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Abstract The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

Background To assess the immunogenicity and safety of two-dose regimen of inactivated COVID-19 vaccines in patients with pulmonary tuberculosis (PTB) and explored the potential benefits of additional dose.Research design and methods In total, 182 PTB patients were randomly (1:1) assigned to the standard-dose group to receive three standard doses of inactivated COVID-19 vaccines, or the double-dose boosting group to receive two standard doses plus a double dose, with a 28-day interval. Forty healthy controls were assigned to receive two doses of inactivated COVID-19 vaccines 28 days apart. The primary endpoint was neutralizing antibodies 28 days after the second vaccination.Results Two doses of inactivated COVID-19 vaccines induced comparable neutralizing antibodies in PTB patients and the healthy controls, with GMTs against ancestral SARS-CoV-2 of 36.8 vs 31.4 (p = 0.4618) and seroconversion rates of 83.9% vs 87.5% (p = 0.6965). In the PTB patients, a third dose at day 56 led to a modest increase in neutralizing antibodies compared to the second dose, with a GMT fold increase of 1.3–1.8. Most adverse reactions were mild pain at the injection site.Conclusions Inactivated COVID-19 vaccine was safe and immunogenic in PTB patients, and two-dose immunization could induce moderate level of humoral responses similar to the healthy adults.Clinical trials registration www.clinicaltrials.gov identifier: NCT05148949.

Abstract The subgrade crushed-rocks of Gonghe-Yushu (Gongyu) Expressway in Qinghai Province are seriously weathered, resulting in a series of pavement diseases. Among the weathered crushed-rocks, the weathering degree of slate is particularly serious, and its physical and mechanical properties, weathering resistance and applicability are not clear. Therefore, this paper takes the slate in the subgrade crushed-rocks of Gongyu Expressway as the research object, and drills the core of the slate rock block to make a cylindrical standard sample, and uniaxial and triaxial compression tests, nuclear magnetic resonance tests, and electron probe micro-analysis tests were performed on it within 50 freeze–thaw cycles (FTC) under saturated conditions. According to the test results, the mass, longitudinal wave velocity, and strength of the slate specimens all decrease with the increase of the number of FTC, the cohesion $$({\text{C}})$$ ( C ) increases first and then decreases, and the change trend of internal friction angle (φ) is completely opposite to the cohesion. The FTC has an expansion effect on the pores of the slate specimens, and the microstructure of the rock particles on the specimen’s surface is removed and becomes smooth. The results of mechanical tests are used in the Hoek–Brown (H-B) strength criterion, and a unified expression of the H-B criterion suitable for slate in permafrost regions is established. The above conclusions can provide some construction reference and maintenance of high-grade highways in cold regions.

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with all-cause mortality increasing globally. Dietary magnesium (Mg), an anti-inflammatory nutrient, has been proven to be associated with the all-cause mortality. The association of dietary Mg intake and all-cause mortality in RA patients remains unknown. The aim of this study was to assess the association between dietary Mg intake and all-cause mortality in RA patients. Methods RA patients were extracted from the NHANES 1999–2018, and followed for survival through December 31, 2019. Dietary Mg intake data were obtained from 24-h dietary recall interview. The association between dietary Mg intake and RA patients’ all-cause mortality was explored based on weighted univariate and multivariate Cox proportional hazard models and described as absolute risk difference (ARD), hazard ratios (HRs) and 95% confidence intervals (CIs). This association was further explored in subgroup analyses based on different age, gender and body mass index (BMI). Results Totally 2,952 patients were included. Until 31 December 2019, a total of 825 deaths were documented. RA patients with higher dietary Mg intake had a 11.12% reduction of all-cause mortality (ARD=-11.12%; HR = 0.74, 95%CI: 0.56–0.99) in the fully adjusted model, especially in female (HR = 0.68, 95%CI: 0.47–0.98), aged

The location of offshore and coastal marine engineering projects often shows considerable overlap with the foraging and breeding grounds of marine mammals. Lingding Bay, located in the Chinese Pearl River Delta, is home to the world’s largest known population of Indo-Pacific humpback dolphins (Sousa chinensis). The bay is also the site of the Hong Kong–Zhuhai–Macao Bridge mega-engineering project. This study assessed the responses of the dolphins to the bridge construction. Data were collected on dolphin sightings by survey vessels following standard line-transect tracks, with surveys conducted during the pre-construction (2005–2006), construction (2015–2016), and post-construction (2020–2021) phases. The dolphin distribution patterns, density, group sizes, and presence of calves were compared across these three periods. Additionally, the range patterns of the dolphins were analyzed following the identification of individuals during the post-construction phase. The average distance at which humpback dolphins were sighted from the bridge was significantly shorter after the completion of the bridge than during the pre-construction and construction phases. Furthermore, the density of humpback dolphins in the southern region of the bay—where the bridge is located—was significantly higher post-construction compared with that recorded during the pre-construction and construction phases. A noticeable increase in dolphin group sizes post-construction may indicate a shift in foraging strategy. The post-construction phase coincided with the COVID-19 pandemic lockdown period, and the resultant reduced human activity in Lingding Bay may have influenced the distribution of dolphins and other animals to some extent. Individual identification results demonstrated that the waters near the bridge remained an integral habitat for the dolphins post-construction, as they freely traversed underneath the bridge. The results of this study hold considerable importance within the realm of marine engineering, offering valuable guidance and references for informed decision-making and operational practices in associated domains.

