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Abstract This study investigates the precision measurement of the CKM matrix element |V cb | through semileptonic WW events at future Higgs factories, i.e., FCC-ee, ILC, C3, and CEPC. We use full detector simulation to generate the WW → ℓνcb signal events and various backgrounds at s $$ \sqrt{s} $$ = 240 GeV with unpolarized beams. The relative statistical uncertainties of |V cb | are projected to be 0.91% for the muon channel and 1.2% for the electron channel, assuming a baseline integrated luminosity of 5 ab−1. The sensitivities at other Higgs factory scenarios are also projected. Possible contributors to systematic uncertainties are discussed, with the most prominent one being the systematics of flavor-tagging and mistagging rates. Combining with WW threshold runs, the relative systematic uncertainty can be further reduced.

Abstract Urinary incontinence (UI) in females is a prevailing condition that affects individuals across various age groups and is not limited to older females. The presence of serum alpha-Klotho (α-klotho) serves as a reliable biomarker to indicate the effects of antiaging. Nevertheless, the scientific research on the association between α-klotho and UI remains limited. Therefore, the purpose of this study is to investigate and evaluate the connection between α-klotho levels and the UI among females in the US. We utilized data from the National Health and Nutrition Examination Survey 2007–2016 to investigate the potential connection between α-klotho levels and the UI among females aged 40 to 79. Weighted linear regression models and sensitivity tests were conducted to explore the correlation. 2628 females were involved in this study, representing 22,492,348 non-institutionalized residents in the US. The mean age was 53.9 ± 0.2 years and the mean level of α-klotho was 873.0 ± 8.9 pg/mL. After adjusting for relevant covariables, weighted linear regression models revealed that individuals with severe UI exhibited significantly lower serum α-klotho levels (β = − 100.66; 95% CI: − 156.31, − 45.01; P

Abstract Background There are various frailty assessment tools in the world, and the application choice of frailty assessment tools for the elderly perioperative population varies. It remains unclear which frailty assessment tool is more suitable for the perioperative population in China. To validate the Perioperative Frailty Index (FI-32) derived from the Chinese Hospital Information System by investigating the impact of preoperative frailty on postoperative outcomes, and ascertain the diagnostic value of FI-32 for predicting postoperative complications through comparing with the FRAIL scale and the modified Frailty Index (mFI-11). Methods A prospective cohort study was conducted in a tertiary hospital. Elderly patients who were 60 years or older and underwent selective operation were included. The FI-32, FRAIL scale, and mFI-11 were assessed. Demographic, surgical variables and outcome variables were extracted from medical records. The data of readmission and mortality within 30 days and 90 days of surgery were ascertained by Telephone follow-up by professionally trained researchers. Multiple logistic regression was used to examine the association between frailty and complications. Receiver operating characteristic curves(ROC) were used to compare FI-32 with mFI-11 and FRAIL, to explore the predictive ability of frailty. Results 335 patients qualified for the inclusion criteria and were enrolled in the study, and among them, 201 (60.0%) were females, and the Median(P 25, P 75)age at surgery was 69 (65,74) years. The prevalence of frailty in the study population was 16.4% (assessed by FI-32). After adjusting for concomitant variables including demographic characteristics (such as gender, BMI, smoking, drinking, average monthly income and educational level) and surgical factors (such as surgical approach, surgical site, anesthesia method, operation time, intraoperative bleeding, and intraoperative fluid intake), there was a statistically significant association between frailty and the development of postoperative complication after surgery (OR = 3.051, 95% CI:1.460–6.378, P = 0.003). There were also significant differences in mortality within 30 days of surgery, the length of hospital stay (LOS) and the hospitalization costs. FI-32, FRAIL and mFI-11 showed a moderate predictive ability for postoperative complications, the Area Under Curves (AUCs) were 0.582, 0.566 and 0.531, respectively. With adjusting concomitant variables associated with postoperative complications, the AUCs of FI-32, FRAIL and mFI-11 in the adjusted prediction models were 0.824, 0.827 and 0.820 respectively. Conclusions The FI-32 has a predictive effect on postoperative adverse outcomes in elderly Chinese patients. Compared to FRAIL and mFI-11, the FI-32 had the same ability to predict postoperative complications, and FI-32 can be extracted directly from HIS, which greatly saves the time for clinical medical staff to evaluate perioperative frailty.

Abstract Pancreas segmentation has great significance in computer‐aided diagnosis of pancreatic diseases. The small size of the pancreas, high variability in shape, and blurred edges make the task of pancreas segmentation challenging. A new model called SEY‐Net is proposed to solve the above problems, which is a one‐stage model with multi‐inputs. SEY‐Net is composed of three main components. Firstly, the edge information extraction (EIE) module is designed to improve the segmentation accuracy of the pancreas boundary. Then, the SE_ResNet50 is selected as the encoder's backbone to fit the size of the pancreas. Finally, the dual cross‐attention is integrated into the skip connection to better focus on the variable shape of the pancreas. The experimental results shows that the proposed method has better performance and outperforms the other existing state‐of‐the‐art pancreas segmentation methods.

Abstract Background Microecological equilibrium is essential for human health. Previous research has demonstrated that Streptococcus strain A, the main bacterial group in the respiratory tract, can suppress harmful microbes and protect the body. In this study, Streptococcus strain D19T was isolated from the oral and pharyngeal cavities of healthy children. Its antibacterial mechanism against Acinetobacter baumannii was examined, as well as its potential to prevent inflammatory damage to cells. We evaluated the effect of the fermentation conditions of D19T on inhibition of Acinetobacter baumannii growth; Isolation and purification of antibacterial active components of strain D19T and molecular mechanism of inhibition of Acinetobacter baumannii; Molecular mechanism of D19T antibacterial protein reversing cellular inflammatory injury induced by Acinetobacter baumannii. Results The supernatant of fermentation broth of Streptococcus D19T was the active component against Acinetobacter baumannii, but the bacteria had no antibacterial activity. The supernatant of D19T fermentation broth was precipitated by (NH4)2SO4 solution, and the protein was the active antibacterial component. After gel filtration chromatography and anion gel filtration chromatography, the molecular weight of antibacterial protein was 53kD. D19T antibacterial protein can improve cell membrane permeability, limit extracellular soluble protein release, inhibit Acinetobacter baumannii biofilm formation, and prevent Acinetobacter baumannii adhesion. Acinetobacter baumannii induces inflammatory damage to respiratory cells via ferroptosis, and the D19T antibacterial protein can counteract this damage, protecting the respiratory tract. Conclusion Streptococcus strain D19T, as a potential probiotic, inhibits the growth of Acinetobacter baumannii and the inflammatory damage of respiratory cells, playing a protective role in human respiratory health.

