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Abstract High-intensity coal mining has induced a series of ecological and environmental problems issues, including surface subsidence, the development of ground cracks, and the deterioration of vegetation. The disruption of water circulation systems induced by mining, such as perched groundwater, groundwater of aeration zone, and phreatic water, is the root cause of vegetation withering. The aeration zone serves as a crucial nexus in the process of water cycling and exerts a significant influence on soil fertility. To explore the characteristics of soil moisture transport in subsidence areas under the mining disturbance, on-site monitoring of the size and morphology characteristics of subsidence areas and ground cracks was conducted in typical mining areas in Inner Mongolia, China. Subsequently, a typical soil moisture transport model was constructed in subsidence areas, the soil moisture transport patterns under the influence of different types of subsidence and cracks were analyzed, and the influence law of soil damage on soil moisture transport in the aerated zone was clarified. The results indicate that (1) Based on the occurrence and distribution characteristics of subsidence cracks, the subsidence area can be divided into tension zone, compression zone, and neutral zone; the ground cracks are divided into permanent tension cracks and dynamic cracks. (2) The drought stress effect of soil in the subsidence area is significant. Under the influence of soil structure variation, the water-holding capacity of the soil in the subsidence area decreases, and the soil moisture dissipation is strong. The soil moisture transport rate in the aeration zone of the subsidence area is ranked as follows: tension zone > neutral zone > compression zone. (3) Ground cracks can exacerbate the soil moisture transport rate in the aeration zone. After 15 d of crack appearance, the soil moisture transport reaches a relatively stable state, and the soil moisture transport rate in the surface layer of the crack is the fastest, and the loss of soil moisture is the most significant. The crack effect is not significant beyond 100 cm from the crack. This study provides a theoretical and data support for soil and vegetation remediation in mining subsidence areas.

Abstract Power system unreliability tracing model allocates the system's reliability index to individual components, identifying potential weaknesses. This study expands its scope by considering the impact of storage resources. Unreliable factors leading to load shedding are categorized into two groups: objective factors inherent to the component and insufficient storage resources. The latter requires a retrospective analysis of other components that caused unreliability previously. When allocating responsibility for load shedding at a certain time, it begins by allocating it among components based on differences between fixed expected output and actual supply. Expected output insufficiency is considered as the unreliable factor. This insufficiency due to insufficient storage resources is then decomposed into segments, each caused by excessive output in earlier instances of the same component. The expected output excess is attributed to the expected output insufficiency of other components in previous times, for which responsibility has been allocated to each component. Consequently, the expected output insufficiency at a particular time can be traced back based on a temporal recursive model, with the load shedding further allocated to components before that time. Case studies based on several systems demonstrate that the proposed model's allocation results are reasonable and more accurate than the traditional model.

Abstract Hyperuricemia is associated with an increased risk of gout, hypertension, diabetes, and cardiovascular diseases. Most mammals maintain normal serum uric acid (SUA) via urate oxidase (Uox), an enzyme that metabolizes poorly-soluble UA to highly-soluble allantoin. In contrast, Uox became a pseudogene in humans and apes over the long course of evolution. Here we demonstrate an atavistic strategy for treating hyperuricemia based on endogenous expression of Uox in hepatocytes mediated by mRNA (mUox) loaded with an ionizable lipid nanoparticle termed iLAND. mUox@iLAND allows effective transfection and protein expression in vitro. A single dose of mUox@iLAND lowers SUA levels for several weeks in two female murine models, including a novel long-lasting model, which is also confirmed by metabolomics analysis. Together with the excellent safety profiles observed in vivo, the proposed mRNA agent demonstrates substantial potential for hyperuricemia therapy and the prevention of associated conditions.

Abstract Background Preserved ratio impaired spirometry (PRISm) is a type of abnormal lung function. PRISm and mortality have been explored in several studies, but a comprehensive evaluation of the associations is limited. The current study aims to conduct a systematic review and meta-analysis in order to investigate the mortality and cardiovascular diseases in patients with PRISm. Methods PubMed, Embase, and Web of Science databases, as well as gray literature sources, were searched for relevant studies published up to 7 September 2023 without language restrictions. This review included all published observational cohort studies that investigated the association of PRISm with mortality in the general population, as well as subgroup analyses in smokers and pre-bronchodilation spirometry studies. The outcomes of interest were all-cause mortality, cardiovascular mortality, and respiratory-related mortality. The Newcastle–Ottawa scale assessed study quality. Sensitivity and subgroup analyses explored heterogeneity and robustness. Publication bias was assessed with Egger’s and Begg’s tests. Results Overall, eight studies were included in this meta-analysis. The pooled HR was 1.60 (95% CI, 1.48–1.74) for all-cause mortality, 1.68 (95% CI, 1.46–1.94) for CVD mortality, and 3.09 (95% CI, 1.42–6.71) for respiratory-related mortality in PRISm group compared to normal group. In the subgroup analysis, participants with PRISm had a higher effect (HR, 2.11; 95% CI, 1.74–2.54) on all-cause mortality among smokers relative to participants with normal spirometry. Furthermore, the association between PRISm and mortality risk was consistent across several sensitivity analyses. Conclusions People with PRISm were associated with an increased risk of all-cause mortality, CVD mortality, and respiratory-related mortality as compared to those with normal lung function in the general population. Systematic review registration PROSPERO CRD42023426872.

Abstract Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

ABSTRACTMaize (Zea mays L.) is the most important cereal crop in the world. Flowering period and photoperiod play important roles in the reproductive development of maize. This study, investigated ZmMADS42, a gene that is highly expressed in the shoot apical meristem. Agrobacterium infection was used to successfully obtain overexpressed ZmMADS42 plants. Fluorescence quantitative PCR revealed that the expression of the ZmMADS42 gene in the shoot apical meristem of transgenic plants was 2.8 times higher than that of the wild-type(WT). In addition, the expression of the ZmMADS42 gene in the endosperm was 2.4 times higher than that in the wild-type. The seed width of the T2 generation increased by 5.35%, whereas the seed length decreased by 7.78% compared with that of the wild-type. Dissection of the shoot tips of transgenic and wild-type plants from the 7-leaf stage to the 9-leaf stage revealed that the transgenic plants entered the differentiation stage earlier and exhibited more tassel meristems during their vegetative growth period. The mature transgenic plants were approximately 20 cm shorter in height and had a lower panicle position than the wild-type plants. Comparing the flowering period, the tasseling, powdering, and silking stages of the transgenic plants occurred 10 days earlier than those of the wild-type plants. The results showed that the ZmMADS42 gene played a significant role in regulating the flowering period and plant height of maize.

