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Objective‍ ‍To construct a mammography image classification assistant system suitable for Chinese population， and explore the potential of artificial intelligence technology to assist early screening of breast cancer in China. Methods‍ ‍Curated breast imaging subset of digital database for screening mammography （CBIS-DDSM）， Mammographic image analysis society database （MIAS） and other international open datasets were used to conduct model training respectively in order to reproduce the mainstream in-depth learning methods in the current literature. The model was also tested on the Chinese breast mammography database （CBMD） provided by Huajiao Technology Co.， Ltd， and the performance was compared. Aiming at the problem that the Chinese population data are not ideal in the performance test of the open dataset training model， an optimization strategy based on the sliding window adjustment mechanism was implemented in combination with the characteristics of Chinese population data. Then a two-stage migration learning method was designed to improve the overall performance of the model， and then development of our system was carried out. Results‍ ‍With the sliding window adjustment mechanism and the CBMD training model after two-stage transfer learning， the accuracy of our developed system was improved from 0.50 of the open datasets to 0.80， precision from 0.54 to 0.82， sensitivity from 0.52 to 0.80， F1 value from 0.52 to 0.80， and AUC value from 0.51 to 0.89 based on the Chinese population dataset as the test set. Conclusion‍ ‍Through the introduction of sliding window adjustment mechanism and two-stage migration learning strategy， the performance of the breast molybdenum target image classification model has been significantly improved in the Chinese population dataset， and our system primarily achieves the purpose of assisting the classification of breast molybdenum target images for the Chinese population.

BackgroundHypertension is a prevalent cardiovascular risk factor that significantly contributes to morbidity and mortality worldwide. Previous studies have highlighted the role of inadequate sleep during weekdays in the development of hypertension. However, the potential mitigative effects of weekend catch-up sleep (WCS) on hypertension have been less explored.MethodsThis cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020, focusing on American adults. We assessed the association between WCS (defined as the difference in sleep duration between weekend and weekday) and the presence of hypertension. Participants were classified into two groups based on their WCS duration: none (below 1 hours), yes (over 1 hours). Multivariable logistic regression models adjusted for potential confounders such as age, gender, Body mass index (BMI), and lifestyle factors were utilized to explore this association. A Generalized Additive Model (GAM) was employed to generate smooth curves for a nuanced analysis of the nonlinear relationship.ResultsThe findings indicated that moderate WCS (less than 4 hours) was significantly associated with a reduced risk of hypertension, while excessive WCS (greater than 4 hours) showed no significant protective benefits. ConclusionModerate weekend catch-up sleep could serve as an effective intervention to mitigate hypertension risk, especially in populations with restricted weekday sleep. These results suggest the potential for integrating sleep management strategies into public health recommendations to address hypertension. Future longitudinal studies are needed to confirm these findings and clarify the mechanisms underlying the relationship between WCS and hypertension risk.

ObjectiveTo establish a prediction nomogram for early prediction of neonatal acute respiratory distress syndrome (NARDS).MethodsThis is a retrospective cross-sectional study conducted between January 2021 and December 2023. Clinical characteristics and laboratory results of cases with neonatal pneumonia were compared in terms of presence of NARDS diagnosis based on the Montreux Definition. The NARDS group and non-NARDS group were then compared to establish a prediction nomogram for early prediction of NARDS. The predictive accuracy and compliance of the model were evaluated using subject operating characteristic curves, area under the ROC curve, and calibration curves, and the model performance was estimated by self-lifting weight sampling. The Hosmer–Lemeshow test was used to assess the goodness of fit of the model.FindingsNARDS group consisted of 104, non-NARDS group consisted of 238 newborns in our study. Gestational age, triple concave sign, blood glucose measurement after birth (Glu), Apgar score at the 5th minute (Apgar5), neutrophil count (ANC) and platelet count (PLT) are independent predictors of NARDS in late preterm and term newborns who present with progressive respiratory distress and require varying degrees of respiratory support within the first 24 h of life to minimize work of breathing and restore organismal oxygenation. The area under the ROC curve was 0.829 (95% CI = 0.785–0.873), indicating the model's strong predictive power. In addition, decision curve analysis showed that the model had significantly better net benefits.ConclusionIn this study, a predictive column-line plot was constructed based on six clinically accessible conventional variables. Early application of this model has a better predictive effect on the early diagnosis of NARDS, thus facilitating more timely and effective interventions.

