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Background: Total body water (TBW) increases with growth, but the body water percentage (TBW%) decreases with aging. The objective of our study was to delineate TBW% in males and females by bioelectrical impedance analysis (BIA) from early childhood to old age. Methods: We enrolled 545 participants aged 3 to 98 years (258 male, 287 female). Among the participants, 256 had a normal weight and 289 were overweight. The TBW was measured by BIA, and TBW% was derived by dividing the TBW (L) value by body weight (kg). For analysis, we divided participants into the four age groups of 3–10, 11–20, 21–60, and ≥61 years.Results: In normal-weight subjects, the TBW% was similar at 62% between males and females in the 3–10-year group. It remained unchanged in males until and through adult life, then decreased to 57% in the ≥61-year group. In normal-weight female subjects, the TBW% decreased to 55% in the 11–20-year group, remained relatively unaltered in the 21–60-year group, then decreased to 50% in the ≥61-year group. In overweight subjects, the TBW% values in males, as well as females, were significantly lower as compared to those with normal weight. Conclusion: Our study showed that the TBW% in normal-weight males changes very little from early childhood to adult life compared to that of females, who showed a decrease in TBW% during the pubertal years. In normal-weight subjects of both sexes, the TBW% decreased after the age of 60 years. Overweight subjects had significantly lower TBW% as compared to those with normal weight.

Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.

Abortion is a stressful life event associated with wide variability in women's perceptions and adjustment. There is scarce evidence on interventions to help women cope with abortion and achieve positive psychological health outcomes. This study tested the effect of a stress and coping theory-formed intervention (START) on depression and coping of Chinese women undergoing a first-trimester abortion.A randomized controlled trial was conducted at a Chinese metropolitan hospital. 110 participants were recruited and randomized to intervention group (START + standard care) or control group (standard care) with a 1:1 allocation ratio. The primary outcome was depression at two-week post-abortion. Surveys were completed by participants when they sought abortion services (baseline), two and six-week post-abortion.At two-week post-abortion, women allocated to the intervention group compared to the control group, had significantly lower depression scores (aOR -2.81 [-4.12 to -1.50]), higher problem-focused coping (aOR 1.64 [0.36-2.93]), lower dysfunctional coping (aOR -2.29 [-3.69 to -0.89]), higher self-efficacy (aOR 3.17 [-0.42-5.94]), and higher personal growth scores (aOR 4.41 [0.30-8.53]). Lower depression scores at two-weeks were mediated by lower dysfunctional coping (mediated effect 0.96 [0.25, 1.74]; proportion of overall effect 36 % [9 %, 65 %]).Chinese women allocated to receive START had lower depression and better coping at two-week post-abortion. This brief, online intervention contributed to women's self-efficacy and positive perceptions of social support, abortion experience, and personal growth. Maintenance of the effects need further research.

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p’s role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon H/R, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p’s pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.

Background and objectivesHigh-dose dual therapy [proton pump inhibitor (PPI) + amoxicillin] is recommended as a Helicobacter pylori rescue treatment. However, its efficacy is still controversial. The aim of this study was to evaluate the efficacy and safety of triple therapy containing high dose of PPI and amoxicillin plus metronidazole compared with dual therapy in rescue treatment.MethodsTwo hundred and sixty-eight patients who failed at least two courses of H. pylori treatment were recruited and randomly allocated into two 14-day groups: esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily plus metronidazole 400 mg three times daily (EAM group); or esomeprazole 40 mg twice daily and amoxicillin 1000 mg three times daily (EA group). The agar-dilution method was performed as an antibiotic susceptibility test. The 13C urea breath test was used to assess H. pylori eradication at 6 weeks after the treatment. The study was registered at clinicaltrials.gov (NCT04024527).ResultsH. pylori eradication rates in the EAM group were 85.8% (115/134, 95% CI 79.9%–91.7%) in ITT analysis and 92.6% (113/122, 95% CI 87.9%–97.3%) in PP analysis, significantly higher than those of the EA group, which were 73.1% (98/134, 95% CI 65.6%–80.6%) and 83.1% (98/118, 95% CI 76.8%–89.8%) (P = 0.005, 0.011). Resistance rates of amoxicillin and metronidazole were 6.6% (13/196) and 89.8% (176/196). Metronidazole resistance did not affect the eradication rates in the EAM group. Both groups had similar moderate and severe adverse events and similar compliance.ConclusionsA triple therapy containing high dose of PPI and amoxicillin plus metronidazole could be a potential rescue therapy worldwide even in a high metronidazole-resistance region.

