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Diazinon, an organophosphorus insecticide, is predominantly removed through photodegradation and biodegradation in the environment. However, photodegradation can generate diazoxon, a highly toxic oxidation byproduct, while biodegradation is hard to complete mineralize diazinon, showing limitations in both methods. In this study, we provided an efficient strategy for the complete and harmless removal of diazinon by synergistically employing biodegradation and photodegradation. The diazinon-degrading strain X1 was capable of completely degrading 200 μM of diazinon into 2-isopropyl-6-methyl-4-pyrimidinol (IMP) within 6 h without producing the highly toxic diazoxon. IMP was the only intermediate metabolite in biodegradation process, which cannot be further degraded by strain X1. Through RT-qPCR and prokaryotic expression analyses, the hydrolase OpdB was pinpointed as the key enzyme for diazinon degradation in strain X1. Photodegradation was further used to degrade IMP and a pyridazine ring-opening product of IMP was identified via high resolution mass spectrometry. The acute toxicity of this product to aquatic organisms were 123 times and 6630 times lower than that of diazinon and IMP, respectively. The stepwise application of biodegradation and photodegradation was proved to be a successful approach for the remediation of diazinon and its metabolite IMP. This integrated method ensures the harmless and complete elimination of diazinon and IMP within only 6 h. The research provides a theoretical basis for the efficient and harmless remediation of organophosphorus insecticide residuals in the environment.

AIM: To evaluate the predictive value of superficial retinal capillary plexus (SRCP) and radial peripapillary capillary (RPC) for visual field recovery after optic cross decompression and compare them with peripapillary nerve fiber layer (pRNFL) and ganglion cell complex (GCC). METHODS: This prospective longitudinal observational study included patients with chiasmal compression due to sellar region mass scheduled for decompressive surgery. Generalized estimating equations were used to compare retinal vessel density and retinal layer thickness pre- and post-operatively and with healthy controls. Logistic regression models were used to assess the relationship between preoperative GCC, pRNFL, SRCP, and RPC parameters and visual field recovery after surgery. RESULTS: The study included 43 eyes of 24 patients and 48 eyes of 24 healthy controls. Preoperative RPC and SRCP vessel density and pRNFL and GCC thickness were lower than healthy controls and higher than postoperative values. The best predictive GCC and pRNFL models were based on the superior GCC [area under the curve (AUC)=0.866] and the tempo-inferior pRNFL (AUC=0.824), and the best predictive SRCP and RPC models were based on the nasal SRCP (AUC=0.718) and tempo-inferior RPC (AUC=0.825). There was no statistical difference in the predictive value of the superior GCC, tempo-inferior pRNFL, and tempo-inferior RPC (all P>0.05). CONCLUSION: Compression of the optic chiasm by tumors in the saddle area can reduce retinal thickness and blood perfusion. This reduction persists despite the recovery of the visual field after decompression surgery. GCC, pRNFL, and RPC can be used as sensitive predictors of visual field recovery after decompression surgery.

The Scintillating Bubble Chamber (SBC) collaboration is developing liquid-noble bubble chambers for the detection of sub-keV nuclear recoils. These detectors benefit from the electron recoil rejection inherent in moderately-superheated bubble chambers with the addition of energy reconstruction provided from the scintillation signal. The ability to measure low-energy nuclear recoils allows the search for GeV-scale dark matter and the measurement of coherent elastic neutrino-nucleus scattering on argon from MeV-scale reactor antineutrinos. The first physics-scale detector, SBC-LAr10, is in the commissioning phase at Fermilab, where extensive engineering and calibration studies will be performed. In parallel, a functionally identical low-background version, SBC-SNOLAB, is being built for a dark matter search underground at SNOLAB. SBC-SNOLAB, with a 10 kg-yr exposure, will have sensitivity to a dark matter–nucleon cross section of 2×10−42 cm2 at 1 GeV/c2 dark matter mass, and future detectors could reach the boundary of the argon neutrino fog with a tonne-yr exposure. In addition, the deployment of an SBC detector at a nuclear reactor could enable neutrino physics investigations including measurements of the weak mixing angle and searches for sterile neutrinos, the neutrino magnetic moment, and the light Z’ gauge boson.

Quantitative predictions of total dissolved gas (TDG) super-saturation are essential for developing operation schemes for high dams. Most TDG generation prediction models have various shortcomings that affect the accuracy of TDG super-saturation estimation, such as oversimplification of influencing factors and uncertainty in parameter values. In this study, the TDG generation process was divided into three parts, gas-liquid mass transfer process in the stilling phase, dilution resulting from the water jet plunging into the stilling phase, and outflow of TDG–super-saturated water from the stilling phase, while considering the water body and bubbles in the stilling phase as a whole. The residence time of the water in the stilling phase (Tr) was introduced to estimate mass transfer time, along with dimensional analysis methods. The properties of TDG generation were evaluated experimentally under varying Tr values. Based on the theoretical analysis and experimental results, a basic water renewal model was proposed and was validated using experimental data. Furthermore, prediction results of this model were compared with those of a classical empirical model and mechanical model based on observed data from a field survey at Xiluodu Dam. The results show that the relative errors between the predicted and experimental measurements were all less than 5%, indicating that the developed prediction model has a good performance. Compared with the mechanism model, the developed model could reduce the standard error (SE), normalized mean error (NME), and error of maximum (REMAX) by 60, 96, and 15%, respectively. Meanwhile, the developed model could reduce the SE, NME, REMAX by 17.4, 36, and 23%, respectively, compared with the empirical model. Considering all the error indexes, it can be concluded that the prediction performance of the water renewal model is the best among the three models. The proposed model was also more generically versatile than the existing models. Prediction results of water regeneration model for TDG could aid the drafting of governing strategies to minimize the risk of super-saturated TDG.

