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Abstract Background Many personnel respond to natural disasters like earthquakes and tsunamis and frequent public health events like Ebola and COVID-19. However, research on emergency assistance personnel remains limited. This study aims to describe the perceived well-being among responders deployed in isolated or emergency international missions while providing practical references to intervene in developing similar missions. Methods For this qualitative phenomenological study, purposive sampling was used following the principle of maximum differentiation to select personnel deployed on an emergency mission for over a year. Data collection continued until data saturation. Phenomenologically semi-structured interviews helped explore the physical and psychological status of the participants with Colaizzi’s method. Results Eleven personnel were interviewed after the mission, with four major themes being identified: ‘perceived somatic change,’ ‘perceived emotional change,’ ‘behavioral change,’ and ‘coping with perceived change.’ Conclusions The mental health status of the emergency assistance personnel was affected by multiple factors from external and internal environments. The current study explored the physical and psychological feelings and emotions of emergency assistance personnel during an emergency mission. The study provided a practical reference for health management under similar missions. Registrations Not registered.

Abstract Background GATA1-related cytopenia (GRC) is characterized by thrombocytopaenia and/or anaemia ranging from mild to severe. Haematopoietic stem cell transplantation (HSCT) is a healing therapeutic choice for GRC patients. We identified a novel pathogenic variant (GATA1: c.1019delG) in a boy with GATA1-related cytopenia. Then we performed preimplantation genetic testing (PGT) in this GRC family. After a mosaic embryo transfered, a healthy and HLA-compatible with the proband baby was delivered. Case presentation The proband is a 6-year-old boy who was diagnosed to have transfusion-dependent anaemia since 3 year old. Whole-exome sequencing (WES) showed that the proband has a hemizygous variant c.1019delG in GATA1, which is inherited from his mother. His parents decided to undergo PGT to have a health and HLA-compatible offspring. After whole genome amplification (WGA) of biopsied trophectoderm (TE) cells, next generation sequencing (NGS)-based PGT was preformed to analyse embryos on chromosomal aneuploidy, target mutation and HLA typing. There were 3 embryos HLA-matched to the proband. The genotypes of the 3 embryos were heterozygous variant, hemizygous variant, normal respectively. After a heterozygous, mosaic partial trisomy (chr)16, and HLA-matched embryo transfer, a healthy baby was delivered and whose HSCT is compatible with the proband. Conclusions NGS-based PGT-HLA is a valuable procedure for the treatment of GATA1-related cytopenia caused by GATA1 variants, or other haematological disorders, oncological and immunological diseases. Furthermore, our study reconfirms that mosaic embryos transfer would bring healthy offspring.

Abstract Type II topoisomerases are ubiquitous enzymes that play a pivotal role in modulating the topological configuration of double-stranded DNA. These topoisomerases are required for DNA metabolism and have been extensively studied in both prokaryotic and eukaryotic organisms. However, our understanding of virus-encoded type II topoisomerases remains limited. One intriguing example is the African swine fever virus, which stands as the sole mammalian-infecting virus encoding a type II topoisomerase. In this work, we use several approaches including cryo-EM, X-ray crystallography, and biochemical assays to investigate the structure and function of the African swine fever virus type II topoisomerase, pP1192R. We determine the structures of pP1192R in different conformational states and confirm its enzymatic activity in vitro. Collectively, our results illustrate the basic mechanisms of viral type II topoisomerases, increasing our understanding of these enzymes and presenting a potential avenue for intervention strategies to mitigate the impact of the African swine fever virus.

Abstract Background The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. Methods A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan–Meier analysis were used to assess poor prognosis. Results During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54–5.66]; p = 0.001) and CAD-RADS categories 3–5 (HR = 16.31[6.34–41.92]; p

Objective To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. Methods A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. Results The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P

Objective To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. Methods A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. Results The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P

Objective To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. Methods A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. Results The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P

Objective To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. Methods Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. Results A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. Conclusion A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level

Abstract Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.

Al2O3-supported monometallic Ni, Co, and bimetallic Ni–Co nanocatalysts originated from layered double hydroxide precursors were synthesized by co-precipitation method, and used for the synthesis of useful 5-amino-1-pentanol (5-AP) and 1,5-pentanediol (1,5-PD) by reductive amination (RA) or direct hydrogenation of biofurfural-derived 2-hydroxytetrahydropyran (2-HTHP), respectively. In both reactions, the yield of the target products decreased monotonously with the increasing amounts of Co in the NiCo/Al2O3 catalysts, owing probably to the replacement of highly reactive Ni by Co component with inferior hydrogenation activity at the low reaction temperature of 60 °C. However, the incorporation of Co could improve the reducibility of the NiCo/Al2O3 bimetallic catalysts and promote the reaction stability of the catalysts, especially for Ni2Co1/Al2O3, in both reactions with over 180 h time-on-stream. Characterization of the catalysts before and after the reaction showed that the incorporating Co could inhibit the sintering of metal particles and hinder the surface oxidation of the more reactive Ni0 species, thanks to the formation of Ni–Co alloy in the bimetallic catalysts. DFT-based modeling of the reaction mechanisms is also performed, supporting the reaction pathway proposed previously and also the much higher activity of Ni in the RA of 2-HTHP as compared with Co.

In recent years, along with the widespread use of electric vehicles (EV), EV fires have occurred frequently. However, few studies have investigated EV fires in confined spaces. To address this gap, this paper aims to explore the different aspects of fire evolution of EVs as well as examining the suppression effect of different water mist (WM) settings on these fires. Multiple simulations are carried out, using the Fire Dynamics Simulator (FDS) simulation tool, considering different numbers and working pressures of WM devices. The results highlighted that the number of WM devices had a more significant effect on the fire. Peak heat release was reduced by 17 % and peak arrival time was delayed by 26 % using 6 MPa with 3 nozzles compared to 0 nozzles. Additionally, it leads to accelerated mixing of the smoke layer with the air layer. Moreover, it was shown that the closer to the fire source in the vertical direction, the greater the degree of peak temperature decrease. In this regard, the maximum reduction in the measured temperature was around 70 %.