BackgroundThe current research aimed to demonstrate the independent association between preoperative severe asymptomatic carotid artery stenosis (ACAS) and severe multi-organ dysfunction after off-pump coronary artery bypass grafting (OPCAB), which may further indicate the relationship between severe ACAS and adverse 30-day postoperative outcomes of patients undergoing OPCAB.MethodsThis was a single-center, retrospective observational study including patients without a history of stroke or Transient Ischemic Attacks (TIA) (asymptomatic), who underwent for an isolated OPCAB in the center for operative treatment of coronary artery disease of Beijing Anzhen Hospital from January 2020 to December 2021. All enrolled patients underwent carotid artery ultrasound prior to OPCAB. The information was extracted independently by two authors of the study from the medical records. Both univariate and multivariate analyses were conducted.ResultsA total of 562 patients met the inclusion criteria for the current study. 63 (11.2%) suffered from severe ACAS. The Sequential Organ Failure Assessment (SOFA) maximum in the severe ACAS group was significantly higher than that in the non-severe ACAS group (9.76 ± 3.03 vs. 7.75 ± 2.96, p

This study aimed to investigate the impact of incorporating mature compost on the harmlessness and maturity level of composting from swine manure and carcasses from industrialized pig farms in continuously running large-scale silo reactor systems. The potential human or animal bacterial pathogens and core bacterial community in composting were analyzed by high-throughput sequencing of 16S rRNA gene amplicons. The results showed that the addition of mature compost in the GD group significantly increased the temperature of all depths, the accumulated temperature of compost, and the germination index (75.43%) compared to that in the HN group without mature compost. High-throughput sequencing revealed that the dominated genera in GD were Ureibacillus, Lactobacillus, Corynebacterium, Staphylococcus, and Jeotgalicoccus, and the addition of mature compost could significantly increase the relative abundance of Ureibacillus (16.82%) that was associated with the biodegradation of organics. A total of 421 potential bacterial pathogens were detected, and the dominated genera of pathogens were Streptococcus, Staphylococcus, and Anaerococcus. The potential pathogen in the GD group with mature compost was reduced from 7.16 to 0.77%, which was significantly lower than that (2.97%) in the HN group. Together, these findings revealed that mature compost addition in large-scale reactor composting could accelerate the harmless and humification process, providing an effective and environmentally friendly scheme to deal with the main organic wastes in intensive pig farms.

BackgroundAccurately assessing the postoperative mortality and rehospitalization for heart failure risks in patients undergoing mitral valve repair surgery is of significant importance for individualized medical strategies.ObjectiveWe sought to develop and validate a risk assessment system for the prediction of mortality and rehospitalization for heart failure.MethodsPersonalized risk prediction system of mortality and rehospitalization for heart failure was developed. For developing a prediction system with death as the outcome, there were 965 patients (70%) and 413 patients (30%) were included in the the derivation cohort and the validation cohort. For developing a prediction system with rehospitalization for heart failure as the outcome, there were 927 patients (70%) and 398 patients (30%) were included in the derivation cohort and the validation cohort. There were 42 routine clinical variables used to develop the models. The performance evaluation of the model is based on the area under the curve (AUC). Evaluate the improvement with Euro Score II according to NRI and IDI net reclassification improvement (NRI) and integrated discrimination improvement (IDI).ResultsThe median follow-up time was 685 days, the incidence of death was 3.85% (n = 53), and the incidence of rehospitalization for heart failure was 10.01% (n = 138). The AUC values of the mortality prediction model in the derivation and validation cohorts were 0.825 (0.764–0.886) and 0.808 (0.699–0.917), respectively. The AUC values of the rehospitalization for heart failure prediction model in the derivation and validation cohorts were 0.794 (0.756–0.832) and 0.812 (0.758–0.866), respectively. NRI and IDI showed that the mortality prediction model exhibited superior performance than the Euro Score II. The mortality and rehospitalization for heart failure risk prediction models effectively stratified patients into different risk subgroups.ConclusionThe developed and validated models exhibit satisfactory performance in prediction of all-cause mortality and rehospitalization for heart failure after mitral valve repair surgery.Clinical Trial Registrationhttp://www.clinicaltrials.gov, Unique identifier: (NCT05141292).

IntroductionDiffuse high-grade gliomas are the most common malignant adult neuroepithelial tumors in humans and a leading cause of cancer-related death worldwide. The advancement of high throughput transcriptome sequencing technology enables rapid and comprehensive acquisition of transcriptome data from target cells or tissues. This technology aids researchers in understanding and identifying critical therapeutic targets for the prognosis and treatment of diffuse high-grade glioma.MethodsSpatial transcriptomics was conducted on two cases of isocitrate dehydrogenase (IDH) wild-type diffuse high-grade glioma (Glio-IDH-wt) and two cases of IDH-mutant diffuse high-grade glioma (Glio-IDH-mut). Gene set enrichment analysis and clustering analysis were employed to pinpoint differentially expressed genes (DEGs) involved in the progression of diffuse high-grade gliomas. The spatial distribution of DEGs in the spatially defined regions of human glioma tissues was overlaid in the t-distributed stochastic neighbor embedding (t-SNE) plots.ResultsWe identified a total of 10,693 DEGs, with 5,677 upregulated and 5,016 downregulated, in spatially defined regions of diffuse high-grade gliomas. Specifically, SPP1, IGFBP2, CALD1, and TMSB4X exhibited high expression in carcinoma regions of both Glio-IDH-wt and Glio-IDH-mut, and 3 upregulated DEGs (SMOC1, APOE, and HIPK2) and 4 upregulated DEGs (PPP1CB, UBA52, S100A6, and CTSB) were only identified in tumor regions of Glio-IDH-wt and Glio-IDH-mut, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses revealed that upregulated DEGs were closely related to PI3K/Akt signaling pathway, virus infection, and cytokine-cytokine receptor interaction. Importantly, the expression of these DEGs was validated using GEPIA databases. Furthermore, the study identified spatial expression patterns of key regulatory genes, including those involved in protein post-translational modification and RNA binding protein-encoding genes, with spatially defined regions of diffuse high-grade glioma.DiscussionSpatial transcriptome analysis is one of the breakthroughs in the field of medical biotechnology as this can map the analytes such as RNA information in their physical location in tissue sections. Our findings illuminate previously unexplored spatial expression profiles of key biomarkers in diffuse high-grade glioma, offering novel insight for the development of therapeutic strategies in glioma.

