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The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Abstract Photovoltaic (PV) is essential for global carbon neutrality, it is imperative to forecast PV generation accurately for power operation. With the rapid growth of distributed PV sites, a scalable cloud service tends to play a vital role in PV forecasting to address the increasing cost of computing resources and data subscriptions. Such a scheme creates a possibility to further enhance forecasting performance by re‐using forecasting model, data, and computing resources all in the cloud. In order to achieve this goal, this work proposes a multi‐site PV forecasting system design with a message queue (MQ) and stream computing engine, where a hybrid neural network model is trained and continuously updated using real‐time data. A performance benchmark with up to 60 sites served simultaneously was performed to verify the scalability of the stream computing based approach. Moreover, after incremental updating of the forecasting model, a decrease in normalized root mean square error and normalized mean absolute error of PV forecasting were observed, demonstrating that better short‐term forecasting accuracy was achieved.

Background/purpose: Metagenomic next-generation sequencing (mNGS) has been widely used for the detection of pathogens causing infectious diseases. This study aimed to evaluate the potential ability of mNGS to detect pathogens causing oral and maxillofacial space infection (OMSI) and compare the results with those of the traditional diagnostic microbial culture method. Materials and methods: We retrospectively reviewed the data of 218 patients diagnosed with OMSI who underwent microbial culture and mNGS at the Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from July 2020 to January 2022. Results: The positivity rate of mNGS (216 cases) was significantly higher than that of microbial culture (123 cases). The most frequently detected bacteria were different between these two detection methods. Streptococcus constellatus (16.05%, 35), Streptococcus anginosus (15.69%, 34) and Klebsiella pneumoniae (6.88%, 15) were the most commonly isolated bacteria by culture. However, Peptostreptococcus stomatis (61.47%, 134), Parvimonas micra (68.35%, 149) and Streptococcus constellatus (57.34%, 125) were the most commonly detected bacteria by mNGS. mNGS also has advantages in diagnosing viral infections. The optimal numbers of diagnostic reads were 1162 and 588 for the diagnosis of Streptococcus anginosus and Streptococcus constellatus infections, respectively. Read numbers were significantly correlated with C-reactive protein (CRP), procalcitonin (PCT), and blood glucose levels and neutrophil percentage (NEUT%). Conclusion: For pathogens causing OMSI, mNGS had a higher rate of microbial pathogen detection and remarkable advantages in identifying coinfections involving viruses and fungi. The read numbers for mNGS are important for diagnostic accuracy and disease severity evaluation.

Living convenience in public service facilities has attracted significant attention as a crucial indicator of urban development and quality improvement. However, the performance of plot patterns—a fundamental unit for precise control when measuring urban quality—influencing living convenience requires in-depth exploration. This study integrates multiple urban datasets with quantitative urban morphology methods to investigate the impact of various plot pattern features on living convenience. Specifically, we investigate the Inner Ring area of Shanghai as an empirical case. The assessment considers the diverse effects of facilities at different distances, accounting for the life radiuses of both older individuals and the general population. Additionally, the analysis of plot patterns includes planar and three-dimensional aspects, controlling key variables such as road network accessibility and centrality. The results indicate that, for small-scale plots, shape has a strong impact, while, for large-scale plots, the division and construction intensity within a block has a stronger influence. Furthermore, plots of different area types have different recommended construction intensities. Notably, for large-scale blocks, it is advisable to maintain a building density of around 0.3. In short, this study contributes to human-centered planning by providing targeted recommendations to address the existing deficiencies in plot morphology regulation and control from the perspective of quantitative urban morphology.

Abstract Background Waterlogging is one of the major abiotic stresses in barley and greatly reduces grain yield and quality. To explore the mechanism controlling waterlogging tolerance in barley, physiological, anatomical and transcriptional analyses were performed in two contrasting barley varieties, viz. Franklin (susceptible) and TX9425 (tolerant). Results Compared to Franklin, TX9425 had more adventitious roots and aerenchymas and higher antioxidant enzyme activities. A total of 3064 and 5693 differentially expressed genes (DEGs) were identified in TX9425 after 24 h and 72 h of waterlogging treatment, respectively, while 2297 and 8462 DEGs were identified in Franklin. The results suggested that TX9425 was less affected by waterlogging stress after 72 h of treatment. The DEGs were enriched mainly in energy metabolism, hormone regulation, reactive oxygen species (ROS) scavenging, and cell wall-modifying enzymes. Alcohol dehydrogenase (ADH) plays an important role in response to waterlogging stress. We found that HvADH4 was significantly upregulated under waterlogging stress in TX9425. Transgenic Arabidopsis overexpressing HvADH4 displayed higher activity of antioxidant enzymes and was more tolerant to waterlogging than the wild type (WT). Conclusions The current results provide valuable information that will be of great value for the exploration of new candidate genes for molecular breeding of waterlogging tolerance in barley.