Whole-genome genotyping methods are important for breeding. However, it has been challenging to develop a robust method for simultaneous foreground and background genotyping that can easily be adapted to different genes and species. In our study, we accidently discovered that in adapter ligation-mediated PCR, the amplification by primer-template mismatched annealing (PTMA) along the genome could generate thousands of stable PCR products. Based on this observation, we consequently developed a novel method for simultaneous foreground and background integrated genotyping by sequencing (FBI-seq) using one specific primer, wherein foreground genotyping is performed by primer-template perfect annealing (PTPA), while background genotyping employs PTMA. Unlike DNA arrays, multiple PCR, or genome target enrichments, FBI-seq requires little preliminary work for primer design and synthesis, and it is easily adaptable to different foreground genes and species. FBI-seq therefore provides a prolific, robust, and accurate method for simultaneous foreground and background genotyping to facilitate breeding in the post-genomics era. This article is protected by copyright. All rights reserved.

A theoretical and experimental study on the catalytic activity for the IRR of Mo–NiSe was carried out to guide the design of cost-effective catalysts in the field of energy conversion.

The general aggression model has shown that both individual and situational factors can predict aggression. However, past research has tended to discuss these two factors separately, which might lead to inconsistency. This study addresses this gap by examining the importance of each predictor of aggression in a Chinese compulsory drug treatment population and further explores the predictors of aggression in various substance use disorder populations.Analyses were conducted using a sample of 894 male participants (mean = 38.30, SD = 8.38) in Chinese compulsory drug rehab. A machine learning model named LightGBM was employed to make predictions. We then used a game-theoretic explanatory technique, SHAP, to estimate the effect of predictors.In the full-sample model, psychological security, parental conflict, and impulsivity were the top 3 predictors. Depression, childhood abuse, and alexithymia positively predicted aggression, whereas psychological security, family cohesion, and gratitude negatively predicted aggression. There were significant differences in the predictive effects of depressants and stimulants. Although the importance of predictors varied between drug-use groups, several individual and situational factors were consistently the most important predictors.All participants in this study were male, and the data were acquired through self-reports from the participants. Domestic and nondomestic aggression are not distinguished. Additionally, our findings cannot support causal conclusions.This study tested a series of classical theories of the predictors of aggression in China's compulsory drug treatment context and extended the ideas of the GAM to various substance use disorder groups. The findings have important implications for aggression treatment.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4–12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (−0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

Treatment of epithelial ovarian cancer (EOC) is a challenge because it still leads to unsatisfactory clinical prognosis. This is due to the toxicity and poor targeting of chemotherapeutic agents, as well as metastasis of the tumor. In this study, we designed a targeted liposome with nanostructures to overcome these problems. In the liposomes, epirubicin and curcumin were encapsulated to achieve their synergistic antitumor efficacy, while Epi-1 was modified on the liposomal surface to target epithelial cell adhesion molecule (EpCAM). Epi-1, a macrocyclic peptide, exhibits active targeting for enhanced cellular uptake and potent cytotoxicity against tumor cells. The encapsulation of epirubicin and curcumin synergistically inhibited the formation of neovascularization and vasculogenic mimicry (VM) channels, thereby suppressing tumor metastasis on SKOV3 cells. The dual drug loaded Epi-1-liposomes also induced apoptosis and downregulated metastasis-related proteins for effective antitumor in vitro. In vivo studies showed that dual drug loaded Epi-1-liposomes prolonged circulation time in the blood and increased the selective accumulation of drug at the tumor site. HE staining and immunohistochemistry with Ki-67 also showed that targeted liposomes elevated antitumor activity. Also, targeted liposomes downregulated angiogenesis-related proteins to inhibit angiogenesis and thus tumor metastasis. In conclusion, the production of dual drug loaded Epi-1-liposomes is an effective strategy for the treatment of EOC.

This cross-sectional study investigated the influence of dietary protein intake (DPI) on serum phosphate levels in peritoneal dialysis (PD) patients and determined the DPI cutoff required to prevent hyperphosphatemia.A total of 504 PD patients were categorized into fast (4 h dialysate/plasma [D/P] creatinine clearance ≥0.65) or slow (0.65) peritoneal transporters. Serum phosphorus and peritoneal solute clearance were compared between the groups with different DPI.The fast peritoneal transporters (High DPI increases the hyperphosphatemia risk in PD patients with slower peritoneal transport function.

