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Abstract Overexpression of mitotic arrest deficiency 2 (MAD2/MAD2L1), a pivotal component of the spindle assembly checkpoint (SAC), resulted in many types of cancer. Here we show that the depletion of tumor susceptibility gene 101 (TSG101), causes synthetic dosage lethality (SDL) in MAD2-overexpressing cells, and we term this cell death MAD2-overexpressing interphase cell death (MOID). The induction of MOID depends on PML and DAXX mediating mitochondrial AIFM1-release. MAD2, TSG101, and AIF-PML-DAXX axis regulate mitochondria, PML nuclear bodies (NBs), and autophagy with close inter-dependent protein stability in survival cells. Loss of C-terminal phosphorylation(s) of TSG101 and closed (C-)MAD2-overexpression contribute to induce MOID. In survival cells, both MAD2 and TSG101 localize at PML NBs in interphase, and TSG101 Y390 phosphorylation is required for localization of TSG101 to PML NBs. PML release from PML NBs through PML deSUMOylation contributes to induce MOID. The post-transcriptional/translational cell death machinery and the non-canonical transcriptional regulation are intricately linked to MOID, and ER-MAM, may serve as a crucial intersection for MOID signaling.

Abstract Background Diabetic retinopathy (DR), a prevalent complication in patients with type 2 diabetes, has attracted increasing attention. Recent studies have explored a plausible association between retinopathy and significant liver fibrosis. The aim of this investigation was to develop a sophisticated machine learning (ML) model, leveraging comprehensive clinical datasets, to forecast the likelihood of significant liver fibrosis in patients with retinopathy and to interpret the ML model by applying the SHapley Additive exPlanations (SHAP) method. Methods This inquiry was based on data from the National Health and Nutrition Examination Survey 2005–2008 cohort. Utilizing the Fibrosis-4 index (FIB-4), liver fibrosis was stratified across a spectrum of grades (F0-F4). The severity of retinopathy was determined using retinal imaging and segmented into four discrete gradations. A ten-fold cross-validation approach was used to gauge the propensity towards liver fibrosis. Eight ML methodologies were used: Extreme Gradient Boosting, Random Forest, multilayer perceptron, Support Vector Machines, Logistic Regression (LR), Plain Bayes, Decision Tree, and k-nearest neighbors. The efficacy of these models was gauged using metrics, such as the area under the curve (AUC). The SHAP method was deployed to unravel the intricacies of feature importance and explicate the inner workings of the ML model. Results The analysis included 5,364 participants, of whom 2,116 (39.45%) exhibited notable liver fibrosis. Following random allocation, 3,754 individuals were assigned to the training set and 1,610 were allocated to the validation cohort. Nine variables were curated for integration into the ML model. Among the eight ML models scrutinized, the LR model attained zenith in both AUC (0.867, 95% CI: 0.855–0.878) and F1 score (0.749, 95% CI: 0.732–0.767). In internal validation, this model sustained its superiority, with an AUC of 0.850 and an F1 score of 0.736, surpassing all other ML models. The SHAP methodology unveils the foremost factors through importance ranking. Conclusion Sophisticated ML models were crafted using clinical data to discern the propensity for significant liver fibrosis in patients with retinopathy and to intervene early. Practice implications Improved early detection of liver fibrosis risk in retinopathy patients enhances clinical intervention outcomes.

Abstract Hypertrophic scars arise from aberrant wound healing and can lead to functional and aesthetic impairments. One of the common interventions for treating hypertrophic scars is fractional carbon dioxide (CO2) laser, which employs narrow laser beams to stimulate dermal collagen deposition. Recent studies and reports have suggested that combining laser therapy with other interventions such as botulinum toxin type A (BTX-A) and topical growth factors may enhance treatment outcomes. Here, we examine the efficacy and safety of a sequential combination of BTX-A, fractional CO2 laser, and topical growth factors, referred to as combined therapy, for treating hypertrophic scars compared with only using fractional CO2 laser and topical growth factors, referred to as monotherapy. Our retrospective study includes 128 patients with hypertrophic scars (56 underwent monotherapy and 72 underwent combined therapy), which were followed-up for up to 15 months after the initiation of treatment to collect demographic and clinical data. Our analysis showed that the combined therapy significantly outperformed monotherapy in improving Vancouver scar scale scores (P

Abstract The fiber index including fiber length, width, wall thickness and lumen diameter of Ferrocalamus strictus culms (1, 2, and ≥ 3 years) from Jinping, Mojiang and Lvchun counties of Yunnan Province was determined and the elemental content of the soil was also determined to analyze the fiber characteristics. The average relative fiber index measured for F. strictus culms were fiber length (1.30 mm), width (21.57 μm), slenderness ratio (60.79 μm), wall thickness (4.21 μm), lumen diameter (7.22 μm), and runkel ratio (1.22 μm), which belonged to the range of middle and long fibers. The fiber length increased with the culm age. The proportion of long fiber increased while short fibers decreased along with culm maturing. The fiber morphology did not show a specific trend with the culm height. Fiber length reached the maximum in the bottom portions of the culms. There is a correlation between fiber morphology and soil elements, the content of organic matter, total potassium, total sulfur, total aluminum, total zinc, total iron, total boron, alkali-hydrolyzed nitrogen and available silicon in the soil affects fiber morphology. The content of organic matter, total boron and alkali-hydrolyzed nitrogen in the soil from Mojiang County was largest. Comparatively, the culm fiber in Mojiang County had the best fiber index performance for utilization, since the greatest proportion of medium and long fibers and the optimal distribution of fiber length frequency was obtained from the culms in Mojiang County. This study can provide a theoretical basis for large-scale bamboo forest cultivation and the development and utilization of bamboo culm fiber.

Abstract The minimum velocity (v) for impact ejecta to form secondary craters (secondaries) remains enigmatic, but it is a crucial parameter in untangling the fate of impact ejecta on planetary surfaces. By cataloging the distances (L) of the nearest secondaries from centers of various-sized (D) primary craters (primaries) on the Moon, Mars and Mercury, we find that v can be as small as ~25 m/s, and an unified power-law relationship of L = 1.86D 0.93 (both in meters) works for both simple and complex craters, regardless of different surface gravity and target properties. This relationship also successfully predicts occurrences of secondaries formed by craters on Venus. The constraint on v explains the common concurrences of structural disturbances in crater walls and continuous ejecta deposits caused by landing of cogenetic ejecta, suggesting that ejecta forming self-secondaries do not need near-vertical ejection angles and tertiary craters should be abundant on terrestrial bodies.

