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Abstract An experimental group and control group pretest and posttest design was used to conduct qualitative coding and quantitative analysis on two classes in grade 5. The aim was to investigate whether science education videos can be used in place of simulation experiments. The results showed that (1) in terms of scientific knowledge, the difference between science videos and hands-on experiments was not significant; (2) in terms of modeling capability, the hands-on class had better results regarding the perception and application of materials; and (3) more precise experiments had better effects on health behavior, but there was no significant difference between imprecise experiments and science videos. In the absence of laboratory equipment, science videos could therefore be an alternative solution.

Abstract Background Effective response and reducing the burden of family care for children with cancer is critical, and China currently lacks a specific assessment tool. Aims This study aimed to translate and validate the Caregiving Burden Scale for Family Caregivers of Children with Cancer (CBSFC-CC) and then test and implement the tool. Methods According to the Beaton cross-cultural debugging guide, preliminary Chinese version of CBSFC-CC scale was formed, which was suitable for Chinese language environment and clinical context. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were performed to verify structural validity. Convergent validity, discriminant validity and reliability were also conducted. Results A total of 529 family caregivers of children with cancer participated in the survey. EFA extracts and combines four factors and explained 65.80% of the total variation. CFA proved that all the goodness-of-fit indicators were acceptable. The Cronbach’s alpha of the Chinese version of CBSFC-CC was .96, and the test–retest reliability coefficient was .95. Four dimensions and 29 items were identified in the final Chinese version of CBSFC-CC. Conclusion The chinese version CBSFC-CC is scientifically reasonable and has good reliability and validity, which can be applied to the investigation of the nursing burden of family caregivers of children with cancer in China.

Abstract Background Enhanced glycolysis is a crucial metabolic event that drives the development of liver fibrosis, but the molecular mechanisms have not been fully understood. Lactate is the endproduct of glycolysis, which has recently been identified as a bioactive metabolite binding to G-protein-coupled receptor 81 (GPR81). We then questioned whether GPR81 is implicated in the development of liver fibrosis. Methods The level of GPR81 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and in transforming growth factor beta 1 (TGF-β1)-activated hepatic stellate cells (HSCs) LX-2. To investigate the significance of GPR81 in liver fibrosis, wild-type (WT) and GPR81 knockout (KO) mice were exposed to CCl4, and then the degree of liver fibrosis was determined. In addition, the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) was supplemented in CCl4-challenged mice and TGF-β1-activated LX-2 cells to further investigate the pathological roles of GPR81 on HSCs activation. Results CCl4 exposure or TGF-β1 stimulation significantly upregulated the expression of GPR81, while deletion of GPR81 alleviated CCl4-induced elevation of aminotransferase, production of pro-inflammatory cytokines, and deposition of collagen. Consistently, the production of TGF-β1, the expression of alpha-smooth muscle actin (α-SMA) and collagen I (COL1A1), as well as the elevation of hydroxyproline were suppressed in GPR81 deficient mice. Supplementation with DHBA enhanced CCl4-induced liver fibrogenesis in WT mice but not in GPR81 KO mice. DHBA also promoted TGF-β1-induced LX-2 activation. Mechanistically, GPR81 suppressed cAMP/CREB and then inhibited the expression of Smad7, a negative regulator of Smad3, which resulted in increased phosphorylation of Smad3 and enhanced activation of HSCs. Conclusion GPR81 might be a detrimental factor that promotes the development of liver fibrosis by regulating CREB/Smad7 pathway.

Abstract Background After China ended its ‘dynamic zero-COVID policy’ on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected. Methods All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection. Results A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females [adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07–1.88] and clinical practitioners (aOR: 10.32, 95% CI: 6.57–16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age ≥ 60 years (aOR: 0.30, 95% CI: 0.19–0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23–0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22–0.97 for within 1–3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms. Conclusion Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China’s deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak.

Abstract Predicting and understanding travellers’ mode choices is crucial to developing urban transportation systems and formulating traffic demand management strategies. Machine learning (ML) methods have been widely used as promising alternatives to traditional discrete choice models owing to their high prediction accuracy. However, a significant body of ML methods, especially the branch of neural networks, is constrained by overfitting and a lack of model interpretability. This study employs a neural network with feature selection for predicting travel mode choices and Shapley additive explanations (SHAP) analysis for model interpretation. A dataset collected in Chengdu, China was used for experimentation. The results reveal that the neural network achieves commendable prediction performance, with a 12% improvement over the traditional multinomial logit model. Also, feature selection using a combined result from two embedded methods can alleviate the overfitting tendency of the neural network, while establishing a more robust model against redundant or unnecessary variables. Additionally, the SHAP analysis identifies factors such as travel expenditure, age, driving experience, number of cars owned, individual monthly income, and trip purpose as significant features in our dataset. The heterogeneity of mode choice behaviour is significant among demographic groups, including different age, car ownership, and income levels.

Aqueous zinc ion batteries (AZIBs) have emerged as promising candidates for large-scale energy storage systems during post lithium-ion era, drawing attention for their environmental-friendliness, cost-effectiveness, high safety, and minimal manufacturing constraints. However, the long-standing roadblock to their commercialization lies in the dendrite growth and parasitic reactions (hydrogen evolution reaction and water-induced corrosion) of the metallic zinc anode, which strongly depends on the complicated interphasial chemistries. This review, with a focus on optimizing the zinc anode/electrolyte interphase, begins by elucidating the intrinsic factor of zinc ions’ migration, diffusion, nucleation, electro-crystallization, and growth of the zinc nucleus in AZIBs, along with the underlying scientific principles. Then the electrochemical theories pertinent to the plating behavior of the interphase is systematically clarified, thereby enriching the understanding of how anode structure and electrolyte design principles relate to the electrode interphase. Accordingly, the rational strategies emphasizing structural engineering of the zinc anode and electrolyte have been summarized and discussed in detail. The mechanisms, advances, drawbacks, and future outlook of these strategies are analyzed for the purpose of fabricating a chemically and electrochemically stable interphase. Finally, the challenging perspectives and major directions of zinc anode are proposed. This review is expected to shed light on developing high-performance Zn anodes for use in sustainable AZIBs.

