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Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Background Lung cancer, a major global health concern, disproportionately impacts low socioeconomic status (SES) patients, who face suboptimal care and reduced survival. This study aimed to evaluate the prognostic performance of traditional Cox proportional hazards (CoxPH) regression and machine learning models, specifically Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost), in patients with advanced lung cancer with low SES. Design A retrospective study. Method The 949 patients with advanced lung cancer with low SES who entered the hospice ward of a tertiary hospital in Wuhan, China, from January 2012 to December 2021 were randomized into training and testing groups in a 3:1 ratio. CoxPH regression methods and four machine learning algorithms (DT, RF, SVM, and XGBoost) were used to construct prognostic risk prediction models. Results The CoxPH regression-based nomogram demonstrated reliable predictive accuracy for survival at 60, 90, and 120 days. Among the machine learning models, XGBoost showed the best performance, whereas RF had the lowest accuracy at 60 days, DT at 90 days, and SVM at 120 days. Key predictors across all models included Karnofsky Performance Status (KPS) score, quality of life (QOL) score, and cough symptoms. Conclusions CoxPH, DT, RF, SVM, and XGBoost models are effective in predicting mortality risk over 60–120 days in patients with advanced lung cancer with low SES. Monitoring KPS, QOL, and cough symptoms is crucial for identifying high-risk patients who may require intensified care. Clinicians should select models tailored to individual patient needs and preferences due to varying prediction accuracies. Reporting method This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. Patient or public contribution No patient or public contribution.

Abstract At present, biopharmaceuticals have received extensive attention from the society, among which recombinant proteins have a good growth trend and a large market share. Chinese hamster ovary (CHO) cells are the preferred mammalian system to produce glycosylated recombinant protein drugs. A highly efficient and stable cell screening method needs to be developed to obtain more and useful recombinant proteins. Limited dilution method, cell sorting, and semi-solid medium screening are currently the commonly used cell cloning methods. These methods are time-consuming and labor-intensive, and they have the disadvantage of low clone survival rate. Here, a method based on semi-solid medium was developed to screen out high-yielding and stable cell line within 3 weeks to improve the screening efficiency. The semi-solid medium was combined with an expression vector containing red fluorescent protein (RFP) for early cell line development. In accordance with the fluorescence intensity of RFP, the expression of upstream target gene could be indicated, and the fluorescence intensity was in direct proportion to the expression of upstream target gene. In conclusion, semi-solid medium combined with bicistronic expression vector provides an efficient method for screening stable and highly expressed cell lines.

Abstract Background Plerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni. Methods In this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults. Results A total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni. Conclusions The dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni. Graphical abstract

To investigate the current landscape of the application of machine learning in remote sensing surveys of geological disasters and to support the development of intelligent remote sensing survey technologies for geological disasters, a bibliometric analysis of machine learning and geological disaster remote sensing survey technology was conducted using the China National Knowledge Infrastructure (CNKI) database. Visual analysis was performed from multiple perspectives, including the number of publications, research hotspots, and research institutions, to describe the research progress of machine learning and geological disaster remote sensing survey technology. VOSviewer software was utilized to scrutinize the high-frequency keywords and their associations between machine learning and geological disaster remote sensing survey technology. The results showed that remote sensing survey technology for geological disasters in China is gradually shifting from traditional “topographic measurement” towards more holistic “topographic and geometric measuremen” approaches. With the advancement of unmanned aerial vehicle remote sensing technology, the new generation of intelligent learning algorithms have emerged as the predominant research direction, fostering the growth of automated geological disaster recognition and intelligent extraction techniques. Nevertheless, the future of remote sensing survey technology for geological disasters is poised to evolve into a comprehensive technical system that emphasizes the synergistic “air-space-ground” application and emergency monitoring. Considering the diverse characteristics of remote sensing image data, the primary developmental trajectory will involve an extensive exploration of various machine learning algorithms across different remote sensing interpretation scenarios.

With the development of arid and semi-arid regions in China, the hazards posed by collapsible sands to engineering construction have become increasingly significant. In order to investigate the collapsibility regularity and its influencing factors of sand soils, this paper focuses on the wind-blown sands at the southern edge of the Maowusu Desert. Initially, by controlling the single factor laboratory compression tests, the collapsibility regularity of wind-blown sand under different working conditions was investigated. Subsequently, using PFC3D (three-dimensional particle flow software) for numerical simulation of the laboratory compression tests on wind-blown sands, the paper explores the effects of different porosities and particle compositions on the collapsibility of sandy soils. The research results indicate that the collapsibility coefficient of sandy soils shows a trend of first increasing and then decreasing with pressure, reaching its maximum value at 150 kPa. With the increase in dry density or moisture content, the collapsibility coefficient of sand decreases. Compared to moisture content, dry density has a greater impact on the collapsibility of sandy soils. There is a positive correlation between the collapsibility coefficient of wind-blown sand and its porosity. The initial porosity of the collapsibility of the wind-blown sand on the southern edge of the Maowusu Desert is 0.425. When the ratio of particle content between 0.075～0.25 mm and 0.25～0.5 mm is 0.35∶0.65, the collapsibility of sandy soils is maximized. The research results comprehensively describe the entire process of laboratory compression tests on sand from macro to micro levels, revealing the collapsibility regularity and its influencing factors on wind-blown sand from multiple scales. This can provide a reference for engineering construction in the Maowusu Desert and provide certain ideas and basis for the research on particle flow numerical simulation of sand.