Neonatal calves’ diarrhea, which can be severe enough to cause death, has a significant impact on the global cattle industry. In this study, alfalfa polysaccharides and seaweed polysaccharides were found to significantly improve the diarrhea condition in neonatal calves. To explore the underlying mechanisms, further microbiomic and metabolomic analyses were conducted. This study investigated the impact of alfalfa polysaccharides and seaweed polysaccharides on growth performance, serum metabolites, gut microbiota, and metabolomics in neonatal Holstein calves. A total of 24 newborn calves were randomly assigned to three groups, with 8 calves per treatment group. The control (CON) group was fed a basal diet, the alfalfa polysaccharide (AP) group received a basal diet supplemented with alfalfa polysaccharides (4 g/calf/day), and the seaweed polysaccharide group (SP) received a basal diet supplemented with seaweed polysaccharides (4 g/calf/day). These polysaccharides were plant extracts. Compared to the CON group, the results indicated that SP significantly enhanced the body weight, height, chest circumference, and average daily gain of Holstein calves (p < 0.05), while also reducing the diarrhea rate and improving manure scoring (p < 0.05). Compared to the CON, AP also reduced the diarrhea rate (p < 0.05). In terms of serum biochemistry, supplementation with AP and SP increased serum alkaline phosphatase (ALP) and insulin-like growth factor 1 (IGF-1) levels compared to the CON group (p < 0.05). Both AP and SP elevated serum catalase (CAT) and Total Antioxidant Capacity (T-AOC) levels, indicating enhanced antioxidant status (p < 0.05). Regarding immune responses, supplementation with AP and SP significantly increased serum complement component 3 (C3) and immunoglobulin M (IgM) levels, while significantly reducing pro-inflammatory cytokines interleukin-18 (IL-18), tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) compared to the CON group (p < 0.05). Microbiota analysis revealed that AP modulated the abundance of Firmicutes, while SP influenced the abundance of Prevotella and Succiniclasticum. AP and SP differentially influenced intestinal metabolites compared to the CON group, leading to enrichment in pathways related to immunity, antibacterial, and anti-inflammatory functions. These pathways included the biosynthesis of alkaloids from ornithine, lysine, and nicotinic acid, glucocorticoid and mineralocorticoid receptor canothersis/antagonists, secondary metabolite biosynthesis, and alkaloid biosynthesis from histidine and purine, thus alleviating intestinal inflammation. Therefore, by supplementing with AP and SP, the diarrhea rate in calves was reduced, and the immune function of Holstein calves was enhanced, while simultaneously promoting a higher relative abundance of beneficial gut bacteria and suppressing the relative abundance of pathogenic bacteria. Additionally, gut pathways associated with immune response and inflammation were modulated by AP and SP. This study provided valuable insights and theoretical underpinnings for the use of AP and SP in preventing diarrhea in neonatal calves.

Reportedly, the number of κ-casein (κ-CN) B alleles increases the proportion of κ-CN to total protein and the κ-CN content. This phenomenon is caused by single-nucleotide polymorphisms (SNPs) in the promoter region of CSN3, which encodes the B variant. Therefore, a series of 5′-deleted promoter plasmids were constructed to define the core promoter of CSN3. The promoter activity was analyzed by comparing the luciferase activity among the recombinant vectors with truncated promoters. No mutation occurred in the core promoter region (5′-ctatcgtcagatctttcctttctgtcatcttcctattggtg-3′) of CSN3 in 40 cows. A 2092 bp promoter region of CSN3 was re-sequenced for detection, and nine variants were found, of which only three variants had mutation frequencies > 40%, which were −1002T>−, −1654T>A, and −2039T>G. The CSN3 promoter polymorphisms did not correlate with the CSN3 A and B alleles according to the Pearson’s chi-square test (p > 0.05). Moreover, the luciferase activity analysis of the CSN3 promoter showed no difference among pGL3 recombinants with different polymorphic CSN3 promoters (p > 0.05). In the genetic selection of dairy cows, mutations in the CSN3 core promoter should be focused upon. These findings provide a reference for the regulatory mechanism of bovine milk proteins and offer guidance for the genetic selection and breeding of cows.

Periodontitis, a chronic inflammatory oral disease resulting from plaque biofilms, affects about 743 million individuals worldwide. However, the efficacy of current treatments is hampered by challenges in delivering antibiotics to recalcitrant oral biofilms and bacterial resistance, thereby impeding successful treatment of infectious diseases. To address the issues, an antibacterial photothermal material was designed, comprising a spherical structure of zinc oxide (ZnO) wrapped with triiron tetraoxide (Fe 3 O 4 ). The outer layer of the material adsorbed epsilon-polylysine (EPL) by electrostatic action, ultimately leading to the fabrication of Fe 3 O 4 /ZnO/EPL nanoparticles (FZE NPs). The Fe 3 O 4 core endowed the nanoparticles with efficient photothermal properties, facilitating the dispersion of dense biofilms, which dramatically promoted the adsorption and penetration of ZnO and EPL into the biofilms to effectively kill bacteria in biofilms in vitro with enhanced sterilization ability. Additionally, upon dissolution in aqueous media, EPL acts as a positively charged antimicrobial peptide that adsorbs onto the surface of negatively charged bacterial membranes, thereby effectively modulating inflammatory responses. In order to ascertain the efficacy of FZE NPs, an investigation was conducted into their antimicrobial effects against the periodontitis-associated pathogen Porphyromonas gingivalis ( P. gingivalis ) in vitro . Furthermore, the antiperiodontitis potential of FZE NPs was evaluated in Sprague-Dawley (SD) rats of ligamentous periodontitis. In addition, toxicity evaluations indicated that the material had an acceptable biosafety profile in vitro and in vivo . In summary, the nanospheres (FZE NPs) represent a promising therapeutic strategy for the treatment of periodontitis.

