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The semantic segmentation of remote sensing images is crucial for computer perception tasks. Integrating dual-modal information enhances semantic understanding. However, existing segmentation methods often suffer from incomplete feature information (features without integrity), leading to inadequate segmentation of pixels near object boundaries. This study introduces the concept of integrity in semantic segmentation and presents a complete integrity learning network using contextual semantics in the multiscale feature decoding process. Specifically, we propose a frequency-aware integrity learning network (FILNet) that compensates for missing features by capturing a shared integrity feature, enabling accurate differentiation between object categories and precise pixel segmentation. First, we design a frequency-driven awareness generator that produces an awareness map by extracting frequency-domain features with high-level semantics, guiding the multiscale feature aggregation process. Second, we implement a split–fuse–replenish strategy, which divides features into two branches for feature extraction and information replenishment, followed by cross-modal fusion and direct connection for information replenishment, resulting in fused features. Finally, we present an integrity assignment and enhancement method that leverages a capsule network to learn the correlation of multiscale features, generating a shared integrity feature. This feature is assigned to multiscale features to enhance their integrity, leading to accurate predictions facilitated by an adaptive large kernel module. Experiments on the Vaihingen and Potsdam datasets demonstrate that our method outperforms current state-of-the-art segmentation techniques.

Abstract Background It is known that genomic instability contributes to cancer development. Mitotically associated long non-coding RNA (MANCR) has been reported to promote genomic stability, suggesting its involvement in cancers. Therefore, this study was conducted to investigate the role of MANCR in non-small cell lung cancer (NSCLC). Methods After NSCLC (n = 60) and control (healthy subjects, n = 60) plasma samples, as well as NSCLC and paired non-tumor tissues from patients were collected, the levels of MANCR expression in plasma and tissues was detected using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Then the correlations of MANCR expression with clinical stages were confirmed. The diagnostic values of MANCR in both plasma and tissue samples for stage I/II NSCLC were analyzed using Receiver Operating Characteristic (ROC) curves. All NSCLC patients were monitored for 5 years to investigate the role of MANCR in the prediction of patients’ survival. Results MANCR expression was downregulated in both NSCLC plasma and tissue of NSCLC patients compared to controls (P 0.05). Additionally, stage I/II NSCLC patients were separated from controls using MANCR in plasma and tumor tissues as biomarkers. Lower MANCR levels in plasma and tumor were closely correlated with patients’ higher mortality rate. Conclusion MANCR is down-expressed in NSCLC patients and may serve as a diagnostic and prognostic biomarker for NSCLC.

Abstract Background Paclitaxel-induced peripheral neuropathy (PIPN) is prevalent among patients receiving paclitaxel chemotherapy, which results in sensory abnormality as well as neuropathic pain. Conventional medications lack effectiveness on PIPN. Clinical trials identified beneficial effects of acupuncture on PIPN among patients receiving chemotherapy. Here we explored the mechanisms underlying how acupuncture might alleviate PIPN. Methods A mouse model of PIPN was established by repeated paclitaxel application. Electroacupuncture (EA) was applied at ST36 and BL60 acupoints of model mice. Immunostaining, flow cytometry, behavioral assay, in vivo imaging were utilized for effects determination and mechanism exploration. Results EA ameliorated mechanical and cold pain hypersensitivities, reduced sensory neuron damage and improved loss in intra-epidermal nerve fibers (IENFs) in model mice. Macrophages infiltration were detected in DRG and sciatic nerve of model mice, which was reduced by EA. EA affected M1-like pro-inflammatory macrophage infiltration in DRG, whereas it did not affect M2-like macrophages. DRG neurons released chemoattractant CCL2 that recruited macrophages via CCR2 to DRG. EA reduced CCL2 overproduction by DRG neurons and reduced macrophage infiltration. Blocking CCR2 mimicked EA’s anti-allodynic effect, whereas exogenously applying recombinant CCL2 reversed the ameliorative effect of EA on macrophage infiltration and abolished EA’s anti-allodynia on model mice. EA ameliorated other signs of PIPN, including sensory neuron damage, sciatic nerve morphology impairment and IENFs loss. In mice inoculated with breast cancer cells, EA didn’t affect paclitaxel-induced antitumor effect. Conclusions These findings suggest EA alleviates PIPN by reducing CCL2/CCR2 mediated-pro-inflammatory macrophage infiltration into sensory ganglia as well as the sciatic nerve. Our study supports EA could be used as a potential non-pharmacological therapy for PIPN.

Abstract Strong background interference signals from normal tissues have significantly compromised the sensitive fluorescence imaging of early disease tissues with exogenous probes in vivo, particularly for sensitive fluorescence imaging of early liver disease due to the liver’s significant uptake and accumulation of exogenous nanoprobes, coupled with high tissue autofluorescence and deep tissue depth. As a proof-of-concept study, we herein report a near-infrared-II (NIR-II, 1.0-1.7 μm) light-excited “off-on-off” NIR-II fluorescent probe (NDP). It has near-ideal zero initial probe fluorescence but can turn on its NIR-II fluorescence in liver cancer tissues and then turn off the fluorescence again upon migration from cancer to normal tissues to minimize background interference. Due to its low background, a blind study employing our probes could identify female mice with orthotopic liver tumors with 100% accuracy from mixed subjects of healthy and tumor mice, and implemented sensitive locating of early orthotopic liver tumors with sizes as small as 4 mm. Our NIR-II-excited “off-on-off” probe design concept not only provides a promising molecular design guideline for sensitive imaging of early liver cancer but also could be generalized for sensitive imaging of other early disease lesions.

Abstract Background Maternal stress is a potential factor affecting fetal growth, but it is unknown whether it directly affects fetal growth restriction. This study aims to investigate the association between pre-pregnancy maternal stress with small for gestational age (SGA). Methods This study used a population-based retrospective cohort analysis to examine the association between pre-pregnancy maternal stress and SGA in offspring. Data were extracted from the National Preconception Health Care Project (NPHCP), conducted between 2010 and 2012, which encompassed preconception health-related information from 572,989 individuals across various regions in China. Logistic regression models were used to assess the associations between pre-pregnancy maternal stress variables and the risk of SGA. In addition, Synthetic Minority Over-sampling Technique (SMOTE) and Propensity Scores (PS) methods were used to enhance the model’s ability to the associations between pre-pregnancy maternal stress and SGA. Results Pre-pregnancy maternal stress was significantly associated with an increased the risk of SGA in offspring (OR 1.35, 95% CI 1.20 to 1.51, P 0.05). Specially, individuals with lower socio-economic status that characterized by below high school education levels (OR = 1.45, 95% CI: 1.23 to 1.70), farmer occupation (OR = 1.33, 95% CI: 1.15 to 1.55, P = 0.002), rural residence (OR = 1.38, 95% CI: 1.22 to 1.56, P

Abstract Electrocatalytic oxidation of more stable 2,5-furanedimethanol (FDM) for 2,5-furanediformic acid (FDCA) generation with concurrent hydrogen production is attractive but still nascent compared to 5-Hydroxymethyl-2-furaldehyde (HMF). The need for effective and stable bifunctional electrocatalysts that are efficient for the FDM cell is thus quite significant. Wood serves as an ideal matrix for boosting the performance of catalysts, since its hierarchical porous structures facilitate mass transport and provide abundant active sites. Unfortunately, it has never been demonstrated for electrochemically organic synthesis. Herein, the effectiveness of Fe-CoP in catalyzing FDM oxidation was demonstrated by density functional theory (DFT) calculations and experiments, and a renewable carbonized porous wood decorated with Fe-doped CoP nanoleaves (Fe-CoP/CW) was constructed for electrocatalytic FDCA and hydrogen generation. The obtained Fe-CoP/CW as an anode in FDM solution afforded a current density of 100 mA cm−2 with a yield of 90% FDCA at a potential no more than 1.50 V vs RHE, which was 90 mV and 350 mV lower than Fe-CoP/carbon cloth (CC) and IrO2. In addition, Fe-CoP/CW showed excellent long-term stability for 108-h FDM oxidation in strong alkaline solution. Remarkably, in stark contrast to Fe-CoP/CC and Pt, the hydrogen evolution performance of Fe-CoP/CW was not impacted by FDM at the cathode, and it required exceptionally low overpotentials of 0.19 V to achieve 100 mA cm−2. As a result, in terms of the overall cell, the hydrogen production rate was 0.756 mmol cm−2 h−1, which was 3.57 times higher than those of commonly used commercial Pt | IrO2 cell, presenting a Faraday efficiency of near 100%. This work will pave the way towards the implementation of highly suited bifunctional electrodes and the possibility of affordable, effective, and environmentally-friendly wood-derived electrocatalysts for electrochemically organic synthesis. Graphical Abstract