Abstract Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.

Abstract Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis. Graphical Abstract

Exercise prescriptions play a vital role in the prevention and treatment of chronic diseases. A consensus regarding exercise prescription is important for physical health. The “Consensus statement of Chinese experts on exercise prescription” (hereinafter referred to as “Expert Consensus”) divides exercise prescription into two categories: fitness exercise prescription and medical exercise prescription. Traditional Chinese fitness exercises, exercise risk, exercise prescription, and basic precautions for exercise prescription are explained.

Abstract Ghost imaging in the time domain allows for reconstructing fast temporal objects using a slow photodetector. The technique involves correlating random or pre-programmed probing temporal intensity patterns with the integrated signal measured after modulation by the temporal object. However, the implementation of temporal ghost imaging necessitates ultrafast detectors or modulators for measuring or pre-programming the probing intensity patterns, which are not available in all spectral regions especially in the mid-infrared range. Here, we demonstrate a frequency downconversion temporal ghost imaging scheme that enables to extend the operation regime to arbitrary wavelengths regions where fast modulators and detectors are not available. The approach modulates a signal with temporal intensity patterns in the near-infrared and transfers the patterns to an idler via difference-frequency generation in a nonlinear crystal at a wavelength where the temporal object can be retrieved. As a proof-of-concept, we demonstrate computational temporal ghost imaging in the mid-infrared with operating wavelength that can be tuned from 3.2 to 4.3 μm. The scheme is flexible and can be extended to other regimes. Our results introduce new possibilities for scan-free pump-probe imaging and the study of ultrafast dynamics in spectral regions where ultrafast modulation or detection is challenging such as the mid-infrared and THz regions.

Abstract Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm. Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, plays key roles in larval feeding behavior and, more importantly, is essential for eupyrene spermatogenesis and male fertility. CRISPR/Cas9-mediated loss of BmPiezo function decreases larval appetite and subsequent body size and weight. Immunofluorescence analyses reveal that BmPiezo is intensely localized in the inflatable point of eupyrene sperm bundle induced by peristaltic squeezing. BmPiezo is also enriched in the middle region of apyrene sperm bundle before peristaltic squeezing. Cytological analyses of dimorphic sperm reveal developmental arrest of eupyrene sperm bundles in BmPiezo mutants, while the apyrene spermatogenesis is not affected. RNA-seq analysis and q-RT-PCR analyses demonstrate that eupyrene spermatogenic arrest is associated with the dysregulation of the actin cytoskeleton. Moreover, we show that the deformed eupyrene sperm bundles fail to migrate from the testes, resulting in male infertility due to the absence of eupyrene sperm in the bursa copulatrix and spermatheca. Conclusions In conclusion, our studies thus uncover a new role for Piezo in regulating spermatogenesis and male fertility in insects.

Abstract Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R tdTomato mice to lethally irradiated Ackr1 −/− mice (Ackr1 −/− chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Abstract Background The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance. Objective This research explored the effectiveness of integrating anlotinib (a broad‐spectrum tyrosine kinase inhibitor) with programmed death‐1 (PD‐1) blockade and offers mechanistic insights into more effective strategies for treating HCC. Methods Using patient‐derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD‐1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time‐of‐flight mass cytometry, RNA sequencing, and proteomics across cell lines, mouse models, and HCC patient samples. Results The combination of anlotinib with an anti‐PD‐1 antibody enhanced the immune response against HCC in preclinical models. Anlotinib remarkably suppressed the expression of transferrin receptor (TFRC) via the VEGFR2/AKT/HIF‐1α signaling axis. CD8+ T‐cell infiltration into the tumour microenvironment correlated with low expression of TFRC. Anlotinib additionally increased the levels of the chemokine CXCL14, crucial for attracting CD8+ T cells. CXCL14 emerged as a downstream effector of TFRC, exhibiting elevated expression following the silencing of TFRC. Importantly, low TFRC expression was also associated with a better prognosis, enhanced sensitivity to combination therapy, and a favourable response to anti‐PD‐1 therapy in patients with HCC. Conclusions Our findings highlight anlotinib's potential to augment the efficacy of anti‐PD‐1 immunotherapy in HCC by targeting TFRC and enhancing CXCL14‐mediated CD8+ T‐cell infiltration. This study contributes to developing novel therapeutic strategies for HCC, emphasizing the role of precision medicine in oncology. Highlights Synergistic effects of anlotinib and anti‐PD‐1 immunotherapy demonstrated in HCC preclinical models. Anlotinib inhibits TFRC expression via the VEGFR2/AKT/HIF‐1α pathway. CXCL14 upregulation via TFRC suppression boosts CD8+ T‐cell recruitment. TFRC emerges as a potential biomarker for evaluating prognosis and predicting response to anti‐PD‐1‐based therapies in advanced HCC patients.

Atrial fibrillation (AF) is a common cardiac arrhythmia that seriously affects the quality of life of patients. Effective treatment and prevention are important to control the morbidity and mortality of AF. It has been found that cardiac fibrosis promotes the onset and progression of AF. It is now known that transforming growth factor β (TGF-β), an important fibrotic cytokine, plays an important role in cardiac fibrosis by inducing myofibroblast activation via the activation of classical (SMAD-based) and non-classical (non-SMAD-based) signaling pathways. In addition, specific activation of the Wnt/β-catenin pathway has been shown to promote the transformation of fibroblasts into myofibroblasts. In recent years, a new family of proteins, namely Disheveled-associated antagonist of beta-catenin (DACT) 2, can affect the Wnt/β-catenin and TGF-β signaling pathways by regulating the phosphorylation levels of these target proteins, which in turn affects the progression of fibrosis. The present study focuses on the effect of DACT2-guided β-catenin on atrial fibrosis. It is expected that the summarized information can be helpful in the treatment of AF.

