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Abstract Purpose This study evaluates the efficacy of intrauterine hCG perfusion for RIF, as defined by ESHRE 2023 guidelines, highlighting hCG as a cost-effective alternative to other immunotherapies, especially suitable for less developed regions. It aims to clarify treatment guidance amidst previous inconsistencies. Methods This meta-analysis, registered with PROSPERO (CRD42024443241) and adhering to PRISMA guidelines, assessed the efficacy and safety of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in RIF. Comprehensive literature searches were conducted through December 2023 in major databases including PubMed, Web of Science, Embase, the Cochrane Library, and key Chinese databases, without language restrictions. Inclusion and exclusion criteria were strictly aligned with the 2023 ESHRE recommendations, with exclusions for studies lacking robust control, clear outcomes, or adequate data integrity. The risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I, and RoB2 tools. Data analysis was performed in R using the ‘meta’ package, employing both fixed and random effect models to account for study variability. Subgroup analyses by dosage, volume, hCG concentration, timing of administration, and type of embryo transfer were conducted to deepen insights, enhancing the reliability and depth of the meta-analysis in elucidating the role of hCG perfusion in RIF treatments. Results Data from 13 studies, comprising six retrospective and six prospective studies from single centers, along with one multi-center RCT, totaling 2,157 participants, were synthesized to evaluate the effectiveness of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in patients with RIF. Significant improvements were observed in clinical pregnancy and embryo implantation rates across various dosages, timing of administration, and embryo developmental stages, without impacting miscarriage rates. Notably, the most significant efficacy within subgroups occurred with a 500 IU dosage and perfusion parameters of ≤ 500µL volume and ≥ 2 IU/µL concentration. Additionally, a limited number of studies showed no significant increases in ectopic pregnancy or multiple pregnancy rates, and a modest improvement in live birth rates, although the small number of these studies precludes definitive conclusions. Conclusions The analysis suggests that intrauterine hCG perfusion probably enhances embryo implantation, clinical pregnancy, and live birth rates slightly in RIF patients. Benefits are indicated with a dosage of 500 IU and a maximum volume of 500µL at concentrations of at least 2 IU/µL. However, substantial heterogeneity from varying study types and the limited number of studies necessitate cautious interpretation. These findings underscore the need for more rigorously designed RCTs to definitively assess the efficacy and safety.

Maize plant architecture influences planting density and, in turn, grain yield. Most of the plant architecture-related traits can be described as organ size. We describe a miniature maize mutant, Tiny plant 4 (Tip4), which exhibits reduced size of multiple organs and exhibits a semi-dominant monofactorial inheritance characteristic. Positional cloning confirmed that a 4-bp deletion in the NAC TF with transmembrane motif 1-Like (NTL) gene ZmNTL2, denoted as ZmNTL2Δ, confers the Tip4 mutation. qRT-PCR showed that ZmNTL2 was expressed in all tested tissues. ZmNTL2 functions as a transcriptional activator and is located in both the nucleus and biomembranes. The mutation does not affect the mRNA abundance of ZmNTL2 locus, but it does result in the loss of transmembrane domain and confines the ZmNTL2Δ protein to the nucleus. Knocking out ZmNTL2 has no effect on maize organ size development, indicating that the 4-bp deletion might be a gain-of-function mutation in organ size regulation. Combining transcriptome sequencing with cytokinin and auxin content determination suggests that the decreased organ size may be possibly mediated by changes in hormone homeostasis.

Aim: The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. Methods: The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. Results: The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. Conclusions: The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Abstract Objective IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies. Methods We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD. Results Thirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS. Conclusions This study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape.

The accurate simulation of regional-scale winter wheat yield is important for national food security and the balance of grain supply and demand in China. Presently, most remote sensing process models use the “biomass×harvest index (HI)” method to simulate regional-scale winter wheat yield. However, spatiotemporal differences in HI contribute to inaccuracies in yield simulation at the regional scale. Time-series dry matter partition coefficients (Fr) can dynamically reflect the dry matter partition of winter wheat. In this study, Fr equations were fitted for each organ of winter wheat using site-scale data. These equations were then coupled into a process-based and remote sensing-driven crop yield model for wheat (PRYM-Wheat) to improve the regional simulation of winter wheat yield over the North China Plain (NCP). The improved PRYM-Wheat model integrated with the fitted Fr equations (PRYM-Wheat-Fr) was validated using data obtained from provincial yearbooks. A 3-year (2000–2002) averaged validation showed that PRYM-Wheat-Fr had a higher coefficient of determination (R²=0.55) and lower root mean square error (RMSE=0.94 t ha–1) than PRYM-Wheat with a stable HI (abbreviated as PRYM-Wheat-HI), which had R² and RMSE values of 0.30 and 1.62 t ha–1, respectively. The PRYM-Wheat-Fr model also performed better than PRYM-Wheat-HI for simulating yield in verification years (2013–2015). In conclusion, the PRYM-Wheat-Fr model exhibited a better accuracy than the original PRYM-Wheat model, making it a useful tool for the simulation of regional winter wheat yield.

Drying, as a critical step in the production of air-dried beef, has a direct impact on the quality of the final product. Innovatively, a composite system incorporating contact ultrasound (CU) and infrared radiation (IR) as auxiliary measures within a hot air drying (HAD) framework was built in this research, and the effects of these techniques on the drying kinetics, protein denaturation, and moisture transformation of air-dried beef were investigated. In comparison to HAD treatment, the integrated CU and IR (CU-IRD) system displayed marked enhancements in heat and moisture transport efficiency, thereby saving 36.84% of time expenditure and contributing favorably to the improved moisture distribution of the end-product. This was mainly ascribed to the denaturation of myosin induced by IR thermal effect and the micro-channel produced by CU sponge effect, thus increasing T2 relaxation time and the proportion of free water. In conclusion, the composite system solved the problem of surface hardening and reduces hardness and chewiness of air-dried beef by 40.42% and 45.25% respectively, but inevitably increased the energy burden by 41.60%.

Background: Autoantibodies to type I interferons have been identified in association with a variety of inflammatory and autoimmune diseases. Type I interferons have demonstrated inhibitory effects on mast cell proliferation and degranulation. Systemic mastocytosis (SM) is a disease characterized by increased mast cell burden and mediator release. Whether autoantibodies to type I interferon are present in the sera of patients with SM, and if so, whether they correlate with characteristics of disease, is unknown. Objective: The purpose of this study was to determine whether autoantibodies to type I interferons are observed in the sera of patients with SM, and if so, whether they correlate with biomarkers of disease severity. Methods: We analyzed sera from 89 patients with SM for concentrations of autoantibodies to type I interferon by using a multiplex particle-based assay and signal neutralization capacity by using a STAT1 activity assay and then compared these measurements with those in a database of information on 1284 healthy controls. Results: Our cohort was predominantly female (57.3%), with a median age of 56 years. Of the cohort members, 13 produced autoantibodies to IFN-β, 3 to IFN-ω, and 0 to IFN-α. None of the 13 sera demonstrated signal neutralization. Neither autoantibody concentration nor signaling inhibition measurements correlated with tryptase concentrations or D816V allele burden. Conclusion: Although a small subpopulation of patients with SM have autoantibodies to type I interferons, there was no correlation between autoantibody production and signaling inhibition. These data are consistent with the conclusion that autoantibodies to type I interferon do not play a significant role in the pathogenesis or severity of SM.