Asymmetric carbohydroxylation of alkenes offers an efficient approach to access chiral alcohols, a class of versatile building blocks in pharmaceutical and agrochemical industries, from abundant simple alkenes. Herein we reported a sequential photo-biocatalysis protocol for the asymmetric carbohydroxylation of alkenes, involving a stepwise photocatalytic decarboxylative radical addition/Kornblum oxidation and enzymatic reduction. A series of chiral alcohols with bulky structures were synthesized in up to 75 % isolated yields and 99 % ee from N-hydroxyphthalimide esters and aryl alkenes.

Background The high metastasis rate is one of the main reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC). Coagulation factor Xa (FXa) and its receptor proteinase-activated receptor-2 (PAR-2) proven to promote tumor metastasis in other forms of cancer. Here, we explore the role and mechanism of FXa in the regulation of resistance of anoikis and immune escape of HCC.Methods In vitro and in vivo experiments were conducted to explore the role of FXa in HCC metastasis and its potential mechanism. The effects of FXa inhibitor rivaroxaban on HCC immunotherapy were evaluated using intrahepatic metastasis animal models and clinical trial (No. ChiCTR20000040540). We investigated the potential of FXa inhibition as a treatment for HCC.Results FXa was highly expressed in HCC and promoted metastasis by activating PAR-2. Mechanistically, FXa-activated PAR-2 endows HCC cells with the ability of anoikis resistance to survive in the circulating blood by inhibiting the extrinsic apoptosis pathway. Furthermore, suspension stimulation-induced phosphorylation of STAT2, which promotes programmed death-ligand 1 (PD-L1) transcription and inhibits the antitumor effects of immune cells by inhibiting the infiltration of CD8+T cells in tumors and the levels of secreted cytokines. In vivo inhibition of FXa with rivaroxaban reduced HCC metastasis by decreasing PD-L1 expression and exhausting tumor-infiltrating lymphocytes. Notably, the combination of rivaroxaban and anti-programmed death-1 monoclonal antibody (anti-PD-1) programmed Death-1 monoclonal antibody (anti-PD-1) induced synergistic antitumor effects in animal models. Most importantly, rivaroxaban improved the objective response rate of patients with HCC to immune checkpoint inhibitors and prolonged overall survival time.Conclusions FXa-activated PAR-2 promotes anoikis resistance and immune escape in HCC, suggesting the potential for combining coagulation inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance the therapeutic efficacy of HCC.

Gastric cancer is highly prevalent in China, yet early diagnosis and overall survival rates are low. The primary treatment strategy is comprehensive therapy centered on surgery. Studies indicate that neoadjuvant chemotherapy can enhance radical resection rates and extend survival in locally advanced gastric cancer. Combining VEGFR inhibitors with chemotherapy improves efficacy in digestive system tumors, while PD-1/PD-L1 inhibitors combined with anti-angiogenesis agents or chemotherapy show synergistic effects. This report presents a case of gastric adenocarcinoma (cT3N1M0) treated with SOX, apatinib mesylate, and camrelizumab as neoadjuvant therapy, followed by D2 distal gastrectomy and postoperative adjuvant therapy with the same regimen. The patient completed all treatment cycles successfully. Post-neoadjuvant therapy, only focal residual cancer cells were found in the lamina propria (pT1a). During postoperative adjuvant therapy follow-up, gastroscopic biopsy indicated a pathological complete response with no recurrence or metastasis. The patient primarily experienced dyspepsia, oropharyngeal pain, capillary proliferation, mild bone marrow suppression, nausea, and vomiting as side effects. Therefore, SOX combined with apatinib mesylate and camrelizumab shows promise for treating resectable locally advanced gastric cancer.

BackgroundMultiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC.MethodsWe conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords “tertiary lymphoid structures” and “hepatocellular carcinoma.” The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR).ResultsSix studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50–0.67; p

Water evaporation is a ubiquitous natural process exploiting thermal energy from ambient environment. Hydrovoltaic technologies emerged in recent years offer one prospective route to generate electricity from water evaporation, which has long been overlooked. Herein, we developed a hybrid hydrovoltaic generator driven by natural water evaporation, integrating an “evaporation motor” with an evaporation-electricity device and a droplet-electricity device. A rotary motion of the “evaporation motor” relies on phase change of ethanol driven by water-evaporation induced temperature gradient. This motion enables the evaporation-electricity device to work under a beneficial water-film operation mode to produce output of ~4 V and ~0.2 µA, as well as propels the droplet-electricity device to convert mechanical energy into pulsed output of ~100 V and ~0.2 mA. As different types of hydrovoltaic devices require distinctive stimuli, it was challenging to make them work simultaneously, especially under one single driving force. We here for the first time empower two types of hydrovoltaic devices solely by omnipresent water evaporation. Therefore, this work presents a new pathway to exploiting water evaporation-associated ambient thermal energy and provides insights on developing hybrid hydrovoltaic generators.

Abstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

Abstract Based on the whole life cycle theory, the carbon effect of three different sizes of high-standard basic farmland construction projects is measured and analysed. The results show that the carbon emissions generated during the construction of high-standard basic farmland projects and the carbon absorption capacity at the later stage are different for projects of different sizes. The carbon emissions of different scales of high-standard basic farmland projects will increase during the construction stage. The results of carbon effect changes in the later operation and management stage show that the high-standard basic farmland construction projects will help reduce the carbon emissions of the field ecosystem where the farmland is located and increase its carbon sink capacity after the completion of construction, which is more obvious in larger projects. The emission reduction and carbon sequestration capacity of the farmland after remediation are improved to different degrees, which is more conducive to the ecological development of agricultural production and ecological environmental protection in the relevant areas. The study contributes to the green development of farmland, which is of some significance for the sustainable development of agriculture in Tianjin and the whole country.

