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Abstract The formation of human collagen requires the presence of Prolyl 3-hydroxylase 1 (P3H1), but the regulatory mechanism of P3H1 remained insufficiently understood. Our study aimed to identify the role of P3H1 in clear cell renal cell carcinoma (ccRCC). P3H1 expression in ccRCC was validated using multiple databases and in vitro experiments. We performed a correlation analysis of P3H1 with drug sensitivity, immune checkpoints, and immune cell infiltration using transcriptome and single-cell sequencing. Drawing upon the Encyclopedia of RNA Interactomes database, we selected P3H1 as the focal point of our investigation, meticulously uncovering the intricate network of microRNAs and lncRNAs that potentially orchestrate ceRNA mechanisms. This study employs a multidimensional approach integrating vitro assays and multi-omics bioinformatics analyses to investigate P3H1’s impact on ccRCC prognosis, immune modulation, immune checkpoints, ceRNA regulatory network, drug sensitivity, and therapeutic responses, aiming to uncover new insights into its therapeutic potential and inform future clinical strategies.

Abstract Fluorinated or fluoroalkylated alcohols are common structural motifs in biologically active molecules, natural products, and pharmaceuticals. However, pentafluorosulfanyl (SF5) alcohols, a unique class of SF5 compounds that serve as synthetically valuable building blocks, are difficult to prepare with current methodologies. In this article, we present a single-step, metal-free, and photo-induced hydroxypentafluorosulfanylation of styrenes or α,β-unsaturated esters/amide, producing a series of structurally diverse pentafluorosulfanyl alcohols with up to 89% yields. This reaction is mild and operationally simple, using molecular oxygen as the hydroxy source. The protocol is suitable for a wide range of alkenes, including natural products and drug molecule derivatives. The formed SF5 alcohol units can be readily converted into diverse functionalized SF5 compounds, such as α-SF5 ketones, SF5 diols, and SF5 cyclic carbonates. The potential applications of these SF5 compounds in pharmaceutical and material sciences are vast, making this research a step forward in the field.

Abstract Objective The present study aims to investigate the ultrasound and magnetic resonance imaging (MRI) characteristics of kaposiform hemangioen dothelioma (KHE). Methods A retrospective analysis was conducted on the clinical data of children diagnosed with KHE through postoperative pathology. Patients were divided into two groups: the KHE group and the KHE with Kasabach-Merritt Phenomenon (KMP) group (KMP group). Laboratory indicators, ultrasound, and MRI data were collected and analyzed statistically to summarize the imaging characteristics of the disease. Results The levels of platelets and fibrinogen in the KHE group were significantly higher than those in the KMP group, while D-dimer levels, prothrombin time, and activated partial thromboplastin time were lower (P

Abstract During pregnancy the immune system needs to maintain immune tolerance of the foetus while also responding to infection, which can cause premature activation of the inflammatory pathways leading to the onset of labour and preterm birth. The vaginal microbiome is an important modifier of preterm birth risk, with Lactobacillus dominance during pregnancy associated with term delivery while high microbial diversity is associated with an increased risk of preterm birth. Glycans on glycoproteins along the lower female reproductive tract are fundamental to microbiota-host interactions and the mediation of inflammatory responses. However, the specific glycan epitopes involved in these processes are not well understood. To address this, we conducted glycomic analyses of cervicovaginal fluid (CVF) from 36 pregnant women at high risk of preterm birth and 4 non-pregnant women. Our analysis of N- and O-glycans revealed a rich CVF glycome. While O-glycans were shown to be the main carriers of ABO blood group epitopes, the main features of N-glycans were the presence of abundant paucimannose and high mannose glycans, and a remarkable diversity of complex bi-, tri-, and tetra-antennary glycans decorated with fucose and sialic acid. We identified immuno-regulatory epitopes, such as Lewis antigens, and found that fucosylation was negatively correlated to pro-inflammatory factors, such as IL-1β, MMP-8, C3a and C5a, while glycans with only sialylated antennae were mainly positively correlated to those. Similarly, paucimannose glycans showed a positive correlation to pro-inflammatory factors. We revealed a high abundance of glycans which have previously been identified as hallmarks of cancer and viral glycosylation, such as Man8 and Man9 high mannose glycans. Although each pregnant woman had a unique glycomic profile, longitudinal studies showed that the main glycosylation features were consistent throughout pregnancy in women who delivered at term, whereas women who experienced extreme preterm birth exhibited sharp changes in the CVF glycome shortly before delivery. These findings shed light on the processes underlying the role of glycosylation in maintaining a healthy vaginal microbiome and associated host immune responses. In addition, these discoveries facilitate our understanding of the lower female reproductive tract which has broad implications for women’s health.

Abstract Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are mutated in nearly 25% of cancers. To gain insight into the mechanisms by which SWI/SNF mutations drive cancer, we contributed ten rhabdoid tumor (RT) cell lines mutant for SWI/SNF subunit SMARCB1 to a genome-scale CRISPR–Cas9 depletion screen performed across 896 cell lines. We identify PHF6 as specifically essential for RT cell survival and demonstrate that dependency on Phf6 extends to Smarcb1-deficient cancers in vivo. As mutations in either SWI/SNF or PHF6 can cause the neurodevelopmental disorder Coffin-Siris syndrome, our findings of a dependency suggest a previously unrecognized functional link. We demonstrate that PHF6 co-localizes with SWI/SNF complexes at promoters, where it is essential for maintenance of an active chromatin state. We show that in the absence of SMARCB1, PHF6 loss disrupts the recruitment and stability of residual SWI/SNF complex members, collectively resulting in the loss of active chromatin at promoters and stalling of RNA Polymerase II progression. Our work establishes a mechanistic basis for the shared syndromic features of SWI/SNF and PHF6 mutations in CSS and the basis for selective dependency on PHF6 in SMARCB1-mutant cancers.