ObjectivesThe emergency response to the COVID-19 pandemic may disrupt hospital management activities of antimicrobial resistance (AMR). This study aimed to determine the changing AMR trend over the period in China when stringent COVID-19 response measures were implemented.MethodsThis retrospective study was conducted in a designated hospital for COVID-19 patients in Guangzhou, China from April 2018 to September 2021. The prevalence of 13 antimicrobial-resistant bacteria was compared before and after the COVID-19 responses through Chi-square tests. Interrupted time series (ITS) models on the weekly prevalence of AMR were established to determine the changing trend. Controlled ITS models were performed to compare the differences between subgroups.ResultsA total of 10,134 isolates over 1,265 days were collected. And antimicrobial-resistant strains presented in 38.6% of the testing isolates. The weekly AMR prevalence decreased by 0.29 percentage point (95% CI [0.05–0.80]) after antimicrobial stewardship (AMS) policy, despite an increase in the prevalence of penicillin-resistant Streptococcus pneumoniae (from 0/43 to 15/43, p

Periodontitis, delineated by the destruction of structures that support teeth, is predominantly propelled by intricate immune responses. Immunomodulatory treatments offer considerable promise for the management of this ailment; however, the modulation of the periodontal immune microenvironment to facilitate tissue regeneration presents a substantial biomedical challenge. Herein, our study investigates the role of Wilms’ tumor 1-associating protein (WTAP), a critical m6A methyltransferase, in the immunomodulation of periodontitis and assesses its viability as a therapeutic target. We observed heightened expression of WTAP in macrophages extracted from gingival tissues impacted by periodontitis, with a strong association with M1 polarization. Via loss-of-function experiments, we demonstrated that diminishing WTAP expression precipitates a transition from M1 to M2 macrophage phenotypes amidst inflammatory conditions, thus improving the periodontal immune landscape. Further, RNA sequencing and indirect co-culture assays indicated that suppressing of WTAP expression modulates osteoimmune responses and enhances the osteogenic differentiation of bone marrow stromal cells. The local deployment of adeno-associated virus-shWTAP in murine models of periodontitis robustly validated the therapeutic promise of targeting WTAP in this disease. Collectively, our findings highlight the crucial role of WTAP in orchestrating macrophage-mediated osteoimmune responses and tissue regeneration in periodontitis, proposing novel avenues for immunotherapeutic interventions in its treatment.

BackgroundAnxiety, depression, and sleep problems are prevalent comorbid mental disorders among university students. The World Health Organization (WHO) emphasized a mental health promotion objective, recommending the consideration of protective health-promoting factors in strategies aimed at preventing mental disorders. Integrating theoretically significant constructs (such as protective factors) enhances our comprehension of the intricate mechanisms that underpin mental disorders. This study employed network analysis to first identify core and bridge symptoms within comorbid mental disorders and then explore how health-promoting lifestyles (HPLs) were associated with these disorders. The ultimate goal is to offer health promotion recommendations to enhance students’ quality of life.MethodsA total of 3,896 qualified university students participated in this study. Anxiety, depression, sleep problems, and HPLs were assessed using the GAD-7, PHQ-9, PSQI, and HPLP-II scales. A Gaussian Graphical Model was used to construct the networks. The Network Comparison Test was applied to determine whether the associations between HPLs and comorbid symptoms vary by gender, educational level, family sibling, and mental health status.ResultsLow energy (PHQ4) had the highest strength centrality, followed by Daytime dysfunction (PSQI7) and Trouble relaxing (GAD4). Five bridge symptoms were identified: Daytime dysfunction (PSQI7), Self-harm even suicide (PHQ9), Sad mood (PHQ2), Low energy (PHQ4), and Feeling afraid (GAD7). Regarding protective HPLs, Physical activity, Spiritual growth, and Stress management generally emerged as the top three central mental health-promoting behaviors.ConclusionTargeting core and bridge symptoms with timely and appropriate interventions can alleviate anxiety, depression, and sleep problems in this population. Moreover, promoting physical activity, fostering spiritual growth, and managing stress are likely to significantly enhance the overall mental health of university students.

Manhole cover damage poses significant threats to road safety and infrastructure integrity, necessitating timely detection and repair. To address this, we introduce an enhanced YOLOX model integrated with ECA (High Efficiency Channel Attention) modules for real-time monitoring using car recorder footage. Our method categorizes manhole cover conditions into three distinct states: normal, broken, and down. By in-corporating ECA-Net before the decoupling head of the YOLOX model, we significantly boost its channel feature extraction abilities, critical for distinguishing subtle changes in cover conditions. Experimental results reveal a substantial increase in mean Average Precision (mAP) to 93.91%, with a notable AP of 92.2% achieved in the detection of the ‘down’ state, historically the most challenging category. Despite the en-hancements, our model maintains a high detection speed, processing at an average rate only five images per second slower than the original YOLOX model. Comparative analyses against leading detection models, in-cluding Faster R-CNN, SSD, and CenterNet, underscore the superiority of our approach in terms of both accuracy and speed, particularly in accurately recognizing the ‘down’ condition of manhole covers. This in-novative model provides a reliable tool for swiftly identifying damaged manhole covers and their precise lo-cations, enabling prompt maintenance actions. By improving the monitoring efficiency of urban infrastruc-ture, our solution contributes to enhanced road safety and the advancement of smart city technologies.

Background: Japanese encephalitis (JE) is a serious health concern in China, with approximately 80 % of global infections occurring in China. To develop effective prevention and control strategies, this study explored the epidemiological characteristics of JE in China based on spatiotemporal data, to understand the patterns and trends of JE incidence in different regions and time periods. Method: The incidence and mortality rates of JE were extracted from the Public Health Data Center, the official website of the National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System from 2004 to 2019. Joinpoint regression was applied to examine the spatiotemporal patterns and annual percentage change in incidence and mortality of the JE. Results: From 2004 to 2019, a total of 43,569 cases of JE were diagnosed, including 2081 deaths. The annual incidence rate of JE decreased from 0.4171/100,000 in 2004 to 0.0298/100,000 in 2019, with an annual percentage change (APC) of −13.5 % (P

Abstract Introduction The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. Methods This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. Planned Outcome The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. Conclusion This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. Trial Registration ClinicalTrials.gov identifier, NCT05359601.