Background: The Old World sand fly, Phlebotomus papatasi (Scopoli), a vector of zoonotic cutaneous leishmaniasis, is usually controlled by insecticides, including anticholinesterases. Previous studies have revealed 85% amino acid sequence identity of recombinant P. papatasi acetylcholinesterase (rPpAChE1) to mosquito AChE. They identified synthetic carbamates that selectively inhibited rPpAChE1 and circumvented the G119S mutation responsible for high-level resistance to anticholinesterases. This study reports the construction, baculovirus expression, and biochemical properties of rPpAChE1 containing the F290V and F331W orthologous mutations from mosquitoes., Methods: Recombinant PpAChE1 enzymes with or without the F290V, F331W, and G119S orthologous mosquito mutations were expressed in Sf21cells utilizing the baculoviral system. Ellman assays determined changes in catalytic properties and inhibitor sensitivity resulting from wild type and mutant rPpAChE1 containing single or combinations of orthologous mosquito mutations., Results: Each of the orthologous mutations (F290V, F331W, and G119S) from mosquito AChE significantly reduced inhibition sensitivity to organophosphate or carbamate pesticides, and catalytic activity was lost when they were expressed in combination. Novel synthetic carbamates were identified that significantly inhibited the rPpAChEs expressing each of the single orthologous mosquito mutations., Conclusions: These novel carbamates could be developed as efficacious insecticides, with improved specificity and safety for use in sand fly or mosquito populations expressing the mutant AChEs., Competing Interests: Declarations. Ethics approval and consent to participate: Institutional biosafety committee approval was granted IBC no. 2022–02 for the reported recombinant DNA in vitro expression in cell culture studies. Other ethics and consent to participate is not applicable. Consent for publication: Written informed consent for publication was obtained from all authors. Competing interests: The authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Glyphosate (Glyp) is a widely used herbicide, but its through prolonged and excessive spraying residues pose significant health risks. A ratiometric multimodal sensing platform combining fluorescence, colorimetry, and photothermal detection was developed for Glyp detection using a cerium/polyacrylic acid-modified porphyrin-based metal-organic framework (PCN@PAA-Ce). The detection strategy relies on the inhibition of acetylcholinesterase by Glyp, the oxidase-like activity of PCN@PAA-Ce, and the competition between enzymatic products and 3,3',5,5'-tetramethylbenzidine (TMB). Glyp inhibits acetylcholinesterase, which prevents the hydrolysis of acetylthiocholine and the production of reduced thiocholine. The oxidase-like property of PCN@PAA-Ce facilitates the oxidation of TMB (colorless) to oxidized TMB (oxTMB) (blue-green), while fluorescence resonance energy transfer caused oxTMB to quench the red fluorescence of PCN@PAA-Ce. Under ultraviolet light, the probe solution exhibits yellow-green fluorescence as a reference signal. Additionally, the excellent photothermal conversion of oxTMB enables the probe to respond to Glyp through photothermal responses. The detection ranges in the three modes were 1 × 10 -5 to 4 mg mL -1 , 1 × 10 -4 to 6 mg mL -1 , and 1 × 10 -4 to 6 mg mL -1 , respectively, with detection limits of 9.85 × 10 -6 mg mL -1 , 8.69 × 10 -5 mg mL -1 , and 9.72 × 10 -5 mg mL -1 , respectively. Compared to a single-mode probe, the multimodal probe's self-verification function provides more accurate and stable detection, offering broader potential for application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Dietary intake is a predominant pathway of human exposure to environmental Cadmium (Cd), but wheat (Triticum aestivum L.) has not received enough concerns for its risk of Cd contamination. A field survey of Cd-contaminated rice-wheat rotation farmlands in China provided detailed comparison of Cd accumulation capacity by rice and wheat grains. The results indicated that Cd-BCF of wheat grains (median values 0.42) were obviously higher than those of rice grains (median values 0.12) under wide soil Cd levels and pH ranges. Soil Cd levels rather than pH played a vital role on Cd accumulation by wheat grains, and high wheat grain Cd concentrations (0.12-0.13 mg kg⁻ 1 ) were even observed in mildly alkaline soil that normally have low Cd mobility. Dietary Cd exposure risks were assessed by the crop Cd exposure models considering different soil Cd content, pH and dietary structures of residents. The results indicated that the intake of wheat grains contributed 56.1-86.5% of total crop Cd exposure, with an increase in its contribution with the increase of soil pH. Residents favoring wheat would have a significant Cd exposure risk if consuming crops from soils with Cd levels above 0.41 mg kg⁻ 1 , which was considerably lower than the current soil Cd risk screening value for alkaline soils (0.6 mg kg -1 ). Our findings indicate a high Cd accumulation capacity of wheat grains and consequent risk of dietary Cd exposure, which deserves further exploration on the correlation among soil Cd screening value, grain Cd limit value and its dietary exposure risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Maternal hypertensive disorders during pregnancy are a worldwide health problem, particularly in the countries/regions with low sociodemographic levels. This study aimed to reveal and predict the hypertensive disorders during pregnancy-related epidemiological trends., Methods: Using data from the Global Burden of Disease 2019 study, we constructed an age-period-cohort model to assess the net drift (annual percentage changes), associated age, period, and cohort effects across global and different sociodemographic index (SDI) regions. Moreover, we analyzed attributable risk factors and future trends based on the autoregressive integrated moving average model., Results: The numbers of hypertensive disorders during pregnancy worldwide increased by 10.9% (95% uncertainty interval, 6.1-15.3) from 1990 to 2019 and only increased in the low-SDI countries. The age-standardized incidence rate declined by 23.6% (20.6, 26.9), with a global net drift of -0.8%, whereas some higher-SDI countries showed a positive net drift. After controlling for period and cohort factors, the highest incidence was observed in the 20- to 29-year age group. The period and cohort effects showed decreasing trends, whereas unfavorable period effects occurred after 2010 in high-SDI and middle-high-SDI countries. High-income North America and western sub-Saharan Africa have shown increased numbers of disability-adjusted life years due to malnutrition. The autoregressive integrated moving average model revealed downward trends in the global incidence and age-standardized incidence rate by 2030., Conclusions: Our study highlights significant regional and national variations and age differences in the burden of hypertensive disorders during pregnancy associated with SDI stratification, which will facilitate the targeting of cost-effective health policy planning, resource allocation, and women's health management by policymakers.