Caenorhabditis elegans is a versatile model organism for exploring complex biological systems. Microbes and the external environment can affect the nervous system and drive behavioral changes in C. elegans. For better survival, C. elegans may develop behavioral immunity to avoid potential environmental pathogens. However, the molecular and cellular mechanisms underlying this avoidance behavior are not fully understood. The dissection of sensorimotor circuits in behavioral immunity may promote advancements in research on the neuronal connectome in uncovering neuronal regulators of behavioral immunity. In this review, we discuss how the nervous system coordinates behavioral immunity by translating various pathogen-derived cues and physiological damage to motor output in response to pathogenic threats in C. elegans. This understanding may provide insights into the fundamental principles of immune strategies that can be applied across species and potentially contribute to the development of novel therapies for immune-related diseases.

The effects of extrusion ratio (ER) on the microstructures, static mechanical properties, and tension-compression high cycle fatigue (HCF) behavior of the as-extruded Mg–5Zn–1Mn (ZM51) alloy was investigated systematically, and the HCF mechanism was discussed. The results show that texture weakening and grain refinement caused by increasing the ER can effectively enhance the static mechanical properties and alleviate the tensile-compressive asymmetry of the alloy. The fatigue strength at 107 cycles is 124 ± 5, 138 ± 4, and 142 ± 5 MPa for ER8, ER11.5, and ER23, respectively, and the corresponding fatigue ratio is approximately 0.45, 0.49, and 0.50, which means that the as-extruded ZM51 alloy possesses outstanding fatigue resistance. The failure analysis and microstructure evolution of post-fatigued samples demonstrated that the stress amplitudes and microstructure characteristics strongly influence the HCF mechanism of the alloy. At high-stress load, close to the tensile yield strength 160–180 MPa, abundant {101‾2} residual twin bands were observed near the fracture surface. Twinning/detwinning deformation is the dominant fatigue mechanism due to the plastic deformation incompatibility between the matrix and the residual twins. At low-stress load, close to the fatigue strength 125–145 MPa, the fatigue crack initiation mechanism transits from twinning/detwinning to dislocation slip. Grain refinement and texture weakening inhibit the activation of {101‾2} twins, alleviate the twin-dislocation interaction, and promote dislocation slip to dominate the fatigue deformation, thereby enhancing the fatigue life of the alloy. This work provides new insight into the design and development for enhancing the fatigue resistance of wrought Mg alloy to ensure the long-term service safety of structural materials.

There are several large karst caves at haunch part of the Lidong Tunnel during construction, together with inrush water due to high pressure within these caves. In light of it, this paper takes YK342+113 section as an example and adopts finite difference software FLAC 3D, so as to analyze tunnel deformation when crossing karst caves under six different working conditions, including with or without karst cave, before and after karst treatment, along with support locations. According to analysis results: First, the wall rock mainly had deformation at tunnel vault when evacuating at the third bench, which is a critical monitoring focus for tunnel construction; Second, karst cave treatment contributed to better conduct forces on both sides of wall rock, thus reducing vault settlement, while not affecting horizontal convergence and upturn of vaults; Third, treatment measures were proved to be effective in minimizing wall rock deformation by comparing deformation curves under different conditions; Fourth, after treatment measures, the angular points within the cave’s chamber had stress concentration, which might cause secondary collapse. Field monitoring data revealed that the final settlement of the tunnel vault was relatively consistent with the numerical analysis results, with a distinct change in daily settlement after initial support construction. By integrating numerical analysis and field monitoring, the rationality of the karst treatment plan was fully verified, providing a valuable reference for similar projects.

Backgrounds Hemophagocytic lymphohistiocytosis (HLH) is an acute, rapidly progressive systemic inflammatory disorder that often occurs secondary to hematological malignancies among other conditions in adults. Although the annual incidence of HLH is increasing, detailed epidemiological knowledge of HLH is still limited, especially in patients with hematological malignancies.Objectives To analyze the impact of hematological malignancies on the epidemiology and outcomes of HLH.Study design Data from the National Readmission Database (NRD) from 2011 to 2020 were analyzed to explore the epidemiological trends and in-hospital outcomes of HLH patients, particularly those with hematological malignancies.Results Our analysis included 7579 HLH hospitalizations, with hematological malignancies implicated in 24.01% of cases. Our findings reveal a steady increase in HLH diagnoses from 145 cases in 2011 to 1848 in 2020, with the proportion linked to hematological malignancies remaining consistent. Patients with hematological malignancies-associated HLH exhibited higher rates of in-hospital mortality (31.6%) than those without (14.4%), and a higher 30-day readmission rate, underscoring a critical need for early detection and treatment revision.Conclusions Despite the increasing awareness and diagnosis of HLH, the prognosis of patients with HLH associated with hematological malignancies remains poor, highlighting the urgent need for improved management strategies and therapeutic interventions.

