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ABSTRACTWith global supply chains facing increasing complexity and uncertainty, mitigating sustainable supply chain risks (SSCRs) has become an important research topic. Industry 5.0 (I5.0) is a supplement to, and re-development of, Industry 4.0, but no research on improving supply chain resilience (SCRE) through I5.0 drivers to mitigate SSCRs currently exists. Therefore, we developed a QFD approach to investigate the relationship between SSCRs, SCRE, and I5.0 drivers. This study utilises the FDM-FDISM-ANP-TOPSIS method, considers China’s largest private logistics enterprises as the object of empirical analysis, and establishes a sustainable supply chain identification system and SCRE evaluation index system for logistics enterprises through two-stage House of Quality. The findings reveal that 20 key I5.0 significantly bolster 17 SCRE, thereby mitigating 13 SSCRs by QFD-MCDM framework. These I5.0 drivers play a pivotal role in enhancing SCRE of logistics enterprises. This study contributes to the field of supply chain risk resilience in sustainable engineering by integrating the perspectives of SSCRs, SCRE and I5.0. It underscores the necessity for managers in logistics enterprises to develop SCRE solutions that incorporate both SSCRs and I5.0 considerations. Furthermore, our findings offer valuable insights for other industries aiming to bolster their supply chain competitive advantages in an increasingly complex global landscape.

Abstract The incidence of abdominal aortic aneurysm (AAA) is very high, but there is no risk assessment model for early identification of AAA in clinic. The aim of this study was to develop a nomogram risk assessment model for predicting AAA. The data of 280 patients diagnosed as AAA and 385 controls in The Affiliated Suzhou Hospital of Nanjing Medical University were retrospectively reviewed. The LASSO regression method was applied to filter variables, and multivariate logistic regression was used to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve (AUC). The calibration capability of the model is evaluated by using bootstrap (resampling = 1000) internal validation and Hosmer–Lemeshow test. The clinical utility and clinical application value were evaluated by decision curve analysis (DCA) and clinical impact curve (CIC). In addition, a retrospective review of 133 AAA patients and 262 controls from The First Affiliated Hospital of Soochow University was performed as an external validation cohort. Eight variables are selected to construct the nomogram of AAA risk assessment model. The nomogram predicted AAA with AUC values of 0.928 (95%CI, 0.907–0.950) in the training cohort, and 0.902 (95%CI, 0.865–0.940) in the external validation cohort, the risk prediction model has excellent discriminative ability. The calibration curve and Hosmer–Lemeshow test proved that the nomogram predicted outcomes were close to the ideal curve, the predicted outcomes were consistent with the real outcomes, the DCA curve and CIC curve showed that patients could benefit. This finding was also confirmed in the external validation cohort. In this study, a nomogram was constructed that incorporated eight demographic and clinical characteristics of AAA patients, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors.

Abstract Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Background As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear. Methods and Results A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow‐up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58–0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46–0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24–1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24–1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (P=0.012). Conclusions High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.

Objective:. To investigate the predictive value of carotid-femoral pulse wave velocity (cf-PWV) for assessing major adverse cardiovascular events (MACE) and all-cause mortality in different age groups of a Chinese community. Methods:. This is an observational study which enrolled 1,325 individuals from a community in Beijing from September 2007 to October 2018. They were classified based on age into 0.05). Conclusion:. cf-PWV, a measure of arterial stiffness, emerged as an independent risk factor for MACE and all-cause mortality in subjects below 65 years of age.

Abstract Background Body weight and its changes have been associated with cancer outcomes. However, the associations of short‐term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short‐term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. Methods This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height‐adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight‐related indicators and compared their prognostic performance using Harrell's C‐index, integrated discrimination improvement, continuous net reclassification improvement and time‐dependent C‐index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan–Meier analysis and multivariable‐adjusted Cox regression models. Results The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow‐up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C‐index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P 10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5–10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5–10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. Conclusions The prognostic performance of peridiagnosis RWC is superior to other weight‐related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change‐related premature deaths.