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment and abnormal mental behaviour. There is currently no effective cure. The development of early diagnostic markers and the mining of potential therapeutic targets are one of the important strategies. This study aimed to explore potential biomarkers or therapeutic targets related to AD in the hippocampus and prefrontal cortex, two brain regions highly related to AD. Differentially expressed genes and miRNAs between AD patients and healthy controls were obtained from the Gene Expression Omnibus database. The mRNA-miRNA network was constructed and key genes involved in AD were screened out by protein-protein interaction analysis, and were subsequently verified by independent datasets and qPCR in an AD mouse model. Our findings showed that six hub genes including CALN1, TRPM7, ATR, SOCS3, MOB3A and OGDH were believed to be involved in the pathogenesis of AD. Western blot analysis further determined that CALN1, ATR and OGDH were the possible biomarkers and therapeutic targets for AD. In addition, 6 possible miRNAs biomarkers have also been verified by qPCR on AD animal models. Our findings may benefit clinical diagnosis and early prevention of AD.

Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC.Patients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809).A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported.Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.

Deviant eating behavior such as skipping meals and consuming unhealthy meals has a significant association with mental well-being in college students. However, there is more to what an individual eats. While eating patterns form a critical component of their mental well-being, insights and assessments related to the interplay of eating patterns and mental well-being remain under-explored in theory and practice. To bridge this gap, we use an existing real-time eating detection system that captures context during meals to examine how college students’ eating context associates with their mental well-being, particularly their affect, anxiety, depression, and stress. Our findings suggest that students’ irregularity or skipping meals negatively correlates with their mental well-being, whereas eating with family and friends positively correlates with improved mental well-being. We discuss the implications of our study in designing dietary intervention technologies and guiding student-centric well-being technologies.

Academic early warning is an important educational management means to reflect the current "student-centered" educational concept. On the Cloud class teaching network platform, by setting up experimental teams and control groups, and using the academic early warning mechanism composed of dashboard, learning experience value and intelligent robot, we carried out the experimental research on the online and offline Hybrid Teaching of Chinese synthesis for Chinese zero foundation foreign students. The results show that foreign students can respond positively to the early warning notice issued by the system, and teachers can also master the situation of "students with learning difficulties" according to the visual data on the platform and carry out personalized counseling. The overall teaching effect of the experimental group is better and the passing rate is significantly improved. The early warning mechanism not only has a significant correlation with the improvement of "students with learning difficulties", but also promotes the English learning of other foreign students.

Phosphorus (P) is a macronutrient required for plant growth and reproduction. Orthophosphate (Pi), the preferred P form for plant uptake, is easily fixed in the soil, making it unavailable to plants. Limited phosphate rock resources, low phosphate fertilizer use efficiency and high demands for green agriculture production make it important to clarify the molecular mechanisms underlying plant responses to P deficiency and to improve plant phosphate efficiency in crops. Over the past 20 years, tremendous progress has been made in understanding the regulatory mechanisms of the plant P starvation response. Here, we systematically review current research on the mechanisms of Pi acquisition, transport and distribution from the rhizosphere to the shoot; Pi redistribution and reuse during reproductive growth; and the molecular mechanisms of arbuscular mycorrhizal symbiosis in rice (Oryza sativa L.) under Pi deficiency. Furthermore, we discuss several strategies for boosting P utilization efficiency and yield in rice.

This study aimed to develop a Practice Programme for Upright Positions in the Second Stage of Labour to provide a reference for midwifery professionals in the standardized implementation of upright positions in clinical practice.The adoption of upright positions in the second stage of labour is recommended by many international organizations, but upright positions have not been widely used and their implementation varies greatly across studies.The Practice Programme for Upright Positions in the Second Stage of Labour was developed under the guidance of the Medical Research Council framework for developing and evaluating complex interventions and the World Health Organization handbook for guideline development. Four stages were conducted: (1) establishing the intervention development group, (2) identifying a theoretical basis and forming a content framework, (3) evidence retrieval and synthesis and (4) refining and modelling the practice programme.The content framework of the Practice Programme for Upright Positions in the Second Stage of Labour was formed based on the literature review, semi-structured interviews and expert consultation, including indications and contraindications, implementation methods, observations, potential risks and precautions. According to each item, we conducted a series of systematic reviews, and summarized the available best evidence from clinical guidelines, systematic reviews and original studies. Eventually, the Practice Programme for Upright Positions in the Second Stage of Labour was developed, integrating the findings of the iterative evidence reviews and revised by stakeholders.This study first reported the development process of the Practice Programme for Upright Positions in the Second Stage of Labour, characterized by evidence-based, iteratively processed and highly rigorous. The implications may guide researchers to embed the intervention normatively into clinical practice for improving maternal and infant outcomes.The Practice Programme for Upright Positions in the Second Stage of Labour could facilitatesystematic management of labour positions and guide midwives in the successful implementation of upright positions.