Colon cancer development may be initiated by multiple factors, including chronic inflammation, genetic disposition, and gut dysbiosis. The loss of beneficial bacteria and increased abundance of detrimental microbes exacerbates disease progression. Bacteroides plebeius ( B. plebeius ) is a human gut microbe, and its colon colonization is enhanced by a seaweed-supplemented diet. We found that mice orally administered with B. plebeius and fed a diet containing 1% seaweed developed a unique gut microbial composition. By linear discriminant analysis effect size analysis, we found that B. plebeius colonization increased the abundance of Blautia coccoides and reduced the abundance of Akkermansia sp. and Dubosiella sp. We also showed that colonization of B. plebeius suppressed the colon tumor development induced by azoxymethane/dextran sulfate sodium in specific-pathogen-free mice, coinciding with a reduced abundance of Muribaculaceae sp., Closteridale sp., and Bilophila sp. Moreover, B. plebeius colonization in gnotobiotic mice resulted in enhanced production of selected metabolites, including propionic, taurocholic, cholic, alpha-, and beta-muricholic, as well as ursodeoxycholic acids. Importantly, some of these metabolites show anti-inflammatory and tumor-suppressive effects. We conclude that B. plebeius is able to restructure the gut microbial community and produce beneficial metabolites, leading to inhibition of colitis-associated colon cancer development.IMPORTANCEThis work delves into the pivotal role of gut microbiota in suppressing the progression of colitis-associated colon cancer. By investigating the impact of Bacteroides plebeius that can be colonized in mouse gut by feeding the animal with seaweed diet, we unveil a novel mechanism through which this beneficial bacterium reshapes the gut microbial community and produces metabolites with anti-inflammatory and tumor-suppressive properties. Such findings underscore the potential of harnessing specific microbes, like B. plebeius shown in this study, to modulate the gut ecosystem and mitigate the risk of colitis-associated colon cancer., Competing Interests: The authors declare no conflict of interest.

The angiotensin-converting enzyme 2 (ACE2) receptor is shared by various coronaviruses with distinct receptor-binding domain (RBD) architectures, yet our understanding of these convergent acquisition events remains elusive. Here, we report that two bat MERS-related coronaviruses (MERSr-CoVs) infecting Pipistrellus nathusii (P.nat)-MOW15-22 and PnNL2018B-use ACE2 as their receptor, with narrow ortholog specificity. Cryoelectron microscopy structures of the MOW15-22/PnNL2018B RBD-ACE2 complexes unveil an unexpected and entirely distinct binding mode, mapping >45 Å away from that of any other known ACE2-using coronaviruses. Functional profiling of ACE2 orthologs from 105 mammalian species led to the identification of host tropism determinants, including an ACE2 N432-glycosylation restricting viral recognition, and the design of a soluble P.nat ACE2 mutant with potent viral neutralizing activity. Our findings reveal convergent acquisition of ACE2 usage for merbecoviruses found in European bats, underscoring the extraordinary diversity of ACE2 recognition modes among coronaviruses and the promiscuity of this receptor., Competing Interests: Declaration of interests H.Y. has submitted a patent application to the China National Intellectual Property Administration for the utilization of propagation-competent VSV to evaluate amplification of ACE2-using merbecoviruses in bat ACE2-expressing cells., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has had a significant impact on the physical and mental health of human beings. Most adolescents in mainland of China have been infected with COVID-19 after the adjustment of the dynamic zero-COVID-19 policy. This study aims to analyze the relationship between the COVID-19 pandemic effect and depressive symptoms among adolescents in mainland China., Methods: This school-based repeated cross-sectional study was conducted on students aged 11-19 years from September to October 2022 and September to October 2023 in Ningbo, Zhejiang Province, China, using a stratified cluster, multistage sampling method. Data analysis occurred from January to June 2024. Depression symptoms and bullying victimization, exclusion of cyberbullying, were assessed using the 20-item Center for Epidemiological Studies Depression Scale (CES-D) and Bully/Victim Questionnaire, respectively., Results: In the first survey wave in 2022 during the dynamic zero-COVID-19 policy period in Mainland China, 10,224 participants completed the questionnaires. In wave 2 survey in 2023 which was the first year after lifting of the dynamic zero-COVID-19 policy, 11,604 participants completed the questionnaires. This resulted in a sample of 10,224 in wave 1 and 11,604 in wave 2. The mean age in wave 1 was 15.2 (SD = 1.7) and 15.1 (SD = 1.8) in wave 2. The prevalence of depression symptoms in adolescents in wave 2 was higher than in wave 1 (17.0% vs. 14.6%, P < 0.05). The prevalence of bullying victimization and types of bullying victimization in school among adolescents were higher in 2023 than in 2022. A total of 3.2% of the 2023 participants and 1.7% of the 2022 participants experienced bullying victimization in school (P < 0.05). The odds ratio of experiencing depression (CES-D Score ≧ 16) and bullying victimization in school were 1.18 (95% CI, 1.10-1.28) and 1.86 (95% CI, 1.55-2.24) times higher, respectively, in 2023 than in 2022 (P < 0.01). The mediated regression analysis revealed that after lifting of the dynamic zero-COVID-19 had a significant association with an increase in depression symptoms, which was partially mediated by bullying victimization in school (total association:β = 0.175; SE = 0.038; P < 0.001; direct association:β = 0.138; SE = 0.039; P < 0.001; indirect association: a*b = 0.037; P < 0.001; the proportion of mediation: 20.88%, P < 0.001)., Conclusions: The findings of this repeated cross-sectional study suggest that an increased risk of depression symptoms or bullying victimization has been associated with the COVID-19 pandemic in mainland China after lifting the dynamic zero-COVID-19 policy. In addition, bullying victimization may play a mediating role in the associations between the pandemic and depression symptoms. These findings indicated that additional support should be offered to Chinese adolescents in the period of post-pandemic COVID-19., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol for the research project had been approved by the Ningbo CDC Institutional Review Board (No. 202201) and had therefore been performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Both the participant and his/her parents or guardian have signed written informed consent forms, and all information related to participants and schools is confidential. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study aims to investigate in patients over 65 with neck of femur (NOF) fractures in Rural Australia, does initial presentation to a peripheral hospital result in a delay to surgery?, Design: Retrospective cohort study., Setting: Dubba Base Hospital, Trauma Hospital Rural Australia (Modified Monash Model (MMM) 3) and catchment area (MMM 3-7), NSW, Australia., Participants: The study includes 350 patients over 65, presenting with closed, unilateral NOF fractures who underwent operative management at the operating centre, 203 from peripheral hospitals., Main Outcome Measures: Primary outcomes include time to surgery and adherence to recommended timeframes for NOF fixation. Secondary outcomes encompass complications, hospital length of stay and a subgroup analysis to identify causes of surgery delay., Results: Patients transferred from peripheral hospitals experienced a statistically significant delay in time from presentation to surgery compared to those presenting directly to the operating centre (42 h vs. 24 h, p < 0.001) and were more likely to be outside of current guidelines for NOF fixation within 36 h of presentation (OR 5.1, p < 0.001). There were no differences in mortality at 1 year between the two groups (15% vs. 18%, p = 0.5). On subgroup analysis, distance from the operating centre, time to x-ray and after-hours presentation were associated with increased likelihood of surgery outside of 36 h in the peripheral hospital group., Conclusion: This study underscores an inequity in service delivery for rural patients with NOF fractures, particularly those requiring transfer. Pre-arrival delays necessitate targeted interventions to address diagnostic service delays, logistical challenges and transport issues in rural health care., (© 2024 National Rural Health Alliance Ltd..)

Metabolic reprogramming is a prominent characteristic of tumor cells, evidenced by heightened secretion of lactate, which is linked to tumor progression. Furthermore, the accumulation of lactate in the tumor microenvironment (TME) influences immune cell activity, including the activity of macrophages, dendritic cells and T cells, fostering an immunosuppressive milieu. Anti‑programmed cell death protein 1 (PD‑1)/programmed death‑ligand 1 (PD‑L1) therapy is associated with a prolonged survival time of patients with non‑small cell lung cancer. However, some patients still develop resistance to anti‑PD‑1/PD‑L1 therapy. Lactate is associated with resistance to anti‑PD‑1/PD‑L1 therapy. The present review summarizes what is known about lactate metabolism in tumor cells and how it affects immune cell function. In addition, the present review emphasizes the relationship between lactate secretion and immunotherapy resistance. The present review also explores the potential for targeting lactate within the TME to enhance the efficacy of immunotherapy.

Background: There are mixed findings in the literature regarding the association between HIV status and the risk of COVID-19 infection. Thus, we aimed to estimate the association between characteristics of HIV infection and the risk of COVID-19 Infection in a Chinese sample., Methods: We conducted a cross-sectional survey of 1995 people living with HIV (PLWH) and 3503 HIV-negative adults in Ningbo, China. We compared the prevalence rates of the SARS-CoV-2 infection and the long nucleic acid conversion time (more than 2 weeks) among PLWH and HIV-negative participants, respectively. In addition, we explored the risk factors associated with SARS-CoV-2 infection and the long nucleic acid conversion time among the two groups., Results: Overall, 1485/1995 (74.4%) PLWH and 2864/3503 (81.8%) HIV-negative people were infected with SARS-CoV-2. Among the SARS-CoV-2-infected participants, 437/1485 (29.4%) PLWH and 649/2864 (22.7%) HIV-negative people had the long nucleic acid conversion time. After controlling for the potential confounders, the rate of the SARS-CoV-2 infection was lower among the PLWH than the HIV-negative group (adjusted OR = 0.836, 95% CI = 0.706-0.990). However, PLWH had a significantly higher risk of the long nucleic acid conversion time after the SARS-CoV-2 infection (adjusted OR = 1.417, 95% CI = 1.176-1.707) than the HIV negative participants. Compared with those who did not receive ART, PLWH adults who received ART significantly had the increased risk of SARS-CoV-2 infection. Furthermore, HIV-negative participants receiving COVID-19 vaccines significantly displayed the decreased likelihood of the long nucleic acid conversion time after the SARS-CoV-2 infection., Conclusions: Our study indicates that different HIV Infection status was significantly and differently associated with the SARS-CoV-2 infection and the long nucleic acid conversion time. However, the further studies are needed to confirm the effect of ART and COVID-19 vaccines on SARS-CoV-2 infection in PLWH., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving participants provided informed consent forms when they were enrolled. The study was approved by the Human Research Ethics Committee of Ningbo CDC in Ningbo, China (No. 201913). The study was conducted in accordance with the Declaration of Helsinki.2.2 Data collection. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Marine plastic pollution has emerged as a significant ecological and biological issue impacting global marine ecosystems. To develop real-time cleaning systems for marine plastic litter, we implemented a three-dimensional marine plastic litter real-time detection (3D-MPLRD) system that incorporates deep learning techniques. Specifically, image quality assessment and enhancement are applied to mitigate the adverse effects of harsh underwater conditions on image quality, thereby enhancing the training efficacy of models beyond that achieved by conventional approaches. To facilitate the deployment of the 3D-MPLRD system on embedded devices, the YOLOv5 model is compressed and quantified, capitalizing on its robustness to precision loss and model simplification. Practical experimental results demonstrated that the 3D-MPLRD system outperformed the model trained on original datasets in terms of precision, recall, F1-score, and mean average precision. This innovative 3D-MPLRD system serves as a foundational reference for marine environmental