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Abstract Aim To compare and analyze the clinical efficacy of modified Koyanagi and staged Duckett for proximal hypospadias. Method The clinical and prognostic data of children were treated and underwent surgery (modified Koyanagi or stage Duckett) in the Department of Urology, Kunming Children’s Hospital from January 2020 to January 2023 were retrospectively analyzed. According to different surgical methods, the subjects were divided into the modified Koyanagi group and the staged Duckett group. Patients in both groups were followed up for more than 6 months after surgery. The success rate and complications of postoperative surgery in both groups were analyzed. Result A total of 63 patients were included in this study, 34 in the modified Koyanagi group and 29 in the staged Duckett group. A total of 14 patients in the modified Koyanagi group experienced postoperative complications, the success rate of the surgery was 58.82%, and 5 among them experienced more than two kinds of complications. A total of 5 children in the staging Duckett group experienced postoperative complications, and the success rate of the operation was 82.75%. There were significant differences in the incidence of overall complications and fistula between the two surgical methods (P = 0.028). Conclusion Compare with modified Koyanagi, staged Duckett can significantly reduce the incidence of overall complications and urethral fistula in patients, and have obvious advantages in the treatment of proximal hypospadias.

Arsenic (As) is a naturally occurring chemical element widely distributed in the Earth's crust. Human activities have significantly altered As presence in the environment, posing significant threats to the biota as well as human health. The environmental fates and adverse outcomes of As of various species have been extensively studied in the past few decades. It is imperative to summarize these advances as a whole to provide more profound insights into the As cycle for sustainable development. Embracing the One Health concept, we systematically reviewed previous studies in this work and explored the following three fundamental questions, i.e., what the trends and associated changes are in As contamination, how living organisms interact and cope with As contamination, and most importantly what to do to achieve a sustainable future with As. By focusing on one critical question in each section, this review aims to provide a full picture of the complexity of environmental As. To tackle the significant research challenges and gaps in As pollution and mitigation, we further proposed a One Health framework with potential coping strategies, guiding a coordinated agenda on dealing with legacy As in the environment and ensuring a sustainable As future.

Abstract Background Clinically, most patients with lung cancer (LC) die from tumor spread and metastasis. Specific metastasis‐related molecules can provide reference for clinical prediction of efficacy, evaluation of prognosis, and search for the best treatment plan. Troponin T1 (TNNT1) is highly expressed in various cancer tissues, which affects malignant behavior of tumor cells and is related to patients' survival and prognosis. However, the role and molecular mechanism of TNNT1 in LC invasion and metastasis have not yet been investigated. Methods Gene expression profiling interactive analysis (GEPIA) online analysis was used to analyze TNNT1 expression in LC tissues. Quantitative real‐time‐polymerase chain reaction (qRT‐PCR) or western blot were performed to measure TNNT1 or epithelial‐to‐mesenchymal transition (EMT)‐related and Wnt/β‐catenin pathway‐related protein expression in LC cells. After TNNT1 knockdown, cell scratch healing and transwell assays were introduced to assess cell migration and invasion, respectively. Results TNNT1 expression in LC tissues and cells was increased. TNNT1 knockdown notably impaired LC cell migration, invasion and EMT. TNNT1 knockdown inhibited Wnt/β‐catenin pathway of LC cells. Lithium chloride (LiCl) addition partially restored the inhibition of TNNT1 knockdown on migration, invasion, EMT and Wnt/β‐catenin of LC cells. Conclusion TNNT1 knockdown attenuated LC migration, invasion and EMT, possibly through Wnt/β‐catenin signaling.

Objective To observe and analyze the influence of the improved ultra-low temperature storage box on the quality of fresh frozen plasma (FFP). Methods A total of 80 qualified whole blood samples (400 mL, O type not included) collected from July to November in 2023 were selected, and were divided into 4 groups, with 20 samples in each group. Group A: quick-frozen in a traditional low temperature box for 1 hour and then stored in a -30℃ cold storage; Group B: quick-frozen in the flat freezer for 1 hour and then stored in a -30℃ cold storage; Group C: quick-frozen in a newly improved ultra-low temperature storage box for 1 hour and stored in a -30℃ cold storage; Group D: quick-frozen in a new improved ultra-low temperature storage box for 12 hours and stored in a -30℃ cold storage. The contents of FⅧ and fibrinogen (Fg) in four groups were detected. Results The contents of FⅧ in group B, C and D were significantly higher than those in group A, with statistical difference (P0.05), and no statistical difference in the contents of Fg was found among the four groups(P>0.05). Conclusion The improved ultra-low temperature storage box is superior to the traditional low temperature box in preparing FFP, and there is no obvious difference between the improved ultra-low temperature storage box and the flat-plate quick freezer. However, the improved ultra-low temperature storage box can make the process of preparing FFP more flexible and improve the efficiency of component preparation.

Abstract Genes involved in drug absorption, distribution, metabolism, and excretion (ADME) are named ADME genes. However, the comprehensive role of ADME genes in kidney renal clear cell carcinoma (KIRC) remains unclear. Using the clinical and gene expression data of KIRC patients downloaded from The Cancer Genome Atlas (TCGA), ArrayExpress, and the Gene Expression Omnibus (GEO) databases, we cluster patients into two patterns, and the population with a relatively poor prognosis demonstrated higher level of immunosuppressive cell infiltration and higher proportion of glycolytic subtypes. Then, 17 ADME genes combination identified through the least absolute shrinkage and selection operator algorithm (LASSO, 1000 times) was utilized to calculate the ADME score. The ADME score was found to be an independent predictor of prognosis in KIRC and to be tightly associated with the infiltration level of immune cells, metabolic properties, tumor-related signaling pathways, genetic variation, and responses to chemotherapeutics. Our work revealed the characteristics of ADME in KIRC. Assessing the ADME profiles of individual patients can deepen our comprehension of tumor microenvironment (TME) features in KIRC and can aid in developing more personalized and effective therapeutic strategies.

Abstract Aims Accumulating evidence indicates that the use of antibiotics (ATBs) in cancer patients is potentially correlated with patient prognosis. Interestingly, the use of these agents is not uncommon in colorectal cancer (CRC) patients during surgery; however, their prognostic value in the clinic has never been addressed. Materials and methods Data on ATB use during surgery, including the cumulative defined daily dose (cDDD) and the number of categories, were collected. Differences in the clinical data between the low and high cDDD subgroups and between subgroups with ≤ 4 and >4 categories. Additionally, the disease-free survival (DFS) and overall survival (OS) among these subgroups and the specific categories were compared. Finally, a Cox proportional hazard model was used to validate the risk factors for the outcome. Results The number of categories, rather than the cDDD, was a significant predictor of both DFS (P = 0.043) and OS (P = 0.039). Patients with obstruction are more likely to have a high cDDD, whereas older patients are more likely to have multiple categories. There were no significant differences in the DFS (log rank = 1.36, P = 0.244) or OS (log rank = 0.40, P = 0.528) between patients in the low- and high-cDDD subgroups, whereas patients with ≤ 4 categories had superior DFS (log rank = 9.92, P = 0.002) and OS (log rank = 8.30, P = 0.004) compared with those with >4 categories. Specifically, the use of quinolones was harmful to survival (DFS: log rank = 3.67, P = 0.055; OS: log rank = 5.10, P = 0.024), whereas the use of macrolides was beneficial to survival (DFS: log rank = 12.26, P