Cathodic plasma electrolysis (CPE) process was applied on cast iron samples for about 1 minute to obtain a crater-liked surface texture with intention to reduce the friction and increase the wear resistance. During the treating process, the plasma discharging was initiated at the surface of cast iron samples, leading to the explosion of gas bubbles and then generating an irregular array of micro craters. The scanning electron microscopy (SEM) observations showed that the recessed and protruded surface textures were obtained when the CPE-process was conducted at low and high voltages, respectively. The textured surfaces were measured and characterized using skewness and kurtosis Pin-on-disc tribotests on those textured samples demonstrated that the samples with negative skewness and higher kurtosis had a smaller coefficient of friction (∼0.08), while the samples with positive skewness and higher kurtosis had a larger coefficient of friction (∼0.104), which was even higher than that of untreated blank sample (∼0.1). The results indicate that the applied voltage significantly influences the surface finish in terms of surface texture and morphology, and thus the coefficients of friction.

Currently, polylactic acid (PLA) is an attractive alternative to polypropylene (PP) because of its biodegradability. This study introduces a novel modification strategy for PLA by creating a multifunctional ionization layer with ionic salts. This approach achieves humidity sensing, reliable antibacterial properties, and excellent degradability simultaneously. The modified PLA textile sensor exhibits high sensitivity to respiratory humidity (0.92 at 90% RH), with ultrafast response (0.12 s) and recovery times (0.16 s). Additionally, the textile demonstrates excellent antibacterial performance against both E. coli (99.9%) and S. aureus (99.9%) after 1 h of contact. It also shows notable biodegradability with a weight loss rate of 60.38% after 30 days. Also, the ionic salt mechanism is explained through dynamic ionization interactions attributed to the modified ionic salts, which feature both long-chain alkanes and active ions. This work presents a new method to enhance the respiratory detection and antibacterial performance of biodegradable masks. [ABSTRACT FROM AUTHOR]

Smart dry adhesives, a rapidly growing class of intelligent materials and structures, are engineered to provide strong, robust adhesion when needed while also allowing for controlled, easy detachment in response to specific stimuli. Traditional smart adhesives, often exemplified by fibrillar structures made of elastomers, face a number of challenges. These include limitations on maximum adhesion strength imposed by microstructural dimensions, restricted adaptability to surfaces with varying degrees of roughness, and an inherent trade-off between adhesion strength and switchability. This review explores how shape memory polymers (SMPs) can address these challenges and, through their rubber-to-glass (R2G) transition capability, provide a powerful foundation for the next generation of smart dry adhesives. Specifically, we summarize and elucidate the mechanisms by which SMPs enhance adhesion strength and switchability through material characteristics such as tunable stiffness, shape-locking, and shape-memory effects. Additionally, we discuss a wide range of innovative designs and applications of SMP adhesives, offering insights into the ongoing challenges and emerging opportunities in this rapidly evolving field.

Abstract Objective Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy. Methods A two‐sample MR analysis was conducted using genome‐wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR‐Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's Q test, MR‐Egger intercept test, and leave‐one‐out analysis, was applied to confirm the robustness of results. Results Among the 3117 bacterial taxa examined, we observed that 14 OM, like s_Streptococcus_mitis, s_Streptococcus_pneumoniae, and s_Haemophilus, were positively associated with epilepsy, while 7 OM, like g_Fusobacterium and g_Aggregatibacter, were negatively related to epilepsy. The MR‐Egger intercept suggested that no evidence of horizontal pleiotropy was observed (p > 0.05). The leave‐one‐out analysis validated the robustness of the results. Significance This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in‐depth understanding of the pathogenesis of epilepsy. Plain Language Summary Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in epilepsy.

Abstract Metaverse is a digital value interaction network based on blockchain technology, with an important economic system component. While both traditional financial industries and crypto‐native industries have made significant progress by leveraging blockchain, the value stream of each remains limited to separate ecosystems. To bridge this gap between off‐chain and on‐chain economic systems, an on‐chain trading model was proposed using HD key derivation technique for direct uploading onto chains without going through centralized services for IoT data transmission. To improve the current status of NFTs as static assets, a token protocol binding each NFT with a unique account address was proposed. Additionally, oracle technique was leveraged with a decentralized and distributed trust model spanning across on‐chain and off‐chain components which securely pushes data between smart contracts and Web‐APIs. A decentralized trading model was developed based on smart contracts implementing automated market makers according to CFMM algorithm. Parallel transaction computing was executed based on the DAG model to ensure high operational performance and security standards of underlying blockchain. Finally, the on‐chain trading system of real world asset backed digital assets was developed integrating all the above key techniques that correspond to crucial functions of a complete economic system in Metaverse.