Abstract Background and aims Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation. Methods and results The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow–derived macrophages reduced the osteogenic calcification of valvular interstitial cells. Conclusion Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms. Graphical Abstract

Abstract Head and neck epithelial tissue tumors may be identified as head and neck squamous cell carcinoma (HNSC). Numerous malignancies are encouraged by dysregulation of the FGF19-β-Klotho (KLB) axis in the tumor microenvironment. Using protein databases and RT-qPCR, we examined KLB expression in HNSC. In HNSC, higher KLB expression was linked to longer survival times and better prognoses. Furthermore, variations in drug susceptibility and immunological infiltration were noted according to KLB expression levels. These results underscore the importance of KLB in the course and management of HNSC by indicating that it may function as a possible prognostic marker and influence immunological and therapeutic responses in these individuals. Further study on HNSC is necessary to investigate KLB's potential as a therapeutic target and prognostic indicator.

Abstract This study presents the construction of an urban underground sensing system using distributed acoustic sensing (DAS) technology, which utilizes the existing optical fiber infrastructure around urban roads for communication. To address the challenges posed by the complexity and variability of DAS data in infrastructure monitoring environments such as urban roads, as well as the difficulty and poor effectiveness of raw data visualization, a novel method for visualizing DAS data is proposed. This method involves preprocessing the data through wavelet threshold denoising, combining it with the root-mean-square (RMS) energy index to generate a visualization, and applying the dynamic threshold method to remove and suppress abnormal data indicators. Finally, this paper tested the visualization performance to assess the effectiveness of the proposed method in improving urban road safety management. The study focused on three typical urban road safety risk events: vehicle driving, construction, and road subsurface cavity incidents. The results demonstrate the efficacy of the data visualization method, showing improved visualization of vehicle trajectory directions and numbers, construction segment behaviors, and approximate road subsurface cavity locations in the time domain compared to the original data.

Abstract Background Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. Methods Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. Results A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide “J”-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0–11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132–1.518) and 1.418 (95% CI: 1.191–1.688) at cumulative lag 0–14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0–14 days. The heat effects were higher among male and those aged 18–65 years old. The sensitivity analysis results remained robust. Conclusion Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18–65 years are more susceptible to higher AT.

Abstract Background Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. Methods Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. Results We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. Conclusions These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Inflammatory bowel disease remains a high recurrence rate and broad populations all over the world. Liquiritigenin isolated from licorice possess anti-inflammatory and antioxidative activities, suggesting its potential of treating ulcerative colitis (UC). In this study, we explored the effect of oral liquiritigenin on the DSS-induced mice colitis and underlying mechanisms in the aspect of gut microbiome and intestinal barrier dysfunction. The results showed liquiritigenin had protective effects against DSS-induced mice colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening and histological lesions. In addition, the treatment with liquiritigenin significantly reduced the plasma cytokine levels, TNF-α, IL-1β and IL-6 levels as well as the expression of iNOS and COX-2 compared to control group. Liquiritigenin supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease of myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and total Superoxide Dismutase (T-SOD) activities in the colitis mice. In regulation of mice gut microbiota, liquiritigenin augmented probiotics abundance (e.g., Akkermansia), decreased harmful bacteria (e.g., Turicibacter), and restored Firmicutes/Bacteroidetes balance. Furthermore, the mRNA levels of tight junction (TJ), including ZO-1, occludin, and claudin-1 were downregulated in colitis mice, whereas these changes were reversed by liquiritigenin. As indicated by TEM images and Endoplasmic reticulum stress (ERs) marker genes expression like GRP78, IRE1α, ATF6 and PERK that mice with colitis treated by oral liquiritigenin trended to attenuate ER stress. Collectively, the ameliorating role of liquiritigenin in gut inflammation can be attributed to intestinal barrier modulation, gut microbiome regulation, and ER stress alleviation. These findings provide a new perspective for developing liquiritigenin as a promising functional compound of food origin for preventing and mitigating UC.

Changes in neurovascular unit components and their interactions play a crucial role in epileptogenesis and the pathological process of epilepsy. Currently, there is a lack of animal models that can accurately reflect the etiological impact of cerebrovascular lesions on epilepsy. In this study, we constructed cyclin-dependent kinase 5 conditional knockout mice in Cspg4 (pericyte marker)-positive cells using the Cre-LoxP system. The results revealed that this strain of mice exhibited significant seizure behaviors and epileptiform brain waves, loss of hippocampal and amygdala neurons, astrogliosis, decreased pericyte coverage, and reduced AQP4 polar distribution. Herein, we have developed a novel mouse model of spontaneous epilepsy, providing a critical animal model for studying the involvement of neurovascular unit factors in the development and progression of epilepsy.

