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AIM: To study the causal relationship between obesity-related anthropometric traits and myopia and the mediating role of educational attainment (EA). METHODS: Univariable Mendelian randomization (UVMR) was performed to evaluate the causal association between body mass index (BMI), height, waist-hip ratio (WHR, adjusted for BMI), and mean spherical equivalent (MSE). BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization (MVMR) to explore the roles of different BMI components in the causal relationship between BMI and MSE. A mediation analysis based on two-step Mendelian randomization (MR) was carried out. Specifically, UVMR was conducted to estimate the causal effect of BMI on EA. The direct effect of EA on MSE was estimated from MVMR. The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method. Expression quantitative trait loci (eQTL)-MR, reverse MR, and Linkage Disequilibrium Score Regression (LDSC) were performed to assess the robustness. RESULTS: Genetically predicted higher BMI had a positive total effect on MSE (βIVW=0.26 D, 95%CI=0.14 to 0.37 D, P

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

The timely repair of high-density polyethylene (HDPE) membrane leakage in landfills is an important means of environmental risk control, which is critical for preventing leachate from polluting groundwater and soil. Electric repair technology is expected to become a hot spot in the leakage repair of HDPE films, because it can solve the issues of complex operation, high costs, and security risks during the operation and closure of landfills. To explore the influence law of various technical factors on the electric repair process, we carried out single factor experiments on the main influencing factors such as the operation time, bentonite concentration and dispersant/bentonite dosage ratio, leakage size, and calcium concentration. We then explored the best technological conditions. The results showed that accumulation at the leakage site possessed a good repair effect with a permeability coefficient of 4.22 × 10−6 cm/s. Furthermore, we observed that the Zeta potential played an important role in the electric repair technology, where the higher the absolute value of the Zeta potential, the faster the electrophoretic migration rate of the bentonite particles, and the lower the permeability coefficient of accumulation. This study may serve as a theoretical basis and offer scientific guidance for the directional electric repair of HDPE membrane leakage during the operating period and after the closure of landfills.

As a carnivorous fish, the cannibalism are prone to happen in the early seedling stage in Dongting catfish (Silurus asotus), especailly when there is not enough food, which resulting in the low survival rate of Dongting catfish. To find clues to improve the survival rate of Dongting catfish offspring, the comparative transcriptomics analysis were conducted between normal and malformed larval fish, as well as normal larval fish before and after first food intake. In normal and malformed larval fish groups, a total of 881 differential genes were identified, including 634 up-regulated genes and 247 down-regulated genes. From these genes related to growth hormone synthesis and secretion were screened out as SLA isoform X1, SOCS3, STAT1b, JUNB, respectively. In the group of larval fish before and after the first food intake, 4901 up-regulated genes and 3660 down-regulated genes were found, from which the differential genes related to protein digestion and absorption pathway and pancreatic secretion pathway were screened out as cathepsin D precursor, elastase 2 like precursor, elastase 2 precursor, LPL isoform X1, CTRB1 precursor, CTRL precursor, CPA precursor, FABP, SLC15A1, CEL tandem duplicate 2 precursor. The differential genes screened for association with amino acid metabolism were ASAOC precursor, PLD3, NDPKs, trehalase, UMP-CMP kinase, L-amino-acid oxidase, PLB1, FALDH isoform X2, PLA2 precursor, glucokinase. Meanwhile, nine differential genes were selected for qPCR verification. The results confirmed that the relative expression trends of these genes were consistent with those found in the transcriptome. These findings provide an important reference for developing strategies to enhance the survival rate of Dongting catfish at early seedling stage.

In this investigation, the behavior of a chemically reactive flow of micropolar Eyring–Powell ferrofluids over stretchable surface was examined. The study also considers heterogeneous and homogeneous chemical reactions, as well as thermal radiation and magnetic dipole impacts. By applying suitable similarity variables, the nonlinear partial differential governing equations, which describe the flow and energy dynamics of the micropolar fluid, were transformed into ordinary differential equations. The resultant equations were then numerically solved by using the shooting method with a Runge–Kutta update. The model equations are presented and discussed in dimensionless form through numerical approximations. A variety of numerical tests were performed for the dimensionless parameters to provide a comprehensive understanding. The MATLAB version 2023 was used for the numerical computations as well as graphical illustrations. It was concluded that the velocity field decreases with greater values of the ferro-magnetic parameter ß as well as for other fluid material parameters H, and ß. Whereas the temperature field increases by increasing the thermal radiation R while decreases with a higher dissipation parameter λ1 and Prandtl number Pr. The numerical simulation for these parameters were shown graphically, and the values were tabulated for clear illustration. Moreover, the current work was also compared with the findings of existing studies from recent literature to validate and contextualize the findings.

Most of the complex biological regulatory activities occur in three dimensions (3D). To better analyze biological processes, it is essential not only to decipher the molecular information of numerous cells but also to understand how their spatial contexts influence their behavior. With the development of spatially resolved transcriptomics (SRT) technologies, SRT datasets are being generated to simultaneously characterize gene expression and spatial arrangement information within tissues, organs or organisms. To fully leverage spatial information, the focus extends beyond individual two-dimensional (2D) slices. Two tasks known as slices alignment and data integration have been introduced to establish correlations between multiple slices, enhancing the effectiveness of downstream tasks. Currently, numerous related methods have been developed. In this review, we first elucidate the details and principles behind several representative methods. Then we report the testing results of these methods on various SRT datasets, and assess their performance in representative downstream tasks. Insights into the strengths and weaknesses of each method and the reasons behind their performance are discussed. Finally, we provide an outlook on future developments. The codes and details of experiments are now publicly available at https://github.com/YangLabHKUST/SRT_alignment_and_integration.

