Search

Abstract Reduction of power consumption is the key target for modern electronic devices. To this end, a lot of attention is paid to zero-static power switches, being able to change their state between highly resistive and highly conductive and remain in this state even in the absence of external voltage. Still, the implementation of such switches is slow because of compatibility issues of new materials with CMOS technology. At the same time, printable technology enables low-cost processes at ambient temperature and integration of devices onto flexible substrates. Here we demonstrate that printed Ag/MoS2/Ag heterostructures can be used as zero-static power switches in radiofrequency/microwave spectrum and fully-integrated reconfigurable metasurfaces. Combined with graphene, our printed platform enables reconfigurable metasurface for electromagnetic wave manipulation and control for wireless communications, sensing, and holography. In addition, it is also demonstrated that the localised MoS2 phase change may have promoted Ag diffusion in forming conductive filaments.

Abstract Background Cancer-associated fibroblasts (CAFs), a predominant stromal cell type in the tumor microenvironment, significantly affect the progression of oral squamous cell carcinoma (OSCC). Results The specific mechanisms through which CAFs influence the cancer stem cell phenotype in OSCC are not fully understood. This study explored the effects of lactic acid produced by CAFs on the cancer stem cells (CSCs) phenotype of OSCC cells. Our results demonstrated that CAFs exhibit increased glycolysis and lactic acid production. Lactic acid treatment enhances CSCs-related markers expression, sphere formation, and clonogenic ability of OSCC cells. RNA sequencing revealed that lactic acid treatment elevates Discs Large Homolog 5 (DLG5) expression and markedly affects the Hippo pathway. Further investigation revealed that DLG5 mediates the effects of lactic acid on the CSCs phenotype. DLG5 knockdown results in elevated expression of E3 ubiquitin ligase Cullin 3, which can promote the ubiquitination and degradation of MST1, but the expression of phosphorylated MST1 remains unchanged. This leads to enhanced binding of phosphorylated MST1 to YAP1, increasing YAP1 phosphorylation and activating the Hippo pathway. Conclusion Collectively, our findings suggest that lactic acid from CAFs promotes the CSCs phenotype in OSCC through the DLG5/CUL3/MST1 axis. Therefore, targeting lactic acid exchange between CAFs and tumor cells may provide a novel therapeutic approach to suppress the CSCs phenotype in OSCC.

We first describe a photoinduced decatungstate-catalyzed direct coupling of cycloalkanes and cyclic aldimines. The desired products were generated in moderate to good yields with wide substrate scope under mild reaction conditions. The mechanistic study revealed a radical process. In addition, the usefulness of the reaction in organic synthesis was proved by the scale-up synthesis as well as the late-stage modification of drug-like molecules.

Abstract Background This study aimed to understand the vision health status of adolescents in the Western Pacific Region (WPR) using Global Burden of Disease (GBD) data from 1990 to 2019. Methods We conducted a comprehensive analysis of blindness and vision loss using GBD data from 1990 to 2019, analyzed trends in the prevalence and burden of blindness and vision loss over time using joinpoint regression, and analyzed their independent effects on blindness and vision loss in three dimensions using age-period-cohort (APC) modeling. Results The prevalence of blindness and vision loss among adolescents in the WPR showed an increasing trend between 1990 and 2019 (AAPC: 0.56%) and a slight increase in YLD (AAPC: 0.11%). The joinpoint regression showed a decreasing trend after 2017 (AAPC: -2.45%). The prevalence and burden trended downward in most Western Pacific countries, with only China rising significantly (AAPC prevalence: 0.57%). Refractive disorders had the highest prevalence among the subgroups. The risk of blindness and vision loss in adolescents reduced with age but grew later in time and at later birth. In addition, prevalence and burden were generally higher in females than males. Conclusions In the context of a declining global trend in the prevalence and burden of blindness and vision loss among adolescents, there is an increasing trend among adolescents in WPR, with the most pronounced rise in China. This finding has important implications for WPR, suggesting that more attention should be given to adolescent eye health in the region.

Abstract Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based “2 × 2” symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10–9 M for human PD1 and 2.557 × 10–8 M for human CD47, respectively, where the CD47 binding is significantly weaker as compared to the binding affinity of HX008 to PD1 as well as the binding affinity of SIRPα-Fc to CD47, leading to little binding to RBCs and platelets and is contrasting to many CD47-agents in development. However, HX009 effectively and simultaneously binds to the PD1 and CD47 on PD1+CD47+ T-cells via cis-binding and elicits enhanced T cell activation compared to the parental HX008. HX009 caused little cytokine-release in human peripheral blood mononuclear cells. HX009 cross-species binds to cynomolgus monkey PD1/CD47 but not to rodents, making cynomolgus monkeys the choice of species to investigate the pharmacokinetics (PK) and toxicology of HX009. HX009’s anti-tumor activities were confirmed in several humanized preclinical mouse models by determining either its anti-PD1 (humanized hu-CD47-MC38 models) or anti-CD47 (HuT-102 lymphoma CDX and three PDX-AML models) functions, although limited available humanized models have hindered broadly demonstration of enhanced anti-tumor activities contributed from the dual targeting of the BsAb. The expanded DLBCL-PDX trial data suggested that both EBV-status and OX40 expression could potentially be two positive predictors for response to HX009. An intravenous (IV) infusion PK study in cynomolgus monkey revealed its largely vasculature distribution, terminal half-life (T1/2) of ~ 50 h, and dose-proportional exposure without accumulation. The anti-drug antibody (ADA) was observed in all monkeys as expected, affecting the PK parameters of repeated administration. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009’s candidacy for its clinical development.

Abstract Objective Oral health is a critical area in healthy aging. Oral health literacy (OHL) plays an important role in improving oral health behaviors and oral health status. However, few studies have investigated OHL among community-dwelling older adults and the influential mechanism of OHL on oral health behaviors has not been clarified. The aim of this study is to explore the interaction pathways through which OHL influences oral health behaviors among community-dwelling older adults. Methods This is a cross-sectional study. 429 community-dwelling older adults were recruited by a convenience sampling method from the activity service center in Zhenjiang, Southern China. The data were collected between September and November 2021 using the Oral Health Literacy Adult Questionnaire (OHL-AQ) and other sophisticated scale assessments. A theoretical model based on the information-motivation-behavioral skills model (IMB model) and previous research was developed and then validated using a structural equation model with AMOS v24.0. Results The proposed model revealed a good fit to the data (χ2/df = 3.349, goodness of fit index = 0.957, adjusted goodness of fit index = 0.921, root mean squared error of approximation = 0.074, comparative fit index = 0.955, normed fit index = 0.938). Oral health information (β = 0.23) and motivation (β = 0.56) positively affected OHL. OHL (β = 0.20) and motivation (β = 0.25) positively affected self-efficacy; self-efficacy (β = 0.98) had a direct effect on oral health behavior. OHL had an indirect effect on oral health behaviors through self-efficacy (β = 0.19). Motivation can both directly influence oral health behavior (β = 0.18) and indirectly influence oral health behavior through OHL and self-efficacy(β = 0.35). Conclusions The study findings make a valuable contribution to the influential mechanism of OHL on oral health behaviors. OHL improved oral health behaviors through self-efficacy among community-dwelling older adults. Oral health information directly affected OHL. Motivation directly affected oral health behaviors as well as influence oral health behaviors by changing OHL.