BackgroundThe efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in the treatment of advanced colorectal cancer is controversial. This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors for advanced colorectal cancer.MethodsPubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including median progression-free survival (mPFS), median overall survival (mOS), overall response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs) and ≥grade 3 TRAEs were extracted for further analysis. The risk of bias was assessed by subgroup analysis.Results12 articles with 566 patients were identified and subjected to meta-analysis. With regard to survival analysis, the pooled mOS and mPFS were 6.66 months (95%CI 4.85-9.16) and 2.92 months (95%CI 2.23-3.83), respectively. In terms of tumor response, the pooled ORR and DCR were 21% (95%CI 6%-41%) and 49% (95%CI 27%-71%), respectively. The pooled AEs rate and ≥ grade 3 AEs rate were 94% (95%CI 86%-99%) and 44% (95%CI 30%-58%).ConclusionPD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown promising clinical responses in the treatment of colorectal cancer (CRC). Although the incidence of adverse reactions is high, they are generally tolerable.Systematic review registrationhttps://inplasy.com/, identifier INPLASY202480030.

Abstract Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave‐enhanced multi‐view acoustofluidic rotation cytometry (MARC) technique is developed for pre‐cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi‐angle observations and amplifies subtle cell differences, particularly in the nuclear‐to‐cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC‐screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening.

PurposeAn accurate assessment of the surgical margins of tongue squamous cell carcinoma (TSCC), especially the deep muscle tissue, can help completely remove the cancer cells and thus minimize the risk of recurrence. This study aimed to develop a classification model that classifies TSCC and normal tissues in order to aid in the rapid and accurate intraoperative assessment of TSCC surgical deep muscle tissue margins.Materials and methodsThe study obtained 240 Raman spectra from 60 sections (30 TSCC and 30 normal) from 15 patients diagnosed with TSCC. The classification model based on the analysis of Raman spectral data was developed, utilizing principal component analysis (PCA) and linear discriminant analysis (LDA) for the diagnosis and classification of TSCC. The leave-one-out cross-validation was employed to estimate and evaluate the prediction performance model.ResultsThis approach effectively classified TSCC tissue and normal muscle tissue, achieving an accuracy of exceeding 90%. The Raman analysis showed that TSCC tissues contained significantly higher levels of proteins, lipids, and nucleic acids compared to the adjacent normal tissues. In addition, we have also explored the potential of Raman spectroscopy in classifying different histological grades of TSCC.ConclusionThe PCA–LDA tissue classification model based on Raman spectroscopy exhibited good accuracy, which could aid in identifying tumor-free margins during surgical interventions and present a promising avenue for the development of rapid and accurate intraoperative techniques.

IntroductionWe assessed metabolic and hormonal responses to high-load resistance exercise under varying normobaric hypoxia conditions with a saturation clamp.MethodsEmploying a counterbalanced, crossover test design, ten well-trained men participated in three exercise trials with normoxic or hypoxic gas mixtures to maintain arterial oxygen saturation at −90% and 80% [moderate (MH) and severe (SH) hypoxia, respectively]. The resistance exercise regimen comprised five sets of 10 repetitions of barbell back squats at 70% of one repetition maximum, with 1-min rest between sets. Metabolic and hormonal responses were measured before normoxia or hypoxia exposures (Pre 1), 15 min after the exposures (Pre 2), and at 0-, 15-, and 30-min post-exercises (T0, T15, and T30, respectively).ResultsCompared to Pre 2, blood lactate concentrations and growth hormone values were elevated at T0, T15, and T30 (p ≤ 0.001), while testosterone values increased at T0 in all conditions (p ≤ 0.009). Epinephrine values increased significantly from Pre 2 to T0 in SH only (p < 0.001). SH had significantly higher blood lactate concentrations (p = 0.023), growth hormone (p = 0.050), and epinephrine (p = 0.020) values at T30 compared to NM. Cortisol values were elevated above Pre 2 at T15 in MH and SH, while lower testosterone values were noted at T0 and T15 for SH compared to NM and MH (all p ≤ 0.05).DiscussionSevere simulated hypoxia, achieved through a saturation clamp during barbell back squats, may enhance metabolic and hormonal responses, particularly 30 min post-session. Nevertheless, the acute effects of hypoxia exposure seem to be overridden by the impact of high-load resistance exercise.

Abstract Introduction As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. Method In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. Results We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. Conclusion Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA. Graphical Abstract

INTRODUCTION: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. METHODS: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). RESULTS: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p

Background Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied.Objective To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis.Methods Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models.Results In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage.Conclusion Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.

Digital technology plays a vital role in driving toward a zero-carbon future. This paper explores whether new infrastructure, serving as carriers for digital technology, contributes to carbon reduction and efficiency gains in cities. Drawing on panel data from 280 Chinese cities spanning 2011 to 2019, we establish a theoretical analytical framework to investigate how new infrastructure influences urban carbon performance through the perspectives of influence, threshold, and spatial spillover effects. The study reveals that new infrastructures development has a contributing effect on the total factor carbon productivity of cities, with consistent results across various testing methods. Additionally, the threshold effect test suggests that the dual threshold of regional energy consumption influences the enhancing effect of new infrastructure on total factor carbon productivity, exhibiting nonlinear characteristics. Furthermore, the spatial spillover effect test suggests that new infrastructure construction accelerates the local carbon emission performance, while having a positive spillover effect on neighboring cities. This study provides innovative ideas and experiences from China for the global realization of simultaneous promotion of digital economy development and energy conservation and emission reduction.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor originating from mesenchymal tissue. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) represents a rare and particularly aggressive variant, associated with a worse prognosis. Almost all EIMS cases exhibits activating anaplastic lymphoma kinase (ALK) gene rearrangements, which suggests that EIMS patients may potentially benefit from treatment with ALK tyrosine kinase inhibitors (TKIs). We presented a case involving a 34-year-old woman who was diagnosed with mediastinal EIMS and had a rare echinoderm microtubule-associated protein-like 4 (EML4) -ALK fusion. Following 15 months of neoadjuvant lorlatinib treatment, the patient underwent a complete surgical resection, resulting in a pathological complete response. Given the heightened risk of postoperative recurrence associated with EIMS, the patient’s treatment plan included ongoing adjuvant therapy with lorlatinib. As of the present moment, the patient has achieved an overall survival of over 2 years with no observed tumor recurrence. Consequently, the case offers valuable clinical evidence supporting the potential benefits of neoadjuvant lorlatinib treatment for ALK-positive locally mediastinal EIMS patients, with a demonstrated tolerable safety profile.