China is a nation severely impacted by landslide disasters, which poses a great threat to the lives and properties of people in the disaster-affected areas. Landslide susceptibility assessment, as an important tool for landslide risk prediction, is of great significance for disaster mitigation and prevention. However, traditional landslide susceptibility assessment faces the issue of imbalanced data between landslide and non-landslide samples, leading to the inherent undersampling of non-landslide data in the training set. This results in the loss of important information features related to landslide events, thereby affecting the reliability of landslide susceptibility assessment. In this study, using the Zigui-Badong section of the Three Gorges Reservoir Area as an example, 14 evaluation factors, such as elevation and slope were chosen as landslide susceptibility assessment factors, and the original training set and the validation set were divided. In this study, the synthetic minority oversampling technique - Tomek Links (SMOTE-Tomek) method was employed to process the original training dataset, construct the input training set. A convolutional neural networks (CNN) was then trained using this input data, resulting in the SMOTE-Tomek-CNN coupling model. In addition, by intersecting the SMOTE-Tomek method with undersampling methods (random undersampling, RUS), they were separately coupled with the CNN model and support vector machine model (SVM) to form three coupled models: SMOTE-Tomek-SVM, RUS-CNN, and RUS-SVM. These were compared with the SMOTE-CNN coupled model. The results indicate that, among the four coupling models, the SMOTE-CNN coupled model has higher specific class accuracy and area under the ROC curve, with values of 73.60% and 0.965, respectively. This indicates that this method's predictive ability is superior to that of traditional methods, making it a reliable resource for landslide prediction in the studied area.

Abstract Background Some recent studies have shown that female subclinical hypothyroidism (SCH) is associated with diminished ovarian reserve (DOR). In this study, we aimed to investigate whether serum-free thyroxine (fT4) concentrations within the reference range are associated with ovarian reserve in women. Methods This cross-sectional study included 4933 infertile women with normal-range fT4 concentrations who received assisted reproductive technology treatment in our clinic. The data of women in different fT4 concentration tertiles (namely 12–15.33, 15.34–18.67, and 18.68–22 pmol/L) were compared with ovarian reserve markers, namely the anti-Müllerian hormone (AMH) concentration, the antral follicle count (AFC), and the number of aspirated oocytes. The primary outcomes were the AMH concentration and the risk of DOR, diagnosed as an AMH concentration

Abstract Intercropping, a widely adopted agricultural practice worldwide, aims to increase crop yield, enhance plant nutrient uptake, and optimize the utilization of natural resources, contributing to sustainable farming practices on a global scale. However, the underlying changes in soil physio-chemical characteristics and enzymatic activities, which contribute to crop yield and nutrient uptake in the intercropping systems are largely unknown. Consequently, a two-year (2021–2022) field experiment was conducted on the maize/soybean intercropping practices with/without nitrogen (N) fertilization (i.e., N0; 0 N kg ha−1 and N1; 225 N kg ha−1 for maize and 100 N kg ha−1 for soybean ) to know whether such cropping system can improve the nutrients uptake and crop yields, soil physio-chemical characteristics, and soil enzymes, which ultimately results in enhanced crop yield. The results revealed that maize intercropping treatments (i.e., N0MI and N1MI) had higher crop yield, biomass dry matter, and 1000-grain weight of maize than mono-cropping treatments (i.e., N0MM, and N1MM). Nonetheless, these parameters were optimized in N1MI treatments in both years. For instance, N1MI produced the maximum grain yield (10,105 and 11,705 kg ha−1), biomass dry matter (13,893 and 14,093 kg ha−1), and 1000-grain weight (420 and 449 g) of maize in the year 2021 and 2022, respectively. Conversely, soybean intercropping treatments (i.e., N0SI and N1SI) reduced such yield parameters for soybean. Also, the land equivalent ratio (LER) and land equivalent ratio for N fertilization (LERN) values were always greater than 1, showing the intercropping system’s benefits in terms of yield and improved resource usage. Moreover, maize intercropping treatments (i.e., N0MI and N1MI) and soybean intercropping treatments (i.e., N0SI and N1SI) significantly (p

Abstract Background Diarrhea is a leading cause of death in young children worldwide. Vitamin D deficiency impairs the body's ability to clear pathogens, reduces tight junction protein expression in intestinal epithelial cells, and enhances Th1‐mediated intestinal inflammation. This study aimed to investigate the effects of serum vitamin D levels on acute invasive enteritis in children. Methods This prospective cohort study included 82 children aged 1–3 years with clinically diagnosed acute invasive enteritis at Sichuan Maternal and Child Health Hospital from February 2021 to February 2022, alongside a control group of 80 healthy children. Fecal specimens were collected for routine tests and occult blood analysis, while blood samples were taken for routine tests, C‐reactive protein, and 25‐OHD levels. Comparative analyses were performed between groups, and multifactorial logistic regression was used to identify factors influencing invasive enteritis. Results The study group showed significantly lower serum 25‐OHD levels (27.95 ± 9.91 ng/mL) compared to controls (32.76 ± 10.23 ng/mL, p

Abstract Pine wilt disease (PWD) is a devastating plant disease caused by the pinewood nematode (PWN, Bursaphelenchus xylophilus) that is transmitted by several beetle species in the genus, Monochamus. Once present, the disease is difficult to control. Prevention rather than control is regarded as an effective strategy for PWD management. Central to this prevention strategy is the ability to predict the potential distribution of the disease. Here, we employed an integrated MaxEnt and CLIMEX approach to model the potential distribution of PWD under various climate‐change scenarios. Our results indicate that rising temperatures and lower humidity under climate change will render some of the northern regions of China more suitable for the nematode and these beetles, causing the gradual northward movement of PWD. Furthermore, suitable habitats for three pine species, Pinus massoniana, P. taiwanensis and P. shurbergia, overlap with PWN and Monochamus, suggesting that these three species are potentially at high risk of PWD. Thus, PWD management should target the northern regions of China and the three pine species that are most susceptible to PWD.