Abstract Background Cryptosporidium spp. are important zoonotic parasites that can cause moderate to severe diarrhea in humans and animals. Among the three Cryptosporidium species infecting the intestines of calves, Cryptosporidium parvum has a broad host range and causes severe diarrhea in calves, while Cryptosporidium bovis and Cryptosporidium ryanae mainly infect calves without obvious clinical symptoms. Comparative genomic analysis revealed differences in the copy number of genes encoding the nonfinancial disclosure quality (NFDQ) secretory protein family among the three species, suggesting that this protein family may be associated with the host range or pathogenicity of Cryptosporidium spp. To understand the function of cgd8_10 encoded NFDQ1, tagged and knockout strains were constructed and characterized in this study. Methods To determine the localization of NFDQ1, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to tag the C-terminus of NFDQ1 with three hemagglutinin epitopes (3 × HA). The tagged strain was constructed, and the genomic insertion was confirmed by polymerase chain reaction (PCR). Immunofluorescence assays were performed to observe the localization of NFDQ1 both in extracellular sporozoites and at various intracellular developmental stages. Immunoelectron microscopy was used to study the ultrastructural localization of NFDQ1. Then, the ΔNFDQ1 strain was generated by CRISPR/Cas9 and the in vitro growth assay on HCT-8 cells was used to analyze of phenotypic changes after knockout NFDQ1 in parasites. Results The NFDQ1 tagging and knockout stains were successfully constructed by CRISPR/Cas9 technology and the insertions of transgenic strains were validated by PCR. The expression of NFDQ1 was validated in parasite by western blot. Immunofluorescence and immune-electron microscopy assay showed that NFDQ1 expressed in both asexual and sexual stages of C. parvum, where it was localized to the cytoplasm of the parasite. Upon ablation of NFDQ1, the ΔNFDQ1 strain showed an apparent growth retardation during sexual replication in vitro. Conclusions NFDQ1 is a cytoplasmic protein without specific localization to secretory organelles, and it may participate in C. parvum growth during sexual reproduction. Future study should determine the role of NFDQ1 following C. parvum infection in vivo. Graphical Abstract

Abstract Studies have underscored the pivotal role of metastasis-associated protein 3 (MTA3) as a cancer regulator, yet its potential as a drug target across cancers necessitates comprehensive evaluation. In this study, we analyzed MTA3 expression profiles to ascertain its diagnostic and prognostic value in pan-cancers, probing associations with genetic variations and immunological characteristics. Notably, liver hepatocellular carcinoma (LIHC) exhibited the most significant correlation with MTA3. By transfection of siRNA, interference of MTA3 affected HepG2 and Hepa1-6 cell viability and migration. Through drug screening and drug-likeness evaluation among marine-derived natural products, Jaspamycin was identified as a potential hepatocellular carcinoma treatment by targeting MTA3. By applying in vitro and in vivo experiment, the inhibitory effects of Jaspamycin on hepatocellular carcinoma viability, migration, and tumor progression were observed. To assess the potential of MTA3 as an anticancer drug target, MTA3 overexpression plasmid was transfected together with Jaspamycin treatment, and observed that MTA3 upregulation counteracted the inhibitory effects of Jaspamycin on hepatocarcinoma cell proliferation and migration, underscoring the efficacy of MTA3 as a drug target in hepatocellular carcinoma drug screening. This study highlights the clinical significance of MTA3 in pan-cancer, particularly in hepatocellular carcinoma. Additionally, it identifies Jaspamycin, a marine-derived compound with promising pharmacological properties, as an effective inhibitor of MTA3 activity, suggesting its potential for hepatocellular carcinoma treatment.

Abstract Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by a grim prognosis, in which various forms of cell death are significant contributors to its development. The objective of this study is to explore diagnostic biomarkers and molecular subtypes associated with PANoptosis in IPF, and to develop reliable diagnostic models based on PANoptosis-related mechanisms. The peripheral blood transcriptomic data of IPF from the Gene Expression Omnibus (GEO) database and PANoptosis-related genes from the GeneCards database were utilized to conduct differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), identifying PANoptosis-related differentially expressed genes (PDEGs). We yielded 9 PDEGs and employed machine learning algorithms to identify 3 key diagnostic biomarkers for PANoptosis in IPF: MMP9, FCMR, NIBAN3. Consensus clustering algorithm was applied to recognize two PANoptosis-related subtypes. Cluster 1 exhibited higher abundance of adaptive immune response cells and significant enrichment in DNA damage and repair-related pathways. Cluster 2 exhibited greater prevalence of innate immune response cells and predominant enhancement in pathways related to lipid cholesterol metabolism and vascular remodeling. Diagnostic models were developed with the aid of clinical decision-making and a novel approach to the diagnosis and treatment for IPF.

Abstract Introduction Several risk scores have been proposed to predict venous thromboembolism (VTE) in hospitalized patients. However, their predictive performances in lung cancer patients receiving immune checkpoint inhibitors (ICIs) is unclear. We aimed to validate and compare their performances of the Caprini, Padua and Khorana risk scores in lung cancer patients receiving ICIs. Methods This was a retrospective cohort study of patients with lung cancer treated with ICIs at West China Hospital between January 2018 and March 2022. The primary outcome was VTE during 12 months of follow-up from the first day of treatment with ICIs. The predictive performances of risk scores was determined using receiver operating characteristic (ROC) curve analysis. Results Among the 1115 eligible patients with lung cancer who received ICIs, 105 patients (9.4%) experienced VTE during the 12-month follow-up period. There was a statistically significant difference in the cumulative incidence of VTE between the different risk levels as determined by Caprini and Padua scores (all P

Abstract Background Although the imaging manifestations of pulmonary sarcoidosis have been described in detail in previous studies, a consensus has not been reached on the imaging presentation of non-specific interstitial pneumonia (NSIP) lookalike pattern as a distinct pattern in the diagnosis of pulmonary sarcoidosis in high-resolution computed tomography (HRCT). No cases of pulmonary sarcoidosis comorbid with NSIP have been reported. Case presentation A 53-year-old male presented to the hospital with a five-year history of recurrent coughing up sputum and a four-year history of shortness of breath. In addition to the typical features of pulmonary sarcoidosis, the patient’s HRCT also showed unexpected interstitial changes in the lower lobes of both lungs, suggesting an NSIP pattern. Histopathology of the lung tissue in this region confirmed well-formed noncaseating epithelioid granulomas and pathological modifications of NSIP. After a rigorous exclusion diagnosis combining the patient’s clinical features, radiological and pathological findings, we diagnosed this patient with pulmonary sarcoidosis comorbid with NSIP. Conclusions This suggests that NSIP may act as a rare comorbidity of pulmonary sarcoidosis thereby resulting in the patient’s HRCT presenting differently from routine sarcoidosis imaging.