Abstract The current parallel ankle rehabilitation robot (ARR) suffers from the problem of difficult real-time alignment of the human-robot joint center of rotation, which may lead to secondary injuries to the patient. This study investigates type synthesis of a parallel self-alignment ankle rehabilitation robot (PSAARR) based on the kinematic characteristics of ankle joint rotation center drift from the perspective of introducing "suitable passive degrees of freedom (DOF)" with a suitable number and form. First, the self-alignment principle of parallel ARR was proposed by deriving conditions for transforming a human-robot closed chain (HRCC) formed by an ARR and human body into a kinematic suitable constrained system and introducing conditions of "decoupled" and "less limb". Second, the relationship between the self-alignment principle and actuation wrenches (twists) of PSAARR was analyzed with the velocity Jacobian matrix as a "bridge". Subsequently, the type synthesis conditions of PSAARR were proposed. Third, a PSAARR synthesis method was proposed based on the screw theory and type of PSAARR synthesis conducted. Finally, an HRCC kinematic model was established to verify the self-alignment capability of the PSAARR. In this study, 93 types of PSAARR limb structures were synthesized and the self-alignment capability of a human-robot joint axis was verified through kinematic analysis, which provides a theoretical basis for the design of such an ARR.

CO2 is one of the most important greenhouse gases (GHGs) in the earth’s atmosphere. Since the industrial era, anthropogenic activities have emitted excessive quantities of GHGs into the atmosphere, resulting in climate warming since the 1950s and leading to an increased frequency of extreme weather and climate events. In 2020, China committed to striving for carbon neutrality by 2060. This commitment and China’s consequent actions will result in significant changes in global and regional anthropogenic carbon emissions and therefore require timely, comprehensive, and objective monitoring and verification support (MVS) systems. The MVS approach relies on the top-down assimilation and inversion of atmospheric CO2 concentrations, as recommended by the Intergovernmental Panel on Climate Change (IPCC) Inventory Guidelines in 2019. However, the regional high-resolution assimilation and inversion method is still in its initial stage of development. Here, we have constructed an inverse system for carbon sources and sinks at the kilometer level by coupling proper orthogonal decomposition (POD) with four-dimensional variational (4DVar) data assimilation based on the weather research and forecasting–greenhouse gas (WRF-GHG) model. Our China Carbon Monitoring and Verification Support at the Regional level (CCMVS-R) system can continuously assimilate information on atmospheric CO2 and other related information and realize the inversion of regional and local anthropogenic carbon emissions and natural terrestrial ecosystem carbon exchange. Atmospheric CO2 data were collected from six ground-based monitoring sites in Shanxi Province, China to verify the inversion effect of regional anthropogenic carbon emissions by setting ideal and real experiments using a two-layer nesting method (at 27 and 9 km). The uncertainty of the simulated atmospheric CO2 decreased significantly, with a root-mean-square error of CO2 concentration values between the ideal value and the simulated after assimilation was close to 0. The total anthropogenic carbon emissions in Shanxi Province in 2019 from the assimilated inversions were approximately 28.6% (17%–38%) higher than the mean of five emission inventories using the bottom-up method, showing that the top-down CCMVS-R system can obtain more comprehensive information on anthropogenic carbon emissions.

Abstract Guangxi, China, is one of the world's largest karst regions where potential toxic elements tend to accumulate, resulting in high soil background values. This study explores the ecological risk, elemental baseline values, and sources of potential toxic elements in karst regions, expanding the research to include 21 common elements. The significance of this research lies in its implications for the management of potential toxic element pollution, the formulation of environmental quality standards, and soil remediation in karst areas. In this study, 12,547 topsoil samples (0–20 cm) were collected in the study area. Pollution assessment and ecological risk evaluation of eight potential toxic elements (Zn, Ni, Cu, Pb, Cd, Hg, Cr, and As) were conducted using the geo-accumulation index method and potential ecological risk index method. Multivariate statistical analysis was applied to analyze the total content of 21 common elements (Zn, Ni, Cu, Pb, P, Cd, Hg, Co, Mn, Cr, V, I, S, As, pH, Se, N, CaO, Corg, Mo, and F). Additionally, the potential sources of 21 soil elements were preliminarily quantitatively analyzed using the principal component analysis-absolute principal component scores-multiple linear regression receptor model. The results showed that (1) Zn, Ni, Cu, Pb, Cd, Cr, V, and As were enriched in the research area and Ca, Cd, Mn, Mo, Hg, As, and Cu might have been influenced by human activities; (2) Cr, Pb, As, and Zn were generally lightly polluted, with Hg having a moderate potential ecological risk level; and (3) Ni and Zn have contributions of 37.99% and 35.07% from geological sources, agricultural fertilization, and pesticides. Mo, V, Cr, Se, Hg, and As exhibit contributions ranging from 39.44 to 59.22% originating from geological backgrounds and human activities. Corg, S, N, and P show contributions of 45.39% to 80.33% from surface vegetation. F, Co, Mn, and Pb have contributions ranging from 31.63 to 47.93% from acidic rocks in the soil parent material, mining activities, and transportation. Cd and CaO derive 31.67% and 40.23%, respectively, from soil parent material and industrial sources. I has 31.94% from geological background and human activities, and 31.95% from soil parent material and atmospheric sources. Cu has 30.56% from geological sources. The study results can serve as a scientific basis for element research in karst areas domestically and internationally.