Abstract Background Cognitive frailty (CF) is characterized by the coexistence of physical frailty and cognitive impairment, and it is associated with adverse health outcomes. Older adults are particularly vulnerable to CF due to factors such as age-related brain changes and the presence of comorbidities. Objective To investigate the effect of preoperative CF on postoperative complications in older patients. Methods This prospective cohort study was conducted among 253 patients aged 60–85 years, who underwent elective orthopedic and abdominal surgery (with a postoperative hospital stay of ≥ 3 days) at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2023 to November 2023. CF was assessed using the Montreal Cognitive Assessment (MoCA) for the cognitive status and the Fried criteria for five frailty scales. Participants were split into four groups: Group A (neither frailty nor cognitive impairment), Group B (frailty without cognitive impairment), Group C (cognitive impairment without frailty), and Group D (cognitive frailty). The primary outcome was postoperative complications, while secondary outcomes included mobility disability, prolonged hospital stay (PLOS), re-operation and 90-day readmission. Results The median age (interquartile range) of participants was 69 (65–73) years, of which 40.3% were male. The prevalence of CF was 17.8%. The incidence of postoperative complications was 18.2% in Group A, 50.0% in Group B, 37.4% in Group C, and 75.6% in Group D. Multivariate analysis revealed that, compared to the control group (without cognitive impairment or frailty), patients with CF had a significantly higher risk of postoperative complications (OR, 12.86; 95%CI, 4.23–39.08). “Patients with frailty without cognitive impairment” had an increased risk (OR, 6.53; 95%CI, 2.04–20.9), while “those with cognitive impairment without frailty” also showed a higher risk (OR, 3.46; 95%CI, 1.57–7.64). Conclusions Cognitive frailty is significantly associated with an increased risk of postoperative adverse outcomes in older patients undergoing orthopedic and abdominal surgeries with general anesthesia. It indicates that clinicians should pay much attention to these older adults with CF.

Abstract Objective To develop and validate a machine learning model for predicting mortality-associated prognostic factors in order to reduce in-hospital mortality rates among HIV/AIDS patients with Cryptococcus infection in Guangxi, China. Methods This retrospective prognostic study included HIV/AIDS patients with cryptococcosis in the Fourth People’s Hospital of Nanning from October 2011 to June 2019. Clinical features were extracted and used to train ten machine learning models, including Logistic Regression, KNN, DT, RF, Adaboost, Xgboost, LightGBM, Catboost, SVM, and NBM, to predict the outcome of HIV patients with cryptococcosis infection. The sensitivity, specificity, AUC, and F1 value were applied to assess model performance in both the testing and training sets. The optimal model was selected and interpreted. Results A total of 396 patients were included in the study. The average in-hospital mortality of HIV/AIDS patients with cryptococcosis was 12.9% from 2012 to 2019. After feature screening, 20 clinical features were selected for model construction, accounting for 93.8%, including ART, Electrolyte disorder, Anemia, and 17 laboratory tests. The RF model (AUC 0.9787, Sensitivity 0.9535, Specificity 0.8889, F1 0.7455) and the SVM model (AUC 0.9286, Sensitivity 0.7907, Specificity 0.9786, F1 0.8293) had excellent performance. The SHAP analysis showed that the primary risk factors for prognosis prediction were identified as BUN/CREA, Electrolyte disorder, NEUT%, Urea, and IBIL. Conclusions RF and SVM machine learning models have shown promising predictive abilities for the prognosis of hospitalized HIV/AIDS patients with cryptococcosis, which can aid clinical assessment and treatment decisions for patient prognosis.

Intertrochanteric femur fracture is the most common hip fracture in elderly people, and the academic community has reached a consensus that early surgery is imperative. Proximal femoral nail anti‐rotation (PFNA) and InterTan are the preferred internal fixation devices for intertrochanteric femur fractures in elderly individuals due to their advantages, such as a short lever arm, minimal stress shielding, and resistance to rotation. However, PFNA is associated with complications such as nail back‐out and helical blade cut‐out due to stress concentration. As a new internal fixation device for intertrochanteric femur fractures, the proximal femoral biodegradable nail (PFBN) addresses the issue of nail back‐out and offers more stable fracture fixation, a shorter lever arm, and stress distribution compared to PFNA and InterTan. Clinical studies have shown that compared to PFNA, PFBNs lead to faster recovery of hip joint function, shorter non‐weight‐bearing time, and faster fracture healing. This article provides a literature review of the structural characteristics, biomechanical analysis, and clinical studies of PFBNs, aiming to provide a theoretical basis for the selection of internal fixation devices for the treatment of intertrochanteric femur fractures in elderly patients and to improve the quality of life of patients during the postoperative period.

Abstract SHP-1, a nonreceptor protein tyrosine phosphatase encoded by ptpn6, has been regarded as a regulatory protein of hematopoietic cell biology for years. However, there is now increasing evidence to support its role in tumors. Thus, the role of ptpn6 for prognosis and immune regulation across 33 tumors was investigated, aiming to explore its functional heterogeneity and clinical significance in pan-cancer. Differential expression of ptpn6 was found between cancer and adjacent normal tissues, and its expression was significantly correlated with the prognosis of tumor patients. In most cancers, ptpn6 expression was significantly associated with immune infiltration. This was further confirmed by ptpn6-related genes/proteins enrichment analysis. Additionally, genetic alterations in ptpn6 was observed in most cancers. As for epigenetic changes, it’s phosphorylation levels significantly altered in 6 tumors, while methylation levels significantly altered in 12 tumors. Notably, the methylation levels of ptpn6 were significantly decreased in 11 tumors, accompanied by its increased expression in 8 of them, suggesting that the hypomethylation may be related to its increased expression. Our results show that ptpn6 plays a specific role in tumor immunity and exerts a pleiotropic effect in a variety of tumors. It can serve as a prognostic factor for some cancers. Especially in LGG, KIRC, UCS and TGCT, the increased expression of ptpn6 is associated with poor prognosis and high immune infiltration. This aids in understanding the role of ptpn6 in tumor biology, and can provide insight into presenting a potential biomarker for poor prognosis and immune infiltration in cancers.