Abstract Social anxiety is highly prevalent among nursing students and is associated with poor mental health. However, the underlying mechanism in such an association remains unclear. This study aimed to examine the potential mediating role of social intelligence in the association between social anxiety and mental health using the Stress-Coping Model (SCM) as the theoretical framework. A cross-sectional study was conducted among 748 nursing students recruited from a Chinese University from December 2022 to March 2023. Students completed an online questionnaire to assess their social anxiety, social intelligence, and mental health. The PROCESS SPSS Macro (model 4) was used to test the mediation effect of social intelligence on the association between social anxiety and mental health. The results showed that nursing students had moderate levels of social anxiety, social intelligence, and mental health, which varied according to their profile characteristics. Social anxiety was negatively associated with mental health, and the association was partially mediated by social intelligence. Our study offers fresh insights into the impact of social anxiety on mental health and sheds light on the intricate mediating role of social intelligence. These findings offer valuable insights for research and clinical endeavors aimed at formulating psychosocial interventions to enhance the mental health of nursing students.

Abstract Aims The primary aim of this study was to characterize the health-related quality of life (HRQoL) and identify the associated factors among children aged 2 to 18 in China diagnosed with idiopathic nephrotic syndrome (INS). Additionally, the study aimed to evaluate the HRQoL and caregiving burden of their caregivers and investigate the correlation between the HRQoL of the children and that of their caregivers. Methods This study recruited 181 children diagnosed with INS from Children’s Hospital, Zhejiang University School of Medicine in China. The proxy-reported PedsQL Generic Core Module (PedsQL™ 4.0 GCM) was used to measure the HRQoL of children, and the EuroQol five-dimensional questionnaire, five-level version (EQ-5D-5L) was applied to measure caregivers’ HRQoL. Differences in scale scores and total scores of PedsQL™ 4.0 GCM were assessed using t-tests and one-way ANOVA. Multivariate linear regression analysis was used to identify the factors associated with children’s HRQoL. Pearson correlation analysis evaluated the correlation between children’s HRQoL and caregiver’s HRQoL. Results HRQoL of Children with INS declines with increasing age, and children aged 5-18 had lower scores in physical functioning, emotional functioning, school functioning, psychosocial health summary score, and total PedsQL™ 4.0 GCM score compared to healthy children. Various factors, including the mother filling out the questionnaire, the father being unemployed, and the use of other medications except for steroids, were associated with worse HRQoL of children (p values

Background The incidence of acute ischemic stroke (AIS) remains high, and a timely restoration of cerebral blood flow is crucial for its prognosis. There are less therapeutic approaches to promote recovery of cerebral blood flow in AIS patients treated beyond a limited time window. The analysis of remote ischemic postconditioning (RIPostC) on the efficacy, complications and prognosis of AIS patients beyond the time window is of great significance. Objective To investigate the role of RIPostC on the prognosis of AIS beyond time window, thus providing a safe and effective cerebral blood flow restoration way for AIS beyond time window. Methods It was a randomized, parallel group, placebo-controlled trial involving AIS patients beyond time window (onset time > 6 h) of thrombolysis who were hospitalized in the Department of Neurology, Beijing Aerospace General Hospital from September 2, 2021 to August 31, 2022. They were randomly assigned into the control group and experimental group, and treated and followed up for 90 days. General treatment and conventional treatment of cerebrovascular disease were performed in both groups. RIPostC and simulated RIPostC were respectively given 28 times within 14 days in the experimental group and control group, respectively. Before the intervention, and 30 days and 90 days after the intervention, neurological function was assessed using the modified Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS). Cognitive function was assessed by the Mini-mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Daily living ability was assessed by the Instrumental Activity of Daily Living (IADL). Mental status was assessed by the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). Cerebral blood flow velocity was assessed by the transcranial Doppler ultrasound (TCD). Inflammatory response was assessed by measuring interleukin 6 (IL-6) levels. Results Ninety-nine out of 122 AIS patients finally completed the trial and follow-up, including 49 patients in the experimental group and 50 in the control group. There were no significant differences in gender, age, underlying diseases (hypertension, diabetes, coronary heart disease) and baseline NIHSS scores between the two groups (P>0.05). Repeated measures analysis of variance showed that there was an interaction between time and group on MMSE, MoCA, mRS, NIHSS, cerebral blood flow velocity, and IL-6 (P0.05). The incidence of skin ecchymosis [4.00% (2/50) vs. 12.24% (6/49) ] and the overall incidence of adverse events [12.00% (6/50) vs. 34.69% (17/49) ] in the control group were significantly lower than those of the experimental group (P

Human milk oligosaccharides (HMOs), an important bioactive ingredient in breast milk, have become a popular nutritional fortifier in infant formula. While only a limited variety of synthetic functional oligosaccharides is available now, naturally occurring oligosaccharides from animal milk are a promising substitute for HMOs. Goat milk oligosaccharides (GMOs) are rich in neutral oligosaccharides, which are more similar in structure to HMOs. However, most studies on the separation of milk oligosaccharides concentrate on bovine milk oligosaccharides, while little research has been done on milk oligosaccharides from animal species other than cows, and the structure and composition of animal milk oligosaccharides are different from those of HMOs. In addition, there are few systematic studies on the structures and functions of oligosaccharides, which limits the development and utilization of oligosaccharides in animal milk. This review summarizes the latest progress in research on oligosaccharides in animal milk with a focus on the structures, detection methods and physiological functions of GMOs, and it compares and analyzes the structural differences between animal milk oligosaccharides and HMOs. It is anticipated that this review can provide theoretical support for the development and application of animal milk oligosaccharides in the future.