A series of related experiments were carried out based on prepared hydrocracking catalyst, Catalyst-HC. Ni & W and USY molecular sieve were selected as the hydrogenation active component and the cracking component of Catalyst-HC, respectively. Meanwhile, a kinetic model for paraffin conversion was constructed based on paraffin conversion law. Results obtained through this work indicate that the impact of H2-pressure is relatively complex. As the H2-pressure changes, the degree of hydrocracking reaction may be influenced by both hydrogen supply capacity and hydrogen proton concentration. Obtained conversion priority for three types of hydrocarbons on USY molecular sieve is as follows, aromatic ≫ cycloalkane > paraffin. Aromatic content in SRGO can affect its paraffin-retention in Hydro-D. Compared with the hydrotreating of SRGO with low aromatic content, when SRGO with relatively higher aromatic content is hydrotreated, its paraffin-retention is higher and its paraffin loss is also relatively smaller. Base on constructed model, the calculated values of SRGO-BJ conversion rate and paraffin-retention in Hydro-D are within ±10 % and ±5 % error lines, respectively. Thus, model schematic diagram is reasonable and can provide modeling reference for relevant model research.

Pulmonary neuroendocrine cells (PNECs) are unique airway epithelial cells that blend neuronal and endocrine functions, acting as key sensors in the lung. They respond to environmental stimuli like allergens by releasing neuropeptides and neurotransmitters. PNECs stand out as the only lung epithelial cells innervated by neurons, suggesting a significant role in airway-nerve communication via direct neural pathways and hormone release. Pathological conditions such as asthma are linked to increased PNECs counts and elevated calcitonin gene-related peptide (CGRP) production, which may affect neuroprotection and brain function. CGRP is also associated with neurodegenerative diseases, including Parkinson’s and Alzheimer’s, potentially due to its influence on inflammation and cholinergic activity. Despite their low numbers, PNECs are crucial for a wide range of functions, highlighting the importance of further research. Advances in technology for producing and culturing human PNECs enable the exploration of new mechanisms and cell-specific responses to targeted therapies for PNEC-focused treatments.

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.

To enable the detection and modulation of modularized neural networks in vitro, this study proposes a microfluidic microelectrode array chip for the cultivation, compartmentalization, and control of neural cells. The chip was designed based on the specific structure of neurons and the requirements for detection and modulation. Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software, and the simulation results show that the liquid within the chip can flow smoothly, ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels. By employing MEMS technology in combination with nanomaterial modification techniques, the microfluidic microelectrode array chip was fabricated successfully. Primary hippocampal neurons were cultured on the chip, forming a well-defined neural network. Spontaneous electrical activity of the detected neurons was recorded, exhibiting a 23.7% increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array. This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro, potentially serving as a novel tool in neuroscience research.

Environmental pollution, including air pollution, plastic contamination, and heavy metal exposure, is a pressing global issue. This crisis contributes significantly to pollution-related diseases and is a critical risk factor for chronic health conditions, including cancer. Mounting evidence underscores the pivotal role of N6-methyladenosine (m6A) as a crucial regulatory mechanism in pathological processes and cancer progression. Governed by m6A writers, erasers, and readers, m6A orchestrates alterations in target gene expression, consequently playing a vital role in a spectrum of RNA processes, covering mRNA processing, translation, degradation, splicing, nuclear export, and folding. Thus, there is a growing need to pinpoint specific m6A-regulated targets in environmental pollutant-induced carcinogenesis, an emerging area of research in cancer prevention. This review consolidates the understanding of m6A modification in environmental pollutant-induced tumorigenesis, explicitly examining its implications in lung, skin, and bladder cancer. We also investigate the biological mechanisms that underlie carcinogenesis originating from pollution. Specific m6A methylation pathways, such as the HIF1A/METTL3/IGF2BP3/BIRC5 network, METTL3/YTHDF1-mediated m6A modification of IL 24, METTL3/YTHDF2 dynamically catalyzed m6A modification of AKT1, METTL3-mediated m6A-modified oxidative stress, METTL16-mediated m6A modification, site-specific ATG13 methylation-mediated autophagy, and the role of m6A in up-regulating ribosome biogenesis, all come into play in this intricate process. Furthermore, we discuss the direction regarding the interplay between pollutants and RNA metabolism, particularly in immune response, providing new information on RNA modifications for future exploration.

Abstract Background For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. Methods In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. Discussion Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. Trial registration chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

Abstract The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.

Accurately locating and studying grounding lines is essential for predicting the response of glaciers to climate change. However, it is challenging to find grounding lines since they are subglacial features. In this study, Sentinel-1 synthetic aperture radar (SAR) data were utilized to derive the grounding lines of the Riiser-Larsen Ice Shelf. A new method with inspiration drawn from multi-temporal baseline InSAR techniques is proposed. It takes advantage of the temporal consistency of the vertical displacement gradients and identifies grounding zones pixel-by-pixel on a stack of double differential interferograms, thereby providing grounding line proxies. As it fully exploits coherent signals in both spatial and temporal domains, the maximum possible number of grounding zone pixels can be obtained. Moreover, due to the introduction of the concept of the temporal consistency, the method can cope with short term grounding line fluctuations to some extent and may mitigate the influences of atmospheric disturbances and residual ice displacements. The resulting grounding lines are compared with the MEaSUREs Antarctic grounding line product. The comparison confirms the effectiveness of the proposed method and corroborates that the Riiser-Larsen Ice Shelf should have not undergone significant changes over the past few decades.

The timely and accurate monitoring of high-seas fisheries is essential for effective management. However, efforts to monitor industry fishing vessels in the central-eastern North Pacific have been hampered by frequent cloud cover and solar illumination interference. In this study, enhanced fishing extraction algorithms based on computer vision were developed and tested. The results showed that YOLO-based computer vision models effectively detected dense small fishing targets, with original YOLOv8 achieving a precision (P) of 89% and a recall (R) of 79%, while refined versions improved these metrics to 93% and 99%, respectively. Compared with traditional threshold methods, the YOLO-based enhanced models showed significantly higher accuracy. While the threshold method could identify similar trend changes, it lacked precision in detecting individual targets, especially in blurry scenarios. Using our trained computer vision model, we established a dataset of dynamic changes in fishing vessels over the past decade. This research provides an accurate and reproducible process for precise monitoring of lit fisheries in the North Pacific, leveraging the operational and near-real-time capabilities of Google Earth Engine and computer vision. The approach can also be applied to dynamic monitoring of industrial lit fishing vessels in other regions.