Background: Thyroid cancer (TC) is the most common malignant tumor in the endocrine system, is also one of the head and neck tumor. Follicular Thyroid Carcinoma (FTC) plays an important role in the pathological classification of thyroid cancer. This study aimed to develop an innovative predictive tool, a nomogram, for predicting cancer specific survival (CSS) in middle-aged FTC patients. Methods: We collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. The data from patients between 2004 and 2015 were used as the training set, and the data from patients between 2016 and 2018 were used as the validation set. To identify independent risk factors affecting patient survival, univariate and multivariate Cox regression analyses were performed. Based on this, we developed a nomogram model aimed at predicting CSS in middle-aged patients with FTC. The consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration curve were used to evaluate the accuracy and confidence of the model. Results: A total of 2470 patients were enrolled in this study, in which patients from 2004 to 2015 were randomly assigned to the training cohort (N = 1437) and validation cohort (N = 598), and patients from 2016 to 2018 were assigned to the external validation cohort (N = 435) in terms of time. Univariate and multivariate Cox regression analysis showed that marriage, histological grade and TNM stage were independent risk factors for survival. The C-index for the training cohort was 0.866 (95 % CI: 0.805–0.927), for the validation cohort it was 0.944 (95 % CI: 0.903–0.985), and for the external validation cohort, it reached 0.999 (95 % CI: 0.997–1.001). Calibration curves and AUC suggest that the model has good accuracy. Conclusions: We developed an innovative nomogram to predict CSS in middle-aged patients with FTC. Our model after a rigorous internal validation and external validation process, based on the time proved that the high level of accuracy and reliability. This tool helps healthcare professionals and patients make informed clinical decisions.

Abstract Background Autoimmune diseases (ADs) may be complicated by sepsis when intensive care unit (ICU) admission. But repeated sepsis among AD patients has not been studied yet. The aim of this study is to investigate the impact of repeated in-ICU sepsis on the 1-year overall-cause mortality, septic shock and in-ICU death of AD patients. Methods Data of AD patients with sepsis retrieved from Medical Information Mart for Intensive Care IV (MIMIC-IV) database were divided into the single group and the repeated group according to the frequency of in-ICU sepsis. Propensity score matching was used to balance inter-group bias. Cox proportional hazard regression and sensitivity analysis were utilized to assess the variables on mortality. Results The incidence of repeated in-ICU sepsis in baseline was 19.8%. The repeated in-ICU sepsis was a risk factor for 1-year overall-cause mortality among AD patients (adjusted hazard ratio [HR] = 1.50, 95% CI: 1.16–1.93, P = 0.002), with robust adjusted HRs by the adjustment for confounders in the sensitivity analysis (all P

Abstract Heterotopic brain tissue is rare and has not been reported. Our center made the first report. 4 years and 2 months old Girl presented with a cystic mass in the right adrenal gland 2 weeks after right upper abdominal pain. The operation was successful, and the diagnosis was confirmed by postoperative pathology. 6 months after the procedure, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and satisfactory examination results. It can provide a reference for diagnosing and treating clinical HBT and reduce the risk of misdiagnosis and mistreatment.

The impact of two priming exercise protocols using traditional (TS) or cluster-set (CS) arrangements on explosive performance 6 hours later were examined. Sixteen male collegiate athletes performed three testing sessions (one baseline without any prior exercise in the morning and two experimental sessions) separated by 72 hours. Participants completed two morning (9–11 am) priming protocols in a randomized order, either using a TS (no rest between repetitions) or CS (30 seconds of rest between repetitions) configuration. The protocols consisted of 3 sets×3 repetitions of barbell back squat at 85% of 1 repetition maximum, with 4 minutes of rest between sets. In the afternoon (3–5 pm) of each trial, after a 6-hour rest period, a physical test battery was conducted that replicated baseline testing, including countermovement jump, 20-meter straight-line sprint, and T-test abilities. Across both conditions, participants exhibited increased countermovement jump height, 20-meter sprint time and T-test time compared to baseline (P < 0.05). Improvements in countermovement jump height (+4.4 ± 5.4%; P = 0.008) and 20-meter sprint time (+1.3±1.7%; P = 0.022), but not T-test time (+1.1±3.3%; P = 0.585), were significantly greater for CS than TS. In conclusion, compared to a traditional set arrangement, a morning-based priming protocol using a cluster-set configuration led to superior explosive performance benefits in the afternoon.

Abstract Induction of tumor vascular normalization is a crucial measure to enhance immunotherapy efficacy. cGAS-STING pathway is vital for anti-tumor immunity, but its role in tumor vasculature is unclear. Herein, using preclinical liver cancer models in Cgas/Sting-deficient male mice, we report that the interdependence between tumor cGAS and host STING mediates vascular normalization and anti-tumor immune response. Mechanistically, TET2 mediated IL-2/STAT5A signaling epigenetically upregulates tumor cGAS expression and produces cGAMP. Subsequently, cGAMP is transported via LRRC8C channels to activate STING in endothelial cells, enhancing recruitment and transendothelial migration of lymphocytes. In vivo studies in male mice also reveal that administration of vitamin C, a promising anti-cancer agent, stimulates TET2 activity, induces tumor vascular normalization and enhances the efficacy of anti-PD-L1 therapy alone or in combination with IL-2. Our findings elucidate a crosstalk between tumor and vascular endothelial cells in the tumor immune microenvironment, providing strategies to enhance the efficacy of combinational immunotherapy for liver cancer.

Abstract Objective Prostate cancer (PC) is a significant disease affecting men’s health worldwide. More than 60% of patients over 65 years old and more than 80% are diagnosed with localized PC. The current choice of treatment modalities for localized PC and whether overtreatment is controversial. Therefore, we wanted to construct a nomogram to predict the risk factors associated with cancer-specific survival (CSS) and overall survival (OS) in elderly patients with localized PC while assessing the survival differences in surgery and radiotherapy for elderly patients with localized PC. Methods Data of patients with localized PC over 65 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to determine independent risk factors for CSS and OS. Nomograms predicting CSS and OS were built using multivariate Cox regression models. The consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve were used to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the potential clinical value of this model. Results A total of 90,434 patients over 65 years and diagnosed with localized PC from 2010 to 2018 were included in the study. All patients were randomly assigned to the training set (n = 63,328) and the validation set (n = 27,106). Univariate and multivariate Cox regression model analysis showed that age, race, marriage, T stage, surgical, radiotherapy, prostate-specific antigen (PSA), and Gleason score (GS) were independent risk factors for predicting CSS in elderly patients with localized PC. Age, race, marriage, surgery, radiotherapy, PSA, and GS were independent risk factors for predicting OS in elderly patients with localized PC. The c-index of the training and validation sets for the predicted CSS is 0.802(95%CI:0.788–0.816) and 0.798(95%CI:0.776–0.820, respectively). The c-index of the training and validation sets for predicting OS is 0.712(95%:0.704–0.720) and 0.724(95%:0.714–0.734). It shows that the nomograms have excellent discriminatory ability. The AUC and the calibration curves also show good accuracy and discriminability. Conclusion We have developed new nomograms to predict CSS and OS in elderly patients with localized PC. After internal validation and external temporal validation with reasonable accuracy, reliability and potential clinical value, the model can be used for clinically assisted decision-making.