Summary: Background: Immune dysfunction contributes to a high rate of infection in patients with acute decompensation of cirrhosis. CD52 is a glycoprotein prominently expressed in lymphocytes. Immune regulation by CD52 may be involved in adaptive immune dysfunction in cirrhosis. This study aimed to investigate the function of CD52 on CD4+ T cells on the blood of patients with acute decompensation of cirrhosis. Methods: The expression of CD52 in the peripheral blood lymphocytes of 49 patients with cirrhosis was investigated using flow cytometry and transcriptomics. Potential cis-membrane ligands of CD52 were discovered via proximity labelling followed by proteomics. The function of CD52 on antigen-specific activation of CD4+ T cells was examined using flow cytometry in CD52 CRISPR-Cas9 knockout primary T cells. Findings: CD52 expression was elevated in CD4+ T cells in acute decompensation of cirrhosis, and this elevation was correlated with increased disease severity and mortality. Components of the T cell receptor complex including TCRβ, CD3γ and CD3ε were identified and validated as cis-membrane ligands of CD52. Knockout of CD52 promoted antigen-specific activation, proliferation, and pro-inflammatory cytokine secretion. Interpretation: Membrane bound CD52 demonstrated cis-interaction with the T cell receptor and served as a dynamic regulator of antigen-specific activation of CD4+ T cells. The upregulation of CD52 in the periphery of acute decompensation of cirrhosis hinders the recognition of the T cell receptor by MHC, contributing to impaired T cell function. The development of an alternative anti-CD52 antibody is required to restore T cell function and prevent infections in cirrhosis. Funding: This study was supported by the NIHR Imperial Biomedical Research Centre, Institute for Translational Medicine and Therapeutics (P74713), Wellcome Trust (218304/Z/19/Z), and Medical Research Council (MR/X009904/1 and MR/R014019/1).

Abstract Organic–inorganic hybrid thermoelectric (TE) materials have attracted tremendous interest for harvesting waste heat energy. Due to their mechanical flexibility, inorganic‐organic hybrid TE materials are considered to be promising candidates for flexible energy harvesting devices. In this work, enhanced TE properties of Tellurium (Te) nanowires (NWs)‐ poly (3‐hexylthiophene‐2, 5‐diyl) (P3HT) hybrid materials are reported by improving the charge transport at interfacial layer mediated via controlled oxidation. A power factor of ≈9.8 µW (mK2)−1 is obtained at room temperature for oxidized P3HT‐TeNWs hybrid materials, which increases to ≈64.8 µW (mK2)−1 upon control of TeNWs oxidation. This value is sevenfold higher compared to P3HT‐TeNWs‐based hybrid materials reported in the literature. MD simulation reveals that oxidation‐free TeNWs demonstrate better templating for P3HT polymer compared to oxidized TeNWs. The Kang–Snyder model is used to study the charge transport in these hybrid materials. A large σE0 value is obtained which is related to better templating of P3HT on oxygen‐free TeNWs. This work provides evidence that oxidation control of TeNWs is critical for better interface‐driven charge transport, which enhances the thermoelectric properties of TeNWs‐P3HT hybrid materials. This work provides a new avenue to improve the thermoelectric properties of a new class of hybrid thermoelectric materials.

Prostate cancer is a significant contributor to cancer-related mortality, and the tumor typically develops into castration-resistant prostate cancer (CRPC). Hence, few effective clinical strategies are available to patients with advanced disease. Extrachromosomal circular DNA (eccDNA) is a type of circular DNA originating from the chromosomes but is likely independent of them. Because of its unique structural characteristics, eccDNA has extensive applications as a new biomarker for cancer prevention and treatment. Circle-seq obtains a comprehensive picture of the overall landscape of eccDNA sizes and content in cell populations. In this study, we used Circle-seq and studied the distribution pattern and expression level of eccDNA in prostate cancer. We confirmed that eccDNA is derived from every human chromosome and has sequences from all known types of genomic structures, revealing it is a common mutational element in prostate cancer. We also identified an eccDNA-related gene SPOCK1 that promotes drug resistance, proliferation, and metastasis of many cancers through the epithelial-mesenchymal transition (EMT) mechanism. The SPOCK1-associated eccDNA was highly upregulated in various groups of sequencing results, and SPOCK1 was highly expressed in prostate cancer tissues and cells. Therefore, SPOCK1 exists as eccDNA in prostate cancer and encourages its development and drug resistance via the EMT mechanism. Our results suggest that upregulated genes in the form of eccDNA are oncogenes in prostate cancer and play a pivotal role in carcinogenesis.

ABSTRACT Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients’ gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.IMPORTANCEThis study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.

Abstract Background Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment. Methods The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1. Results Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism. Conclusion USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.

Abstract Background C-X-C motif chemokine ligand (CXCL8), also known as interleukin-8, is a prototypical CXC family chemokine bearing a glutamic acid-leucine-arginine (ELR) motif that plays key roles in the onset and progression of a range of cancers in humans. Many prior studies have focused on exploring the relationship between CXCL8 gene polymorphisms and the risk of cancer. However, the statistical power of many of these reports was limited, yielding ambiguous or conflicting results in many cases. Methods Accordingly, the PubMed, Wanfang, Scopus and Web of Science databases were searched for articles published until July 20, 2023 using the keywords ‘IL-8’ or ‘interleukin-8’ or ‘CXCL8’, ‘polymorphism’ and ‘cancer’ or ‘tumor’. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to examine the association. The CXCL8 +781 polymorphism genotypes were assessed with a TaqMan assay. Results About 29 related publications was conducted in an effort to better understand the association between these polymorphisms and disease risk. The CXCL8 -353A/T polymorphism was associated with an increased overall cancer risk [A vs. T, odds ratio (OR) = 1.255, 95% confidence interval (CI) (1.079–1.459), P heterogeneity = 0.449, P = 0.003]. The CXCL8 +781 T/C allele was similarly associated with a higher risk of cancer among Caucasians [TT vs. TC + CC, OR = 1.320, 95%CI (1.046–1.666), P heterogeneity = 0.375, P = 0.019]. Furthermore, oral cancer patients carrying the CXCL8 +781 TT + TC genotypes exhibited pronounced increases in serum levels of CXCL8 as compared to the CC genotype (P

Abstract Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499–981 bp) and (1053–1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086–1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Highlights Cetyltrimethylammonium cations can shield the repelling force on anions to attract more anions into electric double layer region during lithium plating process, facilitating the formation of inorganic-rich solid-state electrolyte interphase (SEI). An inorganic-rich (N/F-containing species) structure of SEI can be evidenced by the in-depth analysis. The cycling lifetime of Li||Li symmetric cell in the designed electrolyte can be extended from 500 to 1300 h. Moreover, full cells with a high cathode mass loading of >10 mg cm-2 can be stably cycled over 180 cycles.