Abstract Lung cancer is one of the most common types of malignant cancer worldwide, causing a serious social and economic burden. It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for 80–85% of cases. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in NSCLC, playing an important role in regulating tumor growth, angiogenesis, malignant transformation, and phagocytosis. Ubiquitin-specific protease 10 (USP10) functions as a deubiquitinating enzyme to regulate substrate protein deubiquitination and reverse the ubiquitin proteasome degradation pathway. Our previous study identified an interaction between EIF4G1 and USP10; however, their regulatory mechanism remains unclear. Herein, we found that USP10 positively regulates EIF4G1 in NSCLC cells. An in vivo ubiquitination assay demonstrated deubiquitination of EIF4G1 by USP10, which reversed the ubiquitin proteasomal degradation of EIF4G1, thereby increasing its stability. Upregulation of EIF4G1 promoted cell proliferation, migration, and invasion in NSCLC cells. The current study not only reveals a novel mechanism through which USP10 positively regulates EIF4G1 in NSCLC, but also demonstrates the potential of USP10 as a therapeutic target to treat NSCLC.

The medicine field continues to encounter obstacles in understanding the etiology of skin inflammation and the process of skin wound repair. Developing sustainable and effective three-dimensional (3D) skin models for investigating inflammatory skin biology remains a challenge. By incorporating halloysite nanotubes (HNT) into a composite collagen/alginate/hyaluronic acid hydrogel, we created a novel 3D skin model and introduced keratinocytes and fibroblast cells into it. We demonstrate that the modified 3D skin model is capable of enhancing the differentiation and adhesion behaviors of keratinocytes and fibroblast cells in vitro and promoting wound healing in vivo. These characteristics highlight the potential of this approach for the study of skin inflammation, wound healing, regeneration, aging, and beyond.

Abstract Background Walnut is an oilseed tree species and an ecologically important woody tree species that is rich in oil and nutrients. In light of differences in the lipid content, fatty acid composition and key genes expression patterns in different walnut varieties, the key gene regulatory networks for lipid biosynthesis in different varieties of walnuts were intensively investigated. Results The kernels of two walnut varieties, ‘Xilin 3’ (X3) and ‘Xiangling’ (XL) were sampled at 60, 90, and 120 days post-anthesis (DPA) to construct 18 cDNA libraries, and the candidate genes related to oil synthesis were identified via sequencing and expression analysis. A total of 106 differentially expressed genes associated with fatty acid biosynthesis, fatty acid elongation, unsaturated fatty acid biosynthesis, triglyceride assembly, and oil body storage were selected from the transcriptomes. Weighted gene co-expression network analysis (WGCNA), correlation analysis and quantitative validation confirmed the key role of the FAD3 (109002248) gene in lipid synthesis in different varieties. Conclusions These results provide valuable resources for future investigations and new insights into genes related to oil accumulation and lipid metabolism in walnut seed kernels. The findings will also aid future molecular studies and ongoing efforts to genetically improve walnut.

Abstract Background The dimerizable Cre recombinase system (DiCre) exhibits increased leaky activity in Cryptosporidium, leading to unintended gene editing in the absence of induction. Therefore, optimization of the current DiCre technique is necessary for functional studies of essential Cryptosporidium genes. Methods Based on the results of transcriptomic analysis of Cryptosporidium parvum stages, seven promoters with different transcriptional capabilities were screened to drive the expression of Cre fragments (FKBP-Cre59 and FRB-Cre60). Transient transfection was performed to assess the effect of promoter strength on leakage activity. In vitro and in vivo experiments were performed to evaluate the leaky activity and cleavage efficiency of the optimized DiCre system by polymerase chain reaction (PCR), nanoluciferase, and fluorescence analyses. Results The use of promoters with lower transcriptional activity, such as pcgd6_4110 and pcgd3_260, as opposed to strong promoters such as pActin, pα-Tubulin, and pEnolase, reduced the leakage rate of the system from 35–75% to nearly undetectable levels, as verified by transient transfection. Subsequent in vitro and in vivo experiments using stable lines further demonstrated that the optimized DiCre system had no detectable leaky activity. The system achieved 71% cleavage efficiency in vitro. In mice, a single dose of the inducer resulted in a 10% conditional gene knockout and fluorescent protein expression in oocysts. These fluorescently tagged transgenic oocysts could be enriched by flow sorting for further infection studies. Conclusions A DiCre conditional gene knockout system for Cryptosporidium with good cleavage efficiency and reduced leaky activity has been successfully established. Graphical Abstract

Abstract Backgrounds Currently, family with sequence similarity 65 member A (FAM65A) is reported as a pivotal regulator in various cancers. However, the effect of FAM65A in lung squamous cell carcinoma (LSCC) is still unclear, the prime objective of this research is to explore the role of FAM65A in LSCC. Methods Gene expression data and correlated clinical information were downloaded from the public database and the expression of FAM65A was detected. The expression of FAM65A was also detected in our collected clinical samples and LSCC cell lines. Survival package of R language was used to determine the survival significance of FAM65A. Proteins expression level was determined via western blot assay. Cell function experiments and in vivo experiments were performed to explore the effect of FAM65A on LSCC cell biological behaviors. Results FAM65A expression was significantly increased in LSCC clinical samples and cell lines. High FAM65A expression predicted poor prognosis in LSCC patients. After silencing FAM65A, the ability of LSCC cell proliferation, invasion and migration was decreased, and LSCC cell cycle was blocked. Moreover, in vivo experiments revealed that silencing FAM65A could inhibit LSCC cell proliferation. Conclusions High FAM65A expression could enhance proliferative, invasive and migratory abilities of LSCC. FAM65A might be a novel biomarker of LSCC.

Abstract With the continuous advancement of virtualization technology and the widespread adoption of 5G networks, the application of the Network Function Virtualization (NFV) architecture has become increasingly popular and prevalent. While the NFV architecture brings a lot of advantages, it also introduces security challenges, including the effective and efficient verification of the integrity of deployed Virtual Network Functions (VNFs) and ensuring the secure operation of VNFs. To address the challenge of efficiently conducting virtual remote attestation for VNFs and establishing trust in virtualized environments like NFV architecture, we propose TVRAVNF, which is a highly efficient and low-cost TEE-based virtual remote attestation scheme for VNFs. The scheme we proposed ensures the security and effectiveness of the virtual remote attestation process by leveraging TEE. Furthermore, we introduces a novel local attestation mechanism, which not only reduces the overall overhead of the virtual remote attestation process but also shortens the attestation interval to mitigate Time-Of-Check-Time-Of-Use attacks, thereby enhancing overall security. We conduct experiments to validate the overhead of the TVRAVNF scheme and compare its performance with that of a typical remote attestation process within a maximum unattested time interval. The experimental results demonstrate that, by employing the local attestation mechanism, our solution achieves nearly an 80% significant performance improvement with a relatively small time overhead for small to medium-sized files. This further substantiates the significant advantages of our approach in both security and efficiency.