AbstractContext Hawthorn leaves are a kind of widely used medicinal plant in China. The major ingredient, hawthorn leaves flavonoids (HLF), have cardiotonic, cardioprotective, and vascular protective effects.Objective The study evaluated the protective role of HLF in cardiac remodelling and the underlying mechanisms under simulated microgravity by hindlimb unloading rats.Materials and methods Adult male Sprague-Dawley rats were divided into control, HLF, HU (hindlimb unloading) and HU + HLF groups (n = 8). After HU and daily intragastric administration at the dose of 100 mg/kg/d for 8 weeks, cardiac function and structure were evaluated by biochemical indices and histopathology. We identified the main active compounds and mechanisms involved in the cardioprotective effects of HLF via bioinformatics and molecular docking analysis, and relative signalling pathway activity was verified by Western blot.Results HLF treatment could reverse the HU-induced decline in LV-EF (HU, 55.13% ± 0.98% vs. HU + HLF, 71.16% ± 5.08%), LV-FS (HU, 29.44% ± 0.67% vs. HU + HLF, 41.62% ± 4.34%) and LV mass (HU, 667.99 ± 65.69 mg vs. HU + HLF, 840.02 ± 73.00 mg). Furthermore, HLF treatment significantly increased NPRA expression by 135.39%, PKG by 51.27%, decreased PDE5A by 20.03%, NFATc1 by 41.68% and Rcan1.4 by 54.22%.Conclusions HLF plays a protective effect on HU-induced cardiac remodelling by enhancing NPRA-cGMP-PKG pathway and suppressing the calcineurin-NFAT pathway, which provides a theoretical basis for use in clinical therapies.

Energy prices are usually determined by the marginal costs obtained by solving economic dispatch problems without considering commitment costs. Hence, generating units are compensated through uplift payments. However, uplift payments may undermine market transparency as they are not publicly disclosed. Alternatively, energy prices can be obtained from the unit commitment problem which considers commitment costs. But, due to non-convexity, prices may not monotonically increase with demand. To resolve this issue, convex hull pricing has been introduced. It is defined as the slope of the convex envelope of the total cost function over the convex hull of a unit commitment (UC) problem. Although several approaches have been developed, a relevant survey has not been found to aid the understanding of convex hull pricing from the current limited literature. This paper provides a systematic survey of convex hull pricing. It reviews, compares, and links various existing approaches, focusing on the modeling and computation of convex hull prices. Furthermore, this paper explores potential areas of improvement and future challenges due to the ongoing efforts for power system decarbonization.

In this paper, we present a unique multi-functional super-resolution instrument, the SuperNANO system, which integrates real-time super-resolution imaging with direct laser nanofabrication capabilities. Central to the functionality of the SuperNANO system is its capacity for simultaneous nanoimaging and nanopatterning, enabling the creation of anti-counterfeiting markings and precision cutting with exceptional accuracy. The SuperNANO system, featuring a unibody superlens objective, achieves a resolution ranging from 50 to 320 nm. We showcase the instrument’s versatility through its application in generating high-security anti-counterfeiting features on an aluminum film. These ‘invisible’ security features, which are nanoscale in dimension, can be crafted with arbitrary shapes at designated locations. Moreover, the system’s precision is further evidenced by its ability to cut silver nanowires to a minimum width of 50 nm. The integrated imaging and fabricating functions of the SuperNANO make it a pivotal tool for a variety of applications, including nanotrapping, sensing, cutting, welding, drilling, signal enhancement, detection, and nanoscale laser treatment.

ObjectivesThis study aimed to examine Ki-67’s correlation with clinicopathological characteristics of head and neck squamous cell carcinoma (HNSCC), evaluate its prognostic significance, and develop a Ki-67 integrated prognostic model.MethodsThe retrospective study included 764 HNSCC patients hospitalized from 2012 to 2022. Data were sourced from medical records and immunohistochemical analysis of surgical specimens.ResultsKi-67 expression was significantly associated with sex, pathological grade, clinical stage, and metastasis, but not with age or recurrence. Higher Ki-67 levels were linked to poorer prognosis, as indicated by Kaplan-Meier survival analysis. Utilizing a Cox proportional hazards model, four prognostic factors were identified: age, recurrence, metastasis, and Ki-67 expression. These factors were used to construct a prognostic model and a nomogram. The model’s predictive accuracy was confirmed by a high concordance index and a reliable calibration curve.ConclusionKi-67 expression in HNSCC patients correlates with several clinicopathological features and serves as a negative prognostic marker. A prognostic model incorporating Ki-67 was successfully developed, offering a new tool for patient prognosis assessment in HNSCC.

Synthetic antioxidants (AOs) are commonly used in everyday items and industrial products to inhibit oxidative deterioration. However, the presence of AOs in food packaging and packaged foods has not been thoroughly documented. Moreover, studies on human exposure to AOs through skin contact with packaging or ingesting packaged foods are limited. In this study, we analyzed twenty-three AOs—including synthetic phenolic antioxidants (SPAs) and organophosphite antioxidants (OPAs)—along with six transformation products in various food samples and their packaging materials. We found AOs in food products at concentrations ranging from 1.30 × 103 to 1.77 × 105 ng/g, which exceeded the levels in both outer packaging (6.05 × 102–3.07 × 104 ng/g) and inner packaging (2.27 × 102–1.09 × 105 ng/g). The most common AOs detected in foodstuffs were tris(2,4-di-tert-butylphenyl) phosphate (AO168O), butylated hydroxytoluene (BHT), and octadecyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (AO1076), together constituting 95.7 % of the total AOs found. Our preliminary exposure assessment revealed that dietary exposure—estimated at a median of 2.55 × 104 ng/kg body weight/day for children and 1.24 × 104 ng/kg body weight/day for adults—is a more significant exposure route than dermal contact with packaging. Notably, four AOs were identified in food for the first time, with BHT making up 76.8 % and 67.6 % of the total BHT intake for children and adults, respectively. These findings suggest that food consumption is a significant source of BHT exposure. The estimated daily intakes of AOs via consumption of foodstuffs were compared with the recommended acceptable daily intake to assess the risks. This systematic investigation into AOs contributes to understanding potential exposure and health risks associated with AOs in packaged foods. It emphasizes the need for further evaluation of human exposure to these substances.

Objectives To test the hypothesis that ‘live high-base train high-interval train low’ (HiHiLo) altitude training, compared to ‘live low-train high’ (LoHi), yields greater benefits on performance and physiological adaptations. Methods Sixteen young male middle-distance runners (age, 17.0 ± 1.5 y; body mass, 58.8 ± 4.9 kg; body height, 176.3 ± 4.3 cm; training years, 3–5 y; training distance per week, 30–60 km.wk−1) with a peak oxygen uptake averaging ~65 ml.min−1.kg−1 trained in a normobaric hypoxia chamber (simulated altitude of ~2,500 m, monitored by heart rate ~170 bpm; thrice weekly) for 3 weeks. During this period, the HiHiLo group (n = 8) stayed in normobaric hypoxia (at ~2,800 m; 10 h.day−1), while the LoHi group (n = 8) resided near sea level. Before and immediately after the intervention, peak oxygen uptake and exercise-induced arterial hypoxemia responses (incremental cycle test) as well as running performance and time-domain heart rate variability (5-km time trial) were assessed. Hematological variables were monitored at baseline and on days 1, 7, 14 and 21 during the intervention. Results Peak oxygen uptake and running performance did not differ before and after the intervention in either group (all P > 0.05). Exercise-induced arterial hypoxemia responses, measured both at submaximal (240 W) and maximal loads during the incremental test, and log-transformed root mean square of successive R-R intervals during the 4-min post-run recovery period, did not change (all P > 0.05). Hematocrit, mean reticulocyte absolute count and reticulocyte percentage increased above baseline levels on day 21 of the intervention (all P < 0.001), irrespective of group. Conclusions Well-trained runners undertaking base training at moderate simulated altitude for 3 weeks, with or without hypoxic residence, showed no performance improvement, also with unchanged time-domain heart rate variability and exercise-induced arterial hypoxemia responses.