Abstract Background Mother-infant separation, which is occurring with an increasing incidence, is a barrier to direct breastfeeding. Owing to the importance of breast milk to hospitalized infants, mothers are actively encouraged to express milk during their infants’ neonatal intensive care unit (NICU) stay. However, mothers are often faced with a number of challenges in this process. There is a need to understand such mothers’ real-life experiences of breast milk expression to develop supportive strategies to reduce the burden on mothers and increase breastfeeding rates. Methods A comprehensive search of 12 databases was conducted for relevant studies published from database construction to December 2022. All qualitative and mixed-method studies published in English and Chinese that reported on mothers’ experiences of human milk expression during separation from their hospitalized infants were included. Two reviewers independently conducted screening, data extraction, and quality appraisal, with disagreements resolved by a third reviewer. The process of searching followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The JBI Qualitative Assessment and Review Instrument was used to assess study quality and the credibility of study findings. Meta-aggregation was performed to integrate the results. Results This systematic review aggregated mothers’ experiences of milk expression during separation from their hospitalized infants. Database search yielded 600 records, of which 19 full-text documents were screened. Finally, 13 studies of good quality were included with data from 332 mothers across seven countries. A total of 61 primary findings with illustrations were extracted from the 13 eligible studies, the findings were generalized into 16 categories, and further were concluded as four synthesized findings: purpose and motivation, physical and emotional experiences, barrier factors, and coping styles. Conclusion Mothers were driven by extrinsic motivation in their decision to express breast milk. They experienced physical exhaustion and many negative emotional feelings while expressing. This process was affected by numerous barriers. Social support was essential to the initiation and maintenance of milk expression. Medical staff and families should pay more attention to the mental health of mothers with infants in the NICU. Future research should incorporate strategies to cope with emotional responses and offer practical strategies for managing milk expression. Systematic review registration [ www.crd.york.ac.uk ], identifier [PROSPERO 2022 CRD42022383080].

Saliency detection is increasingly a crucial task in the computer vision area. In previous graph-based saliency detection, superpixels are usually regarded as the primary processing units to enhance computational efficiency. Nevertheless, most methods do not take into account the potential impact of errors in superpixel segmentation, which may result in incorrect saliency values. To address this issue, we propose a novel approach that leverages the diversity of superpixel algorithms and constructs a multi-layer graph. Specifically, we segment the input image into multiple sets by different superpixel algorithms. Through connections within and connections between these superpixel sets, we can mitigate the errors caused by individual algorithms through collaborative solutions. In addition to spatial proximity, we also consider feature similarity in the process of graph construction. Connecting superpixels that are similar in feature space can force them to obtain consistent saliency values, thus addressing challenges brought by the scattered spatial distribution and the uneven internal appearance of salient objects. Additionally, we use the two-stage manifold ranking to compute the saliency value of each superpixel, which includes a background-based ranking and a foreground-based ranking. Finally, we employ a mean-field-based propagation method to refine the saliency map iteratively and achieve smoother results. To evaluate the performance of our approach, we compare our work with multiple advanced methods in four datasets quantitatively and qualitatively.

Abstract Background Dietary intakes of vitamins are associated with asthma. However, previous studies mainly explored the association between a single vitamin intake and asthma, which did not take the multivitamins into consideration. Herein, this study aims to explore the overall effect of dietary multivitamins consumption on childhood asthma. Methods Data of children and adolescents (aged 2-17 years old) were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2015-2018 in this cross-sectional study. Weighted univariate logistic regression analysis was used to screen covariates. The association between multivitamins (including vitamin A, C, D, E, B1, B2, B6, B12, K, niacin, folic acid, and choline) and childhood asthma was explored using univariate and multivariate logistic regression analyses. The evaluation indexes were odds ratio (OR) and 95% confidence interval (CI). We further introduced the Bayesian kernel machine regression (BKMR) to assess the joint effect of the twelve vitamins on childhood asthma, the impact of an individual vitamin as part of a vitamin mixture, and the potential interactions among different vitamins. Results Among 4,715 eligible children and adolescents, 487 (10.3%) had asthma. After adjusting for covariates including race, family history of asthma, pregnant smoking, BMI Z-score, energy intake, breast feeding, and low birth weight, we found that for each 1-unit increase in vitamin K consumption, the odds of childhood asthma decreased 0.99 (P=0.028). The overall effect analysis reported a trend of negative relationship between the multivitamins and childhood asthma, especially at the 75th percentile and over. According to the BKMR models, when other vitamins are fixed at the median level, the odds of childhood asthma increased along with the elevated vitamin D (VD) and vitamin B2 (VB2), whereas along with the depressed vitamin C (VC). In addition, no potential interaction has been found between every two vitamins of multivitamins on childhood asthma. Conclusion Among children and adolescents who have high-risk of asthma, it may be beneficial to increase dietary consumption of multivitamins. Our findings recommended that children and adolescents should increase the intake of VC-rich foods, whereas control the dietary consumption of VD and VB2 in daily life.

[INLINE:1] The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

Abstract Background To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone’s effects and safeties in patients with chronic schizophrenia. Methods Sixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included. Results The plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p

Introduction: The aim of this study is to understand nephrology medical staff’s awareness of, basic knowledge of, practical ability of, and the barriers to palliative kidney care to patients on maintenance hemodialysis (HD) in mainland China. Methods: This cross-sectional descriptive study employed convenience sampling of medical staff (physicians and nurses) working in nephrology departments in mainland China. Independent predictors of self-assessment ability for palliative care (PC) were determined using multivariate binary logistic regression. Results: Responses were received from medical staff in 28 provinces and 657 questionnaires were analyzed. Among the participants, 53.1% (349/657) were doctors, and only 4.3% claimed to be confident in providing PC to patients on HD. The average score of self-assessing ability for PC was 2.65 ± 1.15 (range 1–5). Among the 580 participants who experienced patient withdrawal from dialysis, only 16.0% reported that their patients had well-planned withdrawal from dialysis. Male (odds ratio [OR] [95% confidence interval [CI], 0.585 [0.34–0.99], P = 0.048), nurse (OR [95% CI], 1.81 [1.01–3.27], P = 0.047), more experience in dealing with deceased cases (OR [95% CI], 1.28 [1.02–1.61], P = 0.034), less experience of medical disputes before/after withdrawal from dialysis (OR [95% CI], 0.62 [0.40–0.98], P = 0.041), and PC training experiences (OR [95% CI], 2.33 [1.86–2.91], P < 0.001) were independently correlated with significant better self-assessing ability for PC. Conclusion: This study demonstrates that the nephrology medical staff had a positive attitude but lacked relative knowledge and training in PC. Institutionalized education, training models, practice guidelines for kidney PC, and guidelines for well-planned withdrawal from dialysis according to cultural background are urgently needed in mainland China.