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction, leading to loss of salivary function. Histological analysis of salivary glands from SS patients reveals a high infiltration of immune cells, particularly activated CD4+ T cells. Thus, interventions targeting abnormal activation of CD4+ T cells may provide promising therapeutic strategies for SS. Here, we demonstrate that Hect, uba, and wwe domain containing 1 (HUWE1), a member of the eukaryotic Hect E3 ubiquitin ligase family, plays a critical role in CD4+ T-cell activation and SS pathophysiology.Methods: In the context of HUWE1 inhibition, we investigated the impact of the HUWE1 inhibitor BI8626 and sh-Huwe1 on CD4+ T cells in mice, focusing on the assessment of activation levels, proliferation capacity, and cholesterol abundance. Furthermore, we examined the therapeutic potential of BI8626 in NOD/ShiLtj mice and evaluated its efficacy as a treatment strategy.Results: Inhibition of HUWE1 reduces ABCA1 ubiquitination and promotes cholesterol efflux, decreasing intracellular cholesterol and reducing the expression of phosphorylated ZAP-70, CD25, and other activation markers, culminating in the suppressed proliferation of CD4+ T cells. Moreover, pharmacological inhibition of HUWE1 significantly reduces CD4+ T-cell infiltration in the submandibular glands and improves salivary flow rate in NOD/ShiLtj mice.Conclusion: These findings suggest that HUWE1 may regulate CD4+ T-cell activation and SS development by modulating ABCA1-mediated cholesterol efflux and presents a promising target for SS treatment.

With the growing popularity of environmental, social, and governance (ESG), ESG performance is becoming increasingly important in investors’ decisions about firms. Capital market liberalization brings in more sophisticated and mature foreign investors who are more interested in corporate ESG performance. We investigate whether capital market liberalization improves corporate ESG disclosure using Shanghai-Hong Kong Stock Connect and Shenzhen-Hong Kong Stock Connect as exogenous shocks. By compiling a comprehensive dataset of Chinese A-share listed firms from 2006 to 2019 and manually calculating the ESG disclosure score, we find that the mainland-HK Stock Connect scheme enhances corporate ESG disclosure. This effect is heterogeneous for firms with different external environments, corporate characteristics, and environmental performance. The results suggest that the competition effect dominates the role of capital market liberalization in improving ESG disclosure of mainland listed firms and firms disclose their ESG practices to cater to the need of investors. This paper enriches the empirical research on the impact of capital market liberalization on firm behavior and performance and provides a theoretical basis for strengthening regulations in ESG information disclosure.

Waterlogging is the primary abiotic factor that destabilizes the yield and quality of barley (Hordeum vulgare L.). However, the genetic basis of waterlogging tolerance remains poorly understood. In this study, we conducted a genome-wide association study (GWAS) by involving 106,131 single-nucleotide polymorphisms (SNPs) with a waterlogging score (WLS) of 250 barley accessions in two years. Out of 72 SNPs that were found to be associated with WLS, 34 were detected in at least two environments. We further performed the transcriptome analysis in root samples from TX9425 (waterlogging tolerant) and Franklin (waterlogging sensitive), resulting in the identification of 5,693 and 8,462 differentially expressed genes (DEGs) in these genotypes, respectively. The identified DEGs included various transcription factor (TF) genes, primarily including AP2/ERF, bZIP and MYB. By combining GWAS and RNA-seq, we identified 27 candidate genes associated with waterlogging, of which three TFs (HvDnaJ, HvMADS and HvERF1) were detected in multiple treatments. Moreover, by overexpressing barley HvERF1 in Arabidopsis, the transgenic lines were detected with enhanced waterlogging tolerance. Altogether, our results provide new insights into the genetic mechanisms of waterlogging, which have implications in the molecular breeding of waterlogging-tolerant barley varieties.

Oral squamous cell carcinoma (OSCC) is a life-threatening disease, associated with poor prognosis and the absence of specific biomarkers. Studies have shown that the ferroptosis-related genes (FRGs) can be used as tumor prognostic markers. However, FRGs’ prognostic value in OSCC needs further exploration. In our study, gene expression profile and clinical data of OSCC patients were collected from a public domain. We performed univariate and multivariate Cox regression analyses to construct a multigene signature. The Kaplan-Meier and receiver operating characteristic (ROC) methods were used to test the effectiveness of the signature, followed by the expression analysis of human leukocyte antigen (HLA) and immune checkpoints. The Cox regression analysis identified 4 hubs from 103 FRGs expressed in OSCC that were associated with overall survival (OS). A risk model based on the 4 FRGs was established to classify patients into high-risk and low-risk groups. Compared with the low-risk group, the survival time of the high-risk group was significantly reduced. According to the multivariate Cox regression analysis, the risk score acted as an independent predictor for OS. The accuracy of the 4 FRGs risk predictive model was confirmed by ROC curve analysis. Moreover, the low-risk group had the characteristics of higher expression of HLA and immune checkpoints, a lower tumor purity, and a higher immune infiltration, indicating a more sensitive response to immunotherapy. The novel FRGs-OSCC risk score system can be used to predict the prognosis of OSCC patients and their response to immunotherapy.

