response to both biotic and abiotic stress.

Phosphorylation status of CPK28 affects its ubiquitination and protein stability.

Plant innate immunity is tightly regulated. The Arabidopsis thaliana CALCIUM-DEPENDENT PROTEIN KINASE28 (CPK28) functions as a negative immune regulator. We recently demonstrate that CPK28 undergoes ubiquitination that is mediated by two ubiquitin ligases, ARABIDOPSIS TÓXICOS EN LEVADURA31 (ATL31) and ATL6, which results in its proteasomal degradation. CPK28 undergoes both intermolecular autophosphorylation and BIK1-mediated phosphorylation. However, whether the phosphorylation status of CPK28 dictates its ubiquitination and degradation is unknown yet. We used immune response analysis, transient degradation system, ubiquitination assays, co-immunoprecipitation, and other biochemical and genetic approaches to investigate the effect of the phosphorylation status of CPK28 on its degradation mediated by ATL31/6. We found the mutation of Ser318 (a site of both intermolecular autophosphorylation and BIK1-mediated phosphorylation) or a BIK1 phosphorylation site on CPK28 leads to its compromised association with ATL31 and reduced ubiquitination by ATL31. Moreover, we confirm the previous findings that two CPK28s can interact with each other, which likely promotes the intermolecular autophosphorylation. We also show that the phosphorylation status of CPK28 in turn affects its intermolecular association. We demonstrate that the phosphorylation status of CPK28 affects its degradation mediated by ATL31. Our findings reveal a link between phosphorylation of CPK28 and its ubiquitination and degradation.

Novel Tu translation elongation factor, mitochondrial (TUFM) homozygous variant in a consanguineous family with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by cessation of menstruation occurring before the age of 40 years. The genetic causes of idiopathic POI remain unclear. Here we recruited a POI patient from a consanguineous family to screen for potential pathogenic variants associated with POI. Genetic variants of the pedigree were screened using whole-exome sequencing analysis and validated through direct Sanger sequencing. A homozygous variant in TUFM (c.524G>C: p.Gly175Ala) was identified in this family. TUFM (Tu translation elongation factor, mitochondrial) is a nuclear-encoded mitochondrial protein translation elongation factor that plays a critical role in maintaining normal mitochondrial function. The variant position was highly conserved among species and predicted to be disease causing. Our in vitro functional studies demonstrated that this variant causes decreased TUFM protein expression, leading to mitochondrial dysfunction and impaired autophagy activation. Moreover, we found that mice with targeted Tufm variant recapitulated the phenotypes of human POI. Thus, this is the first report of a homozygous pathogenic TUFM variant in POI. Our findings highlighted the essential role of mitochondrial genes in folliculogenesis and ovarian function maintenance.

The Influence of Positional Isomerism of Terminal Alkyl Chains on Mesomorphic and Photophysical Behavior of Unsymmetric α-cyanostilbene-based Tetracatenars.

Two series of unsymmetric α-cyanostilbene-based tetracatenars containing three hexadecyl chains at one end and one alkyl chain with varying lengths at the other end were prepared by using Suzuki coupling and Knoevenagel reactions. These tetracatenars with the terminal three hexadecyl chains, which are adjacent to the cyano group are non-mesogens, whereas the isomers with one alkyl chain, which is adjacent to the cyano group display transition from non-mesogens to monotropic hexagonal columnar liquid crystal upon elongation of the alkyl chain. This transition could be attributed to that the three hexadecyl chains which are adjacent to the cyano group decrease the interactions between π-conjugated rigid cores, hindering the formation of mesophase. In addition, weak slovatochromism implies weak ICT in both series tetracatenars. Both series isomers exhibit distinct AIE characteristics attributing to the presence of α-cyanostilbene, which could induce stereoisomerism and restricted intermolecular rotation in the aggregated state. Different mechanochromism behaviors could be achieved due to the positional isomerism of terminal alkyl chains. Therefore, tuning the position of terminal alkyl chains could give rise to distinct changes in the molecular aggregate, which provides a scheme to build multifunctional materials with diverse potentials.

Comparison of two different methods for cervicovaginal reconstruction: a long-term follow-up.