Age-associated deterioration of physiological functions occur at heterogeneous rates across individual organs. A granular evaluation of systemic metabolic mediators of aging in a healthy human cohort (n = 225) identified prominent increases in circulating uremic toxins that were recapitulated in mice, on which we further characterized the aging phenome across five peripheral organs. Our multi-omics analyses connected systemic aging profiles primarily to kidney metabolism, uncovering a metabolic association between localized glucosylceramide (GluCer) accretion and renal functional decline. Elevated GluCers were also associated with higher risk of deaths in an independent cohort of aged individuals (n = 271). We report GluCer-mTOR signaling commencing at late middle-age that disrupts mitophagy and undermines mitochondrial respiration in kidney. Conserved between human and mice, GluCer-mediated renal dysfunction is female-biased and modulated by intracellular purines. Our work provides molecular basis for the sexually disparate effects of mTOR inhibition on mammalian lifespan, possibly ascribed to the evolutionary cost of female reproduction.

Background Survivors of sepsis may encounter cognitive impairment following their recovery from critical condition. At present, there is no standardized treatment for addressing sepsis-associated encephalopathy. Lactobacillus rhamnosus GG (LGG) is a prevalent bacterium found in the gut microbiota and is an active component of probiotic supplements. LGG has demonstrated to be associated with cognitive improvement. This study explored whether LGG administration prior to and following induced sepsis could ameliorate cognitive deficits, and explored potential mechanisms. Methods Female C57BL/6 mice were randomly divided into three groups: sham surgery, cecal ligation and puncture (CLP), and CLP+LGG. Cognitive behavior was assessed longitudinally at 7-9d, 14-16d, and 21-23d after surgery using an open field test and novel object recognition test. The impact of LGG treatment on pathological changes, the expression level of brain-derived neurotrophic factor (BDNF), and the phosphorylation level of the TrkB receptor (p-TrkB) in the hippocampus of mice at two weeks post-CLP (16d) were evaluated using histological, immunofluorescence, immunohistochemistry, and western blot analyses. Results The CLP surgery induced and sustained cognitive impairment in mice with sepsis for a minimum of three weeks following the surgery. Compared to mice subjected to CLP alone, the administration of LGG improved the survival of mice with sepsis and notably enhanced their cognitive functioning. Moreover, LGG supplementation significantly alleviated the decrease in hippocampal BDNF expression and p-TrkB phosphorylation levels caused by sepsis, preserving neuronal survival and mitigating the pathological changes within the hippocampus of mice with sepsis. LGG supplementation mitigates sepsis-related cognitive impairment in mice and preserves BDNF expression and p-TrkB levels in the hippocampus.

Abstract Background This study aims to explore the effect of nutritional impact symptoms (NIS) on oral nutritional supplements (ONS) energy intake and use days among head and neck cancer (HNC) patients. Methods A cross‐sectional study was conducted among HNC patients in a hospital in western China between January 2019 and June 2020. The NIS was from the Patient‐Generated Subjective Global Assessment (PG‐SGA) scale. Mann–Whitney test was used to examine the differences between different kinds of NIS and ONS use days. Binary logistic regression was used to determine the effect of NIS on ONS energy intake. Results The most prevalent four NIS were no appetite (35.3%), dysphagia (29.4%), vomiting (13.2%) and oral pain (12.5%), respectively. All patients in the study were malnutrition. Patients with xerostomia or oral pain had less ONS use days than those without these symptoms. Patients with vomiting (OR 0.09, 95% CI 0.02–0.50) or pain (OR 0.15, 95% CI 0.02–0.89) were less likely to have ONS energy intake ≥400 kcal/day than those without these symptoms after adjusting the confounding factors. In addition, one‐point increase in total NIS score was associated with a lower proportion of ONS energy intake ≥400 kcal/day (OR 0.77, 95% CI 0.59–0.99). Conclusion Xerostomia, oral pain, vomiting and pain should be strengthened and intervened to improve ONS use and nutritional status among HNC patients with malnutrition.

BackgroundThe Tibetan population residing in high-altitude (HA) regions has adapted to extreme hypoxic environments. However, there is limited understanding of the genetic basis of body compositions in Tibetan population adapted to HA.MethodsWe performed a genome-wide association study (GWAS) to identify genetic variants associated with HA and HA-related body composition traits. A total of 755,731 single nucleotide polymorphisms (SNPs) were genotyped using the precision medicine diversity array from 996 Tibetan college students. T-tests and Pearson correlation analysis were used to estimate the association between body compositions and altitude. The mixed linear regression identified the SNPs significantly associated with HA and HA-related body compositions. LASSO regression was used to screen for important SNPs in HA and body compositions.ResultsSignificant differences were observed in lean body mass (LBW), muscle mass (MM), total body water (TBW), standard weight (SBW), basal metabolic rate (BMR), total protein (TP), and total inorganic salt (Is) in different altitudes stratification. We identified three SNPs in EPAS1 (rs1562453, rs7589621 and rs7583392) that were significantly associated with HA (p

Mercury (Hg), as a global pollutant, is persistent, migratory, insidious, highly biotoxic and highly enriched, and is widely distributed in the atmosphere, hydrosphere, biosphere and lithosphere. Wetland ecosystems, as active mercury reservoirs, have become the most important sources and sinks of heavy metal mercury. Distinguished from natural wetlands, artificial wetlands located in urban sections of rivers face problems such as diverse urban pollution sources and complex spatial and temporal changes. Therefore, in this study, five intermittently distributed artificial wetlands were selected from the upstream to the downstream of the Changchun section of the Yitong River, a tributary of the Songhua River basin in the old industrial base of Northeast China. The mercury levels in the water bodies, sediments and plants of the artificial wetlands were collected and tested in four quarters from April 2023 to analyse the spatial and temporal distribution characteristics of total mercury. The results showed that the mercury levels in the water bodies, sediments and plants of the five wetlands showed a fluctuating trend with the river flow direction and had certain spatial and temporal distribution characteristics. This phenomenon was attributed to the sinking of external mercury pollution sources. In general, the wetland ecosystems showed a decreasing trend in the total Hg output of the downstream watershed. This may be due to the retention of particulate matter by aquatic plants in artificial wetlands to regular salvage of dead aquatic plants. At the same time urbanization and industrialization affect mercury levels in aquatic environments, so the risk of residential exposure needs to be looked at.