Abstract Background Acute exacerbation (AE) of interstitial lung disease (ILD) is one of the most serious complications during perioperative period of lung cancer resection. This study aimed to investigate the correlation between preoperative 2- deoxy-2-[18F]fluoro-D-glucose (18F-FDG) PET/CT findings and AE in lung cancer patients with ILD. Methods We retrospectively reviewed the data of 210 patients who underwent lung resection for non-small cell lung cancer. Relationships between clinical data and PET images and AE were evaluated. The patients were divided into an AE(+) and an AE(-) group for multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was conducted and the area under curve (AUC) was used to assess the predictive values. Results Among 210 patients, 48 (22.8%) were diagnosed with ILD based on chest CT. Among them, 9 patients (18.75%) developed AE after lung resection and were defined as AE(+) group. The course of ILD was longer in AE(+) group compared to AE(-) group. More patients in AE(+) group had a history of AE and chronic obstructive pulmonary disease (COPD) than in AE(-) group. The maximum standardized uptake value (SUVmax) of the noncancerous interstitial pneumonia (IP) area and cancers in AE(+) group was significantly higher compared to AE(-) group. Univariate logistic regression analysis showed that AE, COPD, SUVmax of the noncancerous IP area, SUVmax of cancer, surgical method were significantly correlated with AE. The course of ILD[OR(95%CI) 2.919; P = 0.032], SUVmax of the noncancerous IP area[OR(95%CI) 7.630;P = 0.012] and D-Dimer level[OR(95%CI) 38.39;P = 0.041] were identified as independent predictors for AE in patients with ILD after lung cancer surgery. When the three indicators were combined, we found significantly better predictive performance for postoperative AE than that of SUVmax of the noncancerous IP area alone [0.963 (95% CI 0.914-1.00); sensitivity, 100%, specificity 87.2%, P

Abstract Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.

To explore the differences in the composition, content and comprehensive quality of free amino acids (FAA) in millet from Longzhong area in Gansu Province，12 different cultivars of millet were used as research objects, the types and contents of FAA were determined by liquid chromatography-tandem mass spectrometry. Comprehensive evaluation of FAA quality was performed by principal component analysis (PCA) and hierarchical cluster analysis (HCA). The results showed that 19~20 kinds of FAA were detected in all kinds of millet, and the total content of FAA ranged from 1046.80~1773.85 mg/kg, asparagine (Asn), aspartic acid (Asp), glutamic acid (Glu) and glycine (Gly) were the four main FAA in millet. There were significant differences in the contents of FAA (Pbitter amino acids>sweet amino acids>aromatic amino acids. 9 Medicinal amino acids and 3 branched chain amino acids were found in millet, the average content of medicinal amino acids was 706.34 mg/kg, the percentages of medicinal amino acids to total FAA was 53.63%, so millet had many potential medicinal values. There was a significant relation with FAA in different cultivars of millet, five principal components were extracted after PCA, and the cumulative contribution ratio of the five components was 86.20%, the FAA comprehensive scores of LG-23、LG-11 and YG-18 were ranked as the top three. The 12 different cultivars millet were divided into four groups by HCA, FAA comprehensive quality performances of groups Ⅰ (LG-23) and Ⅲ (LG-11 and YG-18) were optimal, the content of total FAA was significantly higher than the other two groups (P

Background B-cell acute lymphoblastic leukaemia (B-ALL) and T-cell acute lymphoblastic leukaemia (T-ALL) are both types of acute lymphoblastic leukaemia (ALL), which is a cancer of the blood and bone marrow characterized by the rapid proliferation of immature lymphocytes. In ALL, CDKN gene deletions have been extensively studied regarding their prognostic significance. The purpose of this meta-analysis is to determine whether there is a consistent relationship between CDKN gene variations and the incidence of lymphocytic leukaemia.Materials and methods The following databases contain relevant studies published between inception and 25 October 2023: PubMed, EMBASE, the Cochrane library and Web of Science were comprehensively searched. Based on the random-effects or fixed-effects model, the hazard ratio (HR) and its 95% confidence interval (95% CI) were pooled. A subgroup analysis and sensitivity analysis were also conducted. We estimated publication bias using a funnel plot.Results This meta-analysis included 19 studies containing 1333 patients. Among included studies, 12 studies only reported B-ALL, four studies included patients with T-ALL and B-ALL, and three studies reported T-ALL. A deletion of the CDKN gene was found to be an adverse indicator of both EFS (HR = 1.83, 95% CI: 1.03–2.62), DFS (HR = 1.49, 95% CI 1.23–1.77), RFS (HR = 1.34, 95% CI 0.96–1.73) and OS (HR = 1.39, 95% CI 1.19–1.58). Single-arm emphasized the greater influence on OS. The subgroup analysis based on the CDKN2A, CDKN2A/b and different ALL subtypes further strengthen the validity of the findings.Conclusions Our meta-analysis revealed that CDKN gene deletions (including CDKN 2A/B, CDKN 2A) serve as adverse prognostic indicators for T-ALL/B-ALL patients.

Rapid decline in Arctic summer sea ice cover has brought new opportunities for shipping and resource exploitation in the Arctic, and accurate determination of summer sea ice conditions has become increasingly important. Knowledge of sea ice velocity (SIV) is crucial for ice engineering and navigation in the Arctic. This study retrieved SIV in summer based on the polarization difference (PD) of brightness temperatures (TBs) at 36 GHz derived from the recalibrated FY-3D satellite microwave radiometer data FY-3D/MWRI. Compared with swath TB data, swath PD data can better suppress the noise associated with atmospheric wetness (cloud liquid water and water vapor). Moreover, different from the arbitrary template selection scheme used in current algorithms, we propose an optimized template selection scheme based on the image texture, which considers the frequent deformation processes of sea ice in summer. Determination of SIV using templates with irregular distribution presents lower uncertainty and higher computational efficiency compared with templates with regular distribution. Based on the improved algorithm, this study obtained either swath irregular SIV fields with nominal spatial resolution of 30 km or daily gridded SIV fields with 50-km spatial resolution in summer 2019 using 36-GHz PDs.

ABSTRACTEmerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.