AbstractAgricultural modernization urgently requires precise control of pear tree leaf diseases, with accurate identification and segmentation of disease spots becoming crucial aspects for ensuring crop health. Addressing potential issues such as missed segmentation, missegmentation, and low segmentation accuracy in the traditional DeepLabv3+ model for this task, this study proposes an innovative approach based on an improved DeepLabv3+ network model. To enhance computational efficiency, MobileNetV2 is introduced as the backbone network. This reduces the model’s computational load and significantly improves segmentation speed, making it more suitable for real-time applications. Secondly, after the ASPP (Atrous Spatial Pyramid Pooling) convolution, the Squeeze-and-Excitation (SE) attention mechanism is introduced, integrating the features of pear tree leaf diseases to make the network focus more on the critical components of disease spots, thereby enhancing segmentation accuracy. Finally, the loss function is optimized by employing a linear combination of the cross-entropy loss function and Dice loss, encompassing comprehensive overall image loss and accurate loss calculation for the target area. Experimental validation demonstrates a significant improvement in the enhanced DeepLabv3+ across metrics such as MIoU, mPA, mPr, and mRecall, reaching 86.32%, 88.97%, 91.10%, and 88.97%, respectively. The improved model excels in pear tree leaf disease segmentation compared to traditional methods like DeepLabv3+, SegNet, FCN, and PSPNet. This confirms the enhanced model’s outstanding performance and generalization ability in segmenting pear tree leaf lesions, highlighting its potential value in practical applications.

Background: Type 2 diabetes mellitus (T2DM) significantly contributes to sepsis, with patients suffering from both conditions exhibiting greater severity and higher mortality rates compared to those with sepsis alone. Elderly individuals in the intensive care unit (ICU) are particularly prone to these comorbidities. A nomogram prediction model was developed to accurately assess prognosis and guide treatment for elderly patients with sepsis and T2DM. Methods: Data from 1489 patients with sepsis and T2DM in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed and categorized into 28-days survival ( n = 1156) and 28-days death groups ( n = 333). The dataset’s clinical characteristics were employed to create a nomogram predicting 28-days mortality in elderly ICU patients with sepsis and T2DM. The least absolute shrinkage and selection operator (LASSO) regression identified candidate predictors, followed by a multivariate logistic regression analysis incorporating variables with p < .05 into the final model. A nomogram was then constructed using these significant risk predictors. The model’s discriminatory power was evaluated through a receiver operating curve (ROC) and the area under the curve (AUC). Additionally, model performance was assessed using a calibration plot and the Hosmer-Lemeshow goodness-of-fit test (HL test), and clinical utility was examined via decision curve analysis (DCA). Results: Risk factors incorporated into the nomogram included age, ICU length of stay, mean blood pressure (MBP), metastatic solid tumor, Sequential Organ Failure Assessment (SOFA) score, Logistic Organ Dysfunction System (LODS) score, blood urea nitrogen (BUN), and vasopressor use. The predictive model demonstrated robust discrimination, with an AUC of 0.802 (95% CI 0.768–0.835) in the training dataset and 0.753 (95% CI 0.697–0.809) in the validation set. Calibration was confirmed with the HL test ( p > .05), and DCA indicated clinical usefulness. Conclusion: This new nomogram serves as a practical tool for predicting 28-days mortality among elderly ICU patients with sepsis and T2DM. Optimizing treatment strategies based on this model could enhance 28-days survival rates for these patients.

A silicon‐based room temperature (RT) continuous wave (CW) operation quantum well (QW) laser emitting at 850 nm is reported in this article. By applying the dislocation filter superlattice, the threading dislocation density of the GaAs pseudosubstrate on Si is reduced to 1.8 × 107 cm−2. The metal‐organic chemical vapor deposition‐grown laser structure with GaAs/GaAsP QW and InAlAs active region dislocation blocking layer are fabricated into broad‐stripe Fabry–Perot laser diodes. A typical threshold current and threshold current density of 286 mA and 715 Acm−2 are obtained with 2 mm cavity length and 20 um stripe width samples. A 94.2 mW single‐facet output power lasing around 854 nm and a 0.314 WA−1 slope efficiency is measured under RT CW operation. After a 10‐min aging process, the tested laser can operate stably under continuous operation conditions at RT and the lifetime can be approximated using an exponential fitting curve, indicating a good life reliability of this QW laser.

In the current study, a series of A1–π–A2–π–A1 type bisisoindigo-based organic compounds (BTIND1–BTIND9) were designed via the structural tailoring of the reference compound (BTINR) at terminal acceptors for the organic solar cells (OSCs). Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) approaches were utilized to estimate the influence of end-capped engineering over their photovoltaic properties of BTIND1–BTIND9. After their structural optimization, various analyses like, open circuit voltage (Voc), absorption spectra (λmax), frontier molecular orbitals (FMOs), density of states (DOS), binding energy (Eb) and transition density matrix (TDM) were performed at the B3LYP/6-311G(d,p) level. The band gaps range of the engineered molecules was observed as 1.776–1.649 eV, lesser than the BTINR reference (1.812 eV). Their TDM and DOS details further revealed electronic charge transfer in the designed derivatives. The higher λmax values were found in the visible and near-infrared regions i.e., 666.904–701.149 nm in the chloroform solvent and 661.778–895.581 nm in the gaseous phase. Furthermore, their open-circuit voltage (Voc) was determined with PTB7 donor polymer and showed significant values. Among all, BTIND5, BTIND7 and BTIND8 compounds were investigated with remarkable photovoltaic properties. These chromophores possessed least energy gaps (1.649, 1.668 and 1.664 eV) and bathochromic shifts (698.070, 699.646 and 701.149 nm) with least binding energies and prominent Voc results. The above-mentioned outcomes demonstrate that the end-capped modification of bisisoindigo-based molecule is an effective strategy to obtain highly efficient OSCs.