Abstract Elastocaloric cooling has experienced fast development over the past decade owing to its potential to reshape the refrigeration industry. While the solid-state elastocaloric refrigerant is emission-free, the efficiency of the state-of-the-art elastocaloric cooling systems is not sufficient yet to reduce carbon emissions during operation. In this study, we double the coefficient of performance, the most commonly used efficiency metric, via the synergy of material-level advances in TiNiCu and the system-level roller-driven mechanism capable of recovering kinetic energy. On the materials level, a 125% improvement in coefficient of performance is illustrated in TiNiCu compared to NiTi, empowered by the B2-B19 martensitic transformation with improved lattice compatibility and the grain boundary strengthening from the nanocrystalline structure. On the system level, owing to the properly sized angular momentum in rotating parts, 78% work recovery efficiency is reported, transcending the theoretical limit previously unattainable without kinetic energy recovery. This confluence of materials and mechanical innovations propels elastocaloric cooling systems into a new realm of efficiency and paves the way for their practical application.

Abstract Background Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive. Results We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown. Conclusions Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract

Abstract The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Feature extraction and classification is a difficult area in motor imagery electroencephalogram (EEG) signal processing. In order to improve the classification accuracy of EEG signals, both a feature extraction method based on the combination of LMD-CSP and a classification algorithm based on the fusion of PSO-SVM are proposed. Firstly, the extended informax ICA algorithm is used to denoise the signal and reduce the influence of noise on the signal. Then, the pre-processed EEG signals are decomposed into multiple Product Function (PF) components by Local Mean Decomposition (LMD), and the most discriminative PF component is selected. Next, feature extraction is carried out from the selected PF components using the Common Space Pattern (CSP). Finally, the obtained features are input into a Support Vector Machine (SVM) classifier improved by Particle Swarm Optimization (PSO) for classification recognition. The experimental results show that compared with the traditional CSP-SVM method, CapsNet method, WPT-CSP+CNN method, FDCSP-SVM method, and EMD-CNN method, the classification accuracy of the proposed method is increased by 26.94 %, 14.9 %, 13.34 %, 8.34 % and 4.04 %, respectively. This further proves the superiority of the proposed method for EEG signal processing technology.

This study addresses the pivotal challenge of water resource allocation in urban environments by introducing a novel approach – a multi-objective chance-constrained fuzzy interval linear programming model integrated with principal component analysis (PCA). This innovative model aims to alleviate subjectivity in urban water management processes, particularly in adjusting water demands across various sectors. The proposed model incorporates correlation analysis to identify dimensionality-reducing factors of multitarget components, determining the proportion of each target component relative to the total components. Fuzzy sets are applied to irrigation water resource allocation quantity, segmented into six levels of fuzzy membership to analyze the stochasticity of water supply. Results demonstrate the model's efficacy, revealing that variations in risk probabilities impact water supply, necessitating positive water management strategies to enhance agricultural efficiency and negative strategies to mitigate the risk of inadequate water supply. Key findings emphasize the significance of agricultural water availability and the structure of irrigation water use in optimal resource allocation. Importantly, the study showcases the enhanced precision achieved through the proposed multi-objective chance-constrained fuzzy interval linear programming with PCA, thereby refining the optimization outcomes for water management under multifaceted objectives. HIGHLIGHTS Development of a multi-objective chance-constrained fuzzy interval model.; Integration principal component analysis to improve the optimal solutions.; Application of a multidimensional analysis to effectively assess risk probabilities.; Optimization of agricultural water resources under varying constraints.; Offering strategic recommendations for agricultural cropping structures.;

Abstract Prognostics and health management (PHM) has gotten considerable attention in the background of Industry 4.0. Battery PHM contributes to the reliable and safe operation of electric devices. Nevertheless, relevant reviews are still continuously updated over time. In this paper, we browsed extensive literature related to battery PHM from 2018 to 2023 and summarized advances in battery PHM field, including battery testing and public datasets, fault diagnosis and prediction methods, health status estimation and health management methods. The last topic includes state of health estimation methods, remaining useful life prediction methods and predictive maintenance methods. Each of these categories is introduced and discussed in details. Based on this survey, we accordingly discuss challenges left to battery PHM, and provide future research opportunities. This research systematically reviews recent research about battery PHM from the perspective of key PHM steps and provide some valuable prospects for researchers and practitioners.

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in Prdx1-overexpression (Prdx1-OE) mice. Besides, S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS production. Due to the limited druggability of S14 with low bioavailability (2.6%) and poor renal distribution, a pH-sensitive kidney-targeting dodecanamine-chitosan nanoparticle system is constructed to load S14 for precise treatment of AKI. l-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1 (Kim-1)-overexpressed cells. The developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 significantly. By encapsulation with micelles, the AUC0‒t, half-life time, and renal distribution of S14 increase 2.5-, 1.8-, and 3.1-fold, respectively. The main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDP-glycosyltransferase (UGT)-mediated biotransformation. In summary, this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology, thereby driving advancements in marine drug development for AKI.