AIM: To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. METHODS: The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. RESULTS: The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the “leave-one-out” sensitivity analysis demonstrated that the results were stable. CONCLUSION: Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

Abstract Background Phosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment. Methods We analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells. Results PFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects. Conclusion PFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors.

Abstract Background HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. Methods The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014–2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018–2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. Results The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P

As a “cold tumor”, triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an “in situ nanovaccine” Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an “in situ nanovaccine” to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid‐derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, “cold tumor” was transformed into a “hot tumor”, not only implementing a “turning foes to friends” therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

Abstract Background There is an increasing number of human immunodeficiency virus (HIV) reported cases among students in Southwest China. However, the data on HIV/sex-related knowledge, attitude toward sex, sexual behaviors, and correlates of pre-exposure prophylaxis (PrEP)-eligible behaviors among college students in this area is still limited. This study aimed to assess the prevalence of HIV/sex-related knowledge, sexual attitudes, sexual behaviors, and factors associated with PrEP-eligible behaviors among college students. Method An online survey from 2020 to 2021 based on a multistage stratified and cluster sampling method was conducted among college students in Southwest China, and a well-designed questionnaire collected data. Propensity score matching (PSM), logistic, and log-binomial regression were used to identify the determinants of PrEP-eligible behaviors. Result A total of 108,987 students participated in the survey, and 92,946 provided valid responses. 91.6% (85,145/92,946) had good HIV-related knowledge, while only 26.0% (24,137/92,946) reported awareness of sex-related knowledge. Furthermore, more than half of the participants (64.5%) held negative stances towards engaging in “one-night stand”, and 58.9% (617/1,047) reported PrEP-eligible behaviors. Log-binomial regression analysis indicated that unaware of HIV-related knowledge (aPR = 1.66, 95% CI:1.22–2.26, P = 0.001), not discussing about sex with their parent(s) (aPR = 1.16, 95% CI:1.01–1.33, P = 0.021), not receiving sex-related education in school(aPR = 1.24, 95% CI: 1.07–1.45, P = 0.005), not participating in HIV/AIDS prevention activities in the past year (aPR = 1.32, 95%CI:1.09–1.60, P = 0.004), experiencing forced sex (aPR = 2.08, 95% CI: 1.19–3.63, P = 0.010), and having the drug abuse (aPR = 22.21, 95% CI:5.59–88.31, P

Abstract Adversarial training suffers from poor effectiveness due to the challenging optimisation of loss with hard labels. To address this issue, adversarial distillation has emerged as a potential solution, encouraging target models to mimic the output of the teachers. However, reliance on pre‐training teachers leads to additional training costs and raises concerns about the reliability of their knowledge. Furthermore, existing methods fail to consider the significant differences in unconfident samples between early and late stages, potentially resulting in robust overfitting. An adversarial defence method named Clean, Performance‐robust, and Performance‐sensitive Historical Information based Adversarial Self‐Distillation (CPr & PsHI‐ASD) is presented. Firstly, an adversarial self‐distillation replacement method based on clean, performance‐robust, and performance‐sensitive historical information is developed to eliminate pre‐training costs and enhance guidance reliability for the target model. Secondly, adversarial self‐distillation algorithms that leverage knowledge distilled from the previous iteration are introduced to facilitate the self‐distillation of adversarial knowledge and mitigate the problem of robust overfitting. Experiments are conducted to evaluate the performance of the proposed method on CIFAR‐10, CIFAR‐100, and Tiny‐ImageNet datasets. The results demonstrate that the CPr&PsHI‐ASD method is more effective than existing adversarial distillation methods in enhancing adversarial robustness and mitigating robust overfitting issues against various adversarial attacks.

Bladder cancer (BLCA) remains a significant health risk despite advancements in medical science that have led to reduced incidence and death rates. While the molecular regulatory mechanisms of BLCA are not yet fully understood, HSPE1, a member of the heat shock protein family, is regarded as a reliable prognostic target for BLCA. Using data from The Cancer Genome Atlas (TCGA) database, the differential expression levels of HSPE1 and its relationship to GPX4 were examined. Gene Set Enrichment Analysis was used to carry out HSPE1 pathway enrichment analysis. HSPE1 and GPX4 expressions in cells were assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. Cell cycle alternations and apoptosis were evaluated using flow cytometry. Cell proliferation was assessed using EdU and colony formation assays. The lactate dehydrogenase (LDH) test, glutathione (GSH) measurement, and Liperfluo assay were utilized to evaluate the presence of ferroptosis in cells. BLCA tissues and cells had significantly elevated levels of HSPE1. In BLCA, high expression of HSPE1 inhibited apoptosis while promoting cell proliferation and cell cycle progression. Significant enrichment of HSPE1 was found in the GSH metabolism and ferroptosis pathways, according to pathway enrichment analysis. In cancer cells, HSPE1 promoted GSH accumulation, decreased lipid peroxidation, and inhibited cell ferroptosis, as demonstrated in a rescue experiment with the ferroptosis inhibitor Fer-1. Pearson correlation analysis unveiled a substantial positive correlation between HSPE1 and the ferroptosis regulator GPX4. According to the results of rescue experiments, HSPE1 regulated GPX4 to affect cell lipid peroxidation levels and GSH accumulation. HSPE1 plays a crucial role in regulating GPX4 to prevent BLCA cells from undergoing ferroptosis, with this control mechanism dependent on GSH.

Rare earth polishing powder has gained widespread usage in the surface polishing of high-precision materials, exhibiting an annual growth rate exceeding 10 %. However, a significant portion of this powder is discarded due to impurities and the need for particle size refinement. The waste generated from polishing powder contains 10.31 %–86.93 % rare earth elements, making secondary recycling economically viable. This work critically analyses and verifies existing methods for recovering rare earths(REs)from rare earth polishing powder waste (REPPW). It concludes that the acid roasting, water leaching, and reduction, coordination acid-leaching methods can achieve rare earth recovery rates exceeding 98 %, offering a relatively simple and environmentally friendly process. We highlight various rare earth recovery processes from REPPW, including alkaline roasting with acid-leaching, acid roasting with water-leaching, acid-leaching with alkali dissolution and washing, and acid-leaching with the aid of reducing agents. It is found that the acid-leaching-water leaching process and the acid-leaching-reducing agent synergy process demonstrate high recovery rates, ease of operation, reduced environmental impact, and stable product quality. It is recommended that researchers focus on refining leaching theories, optimizing process conditions and determining key parameters to further advance the production of rare earth recovery from REPPW. The findings of this study contribute to the development of sustainable practices for the recovery of valuable REs from industrial waste streams.