(1) Background: Metastatic L-type sarcomas (liposarcoma and leiomyosarcoma) are rare and have a poor prognosis. Trabectedin is an effective agent that can be used after anthracyclines. This study was designed to evaluate the real-life effectiveness and safety of trabectedin. (2) Methods: A retrospective multicenter study was conducted on patients who were treated with trabectedin for metastatic L-type sarcomas at ten tertiary oncology centers between 2015 and 2023. The objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS) were evaluated in the cohort. Cox regression analysis was used to determine prognostic factors for survival. (3) Results: A total of 98 patients (52% liposarcoma and 48% leiomyosarcoma) were included in the study. The median treatment line was three (range: 1 to 6). Thirteen patients (13.3%) underwent local treatment due to oligoprogression, and dose reduction was required in seventeen patients (17.3%) due to toxicity. The ORR and DCR were 16% and 42%, respectively. The median TTF was 3 months, and the median OS was 10 months. In univariate analysis, a significantly longer median TTF was observed in patients who underwent local treatment (p = 0.008), obtained objective responses (p < 0.001), and underwent dose reduction (p = 0.002). No statistical differences were observed according to the histologic subtype and metastatic site. In the multivariate analysis for OS, it was found that obtaining an objective response was a good prognostic factor (p = 0.003), while the presence of liver metastases was associated with a poor prognosis (p = 0.016). (4) Conclusion: Trabectedin is a suitable option for L-type sarcoma after doxorubicin-based treatments. Survival was not worse in patients who underwent dose reduction. The use of local therapies simultaneously with trabectedin can be effective.

Abstract The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.

Abstract Microcirculatory dysfunction, hypoxia, and inflammation are considered to be central in the pathogenesis of sepsis-induced acute kidney injury (AKI). In this experimental study, we hypothesized that extracorporeal removal of inflammatory cytokines by hemoadsorption (HA) therapy may mitigate renal injury associated with sepsis-induced AKI. To this end, we investigated renal microcirculatory oxygenation and perfusion, oxygen consumption, lactate, systemic hemodynamic variables, tubular cell integrity, inflammatory mediators, and kidney function in a rat model of septic AKI elicited by endotoxin infusion. Three groups of rats were investigated on extracorporeal circulation: HA only, LPS, and LPS + HA. Endotoxin infusion reduced cortex microcirculatory oxygenation and raised creatinine and lactate levels. Renal microcirculatory oxygenation, measured by two independent techniques (phosphorescence (µPO2) and spectrophotometry/Doppler (µHbO2sat and $$\mu \text{RBCv}$$ )), was ameliorated by HA therapy. The renal oxygen consumption, lactate and creatinine levels were restored in the LPS + HA group. A reduced amount of injured tubular cells was found in histological analysis of the kidneys. This experimental study demonstrated an improvement in multiple determinants of kidney oxygenation, damage, and systemic blood perfusion by HA in a clinically relevant rat model of septic AKI. Further studies are needed to optimize and support the clinical use of HA as a renal protective strategy.

Abstract Sodium sulfide (Na2S) as an initial cathode material in room-temperature sodium-sulfur batteries is conducive to get rid of the dependence on Na-metal anode. However, the micron-sized Na2S that accords with the practical requirements is obstructed due to poor kinetics and severe shuttle effect. Herein, a subtle strategy is proposed via regulating Na2S redeposition behaviours. By the synergistic effect from both conductive structure and cuprous sulfide (Cu2S) catalysis, the micron-sized Na2S particles are broken down and redeposited to nano-size during the initial cycle which can be fully utilized in subsequent cycles. Consequently, the Na2S/CPVP@Cu2S||Na cell delivers excellent cyclability (670 mAh gS −1 after 500 cycles) with a remarkable average Coulombic efficiency over 99.7% and rate capability (480 mAh gS −1 at 4 A gS −1). Besides, the Na-free anodes are used to prove the application prospects. This work provides an innovative idea for utilizing micron-sized Na2S and offers insights into its conversion pathway.

Abstract Background Predator‒prey interactions and their dynamic changes provide frequent opportunities for viruses to spread among organisms and thus affect their virus diversity. However, the connections between dietary diversity and virus diversity in predators have seldom been studied. The avivorous bats, Ia io, show a seasonal pattern of dietary diversity. Although most of them primarily prey on insects in summer, they mainly prey on nocturnally migrating birds in spring and autumn. Results In this study, we characterized the RNA virome of three populations of I. io in Southwest China during summer and autumn using viral metatranscriptomic sequencing. We also investigated the relationships between dietary diversity and RNA virus diversity by integrating DNA metabarcoding and viral metatranscriptomic sequencing techniques at the population level of I. io. We found 55 known genera belonging to 35 known families of RNA viruses. Besides detecting mammal-related viruses, which are the usual concern, we also found a high abundance of insect-related viruses and some bird-related viruses. We found that insect-related viruses were more abundant in summer, while the bird-related viruses were predominantly detected in autumn, which might be caused by the seasonal differences in prey selection by I. io. Additionally, a significant positive correlation was identified between prey diversity and total virus diversity. The more similar the prey composition, the more similar the total virus composition and the higher the count of potential new viruses. We also found that the relative abundance of Picornaviridae increased with increasing prey diversity and body mass. Conclusions In this study, significant links were found between RNA virus diversity and dietary diversity of I. io. The results implied that dynamic changes in predator–prey interactions may facilitate frequent opportunities for viruses to spread among organisms. Video Abstract

Abstract Background Heart failure (HF) and cancer share common risk factors and pathophysiological mechanisms, including fibrosis. Identifying biomarkers and therapeutic targets for both conditions is crucial. Materials and methods RNA sequencing data from HF patients were analyzed to identify 12 genes associated with myocardial fibrosis. Validation was performed using public datasets, and functional enrichment analyses were conducted. Gene expression patterns and prognostic value in various cancers were assessed. Results Fibromodulin (FMOD), Periostin (POSTN), Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type VIII Alpha 1 Chain (COL8A1), Asporin (ASPN), and Hemoglobin Subunit Beta (HBB) showed significant dysregulation in heart failure tissues and were implicated in multiple cancer types. Pan-cancer analysis revealed associations between these genes and prognosis. Correlations with cancer-associated fibroblasts were also observed. Conclusion FMOD, POSTN, LTBP2, COL1A1, COL8A1, ASPN, and HBB are potential biomarkers for HF and cancer with fibrotic microenvironments. Targeting fibrosis may offer novel therapeutic approaches. Further validation and mechanistic studies are needed. This study contributes to understanding HF and cancer at the molecular level and suggests personalized treatment strategies.