Abstract Background Despite the improved survival observed in PD-1/PD-L1 blockade therapy, a substantial proportion of cancer patients, including those with non-small cell lung cancer (NSCLC), still lack a response. Methods Transcriptomic profiling was conducted on a discovery cohort comprising 100 whole blood samples, as collected multiple times from 48 healthy controls (including 43 published data) and 31 NSCLC patients that under treatment with a combination of anti-PD-1 Tislelizumab and chemotherapy. Differentially expressed genes (DEGs), simulated immune cell subsets, and germline DNA mutational markers were identified from patients achieved a pathological complete response during the early treatment cycles. The predictive values of mutational markers were further validated in an independent immunotherapy cohort of 1661 subjects, and then confirmed in genetically matched lung cancer cell lines by a co-culturing model. Results The gene expression of hundreds of DEGs (FDR p 2) distinguished responders from healthy controls, indicating the potential to stratify patients utilizing early on-treatment features from blood. PD-1-mediated cell abundance changes in memory CD4 + and regulatory T cell subset were more significant or exclusively observed in responders. A panel of top-ranked genetic alterations showed significant associations with improved survival (p

In recent years, the global practice of regional natural disaster reduction and comprehensive risk prevention has promoted the integration of multiple disciplines, and the theory and technology of comprehensive risk assessment for multiple natural disaster chains urgently need innovation. This article is based on multiple natural disaster chain scenarios and sets secondary indicators for multiple influencing factors based on the first level indicators composed of basic risk factors such as hazard factors, vulnerability of disaster bearing bodies, and disaster prevention and reduction capabilities. By using multidimensional information diffusion technology, multiple hazard factor hazard combination factors, vulnerability combination factors of disaster bearing bodies, and comprehensive disaster prevention and reduction capability combination factors reflecting various natural disaster scenarios are constructed, A household comprehensive risk assessment index system for multi-dimensional information diffusion assessment of natural disaster comprehensive risk was designed by quantifying risk factors such as the intensity of comprehensive disaster causing factors, vulnerability of disaster bearing bodies, and comprehensive disaster prevention and reduction capabilities in disaster scenarios. This paper expands the traditional information diffusion comprehensive risk assessment model, makes up for the lack of information on geographical units, establishes a multi impact factor multi dimension natural disaster risk comprehensive assessment model for multi risk factors of complex disaster scenarios with small samples, obtains the theoretical value of multi-dimensional information Diffusion model comprehensive risk assessment for complex disaster scenarios, breaks through the sample size limit of natural disaster risks, and makes up for the lack of information on small samples of small probability events, Improved the reliability and accuracy of comprehensive risk assessment for multiple natural disaster chains. Then, take the disaster scenario formed by the comprehensive risk of earthquake and flood in a place in the upper reaches of the Fujiang River basin as the analysis sample, calculate the comprehensive risk assessment value of flood and earthquake damage in the study area's micro samples (rural households in villages and towns). By comparison, it is found that the comprehensive risk value assessed by the multi-dimensional information Diffusion model has good reliability and high accuracy, which is significantly better than the traditional Kriging interpolation method and geographical weighted regression method. This article provides a comprehensive risk assessment of natural disasters at the micro household level, which can better reflect the diversity and regionality of risks, help clarify the hidden risks of rural natural disasters, and provide scientific basis for government emergency management decision-making.

Chimonobambusa utilis is a unique edible bamboo species valued for its economic and nutritional benefits. However, its existence in natural habitats is at risk due to environmental shifts and human interventions. This research utilised the maximum entropy model (MaxEnt) to predict potential habitats for Ch. utilis in China, identifying key environmental factors influencing its distribution and analysing changes in suitable habitats under future climate conditions. The results show that the results of the MaxEnt model have high prediction accuracy, with an AUC (Area Under the receiver operating characteristic Curve) value of 0.997. Precipitation in the driest month (Bio14), altitude (Alt) and isothermality (Bio03) emerged as the primary environmental factors influencing the Ch. utilis distribution. Currently, the suitable habitats area for Ch. utilis is 10.55 × 104 km2. Projections for the 2050s and 2090s indicate potential changes in suitable habitats ranging from -3.79% to 10.52%. In general, the most suitable habitat area will decrease and shrink towards higher latitude areas in the future. This study provides a scientific basis for the introduction, cultivation and conservation of Ch. utilis.

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by mitochondrial dysfunction and accumulation of alpha-synuclein (α-Syn)-containing protein aggregates known as Lewy bodies (LB). Here, we investigated the entry of α-Syn into mitochondria to cause mitochondrial dysfunction and loss of cellular fitness in vivo. We show that α-Syn expressed in yeast and human cells is constitutively imported into mitochondria. In a transgenic mouse model, the level of endogenous α-Syn accumulation in mitochondria of dopaminergic neurons and microglia increases with age. The imported α-Syn is degraded by conserved mitochondrial proteases, most notably NLN and PITRM1 (Prd1 and Cym1 in yeast, respectively). α-Syn in the mitochondrial matrix that is not degraded interacts with respiratory chain complexes, leading to loss of mitochondrial DNA (mtDNA), mitochondrial membrane potential and cellular fitness decline. Importantly, enhancing mitochondrial proteolysis by increasing levels of specific proteases alleviated these defects in yeast, human cells, and a PD model of mouse primary neurons. Together, our results provide a direct link between α-synuclein-mediated cellular toxicity and its import into mitochondria and reveal potential therapeutic targets for the treatment of α-synucleinopathies.

Abstract The global energy budget is pivotal to understanding planetary evolution and climate behaviors. Assessing the energy budget of giant planets, particularly those with large seasonal cycles, however, remains a challenge without long-term observations. Evolution models of Saturn cannot explain its estimated Bond albedo and internal heat flux, mainly because previous estimates were based on limited observations. Here, we analyze the long-term observations recorded by the Cassini spacecraft and find notably higher Bond albedo (0.41 ± 0.02) and internal heat flux (2.84 ± 0.20 Wm−2) values than previous estimates. Furthermore, Saturn’s global energy budget is not in a steady state and exhibits significant dynamical imbalances. The global radiant energy deficit at the top of the atmosphere, indicative of the planetary cooling of Saturn, reveals remarkable seasonal fluctuations with a magnitude of 16.0 ± 4.2%. Further analysis of the energy budget of the upper atmosphere including the internal heat suggests seasonal energy imbalances at both global and hemispheric scales, contributing to the development of giant convective storms on Saturn. Similar seasonal variabilities of planetary cooling and energy imbalance exist in other giant planets within and beyond the Solar System, a prospect currently overlooked in existing evolutional and atmospheric models.