Introduction Diabetic retinopathy (DR) is a common vascular complication of diabetes mellitus and a leading cause of vision loss worldwide. Endothelial cell (EC) heterogeneity has been observed in the pathogenesis of DR. Elucidating the underlying mechanisms governing EC heterogeneity may provide novel insights into EC-specific therapies for DR.Research design and methods We used the single-cell data from the Gene Expression Omnibus database to explore EC heterogeneity between diabetic retinas and non-diabetic retinas and identify the potential genes involved in DR. CCK-8 assays, EdU assays, transwell assays, and tube formation assays were conducted to determine the role of the identified gene in angiogenic effects.Results Our analysis identified three distinct EC subpopulations in retinas and revealed that Mitochondria-localized glutamic acid-rich protein (Mgarp) gene is potentially involved in the pathogenesis of DR. Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells.Conclusions This study not only offers new insights into transcriptomic heterogeneity and pathological alteration of retinal ECs but also holds the promise to pave the way for antiangiogenic therapy by targeting EC-specific gene.

Long noncoding RNA (lncRNA) cancer susceptibility 9 (CASC9) has been found to be overexpressed and functions as an oncogene in many cancer types. We investigated the molecular mechanism underlying CASC9 overexpression in esophageal squamous cell carcinoma (ESCC). Transcripts containing exons 2 and 6 and exons 4 and 6 showed the highest CASC9 expression levels in ESCC, no transcripts were detected in the normal esophageal epithelial Het1A cell line. The Long Interspersed Nuclear Element-1 (LINE1 or L1) element in the genome was found to participate in the evolution of lncRNA CASC9, the antisense promoter (ASP) of L1 provides the cis-regulatory elements necessary for CASC9 activation, and the antisense chain of L1 participates in the formation of exons of CASC9. The activation of the antisense promoter was due to the aberrant hypomethylation of L1 elements. An active enhancer element was identified in the downstream region of CASC9 gene by ChIP-seq and ChIP-qPCR. The interaction between ASP and the enhancer elements was confirmed by chromosome conformation capture (3C). Thus, our results suggest that the L1 ASP activation due to aberrant hypomethylation and downstream enhancer interaction plays a key role in the overexpression of lncRNA CASC9 in ESCC.

To confront the challenges posed by air pollution and climate change, China has undertaken significant initiatives to develop strategies that address both issues concurrently. However, the health benefits of these initiatives have not been clearly articulated. In this study, the dynamic changes in health impacts under air pollution and carbon reduction actions in China are evaluated by employing the latest concentration–response models and projected PM2.5 concentrations under future scenarios. From 2020 to 2060, the enforcement of clean air and climate mitigation policies is expected to increase the percentage of the population living with PM2.5 concentrations meeting the 10 μg/m3 standard by 79 %. Without the implementation of relevant mitigation measures, PM2.5-associated deaths are projected to double due to an aging population. In comparison to the 2060 reference scenario, the joint implementation of clean air and carbon neutrality measures is expected to reduce nationwide PM2.5-associated mortality by 62 %, equivalent to 2.15 (95 % CI: 1.80–2.48) million deaths. Stringent pollution controls are crucial for reducing PM2.5-associated deaths before 2030, after which carbon neutrality actions become increasingly significant from 2030 to 2060. The challenges of mitigating future PM2.5-associated deaths vary greatly across regions, showing a critical response to pollution control and carbon reduction. The research proves the effectiveness of China's future air pollution control and carbon reduction policies in mitigating PM2.5-associated deaths.

Abstract Background Individuals with pre‐existing chronic kidney disease (CKD) are at an increased risk of experiencing severe symptoms if infected with COVID‐19. This report presents the case of a patient with CKD who contracted COVID‐19 and subsequently experienced rapid deterioration of kidney function, hair loss, and spontaneous remission of facial warts. Case presentation A 60‐year‐old Chinese man with a decade‐long history of abnormal serum creatinine (Scr) levels and recently heightened fatigue sought treatment. The disease was previously managed and deemed resolved in 2020. However, when he contracted the novel coronavirus on December 20, 2022, he experienced persistent fatigue without other symptoms. In early January 2023, Scr levels was examined as more than 300 μmol/L. This was followed by hair loss, including eyebrows and lashes, and the spontaneous resolution of a longstanding facial wart. During this period, although the patient received kidney‐protecting drugs and a lifestyle optimization, Scr increased continuously and the disease eventually progressed to the uremic stage. As the patient still had relatively abundant urine volume, the patient chose peritoneal dialysis treatment. At a two‐month follow‐up, he had adhered to the CAPD protocol without complications and his hair had begun to regrow. After eight months, his hair had mostly regrown, and his Scr levels kept stable. Conclusion This case may represent the inaugural instance of CKD patients experiencing rapid deterioration of renal function, hair loss, and spontaneous remission of common warts. The underlying mechanisms of this unique phenomenon warrant further researches and debate.

Abstract To improve the corrosion resistance of TiNi alloy fabricated by laser powder bed fusion (LPBF), a porous oxidation layer was synthesized by micro-arc oxidation in a sodium aluminate and sodium silicate electrolyte. The influences of the applied voltage and the processing time on the morphology of oxidation layer were investigated, and the corrosion behavior of the oxidation layer in artificial saliva was evaluated and compared with that of the as-fabricated LPBF alloy. The results indicate that, as increasing the applied voltage and the processing time, the oxidation layer becomes uniform and integrated. The optimum parameters are with an applied voltage of 450 V and processing time of 40 min. The oxidation layer primarily contains α-Al2O3 and consists of two layers, i.e., a thin, compact and uniform inner layer and a porous outer layer. The formation of stable α-Al2O3 phase in the coating and its almost non-porous dense structure reduce the channels for corrosion ions to penetrate into the substrate through coating, thereby improving the corrosion resistance of TiNi alloy.

Abstract Background Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism. Methods A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes. Results COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. Conclusions We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.

This mixed-methods study examined the effectiveness of Rosetta Stone, a mobile-based language learning application, on Chinese EFL students’ listening, speaking, foreign language enjoyment (FLE), and foreign language anxiety (FLA). Two groups of intermediate Chinese EFL students from a language institute, with 33 students in the control group and 36 in the experimental group, were recruited as the participants. The treatment lasted for 3 months, with the experimental group using Rosetta Stone in addition to in-class instruction whereas the control group received only the regular in-class instruction. Data collection involved administering IELTS module tests of speaking and listening, FLE and FLA scales, as well as semi-structured interviews. ANCOVA, paired samples test, and content analysis were used for the data analysis of the quantitative and qualitative data. The results indicate that the experimental group showed significant improvements in their listening, speaking, FLE, and reduced FLA more than the control group. The results of the qualitative data indicated that the students had positive attitudes toward mobile-based language learning. The qualitative findings provided further support to the quantitative results and highlighted the convenience, flexibility, and engaging nature of the application. The outcomes stressed the potential benefits of using mobile-based language learning tools like Rosetta Stone as an effective supplementary method for improving EFL learning outcomes and promoting positive affective variables.