Abstract Background The aim is to develop and validate radiomics based on 2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) parameters for predicting the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of clear cell renal cell carcinoma (ccRCC). Methods A total of 209 patients with 214 lesions, who underwent 2-[18F]FDG PET/CT scans between December 2016 to December 2023, were included in our study. All ccRCC lesions were categorized into low grade (WHO/ISUP grade I-II) and high grade (WHO/ISUP grade III-IV). The lesions were allocated into a training group and a testing group in a ratio of 7:3. The radiomics features were extracted by a serious of maximum standardized uptake value (SUVmax) thresholds (0,2.5%,25%,40%) with the utilization of the minimum redundancy and maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithm. The clinical, radiomics and combined models were constructed. The receiver operating characteristic (ROC) curve, decision curve and calibration curves were plotted to assess the predicting performance. Results The area under curve (AUC) of PET-0, PET-2.5%, PET-25%, PET-40% model in the training group were 0.881(95% CI: 0.822–0.940),0.883(95% CI: 0.825–0.942),0.889(95% CI: 0.831–0.946),0.887(95% CI: 0.826–0.948); and 0.878(95% CI: 0.777–0.978),0.876(95% CI: 0.776–0.977),0.871(95% CI: 0.769–0.972),0.882(95% CI: 0.786–0.979) in the testing group. Due to perfect prediction and verification performance, the volume of interest (VOI) from PET images with SUVmax threshold of 40% were selected to construct the radiomics model and combined model. The AUC of the clinical model and radiomics model was 0.859 (sensitivity = 0.846, specificity = 0.747) and 0.909 (sensitivity = 0.808, specificity = 0.751) in the training group, respectively; 0.882 (sensitivity = 0.857, specificity = 0.857) and 0.901 (sensitivity = 0.905, specificity = 0.833) in the testing group, respectively. In combined models, the AUC was 0.916, the sensitivity was 0.923 and the specificity was 0.808 in the training group; the AUC was 0.916, the sensitivity was 0.881 and the specificity was 0.792 in the training group. Conclusion Radiomics based on 2-[18F]FDG PET/CT can be helpful to predict WHO/ISUP grade of ccRCC.

Abstract To study the effect of different sizes and speeds of coal gangue falling on hydraulic supports for top‐coal caving discharge hydraulic support on the bearing characteristics of the hydraulic support, the ADAMS hydraulic support rigid‐flexible coupling analysis model was established. HyperMesh is used to flexibly process the hydraulic support, and the column and jack are equivalently replaced by spring damping system. By applying step loads of different sizes and speeds to simulate the impact force generated when the coal gangue falls on different positions of the cover beam, the dynamic response characteristics of the column, balance jack and other articulation points are obtained. Analyses show that: when the impact load is closer to the roof beam, the articulation point of the roof beam‐cover beam and the balancing jack are easy to be damaged. When the same impact load is applied to the cover beam, the faster the load is applied, the hydraulic support column and balancing jack may not be able to absorb and disperse the pressure effectively in time, resulting in the articulation points being subjected to a larger impact force, which is easy to cause damage or destruction. When different sizes and speeds of impact loads are applied to the cover beam, the latter has a greater impact on the dynamic response of the front and rear connecting rod articulation points and the cover beam‐roof beam articulation point than the former, and the hydraulic bracket will be more prone to vibration, deformation, and stress concentration, thus affecting the stability and safety of the bracket. The article is of guiding significance for designing and optimizing the structure and parameters of the hydraulic support, and improving the support performance and stability of the hydraulic support in the comprehensive release working face.

In this study, the by-products processed from Andrias davidianus were evaluated, and the structure, activity, and functionality of the metallothionein from this amphibian species (AdMT) were investigated. AdMT was extracted from the liver using a centrifugal homogenization method, with the extraction process optimized by means of single-factor and orthogonal experiments. Subsequently, the protein was purified using ion-exchange chromatography. The antioxidative activity of AdMT was assessed by measuring its free radical-scavenging ability, and its cytotoxicity was evaluated using the lactate dehydrogenase release assay. The anti-inflammatory activity of the protein was determined by RAW264.7 cell model of lipopolysaccharide-induced inflammation, and its immunogenicity and effect on cell proliferation were analyzed using the CCK-8 assay. Its effects on the cell cycle and cell migration ability were assessed using flow cytometric and scratch assays, respectively. Its heavy metal detoxification capacity was evaluated using L929 and HaCaT cell models of CdCl2-induced toxicity. Results showed that, the optimal AdMT extraction conditions were determined to be as follows: Liquid-to-material ratio of 5:1, extraction solution concentration of 0.02 mol/L, extraction temperature of 40 ℃, and extraction time of 1 h, yielding 0.362 mg/g of the protein. AdMT exhibited a 95.01% scavenging rate against ABTS+ free radicals and had no significant impact on the lactate dehydrogenase release rates of L929 and HaCaT cells or on the viability of RAW264.7 cells. After 48 h of AdMT treatment, the viability of L929 and HaCaT cells improved to 192.63% and 207.92%, respectively, and their cell proliferation indices increased to 0.56 and 0.53, respectively. Additionally, the migration ability of the L929 and HaCaT cells increased with increasing AdMT concentration, showing scratch healing rates were 63.38% and 76.23%, respectively. In the cell inflammation model, AdMT significantly (P