Abstract Background the salutogenic theory is essential to explain an individual’s ability to maintain health during the perinatal period. While previous studies mainly focused on the perspectives from a family-level orientation and a global orientation, the purpose of the present study was to develop and validate a scale, the childbearing sense of coherence scale (CSOC-scale) from the individual’s perceptions of the stresses, resources, and meaningfulness of childbearing. Methods A total of 3 separate studies contributed to the development of the CSOC-scale between July 2022 and February 2023. In study 1, the initial item pool based on the conceptual framework of the childbearing sense of coherence and the salutogenic theory was developed. Delphi expert consultation was conducted to revise and improve items. Studies 2 and 3 were cross-sectional studies. In study 2, item analysis and explore factor analysis (EFA) (N = 351 for women, N = 256 for men) were used to screen items. In study 3, confirmatory factor analysis (CFA) and reliability analysis (N = 366 for women, N = 308 for men) were used to test the fit indices and reliability of the final scale. Results final analysis suggested the CSOC-scale includes three factors, consisting of 13 items. Confirmatory factor analysis demonstrated good model fit (χ 2 = 157.448, df = 62, χ 2 / df = 2.539, RMSEA = 0.065, CFI = 0.974, TLI = 0.968, SRMR = 0.029 for women; χ 2 = 181.363, df = 62, χ 2 / df = 2.925, RMSEA = 0.079, CFI = 0.968, TLI = 0.960, SRMR = 0.033 for men) and high factor loadings (from 0.751 to 0.929 for women; from 0.746 to 0.947 for men). Internal consistency (Cronbach’s α ranging from 0.895 to 0.933 for women and 0.881 to 0.945 for men in three dimensions; Cronbach’s α was 0.919 for women and 0.821 for men in the entire instrument) and split-half reliability (Spearman-Brown coefficients ranging from 0.876 to 0.921 for women and 0.841 to 0.937 for men in three dimensions; Spearman-Brown coefficient was 0.744 for women and 0.785 for men in the entire instrument) were excellent. Conclusions the CSOC-scale has robust psychometric properties. It is reliable and valid in evaluating the childbearing sense of coherence in women and men during pregnancy. Utilisation of this scale can help healthcare professionals understand the health maintenance competencies of couples during the transition of parenthood and provide health promotion services from a salutogenic perspective.

Abstract CD7 targeted CAR‐T has demonstrated potential in the treatment of T cell malignancies but no study has been reported about its potential in the prophylaxis of GVHD in allo‐HSCT. Here we reported a special case that a boy diagnosed with refractory acute T lymphoblastic leukemia (T‐ALL) was treated with universal CD7 targeted CAR‐T (CD7 UCAR‐T) and parent‐derived peripheral blood stem cells (PBSCs). Complete remission and full engraftment of donor was observed. In the later four months of follow‐up, in the absence of any immunodepression treatment, no signs of GVHD were observed. This case initially demonstrates the potential of CD7 UCAR‐T in the prophylaxis of GVHD.

Abstract Background Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. Methods Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. Results From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1–77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6–14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3–83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3–4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5–1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. Conclusions Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. Trial Registration ClinicalTrials.gov, NCT03781219.

Abstract Background To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. Methods We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. Results The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P

Corrosion poses a significant threat to the structural integrity of steel rails, especially in an acidic environment. In this study, we evaluate the corrosion properties of U75V-welded joints using potentiodynamic polarization curves, electrochemical impedance measurements, and corrosion morphology studies under simulated acidic conditions. Compared to non-normalized joints, the normalized joints exhibit a higher self-corrosion current (4.65 × 10−5 A/cm2) and a more negative self-corrosion potential (−0.56919 mV). The smaller and more uniform grain size obtained after normalizing provides multiple active sites on the surface for polarization reactions. Furthermore, owing to significant erosion caused on the rail surface by the acidic solutions, normalizing treatment enhances the passivation effects on the surface, resulting in increased corrosion resistance (221.96 Ω cm2). Our findings provide insights into the impact of normalizing treatments on the corrosion mechanism of U75V rail joints under acidic conditions.

Abstract Background The incidence of neuroendocrine neoplasms (NENs) is rising rapidly worldwide. However, there are few reports on these heterogeneous diseases in China. Our study aimed to explore the epidemiological characteristics of NENs in Beijing. Methods We conducted a retrospective cohort study using population-based cancer surveillance data in Beijing, China. All data were extracted from the Beijing Cancer Registry with incidence dates from 1 January 1998 to 31 December 2018; the follow-up period was through 31 December 2021. Segi’s world standard population was used to estimate the age-standardized rate. Survival was estimated using the Kaplan–Meier method. Results From 1998 to 2018, the incidence of NENs in Beijing initially showed a significant increasing trend, from 1.07/100,000 to 3.53/100,000; this began to plateau after 2013. The age-specific incidence rate increased with age and peaked in the age group 70–74 years. The incidence in men was significantly higher than that in women (4.41/100,000 vs. 1.69/100,000). The most common sites of NENs were the lung (2.38/100,000) and rectum (0.14/100,000). Most NENs were diagnosed at a late stage. We found that NENs originating from the lung had worse overall survival than extrapulmonary NENs, and male patients had worse survival than female patients. Conclusions This study retrospectively analyzed the epidemiological characteristics of NENs in Beijing from 1998 to 2018. Our findings provide a reference regarding the epidemiological statistics of NENs in Beijing to contribute to the prevention, diagnosis, and treatment of these specific tumors.