The root of Panax notoginseng (Burk.) F.H. is one of the most famous natural medicines and functional foods for numerous diseases. The saponin constituents present in Panax notoginseng leaves (PNGL) demonstrate an elevated level of glycosylation in comparison to those in the roots, resulting in a significantly diminished bioavailability. In this study, we systematically screened nine recombinant thermostable glycosidases and identified a synergistic combination, namely Tpexy3 and Tpebgl3, to catalyze PNGL. At 70 °C, 2000 U of both glycosidases were added before and after 1 g of PNGL, yielding 650 mg of new fractions, of which ginsenosides Rg3, F2, CK, and PPD were identified as the major products. The enzymatic PNGL demonstrated a lipid droplet-lowering effect on the 3 T3-L1 lipid deposition model. Furthermore, the enzymatic PNGL exhibited significant inhibitory effects on weight gain, hyperlipidemia, hyperglycemia, and inflammation in high-fat diet (HFD) mice. Importantly, the enzymatic PNGL restored the HFD-induced increase in the Firmicutes/Bacteroidetes (F/B) ratio and promoted the growth of beneficial gut microbes with anti-inflammatory properties, improved lipid metabolism, and short-chain fatty acid production. These results strongly indicate that enzyme-catalyzed pretreatment of PNGL can effectively enhance its bioavailability and anti-obesity effects. Biological enzyme catalysis not only provides technical support for the development of specific functional products but also promotes the efficient and high-value utilization of natural product resources.

Repair of large bone defects remains challenge for orthopedic clinical treatment. Porous titanium alloys have been widely fabricated by the additive manufacturing, which possess the elastic modulus close to that of human cortical bone, good osteoconductivity and osteointegration. However, insufficient bone regeneration and vascularization inside the porous titanium scaffolds severely limit their capability for repair of large-size bone defects. Therefore, it is crucially important to improve the osteogenic function and vascularization of the titanium scaffolds. Herein, methacrylated gelatin (GelMA) were incorporated with the porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds prepared by the electron beam melting (EBM) method (Ti2448-GelMA). Besides, the deferoxamine (DFO) as an angiogenic agent was doped into the Ti2448-GelMA scaffold (Ti2448-GelMA/DFO), in order to promote vascularization. The results indicate that GelMA can fully infiltrate into the pores of Ti2448 scaffolds with porous cross-linked network (average pore size: 120.2 ± 25.1 μm). Ti2448-GelMA scaffolds facilitated the differentiation of MC3T3-E1 cells by promoting the ALP expression and mineralization, with the amount of calcium contents ∼2.5 times at day 14, compared with the Ti2448 scaffolds. Impressively, the number of vascular meshes for the Ti2448-GelMA/DFO group (∼7.2/mm2) was significantly higher than the control group (∼5.3/mm2) after cultivation for 9 h, demonstrating the excellent angiogenesis ability. The Ti2448-GelMA/DFO scaffolds also exhibited sustained release of DFO, with a cumulative release of 82.3% after 28 days. Therefore, Ti2448-GelMA/DFO scaffolds likely provide a new strategy to improve the osteogenesis and angiogenesis for repair of large bone defects.

Abstract Cable trees are primarily employed in industrial products to facilitate energy transfer and information exchange among various components. When utilizing machines for assembly, it is essential to convert the wiring plan into a sequence of cable insertion operations executed by the machine under various constraints. This poses a combinatorial optimization problem. In this domain, constraint programming (CP) solvers often exhibit outstanding performance by leveraging their robust problem‐modelling capabilities, excellent scalability, and precise solving capabilities. However, CP solvers may achieve various performances for different problem instances. Selecting the most suitable CP solver for each problem instance is crucial. This paper introduces an automatic selection algorithm for CP solvers to solve the cable tree wiring problem (CTW). Firstly, a scoring system is used to conduct an in‐depth analysis and compare four well‐known CP solvers: CPLEX, Chuffed, OR‐Tools, and Gurobi. The results indicate that OR‐Tools and CPLEX outperform other solvers in performance. Moreover, these two solvers exhibit complementary advantages in quickly finding optimal and feasible solutions within specified time limits. Therefore, CP and machine learning are ingeniously integrated, harnessing their complementary advantages. 4240 instances covering various scenarios are randomly generated to form the problem space. This method incorporates decision trees, random forests, K‐nearest neighbours, and naive Bayes, utilizing these four machine learning techniques. The proposed method can achieve better results than traditional single CP solvers. Among all the evaluated machining learning techniques, the automatic solver selection methods based on decision trees and random forests can achieve accuracy rates of 91.29% and 84.15%, respectively.

Summary: Inflammation-mediated crosstalk between neuroglial cells and endothelial cells (ECs) is a fundamental feature of many vascular diseases. Nevertheless, the landscape of inflammatory processes during diabetes-induced microvascular dysfunction remains elusive. Here, we applied single-cell RNA sequencing to elucidate the transcriptional landscape of diabetic retinopathy (DR). The transcriptome characteristics of microglia and ECs revealed two microglial subpopulations and three EC populations. Exploration of intercellular crosstalk between microglia and ECs showed that diabetes-induced interactions mainly participated in the inflammatory response and vessel development, with colony-stimulating factor 1 (CSF1) and CSF1 receptor (CSF1R) playing important roles in early cell differentiation. Clinically, we found that CSF1/CSF1R crosstalk dysregulation was associated with proliferative DR. Mechanistically, ECs secrete CSF1 and activate CSF1R endocytosis and the CSF1R phosphorylation-mediated MAPK signaling pathway, which elicits the differentiation of microglia and triggers the secretion of inflammatory factors, and subsequently foster angiogenesis by remodeling the inflammatory microenvironment through a positive feedback mechanism.

Abstract Stress granules (SGs) are dynamic, membrane-less organelles. With their formation and disassembly processes characterized, it remains elusive how compositional transitions are coordinated during prolonged stress to meet changing functional needs. Here, using time-resolved proteomic profiling of the acute to prolonged heat-shock SG life cycle, we identify dynamic SG proteins, further segregated into early and late proteins. Comparison of different groups of SG proteins suggests that their biochemical properties help coordinate SG compositional and functional transitions. In particular, early proteins, with high phase-separation-propensity, drive the rapid formation of the initial SG platform, while late proteins are subsequently recruited as discrete modules to further functionalize SGs. This model, supported by immunoblotting and immunofluorescence imaging, provides a conceptual framework for the compositional transitions throughout the acute to prolonged SG life cycle. Additionally, an early SG constituent, non-muscle myosin II, is shown to promote SG formation by increasing SG fusion, underscoring the strength of this dataset in revealing the complexity of SG regulation.