Introduction: Small cell lung cancer (SCLC) is prone to chemoresistance, which is closely related to genome homeostasis-related processes, such as DNA damage and repair. Nucleophagy is the elimination of specific nuclear substances by cells themselves and is responsible for maintaining genome and chromosome stability. However, the roles of nucleophagy in tumour chemoresistance have not been investigated. Objectives: The aim of this work was to elucidate the mechanism of chemoresistance in SCLC and reverse this chemoresistance. Methods: RNA-seq data from SCLC cohorts, chemosensitive SCLC cells and the corresponding chemoresistant cells were used to discover genes associated with chemoresistance and patient prognosis. In vitro and in vivo experiments were performed to verify the effect of high-mobility group box 1 (HMGB1) knockdown or overexpression on the chemotherapeutic response in SCLC. The regulatory effect of HMGB1 on nucleophagy was then investigated by coimmunoprecipitation (co-IP) and mass spectrometry (MS), and the underlying mechanism was explored using pharmacological inhibitors and mutant proteins. Results: HMGB1 is a factor indicating poor prognosis and promotes chemoresistance in SCLC. Mechanistically, HMGB1 significantly increases PARP1-LC3 binding to promote nucleophagy via PARP1 PARylation, which leads to PARP1 turnover from DNA lesions and chemoresistance. Furthermore, chemoresistance in SCLC can be attenuated by blockade of the PARP1-LC3 interaction or PARP1 inhibitor (PARPi) treatment. Conclusions: HMGB1 can induce PARP1 self-modification, which promotes the interaction of PARP1 with LC3 to promote nucleophagy and thus chemoresistance in SCLC. HMGB1 could be a predictive biomarker for the PARPi response in patients with SCLC. Combining chemotherapy with PARPi treatment is an effective therapeutic strategy for overcoming SCLC chemoresistance.

Abstract Background This study explores the value of interlobar fissure semilunar sign(IFSS) based on multifactor joint analysis in predicting the invasiveness of ground glass nodules(GGNs) with interlobar fissure attachment in the lungs. Methods This was a retrospective analysis of clinical data and CT images of 203 GGNs attached to the interlobar fissures confirmed by surgery and pathology. According to pathological results, those GGNs were divided into three groups: glandular precursor lesion (atypical adenomatous hyperplasia/adenocarcinoma in situ), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). Various quantitative and qualitative parameters were analyzed. Results Patient age, maximum diameter, mean size, maximum CT value, and mean CT value differed significantly among the three groups and between with the other group (P

Abstract Excessive fertilisation, improper nutrient management, and specific climatic factors are the main reasons for the high environmental risks associated with agricultural production in subtropical plateau regions. However, quantitative data of environmental impacts and emission reduction potential remain unclear. The development potential of such systems is likely to be significant. In that context, we conducted a case study in Yunnan Province, China, to quantify the environmental impact of crop production from 2002 to 2021. A life cycle assessment method was employed to identify the factors driving environmental impacts, and potential mitigation strategies were proposed. The yield and total nutrient input of grain crops in Yunnan Province increased over the 20-year period, and the environmental footprint of crop production in Yunnan Province was higher than that in other regions. The average annual mean greenhouse gas (GHG) emissions, soil acidification potential (AP), and water eutrophication potential (EP) of crop production from 2002 to 2021 were 837 kg CO2-eq·Mg−1, 15.7 kg SO2-eq·Mg−1, and 2.71 kg PO4-eq Mg−1, respectively. Environmental emissions from crops mainly originate from the application of agricultural inputs (including fertilisers (N, P, and K), pesticides, seed, diesel fuels, and plastic film) during the crop life cycle. There was a significant correlation between surplus nitrogen and environmental impacts. Scenario testing showed that optimised nutrient management practices could increase crop yield and reduce environmental costs. GHG emissions, AP, and EP from the production of rice, wheat, and maize are expected to decrease by 43.0–59.5%, 51.5–64.5%, and 57.4–71.5%, respectively (scenario 4, S4). Based on these findings, we propose that com-prehensive agricultural management measures can reduce the negative impacts of crop production on the environment in subtropical plateau areas and help achieve sustainable agricultural development.

Abstract Proinsulin translation and folding is crucial for glucose homeostasis. However, islet β-cell control of Proinsulin translation remains incompletely understood. Here, we identify OSGEP, an enzyme responsible for t6A37 modification of tRNANNU that tunes glucose metabolism in β-cells. Global Osgep deletion causes glucose intolerance, while β-cell-specific deletion induces hyperglycemia and glucose intolerance due to impaired insulin activity. Transcriptomics and proteomics reveal activation of the unfolded protein response (UPR) and apoptosis signaling pathways in Osgep-deficient islets, linked to an increase in misfolded Proinsulin from reduced t6A37 modification. Osgep overexpression in pancreas rescues insulin secretion and mitigates diabetes in high-fat diet mice. Osgep enhances translational fidelity and alleviates UPR signaling, highlighting its potential as a therapeutic target for diabetes. Individuals carrying the C allele at rs74512655, which promotes OSGEP transcription, may show reduced susceptibility to T2DM. These findings show OSGEP is essential for islet β-cells and a potential diabetes therapy target.

Abstract Chimeric antigen receptor (CAR)-T cell therapy has emerged as one of the most rapidly evolving modalities of immunotherapy, with substantial success in the treatment of hematological malignancies and encouraging outcomes in solid tumors. Yet, the efficacy of CAR-T therapy is hindered by challenges such as suboptimal expansion and persistence, adverse events, a scarcity of ideal targets, high immunosuppression, and insufficient infiltration due to the intricate tumor microenvironment, all of which limit its application. The 2024 European Society for Medical Oncology (ESMO) Congress presented novel CAR-T cell therapies for hematologic and solid malignancies, focusing on strategies such as cytokine modulation, innovative targets, allogeneic development, mRNA vaccine synergy, in vivo delivery and conditional activation to surmount these challenges.