Identifying the prevalence and risk factors of secondary human immunodeficiency virus (HIV) transmission from people living with HIV (PLWH) to other people is crucial for ending the HIV epidemic. However, the data among antiretroviral therapy (ART) patients is limited. This study aims to assess the prevalence and risk factors of secondary HIV transmission among PLWH receiving ART by longitudinal molecular networks in China. In this study, the prevalence of secondary HIV transmission was 10.8%. The R0 was greater than 1 from 2017 to 2021 and peaked in 2019. PLWHs who were male sex, older age, engaged in condomless sex, experienced higher ART follow-up viral load, experienced ART medical omissions, infected with non-CRF01_AE subtype, and self-reported sexually transmitted infections (STIs) at HIV diagnosis increased the risk of secondary HIV transmission. However, those participants with higher education were less likely to be involved in secondary HIV transmission. The diagnostic age of the participants was nonlinearly associated with the risk of secondary HIV transmission, with a cutoff value of 43.13 years indicating a higher risk of secondary HIV transmission for patients diagnosed at or above this age. This study revealed substantial secondary HIV transmission and persistent HIV expansion among local PLWH, highlighting the necessity of enhancing viral load monitor, promoting adherence to ART, and promoting safe sex practices, particularly among older adults with HIV, to mitigate secondary HIV transmission.

BackgroundCholangiocarcinoma (CCA) is a malignant tumor of the gastrointestinal tract with a poor prognosis. Immunotherapy plays an important role in the treatment of CCA. This study aimed to investigate the research hotspots and trends in immunotherapy for CCA.MethodsThe Web of Science Core Collection was searched for literature related to CCA immunotherapy research from January 1, 2014, to December 31, 2023, and features such as country, institution, authors, references, and keywords in the included literature were quantitatively and visually analyzed using the VOS viewer and CiteSpace software.ResultsA total of 252 English publications published between 2014 and 2023 were included. The publications were mainly from China and the United States, with Fudan University being the institution that published the most papers. The highest number of publications came from Frontiers in Oncology. The most prolific authors were Jia Fan, Jian Zhou from China and Pa-Thai Yenchitsomanus from Thailand, while the Journal of Clinical Oncology ranked first in the number of citations among the co-cited journals. In recent years, the focus of research has shifted from “immune checkpoint” and “chemotherapy” to “immunotherapy combined therapy.” Currently, the research frontiers are “microenvironment,” “immune cells,” and “macrophages.”ConclusionOur study analyzes the research hotspots and trends in CCA to provide a knowledge map of immunotherapy research, which will serve as a reference and direction for future research.

Polyurethane grouting has garnered increasing attention in road maintenance, owing to its exceptional interfacial adhesion, mechanical robustness, and chemical resilience. In comparison to conventional SBS-modified asphalt, polyurethane grout offers superior durability and demonstrates an enhanced capacity to inhibit crack propagation within asphalt mixtures. This study investigates the anti-cracking performance of polyurethane grout in comparison to traditional SBS-modified asphalt, utilizing the Overlay Test (OT) to simulate real-world conditions of reflective cracking in asphalt pavements. Results demonstrate that polyurethane grout significantly enhances the crack resistance of asphalt mixtures, manifesting superior durability and resistance to crack propagation at a controlled temperature of 25°C, with a marked increase in the number of loading cycles relative to the control. However, the performance of polyurethane grout is notably diminished under adverse conditions of low temperatures and water immersion. The investigation employs a multi-index evaluation, with gray correlation analysis delineating the efficacy of various indices in appraising crack resistance. Recommending the use of loading cycles, allowable failure times, and cumulative fracture energy as key metrics.

The high cost of using the niobium (Nb) barrier for manufacturing magnesium diboride (MgB2) mono-and multi-filamentary wires for large-scale applications has become one of the barriers to replacing current commercial niobium-titanium superconductors. The potential of replacing the Nb barrier with a low-cost iron (Fe) barrier for multifilament MgB2 superconducting wires is investigated in this manuscript. Therefore, MgB2 wires with Fe barrier sintered with different temperatures are studied (from 650 °C to 900 °C for 1 h) to investigate the non-superconducting reaction phase of Fe-B. Their superconducting performance including engineering critical current density (Je) and n-value are tested at 4.2 K in various external magnetic fields. The best sample sintered at 650 °C for 1 h has achieved a Je value of 3.64 × 104 A cm−2 and an n-value of 61 in 2 T magnetic field due to the reduced formation of Fe2B, better grain connectivity and homogenous microstructure. For microstructural analysis, the focused ion beam (FIB) is utilised for the first time to acquire three-dimensional microstructures and elemental mappings of the interface between the Fe barrier and MgB2 core of different wires. The results have shown that if the sintering temperature can be controlled properly, the Je and n-value of the wire are still acceptable for magnet applications. The formation of Fe2B is identified along the edge of MgB2, as the temperature increases, the content of Fe2B also increases which causes the degradation in the performance of wires.

Abstract In deep‐ocean natural gas hydrate exploitation operation, the fatigue failure mechanism has attracted more and more attention from scholars, but it has not been effectively disclosed. Therefore, in this work, a multifield coupling and multiple‐nonlinear vibration model of lifting pipe is established, which can accurately determine the alternating stress of deep‐ocean lifting pipe. Second, according to Forman theory, the calculation method of crack propagation length and depth on the surface of a deep‐water riser is established, which is verified by the comparison between the experimental and theoretical model calculation results. The results demonstrate that, first, the effect of residual stress in the welded joint of deep‐ocean lifting pipe should be considered in the later parameter influence analysis. Second, the fatigue growth life of deep‐water pipe with small outflow velocity is mainly determined by tensile stress, and that is determined by both tensile stress and bending stress with large outflow velocity. Third, more attention should be paid to the vibration of the lower pipe on‐site to reduce its vibration frequency and vibration stress amplitude, which can effectively reduce the surface crack propagation state of the deep‐ocean pipe and improve the service life of the pipe. Fourth, properly adjusting the tension coefficient of the tensioner during field operation can effectively improve the safety of the pipe, and the optimal tension coefficient is related to the configuration of the deep‐ocean pipe system, which can be analyzed and determined by the model.