Abstract Background Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) surgery is associated with poor outcomes. The objective of this study was to apply a new machine learning (ML) method to establish prediction models of AKI after CABG. Methods A total of 2,780 patients from two medical centers in East China who underwent primary isolated CABG were enrolled. The dataset was randomly divided for model training (80%) and model testing (20%). Four ML models based on LightGBM, Support vector machine (SVM), Softmax and random forest (RF) algorithms respectively were established in Python. A total of 2,051 patients from two other medical centers were assigned to an external validation group to verify the performances of the ML prediction models. The models were evaluated using the area under the receiver operating characteristics curve (AUC), Hosmer-Lemeshow goodness-of-fit statistic, Bland-Altman plots, and decision curve analysis. The outcome of the LightGBM model was interpreted using SHapley Additive exPlanations (SHAP). Results The incidence of postoperative AKI in the modeling group was 13.4%. Similarly, the incidence of postoperative AKI of the two medical centers in the external validation group was 8.2% and 13.6% respectively. LightGBM performed the best in predicting, with an AUC of 0.8027 in internal validation group and 0.8798 and 0.7801 in the external validation group. The SHAP revealed the top 20 predictors of postoperative AKI ranked according to the importance, and the top three features on prediction were the serum creatinine in the first 24 h after operation, the last preoperative Scr level, and body surface area. Conclusion This study provides a LightGBM predictive model that can make accurate predictions for AKI after CABG surgery. The LightGBM model shows good predictive ability in both internal and external validation. It can help cardiac surgeons identify high-risk patients who may experience AKI after CABG surgery.

AP2/ERF transcription factors play important roles in plant growth, development and response to abiotic stress. In order to explore the response of AvAP2/ERF genes in Aquilegia vulgaris to salt stress, based on the transcriptome data obtained under salt stress in previous experiments, the AP2/ERF gene family in A. vulgaris were screened by bioinformatic methods, and their physical and chemical properties, conserved motifs, phylogenetic relations and expression changes of these genes in leaves and roots under salt stress were analyzed, etc. The expression of candidate genes was verified by qRT-PCR. The results were as follows：(1) 86 AvAP2/ERF genes were identified which encoded 132-722 amino acids, with molecular weight of 14 763.30-79 069.47 Da and isoelectric point ranged from 4.49 to 9.68. Most of them were slightly acidic proteins and all of them were hydrophilic. Most of AvAP2/ERF were localized in nucleus. (2)The similarity of secondary structure was high, which was proportionally composed of random coil and α-helix. The members all contained AP2 domains, and two conserved motifs were predicted. (3) Under different stages of salt treatment, there were 71 AvAP2/ERF genes responded to salt stress. There were 18 and 19 differentially expressed genes in leaves and roots, respectively. There were 86 AP2/ERF genes of A. vulgaris were divided into five subfamilies clustering with A. thaliana; the AP2/ERF genes of A. vulgaris and Arabidopsis thaliana were clustered into five subfamilies and 15 subgroups. Through expression analysis and homology relationship, AvAP2/ERF-56, AvAP2/ERF-61 and AvAP2/ERF-80 of them might be involved in salt resistance, and the qRT-PCR results were consistent with sequencing expression trends. The results of this study provides a reliable reference for further research on the function and stress response mechanism of AP2/ERF gene in Aquilegia vulgaris.

Understanding the spatial distribution of the crop yield gap (YG) is essential for improving crop yields. Recent studies have typically focused on the site scale, which may lead to considerable uncertainties when scaled to the regional scale. To mitigate this issue, this study used a process-based and remote sensing driven crop yield model for winter wheat (PRYM-Wheat), which was derived from the boreal ecosystem productivity simulator (BEPS), to simulate the YG of winter wheat in the North China Plain from 2015 to 2019. Yield validation based on statistical yield data revealed good performance of the PRYM-Wheat Model in simulating winter wheat actual yield (Ya). The distribution of Ya across the North China Plain showed great heterogeneity, decreasing from southeast to northwest. The remote sensing-estimated results show that the average YG of the study area was 6 400.6 kg ha−1. The YG of Jiangsu Province was the largest, at 7 307.4 kg ha−1, while the YG of Anhui Province was the smallest, at 5 842.1 kg ha−1. An analysis of the responses of YG to environmental factors showed no obvious correlation between YG and precipitation, but there was a weak negative correlation between YG and accumulated temperature. In addition, the YG was positively correlated with elevation. In general, studying the specific features of the YG can provide directions for increasing crop yields in the future.

Based on the self-stress slurry reinforcement method for fractured rock mass proposed by the authors, considering the influence of rock strength on the coupling effect of self-stress slurry and rock mass, the paper selected underground sandstone, carbonaceous mudstone, sandy mudstone, and coal as the research objects. Then, the comparative tests of reinforcing fractured rock mass with different strength by ordinary slurry and self-stress slurry were carried out to further analyze the influence of rock strength on grouting reinforcement effect. The composite reinforcement effect of restrained self-stress slurry on the rock mass fracture interface was investigated from multiple angles to reveal the reinforcement mechanism of slurry self-stress. Through several engineering cases of different rock strength, the macroscopic reinforcement effect of the self-stress slurry system on the engineering surrounding rock with different rock strength was analyzed. The results showed that the reinforcement effect of self-stress slurry on the fractured rock masses with different strength, such as soft and hard rock, was greater than that of ordinary slurry. As the strength of the rock mass became weaker, the repair degree of slurry to the fractured rock mass was gradually reduced, and the grouting reinforced rock mass specimens gradually transited from shear failure along the diagonal direction to splitting collapse failure. The self-stress of the slurry improved the restrained state of the slurry-rock interface, and then increased the shear strength of the interface by increasing the friction force. The contact connection effect of the two mediums of slurry and rock had been improved. The cementation density of self-stress slurry-rock interface was significantly higher than that of ordinary slurry-rock interface. The crystal particle distribution, compactness and mechanical properties of self-stress slurry stone were obviously better than those of ordinary slurry. The ultra-fine siliceous self-stress slurry system had achieved good results in the reinforcement of broken soft rock roadways, relatively hard rock roadways, and soft coal wall.

Accurate estimation of regional winter wheat yields is essential for understanding the food production status and ensuring national food security. However, using the existing remote sensing-based crop yield models to accurately reproduce the inter-annual and spatial variations in winter wheat yields remains challenging due to the limited ability to acquire irrigation information in water-limited regions. Thus, we proposed a new approach to approximating irrigations of winter wheat over the North China Plain (NCP), where irrigation occurs extensively during the winter wheat growing season. This approach used irrigation pattern parameters (IPPs) to define the irrigation frequency and timing. Then, they were incorporated into a newly-developed process-based and remote sensing-driven crop yield model for winter wheat (PRYM–Wheat), to improve the regional estimates of winter wheat over the NCP. The IPPs were determined using statistical yield data of reference years (2010–2015) over the NCP. Our findings showed that PRYM–Wheat with the optimal IPPs could improve the regional estimate of winter wheat yield, with an increase and decrease in the correlation coefficient (R) and root mean square error (RMSE) of 0.15 (about 37%) and 0.90 t ha–1 (about 41%), respectively. The data in validation years (2001–2009 and 2016–2019) were used to validate PRYM–Wheat. In addition, our findings also showed R (RMSE) of 0.80 (0.62 t ha–1) on a site level, 0.61 (0.91 t ha–1) for Hebei Province on a county level, 0.73 (0.97 t ha–1) for Henan Province on a county level, and 0.55 (0.75 t ha–1) for Shandong Province on a city level. Overall, PRYM–Wheat can offer a stable and robust approach to estimating regional winter wheat yield across multiple years, providing a scientific basis for ensuring regional food security.