Abstract Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, influenced by both environmental and genetic factors. Single nucleotide polymorphism (SNP) in the human genome may influence the risk of developing COPD and the response to treatment. We assessed the effects of gene polymorphism of inflammatory and immune-active factors and gene-environment interaction on risk of COPD in middle-aged and older Chinese individuals. Methods In this community-based case–control study, 471 patients with COPD and 485 controls aged 40–76 years in Heilongjiang Province, China were included. Face-to-face interviews, lung function tests, and multiplex polymerase chain reaction were used to obtain data. Logistic regression model, generalized multifactor dimensionality reduction and crossover analysis were used to analyse the effects of SNPs, gene–gene interactions, and gene-environment interactions on COPD. Results CRP gene[rs1130864-A allele (OR, 1.77; 95% CI 1.11–2.81); G/A + A/A genotype (OR, 1.75; 95% CI 1.07–2.84)], FCAR gene[rs4806606-G (OR, 0.72; 95% CI 0.53–0.98); rs8112766-G (OR, 0.79; 95% CI 0.64–0.98)] and FCGR2A gene[rs4656308-C (OR, 0.74; 95% CI 0.55–1.00); rs4656309-T (OR, 0.81; 95% CI 0.66–0.99)] are independent influential factors for COPD. Rs1205 [RERI: 0.15 (0.07–1.00)] and rs1130864 [RERI: 2.45 (0.73–4.18)] of CRP gene, rs11084376 [OR: 0.54 (0.29–0.97)] of FCAR gene, rs844 of FCGR2B [SI: 0.30 (0.11–0.77); OR: 0.46 (0.24–0.90)] gene, rs4656308-rs4656309-rs2165088 haplotype [SI: 0.48 (0.26–0.89)] of FCGR2A gene and exposure to smoking index > 200, indoor coal/wood/straw use, and outdoor straw burning play synergistic or antagonistic roles in the development of COPD. Conclusions Alleles and genotypes of the CRP/FCAR/FCGR2A gene can increase the susceptibility to COPD in the northern Chinese population. For the first time, environmental exposure to the CRP/FCAR/FCGR2A/FCGR2B genes has been shown to have synergistic or antagonistic effects on COPD susceptibility on genotypes or haplotypes.

Abstract Background HER2-positive breast cancer (BC) is a subtype of breast cancer. Increased ERBB3 expression has been implicated as a potential cause of resistance to other HER-targeted therapies. Our study aimed to screen and validate prognostic markers associated with ERBB3 expression by bioinformatics and affecting the prognosis of HER2 staging. Methods Analyzing differences in ERBB3-related groups. ERBB3 expression-related differentially expressed genes (DEGs) were identified and intersected with survival status-related DEGs to obtain intersected genes. Three algorithms, LASSO, RandomForest and XGBoost were combined to identify the signature genes. we construct risk models and generate ROC curves for prediction. Furthermore, we delve into the immunological traits, correlations, and expression patterns of signature genes by conducting a comprehensive analysis that encompasses immune infiltration analysis, correlation analysis, and differential expression analysis. Results Significant variability in ERBB3 expression and prognosis in high and low ERBB3 expression groups. Twenty-five candidate DEGs were identified by intersecting ERBB3-related DEGs with survival-related DEGs. Utilizing three distinct machine learning algorithms, we identified three signature genes-PBX1, IGHM, and CXCL13-that exhibited significant diagnostic value within the diagnostic model. In addition, the risk model had better prognostic and predictive effects, and the immune infiltration analysis showed that IGHM, CXCL13 might affect the proliferation of BC cells through immune cells. Functional studies demonstrated that interference with PBX1 inhibited the proliferation, migration, and epithelial-mesenchymal transition process of HER2-positive BC cells. Conclusion PBX1, IGHM and CXCL13 are associated with the expression level of the ERBB3 and are prognostic markers for HER2-positive in BC, which may play an important role in the development and progression of BC.

Abstract Considerable advances have been achieved in the application of nanomaterials for immunotherapies, yet the precise immune effects induced by protein corona remain elusive. Here, we explore the formation mechanism and immune regulation process of protein corona in acute myeloid leukaemia (AML) mouse models using commercialized iron oxide nanoparticles (IONPs), with different surface modifications, including an FDA-approved variant. Using macrophages depleted or Complement Component 3 (C3) knockout mice, we demonstrate that carboxymethyl dextran-coated IONP (IONP-COOH) reduces leukaemia burden. Mechanistically, IONP-COOH indirectly binds to C3b after activating the complement alternative pathway, subsequently enhancing phagocytosis of macrophages and activating adaptive immunity mediated by complement corona. While aminated dextran-coated IONPs directly absorb C3b and activate the lectin pathway, leading to immune cell exhaustion. Our findings suggest that IONP-COOH may serve as an immune activator for AML treatment, offering a promising approach to developing therapeutic nanomaterials by leveraging surface chemistry to enhance immunotherapy.

Abstract Background Chronic atrophic gastritis (CAG) is a chronic disease of the gastric mucosa characterized by a reduction or an absolute disappearance of the original gastric glands, possibly replaced by pseudopyloric fibrosis, intestinal metaplasia, or fibrosis. CAG develops progressively into intestinal epithelial metaplasia, dysplasia, and ultimately, gastric cancer. Epidemiological statistics have revealed a positive correlation between the incidence of CAG and age. Mesenchymal stem cells (MSCs) are a type of adult stem cells derived from mesoderm, with strong tissue repair capabilities. Therefore, the restoration of the gastric mucosa may serve as an efficacious strategy to ameliorate CAG and avert gastric cancer. However, the mechanisms by which MSCs inhibit the relentless progression of aging atrophic gastritis remain to be elucidated. This study endeavored to assess a novel approach utilizing MSCs to treat CAG and forestall carcinogenics. Methods In this study, we selected mice with atrophic gastritis from naturally aging mice and administered human umbilical cord-derived mesenchymal stem cells (hUMSCs) via tail vein injection to evaluate the therapeutic effects of hUMSCs on age-related chronic atrophic gastritis. Initially, we employed methods such as ELISA, immunohistochemical analysis, and TUNEL assays to detect changes in the mice post-hUMSC injection. Proteomic and bioinformatics analyses were conducted to identify differentially expressed proteins, focusing on NADH: ubiquinone oxidoreductase core subunit S8 (Ndufs8). Co-culturing hUMSCs with Ndufs8 knockout gastric mucosal epithelial cells (GMECs), we utilized flow cytometry, Western blotting, real-time quantitative PCR, and immunofluorescence to investigate the mechanisms of action of hUMSCs. Results We observed that hUMSCs are capable of migrating to and repairing damaged gastric mucosa. Initially, hUMSCs significantly enhanced the secretion of gastric proteins PG-1 and G17, while concurrently reducing inflammatory cytokines. Furthermore, hUMSCs mitigated gastric fibrosis and apoptosis in mucosal cells. Proteomic and bioinformatic analyses revealed alterations in the protein network involved in mitochondrial autophagy, with Ndufs8 playing a pivotal role. Upon knocking out Ndufs8 in GMECs, we noted mitochondrial damage and reduced autophagy, leading to an aged phenotype in GMECs. Co-culturing Ndufs8-knockout GMECs with hUMSCs demonstrated that hUMSCs could ameliorate mitochondrial dysfunction and restore the cell cycle in GMECs.