Abstract Optimizing the efficiency of definitive endoderm (DE) differentiation is necessary for the generation of diverse organ-like structures. In this study, we used the small molecule inhibitor saracatinib (SAR) to enhance DE differentiation of human embryonic stem cells and induced pluripotent stem cells. SAR significantly improved DE differentiation efficiency at low concentrations. The interaction between SAR and Focal Adhesion Kinase (FAK) was explored through RNA-seq and molecular docking simulations, which further supported the inhibition of DE differentiation by p-FAK overexpression in SAR-treated cells. In addition, we found that SAR inhibited the nuclear translocation of Yes-associated protein (YAP), a downstream effector of FAK, which promoted DE differentiation. Moreover, the addition of SAR enabled a significant reduction in activin A (AA) from 50 to 10 ng/mL without compromising DE differentiation efficiency. For induction of the pancreatic lineage, 10 ng/ml AA combined with SAR at the DE differentiation stage yielded a comparative number of PDX1+/NKX6.1+ pancreatic progenitor cells to those obtained by 50 ng/ml AA treatment. Our study highlights SAR as a potential modulator that facilitates the cost-effective generation of DE cells and provides insight into the orchestration of cell fate determination. Graphical Abstract

Abstract Background Women diagnosed with gestational diabetes mellitus often rely on internet-based health information for managing their condition. This study aims to investigate the present state of electronic health literacy among women with gestational diabetes mellitus, analyze the influencing factors, and explore their experiences regarding accessing, comprehending, evaluating, and applying online health information pertinent to gestational diabetes mellitus. Methods A sequential explanatory mixed methods research design was adopted in this study. Initially, 235 women with gestational diabetes mellitus participated in a cross-sectional survey. The research tools included general information and the Chinese version of the electronic Health Literacy Scale (eHEALS). Descriptive analyses were conducted to describe the characteristics of the sample, and multiple linear regression analyses were used to explore the factors influencing electronic health literacy among women with gestational diabetes mellitus. Secondly, 11 women with gestational diabetes mellitus joined semi-structured in-depth interviews to obtain their perceptions about online health information. The data were analyzed using inductive content analysis to develop themes. Results The median score of eHEALS in the Chinese version among 235 women diagnosed with gestational diabetes mellitus was 29 (interquartile range [IQR], 26 to 32). Factors influencing electronic health literacy among these women included accessing health information from medical professionals (β = 0.137, p = 0.029) and utilizing health information from applications (β = 0.159, p = 0.013). From the qualitative phase of the study, four thematic categories emerged: reasons and basis for accessing health information from the Internet; address barriers to accessing and applying online health information; desires for a higher level of online health information services; outcomes of accessing and applying online health information. Conclusion The electronic health literacy of women diagnosed with gestational diabetes mellitus remains suboptimal and warrants improvement. The sources of access to health information affect electronic health literacy in women with gestational diabetes mellitus. Moreover, women facing gestational diabetes encounter numerous impediments when attempting to access health-related information online, underscoring the necessity for enhanced online health information services to meet their needs.

Abstract Background Delayed graft function (DGF) is an important complication after kidney transplantation surgery. The present study aimed to develop and validate a nomogram for preoperative prediction of DGF on the basis of clinical and histological risk factors. Methods The prediction model was constructed in a development cohort comprising 492 kidney transplant recipients from May 2018 to December 2019. Data regarding donor and recipient characteristics, pre-transplantation biopsy results, and machine perfusion parameters were collected, and univariate analysis was performed. The least absolute shrinkage and selection operator regression model was used for variable selection. The prediction model was developed by multivariate logistic regression analysis and presented as a nomogram. An external validation cohort comprising 105 transplantation cases from January 2020 to April 2020 was included in the analysis. Results 266 donors were included in the development cohort, 458 kidneys (93.1%) were preserved by hypothermic machine perfusion (HMP), 96 (19.51%) of 492 recipients developed DGF. Twenty-eight variables measured before transplantation surgery were included in the LASSO regression model. The nomogram consisted of 12 variables from donor characteristics, pre-transplantation biopsy results and machine perfusion parameters. Internal and external validation showed good discrimination and calibration of the nomogram, with Area Under Curve (AUC) 0.83 (95%CI, 0.78–0.88) and 0.87 (95%CI, 0.80–0.94). Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion A DGF predicting nomogram was developed that incorporated donor characteristics, pre-transplantation biopsy results, and machine perfusion parameters. This nomogram can be conveniently used for preoperative individualized prediction of DGF in kidney transplant recipients.