Some numerical simulations were used to study the effects of blowing ratio (0.25–0.5), hole diameters(0.65~1 mm), and hole inclination angle (30~60°) of the film cooling structure on the cooling and aerodynamic characteristics of the axisymmetric plug nozzle under the condition of transonic. The results showed that the bow shocks appear near the film holes on the plug wall in the supersonic region, which cause the wall cooling effectiveness of the plug to decrease. Compared with the baseline plug, the blowing ratio ranged from 0.25 to 0.5, the wall average temperature of the rear plug decreased by 34.4~48.1%, the thrust coefficient and total pressure recovery coefficient decreased by 0.31~0.61% and 0.52~0.93%, respectively. When the perforated percentage is constant, the wall cooling effectiveness increases with the decrease of the hole diameters. The increase in the inclination angle of the film holes lead to the decrease in cooling effectiveness and aerodynamic performance. This is because the penetration ability of the cooling air to the mainstream is enhanced, and the obstruction to the mainstream boundary layer is increased, resulting in the increase of bow shock intensity near the film holes in the supersonic region.

The objective of this study was to evaluate the feasibility, safety, and effectiveness of intravenous stem cell delivery utilizing ultrasound-targeted microbubble destruction (UTMD) in a rat model of middle cerebral artery occlusion (MCAO), while investigating the underlying mechanisms. Acute cerebral infarction (ACI) was induced surgically in adult rats to create the MCAO rat model. Intravenous injection of SonoVue microbubbles and bone marrow–derived mesenchymal stem cells (BMSC) was performed concurrently, with or without ultrasound targeting the stroke. The animals were divided into four groups: sham-operated group, ACI-MCAO rats treated with phosphate-buffered saline (ACI+PBS), rats receiving intravenous delivery of BMSC expressing green fluorescent protein (GFP-BMSC; ACI+BMSC), and rats receiving intravenous GFP-BMSC with simultaneous UTMD exposure (ACI+BMSC+UTMD). The efficacy of the treatments was assessed by evaluating the animals’ neurological function using the Longa score and examining histopathological changes such as cerebral infarct volume, cerebral edema, and cell apoptosis. A rat cytokine array was utilized to identify the potential cytokines that may be responsible for the therapeutic effect of UTMD-mediated BMSC treatment. Optimal UTMD parameters resulted in an increase in blood–brain barrier (BBB) permeability after 30 min, which returned to baseline 72 h later without causing any residual injury. UTMD application significantly increased the homing of intravenously delivered BMSC, resulting in a 2.2-fold increase in GFP-BMSC cell count on day 3 and a 2.6-fold increase on day 7 compared with intravenous delivery alone. This effect persisted for up to 6 weeks after injection. Intravenous BMSC delivery significantly reduced the volume of cerebral infarct and decreased cerebral edema, leading to a lower Longa score. Furthermore, this effect was further enhanced by UTMD. Acute cerebral infarction induced by MCAO led to elevated matrix metalloproteinase 8 (MMP8) levels in the cerebrospinal fluid, which were significantly reduced following UTMD-mediated BMSC treatment. U ltrasound-targeted microbubble destruction facilitates the migration and homing of BMSC into the brain, possibly by transiently increasing blood–brain barrier (BBB) permeability, thereby improving therapeutic outcomes in an ACI rat model. The observed effect may be partly attributed to modulation of MMP8 levels. Advances in knowledge: UTMD-mediated intravenously delivered BMSC transplantation led to a significant increase in cell homing and reduction of MMP8 levels, resulting in increased therapeutic effect in an acute ischemic cerebral infarction model.

Backfill grouting plays a vital role in shield tunneling. This paper aims to present a comprehensive review of the development and progress of backfill grouting materials specifically designed for shield tunneling. Initially, the various components of grouts, such as pozzolanic materials, filling fine aggregates, and chemical additives, are introduced and discussed in detail. Subsequently, this study investigates critical properties including workability, mechanical properties, and durability of the grouts. Additionally, the principal factors influencing the properties are summarized, along with recommended ranges for specific geological conditions. Furthermore, the paper elucidates the diffusion mechanism of grouting mortars by presenting the current grouting models employed in shield tunneling. Recent advancements in grouting materials are extensively studied and extended, offering new perspectives for future grouting technology in shield tunneling. This study provides valuable insights into overcoming the existing challenges associated with shield tunnel grouting and promoting the evolution of current grouting materials.

ABSTRACTChimeric antigen receptor (CAR) T cell immunotherapy has demonstrated success in the treatment of hematological malignancies; however, its efficacy and applications in solid tumors remain limited. Immunosuppressive factors, particularly inhibitory checkpoint molecules, restrict CAR T cell activity inside solid tumors. The modulation of checkpoint pathways has emerged as a promising approach to promote anti-tumor responses in CAR T cells. Programmed cell death protein 1 (PD1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) are two critical immune-checkpoint molecules that suppress anti-tumor activity in T cells. Simultaneous targeting of these two inhibitory molecules could be an efficient checkpoint modulation strategy. Here, we developed a PD1-TIGIT chimeric immune-checkpoint switch receptor (CISR) that enhances the efficacy of CAR T cell immunotherapy by reversing the inhibitory checkpoint signals of PD1/PDL1 and/or TIGIT/CD155. In addition to neutralizing PDL1 and CD155, this chimeric receptor is engineered with the transmembrane region and intracellular domain of CD28, thereby effectively enhancing T cell survival and tumor-targeting functions. Notably, under simultaneous stimulation of PDL1 and CD155, CISR-CAR T cells demonstrate superior performance in terms of cell survival, proliferation, cytokine release, and cytotoxicity in vitro, compared with conventional CAR T cells. Experiments utilizing both cell line- and patient-derived xenotransplantation tumor models showed that CISR-CAR T cells exhibit robust infiltration and anti-tumor efficiency in vivo. Our results highlight the potential for the CISR strategy to enhance T cell anti-tumor efficacy and provide an alternative approach for T cell-based immunotherapies.

Abstract Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8+ cells (representing CD8+ T cells) and CD57+ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA+ cells and GSDMB+ cells were predominantly expressed in immune cells, especially in CD8 + T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA+ merged CD8+ T cells (0.11%) and GSDMB+ merged CD57+ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.

Abstract This paper investigates optimal decisions for private banking development in China under two innovative organizational structures—the big retail mode (BRM) and the independent development mode (IDM). Under the BRM, the retail and private banking divisions form a cooperative relationship wherein the former transfers high-net-worth customers to the latter. In addition, retail banking receives a share of private banking revenues. We investigate the optimal revenue-sharing ratio between the two divisions and the optimal effort by private banking to serve transferred customers within the cooperative relationship. The analytical results show that as the private banking division becomes more developed, the optimal revenue-sharing ratio decreases, and the private banking division’s optimal effort to serve transferred customers decreases because it puts more effort into acquiring new customers. Under the IDM, the two divisions form a competitive relationship since they compete to acquire customers independently. We investigate customer acquisition efforts in this interdivisional competition. Optimal customer acquisition efforts by both divisions increase in potential assets and rates of return. This paper contributes to the literature by (1) analyzing financial innovation by private banks from an organizational perspective; (2) providing an economic analysis for private banking development in China.

Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant associated myocardial injury seriously affected the patient's health. Chest computed tomography (CT) is an essential imaging diagnostic tool for evaluating lung diseases in these patients, but its value in the diagnosis of myocardial injury remains unknown. The purpose of this study was to evaluate the lung lesions in patients with Omicron infection with or without myocardial injury, and to evaluate the predictive value of non-contrast chest CT in such patients with myocardial injury. We enrolled 122 consecutive hospitalized patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) for non-contrast chest CT examination. These patients were divided into two groups according to whether myocardial injury occurred. Myocardial injury was defined as a Troponin I level above the 99th-percentile upper reference limit (0.04 ng/mL). The imaging manifestations of the patients’ lungs were evaluated. Myocardial CT value, left atrium (LA) size, long diameter of left ventricular (LV), and cardiothoracic ratio (CTR) were recorded. Multivariate logistic analysis was performed to identify the predictive factors associated with myocardial injury. Of 122 patients, 61 patients (50%) had myocardial injury. Compared with patients without myocardial injury, there was worse NYHA class, more critical patients, higher incidence of bronchial meteorology, larger area and percentage of lung lesions, diameters of LA, and lower myocardial CT value in the myocardial injury group (P

Considering the damage caused by conventional fracturing fluid in low-permeability reservoirs, a novel fracturing fluid (FNG) combining hydroxypropyl guar (HPG) and functionally modified nano-silica (FMNS) was prepared. The properties of heat/shear resistance, rheological property, proppant transportation, and formation damage were evaluated with systematic experiments. The results showed that the viscosities of FNG before and after the heat/resistance were 1323 mPa·s and 463 mPa·s, respectively, while that of conventional HPG gel was 350 mPa·s. FNG is a pseudoplastic strong gel with a yield stress of 12.9 Pa, a flow behavior index of 0.54, an elastic modulus of 16.2 Pa, and a viscous modulus of 6.2 Pa. As the proportions of proppant mass in further sections transported with FNG were higher than those transported with HPG gel, FNG could transport the proppant better than HPG gel at high temperatures. Because of the amphiphilic characteristics of FMNS, the surface/interface properties were improved by the FNG filtrate, resulting in a lower oil permeability loss rate of 10 percentage points in the matrix than with the filtrated HPG gel. Due to the considerable residual gel in broken HPG gel, the retained conductivity damaged with broken FNG was 9.5 percentage points higher than that damaged with broken HPG gel. FNG shows good potential for reducing formation damage during fracturing in low-permeability reservoirs in China.

The Gangdese metallogenic belt in Tibet is an important polymetallic metallogenic belt formed during the subduction of the Neo-Tethys Ocean and subsequent India–Asia collision. Adakitic rocks are widely distributed in this belt and are considered to be closely related to porphyry–skarn Cu-Mo polymetallic mineralization. However, the petrogenesis and geodynamic setting of the Late Cretaceous adakites in the Gangdese belt remain controversial. In this study, we focus on the quartz diorite in the Nuri Cu-W-Mo deposit along the southern margin of the eastern Gangdese belt. LA-ICP-MS zircon U-Pb dating yields a Late Cretaceous age of 93.6 ± 0.4 Ma for the quartz diorite. Whole-rock geochemistry shows that the quartz diorite possesses typical adakitic signatures, with high SiO2, Al2O3, and Sr contents, but low Y and Yb contents. The relatively low K2O content and high MgO, Cr, and Ni contents, as well as the positive zircon εHf(t) values (+6.58 to +14.52), suggest that the adakites were derived from the partial melting of the subducted Neo-Tethys oceanic slab, with subsequent interaction with the overlying mantle wedge. The Late Cretaceous magmatic flare-up and coeval high-temperature granulite-facies metamorphism in the Gangdese belt were likely triggered by Neo-Tethys mid-ocean ridge subduction. The widespread occurrence of Late Cretaceous adakitic intrusions and associated Cu mineralization in the Nuri ore district indicate a strong tectono-magmatic-metallogenic event related to the Neo-Tethys subduction during this period. This study provides new insights into the petrogenesis and geodynamic setting of the Late Cretaceous adakites in the Gangdese belt, and has important implications for Cu polymetallic deposit exploration in this region.

Glutamic acid decarboxylase antibody (GADAb) has emerged as a significant biomarker for clinical diagnosis and prognosis in type 1 diabetes (T1D). In this study, we investigated the potential utilization of glass capillary solid-state nanopores as a cost-effective and easily preparable platform for the detection of individual antigens, antibodies, and antigen-antibody complexes without necessitating any modifications to the nanopores. Our findings revealed notable characteristic variations in the translocation events of glutamic acid decarboxylase (GAD65) through nanopores under different voltage conditions, discovered that anomalous phenomenon of protein translocation events increasing with voltage may potentially be caused by the crowding of multiple proteins in the nanopores, and demonstrated that there are multiple components in the polyclonal antibodies (GADAb-poly). Furthermore, we achieved successful differentiation between GAD65, GADAb, and GADAb-GAD65 complexes. These results offer promising prospects for the development of a rapid and reliable GADAb detection method, which holds the potential to be applied in patient serum samples, thereby facilitating a label-free, cost-effective, and early diagnosis of type I diabetes.

Accurately predicting actual evapotranspiration (ETa) at the regional scale is crucial for efficient water resource allocation and management. While previous studies mainly focused on predicting site-scale ETa, in-depth studies on regional-scale ETa are relatively scarce. This study aims to address this issue by proposing a MulSA-ConvLSTM model, which combines the multi-headed self-attention module with the Pyramidally Attended Feature Extraction (PAFE) method. By extracting feature information and spatial dependencies in various dimensions and scales, the model utilizes remote sensing data from ERA5-Land and TerraClimate to attain regional-scale ETa prediction in Shandong, China. The MulSA-ConvLSTM model enhances the efficiency of capturing the trend of ETa successfully, and the prediction results are more accurate than those of the other contrast models. The Pearson’s correlation coefficient between observed and predicted values reaches 0.908. The study has demonstrated that MulSA-ConvLSTM yields superior performance in forecasting various ETa scenarios and is more responsive to climatic changes than other contrast models. By using a convolutional network feature extraction method, the PAFE method extracts global features via various convolutional kernels. The customized MulSAM module allows the model to concentrate on data from distinct subspaces, focusing on feature changes in multiple directions. The block-based training method is employed for the large-scale regional ETa prediction, proving to be effective in mitigating the constraints posed by limited hardware resources. This research provides a novel and effective method for accurately predicting regional-scale ETa.