AbstractCombined chemical-biological methods play an important role in ecological restoration. However, it is still unknown whether the addition of calcium peroxide (CaO2) can promote the growth of Pontederia cordata (P. cordata) and the improvement of water quality. Effects of different levels of added CaO2 (0, 0.2, 0.4, 0.6, 0.8, 1, and 2 kg/m2) on P. Cordata growth and water quality were investigated. CaO2 promoted germination and tillering and increased the leaf number (p

AbstractThe primary objective of this paper is to delve into the underlying driving forces behind changes in the ecological environment. To achieve this, the paper not only analyzes the multifaceted social, economic, and natural aspects of the composite ecosystem but also develops an ecological environment change evaluation model employing the topological hierarchy-entropy weight method. This model serves as a valuable tool for assessing trends and determining the drivers of ecological change. As a case study, the paper focuses on Gaoqiao Town, located in Yan’an City, Shaanxi Province. It involves a meticulous process of processing multi-year remote sensing images of the study area,as well as image cropping to extract and decode natural index data. Additionally, the paper utilizes social and economic data alongside survey data from annual reports published by local governments within the study area. These datasets are then subjected to the proposed model to evaluate ecological changes in the region. The results show that the modelling approach introduced in this paper effectively captures the ecological changes and their underlying causes in the selected areas, and can provide valuable references for government departments to formulate wise ecological environmental protection and management policies.

Abstract Triple negative breast cancer (TNBC) is the most aggressive subtype in breast tumors. When re‐analyzing TCGA breast cancer dataset, we found cell adhesion molecules are highly enriched in differentially expressed genes in TNBC samples, among which Focal Adhesion Kinase (FAK) is most significantly associated with poor survival of TNBC patients. FAK is precisely modulated in the focal adhesion dynamics. To investigate whether lncRNAs regulate FAK signaling, we performed RNA immunoprecipitation sequencing and found FAISL (FAK Interacting and Stabilizing LncRNA) abundantly enriched in FAK‐interacting lncRNAs and frequently overexpressed in TCGA TNBC tissues. FAISL promotes TNBC cell adhesion, cytoskeleton spreading, proliferation, and anchor‐independent survival. FAISL doesn't affect FAK mRNA but positively regulates FAK protein level by blocking Calpain 2‐mediated proteolysis. FAISL interacts with the C‐terminus domain of FAK, whereby masks the binding site of Calpain 2 and prevents FAK cleavage. High level of FAISL correlates with FAK expression in tumor tissues and poor prognosis of TNBC patients. A siRNA delivery system targeting FAISL using reduction‐responsive nanoparticles effectively inhibits tumor growth and metastasis in TNBC mouse models. Together, these findings uncover a lncRNA‐mediated mechanism of regulating FAK proteolysis in the TNBC progression, and highlight the potential of targeting lncRNA FAISL for TNBC treatment.

PurposeThis study aimed to compare postoperative gastrointestinal symptoms between patients who underwent laparoscopic distal gastrectomy with Roux-en-Y (R-Y) and Billroth-II with Braun (B-II B) reconstruction.MethodsThis observational study retrospectively analyzed 151 patients (110 in R-Y group and 41 in B-II B group) who underwent laparoscopic distal gastrectomy from January 2020 to December 2021. A comparison was made regarding surgical outcomes, perioperative nutritional and inflammatory markers, postoperative dietary patterns, and gastrointestinal symptoms between the two groups.ResultsThe operation time was longer in the R-Y group than the B-II B group (261.00 ± 56.17 min versus 239.88 ± 57.78 min, p = 0.046). However, there were no significant differences in the length of hospital stay, ASA classification, complications, nutritional and inflammatory indexes, or recovery of postoperative diet between the two groups. Additionally, there were no significant differences in the occurrence of postoperative gastrointestinal symptoms in the post-discharge week (PDW) 1 and postoperative month (POM) 1 between the B-II B and R-Y groups.ConclusionsAbdominal distention emerged as the main gastrointestinal symptom burden in patients with gastric cancer undergoing laparoscopic distal gastrectomy. Both Billroth-II with Braun and R-Y reconstructions exhibited a high and similar incidence of gastrointestinal symptoms in the short term. Therefore, medical staff should pay attention to the management of gastrointestinal symptoms in these patients postoperatively.

PurposeThe infiltration of immune cells and their roles of the infiltrating-immune cells in gastrointestinal stromal tumor (GIST) is still unclear. We aimed to discover the infiltration cell types and the relationship between the infiltrating-immune cells and the progression of GIST.Experimental designSingle-cell RNA sequencing were performed to discover types of the infiltrating-immune cells and to analyze CellChat between cells. Immunohistochemistry of 80 GIST samples were used to clarify the relation between macrophages and recurrence risk. In vitro, flow cytometry and Real-time PCR were performed to uncover a potential mechanism of tumor cell regulation of macrophages.ResultsTumor cells, macrophages, and T-cells were the predominant cell types. The MIF/CXCR4 axis was the most common ligand–receptor interaction between macrophages and tumor cells. As the risk increased, expression levels of CD68, CD206, MIF, and CXCR4 gradually increased. In vitro, we found that GIST882 was able to secrete MIF and GIST882 cell supernatant upregulated M2 polarization. Real-time PCR showed that expression levels of IL-10 mRNA and Arginase-1 mRNA were also the highest in the GIST882 cell supernatant group.ConclusionsThese findings identify that macrophages are the most abundant infiltrating cells in GIST. The MIF/CXCR4 axis is the most common ligand–receptor interaction between macrophages and tumor cells. GIST cells can regulate macrophage M2 polarization through the MIF/CXCR4 axis.

Selenium (Se) deficiency is associated with the development of Keshan disease, a cardiomyopathy associated with massive cardiac immune cell infiltration that can lead to heart failure (HF). The purpose of this study was to determine whether high Se diet can attenuate systolic overload-induced cardiopulmonary inflammation and HF. Briefly, transverse aortic constriction (TAC)-induced cardiopulmonary oxidative stress, inflammation, left ventricular (LV) dysfunction, and pulmonary remodeling were determined in male mice fed with either high Se diet or normal Se diet. High Se diet had no detectable effect on LV structure and function in mice under control conditions, but high Se diet significantly protected mice from TAC-induced LV hypertrophy, dysfunction, increase of lung weight, and right ventricular hypertrophy. As compared with mice treated with normal Se diet, high Se diet also reduced TAC-induced LV cardiomyocyte hypertrophy, fibrosis, leukocyte infiltration, pulmonary inflammation, pulmonary fibrosis, and pulmonary micro-vessel muscularization. In addition, high Se diet significantly ameliorated TAC-induced accumulation and activation of pulmonary F4/80+ macrophages, and activation of dendritic cells. Interestingly, high Se diet also significantly attenuated TAC-induced activation of pulmonary CD4+ and CD8+ T cells. Moreover, we found that TAC caused a significant increase in cardiac and pulmonary ROS production, increases of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), as well as a compensatory increases of LV glutathione peroxidase 1 (GPX1) and 4 (GPX4) in mice fed with normal Se diet. Above changes were diminished in mice fed with high Se diet. Collectively, these data demonstrated that high Se diet significantly attenuated systolic pressure overload-induced cardiac oxidative stress, inflammation, HF development, and consequent pulmonary inflammation and remodeling.