Abstract The shedding of critical distributed energy resources during faults in an islanded microgrid may induce widespread voltage drops, potentially triggering a cascade of reactions leading to the collapse of the entire system. Accurately identifying critical nodes is the key technology to improve the resilience of microgrids. However, multi‐source coupling and the uncertainty in fault‐induced voltage sag can diminish the accuracy of node importance identification. To address this, this paper proposes an adaptive node identification method designed for quick and accurate identification of nodes that cope with various fault scenarios. This method introduces an index for evaluating voltage support capability based on the equivalent voltage drop range. This index adapts to fault uncertainty while integrating electrical parameters with spatial position. Furthermore, a higher‐order transition matrix reconstruction strategy with power propagation characteristics is proposed to reduce the higher‐order complexities arising from remote end faults' current flowing path length. Ultimately, the transition matrix is optimized by integrating it with the PageRank algorithm and highlighting the importance of source nodes. The proposed method is validated by numerical computation and time‐domain simulation results in a benchmark test microgrid, demonstrating its remarkable identification accuracy in a variety of fault scenarios.

This study evaluated the effect of black soldier fly (Hermetia illucens) larvae oil (BO) produced by a novel technique, subcritical butane extraction, on the flesh quality, lipid nutrients and muscle growth of rainbow trout (Oncorhynchus mykiss) fillet, and investigated the alleviating mechanisms of dietary astaxanthin (AST) supplementation. Two hundred and forty fish (215.16 ± 2.30 g) were distributed to three groups with four replicates. Fish were fed three experimental diets for 8 weeks: the control diet (CD diet), total fish oil of the CD diet was replaced with BO to formulate the BO100 diet, and then 1 g/kg AST was supplemented with the BO100 diet to formulate the AST diet. Results showed that the final body weight and the sarcomere length of fillet were significantly increased and the protein phosphorylation levels of mammalian target of rapamycin (mTOR) and p70 S6 kinase were enhanced in the BO100 group compared to the CD group (P

Background and objective: Urinary stones are a significant and common complication among patients with spinal cord injury (SCI), but epidemiological data are scarce and the evidence regarding risk factors remains unclear. Our aim was to investigate the incidence of and risk factors for urinary stones in SCI patients to provide evidence for better prevention and treatment strategies. Methods: Relevant studies were identified from the PubMed, Web of Science, Cochrane, Embase, and Scopus databases. Literature screening, information extraction, and quality evaluation were conducted in accordance with established standards. Data analysis was performed using the metaprop and metan commands in Stata 16.0. Key findings and limitations: A total of 65 studies involving 64 059 patients were included in the analysis. Meta-analysis using a random-effects model revealed that the overall incidence of urinary stones after SCI was 16.6% (95% confidence interval 14.1–19.3%). Over time, the incidence rate has stabilized between 15% and 20%, although annual rates varied significantly, ranging from 2.2% to 68.7%. The highest incidence was observed for bladder stones, with lower incidence rates for kidney and ureteral stones. Among the 13 factors assessed, male sex, a complete injury, and the use of intermittent, indwelling, and condom catheters were identified as independent risk factors for urinary stones. Conclusions and clinical implications: The incidence of urinary stones after SCI is high, with a number of risk factors identified. However, further high-quality research is needed to explore additional potential risk factors. Patient summary: We reviewed the results of previous studies on urinary stones in patients with a spinal cord injury. We found a high rate of urinary stones of about 17% for this patient group. Males are more prone to urinary stones and use of a catheter is a risk factor. More research is needed to identify other risk factors.

Lung cancer is the main cause of cancer-related deaths worldwide. Due to lack of obvious clinical symptoms in the early stage of the lung cancer, it is hard to distinguish between malignancy and pulmonary nodules. Understanding the immune responses in the early stage of malignant lung cancer patients may provide new insights for diagnosis. Here, using high-through-put sequencing, we obtained the TCRβ repertoires in the peripheral blood of 100 patients with Stage I lung cancer and 99 patients with benign pulmonary nodules. Our analysis revealed that the usage frequencies of TRBV, TRBJ genes, and V-J pairs and TCR diversities indicated by D50s, Shannon indexes, Simpson indexes, and the frequencies of the largest TCR clone in the malignant samples were significantly different from those in the benign samples. Furthermore, reduced TCR diversities were correlated with the size of pulmonary nodules. Moreover, we built a backpropagation neural network model with no clinical information to identify lung cancer cases from patients with pulmonary nodules using 15 characteristic TCR clones. Based on the model, we have created a web server named “Lung Cancer Prediction” (LCP), which can be accessed at http://i.uestc.edu.cn/LCP/index.html.