Abstract Background Cell and gene therapy products (CGTPs) often receive accelerated approvals, lacking comprehensive long-term safety and efficacy data, which can raise significant safety concerns. This research aims to study the post-marketing surveillance (PMS) of CGTPs in the European Union (EU), the United States (US), Japan, South Korea, and China, to offer insights for the development of a secure and standardized post-marketing regulatory framework for CGTPs. Methods Related regulations and the implementation effect of PMS for approved CGTPs were studied searching PubMed, CNKI, and the official websites of the European Medicines Agency, the US Food and Drug Administration, Japan’s Pharmaceuticals and Medical Device Agency, South Korea’s Ministry of Food and Drug Safety, and the National Medical Products Administration of China. Results Compared to those in China, the guidelines of PMS for CGTPs in the EU, the US, Japan, and South Korea was more comprehensive. Notably, the EU had dedicated regulations and supporting guidelines of PMS. Of the 26 CGTPs approved in the EU, 88% were under additional monitoring, 38% received conditional marketing authorization, and 12% were authorized under exceptional circumstances, with 77% designated as orphan drugs. The US had released 34 guidelines specifically for CGTPs which, forming the foundation of post-marketing risk management. Among the 27 CGTPs approved in the US, 22% were required to perform risk evaluation and mitigation strategies, 37% added black box warnings in the package inserts, 63% mandated to post-marketing requirements, and 15% subject to post-marketing commitments. In Japan, stringent supervision measures encompassing all-case surveillance (79%) and re-examination (53%) were applied to the 19 approved CGTPs, with 21% approved through conditional and time-limited approval. The PMS for CGTPs in South Korea, mainly included PSUR, re-examination, and re-evaluation. China had introduced several relevant regulations, which consisted of general statements and lacked detailed guidance. Conclusions This study demonstrates that the regulatory policies of PMS for CGTPs in the EU, the US, Japan, and South Korea were comprehensive. The implementation of PMS for CGTPs in the EU, the US, and Japan was well developed. This knowledge holds valuable insights for China’s future learning and development in this field.

Abstract Background With the release of the coronavirus disease 2019 (COVID-19) pandemic in late 2022 in China, the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) roared, including neonatal cases. However, there were few studies on neonatal COVID-19, especially multi-center case reports. This study aimed to explore clinical characteristics and short-term outcomes of neonatal COVID-19 in China. Methods We reviewed 187 cases of neonatal COVID-19 between December 11, 2022, and January 12, 2023. The diagnosis was assessed by symptoms, laboratory tests, X-ray manifestations, and diagnosis code. Clinical characteristics and outcomes were evaluated. Results In 187 neonatal cases with COVID-19, 84 (44.9%) had severe SARS-CoV-2 infection. Most patients had confirmed exposure to SARS-CoV-2. Fever and respiratory symptoms were common (75.4% and 71.7%, respectively). Severe patients were more likely to have high alanine transaminase (ALT) (> 40U/L) (11.9% vs. 3.9%) and high N-terminal pro-brain natriuretic peptide (NT-proBNP) (> 2000pg/mL) (38.0% vs. 19.6%), compared with nonsevere ones (P

Objective To evaluate the quality of laboratory testing using anti-HIV ELISA quality monitoring indicators and continuously improve laboratory testing capabilities. Methods The data of our blood testing laboratory from July 1, 2020 to December 31, 2022 using laboratory quality monitoring indicators were analyzed, including the reaction sample size and reaction rate of initial test and the reaction sample size and compliance rate of retest. The indoor quality control data of two anti HIV ELISA reagents (Xinchuang and Wantai) during the above time period were collected. A line chart or scatter box chart was drawn to monitor the long-term trends and identify the reasons. Inter-laboratory capability comparison and evaluation with the data from the quality monitoring index evaluation report of the National Health Commission′s Clinical Inspection Center and the National Blood Station Blood Testing Laboratory during the same period was conducted. Results From July 1, 2020 to December 31, 2022, the initial reaction rates of Xinchuang and Wantai anti HIV ELISA reagents were 0.052% and 0.080%, respectively (P

Nuclear energy is essential for the future development of countries. However, both structural and functional components of nuclear power equipment are facing severe challenges of nuclear irradiation damage after experiencing irradiation growth and irradiation creep. How to avoid irradiation damage to nuclear power equipment has become a hotspot in international research and development of surface protection technology. Deposition of protective coatings on the underlying object surface or in bulk materials has been considered as a near-term solution to enhanc functional components. Different substrate materials are selected according to other service conditions within the reactor. Suitable material selection combined with relevant optimization can significantly increase the service life of materials. This review summarizes recent research on several categories of anti-irradiation coatings prepared by physical vapor deposition technology for current industrial applications. These includes metallic, ceramic, composite and high entropy alloy coatings. The review endeavors to impart a thorough understanding of the properties of these selected anti-irradiation coatings, from the fundamental aspects of their substrate materials to their practical applications across diverse settings. It explores not only the current research progress but also the potential avenues for future advancements. Additionally, the intricate relationships between coating formulations, their resistance to irradiation, and their ultimate performance in various environments are illuminated in this paper.

Abstract Background Chlorophenoxy compounds represent a group of selective herbicides widely used around the world. Chlorophenoxy herbicides are toxic, chemically stable, and can migrate into groundwater through soil leaching, posing a significant threat to drinking water safety and human health. Chlorophenoxy herbicides in groundwater aquifers are subject to anaerobic processes; however, the pathway and microbiology involved in the attenuation of chlorophenoxy herbicides under anaerobic condition are largely unknown. Here, the anaerobic degradation process of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a typical chlorophenoxy herbicide, was investigated. Results The initial 52.5 ± 2.3 μM 2,4,5-T was completely degraded by a sediment-derived microbial consortium, with 3,4-dichlorophenol, 2,5-dichlorophenol, 3-chlorophenol (3-CP) and phenol being identified as the intermediate products. Reductive dechlorination of 3-CP to phenol and the subsequent elimination of phenol were the key transformation steps in the overall degradation process of 2,4,5-T. Amplicon sequencing suggested that Dehalobacter, Sulfuricurvum, Bacteroides, Acetobacterium, and Clostridium sensu stricto 7 might contribute to the transformation of 2,4,5-T to phenol, and Smithella, Syntrophorhabdus, Methanofollis and Methanosaeta likely cooperated to accomplish the complete mineralization of phenol. Conclusions This study reported the anaerobic degradation of 2,4,5-T via reductive dechlorination and the subsequent syntrophic metabolization of phenol, an intermediate product transformed from 2,4,5-T. Dehalobacter was identified as the organohalide-respiring population catalyzing the reductive dechlorination reaction. Syntrophorhabdus and methanogenic populations were likely involved in anaerobic phenol oxidation and facilitated the complete mineralization of 2,4,5-T.

Abstract Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.

Abstract This study critically examines the factors influencing satisfaction with environmental governance in China, focusing on air pollution perception, environmental tax, and government trust within the Environmental, Social, and Governance (ESG) framework. Utilizing data from Chinese societal surveys, the research investigates the impact of air pollution perception on environmental governance satisfaction, as well as how this relationship is mediated by environmental tax and moderated by government trust. The findings reveal a strong inverse correlation between air pollution perception and satisfaction with environmental governance, highlighting the direct impact of environmental challenges on ESG outcomes. The relationship is nuanced by regional and demographic variations, highlighting the diverse impact of air pollution perception across different segments of society. The study also reveals the pivotal role of environmental tax in mediating this relationship, suggesting that tax policies can effectively enhance ESG strategies. Additionally, government trust is identified as a key moderating factor, underscoring the importance of trust in governance for the effectiveness of ESG practices. This research contributes to the broader field of air pollution perception and environmental governance, providing valuable insights into the complex interplay between public perception, tax policy, and trust in government. It offers practical implications for policymakers seeking to use taxation and trust-building measures to mitigate pollution and improve public satisfaction with environmental governance within the ESG ambit.