[Objective] Conventional positioning stiffness of rail transit vehicle bogies results in significant lateral forces between wheels and rails, leading to substantial wear and reduced operational efficiency when navigating curves with small to medium radii. To enhance the operational stability and curve negotiation performance of rail transit vehicles, an active radial system for bogies is proposed. [Method] The active radial system and the control principles are introduced. The software and hardware design process of the radial controller is outlined. A vehicle dynamics model is established, integrating with other system components. The functionality and performance of the radial controller are verified through semi-physical simulation experiments and circular track tests. [Result & Conclusion] Whether adopting a guided active detection mode or a precise beacon detection mode, the radial controller can effectively detect curve segments, aligning the bogie wheelsets toward radial positions during curve negotiation in accordance with the actual track information. When entering or exiting curves, the radial controller can drive the radial actuator to act immediately or in advance, effectively reducing the lag time. Simulation and circular track test results demonstrate that trains equipped with bogies featuring the active radial system exhibit a consistent and significantly lower variation in wheel-rail lateral force compared to conventional passive curve negotiation states. The performance of the guiding wheelsets is particularly outstanding. The proposed active radial controller improves the curve negotiation performance of trains and reduces wheel-rail wear.

With the rapid advancement of technology and the increasing demand for user-centric products, the integration of machine learning techniques has become imperative. This paper explores the transformative potential of integrating Particle Swarm Optimization (PSO), Deep Reinforcement Learning (DRL), and other machine learning algorithms such as neural networks, decision trees, and support vector machines into product design processes. Our novel hybrid framework leverages PSO’s global search capabilities and DRL’s adaptive learning to optimize product designs in a manner that traditional methods cannot achieve. By employing predictive modeling, clustering, and recommendation systems, designers can gain valuable insights into user needs and preferences, facilitating the creation of more intuitive and personalized products. We demonstrate that this integrated approach significantly improves design efficiency and user satisfaction. Key findings include a 25% reduction in design iteration time and a 30% increase in user satisfaction scores compared to traditional optimization methods. Additionally, our methodology provides a flexible and scalable solution adaptable to various product design contexts, showcasing its broad applicability and effectiveness. The incorporation of real-time feedback mechanisms allows for continuous refinement and adaptation of product designs to meet evolving user expectations. This study contributes to the field by presenting a comprehensive, multi-technique optimization framework that bridges existing gaps and sets a new standard for user-centric product design optimization. Ultimately, this research underscores the significance of embracing machine learning as a powerful tool for revolutionizing the product design landscape and delivering superior user experiences.

The outputs of renewable energy sources (RESs) are inherently variable and uncertain, such as wind power (WP) and photovoltaic (PV). However, the outputs of various types of RESs in different regions are complementary. If the capacity of RESs could be properly allocated during system planning, variability of the total output could be reduced. Consequently, system reliability and renewable energy (RE) consumption could be improved. This paper proposes an analytical model for optimal complementary capacity allocation of RESs to decrease variability of the total output. The model considers the capacity ratio of RESs as decision variables and the coefficient of variation (CV) of the total output as the objective function. The proposed approach transforms the single-level optimization model into a bilevel optimization model and derives an analytical equation that can directly calculate the optimal complementary capacity ratio (OCCR) of system RESs. Case studies on wind and solar farms in Xinjiang and Qinghai, China, are performed to verify the effectiveness of the proposed analytical allocation method.

Water quality predictions have a great importance in water resource managements and water pollution protections. Most the currently used water quality models can only predict time sequence of fixed length and ignore the real hydrological flow information. In this paper, we propose a new water quality prediction framework GTV-STP that adopts an embedding-Encoder-Decoder structure, in which the timestamps are introduced into the water quality information. The spatial embedding method is developed to introduce the spatial hydrological features into the water quality information, in order to achieve multisite parallel predictions. In addition, a variablelength decoder is put forward for the variable-length sequencial predictions. The practical water quality predictions of WT, pH, DO, CODMn, NH3-N, P and N for Taihu Lake with GTV-STP framework are performed on two datasets of 6to12 in smaller-scale and 12to24 in larger-scale. Using the Huber Loss to balance the MAE and the RMSE, the val-Huber Loss of the GTV-STP framework is used to compare with that of the baseline models such as LSTM-CNN-ATT, LSTMNet and MLP in predicting accuracy. Results show that the GTV-STP framework has the highest accuracy with the val-Huber Loss of 0.079183 on 6to12 and 0.033561 on 12to24. It is shown that the GTV-STP framework has highly accurate not only for smaller-scale water quality predictions but also suitable for larger-scale predictions. In future, water quality predictions using other more precise frameworks containing spatial and time series information under deep learning will be one of the research directions.

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis, which is a lytic, inflammatory form of cell death. There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease. In this review, we summarize the possible pathogenic mechanisms of Alzheimer’s disease, focusing on neuroinflammation. We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease. Finally, we examine the neuroprotective activity of small-molecule inhibitors, endogenous inhibitor proteins, microRNAs, and natural bioactive molecules that target NLRP3 and NLRP1, based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

Abstract As one of the most intractable neurological diseases, spinal cord injury (SCI) often leads to permanent neurological impairment in patients. Unfortunately, due to the complex pathological mechanisms and unique postinjury microenvironment, there is currently no way to completely repair the injured spinal cord. In recent years, with the rapid development of tissue engineering technology, the combination of biomaterials and medicine has provided a new idea for treating SCI. Here, we systematically summarize representative biomaterials, including natural, synthetic, nano, and hybrid materials, and their applications in SCI treatment. In addition, we describe several state-of-the-art fabrication techniques for tissue engineering. Importantly, we provide novel insights for the use of biomaterial-based therapeutic strategies to reduce secondary damage and promote repair. Finally, we discuss several biomaterial clinical studies. This review aims to provide a reference and new insights for the future exploration of spinal cord regeneration strategies.