IntroductionAir flow driven by air-conditioner has a significant impact on the indoor environment, however, the bacterial contamination conditions in the different parts of air-conditioners have not been fully elucidated.MethodsIn this study, we assessed the bacterial pollution in the four parts, including air outlet, filter net, cooling fin and water sink, of ten household air-conditioners quantitatively and qualitatively from Chengdu, southwestern China.ResultsThe microbial cultivation results showed the large total bacterial counts of 5042.0, 9127.6, 6595.1, and 12296.2 CFU/cm2 in air outlet, filter net, cooling fin, and water sink. Furthermore, the sequencing data showed that these four parts displayed different bacterial characteristics. At the level of genus, Caproiciproducens and Acidipropionibacterium were predominant in air outlet. Bacillus, Acinetobacter, Paracoccus, and Corynebacterium were detected as the characteristic bacteria in filter net. For cooling fin, Rhodococcus, Achromobacter, and Nocardioides were the dominant bacteria. The genera of Methylobacterium-Methylorubrum, Brevibacterium, Stenotrophomonas, and Psychrobacter were identified as the bioindicators in water sink. The bioinformatic analysis on the sequencing data illustrated that the bacteria from air-conditioners were associated with metabolic disturbance.DiscussionThis study reveals the distinct bacterial compositions in the different parts of air-conditioner, and provides new clues for the non-negligible bacterial pollution in this common appliance from Chinese households.

IntroductionAcute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment.MethodTo investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment.ResultThe analysis discerned 916 differentially expressed genes in moderate/severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators.DiscussionThis study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19.

BackgroundPersistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology.MethodsFrom November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology.ResultsIn the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45–49 and 60–65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015–2017 to 7.0% in 2020–2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group.ConclusionThe study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.

Abstract Background Intrahospital transport of critically ill patients is a common practice in intensive care units (ICUs), where patients’ safety is constantly challenged in high-intensity and dynamic environments. While Intrahospital Transport Safety Scale (IHTSS) is widely used internationally to evaluate the intrahospital transport safety, it has not been introduced in China. Objectives This study aimed to assess the reliability and validity of the Chinese version of the IHTSS scale among critical care nurses in China. Methods A cross-sectional study was conducted using a cluster sampling method. A total of 544 critical care nurses from 25 ICUs in 10 tertiary hospitals were recruited. We employed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to examine the questionnaire’s underlying factor structure, ensuring construct validity. Additionally, internal consistency was assessed using Cronbach’s alpha coefficient, test-retest reliability, and corrected item-total correlation. Results The Chinese version of the scale displayed robust psychometric properties, with a Cronbach’s α coefficient of 0.976, a split-half reliability of 0.906, and a test-retest reliability of 0.856. EFA revealed a robust four-factor model that accounted for 75.970% of the variance, with the factor loadings of the items ranging from 0.433 to 0.951. CFA indicated a strong model fit, with a chi-square to degrees of freedom ratio (CMIN/DF) of 2.765, comparative fit index (CFI) of 0.943, incremental fit index (IFI) of 0.943, and goodness-of-fit index (GFI) of 0.845, supporting the efficacy of the four-factor model in assessing intrahospital transport safety for critically ill patients. Conclusion The Chinese version of the IHTSS demonstrated favourable reliability and validity among critical care nurses in China, making it a suitable tool for measuring the level of intrahospital transport safety for critically ill patients.

Abstract We aimed to identify different trajectories of remnant cholesterol (RC) and investigate the association of RC trajectories with vascular endothelial function and atherosclerosis progression in a longitudinal cohort of the Chinese population. A total of 521 participants were included in the flow-mediated vasodilation (FMD) subcohort study, and 7775 participants were included in the brachial-ankle pulse wave velocity (baPWV) subcohort study. All participants had ≥ 3 medical examinations during the 10-year follow-up period. In the FMD subcohort study, three distinct RC trajectories were identified according to the RC range and changing pattern over time: “low” (57.58%), “moderate” (30.90%) and “high” (11.52%). The proportion of the three groups with vascular endothelial dysfunction (FMD 1400 cm/s) was 38.79%, 51.26% and 59.01% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.46 and 2.16 times the odds of atherosclerosis (P

Abstract Background Some studies have suggested that hepatitis B virus (HBV) infection had a negative association with semen quality, but the conclusions have been inconsistent. The purpose of our study was to systematically assess the association between HBV infection and semen parameters. Methods We searched electronic databases for studies published from January 1980 to August 2023. Eleven studies were included in the analysis. Primary outcomes were semen volume, sperm concentration, sperm morphology, sperm motility and sperm progressive motility. We also conducted a subgroup analysis between China and other countries. Result Compared with the semen quality of HBV-negative men, HBV infection had a negative association with semen volume (MD: −0.20 mL, 95%CI: −0.32 to − 0.09, P = 0.0004), sperm concentration (MD: −4.46 × 106/mL, 95%CI: −7.09 to − 1.84, P = 0.0009), sperm morphology (MD: −2.49%, 95%CI: −4.35 to − 0.64, P = 0.008), sperm motility (MD: −6.85%, 95%CI: −11.53 to − 2.18, P = 0.004), and sperm progressive motility (MD: −6.63%, 95%CI: −10.24 to − 3.02, P = 0.0003). However, HBV infection had no significant association with total sperm count (MD: −31.50 × 106, 95%CI: −74.11 to 11.10, P = 0.15). The association between HBV and semen quality were inconsistent between the subgroups. Conclusion HBV infection had a negative association with sperm concentration, motility, morphology, and semen volume. However, The association between HBV and total sperm count remain unclear. This metaanalysis suggests that we should pay attention to the adverse effect of HBV on sperm quality, and several studies have reported the relevant mechanisms. But due to the significant heterogeneity among studies on some semen parameters, further large and well-designed researches are needed before introducing clinical management recommendations.

Breast cancer ranks the first in the incidence of female cancer and is the most common cancer threatening the life and health of women worldwide.Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) is a pro-apoptotic gene downstream of p53. However, the role of TP53AIP1 in BC needs to be investigated. In vitro and in vivo experiments were conducted to assess the biological functions and associated mechanisms. Several bioinformatics analyses were made, CCK8 assay, wound healing, transwell assays, colony formation assay, EDU, flow cytometry, Immunofluorescence, qRT-PCR and Western-blotting were performed. In our study, we discovered that BC samples had low levels of TP53AIP1 expression, which correlated with a lower survival rate in BC patients. When TP53AIP1 was up-regulated, it caused a decrease in cell proliferation, migration, and invasion. It also induced epithelial-to-mesenchymal transition (EMT) and protective autophagy. Furthermore, the over-expression of TP53AIP1 suppressed tumor growth when tested in vivo. We also noticed that TP53AIP1 up-regulation resulted in decreased levels of phosphorylation in AKT and mTOR, suggesting a mechanistic role. In addition, we performed functional rescue experiments where the activation of AKT was able to counteract the impact of TP53AIP1 on the survival and autophagy in breast cancer cell lines. This suggests that TP53AIP1 acts as an oncogene by controlling the AKT/mTOR pathway. These findings reveal TP53AIP1 as a gene that suppresses tumor growth and triggers autophagy through the AKT/mTOR pathway in breast cancer cells. As a result, TP53AIP1 presents itself as a potential target for novel therapeutic approaches in treating breast cancer.

Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.

Objective Non-malignant pleural effusions (NMPE) are common in hospitalised patients. Data on NMPE inpatients are scarce and the factors influencing the prognosis are unknown.Design This was a retrospective cohort study.Setting and participants We conducted a retrospective cohort of inpatients (n=86 645) admitted to the Chinese PLA General Hospital from 2018 to 2021, based on electronic medical records. The observations of 4934 subjects with effusions confirmed by chest radiological tests (CT or X-ray) without a diagnosis of malignancy were followed during admission. Logistic regression was used to analyse organ damage and other factors associated with in-hospital death. Patients were clustered according to their laboratory indicators, and the association between the clustering results and outcomes was studied.Outcome The outcome of this study was in-hospital mortality.Results Among 4934 patients, heart failure + pneumonia + renal dysfunction was the most common (15.12%) among 100 different diagnostic groups. 318 (6.4%) patients died during hospitalisation. Lung (OR 3.70, 95% CI 2.42 to 5.89), kidney (OR 2.88, 95% CI 2.14 to 3.90) and heart (1.80, 95% CI 1.29 to 2.55) damage were associated with in-hospital mortality. Hierarchical clustering of laboratory indicators (estimated glomerular filtration rate, white blood cell count, platelet count, haemoglobin, N-terminal pro-B-type natriuretic peptide, serum albumin) demonstrated the ability to discriminate patients at high risk of in-hospital death.Conclusion Comorbidities and multiorgan failure are the prominent characteristics of NMPE patients, which increase the risk of in-hospital mortality, and comprehensive intervention for specific comorbidity patterns is suggested.

IntroductionThe influence of excess weight on the development of children's feet remains a subject of debate. To further elucidate whether this relation occurs, this study compared arch morphology and flexibility in three groups of children: underweight, normal, and overweight.MethodsIn total, 1,532 children (807 boys, 725 girls; age range 7–11 years) participated in the study. The researchers measured the participants’ height and weight, calculated their body mass index, and categorized their weight status as underweight, normal weight, or overweight. A three-dimensional foot model was taken using a three-dimensional plantar scanner under non-weight-bearing and weight-bearing conditions to obtain arch morphometric indices (arch index and arch volume) and arch flexibility index (arch volume index).ResultsAnalysis of the data showed that the arch index was higher in overweight children compared to underweight and normal weight children (p 0.05). All children were divided into flatfoot, normal, and pes cavus groups according to arch index, and the arch volume index was statistically significant (p

BackgroundWith the remarkable effect of controlling the increase in drug costs by the first batch of National Key Monitoring and Rational Use Drugs (first NKMRUDs), the National Health Commission of the People’s Republic of China releases the second NKMRUDs to further strengthen the reasonable use of drugs. Unfortunately, the second NKMRUDs include some drugs of National Volume-based Procurement and National Essential Medicines, which challenges the management of pharmaceutical affairs on the three kinds of drugs.ObjectiveThe main objective of this study was to investigate the prevalence of the second NKMRUDs and explore their monitoring indicators.MethodsAn adapted WHO methodology for point prevalence surveys was conducted for the second NKMRUDs. For the monitoring indicators, we sought to explore whether the defined daily dose (DDD) and days of therapy (DOT) can be suitable for the second NKMRUDs through comparing differences between DDD and DOT with the prescribed daily dose (PDD).ResultsAmong the 935 included patients, 29.20% of the patients received at least one of the second NKMRUDs. A total of 273 patients were administered with 487 times of the second NKMRUDs. Among them, 162 , 62 , and 49 patients were receiving one, two, and three or more agents, respectively. The most commonly prescribed second NKMRUDs were compound amino acids, budesonide, and ceftazidime. The total DDDs and DOTs of the second NKMRUDs were 3360.68 and 1819.80, respectively, with the PDDs of 1865.26. The deviations (80.17%) of DDDs from PDDs were significantly greater than those (−2.44%) of DOTs.ConclusionThe prevalence of the second NKMRUDs was obtained by using the adapted PPS methodology at a tertiary university hospital. The DOT indicator is found to more accurately reflect actual consumption than the DDD indicator for second NKMRUDs. It is recommended to use the DOT indicator to monitor second NKMRUDs.

Summary: Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC. Methods: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan–Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135. Findings: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48–1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41–0.66, p

The hiding capacity of the current information hiding field has reached a relatively high level, which can hide two color images into one color image. In order to explore a larger hidden capacity, an information hiding scheme based on an improved FCdDNet is proposed, which can hide large-size color images into small-size color images. An improved FCdDNet network is used as the main structure shared by the hidden network and the extraction network. These two networks promote and improve each other during the confrontation training process and are used in pairs. It can be seen that the proposed scheme achieves a larger information hiding capacity, and the hidden information is four times larger than the scale of the carrier image. At the same time, the visual effect after hiding is guaranteed, and the image extracted from the hidden image also has a high degree of restoration. The scheme can be applied to image authentication, secret image transmission, and other fields.