Summary: Background: There is no trial to assess the benefits of periodically using biologics during the pollen season in patients with uncontrolled seasonal allergic rhinitis (SAR), who have moderate-to-severe symptoms even after standard-of-care. This trial aimed to evaluate the efficacy and safety of the add-on administration of stapokibart, a humanised monoclonal antibody that targets interleukin-4 receptor alpha, in patients with uncontrolled SAR. Methods: In this investigator-initiated, randomised, double-blind, placebo-controlled trial, eligible patients received either stapokibart 600-300 mg weekly (QW), every 2 weeks (Q2W), or placebo QW for 4 weeks. All patients were given mometasone furoate nasal spray and loratadine throughout the trial. The primary endpoint was the mean change from baseline in daily reflective total nasal symptom score (rTNSS) during 2-week treatment. Secondary efficacy outcomes included: the mean change from baseline in daily rTNSS during 4-week treatment; the mean changes and the mean percentage changes from baseline during 2-week and 4-week treatment in 1) daily rTNSS and reflective total ocular symptom score (rTOSS), 2) morning (AM)/evening (PM) rTNSS and rTOSS, 3) AM instantaneous total nasal symptom score (iTNSS) and instantaneous total ocular symptom score (iTOSS), 4) individual nasal and ocular symptoms; the change from baseline in Rhinoconjunctivitis Quality of-Life Questionnaire score during 4-week treatment. Exploratory endpoints included the change of prespecified markers related to type 2 inflammation pre- and post-treatment. Safety, immunogenicity, and pharmacokinetics were also evaluated. This study is registered with www.clinicaltrials.gov (NCT05470647). Findings: Between August 17, 2022, and December 28, 2022, 92 patients with uncontrolled SAR were enrolled from 4 centres in China and randomly assigned to receive stapokibart 600-300 mg QW (n = 31), stapokibart 600-300 mg Q2W (n = 30), or placebo QW (n = 31), of whom 86 (93%) completed the study. Both stapokibart Q2W and QW did not significantly improve mean change from baseline in daily rTNSS compared with placebo in 2 weeks. The least-squares (LS) mean differences (97.5% confidence interval [CI]) compared with placebo were −1.0 (−2.3, 0.2) in stapokibart Q2W group (p = 0.065) and −0.2 (−1.5, 1.0) in stapokibart QW group (p = 0.67). For the secondary outcomes, compared with placebo, stapokibart Q2W presented significant improvements in the mean percentage change from baseline in daily rTNSS in 2 weeks (LS mean difference −12.9%, 95% CI −25.3%, −0.4%, p = 0.043), as well as AM iTNSS over 2 weeks (LS mean difference −17.4%, 95% CI −31.0%, −3.8%, p = 0.013) and 4 weeks (LS mean difference −15.4%, 95% CI −29.0%, −1.9%, p = 0.026). Additionally, the nasal congestion score was significantly lower in stapokibart Q2W than placebo during 2-week (LS mean difference −0.4, 95% CI −0.7, −0.1, p = 0.014) and 4-week (LS mean difference −0.4, 95% CI −0.7, −0.04, p = 0.028) treatment. Treatment-emergent adverse events (TEAEs) occurred in 48% (15/31), 33% (10/30), and 61% (19/31) of patients receiving stapokibart QW, Q2W, and placebo, respectively. Most reported TEAEs were sinus bradycardia, hyperlipidaemia, and blood uric acid increased. Interpretation: In this phase 2 trial, both stapokibart regimens had an acceptable safety and tolerability profile but did not significantly improve daily rTNSS in patients with uncontrolled SAR. The efficacy of stapokibart in patients with uncontrolled SAR is being further investigated in ongoing phase 3 trials (clinicaltrials.gov, NCT05908032). Funding: Ministry of Science and Technology of the People's Republic of China; Ministry of Education of the People's Republic of China; National Natural Science Foundation of China; Chinese Academy of Medical Sciences.

Abstract Deep Reinforcement Learning (DRL) has shown promise for voltage control in power systems due to its speed and model‐free nature. However, learning optimal control policies through trial and error on a real grid is infeasible due to the mission‐critical nature of power systems. Instead, DRL agents are typically trained on a simulator, which may not accurately represent the real grid. This discrepancy can lead to suboptimal control policies and raises concerns for power system operators. In this paper, we revisit the problem of RL‐based voltage control and investigate how model inaccuracies affect the performance of the DRL agent. Extensive numerical experiments are conducted to quantify the impact of model inaccuracies on learning outcomes. Specifically, techniques that enable the DRL agent are focused on learning robust policies that can still perform well in the presence of model errors. Furthermore, the impact of the agent's decisions on the overall system loss are analyzed to provide additional insight into the control problem. This work aims to address the concerns of power system operators and make DRL‐based voltage control more practical and reliable.

Based on vegetation type map， leaf area index and meteorological data for northern Xizang from 1990 to 2019， the relationship between the transition zone of alpine meadow and alpine grassland in northern Xizang and dry-wet climate boundary （1.5 on the dry-wet index， which is the boundary between semi-arid and semi-humid regions） and 400 mm Isohyet was compared to explore the response characteristics of vegetation distribution to different dry-wet boundaries.The results show that the precipitation in northern Xizang decreases from southeast to northwest， the dry-wet index increases， and the surface evolves from wet to dry； from 1990 to 2019， the precipitation increases， and the dry-wet index decreases， showing a wetting trend； the annual LAI value of vegetation increased significantly， indicating that the environment for vegetation growth in 30 years has been improved， and the improvement degree of alpine meadow is higher than that of alpine grassland； the consistency between dry and wet climate boundary and the transition zone of alpine meadow and alpine grassland is high， indicating that the dry wet index can better characterize the vegetation distribution in northern Xizang， while the 400 mm Isohyet is generally to the West； LAI in the east of dry wet boundary is more than 0.6， and LAI in the west of 400 mm Isohyet is less than 0.1； from the correlation analysis among annual LAI value， annual precipitation and annual dry wet index， the increase of precipitation and wet surface conditions in most areas are conducive to vegetation activities.