Abstract The heat shock transcription factor (HSF) family is one of the most widely studied transcription factor families in plants; HSFs can participate in the response to various stressors, such as heat stress, high salt, and drought stress. Based on garlic transcriptome data, we screened and identified 22 garlic HSFs. The HSF proteins of garlic and Arabidopsis can be divided into three (A, B, C) subfamilies. The phylogenetic relationship, chromosome localization, sequence characteristics, conserved motifs, and promoter analysis of the HSF family were analyzed through bioinformatics methods. RT-qPCR analysis showed that the nine selected genes had different degrees of response to heat stress. In addition, we isolated and identified a class B HSF gene, AsHSFB1, from garlic variety ‘Xusuan No.6’. Subsequently, the AsHSFB1 gene was overexpressed in Arabidopsis thaliana. Under heat stress, the germination rate and growth of wild-type plants were better than that of transgenic plants. Moreover, after heat treatment, the contents of peroxidase, catalase, and chlorophyll a and b of transgenic plants were lower, but the contents of malondialdehyde (MDA) and leaf conductivity were higher. Nitroblue tetrazolium (NBT) staining showed that the stained area of transgenic plant leaves was larger than that of the wild type. Further studies showed that AsHSFB1 overexpression inhibited the expression of related reverse resistance genes. These results indicate that AsHSFB1 might play a negative regulatory role in garlic resistance under high stress. Altogether, these findings provide valuable data for revealing the function of HSF genes and lay a foundation for the subsequent selection of heat-resistant garlic varieties.

Abstract Unveiling functional relationships between various molecular cell phenotypes from data using machine learning models is a key promise of multiomics. Existing methods either use flexible but hard-to-interpret models or simpler, misspecified models. VI-VS (Variational Inference for Variable Selection) balances flexibility and interpretability to identify relevant feature relationships in multiomic data. It uses deep generative models to identify conditionally dependent features, with false discovery rate control. VI-VS is available as an open-source Python package, providing a robust solution to identify features more likely representing genuine causal relationships.

Abstract Background Streptococcus pyogenes is a common gram-positive bacterium, belonging to group A Streptococcus (GAS), and is responsible for causing a range of clinical conditions. Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported. Case presentation We present a case of one GAS brain abscess in a previously healthy child with unusual clinical manifestations of decreased muscle strength in the left limbs. The right frontal lobe mass lesion was resected using a microscope-based neuronavigation system. A sole defectively beta-hemolytic Streptococcus pyogenes was isolated from the lesion. The patient’s peripheral blood whole-exome and the pathogen’s whole-genome sequencing were performed respectively, revealing a heterozygous mutation in the interferon regulatory factor-8 (IRF8) gene in the patient and lack of hyaluronic acid capsules in Streptococcus pyogenes (genotype emm22). The patient eventually recovered after prompt surgical drainage of the abscess and appropriate antibiotic treatment. Conclusions It is important to pay attention to Streptococcus pyogenes brain abscesses with mild clinical manifestations. Upon reviewing all the cases of pediatric GAS brain abscess reported in the published literature, we discovered that early diagnosis and treatment are crucial factors that impact the prognosis of GAS brain abscess.

Abstract Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remission in seven cases. The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation. In cases where diagnosis is challenging, kidney biopsy may assist if conditions permit. Comprehensive evaluation of the complement system, including genetic mutations, function, and associated complement inhibitory factor antibodies, should be included in the assessment of PI-TMA. Early administration of eculizumab may be beneficial in cases of suspected complement abnormalities or suboptimal response to initial treatments.

Abstract Unleashing the land sector’s potential for climate mitigation requires purpose-driven changes in land management. However, contributions of past management changes to the current global and regional carbon cycles remain unclear. Here, we use vegetation modelling to reveal how a portfolio of ecological restoration policies has impacted China’s terrestrial carbon balance through developing counterfactual ‘no-policy’ scenarios. Pursuing conventional policies and assuming no changes in climate or atmospheric carbon dioxide (CO2) since 1980 would have led China’s land sector to be a carbon source of 0.11 Pg C yr−1 for 2001–2020, in stark contrast to a sink of 175.9 Tg C yr−1 in reality. About 72.7% of this difference can be attributed to land management changes, including afforestation and reforestation (49.0%), reduced wood extraction (21.8%), fire prevention and suppression (1.6%) and grassland grazing exclusion (0.3%). The remaining 27.3% come from changes in atmospheric CO2 (42.2%) and climate (−14.9%). Our results underscore the potential of active land management in achieving ‘carbon-neutrality’ in China.

Abstract Fibronectin type III domain-containing (FNDC) proteins play critical roles in cellular homeostasis and cardiac injury, and our recent findings define FNDC5 as a promising cardioprotectant against doxorubicin- and aging-related cardiac injury. FNDC4 displays a high homology with FNDC5; however, its role and mechanism in cardiac ischemia/reperfusion (I/R) injury remain elusive. Here, we show that cardiac and plasma FNDC4 levels are elevated during I/R injury in a hypoxia-inducible factor 1α (HIF1α)-dependent manner. Cardiac-specific FNDC4 overexpression facilitates, while cardiac-specific FNDC4 knockdown inhibits cardiomyocyte survival and angiogenesis in I/R-stressed hearts of male mice through regulating the proteasomal degradation of HIF1α. Interestingly, FNDC4 does not directly stimulate angiogenesis of endothelial cells, but increases the expression and secretion of fibroblast growth factor 1 from cardiomyocytes to enhance angiogenesis in a paracrine manner. Moreover, therapeutic administration of recombinant FNDC4 protein is sufficient to alleviate cardiac I/R injury in male mice, without resulting in significant side effects. In this work, we reveal that FNDC4 alleviates cardiac I/R injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis, and define FNDC4 as a promising predictive and therapeutic target of cardiac I/R injury.