ABSTRACT Phages and bacteria have a long history of co-evolution. However, these dynamics of phage-host interactions are still largely unknown; identification of phage inhibitors that remodel host metabolism will provide valuable information for target development for antimicrobials. Here, we perform a comprehensive screen for early-gene products of ΦNM1 that inhibit cell growth in Staphylococcus aureus. A small membrane protein, Gp11, with inhibitory effects on S. aureus cell division was identified. A bacterial two-hybrid library containing 345 essential S. aureus genes was constructed to screen for targets of Gp11, and Gp11 was found to interact with MurG and DivIC. Defects in cell growth and division caused by Gp11 were dependent on MurG and DivIC, which was further confirmed using CRISPRi hypersensitivity assay. Gp11 interacts with MurG, the protein essential for cell wall formation, by inhibiting the production of lipid II to regulate peptidoglycan (PG) biosynthesis on the cell membrane. Gp11 also interacts with cell division protein DivIC, an essential part of the division machinery necessary for septal cell wall assembly, to disrupt the recruitment of division protein FtsW. Mutations in Gp11 result in loss of its ability to cause growth defects, whereas infection with phage in which the gp11 gene has been deleted showed a significant increase in lipid II production in S. aureus. Together, our findings reveal that a phage early-gene product interacts with essential host proteins to disrupt PG biosynthesis and block S. aureus cell division, suggesting a potential pathway for the development of therapeutic approaches to treat pathogenic bacterial infections.IMPORTANCEUnderstanding the interplay between phages and their hosts is important for the development of novel therapies against pathogenic bacteria. Although phages have been used to control methicillin-resistant Staphylococcus aureus infections, our knowledge related to the processes in the early stages of phage infection is still limited. Owing to the fact that most of the phage early proteins have been classified as hypothetical proteins with uncertain functions, we screened phage early-gene products that inhibit cell growth in S. aureus, and one protein, Gp11, selectively targets essential host genes to block the synthesis of the peptidoglycan component lipid II, ultimately leading to cell growth arrest in S. aureus. Our study provides a novel insight into the strategy by which Gp11 blocks essential host cellular metabolism to influence phage-host interaction. Importantly, dissecting the interactions between phages and host cells will contribute to the development of new and effective therapies to treat bacterial infections.

BackgroundOvertreatment design of clear aligner treatment (CAT) in extraction cases is currently primarily based on the clinical experience of orthodontists and is not supported by robust evidence on the underlying biomechanics. This study aimed to investigate the biomechanical effects of overtreatment strategies involving different maxillary anterior teeth intrusion patterns during anterior teeth retraction by CAT in extraction cases.Materials and methodsA finite element model of the maxillary dentition with the first premolar extracted was constructed. A loading method of clear aligners (CAs) based on the initial state field was proposed. The iterative method was used to simulate the long-term orthodontic tooth movement under the mechanical load exerted by the CAs. Three groups of CAs were utilized for anterior teeth retraction (G0: control group; G1: incisors intrusion group; G2: anterior teeth intrusion group). Tooth displacement and occlusal plane rotation tendency were analyzed.ResultsIn G0, CAT caused lingual tipping and extrusion of the incisors, distal tipping and extrusion of the canines, mesial tipping, and intrusion of the posterior teeth. In G1, the incisors showed minimal extrusion, whereas the canines showed increased extrusion and distal tipping tendency. G2 showed the smallest degree of posterior occlusal plane angle rotation, while the inclination tendency of the canines and second premolars decreased.Conclusion1. In CAT, tooth displacement tendency may change with increased wear time. 2. During anterior teeth retraction, the incisor intrusion pattern can provide effective vertical control for the lateral incisors but has little effect on the central incisors. Anterior teeth intrusion patterns can alleviate the inclination of canines and second premolars, resulting in partial relief of the roller-coaster effect.

AimThis study was aimed to summarize the complications and their management associated with XEN gel stent implantation.MethodsA systematic review of literature was conducted using Medline (via PubMed), EMBASE, the Cochrane Library databases, and China National Knowledge Infrastructure, from their inception to February 1, 2024.ResultsA total of 48 studies published between 2017 and 2024 were identified and included in the systematic review, including 16 original studies (retrospective or prospective clinical studies), 28 case reports, and 4 case series, which followed patients for up to 5 years. Early postoperative complications of XEN gel stent implantation include hypotony maculopathy (1.9–4.6%), occlusion (3.9–8.8%), suprachoroidal hemorrhage (SCH), choroidal detachment (0–15%), conjunctival erosion, and exposure of the XEN gel stent (1.1–2.3%), wound and bleb leaks (2.1%) and malignant glaucoma (MG) (2.2%). Mid-postoperative complications of XEN gel stent implantation included migration of XEN (1.5%), ptosis (1.2%), endophthalmitis (0.4–3%), macular edema (1.5–4.3%), hypertrophic bleb (8.8%) and subconjunctival XEN gel stent fragmentation (reported in 2 cases). Late postoperative complications reported in cases included spontaneous dislocation and intraocular degradation.ConclusionXEN gel stent implantation is a minimally invasive glaucoma surgery (MIGS) procedure for glaucoma, known for its potential to minimize tissue damage and reduce surgical duration. However, it is crucial to note that despite these advantages, there remains a risk of severe complications, including endophthalmitis, SCH, and MG. Therefore, postoperative follow-up and early recognition of severe complications are essential for surgical management.

Abstract Objective The aim of this study was to assess the accuracy and test-retest reliability of a wearable inertial measurement unit (IMU) system for gait analysis in healthy female compared to a gold-standard optoelectronic motion capture (OMC) system. Methods In our study, we collected data from 5 healthy young females. Participants were attached with markers from both the OMC system and the IMU system simultaneously. Data was collected when participants walked on a 7 m walking path. Each participant performed 50 repetitions of walking on the path. To ensure the collection of complete gait cycle data, a gait cycle was considered valid only if the participant passed through the center of the walking path at the same time that the OMC system detected a valid marker signal. As a result, 5 gait cycles that met the standards of the OMC system were included in the final analysis. The stride length, cadence, velocity, stance phase and swing phase of the spatio-temporal parameters were included in the analysis. A generalized linear mixture model was used to assess the repeatability of the two systems. The Wilcoxon rank-sum test for continuous variables was used to compare the mean differences between the two systems. For evaluating the reliability of the IMU system, we calculated the Intra-class Correlation Coefficient (ICC). Additionally, Bland-Altman plots were used to compare the levels of agreement between the two systems. Results The measurements of Spatio-temporal parameters, including the stance phase (P = 0.78, 0.13, L-R), swing phase (P = 0.78, 0.13, L-R), velocity (P = 0.14, 0.13, L-R), cadence (P = 0.53, 0.22, L-R), stride length (P = 0.05, 0.19, L-R), by the IMU system and OMC system were similar. Which suggested that IMU and OMC systems could be used interchangeably for gait measurements. The intra-rater reliability showed an excellent correlation for the stance phase, swing phase, velocity and cadence (Intraclass Correlation Coefficient, ICC > 0.9) for both systems. However, the correlation of stride length was poor (ICC = 0.36, P = 0.34, L) to medium (ICC = 0.56, P = 0.22, R). Additionally, the measurements of IMU systems were repeatable. Conclusions The results of IMU system and OMC system shown good repeatability. Wearable IMU system could analyze gait data accurately. In particular, the measurement of stance phase, swing phase, velocity and cadence showed excellent reliability. IMU system provided an alternative measurement to OMC for gait analysis. However, the measurement of stride length by IMU needs further consideration.