Objective Leg problems including lameness and tibial dyschondroplasia (TD) are one of the most important factors affecting health and animal welfare in meat-type poultry, which are considerably impacted by dietary vitamin regimens. The present study was conducted to investigate the effects of dietary vitamin levels on growth performance and tibia quality in 14-d-old meat ducks. Methods One-d-old Cherry Valley meat-type male ducks were allocated to two vitamin regimens for 14 d, which was formulated according to the recommendation of the National Research Council (NRC, 1994) or China Agricultural Industry Standards (NY/T 2122-2012). Each group included 8 replicates with 16 birds per replicate. Results There was no significant difference in the growth performance of ducks, whereas dietary NY/T vitamin supplementation decreased leg abnormalities as compared to the NRC group, along with similar tibia length, perimeter, and the relative weight of tibia. The tibia from the birds that received the NY/T vitamin diet exhibited markedly higher (p 0.05). Conclusion NY/T vitamin diet improved tibia quality and subsequently decreased leg abnormalities in 14-d-old ducks, which was probably linked with the promoted bone formation.

Sourdough flavors were closely related to microbial metabolism. The microbial diversity of foxtail millet dough during fermentation has never been studied. Here, the metabolic potential and diversity of the bacterial community were analyzed by metagenomic during dough fermentation. Firmicutes was the dominant phylum in the dough, within heterofermentative lactic acid bacteria (e.g., Companilactobacillus, Limosilactobacillus, Pediococcus and Lactobacillus) as the most abundant bacteria. Proteobacteria was gradually inhibited after fermentation. Companilactobacillus_crustorum was notably found abundant during dough leavening. Limosilactobacillus_fermentum increased markedly during fermentation, while Companilactobacillus_crustorum decreased significantly. For further exploration, genes associated with metabolism were annotated through metagenomics. Limosilactobacillus, Companilactobacillus and Pediococcus were actively engaged in glycolysis (ko00010), starch and sucrose metabolism (ko00500), and pyruvate metabolism (ko00620), leading in part to lactic and acetic acid accumulations and dough acidification. Limosilactobacillus and Lactiplantibacillus were the main contributors to key aminopeptidases or/and transaminases involved in amino acid metabolism, which was responsible for flavor metabolite formation. This study will provide an enhanced understanding of the predominance and diversity of dough bacterial communities, and contribute to future strain screening in the dough for better flavor.

Abstract. Background:. Rapid initiation of antiretroviral therapy (ART) is recommended by guidelines, however, real-world studies of same-day initiation of ART in China are limited, and an optimal treatment regimen has yet to be identified. The study aims to provide a realistic reference for rapid initiation of ART. Methods:. We retrospectively analyzed the clinical data of treatment-naïve people with human immunodeficiency virus (PWHs) who were diagnosed and prescribed same-day ART initiation from January 1, 2021 to December 31, 2022 at Chongqing Public Health Medical Center. PWHs voluntarily chose an ART regimen that divided them into two groups: National Free Antiretroviral Treatment Program (NFATP)-recommended regimens group (2 nucleoside reverse transcriptase inhibitors + non-nucleoside reverse transcriptase inhibitors/protease inhibitors) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) group. The primary endpoint was the virological outcome of the two groups for same-day ART initiation at 24 weeks and 48 weeks. The secondary endpoints included changes in CD4 counts, maintenance of the original ART regimen at 48 weeks, and lipid levels and renal function at 48 weeks. Results:. A total of 255 PWHs were included in the study, including 131 (51.4%) in the NFATP group and 124 (48.6%) in the BIC/FTC/TAF group. The overall virological suppression rates at 24 weeks and 48 weeks were 78.2% (165/211) and 95.4% (207/217), respectively. At 24 weeks, the virologic suppression rate in the NFATP group was lower than that in the BIC/FTC/TAF group (65.3% [66/101] vs. 90.0% [99/110], P

Abstract Background Recent advancements in spatially resolved transcriptomics (SRT) have opened up unprecedented opportunities to explore gene expression patterns within spatial contexts. Deciphering spatial domains is a critical task in spatial transcriptomic data analysis, aiding in the elucidation of tissue structural heterogeneity and biological functions. However, existing spatial domain detection methods ignore the consistency of expression patterns and spatial arrangements between spots, as well as the severe gene dropout phenomenon present in SRT data, resulting in suboptimal performance in identifying tissue spatial heterogeneity. Results In this paper, we introduce a novel framework, spatially regularized deep graph networks (SR-DGN), which integrates gene expression profiles with spatial information to learn spatially-consistent and informative spot representations. Specifically, SR-DGN employs graph attention networks (GAT) to adaptively aggregate gene expression information from neighboring spots, considering local expression patterns between spots. In addition, the spatial regularization constraint ensures the consistency of neighborhood relationships between physical and embedded spaces in an end-to-end manner. SR-DGN also employs cross-entropy (CE) loss to model gene expression states, effectively mitigating the impact of noisy gene dropouts. Conclusions Experimental results demonstrate that SR-DGN outperforms state-of-the-art methods in spatial domain identification across SRT data from different sequencing platforms. Moreover, SR-DGN is capable of recovering known microanatomical structures, yielding clearer low-dimensional visualizations and more accurate spatial trajectory inferences.