Abstract Background Carbon monoxide (CO), hypothetically linked to prebiotic biosynthesis and possibly the origin of the life, emerges as a substantive growth substrate for numerous microorganisms. In anoxic environments, the coupling of CO oxidation with hydrogen (H2) production is an essential source of electrons, which can subsequently be utilized by hydrogenotrophic bacteria (e.g., organohalide-respring bacteria). While Dehalococcoides strains assume pivotal roles in the natural turnover of halogenated organics and the bioremediation of chlorinated ethenes, relying on external H2 as their electron donor and acetate as their carbon source, the synergistic dynamics within the anaerobic microbiome have received comparatively less scrutiny. This study delves into the intriguing prospect of CO serving as both the exclusive carbon source and electron donor, thereby supporting the reductive dechlorination of trichloroethene (TCE). Results The metabolic pathway involved anaerobic CO oxidation, specifically the Wood-Ljungdahl pathway, which produced H2 and acetate as primary metabolic products. In an intricate microbial interplay, these H2 and acetate were subsequently utilized by Dehalococcoides, facilitating the dechlorination of TCE. Notably, Acetobacterium emerged as one of the pivotal collaborators for Dehalococcoides, furnishing not only a crucial carbon source essential for its growth and proliferation but also providing a defense against CO inhibition. Conclusions This research expands our understanding of CO’s versatility as a microbial energy and carbon source and unveils the intricate syntrophic dynamics underlying reductive dechlorination. Graphical Abstract Video Abstract

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Abstract The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p

Excessive consumption of refined grains harms human health and ecosystem viability. Whole grains, as a healthy and sustainable alternative to refined grains, can benefit individual health by providing dietary fiber, B vitamins, and bioactive substances. Additionally, they aid in improving the environment due to their higher extraction rate and lower carbon emission during the processing stage. However, few studies have attempted to evaluate the economic and social benefits of increasing the amount of whole grain in grain intake. This paper estimates the potential savings in healthcare costs and reduced food carbon footprints (CFs) that could result from a shift toward whole grain consumption following the Chinese Dietary Guidelines (CDG). We investigate hypothetical scenarios where a certain proportion (5–100%) of Chinese adults could increase their whole grain intakes as proposed by CDG to meet the average shortfall of 30.2 g. In that case, the healthcare costs for associated diseases (e.g., type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and colorectal cancer (CRC)) are expected to reduce by a substantial amount, from USD 2.82 to 56.37 billion; the carbon emission levels are also projected to decrease by 0.24–5.72 million tons. This study provides compelling evidence that advocating for the transition towards greater consumption of whole grain products could benefit individual health, the environment, and society, by reducing both healthcare costs and carbon emissions.

Abstract Profile shift is a highly effective technique for optimizing the performance of spur gear transmission systems. However, tooth surface wear is inevitable during gear meshing due to inadequate lubrication and long-term operation. Both profile shift and tooth surface wear (TSW) can impact the meshing characteristics by altering the involute tooth profile. In this study, a tooth stiffness model of spur gears that incorporates profile shift, TSW, tooth deformation, tooth contact deformation, fillet-foundation deformation, and gear body structure coupling is established. This model efficiently and accurately determines the time-varying mesh stiffness (TVMS). Additionally, an improved wear depth prediction method for spur gears is developed, which takes into consideration the mutually prime teeth numbers and more accurately reflects actual gear meshing conditions. Results show that consideration of the mutual prime of teeth numbers will have a certain impact on the TSW process. Furthermore, the finite element method (FEM) is employed to accurately verify the values of TVMS and load sharing ratio (LSR) of profile-shifted gears and worn gears. This study quantitatively analyzes the effect of profile shift on the surface wear process, which suggests that gear profile shift can partially alleviate the negative effects of TSW. The contribution of this study provides valuable insights into the design and maintenance of spur gear systems.

Abstract Bladder cancer is characterized by aberrant activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling, underscoring the significance of directing therapeutic efforts toward the PI3K pathway as a promising strategy. In this study, we discovered that PI3K serves as a potent therapeutic target for bladder cancer through a high-throughput screening of inhibitory molecules. The PI3K inhibitor demonstrated a robust anti-tumor efficacy, validated both in vitro and in vivo settings. Nevertheless, the feedback activation of JAK1-STAT3 signaling reinstated cell and organoid survival, leading to resistance against the PI3K inhibitor. Mechanistically, the PI3K inhibitor suppresses PTPN11 expression, a negative regulator of the JAK-STAT pathway, thereby activating STAT3. Conversely, restoration of PTPN11 enhances the sensitivity of cancer cells to the PI3K inhibitor. Simultaneous inhibition of both PI3K and STAT3 with small-molecule inhibitors resulted in sustained tumor regression in patient-derived bladder cancer xenografts. These findings advocate for a combinational therapeutic approach targeting both PI3K and STAT3 pathways to achieve enduring cancer eradication in vitro and in vivo, underscoring their promising therapeutic efficacy for treating bladder cancer.

"Objective To explore the timing of blood purification (BP) therapy in patients with acute pancreatitis (AP) who develop systemic inflammatory response syndrome (SIRS). Methods A retrospective collection was made of 254 AP patients with SIRS who underwent BP treatment at the Affiliated Baiyun Hospital of Guizhou Medical University from May 2015 to May 2023, and at the Affiliated Hospital of Guizhou Medical University from September 2021 to April 2023. Patients were divided into Group A (＜6 h,n=62), Group B (6-12 h,n=52), Group C (＜12-24 h,n=52), and Group D (＞24 h,n=88) based on the time from SIRS onset to BP treatment. Mortality rate, rate of patient's request for discharge, local complications, systemic complications, ICU transfer, mechanical ventilation, hospital stay, and treatment costs were used as prognostic indicators to study the impact of different BP treatment times on these indicators. Results The incidences of acute peripancreatic fluid collection and renal failure in Groups C and D were significantly higher than those in Group A (P＜0.05); the incidences of circulatory failure and mechanical ventilation in Group D were significantly higher than those in Group A (P＜0.05); the incidence of coagulation dysfunction in Groups C and D was significantly higher than that in Groups A and B (P＜0.05); the incidence of patients transferred to ICU in Groups B, C, and D was higher than that in Group A (P＜0.05); the hospital stay and treatment costs for patients in Group D were significantly higher than those in Groups A, B, and C (P＜0.05). Conclusion BP treatment within 6 hours of diagnosing SIRS can reduce the incidence of patient transfer to ICU; BP treatment within 12 hours can reduce the incidence of pancreatic exudate, renal failure, and coagulation dysfunction; BP treatment within 24 hours can reduce the incidence of circulatory failure and mechanical ventilation, as well as decrease hospital stay and treatment costs."