Abstract Prostate Cancer (PC) is the most common male nonskin tumour in the world, and most diagnosed patients are over 65 years old. The main treatment for PC includes surgical treatment and nonsurgical treatment. Currently, for nonsurgically treated elderly patients, few studies have evaluated their prognostic factors. Our aim was to construct a nomogram that could predict cancer-specific survival (CSS) in nonsurgically treated elderly PC patients to assess their prognosis-related independent risk factors. Patient information was obtained from the Surveillance, Epidemiology and End Results (SEER) database, and our target population was nonsurgically treated PC patients who were over 65 years old. Independent risk factors were determined using both univariate and multivariate Cox regression models. A nomogram was built using a multivariate Cox regression model. The accuracy and discrimination of the prediction model were tested using the consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve. Decision curve analysis (DCA) was used to examine the potential clinical value of this model. A total of 87,831 elderly PC patients with nonsurgical treatment in 2010–2018 were included in the study and were randomly assigned to the training set (N = 61,595) and the validation set (N = 26,236). Univariate and multivariate Cox regression model analyses showed that age, race, marital status, TNM stage, chemotherapy, radiotherapy modality, PSA and GS were independent risk factors for predicting CSS in nonsurgically treated elderly PC patients. The C-index of the training set and the validation set was 0.894 (95% CI 0.888–0.900) and 0.897 (95% CI 0.887–0.907), respectively, indicating the good discrimination ability of the nomogram. The AUC and the calibration curves also show good accuracy and discriminability. We developed a new nomogram to predict CSS in elderly PC patients with nonsurgical treatment. The model is internally validated with good accuracy and reliability, as well as potential clinical value, and can be used for clinical aid in decision-making.

Abstract Background The effects of hypoxia conditioning, which involves recurrent exposure to hypoxia combined with exercise training, on improving body composition in the ageing population have not been extensively investigated. Objective This meta-analysis aimed to determine if hypoxia conditioning, compared to similar training near sea level, maximizes body composition benefits in middle-aged and older adults. Methods A literature search of PubMed, EMBASE, Web of Science, Scopus and CNKI (China National Knowledge Infrastructure) databases (up to 27th November 2022) was performed, including the reference lists of relevant papers. Three independent reviewers extracted study characteristics and health outcome measures. Search results were limited to original studies of the effects of hypoxia conditioning on body composition in middle-aged and older adults. Results Twelve studies with a total of 335 participants were included. Hypoxia conditioning induced greater reductions in body mass index (MD = -0.92, 95%CI: -1.28 to -0.55, I2 = 0%, p 15%) had larger effects than more severe hypoxia (FiO2 ≤ 15%) for improving body mass index in middle-aged and older adults. Hypoxia exposure of at least 60 min per session resulted in larger benefits for both body mass index and body fat. Conclusion Hypoxia conditioning, compared to equivalent training in normoxia, induced greater body fat and body mass index improvements in middle-aged and older adults. Adding hypoxia exposure to exercise interventions is a viable therapeutic solution to effectively manage body composition in ageing population.

Prolonged exposure to high-intensity noise environments in urban rail transit systems can negatively impact the health and work efficiency of drivers. However, there is a lack of comprehensive understanding of the noise pattern and, therefore, effective mitigation strategies. To control the noise in urban rail transit systems, this study proposes a comprehensive noise assessment framework, including metrics such as average sound pressure level, peak sound pressure level, percentile sound pressure levels, dynamic range, main frequency component, and cumulative time energy to evaluate the noise characteristics. We also employ a density-based spatial clustering of applications with noise (DBSCAN) method to identify the noise patterns with the evaluation of their hazard to urban rail transit drivers. The results have revealed that: (1) The equivalent continuous sound pressure level (Leq) in the cab of Lanzhou Urban Rail Transit Line 1 averages 87.12 dB, with a standard deviation of 8.52 dB, which reveals a high noise intensity with substantial fluctuations. (2) Ten noise patterns were identified, with frequencies varying from 14.47 Hz to 69.70 Hz and Leq varying from 60 dB to 115 dB. (3) The major noise sources from these patterns are inferred to be the train’s mechanical systems, wheel–rail interaction, aerodynamic effects, and braking systems. Combined with the noise patterns and urban rail transit’s operation environment, this study proposes tailored mitigation strategies for applications aimed at protecting drivers’ hearing health, enhancing work efficiency, and ensuring driving safety.

The Loess Plateau is an important source of particulate matter pollution in North China. In order to establish and repair shelterbelts and improve their function of inhibiting wind erosion and dust, four typical shelterbelts (Populus simonii, Pinus tabulaeformis Carr., Pinus tabulaeformis Carr. × Populus simonii and Caragana korshinskii Kom.) were selected to investigate the inhibition rate of soil wind-erosion and the reduction rates of PM1, PM2.5 and PM10 by stand type, stand structure and soil properties. A sample plot survey and semi-fixed observation method were used to measure wind speed and particulate matter concentration and to calculate wind protection effect, sand transport rate, vertical flux of particulate matter, wind-erosion inhibition rate and particulate matter reduction rate. The results showed that the Pinus tabulaeformis Carr. forest and Caragana korshinskii Kom. forest had the best windproofing effect, at 2 m (82.9% ± 23.8%) and 0.5 m (54.4% ± 21.5%), respectively. The distribution curve of the sediment flux of shelterbelts is a logarithmic function. The wind-erosion inhibition rate and PM1 reduction rate of the Pinus tabulaeformis Carr. forest were significantly greater than those of other stand types (p < 0.05). The generalized linear mixed model (GLMM) shows that the DBH variation coefficient (CV) can effectively explain the reduction rate of PM1. It is suggested that policies be enacted to add or replace Pinus tabulaeformis Carr. forest in polluted areas to prevent wind erosion and dust.

Congenital birth defects contribute significantly to preterm birth, stillbirth, perinatal death, infant mortality, and adult disability. As a first step to exploring the mechanisms underlying this major clinical challenge, we analyzed the embryonic phenotypes of lethal strains generated by random mutagenesis. In this study, we report the gross embryonic and perinatal phenotypes of 55 lethal strains randomly picked from a collection of mutants that carry piggyBac (PB) transposon inserts. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested most of the analyzed mutations hit genes involved in heart and nervous development, or in Notch and Wnt signaling. Among them, 12 loci are known to be associated with human diseases. We confirmed 53 strains as embryonic or perinatal lethal, while others were subviable. Gross morphological phenotypes such as body size abnormality (29/55, 52.73%), growth or developmental delay (35/55, 63.64%), brain defects (9/55, 16.36%), vascular/heart development (31/55, 56.36%), and other structural defects (9/55, 16.36%) could be easily observed in the mutants, while three strains showed phenotypes similar to those of human patients. Furthermore, we detected body weight or body composition alterations in the heterozygotes of eight strains. One of them was the TGF-β signaling gene Smad2. The heterozygotes showed increased energy expenditure and a lower fat-to-body weight ratio compared to wild-type mice. This study provided new insights into mammalian embryonic development and will help understand the pathology of congenital birth defects in humans. In addition, it expanded our understanding of the etiology of obesity.