Solute atoms and second phases with low thermal conductivity are habitually regarded as the factors to the thermal conductivity of alloys. Nevertheless, the interface that is usually neglected can also be a noteworthy factor influencing the thermal conductivity of alloys due to its inherent nature of defects. The effect of interface on the thermal conductivity of alloys was quantitatively scrutinized in the binary Mg–La, Mg–Ce, Mg–Sm, Mg–Al, Mg–Zn, and Mg–Si alloys with concentration gradients. The effect of diverse excess second phases on the deterioration of thermal conductivity for Mg alloys followed this order: Mg2Si＞Mg17Al12＞Mg17La2＞Mg12Ce＞Mg41Sm5＞MgZn2. The quantitative total interfacial thermal resistance model for alloys was proposed, which was quantitatively understood by R=AGsρs3+BGsρs+CGs3ρs. The sequence of experimental data was conformed to that of the theoretical data acquired by this model. Alloying elements which second phases possess low shear modulus (G) and high density (ρ) were beneficial for the development of the low-thermal-resistance alloys. This rule can reinforce the theoretical basis for the thermal conduction of alloys. The data of the total interfacial thermal resistance was established preliminarily to instruct the design of low-thermal-resistance and high-thermal-conductivity Mg alloys.

ABSTRACTThe air quality in China has changed due to the implementation of clean air actions since 2013. Evaluating the spatial pattern of PM2.5 and the effectiveness of reducing anthropogenic emissions in urban and nonurban areas is crucial. Therefore, the China Long-term Air Pollutant dataset for PM2.5 (CLAP_PM2.5) was generated from 2010 to 2022 with a daily 0.1° resolution using the random forest model and integrating multiple data sources, including extensive in-situ PM2.5 measurements, visibility, satellite retrievals, surface and upper-level meteorological data and other ancillary data. The CLAP_PM2.5 dataset is more reliable and accurate than other public datasets. Analysis of CLAP_PM2.5 from 2010 to 2022 reveals the decrease in positive urban-nonurban PM2.5 differences and higher decreasing rates of PM2.5 in most city clusters in eastern China. Furthermore, separating meteorological and emission contributions to the PM2.5 variability by a meteorological normalization approach indicates that meteorological contribution gradually changed from unfavorable to PM2.5 reduction during 2013–2017 to favorable to decline enhancement during 2018–2022, and in urban regions, meteorological contribution is higher than that in nonurban areas. Overall, the reduction in deweathered PM2.5 concentrations highlights China's significant achievements in terms of comprehensive clean air actions.

In a framework of the Standard Model (SM) simply extended by an SU(2) doublet (X,T) including a vectorlike X-quark (VLQ-X), with electric charge |QX|=5/3, we investigate the single production of the VLQ-X induced by the couplings between the VLQ-X with the first and the third generation quarks at the Large Hadron Collider (LHC) operating at s=14 TeV. The signal is searched in events including same-sign dileptons (electrons or muons), one b-tagged jet and missing energy, where the X quark is assumed to decay into a top quark and a W boson, both decaying leptonically. After a rapid simulation of signal and background events, the 95% CL exclusion limits and the 5σ discovery reach are respectively obtained at the LHC with an integrated luminosity of 300 and 3000 fb−1, respectively.

There is an evident requirement for a rapid, efficient, and simple method to screen the authenticity of milk products in the market. Fourier transform infrared (FTIR) spectroscopy stands out as a promising solution. This work employed FTIR spectroscopy and modern statistical machine learning algorithms for the identification and quantification of pasteurized milk adulteration. Comparative results demonstrate modern statistical machine learning algorithms will improve the ability of FTIR spectroscopy to predict milk adulteration compared to partial least square (PLS). To discern the types of substances utilized in milk adulteration, a top-performing multiclassification model was established using multi-layer perceptron (MLP) algorithm, delivering an impressive prediction accuracy of 97.4 %. For quantification purposes, bayesian regularized neural networks (BRNN) provided the best results for the determination of both melamine, urea and milk powder adulteration, while extreme gradient boosting (XGB) and projection pursuit regression (PPR) gave better results in predicting sucrose and water adulteration levels, respectively. The regression models provided suitable predictive accuracy with the ratio of performance to deviation (RPD) values higher than 3. The proposed methodology proved to be a cost-effective and fast tool for screening the authenticity of pasteurized milk in the market.

BackgroundSerum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain.ObjectiveConduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk.MethodGenome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method.ResultThere were 103 SNPs utilized as instrumental variables (p < 5 × 10−8). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, p = 0.5772). There was no heterogeneity and pleiotropy in the statistical models.ConclusionThe present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.

In serving college students with mental disorders, on-campus mental health professionals have been lacking integrative theoretical frameworks to guide their missions of prevention, remedy, and development facilitation. In the current paper, we propose the positive clinical psychology as a theoretically and practically valuable framework for these missions by narratively reviewing the preventive, remedial, and developmental mechanisms derived from the theory and summarizing the most recent empirical evidence that supports each mechanism. We further discuss why and how these mechanisms and findings can be applied to on-campus mental health services to facilitate the resilience and optimal development of college students with mental disorders. Particularly, the use of resilience-focused and strength-based intervention strategies are promoted for services.

BackgroundDental implants have become an increasingly popular option for replacing missing teeth, and the prevalence of peri-implantitis has also increased, which is expected to become a public health problem worldwide and cause high economic and health burdens. This scenario highlights the need for new therapeutic options to treat peri-implantitis.MethodsIn this study, we proposed a novel sono-responsive antibacterial nanosystem co-loaded with metformin (Met) and bone morphogenetic protein-2 (BMP-2) to promote efficacy in treating peri-implantitis. We introduced the zeolitic imidazolate framework-8 (ZIF-8) as a carrier for hematoporphyrin monomethyl ether (HMME) to enhance the antibacterial effect of sonodynamic antibacterial therapy and tested its reactive oxygen species (ROS) production efficiency and bactericidal effect in vitro. Afterward, HMME-loaded ZIF-8, BMP-2-loaded polylactic acid-glycolic acid (PLGA), and Met were incorporated into gelatin methacryloyl (GelMA) hydrogels to form HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels, and the biocompatibility of which was determined in vitro and in vivo. A bacterial-induced peri-implantitis model in the maxilla of rats was established to detect the effects of the composite hydrogels with adjunctive use of ultrasound on regulating inflammation and promoting bone tissue repair in vivo.ResultsThe results indicated that HMME@ZIF-8 with ultrasound stimulation demonstrated more better ROS production efficiency and antimicrobial efficacy. The composite hydrogels had good biocompatibility. Ultrasound-assisted application of the composite hydrogels reduced the release of the inflammatory factors IL-6 and TNF-α and reduced bone loss around the implant in rats with bacterial-induced peri-implantitis.ConclusionOur observations suggest that HMME@ZIF-8 may be a new good sonosensitizer material for sonodynamic antibacterial therapy. The use of HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels in combination with ultrasound can provide a novel option for treating peri-implantitis in the future.