The beam-column connection is both the critical area and the weak part for the prefabricated reinforced concrete (PC) frame structure. The ductile connection with a U-shaped shell has been well-developed for the PC cross-shaped connection. In this paper, two optimizing reinforcement methods in the U-shell were proposed to improve the seismic performance of the PC beam-column connection. Three full-scale PC beam-column connections were designed and produced. Then, reversed cyclic loading was applied to the connections with acoustic emission (AE) technology as the measuring method to investigate the failure modes and damage mechanisms under seismic actions. The results show that increasing the connecting reinforcement area can effectively promote the bearing capacity of components while setting stirrups enables improving energy-dissipating capacity. Based on the variation of AE hits, the loading process can be divided into three stages, and the optimization effects of two measures were reflected at the different loading stages. According to the Ib-value analysis, it can be seen that the cyclic development of microcrack propagation and macrocrack penetration was the main failure mode of components. Besides, the k-means algorithm was used to classify the AE signals into four clusters with different crack patterns. In addition, based on AE energy calculation, the damage prediction model was constructed for the three full-scale specimens.

BackgroundWuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic.ObjectiveThis study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017–2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools.MethodsThis study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis.ResultsFrom 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools.ConclusionWe successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

Multiple isozymes are encoded in the Caenorhabditis elegans genome for the various sphingolipid biosynthesis reactions, but the contributions of individual isozymes are characterized only in part. We developed a simple but effective reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) method that enables simultaneous identification and quantification of ceramides (Cer), glucosylceramides (GlcCer), and sphingomyelins (SM) from the same MS run. Validating this sphingolipid profiling method, we show that nearly all 47 quantifiable sphingolipid species found in young adult worms were reduced upon RNA interference (RNAi) of sptl-1 or elo-5, which are both required for synthesis of the id17:1 sphingoid base. We also confirm that HYL-1 and HYL-2, but not LAGR-1, constitute the major ceramide synthase activity with different preference for fatty acid substrates, and that CGT-3, but not CGT-1 and CGT-2, plays a major role in producing GlcCers. Deletion of sms-5 hardly affected SM levels. RNAi of sms-1, sms-2, and sms-3 all lowered the abundance of certain SMs with an odd-numbered N-acyl chains (mostly C21 and C23, with or without hydroxylation). Unexpectedly, sms-2 RNAi and sms-3 RNAi elevated a subset of SM species containing even-numbered N-acyls. This suggests that sphingolipids containing even-numbered N-acyls could be regulated separately, sometimes in opposite directions, from those containing odd-numbered N-acyls, which are presumably monomethyl branched chain fatty acyls. We also find that ceramide levels are kept in balance with those of GlcCers and SMs. These findings underscore the effectiveness of this RPLC-MS/MS method in studies of C. elegans sphingolipid biology.

The optimization of the contradiction between the toughness and strength of nacre has become a focus of attention for material researchers. In the present work, objective functions for several parameters, such as tablet shape (flat and wavy), dimensions (length, thickness, dovetail angle), mechanical properties (modulus of elasticity, shear modulus), overlap length of layers, and matrix thickness, were established from the three basic mechanical properties of the bionic mother-of-pearl structure (stiffness, strength, and toughness). Subsequently, the objective function was iteratively optimized using the non-dominated sorting genetic algorithm II (NSGA II) based on the constraint function. Finally, a numerical simulation model was developed using the key parameters derived from the structural optimization to investigate the penetration performance of a 12.7 mm projectile on different structures. Comparing the damage failure scenario, penetration resistance, ballistic performance, and energy absorption efficiency of different structures, it was found that after parameter optimization, wave-staggered composite plate reduced the penetration depth by 31.61 %, improved the ballistic limit by 27.21 %, and enhanced the energy absorption efficiency of ceramic by 8.30 % compared to the block plate.

The Xiaoxing'an Moutains-Sanjiang Plain is currently facing environmental deterioration, economic recession, social development obstruction, population loss, which has been seriously affecting local sustainability. Considering that their solution often requires holistic approaches, which can involve multiple aspects of social-ecological system (SES), it is significant to clarify the evolution of coupling relationship among the subsystems of SES, to identify the obstacle factors that affect the coupling coordination degree (CCD) among them, and to predict the changing trend of their CCD. Basing on the collected panel data, this study established a metrics system to evaluate the CCD among environmental, economic, social, and population subsystems of five prefecture-level cities in the Xiaoxing'an Moutains-Sanjiang Plain. The dynamic laws and characteristics of the CCD were analyzed in spatial and temporal dimensions. The key factors hindering CCD were determined by using obstacle diagnosis model, and the future CCD was predicted based on Bayesian model. It is found that the evaluation values of the environmental, social, and population subsystem as well as the CCD at the region scale showed a fluctuating upward trend, in which the evaluation value of the environmental subsystem increases the most, while the evaluation value of the economic subsystem showed a downward trend; The CCD of 5 cities in studying areas showed different trends of development, and the CCD of Jiamusi City always ranked first, indicating that the CCD of the non-resource-based city with a large population and high GDP tends to be higher than that of other cities; The CCD of 5 cities is spatially “high in the plain area, low in the mountainous area”, and the barycenter of the high CCD area gradually shifted from the northwest to the northeast during the study period; Total volume of foreign trade, total volume of actual use of foreign capital, number of college students per ten thousand people, total retail sale of consumer goods, and harmless treatment rate of domestic garbage are the main obstacle factors metrics for most cities; Environmental state, environmental governance, living standards, opening up, social stability, and population quality are the main obstacle factors at the observation dimension; According to the prediction results, except for Qitaihe, the CCD of other cities in the next 20 years showed a downward trend, and the CCD of Hegang showed the largest decline range and speed. Findings of this study may have important implications to long-term planning and policy formulation for promoting sustainability of the Xiaoxing'an Moutains-Sanjiang Plain and other similar areas.