Abstract Background The Controlling Nutritional Status (CONUT) score has proven to be a potential biomarker for determining the prognosis of patients with various types of cancer. Its value in determining the prognosis of patients with gynecological cancer, however, remains unknown. The present study was a meta-analysis that aimed to evaluate the prognostic and clinicopathological significance of the CONUT score in gynecological cancer. Methods The Embase, PubMed, Cochrane Library, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched through November 22, 2022. A pooled hazard ratio (HR), together with a 95% confidence interval (CI), was used to determine whether the CONUT score had prognostic value in terms of survival outcomes. Using odds ratios (ORs) and 95% CIs, we estimated the relationship between the CONUT score and clinicopathological characteristics of gynecological cancer. Results We evaluated 6 articles, involving a total of 2,569 cases, in the present study. According to the results of our analyses, higher CONUT scores were significantly correlated with decreased overall survival (OS) (n = 6; HR = 1.52; 95% CI = 1.13–2.04; P = 0.006; I2 = 57.4%; Ph = 0.038) and progression-free survival (PFS) (n = 4; HR = 1.51; 95% CI = 1.25–1.84; P

Abstract Energy Storage Resources (ESRs) can help promote high penetrations of renewable generation and shift the peak load. However, the increasing number of ESRs and their features different from conventional generators bring computational challenges to operations of wholesale electricity markets. In order to improve the computational efficiency, this paper tightens the generic ESR formulation for unit commitment. To avoid the complexity caused by ESR operations in both discharge and charge directions, a novel “decoupled analysis” is conducted to analyze one direction at a time. For each direction, ESRs over two and three time periods are categorized into several types based on their parameters. For each type, our recent four‐step systematic formulation tightening approach is used to construct the corresponding tight formulation. In order to consider more periods without analyzing all the drastically increased number of types, a series of major types are selected based on how many periods an ESR is able to discharge (charge) consecutively at the upper power limit. A related generic form of tight constraints over multiple periods is established. Moreover, validity and facet‐defining proofs of our tight constraints have been provided. Numerical testing results illustrate the tightening process and demonstrate computational benefits of the tightened formulations.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus, prevalent in more than 30 countries worldwide. Human infection by this virus leads to severe illness, with an average case fatality of 40%. There is currently no approved vaccine or drug to treat the disease. Neutralizing antibodies are a promising approach to treat virus infectious diseases. This study generated 37 mouse-derived specific monoclonal antibodies against CCHFV Gc subunit. Neutralization assays using pseudotyped virus and authentic CCHFV identified Gc8, Gc13, and Gc35 as neutralizing antibodies. Among them, Gc13 had the highest neutralizing activity and binding affinity with CCHFV Gc. Consistently, Gc13, but not Gc8 or Gc35, showed in vivo protective efficacy (62.5% survival rate) against CCHFV infection in a lethal mouse infection model. Further characterization studies suggested that Gc8 and Gc13 may recognize a similar, linear epitope in domain II of CCHFV Gc, while Gc35 may recognize a different epitope in Gc. Cryo-electron microscopy of Gc-Fab complexes indicated that both Gc8 and Gc13 bind to the conserved fusion loop region and Gc13 had stronger interactions with sGc-trimers. This was supported by the ability of Gc13 to block CCHFV GP-mediated membrane fusion. Overall, this study provides new therapeutic strategies to treat CCHF and new insights into the interaction between antibodies with CCHFV Gc proteins.

Modeling fluid mud in estuaries and coastal areas is a complicated task due to its non-Newtonian characteristics. A continuous modeling approach was adopted to investigate the laminar flow of fluid mud, with a three-dimensional (3D) form of the Herschel–Bulkley rheological model introduced into the finite volume coastal ocean model (FVCOM) to calculate the apparent viscosity of fluid mud. The model was validated against two flume experiments for the laminar flow of fluid mud. The results showed that the developed model was capable of accurately reflecting the continuous distribution of velocity and density from the near-bottom to the upper water column. Based on the validated model, the difference between the 3D rheological model and a 1DV rheological model on the simulation results was assessed. The study found the results of the 1DV model and the 3D model show obvious differences. This illustrates the significant effect of apparent viscosity in horizontal direction taken into account by the 3D rheological model.

The potential energy curves (PECs) and transition dipole moments (TDMs) of PH+ and PO are computed with the multireference configuration interaction method, and the cross-sections for the radiative association (RA) of PH+ and PO, which is the most efficient way to form the ground states, are presented via the quantum mechanical (QM) theory and computed using ab initio molecular data. The thermal rate coefficients are also expressed and fitted with the standard formula kT=AT300αe−βT in the range of 10 K–15,000 K. Meanwhile, the photodissociation, that is the inverse process of RA for PH+, is also studied, including eight photodissociation channels for the computation of state-resolved cross-sections. Careful comparisons with the Leiden Observatory database are made. Considering the cross-sections mentioned above, the local thermodynamic equilibrium cross-sections at the temperatures of 0, 500, 1,000, and 2,000 K are also shown. We expect the results to be helpful for studies of phosphorus chemistry in the interstellar medium and planetary atmospheres.

AbstractBackground Numerous studies have explored whether the prognostic nutritional index (PNI) can predict the prognosis of cervical cancer (CC); however, their findings remain controversial. This meta-analysis focused on evaluating the relationship between the PNI and the prognosis of patients with CC.Methods Relevant articles were collected from specific databases up to March 16, 2023. The relationship between the PNI and survival outcomes in patients with CC was estimated using combined hazard ratios (HRs) and associated 95% confidence intervals (CIs). The association of the PNI with clinicopathological features in patients with CC was assessed by combining odds ratios (ORs) and associated 95% CIs.Results Nine articles with 2508 cases were included in the meta-analysis. According to our pooled findings, a decreased PNI showed a significant association with worse overall survival (OS) (HR = 2.98, 95% CI = 2.22–3.99, p 4 cm (OR = 1.73, 95% CI = 1.21–2.46, p = .002). However, the PNI was not significantly associated with histology, differentiation, or FIGO stage.Conclusion In this study, a low PNI predicted dismal OS and PFS in patients with CC, who also tend to suffer from LN metastasis and larger tumor size. PNI is a promising biomarker for predicting the prognosis of patients with CC in clinical practice.

Objective This study aims to investigate physicians’ familiarity and awareness of four diabetes guidelines and their practice of the recommendations outlined in these guidelines.Design A cross-sectional study.Setting An online questionnaire survey was conducted among physicians affiliated with the Specialist Committee for Primary Diabetes Care of China Association of Chinese Medicine, using the snowball sampling method to ensure a broader representation of physicians.Participants 1150 physicians from 192 cities across 30 provinces in China provided complete data.Results Tertiary care hospital physicians (TCPs) exhibited the highest familiarity with the Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus in China (91.3%), followed by the National Guidelines for the Prevention and Control of Diabetes in Primary Care (76.8%), the Standards of Medical Care in Diabetes (72.2%) and the Guidelines for Prevention and Treatment of Diabetes in Chinese Medicine (63.8%). Primary care practitioners (PCPs) exhibited familiarity with these four guidelines at about 50% or less. Self-reported reference to modern diabetes guidelines by physicians is more frequent than traditional Chinese medicine (TCM) diabetes guidelines, with rates at 73.2% and 33.8%, respectively. Approximately 90% of physicians provided instructions on self-monitoring of blood glucose to their patients with diabetes. Less than one-third of physicians referred patients to a specialised nutritionist. In terms of health education management, TCPs reported having a diabetes health management team at the rate of 75.7%, followed by secondary care hospital physicians at 57.0% and PCPs at 27.5%. Furthermore, approximately 40% of physicians did not fully grasp hypoglycaemia characteristics.Conclusions Familiarity and awareness of the screening guidelines varied among physicians in different hospital settings. Importantly, significant discrepancies were observed between physicians’ awareness and their self-reported reference to modern medicine guidelines and TCM guidelines. It is essential to consistently provide education and training on diabetes management for all physicians, particularly PCPs.