Abstract Background Delays in diagnostic and therapeutic processes are a potentially preventable cause of morbidity and mortality. Process improvement depends on accurate knowledge about as-is processes, historically collected from front-line workers and summarized in flowcharts. Such flowcharts can now be generated by process discovery algorithms supplied with chronological records from real-world cases. However, these algorithms may generate incomprehensible flowcharts when applied to complex unstructured processes, which are common in healthcare. The aim of this study is to evaluate methods for analysing data from real-world cases to determine causes of delay in complex healthcare processes. Methods Physician insurance claims and hospital discharge data were obtained for patients undergoing carotid endarterectomy at a single tertiary hospital between 2008 and 2014. All patients were recently symptomatic with vision loss. A chronological record of physician visits and diagnostic tests (activities) was generated for each patient using claims data. Algorithmic process discovery was attempted using the Heuristic Miner. The effect of activity selection on treatment delay was investigated from two perspectives: activity-specific effects were measured using linear regression, and patterns of activity co-occurrence were identified using K means clustering. Results Ninety patients were included, with a median symptom-to-surgery treatment time of 34 days. Every patient had a unique sequence of activities. The flowchart generated by the Heuristic Miner algorithm was uninterpretable. Linear regression models of waiting time revealed beneficial effects of emergency and neurology visits, and detrimental effects of carotid ultrasound and post-imaging follow-up visits to family physicians and ophthalmologists. K-means clustering identified two co-occurrence patterns: emergency visits, neurology visits and CT angiography were more common in a cluster of rapidly treated patients (median symptom to surgery time of 18 days), whereas family physician visits, carotid ultrasound imaging and post-imaging follow-up visits to eye specialists were more common in a cluster of patients with treatment delay (median time of 57 days). Conclusions Routinely collected data provided a comprehensive account of events in the symptom-to-surgery process for carotid endarterectomy. Linear regression and K-means clustering can be used to analyze real-world data to understand causes of delay in complex healthcare processes.

Abstract Cervical cancer (CC) ranks as the second highest cause of morbidity and mortality among young women; however, there are currently no age-specific definitions for young cervical cancer or prognostic models tailored to this demographic. Data on CC diagnosed between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age stratification is based on the relationship between age and cancer-specific mortality, as demonstrated by restricted cubic spline analyses (RCS). Cox proportional hazards regression analyses were employed to identify independent prognostic factors in the young CC group. Two novel nomograms for this population were developed and validated using an external validation cohort obtained from a local hospital database, evaluated with concordance index (C-index) and calibration plots. Receiver operating characteristic (ROC) curves were utilized to compare the accuracy of the established models against the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2018). A total of 27,658 patients from the SEER database were classified into three age groups (60 years) based on RCS analyses, with 4,990, 16,922, and 5,746 patients in each group, respectively. The independent prognostic factors identified for young CC included stage, tumour size, grade, histologic type, and surgical intervention. The results of the C-index and calibration in both the training and validation sets confirmed that the two nomograms can accurately predict the occurrence and prognosis of young CC patients. The area under the curve (AUC) values indicated that these models demonstrated higher efficacy in predicting overall survival (OS) compared to the FIGO staging system (2018). These models could potentially serve as effective tools for clinicians to estimate the prognosis of young CC patients.

Abstract The behavior of gas migration in goaf under double roof cutting conditions directly influences the effectiveness of gas control measures. This study employs a combination of numerical simulation and field verification to investigate the patterns of gas migration and accumulation in goaf and to develop coordinated gas control methods under the conditions of double roof cutting and retained roadway. The results indicate that with double roof cutting, goaf permeability generally increases from the interior towards the exterior, with significantly higher porosity in the separation range compared to other areas. High permeability channels form along the sides of the open-off cut, the working face, and the two roadways, subsequently becoming areas of gas accumulation. High-level directional long borehole drainage achieves the best gas drainage at the bottom of the goaf on the working face and belt roadway sides, reducing gas concentration in the working face space to below 0.5%. Pipe jacking extraction along the retained roadway effectively reduces gas concentrations on the working face side and both roadway sides, maintaining working face gas concentrations consistently below 0.3%. Supplementary cutting hole drilling and extraction post-goaf formation show optimal gas extraction results on the working face side and near the two roadways, with gas concentration in the upper corner and return airflow remaining below 0.3% and trending downward. Field data validate the numerical simulation experiment theory.

Abstract Background Patients with trigeminal neuralgia frequently undergo magnetic resonance imaging (MRI) prior to surgery. In patients without the signs and symptoms of face discomfort, MRI has shown the presence of neurovascular contact (NVC) in humans. Therefore, its capacity to accurately exclude NVC of the trigeminal nerve is not properly understood. A meta-analysis of the literature satisfied the criteria to further explore the value of MRI for the diagnosis of classical trigeminal neuralgia (CTN). Study design The association between the symptomatic and asymptomatic trigeminal nerves, NVC, root entry zone (REZ), non-REZ, and anatomical variation was measured by a comprehensive review and meta-analysis of 13 observational studies using MRI for CTN neurovascular compression diagnosis. Objectives This study aimed to evaluate the effectiveness of MRI in detecting the neurovascular compression that causes symptoms in individuals with classic trigeminal neuralgia. Setting This study was conducted at the Department of Neurosurgery, Yantai Yuhuangding Hospital, Qingdao University. Methods Digital searches of PubMed, Embase, and the Cochrane Library were performed to identify studies published until December 31, 2023. The following were evaluated: (1) MRI evidence of NVC in symptomatic and asymptomatic trigeminal nerves; (2) MRI indication of NVC at the REZ in symptomatic and asymptomatic trigeminal nerves; (3) MRI substantiation of non-REZ neurovascular contact in patients with CTN; and (4) asymptomatic and symptomatic anatomical changes at the NVC site of the trigeminal nerves. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed effects models. Results We identified 13 observational studies (1 prospective and 12 retrospective studies) with data collected from 1770 nerves (728 symptomatic and 1042 asymptomatic) were meta-analyzed. First, MRI of 649/728 (88.2%) symptomatic versus 378/1042 (36.3%) asymptomatic trigeminal nerves revealed marked differences in NVC in the REZ (OR = 16.3; CI 95%=12.2–21.8; p