Background: Despite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributes with mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). Methods: The PURE-China study recruited 47,931 participants aged 35–70 years from 12 provinces of China between 2005 and 2009. The perceived BE information, including land use, street, aesthetics, and safety, was collected using the neighborhood environment walkability scale (NEWS) questionnaire, with higher scores indicating a more favorable rating. Two primary outcomes are all-cause mortality and major CVD event. The Cox frailty model with random intercepts was used to assess the association between the perceived total BE/subscales score and outcomes. Results: Of 32,163 participants included in this study, 19,253 (59.9 %) were women, and the mean (SD) age was 51.0 (9.5) years. After a median follow-up period of 11.7 years (IQR 9.4 – 12.2), we observed that one standard deviation higher of combined BE scores was related to a lower risk of all-cause mortality (HR = 0.85; 95 %CI, 0.80–0.90), and major CVD events (HR = 0.95; 95 %CI, 0.90–0.99). The subscales of perceived BE were related to a lower risk, although a few were not significant. Land use mix-diversity and safety from crime were the two most significant subscales. Stronger risks were observed among urban and female participants. Conclusion: Favorable perceived BE characteristics were linked with a lower risk of all-cause mortality and major CVD events in Chinese population, especially in urban areas and females. Our findings can be used by policymakers to take action to mitigate the adverse effect of poor community conditions on health, such as improving local amenities and transport connectivity, providing building paths for walking, running and cycling.

BackgroundA patient-centered dialysis treatment option requires an understanding of patient preferences for alternative vascular accesses and nephrologists often face difficulties when recommending vascular access to end-stage kidney disease (ESKD) patients. We aimed to quantify the relative importance of various vascular access characteristics to patients, healthcare providers and general population, and how they affect acceptability for patients and healthcare providers.MethodsIn a discrete choice experiment, patients with maintenance hemodialysis (MHD), healthcare providers, and individuals from the general population were invited to respond to a series of hypothetical vascular access scenarios that differed in five attributes: cumulative patency, infection rate, thrombosis rate, cost, and time to maturation. We estimated the respondents’ preference heterogeneity and relative importance of the attributes with a mixed logit model (MXL) and predicted the willingness to pay (WTP) of respondents via a multinomial logit model (MNL).ResultsHealthcare providers (n = 316) and the general population (n = 268) exhibited a favorable inclination toward longer cumulative patency, lower access infection rate and lower access thrombosis rate. In contrast, the patients (n = 253) showed a preference for a 3-year cumulative patency, 8% access infection rate, 35% access thrombosis rate and 1.5 access maturity time, with only the 3-year cumulative patency reaching statistical significance. Among the three respondent groups, the general population found cumulative patency less important than healthcare providers and patients did. Patients demonstrated the highest WTP for cumulative patency, indicating a willingness to pay an extra RMB$24,720(US$3,708) for each additional year of patency time.ConclusionPatients and healthcare providers had a strong preference for vascular access with superior patency. While the general population preferred vascular access with lower thrombosis rates. These results indicate that most patients prefer autogenous arteriovenous fistula (AVF) as an appropriate choice for vascular access due to its superior patency and lower complications than other vascular access types.

Background: The COVID-19 pandemic disrupted the healthcare system, affecting physician wellbeing. The consequences of reduced time spent with patients at bedside during the pandemic has not been investigated. The objectives of this study include assessing time spent with patients, physician wellbeing and patient satisfaction before and during the pandemic. Methods: A total of 182 internal medicine physicians used Hill-Rom tracking devices to measure time spent at bedside while on the teaching hospital medicine service between September 2019 and November 2020 at Cleveland Clinic in Cleveland, Ohio. Time spent before and after March 2020, the outbreak of the pandemic were compared. Physicians’ wellbeing was evaluated before and during the pandemic using the Accreditation Council for Graduate Medical Education survey. Patients’ satisfaction was assessed via the Hospital Consumer Assessment of Healthcare Providers and Systems questionnaire and correlated to bedside time. Results: From 88,661 time records collected during the 65-week study, 44,710 (50.43%) met the quality standards and were included in the analysis. The average time spent at bedside per patient before and during the pandemic was 12.12 and 7.85 minutes, respectively. Time decreased by 3.33 minutes for interns, 6.10 minutes for residents, and 2.70 minutes for staff. The pandemic correlated with physicians’ decreased vitality and meaning in work. Patients’ satisfaction did not correlate with bedside time. Conclusion: Internal medicine physicians spent less time with patients during the pandemic and had worsened vitality and satisfaction with work. Physicians’ time spent at bedside did not correlate with patients’ satisfaction.

BackgroundIn recent years, immunotherapy has been emerging as a promising alternative therapeutic method for cancer patients, offering potential benefits. The expression of PD-L1 by tumors can inhibit the T-cell response to the tumor and allow the tumor to evade immune surveillance. To address this issue, cancer immunotherapy has shown promise in disrupting the interaction between PD-L1 and its ligand PD-1.MethodsWe used mirror-image phage display technology in our experiment to screen and determine PD-L1 specific affinity peptides (PPL-C). Using CT26 cells, we established a transplanted mouse tumor model to evaluate the inhibitory effects of PPL-C on tumor growth in vivo. We also demonstrated that PPL-C inhibited the differentiation of T regulatory cells (Tregs) and regulated the production of cytokines.ResultsIn vitro, PPL-C has a strong affinity for PD-L1, with a binding rate of 0.75 μM. An activation assay using T cells and mixed lymphocytes demonstrated that PPL-C inhibits the interaction between PD-1 and PD-L1. PPL-C or an anti-PD-L1 antibody significantly reduced the rate of tumor mass development in mice compared to those given a control peptide (78% versus 77%, respectively). The results of this study demonstrate that PPL-C prevents or retards tumor growth. Further, immunotherapy with PPL-C enhances lymphocyte cytotoxicity and promotes proliferation in CT26-bearing mice.ConclusionPPL-C exhibited antitumor and immunoregulatory properties in the colon cancer. Therefore, PPL-C peptides of low molecular weight could serve as effective cancer immunotherapy.