The forging stage of rail flash welding has a decisive influence on joint strength, and the study of the temperature distribution in the process has an important role in further improving joint strength. In this paper, three calculation methods for the temperature field are given. First, the finite element model of the temperature field before forging rail flash welding is established by using the transient heat module of Ansys software and verified by infrared temperature measurement. Second, the temperature distribution of different parts of the rail before flash welding is obtained by using infrared thermal imaging equipment. Third, Matlab software is used to calculate the temperature of the non-measured part. Finally, the temperature distribution function along the rail axis is fitted through the temperature measurement data. The temperature distribution before the top forging of the rail flash welding can be used to analyze the joint and heat-affected zone organization and properties effectively and to guide the parameter setting and industrial production.

Abstract Numerous clinical studies speculated the association between multiple myeloma (MM) and inflammatory diseases; however, there is limited validation of these claims via establishing a causal relationship and revealing the underlying mechanism. This exploratory study employed bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between MM and inflammatory diseases, including atherosclerosis, asthma, ankylosing spondylitis, Alzheimer's disease (AD), Parkinson's disease (PD), sarcoidosis, inflammatory bowel disease, nonalcoholic fatty liver disease, type II diabetes, and schizophrenia (SZ). Transcriptomic and genome‐wide Bayesian colocalization analyses were further applied to reveal the underlying mechanism. A significant and previously unrecognized positive association was identified between genetic predisposition to MM and the risk of SZ. Two independent case reports showed that treatment‐resistant psychosis is due to underlying MM and is resolved by treating MM. From our MR analyses, various statistical methods confirmed this association without detecting heterogeneity or pleiotropy effects. Transcriptomic analysis revealed shared inflammation‐relevant pathways in MM and SZ patients, suggesting inflammation as a potential pathophysiological mediator of MM's causal effect on SZ. Bayesian colocalization analysis identified rs9273086, which maps to the protein‐coding region of HLA‐DRB1, as a common risk variant for both MM and SZ. Polymorphism of the HLA‐DRB1 allele has been implicated in AD and PD, further highlighting the impact of our results. Additionally, we confirmed that interleukin‐6 (IL‐6) is a risk factor for SZ through secondary MR, reinforcing the role of neuroinflammation in SZ etiology. Overall, our findings showed that genetic predisposition to MM, HLA‐DRB1 polymorphism, and enhanced IL‐6 signaling are associated with the increased risk of SZ, providing evidence for a causal role for neuroinflammation in SZ etiology.

Abstract Background Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women’s ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery. Methods We retrospectively analysed data from patients aged 20–40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease. Results With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of ‘exclusive breastfeeding’ was 5.1 months, and the mean duration of ‘any breastfeeding’ was 8.8 months. The rate of ‘ever breastfeeding’ is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery. Conclusions There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.

Although characterized by high reactive oxygen species (ROS) generation, cancer cells maintain redox homeostasis to avoid severe damage (e.g., DNA, protein, and plasma membrane dysfunction) and facilitate cancer progression. Emerging evidence has indicated that targeting the regulation of redox homeostasis to amplify oxidative stress is of value in cancer therapy. However, therapeutic agents like nucleic acids, small molecular inhibitors, and chemotherapeutic drugs fail to exert effective cancer inhibition due to their low bioavailability, susceptibility to serum enzymes, and inefficiency in cell membrane penetrating. Therefore, specific delivery vectors are required to facilitate the intracellular delivery of anti-tumor drugs. In the past few decades, various engineered nanomaterials have been designed and developed for drug delivery. In particular, rational nanoparticles (NPs) have garnered more attention due to their splendid long circulation ability, modification capacity, and stimulation-responded release. In this review, the methods of ROS generation and ROS-regulated signaling in cancer development were firstly briefly introduced. The anti-oxidant system, including the metabolism shifting and anti-oxidant genes, were next reviewed, and the strategies of NPs-mediated targeted regulation of redox homeostasis were emphatically discussed. The main strategies include NPs-induced delivery of nucleic acids, small molecule inhibitors, chemotherapeutic agents, radiosensitizers, and NPs-induced ROS generation and GSH depletion. The future development of NP-mediated redox dyshomeostasis in cancer therapy and their challenges in clinical translation were finally discussed.

Oxide particles with suitable size can refine the microstructure and improve the strength and toughness of steel. In this study, the particles containing Al2O3 were successfully introduced into H13 steel by vacuum casting. The micro-sized Al2O3-containg particles were randomly distributed in the dendritic structure and their number was increased by almost a factor of one. The secondary dendritic arm spacing of the ingot was decreased, which might be attributed to the heterogeneous nucleation of these oxides during solidification. Meanwhile, the alloying element segregation of the ingot was also alleviated. The micro-sized primary carbides were refined as the oxide particles were introduced to H13 steel, especially for V-rich carbides. After hot rolling and heat treatment, the size of austenitic grain was reduced by up to 75% (7.2 ± 1.8 μm), which was due to the particle stimulated nucleation and Zener pinning of micro- and nanoscale oxides in the oxide-added steel. The mechanical properties were obviously modified with the ultimate tensile strength of 1835 MPa, yield strength of 1479 MPa, tensile elongation of 13.4% and impact toughness of 24 J/cm2 after the introduction of oxide particles. It is expected that the introduction of oxide particles by vacuum casting can be applied widely in other die steel for superior performance.

Abstract Molecular computing is an emerging paradigm that plays an essential role in data storage, bio-computation, and clinical diagnosis with the future trends of more efficient computing scheme, higher modularity with scaled-up circuity and stronger tolerance of corrupted inputs in a complex environment. Towards these goals, we construct a spatially localized, DNA integrated circuits-based classifier (DNA IC-CLA) that can perform neuromorphic architecture-based computation at a molecular level for medical diagnosis. The DNA-based classifier employs a two-dimensional DNA origami as the framework and localized processing modules as the in-frame computing core to execute arithmetic operations (e.g. multiplication, addition, subtraction) for efficient linear classification of complex patterns of miRNA inputs. We demonstrate that the DNA IC-CLA enables accurate cancer diagnosis in a faster (about 3 h) and more effective manner in synthetic and clinical samples compared to those of the traditional freely diffusible DNA circuits. We believe that this all-in-one DNA-based classifier can exhibit more applications in biocomputing in cells and medical diagnostics.