This work explores water-to-air optical wireless communication (W2A-OWC) transmission schemes and realizes a prototype of real-time W2A-OWC system based on field programmable gate array. This prototype comprises underwater nodes, aerial nodes, and transmitter-receiver hardware circuits. The real-time system employs multiple-input multiple-output technique and the low density parity check (LDPC) code of 5G-new radio for dynamic W2A-OWC. Additionally, the impact of background radiation is mitigated through spatial optical filtering. To validate the practical feasibility of the system, experiments are conducted in both indoor water tank and outdoor deep pool under strong background radiation. The frame error rate of the real-time system is tested under different LDPC code rates and transmitter-receiver configurations. The experimental results verify the feasibility of the realized W2A-OWC system.

Abstract Background Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. Methods IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. Results Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. Conclusion The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

Abstract Background Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field. Case presentation A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted. Conclusion This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.

Abstract Background and objectives In anterior cruciate ligament reconstruction, the strength of the graft was found to be unsatisfactory usually the anterior half of the peroneus longus tendon was taken for supplementation, but the effect on foot and ankle function and gait in the donor area is unclear. This study aims to explore the changes in the ankle and gait after using the harvested anterior half of the peroneus longus tendon as a reconstruction graft for the anterior cruciate ligament. Methods A total of 20 patients, 6 males and 14 females, aged 18 to 44 years, with unilateral anterior cruciate ligament injuries, underwent reconstruction using the harvested anterior half of the peroneus longus tendon as a graft between June 2021 and December 2021. The part on which the anterior half of the peroneus longus tendon was harvested was considered the experimental group, while the contralateral foot was the control group. At the 6-month follow-up, the Lysholm knee score, AOFAS ankle score, and gait-related data (foot length, arch index, arch volume, arch volume index, and gait cycle parameters: percentage of time in each gait phase, step frequency, step length, foot strike angle, and push-off angle) were assessed using a 3D foot scanner and wearable sensors for both groups. Results All 20 patients completed the six-month follow-up. There were no statistically significant differences between the experimental and control groups regarding knee scores, ankle scores, foot length, arch index, arch volume, arch volume index, step frequency, and step length (P > 0.05). However, there were statistically significant differences between the experimental and control groups in terms of the gait cycle parameters, including the percentage of time in the stance, mid-stance, and push-off phases, as well as foot strike angle and push-off angle (P

Abstract Background Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome. Methods Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group. Results All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures. Conclusion Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.

Abstract Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application. Graphical Abstract

Abstract Objective To evaluate the performance of existing sepsis scores for prediction of adverse outcomes in children with cancer admitted to the ICU with suspected sepsis. Design Retrospective chart review using data available at 1, 6, 12, and 24 h after ICU admission to calculate the Pediatric Risk of Mortality 3 (PRISM‐3), Pediatric Sequential Organ Failure Assessment (pSOFA), Paediatric Logistic Organ Dysfunction 2 (PELOD‐2), and Quick Pediatric Sequential Organ Failure Assessment (qSOFA) scores. Area under the receiver operator characteristic curve (AUROC) was used to evaluate performance for prediction of attributable mortality. Sensitivity analyses included recalculation of scores using worst preceding values for each variable, excluding hematologic parameters, and prediction of alternative outcomes. Setting St. Jude Children's Research Hospital, a pediatric comprehensive cancer center in the USA. Patients Pediatric patients (

AIM: To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography (OCTA) in ischemic branch retinal vein occlusion (BRVO) patients with macular edema (ME) after anti-vascular endothelial growth factor (VEGF) treatment. METHODS: In this retrospective analysis, data from 60 patients (60 eyes) with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography (FFA) were studied. The eyes with ME according to spectral domain optical coherence tomography (SD-OCT) underwent intravitreal conbercept (IVC) and 3+pro re nata (PRN) regimen. The injection times were recorded. Two weeks after injection, fundus laser photocoagulation was performed in the non-perfusion area of the retina. The patients were followed up once a month for 6mo. The best-corrected visual acuity (BCVA), foveal avascular zone (FAZ), and A-circularity index (AI), at 6mo and the baseline were compared. RESULTS: All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR (P

Introduction: Advanced paternal age of reproduction is an increasing trend, especially in developed countries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fertility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging-associated molecular and cellular alterations in testicular tissue is still missing. Objectives: We aimed to dissect aging-associated molecular characteristics in testes of mice. Methods: Single-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to characterize aging-associated phenotypes and verify single cell sequence results. Results: Here, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased ‘senescence-associated secretory phenotype’ and ‘inflammation’, which were major aging-associated characteristics. Further analysis of aging-related differentially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging. Conclusion: Taken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type-specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility.

Objective: This study designed experiments to explore the effects of ischemic preconditioning (IPC) intervention with different cycling periods on the upper limb strength performance of college male bodybuilding athletes. Methods: Ten bodybuilding athletes were recruited for a randomized, double-blind, crossover experimental study. All subjects first underwent pre-tests with two sets of exhaustive bench presses at 60% of their one-repetition maximum (1RM) to assess upper limb strength performance. They then experienced three different IPC intervention modes (T1: 1 × 5 min, T2: 2 × 5 min, T3: 3 × 5 min), as well as a non-IPC intervention mode (CON), followed by a retest of the bench press. An Enode pro device was used to record the barbell’s velocity during the bench press movement (peak velocity (PV), mean velocity (MV)); power (peak power (PP), mean power (MP)); and time under tension (TUT) to evaluate upper limb strength performance. Results: PV values: T1 showed significant increases compared to pre-tests in the first (p = 0.02) and second (p = 0.024) tests, and were significantly greater than the CON (p = 0.032); T2 showed a significant increase in PV in the first test (p = 0.035), with no significant differences in other groups. MV values: T1 showed a significant increase in MV in the first test compared to the pre-test (p = 0.045), with no significant differences in other groups. PP values: T1 showed a highly significant increase in PP in the first test compared to the pre-test (p = 0.001), and was significantly higher than the CON (p = 0.025). MP values: T1 showed highly significant increases in MP in both the first (p = 0.004) and second (p = 0.003) tests compared to the pre-test; T2 showed a highly significant increase in MP in the first test (p = 0.039) and a significant increase in the second test (p = 0.039). T1’s MP values were significantly higher than the CON in both tests; T2’s MP values were significantly higher than the CON in the first (p = 0.005) and second (p = 0.024) tests. TUT values: T1 showed highly significant increases in TUT in the first (p < 0.001) and second (p = 0.002) tests compared to the pre-test, and were significantly higher than the CON. Conclusions: (1) Single-cycle and double-cycle IPC interventions both significantly enhance upper limb strength performance, significantly improving the speed and power in exhaustive bench press tests, with the single-cycle IPC intervention being more effective than the double-cycle IPC intervention. (2) The triple-cycle IPC intervention does not improve the upper limb strength performance of bodybuilding athletes in exhaustive bench presses.