Abstract Many plants associate with endophytic microbes that improve root phosphorus (P) uptake. Understanding the interactions between roots and endophytes can enable efforts to improve P utilization. Here, we characterize the interactions between lateral roots of endophytes in a core collection of 50 rapeseed (Brassica napus L.) genotypes with differing sensitivities to low P conditions. With the correlation analysis result between bacterial abundance and plant physiological indices of rapeseeds, and inoculation experiments on plates and soil, we identify one Flavobacterium strain (C2) that significantly alleviates the P deficiency phenotype of rapeseeds. The underlying mechanisms are explored by performing the weighted gene coexpression network analysis (WGCNA), and conducting genome-wide association studies (GWAS) using Flavobacterium abundance as a quantitative trait. Under P-limited conditions, C2 regulates fatty acid and lipid metabolic pathways. For example, C2 improves metabolism of linoleic acid, which mediates root suberin biosynthesis, and enhances P uptake efficiency. In addition, C2 suppresses root jasmonic acid biosynthesis, which depends on α-linolenic acid metabolism, improving C2 colonization and activating P uptake. This study demonstrates that adjusting the endophyte composition can modulate P uptake in B. napus plants, providing a basis for developing agricultural microbial agents.

Objective The craniovertebral junction (CVJ) presents intricate anatomical challenges. In severe or irreducible malformations, complications such as reduction loss and fixation failure may occur, necessitating revision surgery. The posterior facet joint distraction and fusion (PFDF) technique, offers a solely posterior approach for revisions. Hence, we delineate varied revision scenarios, proposing surgical strategies and technical details to enhance outcomes and mitigate risks, thereby enriching the neurosurgical community's repertoire. Methods This was a retrospective cohort study, analyzed patient data from Xuanwu Hospital, between 2017 to 2023. All patients had a history of surgical treatment for CVJ malformations, and experienced failure or loss of reduction. The distance from the odontoid process tip to the Chamberlain's line (DCL), the atlantodental interval (ADI), clivus‐canal angle, cervicomedullary angle, width of subarachnoid space, CVJ area, and width of syrinx were used for radiographic assessment. Japanese Orthopaedic Association (JOA) scores and SF‐12 scores were used for clinical assessment. Independent sample t‐tests were employed. A significance level of p

Abstract Objective This study aimed to evaluate the feasibility and performance of deep transfer learning (DTL) networks with different types and dimensions in differentiating thymomas from thymic cysts in a retrospective cohort. Materials and Methods Based on chest‐enhanced computed tomography (CT), the region of interest was delineated, and the maximum cross section of the lesion was selected as the input image. Five convolutional neural networks (CNNs) and Vision Transformer (ViT) were used to construct a 2D DTL model. The 2D model constructed by the maximum section (n) and the upper and lower layers (n − 1, n + 1) of the lesion was used for feature extraction, and the features were selected. The remaining features were pre‐fused to construct a 2.5D model. The whole lesion image was selected for input and constructing a 3D model. Results In the 2D model, the area under curve (AUC) of Resnet50 was 0.950 in the training cohort and 0.907 in the internal validation cohort. In the 2.5D model, the AUCs of Vgg11 in the internal validation cohort and external validation cohort 1 were 0.937 and 0.965, respectively. The AUCs of Inception_v3 in the training cohort and external validation cohort 2 were 0.981 and 0.950, respectively. The AUC values of 3D_Resnet50 in the four cohorts were 0.987, 0.937, 0.938, and 0.905. Conclusions The DTL model based on multiple different dimensions can be used as a highly sensitive and specific tool for the non‐invasive differential diagnosis of thymomas and thymic cysts to assist clinicians in decision‐making.

Abstract High-throughput screening techniques are pivotal to unlocking the mysteries of biology. Yet, the promise of droplet microfluidics in enabling single-cell resolution, ultra-high-throughput screening remains largely unfulfilled. Droplet sorting errors caused by polydisperse droplet sizes that are often inevitable in multi-step assays have severely limited the effectiveness and utility of this technique, especially when screening large libraries. Even a relatively low 1% sorting error results in 10,000 false calls in a 1,000,000 droplet screen, imposing an unreasonably large burden on downstream validation. Here, we present NOVAsort (Next-generation Opto-Volume-based Accurate droplet sorter), a device capable of discerning droplets based on both size and fluorescence intensity. With a 1000- and 10,000-fold reduction in false positives and false negatives, respectively. NOVAsort addresses the challenges of conventional droplet sorting approaches and sets standards for accuracy and throughput in droplet microfluidic assays.

A novel artificial bee colony algorithm was introduced for the eruption event of the Sakurajima volcano on August 9, 2020, to invert the magma source characteristics below the volcano based on the point source Mogi model. Considering that the Sakurajima volcano is surrounded by sea, all the deformation data are used to obtain the location and magma eruption volume of the volcano. In response to the weak local search capability of the artificial swarm algorithm, the difference between the global optimal individual and the un-roulette screened individual is introduced as the variance component in the onlooker stage. Detailed simulation experiments verify the improvement of the algorithm in terms of convergence speed. In real experiments, the Sakurajima volcano inversion shows closer fitting results and smaller residuals compared to the existing literature. Meanwhile, the convergence speed of the algorithm echoes with the simulation experiments.

The copper (Cu)-beryllium (Be) alloy is a critical material for high-performance photomultiplier cathodes. The microstructure evolution of the β phase in the Cu-2.8Be alloy subjected to cooling rate ranging from 0.5 to 80 °C/s after heat treatment. The non-isothermal phase transformation kinetics equation of the alloy was derived. At a cooling rate of 0.5 °C/s, the β phase completely transformed into the α phase and γ phase through a eutectoid reaction (β → α + γ). The γ phase preferentially precipitates at locations with higher free energy, such as grain boundaries and defects in the parent phase. The orientation relationship between the α phase and the γ phase follows the Kurdjumov-Sachs (K–S) relationship ([110]α∥[111]γ; (11‾1‾)α∥(01‾1)γ), and the α phase nucleates and grows with a twin relationship to the Cu matrix. As the cooling rate increases, the transformation fraction of the β phase decreases. The critical cooling rate at which the β phase eutectoid reaction is completely suppressed is 80 °C/s. A non-isothermal phase transformation kinetics equation for the β phase eutectoid transformation was established: f(r)=1−exp{−{34.703r−1.062[exp(−0.9107r)−0.3575]}2.2}, elucidating the relationship between the phase transformation fraction and the cooling rate, which provides a theoretical basis for controlling the microstructure of Cu–Be alloy through heat treatment. Validated by the Cu-3.3Be alloy, this equation demonstrates excellent universality.