Background: The causal relationship between chronic venous insufficiency (CVI) and cardiovascular diseases (CVDs) has yet to be elucidated. Herein, we implement Mendelian randomization (MR) analysis to investigate the causal association. Methods: A two-sample MR approach using genetic data from FinnGen and genome-wide association studies (GWAS) Catalog was applied to investigate the causal relationship between CVI and CVDs. This study assessed 77 single nucleotide polymorphisms (SNPs) as instrumental variables, employing random-effect inverse-variance-weighted MR, weighted median, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Robust Adjusted Profile Score (RAPS) methods. Multivariable MR (MVMR) considered confounding factors. Results: Genetically predicted CVI was associated with reduced heart failure risk (odds ratio (OR) = 0.96, 95% confidence interval (95% CI): 0.93–0.99, p = 0.025) and increased atrial fibrillation risk (OR = 1.06, 95% CI: 1.03–1.09, p = 0.0002). MVMR, adjusting for venous thromboembolism (VTE), lower limb ulceration, obesity, smoking, and alcohol, attenuated these associations. No significant links were found with hypertension, aortic aneurysm, coronary artery disease, myocardial infarction, valvular heart disease, or stroke. Conclusions: This MR study supports an association between CVI and CVDs, which may imply CVI should be monitored during the treatment of heart failure and atrial fibrillation.

Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.

Nightly images offer a special data source for monitoring fishing activities. This study used images from the Defense Meteorological Satellite Program (DMSP)/Operational Linescan System (OLS) to analyze the early development of lit fisheries in the open South China Sea (SCS), which mainly occurred around the Zhong Sha and Xi Sha Islands. Based on peak detection and a fixed threshold, lit fishing positions were extracted well from filtered, high-quality DMSP/OLS images. The results indicated that fisheries experienced an apparent rise and fall from 2005 to 2012, with the numbers of lit fishing boats rising to a maximum of ~60 from 2005 to 2008, almost disappearing in 2009, peaking at ~130 from 2010 to 2011, and starting to decline in 2012. The fish price of major fishing targets declined by ~60% in 2009, which obviously impacted the year’s fishing operations. The reason for declined fishing operations in 2012 was that most of the lit fishing operations shifted farther south to fishing grounds around the Nan Sha Islands. We also explored factors shaping the distribution patterns of lit fisheries by using MaxEnt models to relate fishing positions to environmental variables. Major environmental factors influencing the distribution of lit fishing boats varied with years, of which water depth was the most important factor across years, with an optimal depth range of 1000–2000 m. In addition to depth, the distribution of lit fisheries was also influenced by SST, especially for the years 2005–2008, and a suitable SST was found between 26 and 28 °C. This study fills the knowledge gaps of the inception of lit fisheries and their dynamic changes in the SCS.

IntroductionThe positive effect of intercropping on host plant growth through plant–soil feedback has been established. However, the mechanisms through which intercropping induces interspecific competition remain unclear.MethodsIn this study, we selected young apple trees for intercropping with two companion plants: medium growth-potential Mentha haplocalyx Briq. (TM) and high growth-potential Ageratum conyzoides L. (TA) and conducted mixed intercropping treatment with both types (TMA) and a control treatment of monocropping apples (CT).ResultsOur findings revealed that TM increased the under-ground biomass of apple trees and TA and TMA decreased the above-ground biomass of apple trees, with the lowest above-ground biomass of apple trees in TA. The above- and under-ground biomass of intercrops in TA and TMA were higher than those in TM, with the highest in TA, suggesting that the interspecific competition was the most pronounced in TA. TA had a detrimental effect on the photosynthesis ability and antioxidant capacity of apple leaves, resulting in a decrease in above-ground apple biomass. Furthermore, TA led to a reduction in organic acids, alcohols, carbohydrates, and hydrocarbons in the apple rhizosphere soil (FRS) compared to those in both soil bulk (BS) and aromatic plant rhizosphere soil (ARS). Notably, TA caused an increase in pentose content and a decrease in the hexose/pentose (C6/C5) ratio in FRS, while ARS exhibited higher hexose content and a higher C6/C5 ratio. The changes in exudates induced by TA favored an increase in taxon members of Actinobacteria while reducing Proteobacteria in FRS compared to that in ARS. This led to a higher eutrophic/oligotrophic bacteria ratio relative to TM.DiscussionThis novel perspective sheds light on how interspecific competition, mediated by root exudates and microbial community feedback, influences plant growth and development.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles in the brain. The overexpression of amyloid-β precursor protein (APP) in an AD brain results in the binding of APP intracellular domain (AICD) to Fe65 protein via the C-terminal Fe65-PTB2 interaction, which then triggers the secretion of amyloid-β and the consequent pathogenesis of AD. Apparently, targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD. Recently, exosome, a type of extracellular vesicle with diameter around 30–200 nm, has gained much attention as a potential delivery tool for brain diseases, including AD, due to their ability to cross the blood–brain barrier, their efficient uptake by autologous cells, and their ability to be surface-modified with target-specific receptor ligands. Here, the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65, enabled the development of a novel exosome-based targeted drug delivery system, which carried Corynoxine-B (Cory-B, an autophagy inducer) to the APP overexpressed-neuron cells in the brain of AD mice. The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes (Fe65-EXO) loaded with Cory-B (Fe65-EXO-Cory-B) hijacked the signaling and blocked the natural interaction between Fe65 and APP, enabling APP-targeted delivery of Cory-B. Notably, Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells, leading to amelioration of the cognitive decline and pathogenesis in AD mice, demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.