INTRODUCTION AND HYPOTHESIS: As a consequence of the evolution of surgery in reconstructive techniques, cervicovaginal reconstruction has become an option for patients diagnosed with congenital cervical and vaginal atresia. This study was aimed at comparing long-term clinical and anatomical results in patients who had cervicovaginal reconstruction with either a small intestinal submucosa (SIS) graft or a split-thickness skin (STS) graft. METHODS: This was a retrospective study of 34 patients who underwent cervicovaginal reconstruction using SIS or STS grafts between January 2012 and August 2017. The patients' postoperative resumption of menstruation, vaginal length, body image satisfaction, and sexual satisfaction were assessed. Quantitative and categorical variables were compared using Student's t test and Chi-squared test respectively. RESULTS: The mean follow-up time was 81.29 ± 20.69 months. The SIS group had a shorter surgery time, an earlier return to work, and a higher cost (p < 0.05). All patients resumed menstruation, but 4 patients were diagnosed with cervical stricture. There was no significant difference in the length of the neovagina, and the satisfaction score of the sexual life of patients and their sexual partners was similar in both groups. Patients in the SIS group showed greater satisfaction with their bodies (p < 0.001). One patient in the SIS group got pregnant via assisted-reproduction techniques. CONCLUSIONS: Cervicovaginal reconstruction using SIS or STS grafts is an effective treatment for patients diagnosed with congenital cervical and vaginal atresia. The method of SIS graft is simpler, with less surgical injury and greater body satisfaction, but it is more expensive.

Current status and influencing factors of self-management in knee joint discomfort among middle-aged and elderly people: a cross-sectional study.

BACKGROUND: This study aims to identify the current status and factors influencing self-management of knee discomfort in middle-aged and elderly people in China. METHODS: A stratified multistage cluster sampling method was used to select participants from communities in China from January 15 to May 31, 2020. A cross-sectional survey was conducted using the general information questionnaire and the Knee Joint Discomfort Self-management Scale. Univariate analysis and a generalized linear model were used to analyze the factors influencing self-management. RESULTS: The prevalence of knee discomfort was 77%. Moderate to severe discomfort accounted for 30.5%. The average item score of self-management in 9640 participants was 1.98 ± 0.76. The highest and lowest levels were: 'daily life management' and 'information management'. Gender, ethnicity, education level, economic source, chronic disease, knee pain in the past month, and the degree of self-reported knee discomfort were significant predictors of self-management. CONCLUSION: The self-management of knee discomfort in middle-aged and elderly people is poor, and the degree of discomfort is a significant predictor. Healthcare providers should consider socioeconomic demographic and clinical characteristics to help these individuals improve their self-management skills. Attention should also be given to improving their ability to access health information and making them aware of disease risks.

DROOPY LEAF1 controls leaf architecture by orchestrating early brassinosteroid signaling.

Leaf architecture directly determines canopy structure, and thus, grain yield in crops. Leaf droopiness is an agronomic trait primarily affecting the cereal leaf architecture but the genetic basis and underlying molecular mechanism of this trait remain unclear. Here, we report that DROOPY LEAF1 (DPY1), an LRR receptor-like kinase, plays a crucial role in determining leaf droopiness by controlling the brassinosteroid (BR) signaling output in Setaria, an emerging model for Panicoideae grasses. Loss-of-function mutation in DPY1 led to malformation of vascular sclerenchyma and low lignin content in leaves, and thus, an extremely droopy leaf phenotype, consistent with its preferential expression in leaf vascular tissues. DPY1 interacts with and competes for SiBAK1 and as a result, causes a sequential reduction in SiBRI1-SiBAK1 interaction, SiBRI1 phosphorylation, and downstream BR signaling. Conversely, DPY1 accumulation and affinity of the DPY1-SiBAK1 interaction are enhanced under BR treatment, thus preventing SiBRI1 from overactivation. As such, those findings reveal a negative feedback mechanism that represses leaf droopiness by preventing an overresponse of early BR signaling to excess BRs. Notably, plants overexpressing DPY1 have more upright leaves, thicker stems, and bigger panicles, suggesting potential utilization for yield improvement. The maize ortholog of DPY1 rescues the droopy leaves in dpy1, suggesting its conserved function in Panicoideae. Together, our study provides insights into how BR signaling is scrutinized by DPY1 to ensure the upward leaf architecture.