Mycoplasma pneumoniae (M. pneumoniae) is a well-recognized pathogen primarily associated with respiratory tract infections. However, in rare instances, it can lead to extrapulmonary manifestations, including myocarditis. We present a case of a 15-year-old male who developed fulminant myocarditis, cardiogenic shock, and cardiac electrical storm attributed to M. pneumoniae infection. He underwent a combination of intra-aortic balloon pump (IABP) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiac support, ultimately surviving despite the intracardiac thrombus formation and embolic stroke. Following comprehensive treatment and rehabilitation, he was discharged in stable condition. This case underscores the importance of considering atypical pathogens as potential etiological factors in patients presenting with cardiac complications, especially in the adolescents. It also emphasizes the need for clinical vigilance and effective support for potential cardiac complications arising from M. pneumoniae infection.

Abstract Background Previous in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults. Methods Our study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35–70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite. Results A total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses. Conclusions Our findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose–response relationships and to refine global dietary recommendations.

Abstract The realization of compact and efficient broadband mid-infrared (MIR) lasers has enormous impacts in promoting MIR spectroscopy for various important applications. A number of well-designed waveguide platforms have been demonstrated for MIR supercontinuum and frequency comb generations based on cubic nonlinearities, but unfortunately third-order nonlinear response is inherently weak. Here, we propose and demonstrate for the first time a χ (2) micrometer waveguide platform based on birefringence phase matching for long-wavelength infrared (LWIR) laser generation with a high quantum efficiency. In a ZnGeP2-based waveguide platform, an octave-spanning spectrum covering 5–11 μm is generated through optical parametric generation (OPG). A quantum conversion efficiency of 74% as a new record in LWIR single-pass parametric processes is achieved. The threshold energy is measured as ~616 pJ, reduced by more than 1-order of magnitude as compared to those of MIR OPGs in bulk media. Our prototype micro-waveguide platform could be extended to other χ (2) birefringence crystals and trigger new frontiers of MIR integrated nonlinear photonics.

Abstract Background Chimeric antigen receptor (CAR)-T cell therapy has been used to treat pediatric refractory or relapsed mature B-cell non-Hodgkin lymphoma (r/r MB-NHL) with significantly improved outcomes, but a proportion of patients display no response or experience relapse after treatment. To investigate whether tumor-intrinsic somatic genetic alterations have an impact on CAR-T cell treatment, the genetic features and treatment outcomes of 89 children with MB-NHL were analyzed. Methods 89 pediatric patients treated at multiple clinical centers of the China Net Childhood Lymphoma (CNCL) were included in this study. Targeted next-generation sequencing for a panel of lymphoma-related genes was performed on tumor samples. Survival rates and relapse by genetic features and clinical factors were analyzed. Survival curves were calculated using a log-rank (Mantel-Cox) test. The Wilcox sum-rank test and Fisher’s exact test were applied to test for group differences. Results A total of 89 driver genes with somatic mutations were identified. The most frequently mutated genes were TP53 (66%), ID3 (55%), and ARID1A (31%). The incidence of ARID1A mutation and co-mutation of TP53 and ARID1A was high in patients with r/r MB-NHL (P = 0.006; P = 0.018, respectively). CAR-T cell treatment significantly improved survival in r/r MB-NHL patients (P = 0.00081), but patients with ARID1A or ARID1A and TP53 co-mutation had poor survival compared to those without such mutations. Conclusion These results indicate that children with MB-NHL harboring ARID1A or TP53 and ARID1A co-mutation are insensitive to initial conventional chemotherapy and subsequent CAR-T cell treatment. Examination of ARID1A and TP53 mutation status at baseline might have prognostic value, and risk-adapted or more effective therapies should be considered for patients with these high-risk genetic alterations.

When the wind speed changes significantly in a permanent magnet synchronous wind power generation system, the maximum power point cannot be easily determined in a timely manner. This study proposes a maximum power reference signal search method based on fuzzy control, which is an improvement to the climbing search method. A neural network-based parameter regulator is proposed to address external wind speed fluctuations, where the parameters of a proportional-integral controller is adjusted to accurately monitor the maximum power point under different wind speed conditions. Finally, the effectiveness of this method is verified via Simulink simulation

Background: The benefits of early use of norepinephrine in endotoxemic shock remain unknown. We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model. Methods: Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs. Treatment included fluid resuscitation and administration of different doses of norepinephrine, to induce return to baseline mean arterial pressure (MAP). Fluid management, hemodynamic, microcirculation, inflammation, and organ function variables were monitored. All animals were supported for 6 h after endotoxemic shock. Results: Infused fluid volume decreased with increasing norepinephrine dose. Return to baseline MAP was achieved more frequently with doses of 0.8 µg/kg/min and 1.6 µg/kg/min (P

Underwater image enhancement technology is crucial for the human exploration and exploitation of marine resources. The visibility of underwater images is affected by visible light attenuation. This paper proposes an image reconstruction method based on the decomposition–fusion of multi-channel luminance data to enhance the visibility of underwater images. The proposed method is a single-image approach to cope with the condition that underwater paired images are difficult to obtain. The original image is first divided into its three RGB channels. To reduce artifacts and inconsistencies in the fused images, a multi-resolution fusion process based on the Laplace–Gaussian pyramid guided by a weight map is employed. Image saliency analysis and mask sharpening methods are also introduced to color-correct the fused images. The results indicate that the method presented in this paper effectively enhances the visibility of dark regions in the original image and globally improves its color, contrast, and sharpness compared to current state-of-the-art methods. Our method can enhance underwater images in engineering practice, laying the foundation for in-depth research on underwater images.