The safety injection (SI) system might be put into use, and the coolant at high temperature will mix with the supcooled water under Loss Of Coolant Accident (LOCA). The thermo-hydraulic phenomena associated with the thermal mixing of coolant and supcooled water will directly affect the judgment on core reflooding. China General Nuclear Power Group (CGN) independently developed and designed a thermal hydraulic system code named LOCUST, and the verification of thermal mixing models in LOCUST is necessary. This paper will introduce the thermal mixing tests at the T-junction based on Emergency Core Cooling System in Xi'an Jiaotong University (ECCS-XJTU) experimental facility, which were mainly conducted for the mixing between subcooled water injected from the SI pipe with a range of 25–125 kg/h in mass flow and the pure steam in the primary pipe with a range of 100–500 kg/h in mass flow. Besides, the fluid temperature and the dynamic vapor quality after mixing in tests are analyzed, and the simulations of 25 thermal mixing tests using the LOCUST 1.2 code are performed. The results show that the maximum relative error of LOCUST in mass flow of liquid is within 13.8 %, and the maximum relative error of LOCUST in temperature is within 8 %, which validates the reliability and accuracy of simulations of LOCUST for two-phase thermal mixing in LOCA.

Abstract Staging lymph nodes (LN) is crucial in diagnosing and treating cancer metastasis. Biotechnologies for the specific localization of metastatic lymph nodes (MLNs) have attracted significant attention to efficiently define tumor metastases. Bioimaging modalities, particularly magnetic nanoparticles (MNPs) such as iron oxide nanoparticles, have emerged as promising tools in cancer bioimaging, with great potential for use in the preoperative and intraoperative tracking of MLNs. As radiation-free magnetic resonance imaging (MRI) probes, MNPs can serve as alternative MRI contrast agents, offering improved accuracy and biological safety for nodal staging in cancer patients. Although MNPs’ application is still in its initial stages, exploring their underlying mechanisms can enhance the sensitivity and multifunctionality of lymph node mapping. This review focuses on the feasibility and current application status of MNPs for imaging metastatic nodules in preclinical and clinical development. Furthermore, exploring novel and promising MNP-based strategies with controllable characteristics could lead to a more precise treatment of metastatic cancer patients.

Abstract The outbreak of Coronavirus Disease 2019 (COVID-19) has prompted the scientific community to explore potential treatments or vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the illness. While SARS-CoV-2 is mostly considered a respiratory pathogen, several neurological complications have been reported, raising questions about how it may enter the Central Nervous System (CNS). Receptors such as ACE2, CD147, TMPRSS2, and NRP1 have been identified in brain cells and may be involved in facilitating SARS-CoV-2 entry into the CNS. Moreover, proteins like P2X7 and Panx-1 may contribute to the pathogenesis of COVID-19. Additionally, the role of the immune system in the gravity of COVID-19 has been investigated with respect to both innate and adaptive immune responses caused by SARS-CoV-2 infection, which can lead to a cytokine storm, tissue damage, and neurological manifestations. A redox imbalance has also been linked to the pathogenesis of COVID-19, potentially causing mitochondrial dysfunction, and generating proinflammatory cytokines. This review summarizes different mechanisms of reactive oxygen species and neuro-inflammation that may contribute to the development of severe COVID-19, and recent progress in the study of immunological events and redox imbalance in neurological complications of COVID-19, and the role of bioinformatics in the study of neurological implications of COVID-19.

Despite improvements in the early intervention of myocardial infarction (MI) in recent decades, left ventricular aneurysms (LVA) remain a major health concern, particularly in developing nations. The progression of MI can lead to the thinning of the myocardial wall and the formation of a ventricular wall bulge, characteristic of an LVA. Furthermore, cardiac magnetic resonance (CMR) has emerged as the gold standard for LVA diagnosis due to its superior imaging capabilities. Notably, surgical ventricular reconstruction (SVR) is an effective treatment for LVA, aiming to restore the normal volume and structure of the left ventricle, thereby improving cardiac function. However, the criteria for selecting patients for SVR treatment remains a subject of debate. This review focuses on the current understanding of surgical indications, procedures, and prognostic risk factors that influence outcomes in left ventricular reconstruction, highlighting the need for precise patient selection to optimize surgical benefits.

Probiotics have many beneficial physiological activities, but the poor stability during storage and gastrointestinal digestion limits their application. Therefore, in this study, a novel type of shell–core microbead for loading probiotics was prepared through high-precision concentric drop formation technology using gelatin as the shell material and lipids as the core material. The microbeads have a regular spherical structure, uniform size, low moisture content (9.0 log CFU/g). Textural testing showed that the hardness of the medium-chain triglyceride microbeads (MCTBs), cocoa butter replacer microbeads (CBRBs) and hydrogenated palm oil microbeads (HPOBs) increased gradually (319.65, 623.54, 711.41 g), but their springiness decreased (67.7, 43.3, 34.0%). Importantly, lipids with higher melting points contributed to the enhanced stability of probiotics during simulated digestion and storage. The viable probiotic counts of the HCTBs, CBRBs and HPOBs after being stored at 25 °C for 12 months were 8.01, 8.44, and 8.51 log CFU/g, respectively. In the simulated in vitro digestion process, the HPOBs resisted the destructive effects of digestive enzymes and gastric acid on probiotics, with a reduction in the probiotic viability of less than 1.5 log CFU/g. This study can provide new ideas for the preparation of intestinal delivery probiotic foods.