Background/Aims Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Abstract Background LDL receptor‐related protein‐1 (LRP1) is a cell‐surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte‐specific LRP1 deficiency (hLRP1KO) promotes diet‐induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis. Methods Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno‐associated virus serotype 8 vector (AAV8) were used to overexpress the truncated β‐chain (β∆) of LRP1 both in vitro and in vivo. Results On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose‐ and time‐dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3β, increased levels of phosphorylated glycogen synthase (GYS), and diminished glycogen synthesis in insulin‐stimulated HepG2 cells, which was restored by exogenous expression of the β∆‐chain. By contrast, AAV8‐mediated hepatic β∆‐chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high‐fat diet (HFD)‐fed mice. Conclusion Our data revealed that LRP1, especially its β‐chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance‐related diseases.

Sodium iodide (NaI) detector has wide applications in Prompt Gamma-ray Neutron Activation Analysis (PGNAA) due to its excellent detection efficiency and relatively low cost. In order to obtain the response of the detector to gamma-rays during PGNAA measurement process，a Monte Carlo model was established for the NaI detector to simulate the transport processes of neutrons and gamma-rays. Measurements and analyses were conducted on standard point sources of 60Co，137Cs，152Eu，133Ba，and 241Am，as well as a waterborne source of 137Cs. These measurements were compared with MCNP simulation calculations，and the results demonstrated agreement between the two methodologies. Then，measurements were conducted on aqueous solutions using a D-D neutron generator，and the 2.223 MeV characteristic gamma-ray produced by the H element radiative capture reaction was analyzed. The research results show that the deviations between MCNP simulation calculations of characteristic peaks for the H element and experimental measurements were consistently within 13%，demonstrating that the NaI measurement system model established by MCNP can simulate the transport processes of gamma and neutrons，laying a foundation for the subsequent optimization of the system and other related work.

Abstract TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet’s disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.

Abstract Background Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC). Methods This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part. Results The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m2)/cisplatin (75 mg/m2) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m2)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m2)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2–7.5 months), overall survival (29.7 months vs. 16.1–21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months). Conclusions The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin. Trial registration The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017.

Abstract Gliomas are the most common primary malignant tumours of the central nervous system (CNS), which are highly aggressive, with increasing morbidity and mortality rates year after year, posing a serious threat to the quality and expected survival time of patients. The treatment of gliomas is a major challenge in the field of neuro-oncology, especially high-grade gliomas such as glioblastomas (GBMs). Despite considerable progress in recent years in the study of the molecular and cellular mechanisms of GBMs, their prognosis remains bleak. Tumour-associated macrophages (TAMs) account for up to 50% of GBMs, and they are a highly heterogeneous cell population whose role cannot be ignored. Here, we focus on reviewing the contribution of classically activated M1-phenotype TAMs and alternatively activated M2-phenotype TAMs to GBMs, and exploring the research progress in reprogramming M1 TAMs into M2 TAMs.

Abstract Spinal cord injury (SCI) often accompanies impairment of motor function, yet there is currently no highly effective treatment method specifically for this condition. Oxidative stress and inflammation are pivotal factors contributing to severe neurological deficits after SCI. In this study, a type of curcumin (Cur) nanoparticle (HA-CurNPs) was developed to address this challenge by alleviating oxidative stress and inflammation. Through non-covalent interactions, curcumin (Cur) and poly (-)-epigallocatechin-3-gallate (pEGCG) are co-encapsulated within hyaluronic acid (HA), resulting in nanoparticles termed HA-CurNPs. These nanoparticles gradually release curcumin and pEGCG at the SCI site. The released pEGCG and curcumin not only scavenge reactive oxygen species (ROS) and prevents apoptosis, thereby improving the neuronal microenvironment, but also regulate CD74 to promote microglial polarization toward an M2 phenotype, and inhibits M1 polarization, thereby suppressing the inflammatory response and fostering neuronal regeneration. Moreover, in vivo experiments on SCI mice demonstrate that HA-CurNPs effectively protect neuronal cells and myelin, reduce glial scar formation, thereby facilitating the repair of damaged spinal cord tissues, restoring electrical signaling at the injury site, and improving motor functions. Overall, this study demonstrates that HA-CurNPs significantly reduce oxidative stress and inflammation following SCI, markedly improving motor function in SCI mice. This provides a promising therapeutic approach for the treatment of SCI.

Abstract The recently discovered interaction between presenilin 1 (PS1), a subunit of γ-secretase involved in amyloid-β (Aβ) peptide production, and GLT-1, the major brain glutamate transporter (EAAT2 in the human), may link two pathological aspects of Alzheimer’s disease: abnormal Aβ occurrence and neuronal network hyperactivity. In the current study, we employed a FRET-based fluorescence lifetime imaging microscopy (FLIM) to characterize the PS1/GLT-1 interaction in brain tissue from sporadic AD (sAD) patients. sAD brains showed significantly less PS1/GLT-1 interaction than those with frontotemporal lobar degeneration or non-demented controls. Familial AD (fAD) PS1 mutations, inducing a “closed” PS1 conformation similar to that in sAD brain, and gamma-secretase modulators (GSMs), inducing a “relaxed” conformation, respectively reduced and increased the interaction. Furthermore, PS1 influences GLT-1 cell surface expression and homomultimer formation, acting as a chaperone but not affecting GLT-1 stability. The diminished PS1/GLT-1 interaction suggests that these functions may not work properly in AD.