Abstract Background Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. Methods The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. Results RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. Conclusion RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Abstract Triazoles, nitrogen-containing heterocycles, have gained attention for their applications in medicinal chemistry, drug discovery, agrochemicals, and material sciences. In the current study, we synthesized novel derivatives of N-substituted 2-((5-(3-bromophenyl)-4-methyl-4H-1,2,4-triazol-3-yl)thio)-N-phenylpropanamide and conducted a comprehensive investigation using density functional theory (DFT). These novel structural hybrids of 1,2,4-triazole were synthesized through the multi-step chemical modifications of 3-bromobenzoic acid (1). Initially, compound 1 was converted into its methyl-3-bromobenzoate (2) which was then transformed into 3-bromobenzohydrazide (3). The final step involved the cyclization of compound 3, producing its 1,2,4-triazole derivative (4). This intermediate was then coupled with different electrophiles, resulting in the formation of the final derivatives (7a–7c). Additionally, the characterization of these triazole-based compounds (7a, 7b, and 7c) were carried out using techniques such as IR, HNMR, and UV–visible spectroscopy to understand their structural and spectroscopic properties. The DFT study utilized M06/6-311G(d,p) functional to investigate geometrical parameters, HOMO–LUMO energies, natural bond orbital analyses, transition density matrix (TDM), density of states, and nonlinear optical (NLO) properties. The FMO analysis revealed that compound 7c exhibited the lowest band gap value (4.618 eV). Notably, compound 7c exhibited significant linear polarizability (4.195 > × 10–23) and first and second hyperpolarizabilities (6.317 > × 10–30, 4.314 × 10–35), signifying its potential for nonlinear optical applications. These NLO characteristics imply that each of our compounds, especially 7c, plays a crucial part in fabricating materials showing promising NLO properties for optoelectronic applications.

Abstract Elevated serum ferritin (SF) levels have been associated with poor prognosis in various cancer types, but its impact on nasopharyngeal carcinoma (NPC) remains unclear. This retrospective study analyzed clinical data from 252 non-metastatic NPC patients admitted to Hainan General Hospital between January 2014 and May 2016. SF levels were measured using the chemiluminescence method. Patients were categorized into low, medium, and high-level SF groups based on tertile median SF levels. Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. The overall survival rates of the entire patient cohort at 1, 3, 5, and 8 years were 95.2%, 85.7%, 76.2%, and 68.9% respectively. The high-level SF group (SF > 164.00 ng/mL) had significantly worse overall survival (83.1 vs 96.3 months, P = 0.023) and progression-free survival (77.8 vs 93.3 months, P = 0.019) compared to the low-level SF group. Univariate and multivariate analyses confirmed that high SF levels, along with T3/T4 staging and N3 staging, were independent risk factors for poor prognosis. In conclusion, high SF levels are associated with shorter overall survival and progression-free survival in NPC patients.

Abstract Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted ‘reduction, replacement and refinement’ principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.

Abstract Great attention has been given to high‐performance and inexpensive lithium‐ion batteries (LIBs) in response to the ever‐increasing demand for the explosive growth of electric vehicles (EVs). High‐performance and low‐cost Co‐free Ni‐rich layered cathodes are considered one of the most favorable candidates for next‐generation LIBs because the current supply chain of EVs relies heavily on scarce and expensive Co. Herein, we review the recent research progress on Co‐free Ni‐rich layered cathodes, emphasizing on analyzing the necessity of replacing Co and the popular improvment methods. The current advancements in the design strategies of Co‐free Ni‐rich layered cathodes are summarized in detail. Despite considerable improvements achieved so far, the main technical challenges contributing to the deterioration of Co‐free Ni‐rich cathodes such as detrimental phase transitions, crack formation, and severe interfacial side reactions, are difficult to resolve by a single technique. The cooperation of multiple modification strategies is expected to accelerate the industrialization of Co‐free Ni‐rich layered cathodes, and the corresponding synergistic mechanisms urgently need to be studied. More effects will be aroused to explore high‐performance Co‐free Ni‐rich layered cathodes to promote the sustainable development of LIBs.

[Objective] With the theme of promoting urban rail transit information, developing intelligent system, and building 'smart urban rail' for a highly integrated urban rail transit cloud platform is the direction of technological development in the new era. The integration of signaling system and cloud platform is an important development trend of signaling systems. In-depth research is needed on how to build an efficient, reliable, and cost-effective signaling system based on cloud architecture. [Method] Combining the needs of Changzhou Metro new round of urban rail transit construction scheme, based on the technological characteristics of existing cloud platform and current situation of signaling system, the feasibility and construction scheme of signaling system cloudification are analyzed and verified. The research of contents such as line network unified ATS (automatic train supervision) construction scheme, signaling system cloudification scope, cloud platform architecture selection, and signaling system ATS interoperability scheme after cloudification are emphasized. [Result & Conclusion] The definition of signaling system cloudification is clarified, discussing the feasibility of signaling system ATS cloudification. According to the estimation whether the signaling system can pass SIL2 (safety, integrity level 2) after cloudification, a list of specific equipment for ATS cloudification is determined. The new-generation signaling system construction scheme based on cloud architecture is proposed, and the urban rail transit cloud platform architecture carrying ATS is suggested to transit from mode 1 to mode 3 gradually, possessing the ability to update and iterate. Signaling system equipment can level up the processing capacity of the signaling system and reduce hardware device amount after integration into cloud platform, contributing to realizing line network resource/information exchange and promoting modulating the development of intelligent scheduling.