Abstract Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes—SLC7A11, LRPPRC, NDUFS1, and CD2AP—were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier.

Abstract Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Abstract Accurate jet charge identification is essential for precise electroweak and flavor measurements at the high-energy frontier. We propose a novel method called the Leading Particle Jet Charge method (LPJC) to determine the jet charge based on information of the leading charged particle. Tested on Z → b b ¯ $$ b\overline{b} $$ and Z → c c ¯ $$ c\overline{c} $$ samples at center-of-mass energy of 91.2 GeV, the LPJC achieves an effective tagging power ϵ eff of 20%/9% for c/b jet, respectively. In combination with the Weighted Jet Charge method (WJC), we develop a Heavy Flavor Jet Charge method (HFJC), which achieves an effective tagging power ϵ eff of 39%/20% for c/b jet, respectively. This paper also discusses the dependencies between jet charge identification performance and the fragmentation process of heavy flavor jets, as well as critical detector performances.

Abstract Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.

Abstract Background Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. Method Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. Results A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507–0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116–1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425–0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135–0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322–0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells

BackgroundThere is increasing focus on HIV-1 CRF55_01B in China. However, there is limited information regarding the dissemination of CRF55_01B across different regions and populations in Guangxi. This study was performed to elucidate the evolutionary history of the introduction and dissemination of CRF55_01B in Guangxi.MethodsMolecular network and phylogenetic analyses were used to investigate the transmission characteristics of CRF55_01B in China. The analyses particularly focused on the cross-provincial spatial and temporal transmission patterns between Guangdong Province and Guangxi, as well as the transmission dynamics among different regions and populations within Guangxi.ResultsIn total, 2226 partial pol sequences of CRF55_01B strains sampled from 2007 to 2022 were collected, including 1895 (85.09%) sequences from Guangdong, 199 (8.94%) sequences from Guangxi, and 172 (7.59%) sequences from other provinces of China. Most people living with HIV in Guangxi were infected with HIV-1 through heterosexuals (52.76%). Among these, 19.10% had a history of commercial heterosexual contact (CHC) and 15.58% had a history of non-marital non-commercial heterosexual contact (NMNCHC). Overall, 1418 sequences were identified in the molecular network. Notably, the sequences from Guangdong Province were most closely linked to those from Guangxi. Phylogenetic analysis showed that CRF55_01B was first introduced from Shenzhen City to Nanning City around 2007. Subsequently, CRF55_01B established local transmission within Guangxi, with Nanning City serving as the transmission center from 2008 to 2017. After 2017, the CRF55_01B strain spread to other regions of Guangxi. Men who have sex with men (MSM) and men with a history of CHC have played a significant role in the transmission of CRF55_01B among different populations in Guangxi.ConclusionsThis study provides evidence on the transmission trajectory of CRF55_01B among different regions and populations in Guangxi. Given the bridging role of men with a history of CHC in the dissemination of CRF55_01B from MSM to the general population, it is imperative to enhance surveillance among key populations to mitigate the secondary transmission of HIV-1.

An adaptive maneuvering target tracking algorithm based on fuzzy inference is proposed to deal with the low adaptive capacity of variable structure interacting multi-model algorithms for target maneuver uncertainty and measurement uncertainty in maneuvering target tracking. A two-stage maneuvering discrimination model based on fuzzy inference is designed, which uses the probability of models and residual weighted norm of the main model to infer the reliability of the main model and the possibility of maneuvering discrimination. The two-stage maneuvering discriminant is introduced into the framework of expected-model augmentation based on likely model-set (EMA-LMS). A kind of fuzzy inference-based EMA-LMS algorithm is proposed to adjust the parameter and strategy of model-set adaption online. This algorithm generates an expected model that is closer to the real motion model and makes better choices for model selection. The simulation results show that the proposed algorithm can strengthen the adaptive capacity for the uncertainty of target maneuver and measurement, and improve accuracy.

Abstract The close link between HIV-1 infection and the occurrence of pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms of their interrelation remain unclear. The microarray data of HIV-1 and PAH were downloaded from GEO database. We utilized WGCNA to identify shared genes between HIV-1 and PAH, followed by conducting GO and pathway enrichment analyses. Subsequently, differentially genes analysis was performed using external validation datasets to further filter hub genes. Immunoinfiltration analysis was performed using CIBERSORT. Finally, hub gene expression was validated using scRNA-seq data. We identified 109 shared genes through WGCNA, primarily enriched in type I interferon (IFN) pathways. By taking the intersection of WGCNA important module genes and DEGs, ISG15 and IFI27 were identified as pivotal hub genes. Immunoinfiltration analysis and scRNA-seq results indicated the significant role of monocytes in the shared molecular mechanisms of HIV-1 and PAH. In summary, our study illustrated the possible mechanism of PAH secondary to HIV-1 and showed that the heightened IFN response in HIV-1 might be a crucial susceptibility factor for PAH, with monocytes being pivotal cells involved in the type I IFN response pathway. This provides potential new insights for further investigating the molecular mechanisms connecting HIV-1 and PAH.

Abstract Background No uniform consensus has been achieved regarding the ambulation protocol after transfemoral cerebral angiography (TFA). Until now, in most hospitals patients are prescribed 8-12 h strict immobilization along with bed rest in the supine position after TFA in China, which causes great discomfort to patients. Objective To evaluate the effect of an evidence-based early ambulation protocol on the prevention of vascular complications and general discomfort in patients following transfemoral cerebral angiography (TFA). Methods A prospective quasi-experimental study was conducted on 214 patients undergoing TFA with manual compression. Patients in the experimental group were placed supine position for 2 h with a sandbag placed on the wound dressing, followed by a semi-seated position for another 2 h. After this period, patients took 2 h bed rest (move freely) with the sandbag removed, and were allowed to get out of bed 6 h after TFA. Patients in the control group were restricted to an 8 h bed rest in a supine position with the affected leg straight and immobilized. The vascular complications (bleeding, hematoma, ecchymosis) and levels of comfort (low back pain, leg pain, and blood pressure) were evaluated after the procedure. Numeric Rating Scale (NRS) pain scores, systolic blood pressure (SBP); diastolic blood pressure (DBP) were measured hourly for 8 h after TFA. Results There was no significant difference in the two groups with regard to vascular complications including bleeding events (P = 0.621), bleeding volume (P = 0.321), and area of hematoma (P = 0.156). The area of ecchymosis in the experimental group was significantly smaller than the control group (P = 0.031). Compared with the control group, the NRS score for low back pain in the 4th, 5th, 6th, 7th, and 8th hour after TFA were significantly lower (P

Abstract Background The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. Methods We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. Results During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long’an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast–northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west–north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. Conclusions The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.