Abstract In the knowledge economy, expert-led teams emerge as a pivotal strategy for organizations to secure and maintain a competitive edge. Expert leaders have been shown to have a significant influence on team effectiveness in numerous knowledge-intensive teams. Using an evolutionary game model, this study explores the fundamental mechanism in the value creation process by experts-led teams and finds out: First, experts’ role modeling, coaching, and professional authority motivate team members to contribute their efforts and abilities, leading to the 1 + 1 > 2 synergistic effect. Second, among various forms of team value creation, expert-led teams are a crucial organizational structure which enables stable and long-term enhancements in accumulating team human capital to improve productivity. Moreover, the greater the role played by expert leaders, the faster the evolution progresses of team members’ abilities. This study emphasizes the importance of using expert leaders in human resource management to promote the effectiveness of knowledge-intensive teams.

Abstract Objective The potential of immune-related adverse events (irAEs) in predicting the efficacy of PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) has rarely been assessed. This study investigated the associations between irAEs and the clinical efficacy of PD-1 inhibitors combination therapy in patients with advanced NSCLC. Methods A retrospective analysis was conducted of 73 patients with advanced NSCLC receiving PD-1 inhibitors combination therapy from January 2022 and July 2023. Patients were divided into two cohorts: patients with irAEs and patients without irAEs. We conducted an analysis to investigate the impact of irAEs on these different clinical outcomes. Results There were no significant differences observed in clinical characteristics between the two cohorts, except for smoking status (P = 0.011).The cohort with irAEs exhibited a higher objective response rate (ORR) and disease control rate (DCR) compared to the cohort without irAEs (ORR: 32.5% vs 12.1%, P = 0.040; DCR: 80.0% vs 48.5%, P = 0.010).Moreover, the median progression-free survival (PFS) and overall survival (OS) were significantly better in the cohort with irAEs compared to the cohort without irAEs (PFS: 12.4 months vs 6.8 months, P = 0.009; OS: not reached vs 18.3 months, P = 0.024). Additionally, the multivariate COX regression analysis revealed that mild irAEs (PFS: HR = 0.386, 95% CI: 0.199–0.748, P = 0.005; OS: HR = 0.300, 95% CI: 0.105–0.855, P = 0.024) and single-system irAEs (PFS: HR = 0.401, 95% CI: 0.208–0.772, P = 0.006; OS: HR = 0.264, 95% CI: 0.090–0.776, P = 0.015) were identified as independent prognostic factors for both PFS and OS. Conclusions IrAEs, especially thyroid irAEs, as well as mild or single-system irAEs, may serve as predictors of improved efficacy in advanced NSCLC patients receiving PD-1 inhibitors combination therapy.

Abstract Background As a widespread epidemic, obesity poses a significant risk to health and leads to physiological abnormalities, including diabetes mellitus and inflammation. Obesity-induced inflammation can accelerate the development of various cancers; however, the role of obesity in the migration of ovarian carcinoma is still unclear. Results Twenty-four commonly upregulated genes were identified from single-cell RNA sequencing datasets of both ovarian carcinoma and adipose tissue of obese humans, with the chemokine CXCL10 showing a significant increase in adipose tissues associated with obesity. And CXCL10 treated primed macrophages exhibit both direct and indirect effects on the proliferation, apoptosis, migration, and invasion of ovarian adenocarcinoma cells. The treatment of CXCL10 on the SKOV3 cells enhances FAK expression and phosphorylation, thereby accelerating the migration and invasion of ovarian cancer cells. Conditioned medium-derived from CXCL10-treated THP-1 cells significantly promoted ovarian cancer cell migration and invasion, which may be attributed to the increased expression of C1QA, C1QC, CCL24, and IL4R in macrophages. Conclusions Obesity exacerbates the production of CXCL10 from adipose tissues in obese women. CXCL10 is a key hub factor between developments of ovarian cancer and adipose tissues in obese. Targeting adipose-derived CXCL10 or its downstream macrophages may be a potential strategy to alleviate ovarian cancer accompanied by obesity.

Abstract Objective The objective was to explore the characteristics of risk factors in children with cerebral palsy (CP), focusing on the effects of single risk factors and the number of risk factors on the classification, GMFCS level, and comorbidities of children with CP. Methods The medical records of children with CP hospitalized from 2015 to 2023 were reviewed. The effects of nine risk factors, such as hyperbilirubinemia, asphyxia, and HIE, on the classification, GMFCS level and comorbidities of children with CP were studied. Results In Part 1, among the 536 children with CP, 476 (88.8%) had obvious risk factors. Preterm birth and/or low birth weight were the most common risk factor (243 cases (45.3%)). CP combined with two risk factors was the most common, with 147 cases (27.4%). In Part 2, neonatal seizures were associated with epilepsy, and HIE and hyperbilirubinemia were associated with intellectual disability. Asphyxia was associated with high GMFCS levels and mixed CP. Preterm birth and/or low birth weight was associated with spastic diplegia, and hyperbilirubinemia was associated with involuntary movement. In Part 3, the number of risk factors in children with CP with epilepsy and/or hearing impairment seemed to be lower, but those with spastic quadriplegia were more likely to have more risk factors (≥ 4). In the six groups with 1–6 risk factors, intellectual disability and a GMFCS level ≥ level IV were more common in the various risk factor groups, but spastic hemiplegia and ataxia were less common. Conclusion Most children with CP have apparent risk factors, and the combination of two risk factors is relatively common. Preterm birth/low birth weight is the most common risk factor. The analysis of single risk factors revealed that the risk factors were related to the classification, GMFCS level and comorbidities. This correlation is consistent with the current research. Risk factors were more common in children with severe CP, high GMFCS levels, spastic quadriplegia, and intellectual disability.

With the rapid development of satellite communications, satellite antennas attract growing interest, especially the high-throughput SatCom-on-the-move antenna for providing high-speed connectivity in a mobile environment. While conventional antennas, such as parabolic dishes and planar waveguide arrays, enjoy a growing market, new kinds of antennas keep on emerging to meet diversified requirements in various satellite communication scenarios. This paper first introduces the design requirements, categories, and evolutions of SatCom-on-the-move antennas, and then discussed representative designs of mechanical scanning antennas and electronic scanning antennas, including their structures, principles, characteristics, and limitations in practical applications. Given the new requirements of satellite communications, this paper also highlighted some of the latest progress in this field, including the Monolithic Microwave Integrated Circuit (MMIC)-based phased array antenna, the metasurface-based phased array antenna, and their hybrid versions. Finally, some critical challenges facing future antennas are discussed. It is believed that it's necessary to put concerted efforts from antenna, microwave, and material communities, etc., to advance SatCom-on-the-move antennas for the upcoming era of satellite communication.