ObjectiveDespite the developments of in vitro fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure.MethodsWe systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I2 index was analyzed.ResultsWe identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I2 = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I2 = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I2 = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I2 = 24%], but not on LBR. In addition, >150μg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I2 = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I2 = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I2 = 22%], while ≤150μg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I2 = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I2 = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I2 = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection.ConclusionG-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.

IntroductionTirofiban is a non-peptide selective glycoprotein IIb/IIIa receptor inhibitor with a short half-life. The research assesses the efficacy and safety of continuous intravenous tirofiban in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (ET).MethodsA systematic search of Pubmed, Embase, Web of Science, and Cochrane Library databases is conducted from inception until January 26, 2024. Eligible studies are included based on predefined selection criteria. Efficacy outcomes (favorable functional outcome and excellent functional outcome) and safety outcomes (symptomatic intracranial hemorrhage [sICH], any intracranial hemorrhage [ICH], and 90-day mortality) are calculated using odds ratios (OR) and 95% confidence intervals (CI).ResultsA total of 4,329 patients from 15 studies are included in the analysis. The results indicate a significant trend toward favorable functional outcomes in the tirofiban group (OR, 1.24; 95% CI, 1.09–1.42; p = 0.001). In terms of safety outcomes, tirofiban does not increase the risk of sICH (OR, 0.90; 95% CI, 0.71–1.13; p = 0.35) or any ICH (OR, 0.97; 95% CI, 0.70–1.34; p = 0.85), but it significantly decreases 90–day mortality (OR, 0.75; 95% CI, 0.64–0.88; p = 0.0006). A subgroup analysis suggests that continuous intravenous tirofiban demonstrates better efficacy (OR, 1.24; 95% CI, 1.09–1.42; p = 0.001) for patients with AIS undergoing rescue ET with even better results when used in combination with intra–arterial and intravenous administration (OR, 1.25; 95% CI, 1.07–1.451; p = 0.005).ConclusionContinuous intravenous tirofiban is effective and safe for patients with AIS undergoing rescue ET, particularly when combined with intra-arterial tirofiban.Systematic review registrationPROSPERO, identifier CRD42023385695.

Objective To identify the main unqualified items in the external audit of blood station quality management system (referred to as external audit), in order to take necessary measures to continuously improve the quality system. Methods Unqualified items(data) in the national and Shandong provincial blood safety technical audits (referred to as national and provincial audits) and four blood station blood safety technical joint audits (referred to as inter station mutual audits) from 2017 to 2019 were collected and analyzed by Excel and Pareto curves (graphs). Corresponding corrective and preventive measures were developed and implemented, and then tracked and evaluated by the quality management department three months after the external audit to verify their effectiveness. Results In a total of 7 external audits of blood station quality management system that our blood station has participated in over the past 3 years (including 2 national audits, 2 provincial audits, and 3 inter station mutual audits), the main unqualified terms were "12 monitoring and continuous improvement" 11.90% (15/126), "13 blood donation services" 11.90% (15/126), "06 equipment" 10.32% (13/126), "11 records" 10.32% (13/126), "03 organization and personnel" 8.73% (11/126), "15 blood preparation" 7.94% (10/126), "08 safety and health" 7.14% (9/126), and "14 blood testing" 7.14% (9/126). Among them, "monitoring and continuous improvement" ranked first in two national audits and two provincial audits, with 16.67% (5/30) and 14.71% (5/34), respectively, and was 8.06% (5/62) in inter station mutual audit, and the difference between the three kinds of audits was not statistically significant (P>0.05). "Records" accounted the highest proportion in inter station mutual review of 19.35% (12/62), while was respectively 0 and 2.94% (1/34) in national and provincial audits, with statistically significant difference between the three kinds of audits (P

Abstract Cutaneous melanoma is one of the most malignant types of skin cancer, with an extremely poor prognosis. Immune cells infiltrated in the tumor microenvironment (TME) affects melanoma initiation, progression, prognosis and immunotherapy strategies in melanoma. The potential utility of TME-related genes as a prognostic model for melanoma and as a predictor of immunotherapeutic response merits further exploration. In this study, we determined that an immune-related gene, protein tyrosine phosphatase receptor type C (PTPRC), was positively correlated with the positive prognosis of melanoma patients. Integration of this gene with TNM classification created a predictive model that showed better performance in determining overall survival than others. PTPRC expression was positively correlated with the levels of immune checkpoint molecules, and PTPRC knockdown significantly enhanced the migration, invasion, and proliferation of melanoma cells. Finally, immunohistochemical results from HPA and Real-time quantitative PCR of clinical tissues confirmed that PTPRC expression was higher in melanoma than in normal skin. In conclusion, PTPRC served as a potential predictor of survival and response to immunotherapy in melanoma patients. The risk model combining the PTPRC and TNM classifications holds the potential to be a promising tool for prognostic prediction of cutaneous melanoma. This will help in the effective clinical management of melanoma patients.

Abstract The stellar optoelectronic properties of metal halide perovskites provide enormous promise for next-generation optical devices with excellent conversion efficiencies and lower manufacturing costs. However, there is a long-standing ambiguity as to whether the perovskite surface/interface (e.g. structure, charge transfer or source of off-target recombination) or bulk properties are the more determining factor in device performance. Here we fabricate an array of CsPbI3 crystal and hybrid glass composites by sintering and globally visualise the property-performance landscape. Our findings reveal that the interface is the primary determinant of the crystal phases, optoelectronic quality, and stability of CsPbI3. In particular, the presence of a diffusion “alloying” layer is discovered to be critical for passivating surface traps, and beneficially altering the energy landscape of crystal phases. However, high-temperature sintering results in the promotion of a non-stoichiometric perovskite and excess traps at the interface, despite the short-range structure of halide is retained within the alloying layer. By shedding light on functional hetero-interfaces, our research offers the key factors for engineering high-performance perovskite devices.