protection based on intelligence systems, as opposed to traditional manual methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Gastrointestinal Defects and Immunodeficiency Syndrome-1 (GIDID-1), caused by abnormalities in TTC7A, is an autosomal recessive disorder characterized by multiple gastrointestinal malformations and immune deficiencies, often accompanied by inflammatory bowel disease (IBD). This condition typically results in poor treatment outcomes and is usually fatal in early infancy. This paper examined the genetic abnormalities and clinical features of GIDID by analyzing data from three children and one fetus with gastrointestinal dysfunction and immune deficiency associated with TTC7A abnormalities at our hospital, and reviewed reported cases worldwide. Genetic analysis of the four patients identified eight novel variants in the TTC7A, five of which were likely pathogenic variants, while three were of uncertain significance. Including the cases reported in this paper and through a literature review, there were 89 known cases globally, involving 79 TTC7A variants. Patients typically presented with multiple gastrointestinal malformations, immune deficiencies, or IBD. Thus, genetic testing is recommended for patients with multiple gastrointestinal malformations and recurrent infections to determine if GIDID is due to TTC7A abnormalities. The syndrome generally has a poor prognosis, and this information is crucial for treatment planning, prenatal screening, and genetic counseling., Competing Interests: Declarations. Ethics Approval: This study has been reviewed and approved by the Ethics Committee of the Children's Hospital of Zhejiang University School of Medicine (2024-IRB-0253-P-01). All methods were carried out in accordance with relevant guidelines and regulations. Conflict of Interest: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: This study sought to evaluate the value of a CO 2 field-flooding device in cardiopulmonary bypass (CPB) surgical procedures for congenital heart disease (CHD) performed via a right-side small incision approach., Methods: Between April 2022 and December 2023, 234 children with simple CHD who underwent CPB via a right-side small incision approach were separated into a control group (n = 93) without the use of a CO 2 field-flooding device and a treatment group (n = 141) in which this device was added to the traditional surgical manual exhaust. Demographic, perioperative, arterial blood gas (ABG), and laboratory test data were then compared between these groups of patients., Results: There was a significant difference in abnormal electrocardiogram (ECG) after aorta de-clamping during CPB, and interventions for abnormal ECG after aorta de-clamping during CPB between the control and treatment groups (17(18.3%) vs.14(9.9%), P = 0.048;12(85.7%) vs.7(50%),P = 0.013). The treatment group exhibited a lower pH (7.34 ± 0.07 vs. 7.36 ± 0.06, P = 0.039) and a higher PaCO 2 (43.08 ± 7.36 vs. 38.86 ± 5.65 mmHg, P = 0.042) at the time of 30 min after initiation of CPB. A significant reduction in postoperative CK-MB was observed in treatment group (41.20 ± 17.88 vs. 56.57 ± 22.99 U/L, P = 0.002). Lower 3-day postoperative CRP levels were also observed in the treatment group relative to control (5.77 ± 0.48 vs. 9.45 ± 0.98 mg/L, P < 0.001). The S100ß concentration in the relevant patient cohort increased significantly from the time just after induction, intubation, and installation of the right central venous line to the time of admission to CCU (71.61 ± 11.83 vs. 124.04 ± 38.80, P = 0.01) and at the time of 24 h after operation (71.61 ± 11.83 vs. 101.97 ± 30.31, P = 0.01). No differences on S100β serum concentration level were found at the time of installation of the right central venous line between two groups. But there were statistically significant differences in S100β serum concentration level at the time of admission to CCU between control group and treatment group. (161.19 ± 6.62 vs. 86.89 ± 9.69 pg/ml, P = 0.01). Similar results were observed at the time of 24 h after operation. (127.62 ± 19.44 vs. 76.33 ± 10.40, P = 0.01)., Conclusion: These data suggest that the CO 2 field-flooding device can safely be used when performing CPB surgical procedures via a right-side small incision approach to treat CHD without hypercapnia. The use of such a CO2 field-flooding device at a flow rate of 5 L/min may help protect against cardiac and nervous system damage in children undergoing CHD surgery., Competing Interests: Declarations. Ethics approval and consent to participate: This statement confirming the approval of the study by the ethical committee of Beijing Children’s Hospital, Capital Medical University in Beijing, China. ID number [2022]-E-083-Y. All patients were consented for the participation in the study. The ethics declaration: In accordance with the Declaration of Helsinki. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Fiber-based strain sensors, as wearable integrated devices, have shown substantial promise in health monitoring. However, current sensors suffer from limited tunability in sensing performance, constraining their adaptability to diverse human motions. Drawing inspiration from the structure of the spiranthes sinensis, this study introduces a unique textile wrapping technique to coil flexible silver (Ag) yarn around the surface of multifilament elastic polyurethane (PU), thereby constructing a helical structure fiber-based strain sensor. The synergistic interaction between the elastic PU core and the outer helical Ag yarn enhances the mechanical strength and stretchability of the sensor, while the external helical Ag yarn offers high conductivity. By adjusting the spacing of Ag yarn coils on the surface of the fiber-based sensor, we achieve precise control over both sensing sensitivity and strain range. Specifically, experimental results show that with a pitch of 1.25 mm, the strain range reaches up to 150%, and the gauge factor (GF) is 2.6; when the pitch is adjusted to 5 mm, within a 60% strain range, the GF value significantly increases to 9.3. Based on these excellent performance metrics, we further apply the sensor as a conductor in ECG monitoring garments, successfully verifying its practicality in cardiac monitoring. Additionally, we developed a smart glove for hand function rehabilitation training, utilizing wireless signal transmission to promote hand function recovery in hemiplegic patients. The sensor is also capable of effectively monitoring respiratory rate and pulse, showing broad prospects in the fields of rehabilitation medicine and smart healthcare.