Chemical warfare agents primarily comprise organophosphorus nerve agents, saliva alkaloids, cyanides, and mustard gas. Exposure to these agents can result in severe respiratory effects, including spasms, edema, and increased secretions leading to breathing difficulties and suffocation. Protecting public safety and national security from such threats has become an urgent priority. Porous metal–organic framework (MOF) materials have emerged as promising candidates for the degradation of chemical warfare agents due to their large surface area, tunable pore size distribution, and excellent catalytic performance. Furthermore, combining MOFs with polymers can enhance their elasticity and processability and improve their degradation performance. In this review, we summarize the literature of the past five years on MOF-based composite materials and their effectiveness in degrading chemical warfare agents. Moreover, we discuss key factors influencing their degradation efficiency, such as MOF structure, pore size, and functionalization strategies. Furthermore, we highlight recent developments in the design of MOF–polymer composites, which offer enhanced degradation performance and stability for practical applications in CWA degradation. These composite materials exhibit good performance in degrading chemical warfare agents, playing a crucial role in protecting public safety and maintaining national security. We can expect to see more breakthroughs in the application of metal–organic framework porous materials for degrading chemical warfare agents. It is hoped that these innovative materials will play a positive role in achieving social stability and security.

Thermomechanical treatment T10 (extension twinning + aging treatment) can largely enhance the precipitation strengthening effect of magnesium alloys. In this study, dislocation structure evolution and precipitation behavior during T10 treatment of an AZ80 extruded bar were analyzed mainly by two-beam diffraction in TEM. At a compressive strain of 1% in the extrusion direction (ED), a typical dislocation configuration, including basal I1 stacking faults (SFs) and dislocations, has been established in extension twins. As the strain reaches 7%, the volume fraction of extension twins increases to more than 90% at which point high dense I1 SFs and dislocations occur. After aging for 2 h at 150 °C for the 7% strained sample, masses of basal I1 SFs and dislocations remain in the extension twins and can act as effective nucleation sites and solute fast-diffusion channels for continuous precipitates. Consequently, the precipitates in extension twins become highly dense.

Crystal structures, growth characteristics, and transformation of the precipitates in a Mg-7Gd-5Y-1Nd-2Zn-0.5Zr (wt.%) alloy aged at 200 °C for various durations were investigated using transmission electron microscopy (TEM) and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). A detailed Mg-Gd type precipitation sequence for Mg-Gd-Y-Nd-Zn alloys was proposed as follows: supersaturated solid solution → solute clusters → zigzag GP zones + β′′(I) → β′ → β′+ protrusions/joints → pre-β1 → β1 → β. Solute clusters formed in the early stage of aging consisted of one or more rare-earth (RE)/Zn-rich atomic columns with different configurations. RE/Zn-rich solute clusters grew into zigzag GP zones and β′′(I) as aging time extending. The paired-zigzag GP zones might grow up to be β′ precipitates directly. In the peak- and plat-aging stages, the number of solute clusters in the matrix decreased until they disappeared, and most existed as zigzag arrays and super hexagons. Protrusions formed at the end of β′ at an angle of 120°, then grew into joints when two different β′ variants encountered together. Protrusions/joints comprise zigzag arrays, super-hexagons, β′F, β′′(II), βT, and hybrid structures rich in solute atoms, and act as catalysts for the growth of the β′ variants. Larger β′ grow by joints consumption while smaller β′ precipitates dissolve to form joints. β1 precipitates essentially evolve from pre-β1 precipitates, with four-point diamond structures formed by RE/Zn atomic substitution and atomic migration based on the original α-Mg structure.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted.

17β-Estradiol (E2) is a critical sex steroid hormone, which has significant effects on the endocrine systems of both humans and animals. E2 is also believed to play neurotrophic and neuroprotective roles in the brain. Biosensors present a powerful tool to detect E2 because of their small, efficient, and flexible design. Furthermore, Biosensors can quickly and accurately obtain detection results with only a small sampling amount, which greatly meets the detection of the environment, food safety, medicine safety, and human body. This review focuses on previous studies of biosensors for detecting E2 and divides them into non-biometric sensors, enzyme biosensors, antibody biosensors, and aptamer biosensors according to different bioreceptors. The advantages, disadvantages, and design points of various bioreceptors for E2 detection are analyzed and summarized. Additionally, applications of different bioreceptors of E2 detection are presented and highlight the field of environmental monitoring, food and medicine safety, and disease detection in recent years. Finally, the development of E2 detection by biosensor is prospected.

Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01–1.03), 1.04 (1.02–1.06), and 1.02 (1.00–1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05–1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01–1.03), 1.33 (1.18–1.50), and 1.07 (1.03–1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females.

Abstract Objective Nano-hydroxyapatite and its composites(nHA) have been widely used as grafts in inter-vertebral fusion. However, the safety and efficacy of the graft in inter-vertebral fusion is controversial. This meta-analysis aimed at evaluating the safety and efficacy of nHA and non-hydroxyapatite grafts (noHA) (autologous bone, etc.) in inter-body fusion. Materials and methods A comprehensive search was performed in electronic database as follows: PubMed, EMBASE, the Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI) from inception until October 2022. Clinical studies on the effect of nHA and noHA in spinal fusion were collected. Analysis of outcome indicators using RevMan 5.4 statistical software. Results The meta-analysis showed that the operation time of patients who underwent inter-body fusion with nHA grafts was less than that of patients who underwent noHA (p

Abstract The development of a battery management algorithm is highly dependent on high-quality battery operation data, especially the data in extreme conditions such as low temperatures. The data in faults are also essential for failure and safety management research. This study developed a battery big data platform to realize vehicle operation, energy interaction and data management. First, we developed an electric vehicle with vehicle navigation and position detection and designed an environmental cabin that allows the vehicle to operate autonomously. Second, charging and heating systems based on wireless energy transfer were developed and equipped on the vehicle to investigate optimal charging and heating methods of the batteries in the vehicle. Third, the data transmission network was designed, a real-time monitoring interface was developed, and the self-developed battery management system was used to measure, collect, upload, and store battery operation data in real time. Finally, experimental validation was performed on the platform. Results demonstrate the efficiency and reliability of the platform. Battery state of charge estimation is used as an example to illustrate the availability of battery operation data.