Abstract Background Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. Methods We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. Discussion The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. Trial registration This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

The East Asian common octopus (Octopus sinensis), is mainly distributed along the southeast coast of China. It has become an important aquaculture species in the coastal areas of the Fujian and Guangdong province due to its excellent culture features such as high conversion rate, fast growth rate, large size, and high market price. The main culturing methods of O. sinensis are industrialized, indoor, and cage culturing. The density is high during cage culturing. If the feed is insufficient or the feeding interval too long, there are attacks and cannibalism among individuals, which adversely impacts the culturing income. Therefore we urgently need to undertake digestive physiology research to explore the digestive functions of O. sinensis. This research will provide valuable information to identify an appropriate feeding frequency and reduce the economic loss caused by cannibalism. At present, there is no relevant research on the digestive physiology of O. sinensis. In this study, the histological structure of each digestive organ of O. sinensis was observed to explore the relationship between the tissue structure and digestive function. We investigated the trypsin, amylase, and lipase activities in the anterior salivary gland, posterior salivary gland, crop, digestive gland, stomach, cecum, and intestine before and after feeding. The changes in plasma glucose, plasma triglyceride, plasma total cholesterol, plasma total protein and muscle glycogen before and after feeding were analyzed to determine the digestion and absorption duration in O. sinensis.O. sinensis is an aggressive carnivore with a highly developed digestive system. The histological results showed that the crop, stomach, cecum, and intestine of O. sinensis is composed of three layers, the mucosal, submucosal, and muscular, and the inner wall contained many folds. Both the anterior and posterior salivary glands were compound tubular glands, which were composed of oval and circular gland tubes with many secretory ducts. The crop widens and expands from the esophagus into a large lumen, and the cuticle of the mucosal layer was thin (with a thickness of approximately 2.57–5.44 μm). The stomach was spherical, the gastric cavity was biased to one side, and the inner wall contained many folds. The muscular layer of the gastric wall was the most developed layer with the cuticle approximately 99.97–383.82 μm. The cecum was double helix and the inner wall contained rich long folds and secondary folds. The submucosa at the free end of some of the long lateral folds contained some mucous glands, and the mucosal layer without any cuticle. The digestive gland was the largest proportion of the digestive system and was composed of hepatic lobules. The boundary of the hepatic lobules was difficult to distinguish. The diameter of the intestine was approximately 2.50 mm, the tube wall was thin and the mucosal layer had no cuticle. The intestinal mucosa forms wavy longitudinal folds in the mucosa, including a pair of longer folds, which occupied almost the entire intestine. The analysis of the digestive enzyme activities and nutrient metabolism showed that trypsin activity was significantly higher than that of lipase and amylase. The trypsin activity in the digestive gland reached (148.74±21.25) U/mg, and the amylase activity in the digestive gland and stomach reached (3.68±0.59) U/mg and (2.48±0.64) U/mg, respectively. The lipase activities did not vary between the different tissues. After feeding, the plasma total protein concentration reached the lowest levels of (161.50±67.51) mg/mL at 120 min, and then increased. The plasma glucose and muscle glycogen concentrations of O. sinensis reached maximums of (1.54±0.44) mmol/L and (4.75± 0.13) mg/g at 200 min, respectively. Feeding had little effect on the plasma lipid concentration in O. sinensis, the plasma cholesterol concentration did not vary significantly while feeding (P < 0.05), and there was limited variation in the plasma triglyceride concentration. The digestion process was divided into two stages. The first stage occurs in 0~60 min as food entered the crop and stomach, and the digestive gland secreted large doses of trypsin. Initially, the trypsin in the stomach mixed with the food, resulting in decreased trypsin activity. At this stage, only small amounts of nutrients are absorbed and the body needs to consume nutrients to supply energy for the digestion process. Therefore, a decrease in plasma glucose, plasma protein, and muscle glycogen content occurred. The second stage occurs in 120~300 min and involves high trypsin activity. In the progress of extracellular digestion and intracellular digestion, the trypsin activity of various digestive organs decreased gradually, and nutrients increased gradually. At 400 min, the trypsin activity, plasma glucose, plasma protein, and muscle glycogen returned to the pre-feeding levels, indicating the end of the digestion and absorption process. The whole digestion and absorption process of O. sinensis lasted approximately 400 min. Therefore, the appropriate feeding interval for O. sinensis culture is 6~7 h.

Abstract Transposable elements (TEs) serve as both insertional mutagens and regulatory elements in cells, and their aberrant activity is increasingly being revealed to contribute to diseases and cancers. However, measuring the transcriptional consequences of nonreference and young TEs at individual loci remains challenging with current methods, primarily due to technical limitations, including short read lengths generated and insufficient coverage in target regions. Here, we introduce a long-read targeted RNA sequencing method, Cas9-assisted profiling TE expression sequencing (capTEs), for quantitative analysis of transcriptional outputs for individual TEs, including transcribed nonreference insertions, noncanonical transcripts from various transcription patterns and their correlations with expression changes in related genes. This method selectively identified TE-containing transcripts and outputted data with up to 90% TE reads, maintaining a comparable data yield to whole-transcriptome sequencing. We applied capTEs to human cancer cells and found that internal and inserted Alu elements may employ distinct regulatory mechanisms to upregulate gene expression. We expect that capTEs will be a critical tool for advancing our understanding of the biological functions of individual TEs at the locus level, revealing their roles as both mutagens and regulators in biological and pathogenic processes.

The contamination risks of plant-derived foods due to the co-existence of pesticides and veterinary drugs (P&VDs) have not been fully understood. With an increasing number of unexpected P&VDs illegally added to foods, it is essential to develop a non-targeted screening method for P&VDs for their comprehensive risk assessment. In this study, a modified support vector machine (SVM)-assisted metabolomics approach by screening eligible variables to represent marker compounds of 124 multi-class P&VDs in maize was developed based on the results of high-performance liquid chromatography–tandem mass spectrometry. Principal component analysis and orthogonal partial least squares discriminant analysis indicate the existence of variables with obvious inter-group differences, which were further investigated by S-plot plots, permutation tests, and variable importance in projection to obtain eligible variables. Meanwhile, SVM recursive feature elimination under the radial basis function was employed to obtain the weight-squared values of all the variables ranging from large to small for the screening of eligible variables as well. Pairwise t-tests and fold changes of concentration were further employed to confirm these eligible variables to represent marker compounds. The results indicate that 120 out of 124 P&VDs can be identified by the SVM-assisted metabolomics method, while only 109 P&VDs can be found by the metabolomics method alone, implying that SVM can promote the screening accuracy of the metabolomics method. In addition, the method’s practicability was validated by the real contaminated maize samples, which provide a bright application prospect in non-targeted screening of contaminants. The limits of detection for 120 P&VDs in maize samples were calculated to be 0.3~1.5 µg/kg.