Background: Previous studies have suggested that neighborhoods characterized by higher walkability are related to a reduced risk of ischemic heart disease (IHD), whereas exposure to PM 2.5 is positively associated with risk of IHD. Nevertheless, their joint impact on IHD warrants further investigation., Methods: This prospective cohort study was performed in Yinzhou, Ningbo, China, comprising 47,516 participants. Individual-level walkability and PM 2.5 were evaluated using a commercial walkability database and a land use regression (LUR) model, respectively. Hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were calculated using two Cox proportional hazards models: one based on two-year average PM 2.5 levels prior to baseline, and the other incorporating time-varying PM 2.5 assessed on a monthly scale. Dose-response relationships were explored using restricted cubic spline (RCS) functions. Interactions on both additive and multiplicative scales were assessed via relative excess risk due to interaction (RERI) and likelihood-ratio tests. Joint effects were explored and visualized using a 3D wireframe plot., Results: Over a median follow-up of 5.14 years, 1735 incident cases of IHD were identified. Adjusted HRs (95 % CIs) were 1.56 (1.34-1.81) per 10 μg/m 3 increase in PM 2.5 and 0.96 (0.94-0.98) per 10-unit increase in walkability, with both exposures exhibiting non-linear dose-response relationships. Walkability and PM 2.5 were positively correlated (r s = 0.12, P < 0.001), and a multiplicative interaction was detected (P interaction = 0.019)., Conclusion: Walkability was inversely associated with risk of IHD, whereas exposure to PM 2.5 was positively associated with IHD. Notably, the pernicious effects of PM 2.5 could be attenuated in areas with higher levels of walkability. Our findings underscore the significance of walkable urban design, air quality improvement, as preventive strategies for IHD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The exposure to extreme heat at workplaces poses substantial threat to human effort and manual labour. This becomes more prominent due to the global dispersion of labour-intensive production activities via trade. We combine a climate model with an input-output model to quantify the risks associated with trade-related occupational extreme heat exposure. Here we show an 89% surge in trade-related labour exposure to extreme heat, escalating from 221.5 to 419.0 billion person-hours between 1995 and 2020. Lower-middle-income and low-income economies constituted 53.7% and 18.3% of global exposure but only 5.7% and 1.0% of global labour compensation. In countries highly susceptible to extreme heat conditions, workers perform tasks in heated conditions for up to about 50% of their working hours. The disproportionate trade effects in redistributing global benefits and costs leads to the inequality in heat exposure between developed and developing economies. In striving for equitable and safe work conditions, workers vulnerable to heat extremes in developing economies should be protected by climate adaptation infrastructure, given their critical roles in the global production system., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background and Aims: The burden of cardiometabolic multimorbidity (CMM) in hypertensive patients is substantial, and obesity may play an important role in progression of CMM. We aim to explore associations of obesity with the transition patterns from hypertension to first cardiometabolic disease (FCMD), CMM, and death., Methods and Results: 21 286 hypertensive patients over 40 were enrolled in Yinzhou Health Information System from 2010 to 2015, followed until June 30, 2022. CMM was defined as the coexistence of stroke, diabetes, and coronary heart disease. Two indices of obesity including body mass index (BMI) and waist circumference (WC) were assessed at baseline. We used multi-state models to evaluate associations of BMI and WC between risk of CMM trajectories in hypertensive patients. During a median follow-up of 8.06 years, 13 289 hypertensive patients developed CMD, 6401 further developed CMM, and 1648 died. WC in every 1 cm increase was positively associated with risk of transitions from hypertension to FCMD (HR = 1.01, 95 % CI: 1.00-1.01) and from FCMD to CMM (HR = 1.01, 95 % CI: 1.01-1.02). Underweight participants had a 17 % elevated risk of transition from FCMD to CMM, while overweight participants had a 5 % elevated risk of transition from hypertension to FCMD. U-shape curves were observed for the association of WC with transitions from FCMD or CMM to death., Conclusions: Underweight and abnormal WC were associated with an increased risk of CMM and death in hypertensive patients. Our findings emphasize the role of healthy body shape in hypertensive management., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2025 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

In this paper, near-infrared spectroscopy(NIRS) was employed to analyze 129 batches of commercial products of Reduning Injection. The batch reporting rate was estimated according to the report of Reduning Injection in the direct adverse drug reaction(ADR) reporting system of the drug marketing authorization holder of the Center for Drug Reevaluation of the National Medical Products Administration(National Center for ADR Monitoring) from August 2021 to August 2022. According to the batch reporting rate, the samples of Reduning Injection were classified into those with potential risks and those being safe. No processing, random oversampling(ROS), random undersampling(RUS), and synthetic minority over-sampling technique(SMOTE) were then employed to balance the unbalanced data. After the samples were classified according to appropriate sampling methods, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA), uninformative variables elimination(UVE), and genetic algorithm(GA) were respectively adopted to screen the features of spectral data. Then, support vector machine(SVM), logistic regression(LR), k-nearest neighbors(KNN), naive bayes(NB), random forest(RF), and artificial neural network(ANN) were adopted to establish the risk prediction models. The effects of the four feature extraction methods on the accuracy of the models were compared. The optimal method was selected, and bayesian optimization was performned to optimize the model parameters to improve the accuracy and robustness of model prediction. To explore the correlations between potential risks of clinical use and quality test data, TreeNet was employed to identify potential quality parameters affecting the clinical safety of Reduning Injection. The results showed that the models established with the SVM, LR, KNN, NB, RF, and ANN algorithms had the F1 scores of 0.85, 0.85, 0.86, 0.80, 0.88, and 0.85 and the accuracy of 88%, 88%, 88%, 85%, 91%, and 88%, respectively, and the prediction time was less than 5 s. The results indicated that the established models were accurate and efficient. Therefore, near infrared spectroscopy combined with machine learning algorithms can quickly predict the potential risks of clinical use of Reduning Injection in batches. Three key quality parameters that may affect clinical safety were identified by TreeNet, which provided a scientific basis for improving the safety standards of Reduning Injection.