BackgroundWe explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood.MethodsWe integrated scRNA-seq data from melanoma patients sourced from the GEO database. Through the utilization of the Seurat R package, we successfully identified distinct gene clusters associated with patient survival in the scRNA-seq data. Key prognostic genes were identified through single-factor Cox analysis and used to develop a prognostic model using LASSO and stepwise regression algorithms. Additionally, we evaluated the predictive potential of these genes within the immune microenvironment and their relevance to immunotherapy. Finally, we validated the functional significance of the high-risk gene IRX3 through in vitro experiments.ResultsAnalysis of scRNA-seq data identified distinct expression patterns of 4 specific genes (SRGs) in diverse cell subpopulations. Re-clustering cells based on increased SRG expression revealed 7 subgroups with significant prognostic implications. Using marker genes, lasso, and Cox regression, we selected 11 genes to construct a risk signature. This signature demonstrated a strong correlation with immune cell infiltration and stromal scores, highlighting its relevance in the tumor microenvironment. Functional studies involving IRX3 knockdown in A375 and WM-115 cells showed significant reductions in cell viability, proliferation, and invasiveness.ConclusionSRG-based risk signature holds promise for precise melanoma prognosis. An in-depth exploration of SRG characteristics offers insights into immunotherapy response. Therapeutic targeting of the IRX3 gene may benefit melanoma patients.

IntroductionDiabetic macular edema (DME) is a major cause of vision impairment in the patients with diabetes. Optical Coherence Tomography (OCT) is an important ophthalmic imaging method, which can enable early detection of DME. However, it is difficult to achieve high-efficiency and high-precision extraction of DME in OCT images because the sources of OCT images are diverse and the quality of OCT images is not stable. Thus, it is still required to design a model to improve the accuracy of DME extraction in OCT images.MethodsA lightweight model (DME-DeepLabV3+) was proposed for DME extraction using a DeepLabV3+ architecture. In this model, MobileNetV2 model was used as the backbone for extracting low-level features of DME. The improved ASPP with sawtooth wave-like dilation rate was used for extracting high-level features of DME. Then, the decoder was used to fuse and refine low-level and high-level features of DME. Finally, 1711 OCT images were collected from the Kermany dataset and the Affiliated Eye Hospital. 1369, 171, and 171 OCT images were randomly selected for training, validation, and testing, respectively.ConclusionIn ablation experiment, the proposed DME-DeepLabV3+ model was compared against DeepLabV3+ model with different setting to evaluate the effects of MobileNetV2 and improved ASPP on DME extraction. DME-DeepLabV3+ had better extraction performance, especially in small-scale macular edema regions. The extraction results of DME-DeepLabV3+ were close to ground truth. In comparative experiment, the proposed DME-DeepLabV3+ model was compared against other models, including FCN, UNet, PSPNet, ICNet, and DANet, to evaluate DME extraction performance. DME-DeepLabV3+ model had better DME extraction performance than other models as shown by greater pixel accuracy (PA), mean pixel accuracy (MPA), precision (Pre), recall (Re), F1-score (F1), and mean Intersection over Union (MIoU), which were 98.71%, 95.23%, 91.19%, 91.12%, 91.15%, and 91.18%, respectively.DiscussionDME-DeepLabV3+ model is suitable for DME extraction in OCT images and can assist the ophthalmologists in the management of ocular diseases.

African swine fever (ASF) is an infectious disease caused by African swine fever virus (ASFV) that is highly contagious and has an extremely high mortality rate (infected by virulent strains) among domestic and wild pigs, causing huge economic losses to the pig industry globally. In this study, SDS−PAGE gel bands hybridized with ASFV whole virus protein combined with ASFV-convalescent and ASFV-positive pig serum were identified by mass spectrometry. Six antigens were detected by positive serum reaction bands, and eight antigens were detected in ASFV-convalescent serum. In combination with previous literature reports and proteins corresponding to MHC-II presenting peptides screened from ASFV-positive pig urine conducted in our lab, seven candidate antigens, including KP177R (p22), K78R (p10), CP204L (p30), E183L (p54), B602L (B602L), EP402R-N (CD2V-N) and F317L (F317L), were selected. Subunit-Group 1 was prepared by mixing above-mentioned seven ASFV recombinant proteins with MONTANIDETM1313 VG N mucosal adjuvant and immunizing pigs intranasally and intramuscularly. Subunit-Group 2 was prepared by mixing four ASFV recombinant proteins (p22, p54, CD2V-N1, B602L) with Montanide ISA 51 VG adjuvant and immunizing pigs by intramuscular injection. Anticoagulated whole blood, serum, and oral fluid were collected during immunization for flow cytometry, serum IgG as well as secretory sIgA antibody secretion, and cytokine expression testing to conduct a comprehensive immunogenicity assessment. Both immunogen groups can effectively stimulate the host to produce ideal humoral, mucosal, and cellular immune responses, providing a theoretical basis for subsequent functional studies, such as immunogens challenge protection and elucidation of the pathogenic mechanism of ASFV.

Fresh foods especially fruits, vegetables, meat, poultry and aquatic products are highly perishable due to high moisture content and rich nutrient matrix, which leads to microbial growth, enzymatic and oxidative reactions. As a common food processing method, drying inhibits spoilage microorganisms and oxidation reactions as well as retaining nutrients by reducing the moisture content and water activity in food, thus extending product storage life. Pretreatment is a key step for the drying operation. Compared to traditional pretreated and untreated samples, the development and application of new non-thermal pretreatment technologies can not only improve moisture distribution and reduce energy consumption, but also further improve the functional and nutritional attributes of dried products. In the present study, some novel non-thermal pretreatment technologies including cold plasma, ultrasound and pulsed electric field were reviewed. Their detailed working principles and equipment, positive effects on agricultural products and meat products, as well as some possible pros and cons for application are also presented to provide some reference for the development and application of these pretreatment technologies.

Abstract Pancreatic cancer is a rare but fatal disease. Patients present advanced disease due to the lack of or typical symptoms when the tumor is still localized. A high-quality image processing system has been in practice to detect the pancreatic tumor and determine the possibility of surgery, and preoperative methods, such as ERCP are increasingly used to complement the staging modality. Pancreaticoduodenectomy is one of the complicated surgeries with potential morbidity. The minimally invasive pancreatic resections, both robot-assisted and laparoscopic, have become a part of standard surgical practice worldwide over the last decade. Moreover, advancements in adjuvant chemotherapy have improved the long-term outcomes in current clinical practice. The systemic conservative treatment, including targeted agents, remains the mainstay of treatment for patients with advanced disease. An increasing number of studies are focused on modulating the pancreatic tumor microenvironment to improve the efficacy of the immunotherapeutic strategies. Herein, the role of preoperative therapy, the novel surgical strategy, and individualized systemic treatment in pancreatic cancer is investigated. Also, the randomized controlled studies that have defined the neoadjuvant and surgical management of pancreatic cancer have been summarized.