Abstract Background Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. Methods We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno‐collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in‐house samples. Additionally, novel therapeutic targets were identified based on these established immuno‐collagenic subtypes. Results Our categorization divided tumors into three subtypes: “soft & hot” (low collagen activity and high immune infiltration), “armored & cold” (high collagen activity and low immune infiltration), and “quiescent” (low collagen activity and immune infiltration). Notably, “soft & hot” tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7‐H3), an available drug target, as strongly expressed in “armored & cold” tumors, relating with poor prognosis. Conclusion This study introduces histopathology‐based universal immuno‐collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Abstract Brain tumour segmentation (BTS) is crucial for diagnosis and treatment planning by delineating tumour boundaries and subregions in multi‐modality bio‐imaging data. Several BTS models have been proposed to address specific technical challenges encountered in this field. However, accurately capturing intricate tumour structures and boundaries remains a difficult task. To overcome this challenge, HAB‐Net, a model that combines the strengths of convolutional neural networks and transformer architectures, is presented. HAB‐Net incorporates a custom‐designed hierarchical and pseudo‐convolutional module called hierarchical asymmetric convolutions (HAC). In the encoder, a coordinate attention is included to extract feature maps. Additionally, swin transformer, which has a self‐attention mechanism, is integrated to effectively capture long‐range relationships. Moreover, the decoder is enhanced with a boundary attention module (BAM) to improve boundary information and overall segmentation performance. Extensive evaluations conducted on the BraTS2018 and BraTS2021 datasets demonstrate significant improvements in segmentation accuracy for tumour regions.

Abstract Background Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. Methods The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration. Results The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro. Conclusions Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.

Abstract Background Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. Methods Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. Results This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. Conclusions Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.

Abstract In the natural world, the human brain is the most powerful information processor, using a highly parallel, efficient, fault‐tolerant, and reconfigurable neural network. Taking inspiration from this impressive architecture, optoelectronic synaptic devices have gained considerable attention for their ability to process and retain data simultaneously, making them essential components in the upcoming era of neuromorphic computing systems. In recent years, significant progress has been made in the development of optoelectronic neuromorphic synaptic devices using two‐dimensional (2D) material heterostructures. This review focuses on the use of 2D materials in creating optoelectronic synaptic devices. It discusses the recent progress made in utilizing 2D material heterostructures in these devices and examines their potential in different areas such as image recognition, neuromorphic wearable electronics, logical operations, and neuromorphic computing systems. Heterostructures made with 2D materials provide a wide range of possibilities as their electronic band structures can be easily tailored to achieve effective optical and electrical modulation. Optoelectronic synaptic devices based on 2D materials simultaneously exhibit two functionalities: detection and memory. Furthermore, these materials have strong interatomic bonding within layers and possess a thickness of only one atomic layer, giving them exceptional flexibility, optical transparency, and mechanical strength. By utilizing 2D materials for solution processing and their ultra‐thin profile, the manufacturing of three‐terminal synapses becomes cost‐effective, simplifying integration processes.

In order to reveal the destructive mechanism of loess landslide induced by stagnant water on the combined surface, and to clarify the influence of the main control factors, this paper takes a typical loess landslide in northern Shaanxi as the research object, analyzes the structure of the rock and soil body, and the excavation and filling construction through the geohazard survey, and analyzes the process of traction sliding caused by the stagnant water on the combined surface at the different stages of the project by combining with the calculation of the stability of the slope body. Further the article analyses the process of traction sliding caused by water on the combined area due to construction by means of a discrete element model, and delves into the mechanism of strength reduction of saturated loess. The results show that: 1) the combined surface stagnant water type loess landslide has the characteristics of sudden sliding and rapid evolution, which is highly hazardous and difficult to prevent and control; 2) the slope destabilization is controlled by the engineering geological conditions, and the slope excavation changes the original mechanical equilibrium conditions of the slope, which provides the dynamic conditions for the traction sliding of the slope; 3) the change of the hydrogeological environment results in the obstruction of the natural drainage channel, which leads to the formation of continuous sliding surface due to stagnant water on the combined surface, and the formation of a continuous sliding surface due to stagnant water on the combined surface. Surface stagnant water to form a continuous slippery surface, inducing the overall destabilization of the slope damage; 4) loess strength index with the increase of saturation and the exponential function form of reduction, and when the saturation degree reaches more than 80%, the strength index of the soil body to reach the basic stability. The article expanding the ideas of landslide control and analysis, and the research results will provide a theoretical basis for the design of junction landslide management in the loess areas of northern Shaanxi.

Background: Lactate is a crucial intermediary, facilitating communication between myocardial energy metabolism and microenvironmental regulation. The present study aimed to investigate the relationship between lactate-related genes (LRGs) and myocardial infarction (MI). Methods: A total of 23 LRGs exhibited differential expression between individuals with MI and healthy controls. Lasso regression analysis and validation with the GSE61144 dataset identified three hub genes: COX20, AGK, and PDHX. Single-gene GSEA of these genes revealed strong enrichment in pathways related to amino acid metabolism, cell cycle, and immune functions. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was utilized to validate the expression levels of the hub genes. Results: Immune infiltration analysis revealed differences in CD4+ T and CD8+ T cells between the MI and control groups. Additionally, 67 candidate drugs targeting the three hub LRGs were identified, and a ceRNA network was constructed to explore the intricate interactions among these genes. Conclusions: These findings enhance the understanding of MI and have potential therapeutic implications.

With the increasing penetration of electric vehicles (EVs) in road traffic, the spatial and temporal stochasticity of the travel pattern and charging demand of EVs as a mode of transportation and an electrical load have generated different degrees of congestion impacts on both the power grid and the transportation network. Based on this, this paper proposes a power–transportation-coupled distribution network optimization strategy based on stochastic user traffic equilibrium theory. First, a stochastic user equilibrium-mixed traffic flow allocation model that expresses user non-completely rational path selection behavior is established, and the traffic flow equilibrium solution is obtained using an improved method of successive algorithm and mapped to charging loads. Second, a distribution network power flow optimization model under the coupled power–transportation architecture is established to optimize the operation state of the distribution network by combining distributed resources such as energy storage, demand response loads, wind power, photovoltaic, and gas turbines.