Abstract Co-combustion is a technology that enables the simultaneous and efficient utilization of biomass and coal gangue (CG). Nevertheless, the factors that affect the combustibility of co-pyrolytic char, which represents the rate-determining step of the entire co-combustion process, remain unclear. This study investigates the impact of the physicochemical properties of co-pyrolytic char, including pore structure, carbon structure, and alkali metals, on the combustion characteristics. The TGA analysis indicates that the ignition and burnout temperatures of the co-pyrolytic char increase as the CG mixing ratio increases, resulting in a prolonged combustion. This is due to the fact that the carbon structure of the co-pyrolytic char becomes increasingly aromatic, accompanied by a reduction in aliphatic hydrocarbons and oxygen-containing groups as the CG mixing ratio increases. Furthermore, the high ash content of the CG is another significant factor contributing to the observed reduction in combustibility. The reaction between mullite, quartz in CG, and alkali metals in biomass results in the formation of aluminosilicate, which reduces the catalytic ability of alkali metals. Furthermore, the char combustion kinetics are analyzed by the KAS method, and the results indicate that the introduction of CG increases the activation energy of the entire char combustion process. The activation energy of the 80RS20CG is within the range of 102.22–164.99 kJ/mol, while the RS char is within the range of 89.87–144.67 kJ/mol.

Abstract Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17–2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.

As a typical religious cultural heritage, Tibetan Buddhist monasteries in the Hehuang region of northwest China have strong connections with surrounding villages that practice Tibetan Buddhism. This article investigates the spatial distribution correlation between the two entities using methods such as kernel density, spatial quantity relationship model, gravity center model, and qualitative description. It analyzes the relationship between Tibetan Buddhist monasteries and traditional Tibetan villages at three levels: macro, meso, and micro, exploring the spatial correlation and influence factors. The study results are as follows: Firstly, the spatial distribution of traditional villages and Tibetan Buddhist monasteries in the Hehuang region exhibits a positive correlation with a moderate spatial correlation. Secondly, the distribution of traditional villages and Tibetan Buddhist monasteries in the Hehuang region demonstrates a high spatial balance. Yet, there are instances where certain counties have an abundance of monasteries but lack traditional villages, particularly in Minhe County, Guide County, Hualong County, and Ledu County. Various factors such as economic, policy, and cultural integration contribute to this phenomenon. Thirdly, the location relationship between traditional villages and Tibetan Buddhist monasteries in the Hehuang region can be categorized into three types: Villages separated from Tibetan Buddhist monasteries, Tibetan Buddhist monasteries in villages, and Tibetan Buddhist monasteries near villages. Finally, it is proposed to protect traditional villages in the area based on the principle of protecting cultural diversity. To safeguard Chinese traditional villages in the future, it is essential to comprehensively analyze the spatial relationship between villages and religious architectural heritage, and prioritize the preservation of significant villages located within the influence zone of these religious architectural heritage by incorporating them into the list of protected traditional villages. This study aims to enhance theoretical research on traditional villages in ethnic minority regions and provide a scientific basis for the comprehensive protection and coordinated utilization of traditional villages and religious architectural heritage in the Hehuang region and other ethnic regions.

Abstract Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Background/Objectives: This study examined the relationships between 24-h movement behaviors and physical fitness (PF) in preschool children. Methods: The study was conducted on 474 children aged 3–6 years in Zhuhai. Physical activity (PA) and sedentary behavior (SB) were collected by the accelerometer, and sleep time was assessed through the parent-report questionnaire. Balance, cardiorespiratory fitness (CRF), flexibility, muscle strength, muscular endurance, and speed-agility were measured using a balance beam test, 20 m shuttle run test, sit and reach test, handgrip test, sit-ups, and 4 × 10 m shuttle run test respectively. The compositional data analysis was used to examine the association between 24-h movement behaviors and PF, and the compositional isotemporal substitution analysis was used for the time reallocation. Results: The daily composition, adjusted for age, gender, and body mass index (BMI), was significantly associated with CRF (p

The industrial economy occupies a crucial position in China’s national economy, and industrial eco-efficiency (IEE) as a significant indicator of regional green development levels. Balancing the positive interaction between industrial economy and resource environment, and enhancing ecological efficiency in industrial development are vital for achieving sustainable regional economic development. This study measures the IEE of 115 cities in coastal China based on panel data of industrial resources and the environment factors. Subsequently, it further analyzes the influencing mechanisms and future trends of IEE. The results indicate that the overall IEE in coastal China is on an upward trend, with higher efficiency values in provinces and regions characterized by faster economic development and better environmental conditions. Significant changes in spatial patterns are observed, with the gaps between cities narrowing and a “multi-core” development model emerging. Factors such as per capita GDP, the ratio of industrial pollution control investment to GDP, innovation index, the proportion of foreign direct investment to GDP, and industrial labor productivity significantly positively influence IEE. In contrast, the proportion of industrial added value to GDP, urbanization rate, and the number of industrial enterprises exhibit notable negative inhibitory effects. Moreover, the interaction effect between industrialization level and other factors is most significant. In the future, IEE is expected to continue improving, although the sustainability of these changes appears weak. These findings reveal the potential impact mechanisms of resource consumption and environmental pollution caused by industrial activities on economic benefit output. This study provides a scientific basis for optimizing energy development layout, enhancing the comprehensive utilization of energy resources, and improving ecological compensation and protection mechanisms.

BackgroundPlatelets are associated with poor prognosis in most tumors, but their specific pathogenic mechanism in osteosarcoma is not yet clear. The objective of this study is to conduct an in-depth analysis of how genes closely related to platelet function impact the prognosis of osteosarcoma patients. We hope that through this research, we can uncover the potential mechanisms of these genes in the development and progression of osteosarcoma, thereby providing new therapeutic strategies and theoretical foundations for improving the prognosis of osteosarcoma patients.MethodWe collected the blood routine test data of patients who were initially diagnosed with osteosarcoma at the Department of Bone Tumors, West China Hospital, from January 2012 to January 2022. By applying the LASSO-COX regression analysis, a statistical method, we found that the platelet count is associated with the prognosis of osteosarcoma patients. To further explore this relationship, we obtained single-cell data and bulk RNA data of osteosarcoma patients from the TARGET database and GEO database, respectively. By analyzing these data, we revealed at the transcriptomic level how platelets contribute to the poor prognosis in osteosarcoma patients.ResultPlatelets are associated with the prognosis of osteosarcoma patients (HR = 3.9, 95% CI = 1.9–8.1, P < 0.001). Through the analysis of transcriptomic data from the TARGET database and GEO database, we found significant heterogeneity in tumor-specific pathways and immune infiltration under different platelet-related gene expression patterns. Among these, TBXAS1 was identified as a key gene that affects the prognosis of osteosarcoma patients. In addition, single-cell data analysis showed that the platelet-related gene TBXAS1 is mainly enriched in macrophages, and markers of macrophages are significantly associated with poor prognosis in osteosarcoma patients.ConclusionTBXAS1 is a key platelet-related gene that leads to poor prognosis in osteosarcoma, and this gene may affect the prognosis of osteosarcoma patients by interacting with macrophages.