OsNRAMP5 is a pivotal gene involved in the uptake and transport of cadmium and manganese in rice plants. While the knockout of OsNRAMP5 has significantly decreased cadmium accumulation in rice grains, its impact on the adaptability of indica hybrid rice and its paternal parent still needs to be more adequately explored. This study conducted a three-year field experiment with two of the OsNRAMP5 knockout lines (indica hybrid rice LYDG-1 and its paternal parent DG-1) and their wild-type at four distinct locations in the middle reaches of the Yangtze River. Their adaptability was evaluated by cadmium and manganese accumulation, yield traits, and grain quality. The findings reveal that OsNRAMP5 knockout lines, when grown in mildly and moderately Cd-contaminated paddies, exhibit significantly and stably lower cadmium and manganese accumulation compared with the wild-type. However, there were no significant differences in cadmium and manganese content between LYDG-1 and DG-1. Regarding yield traits, OsNRAMP5 knockout lines did not show a significant reduction compared with the wild-type, except for DG-1 in soil with lower manganese content. For grain quality, the quality of the appearance of OsNRAMP5 knockout lines significantly improved compared with the wild-type. However, the milling quality of DG-1 significantly reduced compared with the wild-type, while this negative impact for LYDG-1 was only observed in soils with lower manganese content. Overall, the indica hybrid rice with an OsNRAMP5 knockout exhibits better adaptability than its paternal parent in the middle reaches of the Yangtze River. These findings offer valuable insights into the potential application and promotion of OsNRAMP5 mutant rice varieties in the middle reaches of the Yangtze River.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19–induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24− cells among CD19+ B cells (termed ‘plasmablasts’ for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Objective: To investigate the impact of extreme climate on geological disasters in Shanxi and propose effective disaster prevention and mitigation strategies. Methods: Using daily temperature and precipitation data from 27 meteorological stations in Shanxi Province from 1975 to 2020, 32 extreme climate indices were calculated. Combined with geological disaster site data, the distribution characteristics of extreme climates and their relationship with geological disasters were analyzed, and a regression model for geological disaster risk zones was constructed. Results: Sixteen extreme climate indices in Shanxi Province showed significant changes, especially TMAXmean (100% significant). Indices related to negative precipitation effects showed a declining trend, with 77.78% being significant, while 96.3% of positive temperature effect indices showed an increasing trend, with 73.6% being significant. Geological disaster hotspots were concentrated in the mid-altitude (500–1500 m) hilly and low mountain areas along the central north–south axis and on Q and Pz strata. Extreme high-temperature indices were significantly positively correlated with geological disaster hotspots, while extreme low-temperature indices were negatively correlated. Indices related to extreme heavy precipitation (e.g., R99p.Slope, RX5day.Slope) were associated with an increase in geological disaster hotspots, whereas higher total precipitation and frequent heavy precipitation events were associated with a decrease in disaster hotspots. The grey relational degree between the Z-score and TXn.Slope, TXx.Slope, GSL.Slope, and TX90P.Slope was greater than 0.8. The random forest model performed best in evaluation metrics such as MAE, RMSE, and R2. Conclusions: Shanxi is likely to experience more extreme high-temperature and precipitation events in the future. The low-altitude hilly and terraced areas in Zones III and VII are key regions for geological disaster prevention and control. High temperatures and extreme rainfall events generally increase the disaster risk, while higher total precipitation reduces it. The random forest model is the optimal tool for predicting geological disaster risks in Shanxi Province.

Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.

In the field of computer-assisted medical diagnosis, developing medical image segmentation models that are both accurate and capable of real-time operation under limited computational resources is crucial. Particularly for skin disease image segmentation, the construction of such lightweight models must balance computational cost and segmentation efficiency, especially in environments with limited computing power, memory, and storage. This study proposes a new lightweight network designed specifically for skin disease image segmentation, aimed at significantly reducing the number of parameters and floating-point operations while ensuring segmentation performance. The proposed ConvStem module, with full-dimensional attention, learns complementary attention weights across all four dimensions of the convolution kernel, effectively enhancing the recognition of irregularly shaped lesion areas, reducing the model’s parameter count and computational burden, thus promoting model lightweighting and performance improvement. The SCF Block reduces feature redundancy through spatial and channel feature fusion, significantly lowering parameter count while improving segmentation results. This paper validates the effectiveness and robustness of the proposed SCSONet on two public skin lesion segmentation datasets, demonstrating its low computational resource requirements. https://github.com/Haoyu1Chen/SCSONet.

IntroductionContinuous cropping challenges have gradually emerged as pivotal factors limiting the sustainable development of agricultural production. Allelopathicals are considered to be the primary obstacles. However, there is limited information on allelopathic accumulation across various continuous cropping years and its correlation with the associated challenges.MethodsTobacco was subjected to varying planting durations: 1 year (CR), 5 years (CC5), 10 years (CC10), and 15 years (CC15).ResultsOur findings unveiled discernible disparities in tobacco growth patterns across diverse continuous cropping periods. Notably, the most pronounced challenges were observed in the CC5 category, characterized by yield reduction, tobacco black shank outbreaks, and a decline in beneficial flora. Conversely, CC15 exhibited a substantial reduction in challenges as the continuous cropping persisted with no significant differences when compared to CR. Within the tobacco rhizosphere, we identified 14 distinct allelopathic compounds, with 10 of these compounds displaying noteworthy variations among the four treatments. Redundancy analysis (RDA) revealed that eight allelopathic compounds exhibited autotoxic effects on tobacco growth, with MA, heptadecanoic acid, and VA ranking as the most potent inhibitors. Interaction network highlighted the pivotal roles of VA and EA in promoting pathogen proliferation and impeding the enrichment of 13 beneficial bacterial genera. Furthermore, a structural equation model elucidated that MA and EA primarily exert direct toxic effects on tobacco, whereas VA fosters pathogen proliferation, inhibits the enrichment of beneficial bacteria, and synergistically exacerbates the challenges associated with continuous cropping alongside EA.DiscussionThese findings suggested discernible disparities in tobacco growth patterns across the various continuous cropping periods. The most pronounced challenges were observed in CC5, whereas CC15 exhibited a substantial reduction in challenges as continuous cropping persisted. VA may play a pivotal role in this phenomenon by interacting with pathogens, beneficial bacterial genera, and EA.