Abstract N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC–MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. With a favorable bioavailability of 24.0%, N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs. Graphical Abstract

Agrobacterium-mediated plant transformation is widely used in plant genetic engineering. However, its efficiency is limited by plant immunity against Agrobacterium. Chili pepper (Capsicum annuum L.) is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation. In this work, Agrobacterium was found to induce a strong immune response in pepper, which might be the reason for T-DNA being difficult to express in pepper. An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves. Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death, presumably due to reduced bacterial growth. However, mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response. The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.

Titanium alloys have excellent properties and are widely used in aerospace, medicine, chemical industry, and other fields. With the rapid development of the powder metallurgy and 3D printing industries, the demand for ultra-fine titanium alloy powders has increased significantly. It should be noted that the particle size of titanium alloy powders determines the application process. However, the high melting point of titanium and titanium alloys and the limitation of many factors, such as the prepared powders being easily contaminated by secondary pollution, make the preparation cost higher, which restricts their promotion and application. In this study, the research progress of micro and nano titanium alloy powder preparation process is described, and the existing problems of various processes are analyzed and discussed, and it is proposed that the direct reduction in TiO2 to obtain micro and nano titanium alloy powder is the key research direction in the future. In particular, the preparation of micro and nano titanium alloy powder by “calciothermic self-propagation process” has great industrial potential.

Abstract Production of liquid fertilizers containing nitrogenous nutrients and biostimulants from sewage sludge (SS-NB) has been attracting increasing attention due to its excellent fertilization effect and resource recycling attributes. To better understand the functional effects of nutrients and biostimulants in SS-NB on soil, the adsorption capacity and mechanism of straw biochar (SB) and wood chip biochar (WCB) for alkaline and neutral SS-NB components were investigated. The adsorption of total organic carbon (TOC) from alkaline and neutral SS-NB by WCB was 61.14% and 89.73%, respectively, higher than that by SB, which was 56.25% and 83.36%. Moreover, TOC from neutral SS-NB was more readily adsorbed, especially for fulvic and humic acids. SB had a strong adsorption capacity for calcium ions and nitrogen (TKN, nitrate N, protein, amino acid) and released large amounts of P. In addition, WCB and SB showed a strong affinity for macromolecules (proteins) and reducing substances (lignin and lipids) and excellent fixation ability for phytohormones and allelochemicals. However, WCB adsorbed more types of molecular substances than SB while maintaining a high immobilization rate. Analysis of the adsorption mechanism showed that surface amino groups of the biochar were involved in adsorption, while WCB had additionally high adsorption efficiencies through pore adsorption, hydrogen bonding adsorption and pore size-exclusion effects. The study revealed that biochar can be used as an efficient adsorption carrier for SS-NB to improve soil fertility management. Graphical Abstract

Abstract Background The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC. Methods From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients’ demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression. Findings In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307). Interpretation In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.

Objective Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn’s disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association.Methods This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted.Results During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05–1.23), p=0.001) and 12% for disease progression (1.12 (1.05–1.19), p

The dependence of tumor cells on glycolysis provides essential energy and raw materials for their survival and growth. Recent research findings have indicated that long chain non-coding RNAs (LncRNAs) have a key regulatory function in the tumor glycolytic pathway and offer new opportunities for cancer therapy. LncRNAs are analogous to a regulatory key during glycolysis. In this paper, we review the mechanisms of LncRNA in the tumor glycolytic pathway and their potential therapeutic strategies, including current alterations in cancer-related energy metabolism with lncRNA mediating the expression of key enzymes, lactate production and transport, and the mechanism of interaction with transcription factors, miRNAs, and other molecules. Studies targeting LncRNA-regulated tumor glycolytic pathways also offer the possibility of developing new therapeutic strategies. By regulating LncRNA expression, the metabolic pathways of tumor cells can be interfered with to inhibit tumor growth and metastasis, thus affecting the immune and drug resistance mechanisms of tumor cells. In addition, lncRNAs have the capacity to function as molecular markers and target therapies, thereby contributing novel strategies and approaches to the field of personalized cancer therapy and prognosis evaluation. In conclusion, LncRNA, as key molecules regulating the tumor glycolysis pathway, reveals a new mechanism of abnormal metabolism in cancer cells. Future research will more thoroughly investigate the specific mechanisms of LncRNA glycolysis regulation and develop corresponding therapeutic strategies, thereby fostering new optimism for the realization of precision medicine.

Nitrogen mustard (NM) is a chemotherapeutic agent capable of alkylating nucleophilic proteins and DNA, causing severe cell damage. However, no reports have been on the dynamic changes in proteomics induced by NM. In this study, we established a model of acute exposure to NM for 1 h and a continuous cultured model for 24 h after NM removal (repair stage) using 16HBE cells. The nuclear protein spectrum and nuclear proteins crosslinked with DNA were analyzed, and the function of p97 during NM damage was examined. An hour of NM exposure resulted in severe changes in the nuclear protein spectrum and protein into the cell nucleus, which is mainly involved in nuclear acid-related issues. After 24 h, the return to normal process of the types and amounts of differentially expressed proteins was inhibited by si-p97. The main processes involved in si-p97 intervention were nucleocytoplasmic transport, processing in the endoplasmic reticulum, metabolic abnormalities, and DNA-response; however. An hour of exposure to NM increased DNA-protein crosslinking (DPC), total-H2AX, and p-H2AX. In contrast, si-p97 only further increased or maintained their levels at 24 h yet not at 1 h. The effect of the proteasome inhibitor, MG132, was similar to that of si-p97. The siRNA of DVC1, a partner of p97, also increased the DPC content. Both si-p97 and si-DVC1 increased the cytoplasmic levels of the proteasome (PSMD2). These results suggest acute NM exposure induces severe nuclear protein spectral changes, rapid protein influx into the nucleus, DPC formation, and DNA double-strand breaks. Furthermore, our data indicated that p97 is involved in normal protein spectrum maintenance and DPC removal after NM withdrawal, requiring the participation of DVC1 and the proteasome.