Evaluating the effects of revegetation on runoff and erosion reduction is essential for studying soil and water conservation on the Loess Plateau after implementation of China's Grain for Green Project. However, quantifying the influence of revegetation on the erosion caused by concentrated runoff in extreme rainstorms is still challenging. To evaluate this influence, scouring-erosion experiments were implemented in situ on the vegetated hillslope plots (GR) and bare hillslope plots (CK). The runoff-reducing effects of grass (GRR) averaged 31%, 20% and 8%, and the erosion-reducing effects of grass (GER) averaged 93%, 95% and 93% on the 5°-plots, 10°-plots and 18°-plots, respectively. The ratios of GRR to GER were 0.09–0.33, implying that the ability of vegetation to reduce erosion was greater than its ability to reduce runoff. The GRR and GER obviously decreased as the inflow rate increased, and the GRR decreased as the hillslope gradient increased, but there were no obvious differences in the GER between hillslope gradients. Vegetation could decrease the ability of the concentrated flow to carry and transport sediment and increase the energy consumption of the concentrated flow in response to hydraulic resistance. Vegetation also significantly reduced the degree of rill development. The degree of rill dissection on the GR (0.054–0.087 m2 m−2) was lower than that on the CK (0.061–0.184 m2 m−2). Our findings provide an essential reference for ecological environment and vegetation restoration on loess hillslopes.

Ovarian cancer (OC) is a highly malignant cancer with great metastatic potential. Here we aimed to investigate the role of Piezo1, a gene related to the mechanical environment of the tumor, in promoting the metastasis of OC. We performed Piezo1 knockdown in A-1847 cells using small hairpin RNAs, and the cells were inoculated subcutaneously in nude mice. Piezo1 knockdown decreased the tumor growth rate of OC tumor xenografts in mice and reduced cell migration in vitro. Metastasis in the lung was also attenuated after Piezo1 knockdown as revealed by HE staining of the lung tissues, which was concomitant with downregulation of E-Cadherin and vimentin and upregulation of N-Cadherin analyzed using western blot analysis, suggesting suppressed epithelial-to-mesenchymal transition. Migration of Piezo1-knockdown cells was also analyzed for their migratory capabilities using the scratch assay. We also analyzed the key proteins in the Hippo/YAP signaling pathway using western blot after treating A-1847 and 3AO cells with a Piezo1 inducer, Yoda1. Piezo1 inducer Yoda1 activated Hippo/YAP signal in OC cells. In conclusion, Piezo1 is overexpressed in OC tissues and contributes to OC tumor growth and metastasis. Suppression of Piezo1 is a potential therapeutic strategy for OC.

Diabetic retinopathy (DR) is a microvascular complication of diabetes. Microaneurysms (MAs) are often observed in the retinal vessels of diabetic patients and represent one of the earliest signs of DR. Accurate and efficient detection of MAs is crucial for the diagnosis of DR. In this study, an automatic model (MA-YOLO) is proposed for MA detection in fluorescein angiography (FFA) images. To obtain detailed features and improve the discriminability of MAs in FFA images, SwinIR was utilized to reconstruct super-resolution images. To solve the problems of missed detection of small features and feature information loss, an MA detection layer was added between the neck and the head sections of YOLOv8. To enhance the generalization ability of the MA-YOLO model, transfer learning was conducted between high-resolution images and low-resolution images. To avoid excessive penalization due to geometric factors and address sample distribution imbalance, the loss function was optimized by taking the Wise-IoU loss as a bounding box regression loss. The performance of the MA-YOLO model in MA detection was compared with that of other state-of-the-art models, including SSD, RetinaNet, YOLOv5, YOLOX, and YOLOv7. The results showed that the MA-YOLO model had the best performance in MA detection, as shown by its optimal metrics, including recall, precision, F1 score, and AP, which were 88.23%, 97.98%, 92.85%, and 94.62%, respectively. Collectively, the proposed MA-YOLO model is suitable for the automatic detection of MAs in FFA images, which can assist ophthalmologists in the diagnosis of the progression of DR.

Cancer treatments, including traditional chemotherapy, have failed to cure human malignancies. The main reasons for the failure of these treatments are the inevitable drug resistance and serious side effects. In clinical treatment, only 5 percent of the 50 percent of cancer patients who are able to receive conventional chemotherapy survive. Because of these factors, being able to develop a drug and treatment that can target only cancer cells without affecting normal cells remains a big challenge. Since the special properties of cisplatin in the treatment of malignant tumors were accidentally discovered in the last century, metal anticancer drugs have become a research hotspot. Metal anticancer drugs have unique pharmaceutical properties, such as ruthenium metal drugs with their high selectivity, low toxicity, easy absorption by tumor tissue, excretion, and so on. In recent years, efficient and low-toxicity metal antitumor complexes have been synthesized. In this paper, the scientific literature on platinum (Pt), ruthenium (Ru), iridium (Ir), gold (Au), and other anticancer complexes was reviewed by referring to a large amount of relevant literature at home and abroad.

ObjectiveTo investigate the feasibility and efficiency of automatic segmentation of contrast-enhanced ultrasound (CEUS) images in renal tumors by convolutional neural network (CNN) based models and their further application in radiomic analysis.Materials and methodsFrom 94 pathologically confirmed renal tumor cases, 3355 CEUS images were extracted and randomly divided into training set (3020 images) and test set (335 images). According to the histological subtypes of renal cell carcinoma, the test set was further split into clear cell renal cell carcinoma (ccRCC) set (225 images), renal angiomyolipoma (AML) set (77 images) and set of other subtypes (33 images). Manual segmentation was the gold standard and serves as ground truth. Seven CNN-based models including DeepLabV3+, UNet, UNet++, UNet3+, SegNet, MultilResUNet and Attention UNet were used for automatic segmentation. Python 3.7.0 and Pyradiomics package 3.0.1 were used for radiomic feature extraction. Performance of all approaches was evaluated by the metrics of mean intersection over union (mIOU), dice similarity coefficient (DSC), precision, and recall. Reliability and reproducibility of radiomics features were evaluated by the Pearson coefficient and the intraclass correlation coefficient (ICC).ResultsAll seven CNN-based models achieved good performance with the mIOU, DSC, precision and recall ranging between 81.97%-93.04%, 78.67%-92.70%, 93.92%-97.56%, and 85.29%-95.17%, respectively. The average Pearson coefficients ranged from 0.81 to 0.95, and the average ICCs ranged from 0.77 to 0.92. The UNet++ model showed the best performance with the mIOU, DSC, precision and recall of 93.04%, 92.70%, 97.43% and 95.17%, respectively. For ccRCC, AML and other subtypes, the reliability and reproducibility of radiomic analysis derived from automatically segmented CEUS images were excellent, with the average Pearson coefficients of 0.95, 0.96 and 0.96, and the average ICCs for different subtypes were 0.91, 0.93 and 0.94, respectively.ConclusionThis retrospective single-center study showed that the CNN-based models had good performance on automatic segmentation of CEUS images for renal tumors, especially the UNet++ model. The radiomics features extracted from automatically segmented CEUS images were feasible and reliable, and further validation by multi-center research is necessary.

Low modulus materials that can change shape in response to external stimuli are promising for a wide range of applications. The authors here introduce a shape-reprogrammable construct, based on liquid metal microfluidic networks and electromagnetic actuation, that supports a unique collection of capabilities.