The rheological properties of red blood cells (RBCs) are crucial for human health. Combining optical tweezers with microfluidics provides a non-contact, sensitive, and high-throughput method for studying RBC rheology. However, the limited trapping capacity of optical tweezers restricts RBC flow within microchannels, reducing individual RBC capture efficiency. To address this, we developed a multichannel microfluidic chip with a pressure relief structure. Integrating this with optical tweezers using time-division multiplexing enabled simultaneous capture of RBCs across multiple microchannels. This method not only enhances sample throughput during optical tweezer measurements but also allows individual capture and analysis of multiple flowing RBCs in the same timeframe. Image recognition analysis of RBCs captured by optical tweezers revealed distinct morphological differences between normal and diseased RBCs, consistent with finite element method simulations of RBC rheological behavior. This approach provides quantitative characterization of RBC rheology and enables effective detection.

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD.

Abstract Direct in situ imaging of nucleic acids on biological samples is advantageous for rapid analysis without DNA extraction. However, traditional nucleic acid amplification in aqueous solutions tends to lose spatial information because of the high mobility of molecules. Similar to a cellular matrix, hydrogels with biomimetic 3D nanoconfined spaces can limit the free diffusion of nucleic acids, thereby allowing for ultrafast in situ enzymatic reactions. In this study, hydrogel‐based in situ space‐confined interfacial amplification (iSCIA) is developed for direct imaging of single nucleic acid and single pathogen on biological samples without formaldehyde fixation. With a polyethylene glycol hydrogel coating, nucleic acids on the sample are nanoconfined with restricted movement, while in situ amplification can be successfully performed. As a result, the nucleic acids are lighted‐up on the large‐scale surface in 20 min, with a detection limit as low as 1 copy/10 cm2. Multiplex imaging with a deep learning model is also established to automatically analyze multiple targets. Furthermore, the iSCIA imaging of pathogens on plant leaves and food is successfully used to monitor plant health and food safety. The proposed technique, a rapid and flexible system for in situ imaging, has great potential for food, environmental, and clinical applications.

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a highly aggressive malignancy with a significant risk of recurrence even after surgical intervention, leading to a dismal prognosis. In recent years, perioperative immunotherapy has demonstrated promising results in resectable non-small cell lung cancer (NSCLC). However, there is a lack of studies reporting the efficacy of perioperative immunotherapy in PSC.Case presentationWe report the clinical outcomes of four patients diagnosed with locally advanced PSC who underwent neoadjuvant immunotherapy in combination with chemotherapy from 2021 to 2023 in our hospital. Prior to surgery, these patients received 2 to 4 cycles of neoadjuvant treatment. Post-treatment imaging assessments indicated a partial response (PR) in all cases, and each patient successfully achieved R0 resection. Pathological evaluations demonstrated significant pathological responses: one patient attained Pathological Complete Response (PCR), two patients exhibited Major Pathological Response (MPR), and one patient showed PR. Currently, all four patients remain alive without evidence of tumor progression. Notably, the patient who achieved PCR has maintained a disease-free survival (DFS) exceeding 32 months post-surgery, while their event-free survival (EFS) has surpassed 36 months.ConclusionsNeoadjuvant immunotherapy in combination with chemotherapy has provided new promise for the treatment of locally advanced PSC with surgical potential. But these findings still need to be verified by further prospective researches.

In teleosts, the immunoglobulin classes produced by B cells are IgM, IgD, and IgT/IgZ. IgT was initially described as an immunoglobulin specialized in mucosal responses; accumulating evidence, however, shows that it is also involved in systemic immune responses. Two types of IgT/IgZ (IgT1 and IgT2) were previously described in common carp, but their further characterization was hampered by the lack of specific tool. In the current study, we developed and validated polyclonal antibodies against carp IgT1 and IgT2 and used them in combination with well validated monoclonal antibody against carp IgM (WCI12), to study the distribution of IgM+, IgT1+ and IgT2+ B cells or their secreted immunoglobulins in various mucosal and systemic organs of carp. Finally, we also preliminary assessed the B cell response to infection with the blood-borne parasite Trypanoplasma borreli. Using these tools, we report on the distinct expression of soluble immunoglobulins in systemic and mucosal compartments. IgT1 and IgM were expressed in mucosal as well as systemic organs and responded to systemic parasitic infection, whereas IgT2 was preferentially expressed at mucosal sites and did not respond to systemic infections. By studying the distribution of B cells in different organs, compartmentalization of the three B cell subtypes was observed in gills and gut, whereas splenic B cells appeared as organized clusters around ellipsoids. Our results provide insights into the distribution and to some extent the function of B cells in carp, indicating that our newly developed tools are valuable for future studies aiming at the further characterization of immune responses of carp to infections and vaccination.

NNK, formally known as 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanoe, is a potent chemical carcinogen prevalent in cigarette smoke and is a key contributor to the development of human lung adenocarcinomas. On the other hand, autophagy plays a complex role in cancer development, acting as a ''double-edged sword'' whose impact varies depending on the cancer type and stage. Despite this, the relationship between autophagy and NNK-induced lung carcinogenesis remains largely unexplored. Our current study uncovers a marked reduction in p62 protein expression in both lung adenocarcinomas and lung tissues of mice exposed to cigarette smoke. Interestingly, this reduction appears to be contingent upon the activity of extrahepatic cytochrome P450 (CYP450), revealing that NNK metabolic activation by CYP450 enzyme escalates its potential to induce p62 downregulation. Further mechanistic investigations reveal that NNK suppresses autophagy by accelerating the degradation of p62 mRNA, thereby promoting the malignant transformation of human bronchial epithelial cells. This degradation process is facilitated by the hypermethylation of the Human antigen R (HuR) promoter, resulting in the transcriptional repression of HuR - a key regulator responsible for stabilizing p62 mRNA through direct binding. This hypermethylation is triggered by the activation of ribosomal protein S6, which is influenced by NNK exposure and subsequently amplifies the translation of DNA methyltransferase 3 alpha (DNMT3a). These findings provide crucial insights into the nature of p62 in both the development and potential treatment of tobacco-related lung cancer.