Background: Although studies in China have found that school bullying is prevalent among adolescents, most relevant research has focused on southern China, while research in northern China is limited. This study aimed to explore ethnic disparities in the socio-demographic determinants of school bullying in Inner Mongolia, a northern region of China. Methods: A cross-sectional study was conducted among 2891 adolescents in Inner Mongolia, China, from September to December 2022. Data on participants' sociodemographic characteristics and school bullying experiences were collected through questionnaires. Multivariate logistic regression analyses, stratified by ethnicity, were employed to examine factors associated with school bullying. Furthermore, subgroup analyses and interaction tests were conducted to explore potential effect modifiers of the relationship between ethnicity and bullying. Results: The prevalence of school bullying was 18.99 % (549/2891) overall, with 17.96 % (420/2339) among Han and 23.37 % (129/552) among ethnic minorities. Minority adolescents faced a higher risk of bullying compared to Han (OR = 1.35, 95 % CI: 1.08–1.69, P 0.05). Limitations: This cross-sectional study has limitations in establishing causal relationships between identified associated factors and school bullying. Conclusions: Ethnic minority adolescents in Inner Mongolia, China, especially middle school students, face a higher risk of school bullying than their Han peers. The differential impact of maternal education, family economic status, and family structure on bullying risk between Han and minority adolescents underscores the need for culturally sensitive, targeted interventions that consider the unique challenges faced by ethnic minority students.

Breast cancer is one of the most prevalent malignancies among women. Enhancing the prognosis is an effective approach to enhance the survival rate of breast cancer. Cuproptosis, a copper-dependent programmed cell death process, has been associated with patient prognosis. Inducing cuproptosis is a promising approach for therapy. However, there is currently no anti-breast cancer drug that induces cuproptosis. In this study, we repositioned the clinical drug fluphenazine as a potential agent for breast cancer treatment by inducing cuproptosis. Firstly, we utilized the Cancer Genome Atlas (TCGA) database and Connectivity Map (CMap) database to identify 22 potential compounds with anti-breast cancer activity through inducing cuproptosis. Subsequently, our findings demonstrated that fluphenazine effectively suppressed the viability of MCF-7 cells. Fluphenazine also significantly inhibited the viability of triple negative breast cancer cells MDA-MB-453 and MDA-MB-231. Furthermore, our study revealed that fluphenazine significantly down-regulated the expression of potential prognostic biomarkers associated with cuproptosis, increased copper ion levels, and reduced intracellular pyruvate accumulation. Additionally, it up-regulated the expression of FDX1 at both the mRNA and protein levels, which has been reported to play a crucial role in the induction of cuproptosis. These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

Abstract Background Head and neck malignancy, and in particular squamous cell carcinoma (SCC), is responsible for a significant disease burden globally. The lack of an optimal in vitro model system to accurately recapitulate in vivo response to therapy in HNSCC remains a challenge. The development of patient‐derived three‐dimensional tumour cultures, or tumoroids, has enabled improved modelling of the tumour microenvironment through simulation of important characteristics such as tumour hypoxia, cell–cell interactions and nutrient diffusion characteristics. Methods We performed a comprehensive English‐language literature review of current methods of tumoroid development utilising Matrigel and Cultrex Basement Membrane Extract 2 (key terms: tumour organoids, tumoroids, hydrogels, Matrigel, Cultrex, squamous cell carcinoma, head and neck)—two common proprietary murine‐derived hydrogels containing extracellular matrix proteins. Nascent literature on the establishment of a novel hydrogel‐free platform for tumoroid development as distinct from these existing methods was also explored. Results Whilst useful for facilitating cell‐matrix interactions and providing a scaffold for three‐dimensional cell growth and organisation, murine‐derived cell matrix methods were noted to have notable limitations including temperature sensitivity and the medium forming a barrier to analysis of the supernatant. A novel hydrogel‐free method of establishing in vitro tumoroid cultures has been subject to experimentation in colorectal but not head and neck malignancy. The absence of a hydrogel provides for the de novo synthesis of extracellular matrix native to the tumour and self‐organisation of cells within this scaffold through the use of ultralow attachment plates. This model demonstrates similar structural and physiological properties to native tissue, whilst enabling more accurate biomimicry of the tumour microenvironment for drug testing. Conclusions In the absence of prior experimentation on a hydrogel‐free method for establishing HNSCC tumoroids, and comparisons between hydrogel and hydrogel‐free models, the future development of a comparative protocol encompassing recruitment, collection, processing and analysis represents a valuable opportunity.

Not available.