Abstract Background Scutellaria baicalensis Georgi, a traditional Chinese herb, is known for its various biological effects, including antibacterial, anti-inflammatory, antioxidative, and antitumor properties. However, the function and mechanisms of methanol extract of Scutellaria baicalensis Georgi (MESB) in treating hepatic fibrosis remain unclear. Methods This study utilized a CCl4-induced mouse model of hepatic fibrosis to assess the effects of MESB through histopathological analysis and serum tests. The anti-fibrosis mechanism of MESB was investigated using qPCR, Western blotting, RNA interference, proteomics, and metabolomics. Spatial metabolomics identified key components of MESB in liver tissue, while molecular docking determined their targets. Results Treatment with MESB alleviated hepatic pathological changes and reversed hepatic fibrosis in the CCl4-induced models, as evidenced by decreased collagen fibers deposition, reduced expression of hepatic fibrosis markers COL1A1, FN, and PAI-1, and lowered serum levels of AST and ALT. In vitro, MESB inhibited the proliferation of LX-2 cells and the expression of hepatic fibrosis markers. Furthermore, MESB intervention modulated various pathways, particularly those involved in metabolic pathways. Subsequent metabolomics analysis demonstrated that MESB disrupted glycerophospholipid metabolism and suppressed arachidonic acid metabolism. MESB downregulated the expression of cPLA2 in LX-2 cells, leading to decreased production of arachidonic acid and its downstream inflammatory mediators. Meanwhile, MESB inhibited the expression of cPLA2 and its downstream NF-κB pathway in the liver tissues of models induced by CCl4. Additionally, silencing cPLA2 markedly reduced the expressions of COL1A1, FN, and PAI-1. Spatial metabolomics analysis confirmed the penetration of baicalein, wogonin and wogonoside into liver tissue. Further results indicated that baicalein and wogonin inhibited the expression of cPLA2, while baicalin and wogonoside do not exhibit this effect. Moreover, molecular docking suggested that baicalein and wogonin possess the potential to directly interact with cPLA2. Conclusion This study reveals that MESB is crucial in preventing hepatic fibrosis via the cPLA2-mediated arachidonic acid metabolic pathway, highlighting its key active components as potential drugs for fibrosis treatment.

Abstract Background The mucus layer provides the first defense that keeps the epithelium free from microorganisms. However, the effect of the small intestinal mucus layer on pathogen invasion is still poorly understood, especially for swine enteric coronavirus. To better understand virus‒mucus layer‒intestinal epithelium interactions, here, we developed a porcine intestinal organoid mucus‒monolayer model under air‒liquid interface (ALI) conditions. Results We successfully established a differentiated intestinal organoid monolayer model comprising various differentiated epithelial cell types and a mucus layer under ALI conditions. Mass spectrometry analysis revealed that the mucus derived from the ALI monolayer shared a similar composition to that of the native small intestinal mucus. Importantly, our results demonstrated that the ALI monolayer exhibited lower infectivity of both TGEV and PEDV than did the submerged monolayer. To further confirm the impact of ALI mucus on coronavirus infection, mucus was collected from the ALI monolayer culture system and incubated with the viruses. These results indicated that ALI mucus treatment effectively reduced the infectivity of TGEV and PEDV. Additionally, Mucin 2 (Muc2), a major component of native small intestinal mucus, was found to be abundant in the mucus derived from the ALI monolayer, as determined by mass spectrometry analysis. Our study confirmed the potent antiviral activity of Muc2 against TGEV and PEDV infection. Considering the sialylation of Muc2 and the known sialic acid-binding activity of coronavirus, further investigations revealed that the sialic acid residues of Muc2 play a potential role in inhibiting coronavirus infection. Conclusions We established the porcine intestinal organoid mucus monolayer as a novel and valuable model for confirming the pivotal role of the small intestinal mucus layer in combating pathogen invasion. In addition, our findings highlight the significance of sialic acid modification of Muc2 in blocking coronavirus infections. This discovery opens promising avenues for the development of tailor-made drugs aimed at preventing porcine enteric coronavirus invasion.

Abstract Objective This study aimed to investigate a range of insomnia-related factors, including difficulty with sleep induction, nocturnal awakenings, early awakenings, total sleep time, overall sleep quality, well-being, functioning, and daytime drowsiness, to determine which variables were significantly associated with subsequent adolescent suicide attempts. Method A total of 782 students aged 11–16 years old from one middle school in Changsha, China completed the survey at baseline and 6 months follow-up with a prospective cohort design. The binary logistic regression models were used to analyze the associations between insomnia variables and suicide attempts during the 6 months follow-up. Results The new incidence rate of suicide attempts was 4.60% (36/782) at 6-month follow-up. Insomnia was a significant predictor of incident suicide attempts (OR = 6.00; 95%CI, 2.47–14.60). After adjusting for age, gender, nationality, stress, anxiety and depression, insomnia was found to predict suicide attempts only among female (OR = 4.28; 95%CI, 1.41–12.98) and only nocturnal sleep disruption was significantly associated with an increased risk of suicide attempts (OR = 2.74; 95%CI, 1.32–5.71). Conclusions Nocturnal sleep disruption are independently associated with increased risk of suicide attempts. Intervention for nocturnal sleep disruption may be important for early identification as well as prevention of adolescent suicide, especially among adolescent girls.

Abstract Sequential recommendation systems capture the dynamic interests of users and predict their future preferences. A noteworthy problem in sequential recommendation is coping with the intrinsic changes of user interests. The sequence of user interactions is generated by more than a single and stable global preference, users may have interest drift that occur in a short period of time. We call this short-term interest drift as the local preference of users, which is often a key factor affecting the final choice of users. However, existing methods have limitations in observing local preferences, which leads to an incomplete consideration of the local preferences. Moreover, using a single model to represent global–local preferences obscure the distinct features of each, limiting the potential synergistic benefits. To alleviate the above limitations, we propose a novel model with a dual-channel structure to monitor both global and local preferences and ensure they complement each other. The model extracts the global preferences of users with a bidirectional Transformer using random masking and a sliding window, and extracts the local preferences with a patch-based stacked bottleneck residual convolution. To enable the model to consider both the global and local preferences of users, we design an adaptive orthogonal fusion module, which effectively fuses the two preferences and enables the two feature types to complement and enhance each other. We integrate the fused user preferences with a knowledge distillation method that further improves the model’s expressive ability. We conduct extensive experiments on three widely used datasets, and the results show that our model outperforms current state-of-the-art models.

Abstract Background Global climate change significantly impacts ecosystems, particularly through temperature fluctuations that affect insect physiology and behavior. As poikilotherms, insect pests such as the globally devastating diamondback moth (DBM), Plutella xylostella, are especially vulnerable to rising temperatures and extreme heat events, necessitating effective adaptive mechanisms. Results Here we demonstrate the roles of zinc finger proteins (ZFPs) in mediating thermal adaptability in DBM. We utilized a comprehensive approach involving cloning and bioinformatics analysis of three ZFPs, PxZNF568, PxZNF93, and PxZNF266, measurement of their expression levels in hot-evolved and control strains, and assessment of catalase enzymatic activity and total antioxidant capacity. We also employed CRISPR/Cas9 technology to create five stable homozygous knockout strains to elucidate ZFP functions in high-temperature tolerance. Survival rates under high-temperature stress and the critical thermal maxima (CTMax) of the knockout strains were significantly lower than the wild-type strain, and exhibited marked decreases in antioxidant capacity. Conclusion Findings reveal the importance of ZFPs in thermal adaptability of DBM, contributing critical insights for future pest management strategies in the context of a warming climate and laying the foundation for further exploration of ZFP functionality in agricultural pest control.

Abstract Background Human immunodeficiency virus (HIV) is a retrovirus mainly infecting immune cells. Central nervous system diseases in HIV-infected patients can be caused by HIV or opportunistic infections. Neurological diseases associated with HIV have diverse manifestations and may occur in early or late stages. This article reports an HIV patient with myelopathy as initial symptom and negative spinal cord magnetic resonance imaging (MRI) and reviews common classifications of HIV-related spinal cord diseases. Case presentation A 50-year-old male presented with weakness in both lower limbs and gait disorders for more than three months. Physical examination and various tests ruled out many possible causes. Given positive HIV and syphilis antibody in serological examination, normal spinal cord MRI and electromyogram, and after excluding other potential diagnoses through comprehensive analysis, the diagnosis of HIV-related myelopathy was established. Conclusions Spinal cord lesions caused by HIV infection involve multiple aspects in terms of etiology and mechanism. HIV infection-related vacuolar myelopathy (HIV-VM) is the most common and typical spinal cord lesion. It usually appears at a relatively late stage of HIV infection, but it may also occur in the early stage and even serve as the initial manifestation of newly diagnosed HIV. The diagnosis of HIV myelopathy is usually exclusionary. In imaging, it often shows high T2 signal and spinal cord atrophy on spinal cord MRI, or it may also appear normal. Clinical Trial Not applicable.