BackgroundObservational studies have identified a heightened risk of osteoporosis and fractures in patients with primary biliary cholangitis (PBC). However, conclusive evidence establishing a causal relationship between the two, and a clear mechanism explaining this association, remains elusive.MethodsWe conducted a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between PBC and osteoporosis. This analysis utilized five MR methods: inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analyses were performed, employing various models and testing methods, to assess the impact of heterogeneity and pleiotropy on the results and to confirm their robustness.ResultsA causal relationship between PBC and osteoporosis risk was established through IVW analysis (OR: 1.049, 95%CI: 1.017–1.082, P=0.002). Three other MR analyses corroborated these findings. Conversely, osteoporosis was not found to causally affect PBC risk, as evidenced by IVW analysis (OR: 0.941, 95%CI: 0.783–1.129, P=0.511). Across all MR analyses, no heterogeneity or horizontal pleiotropy was detected among the instrumental variables (IVs). Furthermore, the leave-one-out analysis indicated that no single SNP disproportionately influenced the results, affirming the reliability of the bidirectional MR findings.ConclusionThis study establishes a positive causal relationship between PBC and the risk of osteoporosis, while no definitive causal link was found from osteoporosis to PBC. These findings offer new insights and guidance for managing bone health in PBC patients.

Summary: The inheritance of a functional endoplasmic reticulum (ER) is ensured by the ER stress surveillance (ERSU) pathway. Here, we made the unexpected discovery that reticulon 1 (Rtn1) and Yop1, well-known ER-curvature-generating proteins, each possess two sphingolipid-binding motifs within their transmembrane domains and that these motifs recognize the ER-stress-induced sphingolipid phytosphingosine (PHS), resulting in an ER inheritance block. Upon binding PHS, Rtn1/Yop1 accumulate on the ER tubule, poised to enter the emerging daughter cell, and cause its misdirection to the bud scars (i.e., previous cell division sites). Amino acid changes in the conserved PHS-binding motifs preclude Rtn1 or Yop1 from binding PHS and diminish their enrichment on the tubular ER, ultimately preventing the ER-stress-induced inheritance block. Conservation of these sphingolipid-binding motifs in human reticulons suggests that sphingolipid binding to Rtn1 and Yop1 represents an evolutionarily conserved mechanism that enables cells to respond to ER stress.

With the growing maturity of millimeter wave technology and high-throughput satellite communication technology, as well as the urgent need for global broadband communication services, the construction of LEO giant communication constellation has attracted great attention, and up to thousands of satellites have been deployed.A large number of LEO communication satellites have realized multiple and repeated coverage of high-frequency radio frequency signals on the ground.At the same time, ground communication resources provide a hardware platform for signal reception and create conditions for the development of integrated communication and navigation.The status quo, opportunities and challenges of the integrated LEO navigation constellation were discussed, and the differences of resources required by the integrated LEO navigation constellation and the global navigation satellite system were emphatically expounded.In terms of space segment, ground segment and user segment, the conclusions and prospects for future research were presented.

Abstract Small cell carcinoma of the bladder (SCCB) is a rare urological tumor. The prognosis of SCCB is abysmal. Therefore, this study aimed to construct nomograms that predict overall survival (OS) and cancer-specific survival (CSS) in SCCB patients. Information on patients diagnosed with SCCB during 2004–2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models analyzed Independent risk factors affecting patients' OS and CSS. Nomograms predicting the OS and CSS were constructed based on the multivariate Cox regression model results. The calibration curve verified the accuracy and reliability of the nomograms, the concordance index (C-index), and the area under the curve (AUC). Decision curve analysis (DCA) assessed the potential clinical value. 975 patients were included in the training set (N = 687) and the validation set (N = 288). Multivariate COX regression models showed that age, marital status, AJCC stage, T stage, M stage, surgical approach, chemotherapy, tumor size, and lung metastasis were independent risk factors affecting the patients' OS. However, distant lymph node metastasis instead AJCC stage is the independent risk factor affecting the CSS in the patients. We successfully constructed nomograms that predict the OS and CSS for SCCB patients. The C index of the training set and the validation set of the OS were 0.747 (95% CI 0.725–0.769) and 0.765 (95% CI 0.736–0.794), respectively. The C index of the CSS were 0.749 (95% CI 0.710–0.773) and 0.786 (95% CI 0.755–0.817), respectively, indicating that the predictive models of the nomograms have excellent discriminative power. The calibration curve and the AUC also show good accuracy and discrimination of the nomograms. To sum up, We established nomograms to predict the OS and CSS of SCCB patients. The nomograms have undergone internal cross-validation and show good accuracy and reliability. The DCA shows that the nomograms have an excellent clinical value that can help doctors make clinical-assisted decision-making.

Abstract Shotgun metagenome sequencing provides the opportunity to recover underexplored rare populations and identify difficult-to-elucidate biochemical pathways. However, information on sulfur genes, including their sequences, is scattered in public databases. Here, we introduce SMDB ( https://smdb.gxu.edu.cn/ )—a manually curated database of sulfur genes based on an in-depth review of the scientific literature and orthology database. The SMDB contained a total of 175 genes and covered 11 sulfur metabolism processes with 395,737 representative sequences affiliated with 110 phyla and 2340 genera of bacteria/archaea. The SMDB was applied to characterize the sulfur cycle from five habitats and compared the microbial diversity of mangrove sediments with that of other habitats. The structure and composition of microorganism communities and sulfur genes were significantly different among the five habitats. Our results show that microorganism alpha diversity in mangrove sediments was significantly higher than in other habitats. Genes involved in dissimilatory sulfate reduction were abundant in subtropical marine mangroves and deep-sea sediments. The neutral community model results showed that microbial dispersal was higher in the marine mangrove ecosystem than in others habitats. The Flavilitoribacter of sulfur-metabolizing microorganism becomes a reliable biomarker in the five habitats. SMDB will assist researchers to analyze genes of sulfur cycle from the metagenomic efficiently.

Abstract Aims The preoperative serum levels of inflammatory mediators, including C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), have been demonstrated to be correlated with patient outcomes in colorectal cancer (CRC); however, the prognostic role of these levels has been less well-studied in postoperative settings. Materials and methods A total of 122 stage I-III CRC patients were retrospectively enrolled. Serum levels of CRP, PCT and IL-6 were measured after surgery, and their prognostic value was evaluated. Kaplan-Meier analysis was used to determine the differences in disease-free survival (DFS) and overall survival (OS) between patients with different levels of these mediators, and the Cox proportional hazards model was used to estimate the risk factors. Results In contrast to CRP and PCT, only the level of IL-6 was significant in predicting DFS (P = 0.01) but not OS (P = 0.07). A total of 66.39% (81/122) of patients were assigned to the low IL-6 group and no significant differences were found in the collected clinicopathological parameters among the low or high IL-6 subgroups. The level of IL-6 was negatively correlated with postoperative (1 w) (R=-0.24, P = 0.02) absolute lymphocyte counts. Patients with low levels of IL-6 had better DFS (log rank = 6.10, P = 0.01) but not OS (log rank = 2.28, P = 0.13). Finally, the level of IL-6 was an independent risk factor for DFS (HR: 1.81, 95% CI: 1.03–3.15, P = 0.04). Conclusions Compared to CRP and PCT, the level of IL-6 was observed to be the only significant factor in predicting the prognosis of stage I-III CRC patients after surgery, and a low level of IL-6 was associated with good DFS.