Abstract Background The past few years have witnessed a significant increase in research related to plant-derived extracellular vesicles (PDEVs) in biological and medical applications. Using biochemical technologies, multiple independent groups have demonstrated the important roles of PDEVs as potential mediators involved in cell-cell communication and the exchange of bio-information between species. Recently, several contents have been well identified in PDEVs, including nucleic acids, proteins, lipids, and other active substances. These cargoes carried by PDEVs could be transferred into recipient cells and remarkably influence their biological behaviors associated with human diseases, such as cancers and inflammatory diseases. Main body of the abstract This review summarizes the latest updates regarding PDEVs and focuses on its important role in nanomedicine applications, as well as the potential of PDEVs as drug delivery strategies to develop diagnostic and therapeutic agents for the clinical management of diseases, especially like cancers. Conclusion Considering its unique advantages, especially high stability, intrinsic bioactivity and easy absorption, further elaboration on molecular mechanisms and biological factors driving the function of PDEVs will provide new horizons for the treatment of human disease.

Long-term variations in population structure, growth, mortality, exploitation rate, and recruitment pattern of two major commercial small pelagic fishes (CSPFs) (Decapterus maruadsi and Trachurus japonicus) are reported based on bottom trawl survey data collected during 2006–2020 in the Beibu Gulf, South China Sea. All individuals collected during each sampling quarter over a period of 15 years were subjected to laboratory-based analysis. In this study, the stock of D. maruadsi and T. japonicus inhabiting the Beibu Gulf was assessed using length-based methods (bootstrapped electronic length frequency analysis (ELEFAN)) to complete stock assessment in different fishery management periods (the division of fisheries management periods was based on China’s input and output in the South China Sea offshore fisheries over 15 years, specifically divided into period I (2006–2010), period II (2011–2015), and period III (2016–2020)). The results showed that the mean body length, dominant body size, and estimated asymptotic length of two CSPFs decreased, whereas their growth coefficient decreased, indicating miniaturization and slower growth, respectively. Estimated exploitation rates and catching body length for two CSPFs indicated that both stocks in the Beibu Gulf were overexploited in period I and moderately exploited after 2011. These stocks were taking a good turn in status in period III, with the exploitation rate much lower than the initial period and reversing the downward trend in catching body length. Furthermore, the variations in the spawning season of the two CSPF stocks and their barely satisfactory expected yield indicated the complexity of the current fishery management in the Beibu Gulf. These results suggest that management measures to reduce fishing pressure may have a positive influence on the biological characteristics of those CSPFs in the Beibu Gulf; however, the stock structure already affected by overfishing will be a huge challenge for the conservation and restoration of fisheries resources in the future. Given that the current stocks of D. maruadsi and T. japonicus in the Beibu Gulf still have low first-capture body length (Lc) and high fishing mortality (F) (compared to F0.1), we identify a need to refine population structure by controlling fishing efforts and increasing catchable size, and more consideration should be given to the local fishery resource status in fisheries management.

The effects of Sn in as-extruded Mg-1.2Ga alloys on the electrochemical and discharge properties were investigated by in-situ electrochemistry, half-cell and air-cell tests to provide new ideas for the development of magnesium alloy anode materials. The addition of Sn promoted grain refinement and deformation precipitation on the extrusion streamlines. Extrusion can effectively reduce the |bc| value of the alloy, improving the cathodic hydrogen control process. After the addition of Sn, more secondary phases are introduced. The redeposition and dissolution of Sn and Ga are enhanced. In conclusion, the GT12 alloy has excellent anode efficiency and average cell voltage, and its maximum discharge capacity (1292.98 mAh·g−1 at 75 mA·cm−2) is 55 mAh·g−1 higher than that of the as-cast alloy, showing great potential for development.

Abstract In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human‐induced pluripotent stem cell (hiPSC) derived neurons (hiPSC‐DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two‐dimensional (2D), and more recently, three‐dimensional (3D) neural stem cell‐derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real‐time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA's role in analyzing neural disease models established by hiPSC‐DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC‐DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC‐DNs. The paper also highlights the application of MEAs combined with hiPSC‐DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.

A detailed understanding of the impact of climate variability on fish life histories provides a fundamental basis for the ecosystem approach to fisheries management. In this study, we evaluated the relationship between fish life-history trait parameters and climate periods, using survey data from 2006−2020 for the Beibu Gulf of the northwestern South China Sea, a fishing ground with high commercial and ecological value. We show that climate events can significantly alter the structure of the life history for major commercial fishes, with more diverse life-history strategies during warm events and more concentrated mortality during cold events. Additionally, we detected special relationships between climate events and the life-history trait composite index (LTCI) in Psenopsis anomala and Trichiurus lepturus. It is possible that other indicators would be more appropriate than variability in Oceanic Niño Index (ONI), such as variation in fishing effort or the environmental resistance of fish. Anthropogenic disturbance and biological features may also help explain the magnitude of population variability. We found that changes in life-history traits of only a few commercial fishes (Decapterus maruadsi, Pennahia macrocephalus, and Upeneus sulphureus) were related to the shift in climate periods; these fishes were generally characterized by faster growth and higher mortality rates in the normal and El Niño periods, with the opposite trends in La Niña periods. However, the emergence of climate events has led to a clear complementarity of life-history strategies among some fish in the same ecological niche (same genus and/or feeding group), which may be explained by a balance between habitat conditions and fishing pressures. This study of fish life-history strategies under climate anomalies provides key insights into important attributes for managers to consider when implementing relevant measures to promote fisheries sustainability in the subtropical bay.