Background: Sentinel lymph node biopsy (SLNB) using radioisotope tracer plus blue dye is the gold standard after neoadjuvant chemotherapy (NAC) in initially cN1 breast cancer patients, but clinical use still has limitations. This study aims to examine diagnostic performance of dual indocyanine green (ICG) and methylene blue tracing for SLNB in patients who have completed NAC for breast cancer with initially cN1 disease., Methods: Adult women (20-80 years of age) scheduled to undergo NAC for biopsy-proven cT0-3N1M0 primary invasive breast cancer were consecutively enrolled in this prospective, multicenter, cohort study. Upon the completion of NAC, SLNB was conducted using ICG and methylene blue, followed by axillary lymph node dissection. The primary outcome was the detection rate (DR); secondary outcomes included the false-negative rate (FNR) and adverse events associated with the use of tracers., Results: A total of 156 patients were enrolled; all underwent SLNB after NAC. The median number of lymph nodes retrieved during SLNB was 3 (range: 0-11). The DR was 97.4% (152/156; 95% CI, 93.6%-99.0%). The FNR was 6.7% (4/60; 95% CI, 2.6%-15.9%). Negative predictive value was 95.7% (88/92; 95% CI, 89.4%-98.3%). In the subgroup analysis stratified by ycN status, FNR was 4.0% (1/25; 95% CI, 0.7%-19.5%) and 8.6% (3/35; 95% CI, 3.0%-22.4%) in the ycN0 and ycN+ subgroups, respectively. No allergic reaction was reported., Conclusions: SLNB with ICG plus methylene blue achieved a high DR and a very low FNR in breast cancer patients with initially cN1 disease., Trial Registration: ClinicalTrials.gov (https://www., Clinicaltrials: gov/), NCT02869815., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

N 6 -acetyl-L-lysine residue is abundant in dietary protein but little is known about its potential influences on the diet-consumers. Herein, it is reported that Lysyl-tRNA synthetase (KARS) mediates co-translational deposition of diet-derived N 6 -acetyl-L-lysine (AcK) in nascent proteins to contribute to the acetylome in cells. Acetylated dietary protein is a direct source of AcK that can widely and substantially regulate the acetylome in multiple organs of mice. By analyzing the mechanisms underlying AcK contributing to the acetylome in mammalian cells, it is found that KARS can utilize AcK as an alternative substrate to produce N 6 -acetyl-l-lysyl-tRNA. The crystal structure of KARS in complex with AcK at 2.26 Å resolution shows that AcK shares the same substrate-binding pocket as L-lysine, allowed by a sidechain flip of Tyr499. The generated N 6 -acetyl-L-lysyl-tRNA introduces AcK into growing nascent polypeptide and results in protein acetylation, including the regions buried inside folded proteins that are post-translational modification (PTM)-inaccessible and functionally important. This undocumented protein modification mechanism is inherently different from PTM and termed as co-translational modification (coTM). It is expected to extend the repertoire of acetylome and improve the understanding of protein modification mechanisms in cells., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: Ischemia-reperfusion of the abdominal aorta often results in damage to distant organs, such as the heart and brain. This cellular heterogeneity within affected tissues complicates the roles of specific cell subsets in abdominal aorta occlusion model (AAO) injury. However, cell type-specific molecular pathology in the hippocampus after ischemia is poorly understood., Aims: In this study, we adopted a mouse AAO to investigate the single-cell transcriptome in the hippocampi in AAO mice., Methods: Male C57BL/6 mice (8 weeks old) were used to create an AAO model, with animals divided into Sham and I/R groups. The I/R group was subjected to 2 h of ischemia followed by 24 h of reperfusion, after which hippocampal tissues were collected for single-cell RNA sequencing and histological analysis. Behavioral tests, including the Rotarod, Y-maze, and new object recognition tests, were performed daily for 28 days post-surgery to evaluate neurological function. A total of 62,624 cells were corresponding 7 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in AAO mice and the function of these cell-specific Genes., Results: AAO injury upregulated astrocyte and oligodendrocyte precursor cell (OPC) proportions (p-value < 0.05). Astrocytes showed unique gene expression related to neurogenesis and mRNA processing. Five distinct astrocyte subtypes emerged post-injury. OPCs exhibited enhanced synapse organization. Microglia activation and the elevated expression level of the epithelial cell oxidative phosphorylation protein-protein interaction (PPI) module indicate an inflammatory response and metabolic changes in response to AAO injury., Conclusions: Our scRNA-seq analysis provides insights into transcriptional changes at the single-cell level in response to AAO-induced hippocampal injury. This study illustrates how the hippocampal region responds to such injury and identifies potential therapeutic targets for intervention, thereby paving the way for future research and treatment strategies., (© 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)