Introduction: The prevention and treatment of chronic obstructive pulmonary disease (COPD) is closely tied to antioxidation and anti-inflammation. Phycocyanin (PC) has numerous pharmacological effects, such as antioxidation and anti-inflammation. However, it remains unclear whether PC can play a therapeutic role in COPD. Objective: As inflammation and oxidative stress can aggravate COPD, this study is to explore the effect of PC on COPD mice and its mechanisms. Methods: The COPD mice model was established by exposing them to lipopolysaccharide (LPS) and cigarette smoke (CS); PC was administrated in a concentration of 50 mg/kg for 30 days. On the last day, lung function was measured, and bronchoalveolar lavage fluid (BALF) was obtained and classified for cells. Lung tissue pathological change was analyzed, and organ indices statistics were measured. Based on molecular docking, the mechanism was explored with Western blotting, immunohistochemical, and immunofluorescence in vivo and in vitro. Results: PC significantly ameliorated the pulmonary function of COPD mice and reduced inflammation of the lung (p

Abstract Background Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Dysbiosis of gut microbiota acts as a cause of Treg abnormalities. However, the intestinal metabolic impact of PNS with children remains poorly understood. This study aims to investigate the dynamic changes of gut microbiota and it’s metabolism in children with PNS. Methods Fecal and peripheral blood samples were separately collected from patients with initial diagnosis of PNS (PNS_In group), recurrence of PNS (PNS_Re group), and healthy controls (HCs group). The fecal samples were subjected to the microbiome and metabolome by the multi-omics analysis. Additionally, the peripheral blood samples were collected and associated inflammatory indicators were determined. Results We found that in PNS_In group, lipopolysaccharide (LPS), pro-inflammatory interleukin (IL)-6, IL-17A, IL-23p19, and IL-1β were significantly increased compared with those in HCs group. However, these abnormalities were dramatically reversed in PNS_Re group treated with prednisone acetate. Moreover, the crucial Treg/Th17 axis in PNS inflammation was also proved to be discriminated between PNS and HCs. Gut microbial dysbiosis was identified in PNS_In and PNS_Re patients. At the genus level, compared to HCs group, the abundance of Faecalibacterium notably changed in PNS_In and PNS_Re groups, showing negatively correlated with inflammatory factors. Moreover, the fecal metabolome of PNS_In and PNS_Re remarkably altered with the major impacts in the metabolism of phenylalanine, ABC transporters, arginine and proline. Conclusion The dynamic changes of gut microbiota and associated metabolites are closely correlated with initial period and recurrence of PNS in children via probably regulating inflammatory Th17/Treg axis, which may potentially provide novel targets for the control of the disease. Clinical trial number Not applicable.

Abstract Abnormal antioxidant capacity of cancer is closely related to tumor malignancy. Modulation of oxidative stress status is a novel anticancer therapeutic target. Nrf2 is a key regulator of various antioxidant enzymes, but the mechanism of its deubiquitination remains largely unclear. This study unveiled that Nrf2 received post-transcriptional regulation from a proteasome-associated deubiquitinating enzyme, USP11, in colorectal cancer (CRC). It was found that USP11 was overexpressed in CRC tissues acting as an oncogene by inhibiting mitochondrial apoptosis, and USP11 managed to maintain balance in the production and elimination of reactive oxygen species (ROS). Mechanistically, we identified a feedback loop between USP11 and Nrf2 maintaining the redox homeostasis. USP11 stabilized Nrf2 by deubiquitinating and protecting it from proteasome-mediated degradation. Interestingly, we also map that Nrf2 could bind to the antioxidant reaction element (ARE) in the USP11 promoter to promote its transcription. Hence, USP11/Nrf2 positive feedback loop inhibited mitochondrial apoptosis of CRC cells by activating Nrf2/ARE signaling pathway, thus promoting CRC progression. Schematic diagram of the mechanism by which USP11/Nrf2 positive feedback loop inhibited mitochondrial apoptosis in CRC cells. This study found that USP11 was highly expressed in colorectal cancer (CRC) tissue and was associated with poor prognosis. In CRC, the inhibition of USP11 expression could promote the ubiquitination degradation of Nrf2, thereby inhibiting the Nrf2/ARE signaling pathway. This led to an increase in reactive oxygen species in the cell, causing mitochondrial apoptosis. In addition, Nrf2 could bind to the promoter region of USP11 to promote its transcription, both of which formed positive feedback loop.

Regulated cell death is a pivotal regulatory mechanism governing the development and homeostasis of multicellular organisms. A comprehensive understanding of RCD's regulatory mechanisms is crucial for developing novel therapeutic strategies against diseases associated with cell death, such as cancer and neurodegenerative diseases. However, existing data repositories support limited types of cell death data and lack comprehensive annotation and analytical functionalities. Thus, establishing an extensive cell death database is an urgent imperative. To address this gap, we developed the Regulated Cell Death Database (RCDdb, chenyclab.com/RCDdb), the first comprehensively manually annotated database designed to support annotations and analytical capabilities across all RCD types. We compiled 3090 marker gene annotations associated with 15 RCD types from 2180 relevant articles. The RCDdb includes annotation data on these marker genes concerning diseases, drugs, pathways, proteins, and gene expressions. Furthermore, it provides 49 diverse visualization methods to present this information. More importantly, the RCDdb features three online analysis tools for identifying and analyzing RCD-related features within user-submitted data. Furthermore, the RCDdb offers a user-friendly interface for querying, browsing, analysis, and visualization of detailed information associated with each RCD category. This resource promises to significantly aid researchers in better understanding the mechanisms of cell death, thereby accelerating progress in research and therapeutic strategies aimed at combating RCD-related diseases.

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

ObjectiveTo analyze the historical development and policy structure of China′s Patriotic Health Campaign policy, in order to provide theoretical, methodological and empirical references for the optimization of relevant policies. MethodsWe collected documents relevant to the Patriotic Health Campaign issued by Chinese national government agencies from 1952 to 2023 from relevant government portals, such as the State Council and the National Health Commission, as well as from Peking University′s Fabao and Legal Star databases. From the perspective of policy instruments, we established a three-dimensional analytical framework by organically combining policy instruments and policy objectives with the policy change process. Content analysis was used to systematically analyze policy goal setting and policy instrument selection at different stages. ResultsA total of 79 policy documents were included in this study. From the perspective of policy instruments, command and control instruments were most frequently used (54.82%) and were the main tools to achieve policy objectives in the process of policy development. Capacity building instruments (23.57%) and information and persuasion instruments (16.28%), as commonly used policy instruments, played an important role in achieving policy objectives. Incentive instruments (3.39%) and systems change instruments (1.95%) were used less frequently. In terms of policy objectives, population health (40.34%) and regional health (50.43%) accounted for a relatively high proportion, while social-ecological system health accounted for a relatively low proportion (9.23%). ConclusionsFrom the perspective of policy instruments, China′s Patriotic Health Campaign-related policies are dominated by command and control instruments, with a lack of use of incentive and system change instruments. In terms of policy objectives, more attention has been paid to population health and regional health objectives, and the preference for policy instrument selection varies with different policy objectives. With the development of policy stages, policy instruments have become increasingly rich and diverse, but their internal distribution is still uneven.