Abstract To further raise the gas extraction efficiency of the tight sandstone, the liquid nitrogen (LN2) freezing-thawing cycles method can be employed to improve the permeability of the low-permeability reservoirs. Permeability is generally regarded as a macroscopic description of the pore structure and usually has functional relationship to pore structure properties. The permeability of the rock is closely related to the change of microscopic pore structure. The permeability of rock depends on how the subzero temperatures changed the microscopic pore structure of rock, but it has not yet been confirmed obviously. In this study, the nuclear magnetic resonance (NMR) technique was adopted to investigate the pore structure evolution law and permeability of the tight sandstone with different LN2 freezing-thawing cycles. The results demonstrate that the LN2 freezing-thawing cycles promotes pore development and micro-fracture connection, and enhances the pore connectivity. The proportion of meso-pores, macro-pores and micro-fractures in the sandstone samples increases significantly, which provides a channel for the sandstone gas flow and extraction. Total porosity and effective porosity of the samples present a trend of rapid increase as the number of LN2 freezing-thawing cycles increasing, while the residual porosity decreases as the number of LN2 freezing-thawing cycles increasing. Coates model, SDR model (mean T2 model) and PP model were used to calculate and evaluate the permeability of the samples subjected to different LN2 freezing-thawing cycles. Furthermore, PP model can provide a better permeability estimate than the classical Coates and SDR model.

Primula meishanensis K.Huang & Z.X.Fu, sp. nov., a new species of Primulaceae from Meishan City, Sichuan Province, China, is described and illustrated. The morphological data and phylogenetic analysis, based on the complete chloroplast genome, suggest that Primula meishanensis is a separate species closely related to Primula dejuniana. The complete chloroplast genome of Primula meishanensis was 152,175 bp and the complete chloroplast genome of Primula dejuniana was 151,988 bp. The new species differs from the latter by the solitary scape, the length of petiole, acute leaf blade apex and pin flower. The distribution map, morphological comparison of related species and conservation status of the new species are also provided.

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to the pro-tumor effect of M2-like TAMs, M1-like TAMs account for a small proportion and have anti-tumor effects. Since TAMs can switch from one type to another, reprogramming TAMs may be an important treatment for HCC therapy. However, the mechanisms of phenotypic switch and reprogramming TAMs are still obscure. In this study, we analyzed differential genes in normal macrophages and TAMs, and found that loss of MANF in TAMs accompanied by high levels of downstream genes negatively regulated by MANF. MANF reprogrammed TAMs into M1 phenotype. Meanwhile, loss of MANF promoted HCC progression in HCC patients and mice HCC model, especially tumor neovascularization. Additionally, macrophages with MANF supplement suppressed HCC progression in mice, suggesting MANF supplement in macrophage was an effective treatment for HCC. Mechanistically, MANF enhanced the HSF1–HSP70-1 interaction, restricted HSF1 in the cytoplasm of macrophages, and decreased both mRNA and protein levels of HSP70-1, which in turn led to reprogramming TAMs, and suppressing neovascularization of HCC. Our study contributes to the exploration the mechanism of TAMs reprogramming, which may provide insights for future therapeutic exploitation of HCC neovascularization.

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors. Cell expression systems play crucial roles in the GPCR drug discovery field, including novel target identification, structural and functional characterization, potential ligand screening, signal pathway elucidation, and drug safety evaluation. Here, we discuss the principles, applications, and limitations of widely used cell expression systems in GPCR-targeted drug discovery, GPCR function investigation, signal pathway characterization, and pharmacological property studies. We also propose three strategies for constructing genome-wide pan-GPCR cell libraries, which will provide a powerful platform for GPCR ligand screening, and facilitate the study of GPCR mechanisms and drug safety evaluation, ultimately accelerating the process of GPCR-targeted drug discovery.

Abstract Crystalline-silicon heterojunction back contact solar cells represent the forefront of photovoltaic technology, but encounter significant challenges in managing charge carrier recombination and transport to achieve high efficiency. In this study, we produced highly efficient heterojunction back contact solar cells with a certified efficiency of 27.09% using a laser patterning technique. Our findings indicate that recombination losses primarily arise from the hole-selective contact region and polarity boundaries. We propose solutions to these issues and establish a clear relationship between contact resistivity, series resistance, and the design of the rear-side pattern. Furthermore, we demonstrate that the wafer edge becomes the main channel for current density loss caused by carrier recombination once electrical shading around the electron-selective contact region is mitigated. With the advanced nanocrystalline passivating contact, wafer edge passivation technologies and meticulous optimization of front anti-reflection coating and rear reflector, achieving efficiencies as high as 27.7% is feasible.

Abstract Solid fuel combustion exposure is a leading global health risk factor, yet evidence on its effects, especially on vulnerable children, is sparse. This large-scale, multi-center prospective study aimed to address this gap by involving 9997 schoolchildren across China between 2013 and 2015. Here we show that lung function levels exhibited a marginally significant decline among children exposed to solid fuel usage. Specifically, FVC and FEV1 decreased by 21.2 mL (95% CI: −15.7, 58.1) and 24.1 mL (−8.4, 56.6), respectively. Additionally, PEF, FEF25 and FEF75 decreased by 25.7 mL/s (−46.5, 98.0), 32.7 mL/s (−42.7, 108.2), and 35.4 mL/s (−5.9, 76.7), respectively. Persistent exposure to solid fuel usage in children led to greater lung damage. Children with allergy history were more susceptible to solid fuel exposure. Our study highlights the adverse impact of solid fuel usage on children and the need to promote clean fuel usage for this vulnerable population.

Abstract Drilled cores provide first‐hand data for deposit research. The element compositions at different depths of cores are an important basis for evaluating the reserves of mineral deposits. Therefore, a dataset containing a complete drill core element content has great value on practicality. In this study, a pXRF analyser was used to measure the element contents in eight cores of the Xuancheng Qiaomaishan copper–sulphur deposit ZK16 + 02, ZK16 + 03, ZK16 + 04, ZK1804, ZK18 + 02, ZK1403, ZK1602, and ZK1604, and a geochemical dataset was obtained. The dataset includes Cu, S, Fe, W, Mg, Al, Si, As, Mn, Co, Ni, Zn, Se, Ti, V, Cr, Ca, Cl, P, Sr, Y, Zr, Nb, Mo, Pb, Th, U, and other 27 major and trace elements. Based on this dataset, the vertical variation pattern of main and trace element content in drill cores can be examined, the distributions of elements in full hole or exploration line profile can be drawn, and element correlation analysis and principal component analysis can be performed.