Immune cell infiltration and tumor-related immune molecules play key roles in tumorigenesis and tumor progression. The influence of immune interactions on the molecular characteristics and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. A machine learning algorithm was applied to the transcriptome data from The Cancer Genome Atlas database to determine the immunophenotypic and immunological characteristics of ccRCC patients. These algorithms included single-sample gene set enrichment analyses and cell type identification. Using bioinformatics techniques, we examined the prognostic potential and regulatory networks of immune-related genes (IRGs) involved in ccRCC immune interactions. Fifteen IRGs (CCL7, CHGA, CMA1, CRABP2, IFNE, ISG15, NPR3, PDIA2, PGLYRP2, PLA2G2A, SAA1, TEK, TGFA, TNFSF14, and UCN2) were identified as prognostic IRGs associated with overall survival and were used to construct a prognostic model. The area under the receiver operating characteristic curve at 1 year was 0.927; 3 years, 0.822; and 5 years, 0.717, indicating good predictive accuracy. Molecular regulatory networks were found to govern immune interactions in ccRCC. Additionally, we developed a nomogram containing the model and clinical characteristics with high prognostic potential. By systematically examining the sophisticated regulatory mechanisms, molecular characteristics, and prognostic potential of ccRCC immune interactions, we provided an important framework for understanding the molecular mechanisms of ccRCC and identifying new prognostic markers and therapeutic targets for future research.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

The Arabidopsis thaliana FLAGELLIN-SENSITIVE2 (FLS2), a typical receptor kinase, recognizes the conserved 22 amino acid sequence in the N-terminal region of flagellin (flg22) to initiate plant defense pathways, which was intensively studied in the past decades. However, the dynamic regulation of FLS2 phosphorylation at the plasma membrane after flg22 recognition needs further elucidation. Through single-particle tracking, we demonstrated that upon flg22 treatment the phosphorylation of Ser-938 in FLS2 impacts its spatiotemporal dynamics and lifetime. Following Förster resonance energy transfer-fluorescence lifetime imaging microscopy and protein proximity indexes assays revealed that flg22 treatment increased the co-localization of GFP-tagged FLS2/FLS2S938D but not FLS2S938A with AtRem1.3-mCherry, a sterol-rich lipid marker, indicating that the phosphorylation of FLS2S938 affects FLS2 sorting efficiency to AtRem1.3-associated nanodomains. Importantly, we found that the phosphorylation of Ser-938 enhanced flg22-induced FLS2 internalization and immune responses, demonstrating that the phosphorylation may activate flg22-triggered immunity through partitioning FLS2 into functional AtRem1.3-associated nanodomains, which fills the gap between the FLS2S938 phosphorylation and FLS2-mediated immunity.

Objective: Minimally invasive surgery has been widely used for diaphragmatic eventration (DE). We aimed to compare the mid-term outcomes of robot-assisted thoracoscopic (RTP) and conventional thoracoscopic plication (CTP) for DE and to discuss the technical advantages of RTP. Methods: From January 2015 to July 2022, the clinical outcomes of 30 RTP patients and 35 CTP patients were retrospectively analyzed. The baseline data, surgical outcomes and surgical technique will be compared in detail. Results: The baseline data of two groups were comparable. No intraoperative conversion or complications occurred. The total operation time and intraoperative blood loss were similar between two groups, but RTP group had a significantly shorter diaphragmatic plication time compared to CTP group (25.77±3.55 min vs 44.49±4.43 min, p < 0.001). The total surgical cost of RTP group was higher than that of CTP group (48,593.06±2752.33 RMB vs 25,181.23±5681.51 RMB, p < 0.001). No significant differences were found in postoperative hospital stay, diclofenac suppository dosage, unplanned readmission rate within 30 days postoperatively, recurrence rate, or postoperative complications within 1 year postoperatively between RTP and CTP groups. Sixty patients had preoperative symptoms resolved or significantly improved with normal diaphragmatic position. However, two patients in CTP group encountered recurrence, and one patient in CTP group and two patients in RTP group had a diaphragm descent in only one intercostal space. Conclusion: RTP is a feasible and effective minimally invasive option for the treatment of DE, with mid-term outcomes comparable to CTP, which has a great advantage in terms of easier suturing and free knotting. DE can serve as an ideal disease type to train robots for thoracoscopic surgery by young doctors. Level of evidence: Level III.

BackgroundThe anterior cingulate gyrus (ACG) is an important regulatory region for pain-related information. However, the ACG is composed of subregions with different functions. The mechanisms underlying the brain networks of different subregions of the ACG in patients with migraine without aura (MwoA) are currently unclear.MethodsIn the current study, resting-state functional magnetic resonance imaging (rsfMRI) and functional connectivity (FC) were used to investigate the functional characteristics of ACG subregions in MwoA patients. The study included 17 healthy volunteers and 28 MwoA patients. The FC calculation was based on rsfMRI data from a 3 T MRI scanner. The brain networks of the ACG subregions were compared using a general linear model to see if there were any differences between the two groups. Spearman correlation analysis was used to examine the correlation between FC values in abnormal brain regions and clinical variables.ResultsCompared with healthy subjects, MwoA patients showed decreased FC between left subgenual ACG and left middle cingulate gyrus and right middle temporal gyrus. Meanwhile, MwoA patients also showed increased FC between pregenual ACG and right angular gyrus and increased FC between right pregenual ACG and right superior occipital gyrus. The FC values between pregenual ACG and right superior occipital gyrus were significantly positively correlated with the visual analogue scale.ConclusionDisturbances of FC between ACG subregions and default model network and visual cortex may play a key role in neuropathological features, perception and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.