Abstract This study investigates the effectiveness of Azvudine and nirmatrelvir-ritonavir (Paxlovid) in treating COVID-19 pneumonia through an analysis of real-world clinical data. We retrospectively collected data from COVID-19 patients hospitalized at the Second Xiangya Hospital of Central South University between December 21, 2022, and January 18, 2023. Using kernel density estimation, box-and-whisker plots, and Schoenfeld residual plots, we evaluated the transition of patients to negative status and assessed factors such as age, disease severity, and treatment effects. The findings revealed that both Azvudine and Paxlovid significantly reduced recovery times, with Azvudine showing notable benefits for patients aged 50–80. Our analysis indicated that these drugs improved lung CT values and reduced disease severity in moderate cases. The Cox model demonstrated robustness in predicting outcomes, and a nomogram was developed for individualized recovery probability assessment. These results provide important insights into optimizing COVID-19 treatment and the potential of predictive models in clinical decision-making.

Abstract We conducted a large-scale whole-brain morphometry study by analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We registered 204 mouse brains of three major imaging modalities to the Allen Common Coordinate Framework (CCF) atlas, annotated 182,497 neuronal cell bodies, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1876 neurons along with their axonal motifs, and detected 2.63 million axonal varicosities that indicate potential synaptic sites. Our analyzed six levels of information related to neuronal populations, dendritic microenvironments, single-cell full morphology, dendritic and axonal arborization, axonal varicosities, and sub-neuronal structural motifs, along with a quantification of the diversity and stereotypy of patterns at each level. This integrative study provides key anatomical descriptions of neurons and their types across a multiple scales and features, contributing a substantial resource for understanding neuronal diversity in mammalian brains.

Abstract Introduction Developmental delay (DD) and intellectual disability (ID) are key manifestations of neurodevelopmental disorders (NDDs), characterized by considerable clinical and genetic variability, which complicates genetic diagnosis. Whole exome sequencing (WES) has become an effective method for uncovering genetic causes in patients with unexplained DD/ID. Methods We retrospectively analyzed WES data from 280 patients diagnosed with unexplained DD/ID. Demographic information and genetic variants identified through WES were assessed, along with an evaluation of clinical factors that might influence the detection of genetic causes. Results Pathogenic variants were detected in 73 cases (36.07%), including 25 cases involving pathogenic chromosomal copy number variations. Clinical factors such as age, sex, gestational age, birth weight, anoxia, jaundice, associated symptoms, family history, muscle strength, muscle tone, epilepsy, brain MRI findings, EEG results, and the severity of DD/ID did not significantly impact the WES outcomes. However, a significant correlation was observed between delivery mode and positive WES results, with a higher diagnostic yield among patients delivered via caesarean section. Conclusions WES is a valuable approach for identifying genetic causes in patients with unexplained DD/ID, providing benefits for patient management, family genetic counseling, and long-term prognosis assessment. Clinical trial number Not applicable.

Abstract Background While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom. Methods This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence. Results After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95%CI:0.99–1.30) approached statistical significance after full adjustment for mediators. In contrast, in the UK cohort, significant associations persisted for most TyG Index indicators when full adjustment for mediators, including BMI (HR: 1.17, 95% CI: 1.09–1.26), TyG-BMI (HR: 1.16, 95% CI: 1.07–1.26), TyG-WC (HR: 1.13, 95% CI: 1.03–1.25), TyG-FMI (HR: 1.17, 95% CI: 1.07–1.28), and TyG-RBI (HR: 1.15, 95% CI: 1.06–1.24). TyG-BRI also showed the best predictive performance for ischemic stroke in Chinese rural residents (AUC > 0.7) and exhibited an almost linear relationship with ischemic stroke occurrence. Additionally, TyG-BRI presented a U-shaped relationship with the risk of hemorrhagic stroke incidence in the UK (p overall = 0.041, p non-linear = 0.017). Multimorbidity mediated the relationship between TyG indices, and ischemic stroke incidence in both cohorts. The mediation percentage for multimorbidity was higher than the sum of individual chronic diseases, with a higher mediation percentage in the Chinese cohort (up to 51%) compared to the UK cohort (up to 27.2%). Conclusions Chinese rural residents exhibit higher levels of visceral obesity compared to residents in UK, leading to greater stroke susceptibility mediated by multimorbidity. These findings underscore the importance of comprehensive management of multimorbidity for stroke prevention. The TyG-BRI may serve as a promising predictor of ischemic stroke incidence among rural community residents.

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder accompanied by ovulatory dysfunction. Insulin resistance (IR) is a key pathogenic mechanism in PCOS, and insulin sensitizers, such as metformin and pioglitazone, can improve PCOS symptoms. Chiglitazar, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is also an insulin sensitizer; however, its therapeutic effects have not yet been studied in PCOS. We evaluated the therapeutic effects of chiglitazar in a rat model of PCOS. Methods Sprague–Dawley rats aged 4 weeks were injected subcutaneously with dehydroepiandrosterone (DHEA) (6 mg/100 g/day) to establish PCOS, and a control (CON) group was established. The rats were divided into the CON, PCOS model (DHEA), pioglitazone-treated (DHEA + PIO), and chiglitazar-treated (DHEA + CHI) groups. The DHEA + PIO group received pioglitazone (20 mg/kg/day) and the DHEA + CHI group received chiglitazar (20 mg/kg/day), each for 15 days. Body weight, estrous cycle, and glucose tolerance test (GTT) and insulin resistance test (ITT) results were monitored. Experimental animal energy metabolism systems were utilized to assess metabolic parameters. Enzyme-linked immunosorbent assay was conducted to detect changes in serum hormones, including insulin, adiponectin, sex-related hormones, and lipid metabolism indicators. The ovaries were used for molecular biology experiments to detect changes in Akt/phosphorylated Akt and glucose transporter 4 (GLUT4) expression by Western blotting and quantitative polymerase chain reaction. Results Chiglitazar and pioglitazone improved PCOS symptoms. However, chiglitazar demonstrated a more pronounced effect on lipid improvement and weight gain than pioglitazone. In the DHEA + PIO and DHEA + CHI groups, there was notable recovery in oxygen consumption and carbon dioxide output; substantial improvement in GTT and ITT results; an increase in adiponectin; and a reduction in serum insulin, androgens, luteinizing hormone (LH), and LH/follicle-stimulating hormone ratio. Compared with the DHEA group, the DHEA + CHI group exhibited notable decreases in triglycerides, free fatty acids, and atherosclerosis index, while the DHEA + PIO group demonstrated no changes. Granulosa cells and healthy follicles increased in ovarian sections. Ovarian steroidogenic enzymes also increased in the DHEA + PIO and DHEA + CHI groups compared with the DHEA group. Mechanistically, chiglitazar increased Akt phosphorylation. Conclusion Chiglitazar significantly improved ovulation in rats with PCOS and may be a potential novel therapeutic strategy for PCOS.

In this work, a novel hot-dipped Zn–6Al–3Mg-0.1Si-0.05Ti alloy coating was designed through (Si, Ti) microalloying, and the related microstructure and corrosion behavior in Cl− containing environment were studied. The results show that the mainly microstructures of the coating consist of Al dendrites, primary MgZn2, peritectic and ternary eutectic. The addition of trace quantity of Si and Ti leads to the formation of (Al,Si)3Ti and Mg2Si intermetallic compounds. The corrosion process can be divided into four stages, including the formation of non-protective products and Si-based oxide, the formation protective products, the coverage of the coating surface by corrosion products and the establishment of stable double corrosion product layers. The corrosion products of Mg2Si are beneficial in enhancing the insulating properties of protective corrosion products. (Al,Si)3Ti, acting as a cathode in the corrosion process, leads to a decrease in the rate of corrosion by decreasing the current density at the anode. Additionally, the oxide passive film formed subsequent to its corrosion help inhibit the transfer of charge over the coating surface.