Abstract Considerable advances have been achieved in the application of nanomaterials for immunotherapies, yet the precise immune effects induced by protein corona remain elusive. Here, we explore the formation mechanism and immune regulation process of protein corona in acute myeloid leukaemia (AML) mouse models using commercialized iron oxide nanoparticles (IONPs), with different surface modifications, including an FDA-approved variant. Using macrophages depleted or Complement Component 3 (C3) knockout mice, we demonstrate that carboxymethyl dextran-coated IONP (IONP-COOH) reduces leukaemia burden. Mechanistically, IONP-COOH indirectly binds to C3b after activating the complement alternative pathway, subsequently enhancing phagocytosis of macrophages and activating adaptive immunity mediated by complement corona. While aminated dextran-coated IONPs directly absorb C3b and activate the lectin pathway, leading to immune cell exhaustion. Our findings suggest that IONP-COOH may serve as an immune activator for AML treatment, offering a promising approach to developing therapeutic nanomaterials by leveraging surface chemistry to enhance immunotherapy.

Abstract Alteration or abnormal activation of RTKs have been recurrently observed and recognized as an important driving factor in the progression of many human cancers. Ferroptosis, an iron-dependent form of regulated necrosis triggered by the accumulation of lethal lipid peroxides on cell membranes, has been implicated in various tumor types. Here we reported that oncogenic RTKs/RAS/RAF/c-Myc axis promotes cancer cells to ferroptosis. Mechanistically, c-Myc binds to the promoter region of ACSL4 and promotes the expression of ACSL4, thereby sensitizes cells to ferroptosis. We further showed that RTKs/RAS/RAF promote ferroptosis by upregulating c-Myc mediated expression of ACSL4 in cancer cells. Notably, overexpression of RTKs enhances the vulnerability of melanoma to the ferroptosis inducer in mouse xenograft model. These findings may provide an attractive intervention strategy to target cancers with oncogenic activation of RTKs via a ferroptosis-inducing approach.

Abstract Background Gastrointestinal (GI) cancers have heavily burdened public health. Few studies reported GI cancer burden among adolescents and young adults (AYA). To address this gap, we explored the burden of GI cancer among people aged 15–39. Methods We retrieved data from the Global Burden of Disease Study 2019 Data Resources. The average annual percent change (AAPC) of rates was calculated by linear regression analysis of the natural logarithm. Bayesian age-period-cohort model was applied to predict the future burden. Results In 2019, there were 171,857 (95% uncertain interval [95% UI]: 157,092–187,974) new GI cancer cases with a rate of 5.79/100,000 (95% UI: 5.29–6.33) and 91,033 (95% UI: 83,156–99,399) deaths at a rate of 3.07/100,000 (95% UI: 2.80–3.35) among AYA. The number of prevalent cases and disability-adjusted life years (DALYs) were 722,573 (95% UI: 660,806–789,476) and 5,151,294 (95% UI: 4,706,065–56,188,77), with rates of 24.35/100,000 (95% UI: 22.27–26.60) and 173.57/100,000 (95% UI: 158.57–189.32) respectively. The overall rates of mortality (AAPC = -1.281, p

Abstract Background While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom. Methods This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence. Results After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95%CI:0.99–1.30) approached statistical significance after full adjustment for mediators. In contrast, in the UK cohort, significant associations persisted for most TyG Index indicators when full adjustment for mediators, including BMI (HR: 1.17, 95% CI: 1.09–1.26), TyG-BMI (HR: 1.16, 95% CI: 1.07–1.26), TyG-WC (HR: 1.13, 95% CI: 1.03–1.25), TyG-FMI (HR: 1.17, 95% CI: 1.07–1.28), and TyG-RBI (HR: 1.15, 95% CI: 1.06–1.24). TyG-BRI also showed the best predictive performance for ischemic stroke in Chinese rural residents (AUC > 0.7) and exhibited an almost linear relationship with ischemic stroke occurrence. Additionally, TyG-BRI presented a U-shaped relationship with the risk of hemorrhagic stroke incidence in the UK (p overall = 0.041, p non-linear = 0.017). Multimorbidity mediated the relationship between TyG indices, and ischemic stroke incidence in both cohorts. The mediation percentage for multimorbidity was higher than the sum of individual chronic diseases, with a higher mediation percentage in the Chinese cohort (up to 51%) compared to the UK cohort (up to 27.2%). Conclusions Chinese rural residents exhibit higher levels of visceral obesity compared to residents in UK, leading to greater stroke susceptibility mediated by multimorbidity. These findings underscore the importance of comprehensive management of multimorbidity for stroke prevention. The TyG-BRI may serve as a promising predictor of ischemic stroke incidence among rural community residents.