To address the issue of model performance degradation in combat intention recognition caused by the long-tailed distribution of battlefield data and the neglect of the spatial dimension information of multivariate time series data, this paper proposes a class balanced spatio-temporal self-attention (CBSTSA) model. By incorporating spatial and temporal attention mechanisms, the model captures interdependencies among features and extracts salient information from both temporal and spatial dimensions. Furthermore, taking the long-tailed distribution of battlefield data into account, a re-weighted class balanced loss function is introduced to train the model. Experimental results show the superiority of our CBSTSA model, e.g. achieving approximately 95.67% accuracy in typical scenarios, surpassing benchmark schemes by 4–5%.

Abstract Miniaturized spectrometers have great potential for use in portable optoelectronics and wearable sensors. However, current strategies for miniaturization rely on von Neumann architectures, which separate the spectral sensing, storage, and processing modules spatially, resulting in high energy consumption and limited processing speeds due to the storage-wall problem. Here, we present a miniaturized spectrometer that utilizes a single SnS2/ReSe2 van der Waals heterostructure, providing photodetection, spectrum reconstruction, spectral imaging, long-term image memory, and signal processing capabilities. Interface trap states are found to induce a gate-tunable and wavelength-dependent photogating effect and a non-volatile optoelectronic memory effect. Our approach achieves a footprint of 19 μm, a bandwidth from 400 to 800 nm, a spectral resolution of 5 nm, and a > 104 s long-term image memory. Our single-detector computational spectrometer represents a path beyond von Neumann architectures.

Abstract Radioresistance is a major constraint on the efficacy of lung cancer radiotherapy, but its mechanism has not been fully elucidated. Here, we found that FBXO22 was aberrantly highly expressed in lung cancer and that FBXO22 knockdown increased the radiosensitivity of lung cancer cells. Mechanistically, FBXO22 promoted Rad51 gene transcription by increasing the level of FOXM1 at the Rad51 promoter, thereby inducing the formation of lung cancer radioresistance. Furthermore, we found that deguelin, a potential inhibitor of FBXO22, enhanced radiosensitivity in an FBXO22/Rad51-dependent manner and was safely tolerated in vivo. Collectively, our results illustrate that FBXO22 induces lung cancer radioresistance by activating the FOXM1/Rad51 axis and provide preclinical evidence for the clinical translation of this critical target.

Abstract Objective This study aims to explore the prognostic significance of Proline-rich γ-carboxyglutamic acid protein 2 (PRRG2) in Kidney Renal Clear Cell Carcinoma (KIRC), a prevalent and deadly cancer, and its association with immune cell infiltration, a key strategy in developing effective biomarkers. Methods The study meticulously elucidated the prognostic significance and potential role of PRRG2 in KIRC, correlating its expression with patient sex, age, metastasis, and pathological stage. Utilizing Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the involvement of PRRG2 in immune response was investigated. The association between PRRG2 expression and immune cell infiltration was also scrutinized. Ultimately, cellular and tissue identity were confirmed via immunohistochemical staining and quantitative real-time PCR. Results The study elucidates a notable decrease in PRRG2 expression in KIRC patients, correlating with demographic factors, metastasis, and pathological staging, and portending an unfavorable prognosis. Bioinformatic analyses underscore PRRG2’s role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. Conclusion PRRG2 may potentially impact prognosis in KIRC patients by regulating immune infiltration, thus rendering PRRG2 a promising candidate prognostic biomarker for KIRC-associated immune infiltration.

Abstract Although prognostic prediction of nasopharyngeal carcinoma (NPC) remains a pivotal research area, the role of dynamic contrast-enhanced magnetic resonance (DCE-MR) has been less explored. This study aimed to investigate the role of DCR-MR in predicting progression-free survival (PFS) in patients with NPC using magnetic resonance (MR)- and DCE-MR-based radiomic models. A total of 434 patients with two MR scanning sequences were included. The MR- and DCE-MR-based radiomics models were developed based on 289 patients with only MR scanning sequences and 145 patients with four additional pharmacokinetic parameters (volume fraction of extravascular extracellular space (v e ), volume fraction of plasma space (v p ), volume transfer constant (K trans ), and reverse reflux rate constant (k ep ) of DCE-MR. A combined model integrating MR and DCE-MR was constructed. Utilizing methods such as correlation analysis, least absolute shrinkage and selection operator regression, and multivariate Cox proportional hazards regression, we built the radiomics models. Finally, we calculated the net reclassification index and C-index to evaluate and compare the prognostic performance of the radiomics models. Kaplan-Meier survival curve analysis was performed to investigate the model’s ability to stratify risk in patients with NPC. The integration of MR and DCE-MR radiomic features significantly enhanced prognostic prediction performance compared to MR- and DCE-MR-based models, evidenced by a test set C-index of 0.808 vs 0.729 and 0.731, respectively. The combined radiomics model improved net reclassification by 22.9%–52.6% and could significantly stratify the risk levels of patients with NPC (p = 0.036). Furthermore, the MR-based radiomic feature maps achieved similar results to the DCE-MR pharmacokinetic parameters in terms of reflecting the underlying angiogenesis information in NPC. Compared to conventional MR-based radiomics models, the combined radiomics model integrating MR and DCE-MR showed promising results in delivering more accurate prognostic predictions and provided more clinical benefits in quantifying and monitoring phenotypic changes associated with NPC prognosis.