Abstract Background The risk of liver fibrosis in HBeAg-positive chronic hepatitis B (CHB) patients with indeterminate phase is not well characterized. We aimed to compare the presence of liver fibrosis in HBeAg-positive CHB patients between indeterminate phase and immune-tolerant phase. Methods This multi-center, retrospective cohort study included 719 treatment-naïve HBeAg-positive CHB patients with normal alanine aminotransferase (ALT). Patients with HBV DNA > 106 IU/mL were categorized into immune-tolerant phase, whereas those with HBV DNA ≤ 106 IU/mL were classified into indeterminate phase. Significant liver fibrosis and cirrhosis were determined by APRI, FIB-4, transient elastography, or liver biopsy. Results The median age of patients was 33.0 years and 59.8% of patients were male. 81.5% and 18.5% of patients were in the immune-tolerant phase and indeterminate phase, respectively. The APRI (0.33 vs. 0.27, P

Abstract Human genetics analysis has identified many noncoding SNPs associated with diabetic traits, but whether and how these variants contribute to diabetes is largely unknown. Here, we focus on a noncoding variant, rs6048205, and report that the risk-G variant impairs the generation of PDX1+/NKX6-1+ pancreatic progenitor cells and further results in the abnormal decrease of functional β cells during pancreatic differentiation. Mechanistically, this risk-G variant greatly enhances RXRA binding and over-activates FOXA2 transcription, specifically in the pancreatic progenitor stage, which in turn represses NKX6-1 expression. Consistently, inducible FOXA2 overexpression could phenocopy the differentiation defect. More importantly, mice carrying risk-G exhibit abnormal pancreatic islet architecture and are more sensitive to streptozotocin or a high-fat diet to develop into diabetes eventually. This study not only identifies a causal noncoding variant in diabetes susceptibility but also dissects the underlying gain-of-function mechanism by recruiting stage-specific factors.

Abstract K-containing polyanion compounds hold great potential as anodes for sodium-ion batteries considering their large ion transport channels and stable open frameworks; however, sodium storage behavior has rarely been studied, and the mechanism remains unclear. Here, using a noninterference KTiOPO4 thin-film model, the Na+ storage mechanism is comprehensively revealed by in situ/operando spectroscopy, aberration-corrected electron microscopy and density functional theory calculations. We find that incomplete K+/Na+ ion exchange occurs and eventually 0.15 K+ remains as a pillar to stabilize the tunnel structure. The pillar effect substantially maintains the volume change within 3.9%, much smaller than that of K+(Na+) insertion into KTiOPO4(NaTiOPO4) (9.5%; 5%), thus enabling 10,000 cycles. The powder electrode demonstrates comparable capacity and can work efficiently at commercial-level areal capacity of 2.47 mAh cm−2. The quasi-solid-state pouch cell with high safety under extreme abuse also manifests long-term cycling stability. This pillar chemistry will inspire alkali metal ion storage in hosts containing heterogeneous cations.

The semi-solid Al80Mg5Li5Zn5Cu5 light weight high entropy alloys were prepared by strain induced melting activation method (SIMA), and the microstructure evolution, mechanical properties and corrosion resistance of semi-solid Al80Mg5Li5Zn5Cu5 light weight high entropy alloys were investigated. The results indicate that the ideal globular or near-globular microstructures with an average grain size of 29.1 μm and a shape factor of 0.86 can be obtained when the Al80Mg5Li5Zn5Cu5 light weight high entropy alloys with 20% deformation held at 500 °C for 15 min. The coarsening coefficient is 35.8 μm3/s when the temperature is 500 °C, which is lower than the traditional single major element alloys due to the sluggish diffusion effect of high entropy alloys. The compression strength of semi-solid Al80Mg5Li5Zn5Cu5 light weight high entropy alloys is 558.4 MPa, which is 11% higher than that of as-cast state. The corrosion resistance of semi-solid Al80Mg5Li5Zn5Cu5 light weight high entropy alloys is also significantly improved.

Double-cropping rice in South China continues to break the total yield record, but the yield potential of single-cropping rice is not being realized. Radiation use efficiency (RUE) has been singled out as an important determinant of grain yield in many cereal species. However, there is no information on whether the yield gaps in double-cropping rice involve differences in RUE. Field experiments were performed over two years to evaluate the effects of intercepted radiation (IP) and RUE on the above-ground biomass production, crop growth rate (CGR), and harvest index (HI), in four representative rice varieties, i.e., Xiangyaxiangzhan (XYXZ), Meixiangzhan 2 (MXZ2), Nanjingxiangzhan (NJXZ), and Ruanhuayoujinsi (RHYJS), during the early and late seasons of rice cultivation in South China. The results revealed that grain yield in the early season was 8.2% higher than in the late season. The yield advantage in the early season was primarily due to higher spikelets per panicle and above-ground biomass resulting from a higher RUE. The spikelets per panicle in the early season were 6.5, 8.3, 6.9, and 8.5% higher in XYXZ, MXZ2, NJXZ, and RHYJS, respectively, than in the late season. The higher early season grain yield was more closely related to RUE in the middle tillering stage (R2=0.34), panicle initiation (R2=0.16), and maturation stage (R2=0.28), and the intercepted photosynthetically active radiation (IPAR) in the maturation stage (R2=0.28), while the late season grain yield was more dependent on IPAR in the middle tillering stage (R2=0.31) and IPAR at panicle initiation (R2=0.23). The results of this study conclusively show that higher RUE contributes to the yield progress of early season rice, while the yield improvement of late season rice is attributed to higher radiation during the early reproductive stage. Rationally allocating the RUE of double-cropping rice with high RUE varieties or adjustments of the sowing period merits further study.

Abstract Survival in host macrophages is an effective strategy for pathogenic bacterial transmission and pathogenesis. Our previous study found that viable but non-culturable (VBNC) Cronobacter Sakazakii (C. sakazakii) can survive in macrophages, but its survival mechanism is not clear. In this study, we investigated the possible mechanisms of VBNC C. sakazakii survival in macrophages in terms of environmental tolerance within macrophages and evasion of macrophages recognition. The results revealed that VBNC C. sakazakii survived under oxidative conditions at a higher rate than the culturable C. sakazakii. Moreover, the stringent response gene (relA and spoT) and the antioxidant-related genes (sodA, katG, and trxA) were up-regulated, indicating that VBNC C. sakazakii may regulate antioxidation through stringent response. On the other hand, compared with culturable C. sakazakii, VBNC C. sakazakii caused reduced response (Toll-like receptor 4) in macrophages, which was attributed to the suppression of biosynthesis of the lipopolysaccharides (LPS). Furthermore, we found that ellagic acid can reduce the survival rate of bacteria in macrophages by improving the immune TLR4 recognition ability of macrophages. In conclusion, VBNC C. sakazakii may survive in macrophages by regulating oxidative tolerance through stringent response and altering LPS synthesis to evade TLR4 recognition by macrophages, which suggests the pathogenic risk of VBNC C. sakazakii.

Abstract In this paper, we examined the elevation-dependent warming (EDW) patterns of MODIS LST across different seasons in the Qinling-Daba Mountains, further investigate the connections between the EDW patterns of Land surface temperature (LST) and land surface albedo (ALB) as well as aerosol optical depth (AOD). The key findings include: (1) Our study reveals a robust correlation between LST and air temperature in the Qinling-Daba Mountains, suggesting the feasibility of using MODIS LST to predict the temperature trends (2) During the period from 2001 to 2010, MODIS LST shows a significant EDW trend, primarily in the spring season. In contrast, a negative EDW is observed in the period during 2011–2021, which is contrary to the earlier decade, particularly during the autumn and winter seasons. (3) EDW of MODIS LST is affected by the combination of ALB and AOD. The former has a negative influence on the change of LST, particularly above 2500 m in elevation. However, the latter is negatively correlated with the trend of MODIS LST, primarily at lower and middle altitudes (0–2500 m). This study gives a comprehensive explanation for the EDW of the temporal variations of LST in the Qinling-Daba Mountains to improve our understanding of the complex interactions and potential future climate scenarios in the region.