The genus Leptobrachella is a species-rich genus of megophrid frog. Rapid discovery of many new species within this genus emphasizes the importance of regional research. In this study, we describe a new species of Leptobrachella, Leptobrachella verrucosasp. nov., from northwestern Guangdong Province, China, based on a combination of molecular and morphological data. A key including congeners from the same province, namely L. laui, L. liui, L. mangshanensis, L. shimentaina, and L. yunkaiensis, is provided.

Alcoholic hepatitis is a major health and economic burden worldwide. Glucocorticoids (GCs) are the only first-line drugs recommended to treat severe alcoholic hepatitis (sAH), with limited short-term efficacy and significant side effects. In this review, I summarize the major benefits and side effects of GC therapy in sAH and the potential underlying mechanisms. The review of the literature and data mining clearly indicate that the hepatic signaling of glucocorticoid receptor (GR) is markedly impaired in sAH patients. The impaired GR signaling causes hepatic down-regulation of genes essential for gluconeogenesis, lipid catabolism, cytoprotection, and anti-inflammation in sAH patients. The efficacy of GCs in sAH may be compromised by GC resistance and/or GC’s extrahepatic side effects, particularly the side effects of intestinal epithelial GR on gut permeability and inflammation in AH. Prednisolone, a major GC used for sAH, activates both the GR and mineralocorticoid receptor (MR). When GC non-responsiveness occurs in sAH patients, the activation of MR by prednisolone might increase the risk of alcohol abuse, liver fibrosis, and acute kidney injury. To improve the GC therapy of sAH, the effort should be focused on developing the biomarker(s) for GC responsiveness, liver-targeting GR agonists, and strategies to overcome GC non-responsiveness and prevent alcohol relapse in sAH patients.

To evaluate the accuracy of contrast-enhanced (CE) fat-suppressed three-dimensional (3D) T1-weighted imaging with volumetric interpolated breath-hold examination (FS-T1-3D-VIBE) and fat-suppressed T1-weighted turbo spin echo (FS-T1-TSE) sequence in characteristics of anal fistula.One hundred and two patients underwent perianal CE-MRI examination on a 3T scanner including FS-T1-3D-VIBE and FS-T1-TSE sequences before surgery. The performance of each sequence was evaluated in terms of fistula classification, clarity of internal opening, number and position of internal openings including the distance between internal opening and anal verge, presence of secondary tracts and blind-ending sinus tracts. MRI findings were compared with surgical findings. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of fistula, gluteus maximus, and subcutaneous fat were compared between CE FS-T1-TSE and CE FS-T1-3D-VIBE.Compared with CE FS-T1-TSE, CE FS-T1-3D-VIBE displayed more accurate in secondary tract, lithotomy position of the internal opening and the distance between internal opening and anal verge (P 0.05). CE FS-T1-3D-VIBE was found superior to CE FS-T1-TSE in the clarity of the internal openings and in the diagnostic accuracy of blind-ending sinus tracts and complex fistulas in Standard Practice Task Force classification (P 0.05). CE FS-T1-3D-VIBE achieved higher SNRs and CNRs in fistula and gluteus maximus than CE FS-T1-TSE (P ≤ 0.001).CE-MRI of FS-T1-3D-VIBE might be a more valuable noninvasive technique than FS-T1-TSE to evaluate the anal fistula on evaluating the lithotomy position of internal opening, distance between internal opening and anal verge, clarity of internal opening, secondary tract, blind-ending sinus tract and classification of the complex fistula. The trial registration number for this prospective trial was Chi-TR1800020206 and the trial registration date was December 20, 2018.