BackgroundRecent research has indicated a potential association between thyroid function and sarcopenia, but the specific mechanisms and a definitive causal relationship have yet to be established. Therefore, the objective of this study is to examine the potential causal connection between thyroid function and sarcopenia-related traits, including hand-grip strength, appendicular lean mass (ALM), and walking pace.MethodsThe study used a bi-directional two-sample MR design, with thyroid function examined as the exposure and sarcopenia-related traits as the outcome in the first stage, and then reversed in the second stage. The genetic instruments for thyroid function were obtained from a comprehensive meta-analysis involving 271,040 participants. Data on sarcopenia-related traits based on GWASs were collected from the UK Biobank, which includes up to 461,026 European participants. The estimates for MR were calculated using the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed.ResultsAfter applying the Bonferroni correction for multiple testing, our MR analyses revealed no significant impact of thyroid function liability on sarcopenia-related traits. Similarly, our reverse MR analysis did not provide evidence supporting the influence of liability to sarcopenia-related traits on thyroid function. The results of the primary IVW MR analyses were largely in line with those obtained from our sensitivity MR analyses.ConclusionOur research findings do not suggest a link between thyroid function and sarcopenia-related traits. The associations identified in epidemiological studies may be influenced, at least in part, by shared biological mechanisms or environmental confounders.

Background: This study delves into the intricacies of resistant hypertension (RH), a prevalent yet enigmatic chronic cardiovascular ailment that is linked to a myriad of complications. Although its full pathogenesis is still shrouded in mystery, the field of proteomics offers a beacon of hope, with its potential to shed light on the proteins that orchestrate the tapestry of life. Harnessing the power of proteomics is essential for demystifying the pathogenesis of RH, enabling more precise diagnostics and treatments, and ultimately improving prognostic outcomes. Methods: Our approach was to employ rigorous statistical analyses to home in on proteins with significant expression variances between our two cohorts. We complemented this with bioinformatics tools to unravel the intricate functions and pathways of these proteins. By synthesizing these insights with the clinical profiles of our patients, we were able to distill a set of definitive biomarkers with diagnostic potential. In our quest for clarity, we also embarked on a retrospective journey, amassing and scrutinizing clinical data from both RH and hypertension (HTN) patients. We crafted and rigorously assessed risk factor models to evaluate their diagnostic prowess. Results: Our exploration spanned across 30 blood samples from RH patients and 20 from those grappling with HTN. Our inquiry yielded some compelling revelations: (1) RH patients showcased 29 unique proteins, in contrast to the 59 unique proteins found in HTN patients. A deeper dive into the proteomic data unveiled molecular functions predominantly tied to lipid metabolism, protein networking, and oxidative stress, with a spotlight on pathways such as cholesterol metabolism, coagulation, and the complement cascade. (2) By charting receiver operating characteristic curves and rigorously analyzing the proteomic data, we surfaced 11 proteins with notable diagnostic potential, tightly interwoven with clinical metrics. Conclusion: Our research has pinpointed 11 proteins that stand as promising serum biomarkers, endowed with significant diagnostic value. This discovery marks a stride towards a more nuanced understanding and management of resistant hypertension.

Forest canopy height (FCH) is crucial for monitoring forest structure and aboveground biomass. Light detecting and ranging (LiDAR), as a promising remote sensing technology, provides various forms of data for measuring and mapping FCH. Airborne laser scanning (ALS) could accurately measure FCH at the plot-level. Spaceborne lidar system (SLS) allows for global sampling of FCH at the footprint-level. However, ALS data has limited spatial coverage, while SLS data has relatively lower estimation accuracy. To this end, we proposed a two-step FCH mapping framework by combining ALS, SLS and auxiliary data. Firstly, using the ALS-derived FCH as reference, the SLS-derived relative height metrics were calibrated at the footprint-level using a regression method. Secondly, to further address the spatial discontinuities in SLS-derived FCH maps, a site-level FCH model was built using a weighted ensemble multi-machine learning model incorporating spatial effects (WEML_SE). The calibrated footprint-level calibration FCH model was used as a reference, and multiple remote sensing data metrics were selected and subjected to important variable selection. Specifically, a spatial adjacency matrix was established based on the spatial locations of SLS footprints, and spatial feature vectors were extracted. The result indicated that the correlation coefficient between the SLS-derived FCH and the ALS-derived FCH (r = 0.39–0.73, MRE=10.6–25.9 %, and RMSE=2.58–9.37 m) improved at footprint-level (r = 0.71–0.84, MRE=7.7–18.7 %, RMSE=1.96–7.68 m). Moreover, the WEML_SE exhibited better performance (r = 0.59–0.75, MRE=8.8–14.8 %, RMSE=2.12–5.4 m) compared to the model without incorporating spatial effects (r = 0.45–0.71, MRE=9.4–15.8 %, RMSE=2.28–5.89 m). This study emphasizes the advantages of integrating spaceborne and airborne LiDAR data to construct footprint-level estimation of FCH. The proposed WEML_SE model provides new possibilities for accurately generating wall-to-wall estimates of forest biomass.

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs’ regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.

BackgroundRecent epidemiological studies have indicated a correlation between platelet indices and pulmonary arterial hypertension (PAH), yet the causality between them remains unclear. To explore the causal relationship between four platelet indices and PAH, with the aim of providing a theoretical basis for clinical prevention and treatment.MethodsSingle-nucleotide polymorphisms (SNPs) associated with platelet-related traits were selected as exposure factors from published genome-wide association studies (GWAS), including: platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW). Summary-level data for PAH were obtained from the FinnGen study (248 cases and 289,117 controls). Two-sample and multivariable Mendelian randomization (MR) analyses were conducted to assess the causal relationship between exposure factors and the risk of outcomes. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach, supplemented by weighted median, mode-based estimation, MR-Egger regression, and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test to detect and adjust for pleiotropy, ensuring the reliability of the results through sensitivity analysis.Results(1) The IVW results from the two-sample MR analysis showed a positive causal association between PLT and the risk of developing PAH [(OR = 1.649, 95%CI: 1.206–2.256, P = 0.0017)], with the sensitivity analysis confirming the robustness of the causal relationship. The MR-Egger intercept analysis did not detect potential pleiotropy (P = 0.879). (2) The MVMR results showed no statistically significant causal relationship between these four markers and the risk of developing PAH. After adjusting for collinearity, a direct positive causal association was observed between PLT and the risk of developing PAH (OR = 1.525, 95%CI: 1.063–2.189, P = 0.022).ConclusionThe positive correlation between PLT and the risk of PAH suggests that correcting elevated platelet levels may reduce the risk of developing PAH.