The type III secretion system (T3SS) of Rhizobium plays a crucial role during the establishment of the soybean (Glycine max (L.) Merr.)-Rhizobium symbiosis system. Additionally, host-specific nodulation may also depend on the Nops (nodulation outer proteins) secreted by the T3SS of Rhizobium. However, there is limited understanding of the response of soybean genes to Nops. In this study, a NopC mutant, HH103ΩNopC, was constructed from Sinorhizobium fredii HH103 and then utilized to assess the impact of the NopC on nodulation. An RNA-seq analysis revealed that the GmERF5 (Glycine max Ethylene Responsive Factor 5) gene was induced by NopC, which was confirmed by qRT-PCR. Furthermore, an overexpression of the GmERF5 hair-root system was constructed to investigate the effect of GmERF5 on nodulation and its interaction with NopC. Differences in nodule number and nodule dry weight in the overexpression of the GmERF5 hair-root system supported the conclusion that GmERF5 can regulate soybean nodule phenotype via NopC. These results elucidate the genetic mechanisms that regulate nodule phenotype in soybean.

Ecosystem resilience plays a vital role for security and resilience in the urban system which experiences the combined effects of anthropogenic activities and natural disasters. Nonetheless, there is currently no unified indicator for assessing urban resilience. Therefore, this study aims to examine the changes of ecosystem resilience in the Guangdong-Hong Kong-Macao Great Bay Area (GBA) based on land use, using the framework of resistance, adaption, and elasticity. The study's results revealed that between 2000 and 2020, the increase in ecosystem resilience in peripheral GBA cities outpaced the decrease in central cities, leading to a yearly rise in overall ecosystem resilience. Nighttime light (NL), population density (PD), urbanization rate (UR), and the normalized difference vegetation index (NDVI) were the primary driving factors influencing resistance and elasticity resilience in the GBA, thereby shaping overall ecosystem resilience. Findings from the multi-scale geographical weighted regression (MGWR) analysis demonstrated that ecosystem resilience decreased as NL, PD, and UR increased, while it exhibited an increase in areas with higher NDVI. This study contributes to the improvement of urban resilience in cities by providing targeted strategies, expediting the development of resilient cities, and offering theoretical insights for land management, urban planning, and policy formulation.

Objective: This study investigated the predicting value of the ratio of levator hiatus diameter (LHS) to fetal head circumference (HC) in pregnant women at 37 weeks of gestation in the progression of the second stage of labor and levator ani injury 6 weeks postpartum. Methods: A total of 120 first-time women who gave vaginal delivery at 37 weeks of pregnancy were selected as the subjects in our hospital during March 2021 to March 2022. The subjects were divided into the second stage of labor > 1 h group and the second stage of labor ≤ 1 h group, according to the delivery time of the second stage of labor. According to the 6-week postpartum follow-up ultrasound examination with or without levator ani injury, they were divided into levator ani injury group and no injury group. All primipara women underwent three-dimensional ultrasonography at 37 weeks of gestation, and the resting LHS, Valsalva LHS, fetal HC and the ratio of resting LHS and fetal HC were compared. The correlation between these factors and the length of the second labor stage was analyzed using Pearson correlation analysis. The value of these factors in predicting labor progression and postpartum levator ani injury was assessed by receiver operating characteristic (ROC) curves. Results: The resting LHS, Valsalva LHS and the ratio of resting LHS and fetal HC in the levator ani injury group were lower than these in the no injury group, while fetal HC in the levator ani injury group was higher than that in the no injury group (P 1 h group were lower than these in the second stage of labor ≤ 1 h group, while fetal HC in the second stage of labor > 1 h group was higher than that in the second stage of labor ≤ 1 h group (P

Tobacco plants (Nicotiana tabacum L.) exhibit considerable potential for phytoremediation of soil cadmium (Cd) pollutants, owing to their substantial biomass and efficient metal accumulation capabilities. The reduction of Cd accumulation in tobacco holds promise for minimizing Cd intake in individuals exposed to cigar smoking. NRAMP transporters are pivotal in the processes of Cd accumulation and resistance in plants; however, limited research has explored the functions of NRAMPs in tobacco plants. In this investigation, we focused on NtNRAMP6c, one of the three homologs of NRAMP6 in tobacco. We observed a robust induction of NtNRAMP6c expression in response to both Cd toxicity and iron (Fe) deficiency, with the highest expression levels detected in the roots. Subsequent subcellular localization and heterologous expression analyses disclosed that NtNRAMP6c functions as a plasma membrane-localized Cd transporter. Moreover, its overexpression significantly heightened the sensitivity of yeast cells to Cd toxicity. Through CRISPR-Cas9-mediated knockout of NtNRAMP6c, we achieved a reduction in Cd accumulation and an enhancement in Cd resistance in tobacco plants. Comparative transcriptomic analysis unveiled substantial alterations in the transcriptional profiles of genes associated with metal ion transport, photosynthesis, and macromolecule catabolism upon NtNRAMP6c knockout. Furthermore, our study employed plant metabolomics and rhizosphere metagenomics to demonstrate that NtNRAMP6c knockout led to changes in phytohormone homeostasis, as well as shifts in the composition and abundance of microbial communities. These findings bear significant biological implications for the utilization of tobacco in phytoremediation strategies targeting Cd pollutants in contaminated soils, and concurrently, in mitigating Cd accumulation in tobacco production destined for cigar consumption.

BackgroundThe burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential.MethodsThis study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration.ResultsOf all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (β=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 μmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS.ConclusionMetabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.