Previous studies have shown that abnormal metabolic reprogramming in CD4+ T cells could explain the occurrence of several autoimmune disorders, including Sjogren’s syndrome (SS). However, therapeutic targets of the abnormal metabolism of CD4+ T cells remain to be explored. Here, we report that glutaminase 1 (Gls1), a pivotal factor in glutaminolysis, might be involved in the pathogenesis of SS. The expression of Gls1 was upregulated in infiltrated labial CD4+ T cells and circulating CD4+ T cells of SS patients. Inhibiting Gls1 with BPTES significantly abolished the proliferation rate, as indicated by EdU, CFSE, and Western blot analyses. Additionally, BPTES downregulated the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) values of activated CD4+ T cells from SS mice. In vivo, we injected different doses of BPTES into SS-like NOD/Ltj mice and found that 10 mg/kg BPTES significantly restored the salivary flow rate. Histological and qRT–PCR analyses showed that this concentration of BPTES attenuated lymphocytic infiltration and the numbers of PCNA-positive cells and CD4+ T cells. The proportions of IFNγ-producing cells and IL-17A-producing cells and the expression of several proinflammatory cytokines, including IFNγ and IL-17A, were also affected in the salivary glands of SS-like mice. Cytokine production in circulating serum was analyzed and showed that BPTES downregulated the effector functions of Th17 cells and Th1 cells. Collectively, these results indicate a positive relationship between Gls1 and SS development. Pharmacological inhibition of Gls1 with BPTES could normalize the effector functions of CD4+ T cells and effectively attenuate the symptoms of SS.

Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3’UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.

Insects have evolved highly specific and sensitive olfactory sensory systems to detect plant hosts and mates. Chemosensory proteins (CSPs) play an important role in this process, but in this respect there is limited information on Clostera restitura, one of the most destructive defoliators of poplars in China. In the present study, we first identified seven candidate CSPs in C. restitura. Sequence alignment and phylogenetic analysis showed that these candidate proteins possessed typical characteristics of the insect CSP family and were similar to those of other Lepidoptera. These genes were expressed in different developmental stages and tissues, and the levels of expression differed after mating. Some CresCSPs were more associated with development and others with mating. They may play an important role in host recognition, egg development and mating behaviour. Furthermore, the CSPs were ubiquitously detected in all tissues and most of them were highly expressed in antennae, especially female antennae. We suggest the CresCSPs may contribute to female oviposition site recognition. CresCSPs that are highly transcribed in wings and legs, may function in gustation. This study provides a better understanding of the molecular mechanisms of olfaction in C. restitura and environmentally friendly pest management strategy for controlling C. restitura.

Survival rates for patients with gastric cancer, especially the advanced form, remain poor and the development of targeted treatments is hampered by a lack of efficient biological targets. Poly(rC) binding protein 2 (PCBP2) is an RNA‐binding protein that contributes to mRNA stabilization, translational silencing and enhancement and it has been implicated as a promoter of gastric cancer growth. In the present study, we demonstrated that the expression level of PCBP2 was higher in human gastric cancer tissues compared to adjacent normal gastric tissues. A high level of PCBP2 was correlated with worse postoperative relapse‐free survival and overall survival rates of gastric cancer patients. Small hairpin RNA‐mediated depletion of PCBP2 dramatically decreased the viability of gastric cancer cells. Cyclin‐dependent kinase 2 (CDK2) was positively regulated by PCBP2 via a direct 3′ UTR binding pathway as determined using a ribonucleoprotein immunoprecipitation assay and a biotin pulldown assay. CDK2 mediated the promoting role of PCBP2. These results suggest that PCBP2 acts as an oncogene in human gastric cancer cells and that functionally depleting PCBP2 could be considered as a potential target for gastric cancer therapy.

In spatial databases, the objects have semantic attributes as well as geographic coordinates. Considering the two aspects, we propose the diameter-aware extreme group query (DiaEG query), which searches for good $k$ -item groups of objects. We mark the $k$ -groups according to both semantic closenesses and geographic diameters. On the one hand, the semantic closeness ensures that in the good group the members should be close to the semantic query point $q$ . On the other hand, the geographic diameter ensures that the members should be close to (or far from) each other geographically. The importances of the two aspects are evaluated by the weights $\alpha $ and $1-\alpha $ . Since for non-expert users it is difficult to assign an appropriate $\alpha $ , we propose two types of DiaEG queries, namely, the threshold-satisfaction query and the best-satisfaction query. The first type searches for good groups such that their total satisfaction is not smaller than a given threshold. The second type searches for the best group that has the highest satisfaction. The satisfaction of a group is the length of the $\alpha $ range, where the group keeps having the highest score. If we map the groups into the (semantic, geographic)-space, the query results are in fact the extreme points on the convex hull in the space. Using the properties of the convex hull, we propose efficient algorithms to answer two types of queries. Instead of enumerating all $k$ -groups, our algorithms can construct the groups incrementally and terminate once the results have been found. We conduct experiments on both real and synthetic data sets, and the experimental results show that the proposed algorithms can answer the DiaEG queries efficiently.