Chinese cabbage (Brassica rapa ssp. pekinensis) has a long cultivation history and is one of the vegetable crops with the largest cultivation area in China. However, salt stress severely damages photosynthesis and hormone metabolism, nutritional balances, and results in ion toxicity in plants. To better understand the mechanisms of salt-induced growth inhibition in Chinese cabbage, RNA-seq and physiological index determination were conducted to explore the impacts of salt stress on carbon cycle metabolism and photosynthesis in Chinese cabbage. Here, we found that the number of thylakoids and grana lamellae and the content of starch granules and chlorophyll in the leaves of Chinese cabbage under salt stress showed a time-dependent response, first increasing and then decreasing. Chinese cabbage increased the transcript levels of genes related to the photosynthetic apparatus and carbon metabolism under salt stress, probably in an attempt to alleviate damage to the photosynthetic system and enhance CO2 fixation and energy metabolism. The transcription of genes related to starch and sucrose synthesis and degradation were also enhanced; this might have been an attempt to maintain intracellular osmotic pressure by increasing soluble sugar concentrations. Soluble sugars could also be used as potential reactive oxygen species (ROS) scavengers, in concert with peroxidase (POD) enzymes, to eliminate ROS that accumulate during metabolic processes. Our study characterizes the synergistic response network of carbon metabolism and photosynthesis under salt stress.

Abstract Background HIV-1 CRF65_cpx strain carries drug-resistant mutations, which raises concerns about its potential for causing virologic failure. The CRF65_cpx ranks as the fourth most prevalent on Hainan Island, China. However, the origin and molecular epidemiology of CRF65_cpx strains in this area remain unclear. This study aims to estimate the spatial origins and dissemination patterns of HIV-1 CRF65_cpx in this specific region. Methods Between 2018 and 2021, a total of 58 pol sequences of the CRF65_cpx were collected from HIV-positive patients on Hainan Island. The available CRF65_cpx pol sequences from public databases were compiled. The HIV-TRACE tool was used to construct transmission networks. The evolutionary history of the introduction and dissemination of HIV-1 CRF65_cpx on Hainan Island were analyzed using phylogenetic analysis and the Bayesian coalescent-based approach. Results Among the 58 participants, 89.66% were men who have sex with men (MSM). The median age was 25 years, and 43.10% of the individuals had a college degree or above. The results indicated that 39 (67.24%) sequences were interconnected within a single transmission network. A consistent expansion was evident from 2019 to 2021, with an incremental annual addition of four sequences into the networks. Phylodynamic analyses showed that the CRF65_cpx on Hainan Island originated from Beijing (Bayes factor, BF = 17.4), with transmission among MSM on Hainan Island in 2013.2 (95%HPD: 2012.4, 2019.5), subsequently leading to an outbreak. Haikou was the local center of the CRF65_cpx epidemic. This strain propagated from Haikou to other locations, including Sanya (BF > 1000), Danzhou (BF = 299.3), Chengmai (BF = 27.0) and Tunchang (BF = 16.3). The analyses of the viral migration patterns between age subgroups and risk subgroups revealed that the viral migration directions were from "25–40 years old" to "17–24 years old" (BF = 14.6) and to "over 40 years old" (BF = 17.6), and from MSM to heterosexuals (BF > 1000) on Hainan Island. Conclusion Our analyses elucidate the transmission dynamics of CRF65_cpx strain on Hainan Island. Haikou is identified as the potential hotspot for CRF65_cpx transmission, with middle-aged MSM identified as the key population. These findings suggest that targeted interventions in hotspots and key populations may be more effective in controlling the HIV epidemic.

Abstract The limited differentiation ability of adipose-derived stem cells (ADSCs) limits their application in stem cell therapy and regenerative medicine. Here, we explore the molecular mechanism by which miR-204-5p regulates ADSCs differentiation into cells derived from the three germ layers (i.e., adipocytes, neurocytes, and hepatocytes). Although miR-204-5p overexpression inhibited ADSCs differentiation into adipocytes, neurocyte and hepatocyte differentiation were promoted. Mechanistically, miR-204-5p inhibited the expression of PPARG by regulating the AMPK signaling pathway, thereby inhibiting ADSCs differentiation into adipocytes. Further, miR-204-5p regulated JAG1/NOTCH3 axis for the inhibition of differentiation into adipocytes and promotion of differentiation into neurocytes. miR-204-5p might also promote ADSCs differentiation into hepatocytes by upregulating E2F8. The findings of this study provide novel insights into the regulatory mechanisms underlying early embryonic development and will help to facilitate the application of ADSCs in stem cell therapy and regenerative medicine.

Abstract Quarks (except top quarks) and gluons produced in collider experiments hadronize and fragment into sprays of stable particles, called jets. Identification of quark flavor is desired for collider experiments in high-energy physics, relying on flavor tagging algorithms. In this study, using a full simulation of the Circular Electron Positron Collider (CEPC), we investigate the flavor tagging performance of two different algorithms: ParticleNet, based on a Graph Neural Network, and LCFIPlus, based on the Gradient Booted Decision Tree. Compared to LCFIPlus, ParticleNet significantly enhances flavor tagging performance, resulting in a significant improvement in benchmark measurement accuracy, i.e., a 36% improvement for $$\sigma (ZH)\cdot Br(Z\rightarrow \nu \bar{\nu }, H\rightarrow c\bar{c})$$ σ ( Z H ) · B r ( Z → ν ν ¯ , H → c c ¯ ) measurement and a 75% improvement for $$|V_{cb}|$$ | V cb | measurement via W boson decay, respectively, when the CEPC operates as a Higgs factory at the center-of-mass energy of 240 GeV and collects an integrated luminosity of 5.6 ab $$^{-1}$$ - 1 . We compare the performance of ParticleNet and LCFIPlus at different vertex detector configurations, observing that the inner radius is the most sensitive parameter, followed by material budget and spatial resolution.