Background The change in the soil carbon bank is closely related to the carbon dioxide in the atmosphere, and the vegetation litter input can change the soil organic carbon content. However, due to various factors, such as soil type, climate, and plant species, the effects of vegetation restoration on the soil vary. Currently, research on aggregate-associated carbon has focused on single vegetation and soil surface layers, and the changes in soil aggregate stability and carbon sequestration under different vegetation restoration modes and in deeper soil layers remain unclear. Therefore, this study aimed to explore the differences and relationships between stability and the carbon preservation capacity (CPC) under different vegetation restoration modes and to clarify the main influencing factors of aggregate carbon preservation. Methods Grassland (GL), shrubland (SL), woodland (WL), and garden plots (GP) were sampled, and they were compared with farmland (FL) as the control. Soil samples of 0–40 cm were collected. The soil aggregate distribution, aggregate-associated organic carbon concentration, CPC, and stability indicators, including the mean weight diameter (MWD), fractal dimension (D), soil erodibility (K), and geometric mean diameter (GMD), were measured. Results The results showed that at 0–40 cm, vegetation restoration significantly increased the >2 mm aggregate proportions, aggregate stability, soil organic carbon (SOC) content, CPC, and soil erosion resistance. The >2 mm fractions of the GL and SL were at a significantly greater proportion at 0–40 cm than that of the other vegetation types but the CPC was only significantly different between 0 and 10 cm when compared with the other vegetation types (P 2 mm aggregates showed a significant positive correlation with the CPC, MWD, and GMD (P

Background: Sorafenib is a classic molecular targeted drug approved for hepatocellular carcinoma (HCC) therapy. However, a poor response rate and increasing resistance to sorafenib make its therapeutic efficacy suboptimal. Combination treatment with an agent capable of potentiating sorafenib sensitivity may be a promising solution. Aim: The aim of this study was to determine the synergistic effect of ellagic acid (EA), a natural polyphenol, and sorafenib on HCC. Methods: CCK-8, EdU incorporation and colony formation assays were used to study the effect of EA on HCC cell proliferation. Apoptosis was detected by flow cytometry in HCC cells and TUNEL assay in xenograft tumors. Transcriptome analysis was utilized to investigate alterations in signaling pathways with EA treatment. A xenograft mouse model was used to confirm the synergistic effect of sorafenib and EA on HCC tumors in vivo. Results: We found that EA inhibited growth and induced apoptosis in both HCC cells and xenograft tumors. Mechanistically, EA treatment reduced the activation of the MAPK and Akt/mTOR signaling pathways in HCC cells. Furthermore, combined EA and sorafenib treatment further inhibited the MAPK and Akt/mTOR signaling pathways compared to EA or sorafenib alone. EA synergistically potentiated the anticancer activity of sorafenib against HCC both in vitro and in vivo. Conclusion: EA inhibits HCC growth by inducing apoptosis through attenuation of the MAPK and Akt/mTOR signaling pathways. EA potentiates the response of HCC tumors to sorafenib both in vitro and in vivo, an effect that may be attributed to further inhibition of the MAPK and Akt/mTOR signaling pathways. These results suggest that EA is an effective adjuvant option for sorafenib therapy.

Objective – The purpose of this research is to examine the experiences of mentors and mentees in the formal mentorship program offered by the Visible Minority Librarians of Canada Network (ViMLoC) from 2018-2022. Findings from this research will help mentors and mentees understand how to establish an effective mentoring relationship. Professional library associations and libraries can also gain valuable insights to support the visible minority library professionals within their own mentorship programs. Methods – Between 2018 and 2022, 113 mentors and 145 mentees participated in four sessions of the ViMLoC mentorship program. The ViMLoC Mentorship Committee designed and delivered a survey for mentors and a survey for mentees at the end of each session. Over four sessions, 81 mentors and 82 mentees completed the surveys, representing a 72% and 57% completion rate, respectively. Fisher's Exact Tests were performed to examine if there were significant differences between mentors and mentees in their perceptions regarding ease of communication, relationship, helpfulness of mentorship, likeliness of keeping in contact, and importance of having a visible minority partner. Results – The mentees perceived mentoring support to be more helpful than the mentors perceived it themselves. The mentees were more likely to keep in contact with their mentors beyond the mentorship program while the mentors did not show as much interest. The mentees who had a positive experience from the formal mentorship program were found to be more likely to mentor others in the future, whereas the same effect did not hold true for the mentors. On the other hand, some findings were the same for both mentors and mentees. Both stated that effective communication would facilitate a good mentoring relationship, which in turn, would lead to positive outcomes and greater likelihood of keeping in contact beyond the mentoring program. There was also consensus of opinion about the most important areas of mentoring support and some essential skills for building a successful mentoring relationship. Conclusion – This research contributes to the literature by using an empirical research method and comparative analyses of the experiences between mentors and mentees over four sessions of the ViMLoC mentorship program. The study focuses on the perceptions of participants regarding their communication, relationship, helpfulness of mentorship, associations between their past and present mentoring experiences, areas of support, importance of having a visible minority partner, and essential skills for building a successful mentoring relationship. Mentors and mentees differed significantly in how they perceived the helpfulness of mentorship support and how likely they would like to maintain the ties beyond the program. For both sides, effective and easy communication was found to be critical for building a good mentoring relationship and achieving a satisfactory experience.

AbstractBackground Diet management is an effective way to retard the progression of chronic kidney disease (CKD). However, very few studies investigated the influence of carbohydrate intake on CKD patients. In this prospective cohort study, the associations between carbohydrate intake and all-cause mortality were investigated in US adult CKD patients.Methods Multivariable Cox proportional hazard models and iso-caloric replacement analysis were used to investigate the associations between the macronutrients and the all-cause mortality risk. Total 3683 US adult CKD patients 20 years or older from the National Health and Nutrition Examination Survey (NHANES, 2003–2014) were analyzed (mean age ± SD, 62.4 ± 17.1; 56.5% female), of which 1082 participants with CKD died with a median follow-up time of 67 (IQR 36–99) months.Results Most macronutrients were non-linearly associated with all-cause mortality risk, including carbohydrates and sugar. Participants with CKD had lower mortality risk when consuming 30–45% energy from carbohydrates (average HR 0.76, 95%CI 0.62–0.93, compared with 60%), 5–20% energy from sugar (average HR 0.75, 95% CI 0.59–0.96 compared with 40%). Replacing the energy intake from carbohydrates with protein (up to 30%) and/or replacing the sugar with non-sugar carbohydrates (up to 55%) reduced the all-cause mortality risk, while the total energy intake remained constant.Conclusions Diet advice should be given according to the current diet status, and constituents of carbohydrates should also be taken into consideration.

Abstract Background Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. Methods The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3β/β-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. Results DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted β-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3β signaling was enhanced to inhibit the degradation of β-catenin, which regulates the process of EndMT. Conclusions PECAM-1 defects and/or internalization are key events for β-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3β signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Graphical Abstract Video Abstract