Abstract Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

ObjectiveVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a critical support technique for cardiac surgery patients. This study compares the outcomes of femoral artery cannulation vs. combined femoral and axillary artery cannulation in post-cardiotomy VA-ECMO patients. This study aimed to compare the clinical outcomes of critically ill patients post-cardiac surgery under VA-ECMO support using different cannulation strategies. Specifically, the focus was on the impact of femoral artery (FA) cannulation vs. combined femoral artery and axillary artery (FA+AA) cannulation on patient outcomes.MethodsThrough a retrospective analysis, we compared 51 adult patients who underwent cardiac surgery and received VA-ECMO support based on the cannulation strategy employed—FA cannulation in 27 cases vs. FA+AA cannulation in 24 cases.ResultsThe FA+AA group showed significant advantages over the FA group in terms of the incidence of chronic renal failure (CRF) (37.50% vs. 14.81%, p = 0.045), preoperative blood filtration requirement (37.50% vs. 11.11%, p = 0.016), decreased platelet count (82.67 ± 44.95 vs. 147.33 ± 108.79, p = 0.014), and elevated creatinine (Cr) levels (151.80 ± 60.73 vs. 110.26 ± 57.99, p = 0.041), although the two groups had similar 30-day mortality rates (FA group 40.74%, FA+AA group 33.33%). These findings underscore that a combined approach may offer more effective hemodynamic support and better clinical outcomes when selecting an ECMO cannulation strategy.ConclusionDespite the FA+AA group patients presenting with more preoperative risk factors, this group has exhibited lower rates of complications and faster recovery during ECMO treatment. While there has been no significant difference in 30-day mortality rates between the two cannulation strategies, the FA+AA approach may be more effective in reducing complications and improving limb ischemia. These findings highlight the importance of individualized treatment strategies and meticulous monitoring in managing post-cardiac surgery ECMO patients.

Abstract Circular RNAs (circRNAs) are a unique class of RNA molecules formed through back‐splicing rather than linear splicing. As an emerging field in molecular biology, circRNAs have garnered significant attention due to their distinct structure and potential functional implications. A comprehensive understanding of circRNAs’ functions and potential clinical applications remains elusive despite accumulating evidence of their involvement in disease pathogenesis. Recent research highlights their significant roles in various human diseases, but comprehensive reviews on their functions and applications remain scarce. This review provides an in‐depth examination of circRNAs, focusing first on their involvement in non‐neoplastic diseases such as respiratory, endocrine, metabolic, musculoskeletal, cardiovascular, and renal disorders. We then explore their roles in tumors, with particular emphasis on exosomal circular RNAs, which are crucial for cancer initiation, progression, and resistance to treatment. By detailing their biogenesis, functions, and impact on disease mechanisms, this review underscores the potential of circRNAs as diagnostic biomarkers and therapeutic targets. The review not only enhances our understanding of circRNAs’ roles in specific diseases and tumor types but also highlights their potential as novel diagnostic and therapeutic tools, thereby paving the way for future clinical investigations and potential therapeutic interventions.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10–100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

BackgroundProstate cancer (PCa) is one of the most prevalent malignancies affecting males; however, the role of inflammatory activity in the pathogenesis of this disease is not yet fully elucidated. Although inflammation is recognized as being closely associated with the onset and progression of PCa, the specific causal relationships between individual inflammatory factors and the disease require further clarification.MethodsMendelian randomization (MR) methodologies can mitigate bias by utilizing whole-genome sequencing data, leveraging specific genetic variants to assess causal relationships between a given exposure and an outcome of interest. This research employed an MR approach to investigate the association between inflammatory cytokines and PCa.ResultsIn total, 44 inflammatory cytokines were evaluated in a large GWAS dataset to enable the drawing of robust conclusions. Elevated circulating C-reactive protein (CRP) and prostaglandin E2 (PGE-2) levels were related to greater PCa risk. The reverse Mendelian randomization (MR) study indicates a causal relationship between prostate cancer and stem cell factor (SCF) (P=0.025).ConclusionCRP and PGE-2 play crucial roles in the regulation of PCa development. Moreover, PCa may have an impact on SCF levels. Further research is imperative to elucidate whether these biomarkers can be effectively utilized to prevent or treat PCa.