Metasurfaces have shown unique application value in the field of holography due to its outstanding ability to manipulate electromagnetic waves. However, improving the design efficiency and imaging quality remains a challenging task. In this work, we propose a deep learning method that can design holographic metasurface structures on demand, with the Mean Absolute Error (MAE) of 0.04 for both amplitude and phase. We utilize this method to inverse design all-silicon-based metasurfaces operating in the terahertz range, achieving a MAE of 0.015 for two target images. This method not only significantly enhances the design efficiency of holographic metasurfaces but also enables continuous modulation of both phase and amplitude. Consequently, it greatly improves both the design efficiency and imaging quality of holographic metasurfaces, providing a new direction for their design.

PurposeLefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis.MethodsThe population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150 mg q12 h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12 h were assessed, considering original and higher plasma protein binding.ResultsLefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150 mg q12 h via intravenous infusion for 1/1.5/2 h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h–2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12 h lefamulin via oral administration proved comparable to those for intravenous administration.ConclusionThis study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.

IntroductionPathogen introduction and transmission at the farm, regional, or national level are associated with reduced animal welfare and negative impacts on herd economics. Ongoing infectious disease surveillance, active or passive, is therefore of high importance. For optimal resolution, each pig is sampled individually, for example by collecting blood or nasal swabs. In recent years, oral fluids have become very useful for population surveillance at the pen level. Another alternative is sampling the air to capture pathogens circulating across the entire barn via bioaerosols.ObjectiveThis study aimed to examine the potential utility of bioaerosol metagenomics for pathogen detection on pig farms.MethodsBioaerosols via automated air sampler, and oral fluid via pen-based ropes, were collected from each of two Scottish indoor pig farms. All samples were subjected to conventional routine bacterial isolation. Total genomic nucleic acids were extracted for PCR screening for three pig DNA viruses, three bacterial Mycoplasma species and an RNA virus. Illumina shotgun metagenomic sequencing was also conducted.ResultsOral fluids contained more DNA compared to bioaerosol samples. DNA integrity exhibited limited impact on PCR or sequence yield. While Streptococcus suis could be cultured from a single oral fluid sample, reads mapped to S. suis were detectable in all metagenomic samples. Other bacterial pig pathogens, including Mycoplasma hyorhinis, M. hyopneumoniae and M. hyosynoviae, were detected in oral fluid and aerosols by PCR and metagenomics. One of the two farms was PRRSV positive, and the virus was detectable via PCR in oral fluids but not in bioaerosols. Antimicrobial resistance (AMR) gene profiles had less variation between bioaerosols and oral fluids. Some identified AMR genes had strikingly similar abundance overall.ConclusionOverall, these findings indicate that there is potential utility of bioaerosol metagenomics for pathogen surveillance on pig farms; however, more research is needed for technical and cost optimization to allow for routine pathogen detection on livestock farms.

BackgroundAcute kidney injury (AKI) is common in cirrhotic patients, especially in the intensive care unit (ICU), and is often associated with poor prognosis. Albumin is often used for plasma volume expansion, but its efficacy in cirrhotic patients with AKI [excluding hepatorenal syndrome (HRS)] is debated. This study aimed to assess the impact of albumin therapy on prognosis in ICU patients with cirrhosis and non-HRS AKI.MethodsA retrospective analysis was conducted using the MIMIC-IV 2.2 database. The primary endpoint was 28-day mortality. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics between the albumin and non-albumin groups.ResultsA total of 1,623 patients were included, with 586 receiving albumin. After IPTW, the sample sizes were 1,713 in the non-albumin group and 1,490 in the albumin group. Albumin administration was associated with higher rates of AKI recovery at 48 h but did not improve 28-day mortality in the overall cohort. Further analysis revealed that using 5% albumin concentration was associated with improved 28-day mortality (HR 0.68; 95% CI 0.49–0.95; p = 0.025), whereas 25% albumin did not show benefit. In patients with high bilirubin levels, albumin treatment significantly reduced 28-day mortality. However, albumin therapy may increase 28-day mortality in certain subgroups, including patients with chronic kidney disease and baseline albumin levels >3.3 g/dL.ConclusionAlthough albumin therapy improved 28-day mortality in some cases, it may also increase mortality in certain subgroups. The use of albumin in critically ill patients with cirrhosis and AKI should be approached with greater consideration of its risks and benefits.

Diabetic nephropathy (DN) is a common and serious micro-vascular complication of diabetes and a leading cause of end-stage renal disease globally. This disease primarily affects middle-aged and elderly individuals, especially those with a diabetes history of over 10 years and poor long-term blood glucose control. Small ubiquitin-related modifiers (SUMOs) are a group of reversible post-translational modifications of proteins that are widely expressed in eukaryotes. SUMO proteins intervene in the progression of DN by modulating various signaling cascades, such as Nrf2-mediated oxidative stress, NF-κB, TGF-β, and MAPK pathways. Recent advancements indicate that natural products regulating SUMOylation hold promise as targets for intervening in DN. In a previous article published in 2022, we reviewed the mechanisms by which SUMOylation intervenes in renal fibrosis and presented a summary of some natural products with therapeutic potential. Therefore, this paper will focus on DN. The aim of this review is to elucidate the mechanism of action of SUMOylation in DN and related natural products with therapeutic potential, thereby summarising the targets and candidate natural products for the treatment of DN through the modulation of SUMOylation, such as ginkgolic acid, ginkgolide B, resveratrol, astragaloside IV, etc., and highlighting that natural product-mediated modulation of SUMOylation is a potential therapeutic strategy for the treatment of DN as a potential therapeutic strategy.

BackgroundPatients recovering from stroke experience a variety of symptoms that present as a synergistic and mutually reinforcing “symptom cluster,” rather than as singular symptoms. In this study, we researched and systematic analyzed these symptom clusters, including core and bridge symptoms, to help determine the relationships between symptoms and to identify key symptom targets, providing a new approach for formulating precise symptom management interventions.MethodsConvenience sampling was applied to select 432 stroke recovery patients treated in the Seventh People’s Hospital of Changzhou City from August 1, 2023 to April 14, 2024. Subsequently, a cross-sectional survey was conducted using the General Information Questionnaire and Stroke Symptom Experience Scale to extract symptom clusters via exploratory factor analysis. Finally, the “qgraph” and “bootnet” packages in the R language were used to construct a network layout to describe the relationships between symptoms and calculate the centrality index.ResultsThe average age of the 432 enrolled recovering stroke patients was 68.17 ± 12.14 years, including 268 males (62.04%) and 164 females (37.96%), none of whom underwent surgical intervention. Among this cohort, the 3 symptoms with the highest incidence rates were “limb weakness” (A2, 80.56%), “fatigue” (A5, 77.78%), and “limitations of limb movement” (A1, 68.06%). A total of 5 symptom clusters were extracted: the somatic activity disorder, mood-disorder-related, cognitive–linguistic dysfunction, somatic-pain-related, and foot dysfunction symptom clusters. In the symptom network, the 2 most common symptoms in terms of intensity and expected impact were “fatigue” (A5, rs = 1.14, re = 1.00) and “pessimism about the future” (B3, rs = 1.09, re = 1.02). The symptom with the strongest bridge intensity was “limb pain” (D1, rs = 2.64).ConclusionThis study uses symptom network analysis to explore the symptoms of stroke patients during recovery, identifying core symptoms and bridge symptoms. Based on these findings, we can develop more targeted management plans to improve the accuracy and efficiency of interventions. Through this management approach, we can enhance treatment effectiveness, reduce unnecessary medication, lower adverse drug reactions, and optimize the allocation of medical resources.