Abstract Background MicroRNA (miRNA)-based therapies have shown great potential in myocardial repair following myocardial infarction (MI). MicroRNA-302 (miR302) has been reported to exert a protective effect on MI. However, miRNAs are easily degraded and ineffective in penetrating cells, which limit their clinical applications. Exosomes, which are small bioactive molecules, have been considered as an ideal vehicle for miRNAs delivery due to their cell penetration, low immunogenicity and excellent stability potential. Herein, we explored cardiomyocyte-targeting exosomes as vehicles for delivery of miR302 into cardiomyocyte to potentially treat MI. Methods To generate an efficient exosomal delivery system that can target cardiomyocytes, we engineered exosomes with cardiomyocyte specific peptide (CMP, WLSEAGPVVTVRALRGTGSW). Afterwards, the engineered exosomes were characterized and identified using transmission electron microscope (TEM) and Nanoparticle Tracking Analysis (NTA). Later on, the miR302 mimics were loaded into the engineered exosomes via electroporation technique. Subsequently, the effect of the engineered exosomes on myocardial ischemia and reperfusion (I/R) injury was evaluated in vitro and in vivo, including MTT, ELISA, real-time quantitative polymerase chain reaction (PCR), western blot, TUNNEL staining, echocardiogram and hematoxylin and eosin (HE) staining. Results Results of in vitro experimentation showed that DSPE-PEG-CMP-EXO could be more efficiently internalized by H9C2 cells than unmodified exosomes (blank‐exosomes). Importantly, compared with the DSPE-PEG-CMP-EXO group, DSPE-PEG-CMP-miR302-EXO significantly upregulated the expression of miR302, while exosomes loaded with miR302 could enhance proliferation of H9C2 cells. Western blot results showed that the DSPE-PEG-CMP-miR302-EXO significantly increased the protein level of Ki67 and Yap, which suggests that DSPE-PEG-CMP-miR302-EXO enhanced the activity of Yap, the principal downstream effector of Hippo pathway. In vivo, DSPE-PEG-CMP-miR302-EXO improved cardiac function, attenuated myocardial apoptosis and inflammatory response, as well as reduced infarct size significantly. Conclusion In conclusion, our findings suggest that CMP-engineered exosomes loaded with miR302 was internalized by H9C2 cells, an in vitro model for cardiomyocytes coupled with potential enhancement of the therapeutic effects on myocardial I/R injury.

At present, researchers in the field of pipeline inspection focus on pipe wall defects while neglecting pipeline defects in special situations such as welds. This poses a threat to the safe operation of projects. In this paper, a multi-node fusion and modal projection algorithm of steel pipes based on guided wave technology is proposed. Through an ANSYS numerical simulation, research is conducted to achieve the identification, localization, and quantification of axial cracks on the surface of straight pipelines and internal cracks in circumferential welds. The propagation characteristics and vibration law of ultrasonic guided waves are theoretically solved by the semi-analytical finite element method in the pipeline. The model section is discretized in one-dimensional polar coordinates to obtain the dispersion curve of the steel pipe. The T(0,1) mode, which is modulated by the Hanning window, is selected to simulate the axial crack of the pipeline and the L(0,2) mode to simulate the crack in the weld, and the correctness of the dispersion curve is verified. The results show that the T(0,1) and L(0,2) modes are successfully excited, and they are sensitive to axial and circumferential cracks. The time–frequency diagram of wavelet transform and the time domain diagram of the crack signal of Hilbert transform are used to identify the echo signal. The first wave packet peak point and group velocity are used to locate the crack. The pure signal of the crack is extracted from the simulation data, and the variation law between the reflection coefficient and the circumferential and radial dimensions of the defect is calculated to evaluate the size of the defect. This provides a new and feasible method for steel pipe defect detection.

The winter planting of green manure (GM) is widely used in South China to reduce chemical nitrogen (N) fertilizer use, improve soil fertility, and maintain rice yields, but its effect on N runoff loss in paddy fields remains unclear. This study combines multi-site field experiments with a process model (WHCNS-Rice) to assess how GM with reduced N fertilizer impacts N runoff loss and its forms in the Yangtze River’s middle and lower reaches, considering different rainfall years. The network field experiments included four treatments: conventional fertilization (FR), conventional fertilization plus straw return (FRS), GM with a 40% N reduction (MR), and GM-straw combined return with a 40% N reduction (MRS). Monitoring the results showed that compared to the winter fallow treatment, the GM treatments reduced the peak and average total N (TN) concentrations by 11.1–57.9% (average 26.9%) and 17.1–27.3% (average 22.3%), respectively. The TN runoff loss under the GM treatment decreased by 3.50–10.61 kg N ha−1 (22.5–42.1%). GM primarily reduced the runoff loss of dissolved inorganic N (DIN), with reductions at different sites ranging from 0.22 to 9.66 kg N ha−1 (8.4–43.4%), indicating GM effectively decreases N runoff by reducing DIN. Model simulations of ponding water depth, runoff, TN concentration in surface water, and TN loss in paddy fields produced the consistency indices and simulation efficiencies of 0.738–0.985, 0.737–0.986, 0.912–0.986, and 0.674–0.972, respectively, indicating that the model can be used to evaluate water consumption and N runoff loss in the GM-paddy system. The simulations showed that GM with a 40% N fertilizer significantly reduced N runoff loss under all rainfall conditions, with the greatest reductions in wet years. Under wet, normal, and dry conditions, the GM treatments significantly reduced average TN loss by 0.37–5.53 kg N ha−1 (12.77–29.17%), 0.21–5.32 kg N ha−1 (9.95–24.51%), and 0.02–3.2 kg N ha−1 (1.78–23.19%), respectively, compared to the winter fallow treatment. These results indicate that the combination of GM and a 40% reduction in N fertilizer can significantly reduce N runoff loss from paddy fields, demonstrating good effectiveness under various rainfall conditions, making it a green production model worth promoting.