Abstract Background The worldwide prevalence of multi-drug resistance (MDR) in Gram-negative bacteria (GNB), particularly related to extended-spectrum beta-lactamases (ESBLs) and carbapenemases, poses significant global public health and clinical challenges. Objectives To characterize ESBL-producing Gram-negative bacilli, within a pediatric hospital in Gaza using whole genome sequencing (WGS). Methods A total of 158 clinical isolates of Gram-negative bacilli were collected from Al-Nasser Pediatric Hospital. These isolates were tested for ESBL production using the double disk synergy test. The antibiotic susceptibility profile was determined using the Kirby Bauer method following the Clinical and Laboratory Standard Institute guidelines. Selected 15 phenotypically MDR isolates were whole-genome sequenced and characterized for their genome-based species identity and antibiotic resistance gene profile. Results Of the 158 isolates, 93 (58.9%) were positive for ESBL production. The frequency of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Proteus mirabilis, and Serratia marcescens was 50%, 22.7%, 22.7%, 1.8%, 1.2%, and 1.2% respectively. The prevalence of ESBL among urine, pus, blood, and sputum was 64%, 44%, 23%, and 63.6%, respectively. Chloramphenicol, Imipenem, and Meropenem were the most effective antibiotics against ESBL producers. In sequenced isolates, an average of six anti-microbial resistance (AMR) genes were noted per isolate, where one of them carried up to 13 antibiotic resistance genes. Carbapenem resistance genes such as blaKPC-2(6.6%), blaPDC-36/12 (6.6%), and blaPOM-1 (6.6%) were detected. All the sequenced E. coli isolates (n = 8) showed multiple resistance genes, mainly against β-lactamase (25.0%), aminoglycosides (37.5%), sulfonamides (37.5%), and genes conferring resistance to tetracyclines (25.0). Conclusion Our results showed a high prevalence of ESBL-producing GNB isolated from a pediatric hospital in the Gaza Strip. Various antibiotic resistance genes were identified, including those encoding ESBL and carbapenems. The results highlight the significant challenge posed by MDR in GNB and emphasize the need for effective antibiotic strategies. Given the high endemicity observed in various studies from Palestine, it is important to conduct clinical and molecular epidemiology research to identify risk factors, transmission patterns, and clinical outcomes associated with GNB strains that carry ESBL and carbapenem resistance genes.

Abstract Objectives To assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis. Methods In this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007–2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge. Results In total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1–5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5–53). The median extent of LGE was 7% (IQR, 4–10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29–17.49; p

Abstract Background The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus’s high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential. Methods We analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits. Results Our analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10−9 within the 24 HASV traits, located across 93 chromosomal regions. Notably, the regions 12q14.3, 17q21.31, 12q24.22, 6q21, 9q33.1, 6q25.1, and 2q24.2 were found to influence multiple HASVs. Gene set analysis revealed enrichment of neural differentiation and signaling pathways, as well as protein binding and degradation. Of 240 HASV-neuropsychiatric trait pairs, 75 demonstrated significant genetic correlations (P

Abstract Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis for maintaining redox balance and countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) and soybean phospholipid (SP) as pyroptosis promoters (Pd2Sn@GOx-SP), that not only induce pyroptosis by cascade biocatalysis for remodeling tumor microenvironment and facilitating tumor cell immunogenicity, but also trigger disulfidptosis mediated by cystine accumulation to further promote tumor pyroptosis in female mice. Experiments and density functional theory calculations show that Pd2Sn nanorods with an intermediate size exhibit stronger photothermal and enzyme catalytic activity compared with the other three morphologies investigated. The peroxidase-mimic and oxidase-mimic activities of Pd2Sn cause potent reactive oxygen species (ROS) storms for triggering pyroptosis, which could be self-reinforced by photothermal effect, hydrogen peroxide supply accompanied by glycometabolism, and oxygen production from catalase-mimic activity of Pd2Sn. Moreover, the increase of NADP+/NADPH ratio induced by glucose starvation could pose excessive cystine accumulation and inhibit glutathione synthesis, which could cause disulfidptosis and further augment ROS-mediated pyroptosis, respectively. This two-pronged treatment strategy could represent an alternative therapeutic approach to expand anti-tumor immunotherapy.

Abstract The development of adaptive survival strategies is crucial for human occupation of the high-altitude areas of the Tibetan Plateau (TP). However, the history of this adaptation and its driving mechanisms are poorly understood. We used records of pollen, coprophilous fungal spores, and charcoal from a well-dated, high-resolution lake sediment core from the Southern Tibetan Plateau (STP) to investigate the history of high-altitude survival strategies, including arable agriculture and pastoralism, spanning the past 3600 years. The results revealed that survival strategies were dominated by arable agriculture, supplemented by pastoralism, from ~3600 to 1800 cal yr BP. However, after 1800 cal yr BP, this strategy shifted to low-level arable agriculture with intensified pastoralism. Comparison of our findings with regional paleoclimatic and archaeological records revealed that this transformation was an adaptive response to drought intensification. This adaptive resilience was a key aspect of human occupation of the high-altitude regions of the TP during the late Holocene.

Understanding the vibrational behavior of bars is crucial in engineering structures due to their extensive use in mechanical applications. Hence, exploring the longitudinal vibrations of rods under different support conditions, particularly in the presence of cracks, holds significant importance. This study examines the vibrations of a viscoelastic rod containing a crack exposed to a magnetic field. The crack is modeled as a reduction in local stiffness, with a novel approach introduced by treating the crack as viscoelastic. The motion equations are developed by utilizing Newton’s second law and considering structural damping. Boundary conditions and compatibility conditions at the crack location are used to extract the eigenvalue problem. Natural frequencies, influenced by boundary conditions and geometric properties such as crack position and depth, are determined from the solution. Validation of this method is performed by comparing results with existing literature, demonstrating satisfactory accuracy. Additionally, the effect of various parameters on the dynamic features of the rod is investigated.