Breast cancer (BC) is a disease highly associated with epigenetic modification, and arginine methylation is particularly important in its genetic regulation. However, the role of arginine methylation related lncRNAs in breast cancer has not been studied. First, we identified the related lncRNAs (from TCGA database) according to the differentially expressed genes related to arginine methylation in breast cancer. Then the lncRNAs related to protein arginine methylation were obtained by regression analysis, and the risk score model was constructed. Finally, the cell experiment and subcutaneous tumor model verified that the arginine methylation related lncRNA z68871.1 in the model had a significant effect on the proliferation and invasion of breast cancer cells. In conclusion, we successfully constructed an arginine methylation related lncRNA model, which has strong predictive ability. At the same time, this study provides an experimental basis for exploring the mechanism of arginine methylation in BC and helps to find new biomarkers of BC.

A novel method is introduced to improve the detection performance of photoacoustic spectroscopy for trace gas detection. For effectively suppressing various types of noise, this method integrates photoacoustic spectroscopy with residual networks model which encompasses a total of 40 weighted layers. Firstly, this approach was employed to accurately retrieve methane concentrations at various levels. Secondly, the analysis of the signal-to-noise ratio (SNR) of multiple sets of photoacoustic spectroscopy signals revealed significant enhancement. The SNR was improved from 21 to 805, 52–962, 98–944, 188–933, 310–941, and 587–936 across the different concentrations, respectively, as a result of the application of the residual networks. Finally, further exploration for the measurement precision and stability of photoacoustic spectroscopy system utilizing residual networks was carried out. The measurement precision of 0.0626 ppm was obtained and the minimum detectable limit was found to be 1.47 ppb. Compared to traditional photoacoustic spectroscopy method, an approximately 46-fold improvement in detection limit and 69-fold enhancement in measurement precision were achieved, respectively. This method not only advances the measurement precision and stability of trace gas detection but also highlights the potential of deep learning algorithms in spectroscopy detection.

Oxidative stress during sepsis could play a crucial role in the pathogenesis of several diseases, especially cardiovascular disorders. In fact, myocardial dysfunction during sepsis is caused by a number of chemicals, one of which is hydrogen peroxide (H2O2). Therefore, sepsis‐induced cardiomyopathy can be controlled through modulation of oxidative stress. Despite the encouraging pharmacological activities demonstrated by inorganic nanostructures, the mechanisms behind their blood protein interaction and antioxidant activity remain unclear. In order to advance the investigation for fabricating nanostructure platforms and studying their antioxidant effects as well as blood protein binding affinities, we explored the synthesis of manganese oxide (Mn3O4) nanorods via hydrothermal method and subsequent characterization using various techniques. The antioxidant effects against H2O2-induced oxidative stress in AC16 cardiomyocytes were then evaluated by different cellular and molecular assays. Additionally, the interaction of Mn3O4 nanorods with hemoglobin was investigated by experimental and and docking analyses. The results showed that synthesized Mn3O4 nanorods had an absorption peak in the range of 260 to 420 nm, vibration bands centered at 510 cm−1, 629 cm−1 and 410 cm−1, 13 distinct XRD peaks, a rod-like morphology with a diameter range of 10 to 75 nm, a hydrodynamic size of 371.7 nm, and a zeta potential of −43.3 mV. Moreover, the antioxidant assays indicated that synthesized Mn3O4 nanorods can trigger a protective effect against H2O2-induced oxidative stress in AC16 cardiomyocytes through inhibition of reactive oxygen species (ROS) overproduction, increased content of superoxide dismutase (SOD) and catalase and glutathione (GSH), and reduction of caspase-3 activity. Furthermore, the fluorescence quenching mechanism of hemoglobin by Mn3O4 nanorods was determined to be controlled by a spontaneous and static quenching process, involvement of hydrogen bonds, a binding affinity (Kb) value of 104 M−1, and number of binding site (n) of around 1.03. Additionally, it was found that Mn3O4 nanorods induced a slight conformational change in the hemoglobin structure, where Tyr35 and Trp37 move to a hydrophilic microenvironment. In conclusion, it can be suggested that Mn3O4 nanorods with a reasonable plasma protein binding affinity can be used as an antioxidant co-therapy in cardiac dysfunction during sepsis.

To obtain nutritious, healthy, and flavor-enriched sour meat products, the effects of different frying methods (microwave, air-frying, and traditional frying) on the flavor quality of low-salt sour meat were evaluated using metabolomics and other flavor analysis techniques. The pH value of the sour meat rose dramatically, while the TBARS value dropped significantly after frying. E-nose and E-tongue results showed that air-frying could reduce acidity and improve umami. The comprehensive analysis of all samples revealed the identification of 107 volatile flavor compounds, including 10 unique aroma compounds that were specifically detected in the AF group. Additionally, the air frying process notably increased the free amino acid and nucleotide concentrations in sour meat by 53.58% and 159.29%, respectively, while causing a significant reduction in both fatty acid and lactic acid content by 22.84% and 49.29%, respectively. All three frying methods altered the flavor of the samples, but air frying performed better in terms of flavor and texture.

Fruit preservation after harvest is one of the key issues in current agriculture, rural areas, and for farmers. Using chitosan to keep fruits fresh, which can reduce the harm caused by chemical preservative residue to human health. It also helps avoid the disadvantages of the high cost of physical preservation and the challenges associated with difficult operation. This review focuses on the application progress of chitosan in fruit preservation. Studies have shown that chitosan inhibits the growth of bacteria and fungi, and delays fruit aging and decay. Furthermore, it can regulate the respiration and physiological metabolism of fruit, helping to maintain its quality and nutritional value. The preservation mechanism of chitosan includes its antibacterial properties, film-forming properties, and its effects on the physiological processes of fruit. However, in practical applications, issues such as determining the optimal concentration and treatment of chitosan still require further research and optimization.