Background: Yi-Qi-Jian-Pi Formula (YQJPF) is a herbal medicine that is used to treat patients with liver failure. However, scientific evidence supporting the treatment of hepatic fibrosis with YQJPF has not been forthcoming. The present study aimed to determine the mechanisms underlying the anti-fibrotic effects of YQJPF in mouse models of hepatic fibrosis. Methods: Mice were randomly assigned to control, hepatic fibrosis model, silymarin (positive treated), and low-, medium- and high-dose YQJPF (7.5, 15, and 30 g/kg, respectively) groups. Liver function, inflammatory cytokines, and oxygen stress were analyzed using ELISA kits. Sections were histopathologically stained with hematoxylin-eosin, Masson trichrome, and Sirius red. Macrophage polarization was measured by flow cytometry and immunofluorescence. Potential targets of YQJPF against hepatic fibrosis were analyzed by network pharmacology of Chinese herbal compound and the effects of YQJPF on the transforming growth factor-beta (TGF-β)/Suppressor of Mothers against Decapentaplegic family member 3 (Smad3) signaling pathway were assessed using qRT-PCR and immunohistochemical staining. Finally, metagenomics and LC-MS/MS were used to detect the intestinal flora and metabolites of the mice, and an in-depth correlation analysis was performed by spearman correlation analysis. The data were compared by one-way ANOVA and least significant differences (LSDs) or ANOVA-Dunnett's T3 method used when no homogeneity was detected. Results: We induced hepatic fibrosis using CCl4 to establish mouse models and found that YQJPF dose-dependently increased body weight, improved liver function, and reversed hepatic fibrosis. Elevated levels of the pro-inflammatory factors IL-1β, IL-6, and TNF-α in the model mice were substantially decreased by YQJPF, particularly at the highest dose. Levels of serum malondialdehyde and superoxide dismutase (SOD) activity were elevated and reduced, respectively. The malondialdehyde concentration decreased and SOD activity increased in the high-dose group. M1 polarized macrophages (CD86) in the mouse models were significantly decreased and M2 polarization was mildly decreased without significance. However, high-dose YQJPF increased the numbers of M2 macrophages and inhibited TGF-β/Smad3 signaling. Metagenomic and non-targeted metabolomics detection results showed that YQJPF could regulate intestinal homeostasis, and Spearman correlation analysis showed that the abundance of Calditerrivibrio_nitroreducens was significantly negatively correlated with 18β-glycyrrhetinic acid. It is suggested that Calditerrivibrio_nitroreducens may reduce the anti-fibrosis effect of licorice and other Chinese herbs by digesting 18β-glycyrrhetinic acid. Conclusions: YQJPF can reverse liver fibrosis by inhibiting inflammation, suppressing oxidative stress, regulating the immunological response initiated by macrophages, inhibiting TGF-β/Smad3 signaling and regulating intestinal flora homeostasis. Therefore, YQJPF may be included in clinical regimens to treat hepatic fibrosis.

BackgroundCardiovascular diseases remain a leading cause of morbidity and mortality worldwide. Accurately predicting the 10-year risk of Atherosclerotic Cardiovascular Disease (ASCVD) is crucial for timely intervention and management. This study aimed to evaluate the predictive performance of six anthropometric indices in assessing the 10-year ASCVD risk.MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) database (1999–2018), the study involved 11,863 participants after applying exclusion criteria. Six anthropometric indices—waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and waist-to-height0.5 ratio (WHT.5R)—were calculated. The 10-year ASCVD risk was assessed using the 2013 ACC/AHA guidelines & pooled cohort equations model. Participants were divided into two groups based on an ASCVD risk threshold of 7.5%. Statistical analysis included chi-square tests, odds ratios, and receiver operating characteristic (ROC) curves.ResultsThe study found significant differences in baseline characteristics between participants with ASCVD risk less than 7.5% and those with a risk greater than or equal to 7.5%, stratified by gender. In both male and female groups, individuals with higher ASCVD risk exhibited higher age, waist circumference, BMI, and a higher prevalence of health-compromising behaviors. ABSI emerged as the most accurate predictor of ASCVD risk, with the highest area under the curve (AUC) values in both genders. The optimal cut-off values for ABSI was established for effective risk stratification (cut-off value = 0.08).ConclusionThe study underscores the importance of anthropometric indices, particularly ABSI, in predicting the 10-year risk of ASCVD. These findings suggest that ABSI, along with other indices, can be instrumental in identifying individuals at higher risk for ASCVD, thereby aiding in early intervention and prevention strategies.

The rock mass rating (RMR) system plays a crucial role in geomechanics assessments for tunnel projects. However, conventional methods combining empirical and geostatistical approaches often yield inaccuracies, particularly in areas with weak strata such as faults and karst caves. To address these uncertainties and errors inherent in empirical techniques, we propose a progressive RMR prediction strategy based on the Bayesian framework. This strategy incorporates three key components: 1) Variogram modeling: utilizing observational data from the excavation face, we construct and update a variogram model to capture the spatial variability of RMR. 2) TSP-RMR statistic model: we integrate a TSP-RMR statistical model into the Bayesian sequential update process. 3) Bayesian maximum entropy (BME) integration: the BME method combines geological information obtained from tunnel surface excavation with tunnel seismic prediction (TSP) data, ultimately enhancing the RMR prediction accuracy. Our methodology is applied to the Laoying rock tunneling project in Yunnan Province, China. Our findings demonstrate that the fusion of soft data and geological interpretation significantly improves the accuracy of RMR predictions. At selected prediction points, the relative error of our method is less than 15% when compared to the traditional Kriging method. This approach holds substantial potential for advancing RMR estimation ahead of tunnel excavation, particularly when advanced geological forecast data are available.