Betula luminifera, an indigenous hardwood tree in South China, possesses significant economic and ecological value. In view of the current severe drought situation, it is urgent to enhance this tree’s drought tolerance. However, traditional artificial methods fall short of meeting the demands of breeding efforts due to their inefficiency. To monitor drought situations in a high-throughput and automatic approach, a deep learning model based on phenotype characteristics was proposed to identify and classify drought stress in B. luminifera seedlings. Firstly, visible-light images were obtained from a drought stress experiment conducted on B. luminifera shoots. Considering the images’ characteristics, we proposed an SAM-CNN architecture by incorporating spatial attention modules into classical CNN models. Among the four classical CNNs compared, ResNet50 exhibited superior performance and was, thus, selected for the construction of the SAM-CNN. Subsequently, we analyzed the classification performance of the SAM-ResNet50 model in terms of transfer learning, training from scratch, model robustness, and visualization. The results revealed that SAM-ResNet50 achieved an accuracy of 1.48% higher than that of ResNet50, at 99.6%. Furthermore, there was a remarkable improvement of 18.98% in accuracy, reaching 82.31% for the spatial transform images generated from the test set images by applying movement and rotation for robustness testing. In conclusion, the SAM-ResNet50 model achieved outstanding performance, with 99.6% accuracy and realized high-throughput automatic monitoring based on phenotype, providing a new perspective for drought stress classification and technical support for B. luminifera-related breeding work.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The “gut-heart” axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg−1·d−1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.

BackgroundYunnan, a southwest highland and newly industrialized region of China, has an unknown hospitalization burden of inflammatory bowel disease (IBD). The study was conducted to explore territorial hospitalization burden of IBD.MethodsThe formatted medical records of patients with IBD were collected from a territory-wide database in Yunnan Province, China, from 2015 to 2020. General characteristics of the study population were reported using descriptive statistics. To evaluate the length of stay, hospitalization costs, surgery, complications, and trends in patients with inflammatory bowel disease. The logistic regression analysis was established to explore the factors affecting the hospitalization costs.ResultsA total of 12,174 records from 8192 patients were included. The annual hospitalization cost of IBD in Yunnan Province increased significantly from 2015 to 2020. From 2015 to 2020, the regional hospitalization burden of IBD increased, but it represented a decline in cost per hospitalization (r = −0.024, P = 0.008) and the length of stay (r = −0.098, P < 0.001). Surgery rates for hospitalized patients with Crohn’s disease (CD) did not decrease (r = −0.002, P = 0.932), and even increased for patients with ulcerative colitis (UC) (r = 0.03, P = 0.002). The costs per hospitalization were $ 827.49 (540.11–1295.50) for UC and $ 1057.03 (644.26–1888.78) for CD. Among the identifiable cost items during the period, drug costs accounted for the highest proportion, accounting for 33% and 37.30% in patients with UC and CD, respectively. Surgical intervention [OR 4.87 (3.75–6.31), P < 0.001], comorbidities [OR 1.72 (1.52–1.94), P < 0.001], complications [OR 1.53 (1.32–1.78), P < 0.001], and endoscopy [OR 2.06 (1.86–2.28), P < 0.001] were predictor of high hospitalization costs.ConclusionThe increasing burden of IBD is noteworthy a newly industrialized region of China. Interventions targeting surgery, complications, and comorbidities may be effective means of controlling the increasing hospitalization costs of IBD in the regions.

With the recent expansion of structural variant identification in the human genome, understanding the role of these impactful variants in disease architecture is critically important. Currently, a large proportion of genome-wide-significant genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) are functionally unresolved, raising the possibility that some of these SNPs are associated with disease through linkage disequilibrium with causal structural variants. Hence, understanding the linkage disequilibrium between newly discovered structural variants and statistically significant SNPs may provide a resource for further investigation into disease-associated regions in the genome. Here we present a resource cataloging structural variant-significant SNP pairs in high linkage disequilibrium. The database is composed of (i) SNPs that have exhibited genome-wide significant association with traits, primarily disease phenotypes, (ii) newly released structural variants (SVs), and (iii) linkage disequilibrium values calculated from unphased data. All data files including those detailing SV and GWAS SNP associations and results of GWAS-SNP-SV pairs are available at the SV-SNP LD Database and can be accessed at ‵https://github.com/hliang-SchrodiLab/SV_SNPs. Our analysis results represent a useful fine mapping tool for interrogating SVs in linkage disequilibrium with disease-associated SNPs. We anticipate that this resource may play an important role in subsequent studies which investigate incorporating disease causing SVs into disease risk prediction models.

BackgroundProstate cancer (PCa) is the second most prevalent malignant tumor in male, and bone metastasis occurs in about 70% of patients with advanced disease. The STING pathway, an innate immune signaling mechanism, has been shown to play a key role in tumorigenesis, metastasis, and cancerous bone pain. Hence, exploring regulatory mechanism of STING in PCa bone metastasis will bring novel opportunities for treating PCa bone metastasis.MethodsFirst, key genes were screened from STING-related genes (SRGs) based on random forest algorithm and their predictive performance was evaluated. Subsequently, a comprehensive analysis of key genes was performed to explore their roles in prostate carcinogenesis, metastasis and tumor immunity. Next, cellular experiments were performed to verify the role of RELA in proliferation and migration in PCa cells, meanwhile, based on immunohistochemistry, we verified the difference of RELA expression between PCa primary foci and bone metastasis. Finally, based on the key genes to construct an accurate and reliable nomogram, and mined targeting drugs of key genes.ResultsIn this study, three key genes for bone metastasis were mined from SRGs based on the random forest algorithm. Evaluation analysis showed that the key genes had excellent prediction performance, and it also showed that the key genes played a key role in carcinogenesis, metastasis and tumor immunity in PCa by comprehensive analysis. In addition, cellular experiments and immunohistochemistry confirmed that overexpression of RELA significantly inhibited the proliferation and migration of PCa cells, and RELA was significantly low-expression in bone metastasis. Finally, the constructed nomogram showed excellent predictive performance in Receiver Operating Characteristic (ROC, AUC = 0.99) curve, calibration curve, and Decision Curve Analysis (DCA) curve; and the targeted drugs showed good molecular docking effects.ConclusionIn sum, this study not only provides a new theoretical basis for the mechanism of PCa bone metastasis, but also provides novel therapeutic targets and novel diagnostic tools for advanced PCa treatment.

Summary: ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1D325A/D325A) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.