Thebes is among the best-documented Venetian colonies in Byzantium, with records dating back to 1072. While it is widely acknowledged that Venetians played a crucial role in the development of Byzantine Thebes, the details about the Venetian community of the city remain largely unexplored, which has hindered a deeper understanding of the true extent of the Venetian impact on Thebes. To address this scholarly gap, the article examines the community using Venetian documentary sources, focusing on the works of R. Morozzo della Rocca and A. Lombardo. The study adopted a prosopography methodology, reconstructing and analysing the biographies of individuals and families in groups. The investigation covers the community’s leading families and individuals, as well as clergy and ecclesiastical establishments of special interest. Following this vein, the author of the article concludes with a more detailed picture of the Venetian community. It seems to have played a notable and persistent role in Thebes. Ecclesiastical establishments and the clergy constituted the basis of Venetian activities. Bolstered by reliable and sustainable sources of income, these institutions fulfilled the basic religious and administrative needs of the Venetian community. Apart from possible industrial and agricultural engagements, the community members predominantly emerge as active participants in commercial ventures, linking in particular to the renowned Theban silk textiles. While Venetians did form matrimonial and commercial alliances amongst themselves, their assimilation with the native Byzantine populace of the city seems to have been minimal.

Abstract Background Lactate, a glycolytic metabolite mainly produced in muscles, has been suggested to regulate myoblast differentiation, although the underlying mechanism remains elusive. Recently, lactate‐mediated histone lactylation is identified as a novel epigenetic modification that promotes gene transcription. Methods We used mouse C2C12 cell line and 2‐month‐old male mice as in vitro and in vivo models, respectively. These models were treated with lactate to explore the biological function and latent mechanism of lactate‐derived histone lactylation on myogenic differentiation by quantitative real‐time PCR, western blotting, immunofluorescence staining, chromatin immunoprecipitation, cleavage under targets and tagmentation assay and RNA sequencing. Results Using immunofluorescence staining and western blotting, we proposed that lactylation might occur in the histones. Inhibition of lactate production or intake both impaired myoblast differentiation, accompanied by diminished lactylation in the histones. Using lactylation site‐specific antibodies, we demonstrated that lactate preferentially increased H3K9 lactylation (H3K9la) during myoblast differentiation (CT VS 5, 10, 15, 20, 25 mM lactate treatment, P = 0.0012, P = 0.0007, and the rest of all P

In recent years, with the rapid construction of a safe, clean, efficient and sustainable modern energy system, the intelligence of coal mining has become the inevitable direction of the development of the coal mining industry. The intelligence of coal mining system and equipment is the core of intelligent mining, and the positioning technology of mining equipment is the key to underground intelligent mining. The strapdown inertial navigation system can make up for the shortcomings of traditional GPS positioning systems and laser positioning because of its strong anti-interference, high precision and real-time monitoring, and ability to carry out real-time dynamic positioning of mining equipment in underground coal mines. This paper briefly introduces the basic principle of the strapdown inertial navigation system, analyzes the application of the existing strapdown inertial navigation system in mining equipment, and lists and analyzes the research status of the improvement strategy of the inertial navigation system, such as zero speed correction and integrated navigation technology. Finally, by analyzing the application and future development trend of inertial navigation systems in mining equipment, this paper provides more data and method support for the positioning of mining equipment in the future.

Clarifying the complex relationships among ecosystem services (ESs) and their driving mechanisms is essential for effective ecosystem management and enhancing human welfare. Nonetheless, the current research on these issues still remains limited; therefore, further theoretical exploration is required. This study aims to quantitatively illustrate the trade-off strength of ESs and investigate the spatiotemporal heterogeneity connections between these relationships and various anthropogenic and natural factors in Baiyangdian basin, China, integrating InVEST, RMSE, geographical detector and MGWR methods. From 2000 to 2020, the total water yield (WY) and nutrient export (NE) increased, while the total carbon storage (CS) and habitat quality (HQ) decreased slightly. The trade-offs of ESs showed spatiotemporal heterogeneity. The most serious trade-off occurred between regulating services (CS and NE) and supporting services (HQ) in 2000, which was mainly distributed in the densely forested and grassed western and northern regions of the basin. The trade-off intensities of half of the pairwise ESs in 2020 increased, with the strengthened areas mainly located in the southeast of the watershed where built-up lands are concentrated. Various factors dominated the trade-offs among ESs, with the interactive effects of multiple drivers being more significant than those of individual factors. Land use type, vegetation cover and precipitation have the most pronounced effect on the trade-offs among ESs. The findings of this study may suggest and advocate for spatial ecological strategies to enhance the integrated and holistic advancement of various ESs and also serve as a reference for regional ecosystem governance and the attainment of sustainable growth.

Trigger–action programming (TAP) enables users to automate Internet of Things (IoT) devices by creating rules such as “IF Device1.TriggerState is triggered, THEN Device2.ActionState is executed”. As the number of IoT devices grows, the combination space between the functions provided by devices expands, making manual rule creation time-consuming for end-users. Existing TAP recommendation systems enhance the efficiency of rule discovery but face two primary issues: they ignore the association of rules between users and fail to model collaborative information among users. To address these issues, this article proposes a graph contrastive learning-based recommendation system for TAP rules, named GCL4TAP. In GCL4TAP, we first devise a data partitioning method called DATA2DIV, which establishes cross-user rule relationships and is represented by a user–rule bipartite graph. Then, we design a user–user graph to model the similarities among users based on the categories and quantities of devices that they own. Finally, these graphs are converted into low-dimensional vector representations of users and rules using graph contrastive learning techniques. Extensive experiments conducted on a real-world smart home dataset demonstrate the superior performance of GCL4TAP compared to other state-of-the-art methods.