BackgroundThe gut microbiota (GM) has been implicated in neurological disorders, but the relationship with hydrocephalus, especially the underlying mechanistic pathways, is unclear. Using Mendelian randomization (MR), we aim to discover the mediating role of inflammatory factors in the relationship between GM and hydrocephalus.MethodsAfter removing confounders, univariable and multivariable MR analyses were performed using summary statistics to assess the causal relationships between GM, inflammatory factors (IL-17A and IL-27), and types of hydrocephalus. Meta-analyses were used to reconcile the differences in MR results between different hydrocephalus sources. Finally, mediator MR analyses were applied to determine the mediating effect of inflammatory factors. Various sensitivity analysis methods were employed to ensure the reliability and stability of the results.ResultsAfter correction for P-values, Firmicutes (phylum) (OR, 0.34; 95%CI, 0.17–0.69; P = 2.71E-03, PFDR = 2.44E-02) significantly reduced the risk of obstructive hydrocephalus. The remaining 18 different taxa of GM had potential causal relationships for different types of hydrocephalus. In addition, Firmicutes (phylum) decreased the risk of obstructive hydrocephalus by increasing levels of IL-17A (mediating effect = 21.01%), while Eubacterium ruminantium group (genus) increased the risk of normal-pressure hydrocephalus by decreasing levels of IL-27 (mediating effect = 7.48%).ConclusionWe reveal the connection between GM, inflammatory factors (IL-17A and IL-27), and hydrocephalus, which lays the foundation for unraveling the mechanism between GM and hydrocephalus.

The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.

Recent research emphasised the indispensable role of histone lactylation in the activation of hepatic stellate cells. The VHL mutation is extremely common in clear cell renal cell carcinoma, which normally causes a metabolic shift in cancer cells and increases lactate production, eventually creating a lactate-enriched tumour microenvironment. Cancer-associated fibroblasts (CAFs) promote tumour progression, which is also vital in clear cell renal cell carcinoma. Therefore, this study investigated histone lactylation in CAFs and its impact on patient survival. Multiomics technology was employed to determine the role of histone lactylation-related genes in the evolution of CAFs which correlated with the function and molecular signatures of CAFs. The results suggested that TIMP1 was the hub gene of histone lactylation-related genes in clear cell renal cell carcinoma.

Cement tailings storage (CTS) in goaf may experience static and dynamic loading, such as rock stress, mine earthquake and blasting stress. When subject to dynamic loading, the risk for liquefaction of CTS may cause goaf barricade instability. To better understand the effect of cement content on CTS liquefaction resistance. Static and cyclic triaxial tests were conducted to determine the parameters required for the dynamic response analysis of CTS storage. A finite element analysis using LS-DYNA carried out to study the blasting response of CTS storage. The results indicated that the liquefaction resistance of CTS significantly improved with the cement content increased. The CTS exhibited near-static liquefaction when cement content was less than 2.42%. However, CTS cement content greater than 2.93% exhibited strain hardening or weak strain softening with low liquefaction index. The CTS with cement content 0–2.93% initial liquefaction less than 38 cyclic loading. Dynamic response analyzed showed liquefaction risk decreases as blasting distance and cement content increased. For blasting distances greater than 30 m, the CTS cement content of 3% is sufficient to resist liquefaction under blasting. The findings are conducive to the design of appropriate CTS underground storage parameters.

The functional connectivity (FC) graph of the brain has been widely recognized as a ``fingerprint'' that can be used to identify individuals from a group of subjects. Research has indicated that individual identification accuracy can be improved by eliminating the impact of shared information among individuals. However, current research extracts not only shared information of inter-subject but also individual-specific information from FC graphs, resulting in incomplete separation of shared information and fingerprint information among individuals, leading to lower individual identification accuracy across all functional magnetic resonance imaging (fMRI) states session pairs and poor cognitive behavior prediction performance. In this paper, we propose a method to enhance inter-subject variability combining conditional variational autoencoder (CVAE) network and sparse dictionary learning (SDL) module. By embedding fMRI state information in the encoding and decoding processes, the CVAE network can better capture and represent the common features among individuals and enhance inter-subject variability by residual. Our experimental results on Human Connectome Project (HCP) data show that the refined connectomes obtained by using CVAE with SDL can accurately distinguish an individual from the remaining participants. The success accuracies reached 99.7 % and 99.6 % in the session pair rest1-rest2 and reverse rest2-rest1, respectively. In the identification experiment involving task-task combinations carried out on the same day, the identification accuracies ranged from 94.2 % to 98.8 %. Furthermore, we showed the Frontoparietal and Default networks make the most significant contributions to individual identification and the edges that significantly contribute to individual identification are found within and between the Frontoparietal and Default networks. Additionally, high-level cognitive behaviors can also be better predicted with the obtained refined connectomes, suggesting that higher fingerprinting can be useful for resulting in higher behavioral associations. In summary, our proposed framework provides a promising approach to use functional connectivity networks for studying cognition and behavior, promoting a deeper understanding of brain functions.

With the digital transformation of the global economy, a new mode of knowledge service has emerged on open innovation platforms such as those for the sharing economy. This mode is the paid knowledge-sharing service, where knowledge providers share knowledge with only those who have paid for it. Since an individual customer's purchases are influenced by others around them, we adopted social influence theory to explain sales of such services on paid knowledge-sharing platforms. A machine learning approach was applied to analyze 27,223 text reviews from the Zhihu Live platform (a well-known and large-scale open knowledge community in China). Hierarchical regression models were built to verify twelve proposed hypotheses about the knowledge providers, knowledge quality, interaction quality, and ratings. The results confirm the positive effect on sales of responsiveness (a dimension of interaction quality), and the negative effect on sales of free provider-driven knowledge contributions.In summary, this study provides a comprehensive framework for antecedent factors of sales of knowledge-sharing services. By introducing to knowledge management notions from the field of e-commerce (e.g., price, quality), this study broadens the understanding of the free-to-paid phenomenon on knowledge-sharing platforms.