The cladding layer of high entropy alloy (HEA), specifically AlCoCrFeNiMo, was fabricated using both continuous wave (CW) and pulse wave (PW) laser techniques, with pulse frequencies set at 0.5 Hz, 5 Hz, 50 Hz, 500 Hz, and 5000 Hz. The microstructure of the cladding layer was analyzed using X-ray diffraction, ultra-depth-of-field metallographic microscopy, and scanning electron microscopy. The wear resistance, corrosion resistance, and combined corrosion-wear resistance of the cladding layer were assessed using friction and wear tests, electrochemical corrosion tests, and corrosion-wear experiments. Additionally, the impact of pulse frequency on the microstructure and properties of HEA cladding layers was examined and compared with CW cladding layers. The research results indicate the presence of body-centered cubic (BCC), σ, and B2 phases in all cladding layers. Compared to the CW cladding layer, the PW cladding layer exhibits smaller grain sizes and a reduced proportion of the σ phase. With an increase in pulse frequency, there is a gradual increase in the proportion of the σ phase and a corresponding evolution in the grain sizes within the HEA cladding structure. Notably, at a specific pulse frequency of 50 Hz, the grain size reaches its minimum. PW cladding exhibited superior wear resistance, corrosion resistance, and corrosion-wear resistance compared to CW cladding, primarily due to the finer grain size observed in the former. The optimal performance of the cladding layer can be achieved when the pulse frequency was set at 50 Hz. The refinement of grain size, combined with an appropriate presence of the σ phase, synergistically contributes to enhancing cutting resistance during friction processes. This collaborative effect further hinders plastic deformation, consequently improving the wear resistance of HEA cladding. Furthermore, the grain refinement in PW cladding promotes the development of surface oxide films, which play a crucial role in reducing galvanic corrosion of alloying elements and minimizing oxygen atom diffusion rates during corrosion processes. Consequently, both corrosion resistance and corrosion wear resistance of PW cladding are significantly enhanced.

Abstract Ultrasonography (US) of thyroid nodules is often time consuming and may be inconsistent between observers, with a low positivity rate for malignancy in biopsies. Even after determining the ultrasound Thyroid Imaging Reporting and Data System (TIRADS) stage, Fine needle aspiration biopsy (FNAB) is still required to obtain a definitive diagnosis. Although various deep learning methods were developed in medical field, they tend to be trained using TI-RADS reports as image labels. Here, we present a large US dataset with pathological diagnosis annotation for each case, designed for developing deep learning algorithms to directly infer histological status from thyroid ultrasound images. The dataset was collected from two retrospective cohorts, which consists of 8508 US images from 842 cases. Additionally, we explained three deep learning models used as validation examples using this dataset.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most poorly prognostic digestive tract malignancies. CLDN18.2 CAR-T therapy has recently shown promising clinical effects in PDAC. Radiotherapy, a traditional treatment, can induce systemic immune activation and abscopal effects. However, the synergistic effect and mechanism of their combination in PDAC treatment remain poorly understood. In this study, we developed a CLDN18.2-specific CAR-T and applied it to unilateral and bilateral mouse tumor models. Our results demonstrated that this synergy therapy not only improved tumor-killing effects in unilateral tumor-bearing mice but also induced regression in both local and distant tumors in bilateral tumor models. Mechanistically, early radiation-induced apoptosis promoted the proliferation of CD8 + T cells, while increased chemokine CCL2 levels from localized and distant tumor sites facilitated CAR-T and endogenous T cell infiltration, leading to systemic tumor suppression. This study proposes a promising approach for treating metastatic pancreatic cancer by combining radiotherapy and CAR-T therapy, elucidating the mechanism of CAR-T cell-enhanced radiotherapy effects ex vivo, and highlighting a novel strategy for combating metastatic pancreatic cancer.

Abstract Background The genus Sapovirus in the family Caliciviridae comprises of a genetically diverse group of viruses that are responsible for causing acute gastroenteritis in both human and animals globally. As the number of sequences continues to grow and more recombinant sequences are identified, the classification criteria of genogroups and genotypes of sapovirus need to be further refined. In this study, we aimed to optimize the classification of sapoviruses. Results Through evolutionary clustering and genetic distance analysis, we have updated the classification criteria for VP1 genogroup and genotypes. We adjusted the original mean values ± 3 standard deviations (SD) of genetic distances to mean values ± 2.5SD, resulting the corresponding cutoff values for the same genotype and genogroup set at

Abstract Background Endophytes play an important role in promoting plant growth. To date, although many reports provided insight into the function of endophytes in their hosts, few reports focus on their impact on nearby plants. Intraspecific allelopathy in plant community is common and presents a notable challenge to medicinal plant yield and productivity. Atractylodes lancea is a perennial herb that has relatively low yields due to intraspecific allelopathy. The bacterial endophyte Pseudomonas fluorescens ALEB7B has previously been found to increase essential oil content of A. lancea, but the role of ALEB7B in A. lancea allelopathy is still unknown. Results Noninoculated A. lancea exhibited growth retardation when it was grown in a community, which was related to ethylene-induced intraspecific allelopathy. Further experiment showed that exposing A. lancea to volatile from noninoculated A. lancea or same concentration of ethylene reduced growth of A. lancea. P. fluorescens-inoculated plants showed reduced ethylene emission and relieved growth retardation on neighboring noninoculated A. lancea. Moreover, P. fluorescens inoculation had little allelopathic effect when receivers were treated with ethylene receptor inhibitor or when emitters were treated with ethylene production inhibitor. Transcriptomic analysis revealed that endophyte ALEB7B altered transcriptional response associated with ethylene response and essential oil production in neighboring A. lancea. Conclusions Our results demonstrated that the bacterial endophyte ALEB7B provides fitness benefits for both hosts and neighbors. The allelopathic effect on nearby plants can be alleviated by altering airborne signals, such as ethylene, in endophytic bacteria.