Abstract Breast and gynecological cancers are common cancers with high mortality and have profound effects on the various physical functions of women. This study assessed trends in the number of hospitalizations, in-hospital mortality, length of stay (LOS), and hospital charges for female breast and gynecological cancer from 2004 to 2020. The data for this study come from the China Health Statistics Yearbook. Time trends of categorical variables were assessed with the Cochran-Armitage Test. The linear model was used to test for the trend of continuous variables. The hospitalizations for breast cancer increased from 15,204 to 276,387 (P for trend

Polysomnography (PSG) measures brain activity during sleep via electroencephalography (EEG) using six leads. Artifacts caused by movement or loose leads distort EEG measurements. We developed a method to automatically identify such artifacts in a PSG EEG trace. After preprocessing, we extracted power levels at frequencies of 0.5–32.5 Hz with multitaper spectral analysis using 4 s windows with 3 s overlap. For each resulting 1 s segment, we computed segment-specific correlations between power levels for all pairs of leads. We then averaged all pairwise correlation coefficients involving each lead, creating a time series of segment-specific average correlations for each lead. Our algorithm scans each averaged time series separately for “bad” segments using a local moving window. In a second pass, any segment whose averaged correlation is less than a global threshold among all remaining good segments is declared an outlier. We mark all segments between two outlier segments fewer than 300 s apart as artifact regions. This process is repeated, removing a channel with excessive outliers in each iteration. We compared artifact regions discovered by our algorithm to expert-assessed ground truth, achieving sensitivity and specificity of 80% and 91%, respectively. Our algorithm is an open-source tool, either as a Python package or a Docker.

Abstract Cadmium (Cd) is an unessential and pervasive contaminant in agricultural soil, eventually affecting the food and instigating health issues. The implication of nanocomposites in agriculture attained significant attention to drive food security. Nanocomposites possess exceptional characteristics to stun the challenges of chemical fertilizers that can enhance plant yield and better nutrient bioavailability. Similarly, biochar has the ability to immobilize Cd in soil by reducing mobility and bioavailability. Rice husk biochar is produced at high temperature pyrolysis under anoxic conditions and a stable carbon-rich material is formed. To strive against this issue, rice plants were subjected to Cd (15, 20 mg kg− 1) stress and treated with alone/combined Ca + Mg (25 mg L− 1) nanocomposite and rice husk biochar. In our study, growth and yield traits showed the nurturing influence of Ca + Mg nanocomposite and biochar to improve rice defence mechanism by reducing Cd stress. Growth parameters root length 28%, shoot length 34%, root fresh weight 19%, shoot fresh weight 16%, root dry weight 9%, shoot dry weight 8%, number of tillers 32%, number of grains 20%, and spike length 17% were improved with combined application of Ca + Mg and biochar, with Cd (20 mg kg− 1), rivalled to alone biochar. Combined Ca + Mg and biochar application increased the SPAD 23%, total chlorophyll 26%, a 19%, b 18%, and carotenoids 15%, with Cd (20 mg kg− 1), rivalled to alone biochar. MDA 15%, H2O2 13%, and EL 10% were significantly regulated in shoots with combined Ca + Mg and biochar application with Cd (20 mg kg− 1) compared to alone biochar. POD 22%, SOD 17%, APX 18%, and CAT 9% were increased in shoots with combined Ca + Mg and biochar application with Cd (20 mg kg− 1) compared to alone biochar. Cd uptake in roots 13%, shoots 14%, and grains 21% were minimized under Cd (20 mg kg− 1) with combined Ca + Mg and B. pumilus application, compared to alone biochar. Subsequently, combined Ca + Mg and biochar application is a sustainable solution to boost crop production under Cd stress.

Abstract Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations.

Abstract Ni-based catalysts are highly reactive for dry reforming of methane (DRM) but they are prone to rapid deactivation due to sintering and/or coking. In this study, we present a straightforward approach for anchoring dispersed Ni sites with strengthened metal-support interactions, which leads to Ni active sites embedded in dealuminated Beta zeolite with superior stability and rates for DRM. The process involves solid-state grinding of dealuminated Beta zeolites and nickel nitrate, followed by calcination under finely controlled gas flow conditions. By combining in situ X-ray absorption spectroscopy and ab initio simulations, it is elucidated that the efficient removal of byproducts during catalyst synthesis is conducted to strengthen Ni–Si interactions that suppress coking and sintering after 100 h of time-on-stream. Transient isotopic kinetic experiments shed light on the differences in intrinsic turnover frequency of Ni species and explain performance trends. This work constructs a fundamental understanding regarding the implication of facile synthesis protocols on metal-support interaction in zeolite-supported Ni sites, and it lays the needed foundations on how these interactions can be tuned for outstanding DRM performance.

Abstract LncRNAs are highly implicated in oxidative stress (OS) during the growth of mammalian follicles. TAK1 binding protein 2 gene (TAB2) has been suggested to involve in the normal apoptosis and proliferation of granulosa cells (GCs), the main supporting cells in ovarian follicles. In this study, we found that TAB2 increased the expressions of SOD1, P50, and P65 to suppress the OS, thereby inhibiting the apoptosis and promoting the proliferation in GCs. Notably, DNMTs appeared to mediate the expression of TAB2 without the changes of DNA methylation at TAB2’s promoter. We identified an antisense lncRNA of TAB2, discovered that DNA methylation regulated the transcription of TAB2-AS in GCs, and found TAB2-AS medicated the follicular growth of ovaries in vivo. Mechanistically, the hypomethylation of the CpG site (−1759/−1760) activated the transcription of TAB2-AS, and the 1–155 nt and 156-241 nt of TAB2-AS were respectively complementary to 4368–4534 nt and 4215–4300 nt of TAB2’s mRNA to increase the expression of TAB2. Moreover, TAB2-AS inhibited the OS and apoptosis of GCs, while promoted the proliferation of GCs to expedite the follicular growth, which was in line with that of TAB2. Collectively, these findings revealed the antisense lncRNA mechanism mediated by DNA methylation, and TAB2-AS might be the target to control OS during follicular growth in mammals.

Abstract Background Postmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. In recent years, the “gut-immune response-bone” axis has been proposed as a novel potential approach in the prevention and treatment of PMO. Studies on ovariectomized murine model indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. However, the relationship among gut microbiota, immune cells and bone metabolic indexes remains unknown in PMO. Methods A total of 77 postmenopausal women were recruited for the study and divided into control (n = 30), osteopenia (n = 19), and osteoporosis (n = 28) groups based on their T score. The frequency of Treg and Th17 cells in lymphocytes were analyzed by flow cytometry. The serum levels of interleukin (IL)-10, 17 A, 1β, 6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing analysis was performed to investigate the gut microbiota of the participants. Results The results demonstrated decreased bacterial richness and diversed intestinal composition in PMO. In addition, significant differences of relative abundance of the gut microbial community in phylum and genus levels were found, mainly including increased Bacteroidota, Proteobacteria, and Campylobacterota, as well as reduced Firmicutes, Butyricicoccus, and Faecalibacterium. Intriugingly, in the osteoporosis group, the concentration of Treg cells and associated IL-10 in peripheral circulation was negatively regulated, while other chronic systemic proinflammatory cytokines and Th17 cells showed opposite trends. Moreover, significantly elevated plasma lipopolysaccharide (LPS) in patients with osteoporosis indicated that disrupted intestinal integrity and permeability. A correlation analysis showed close relationships between gut bacteria and inflammation. Conclusions Collectively, these observations will lead to a better understanding of the relationship among bone homeostasis, the microbiota, and circulating immune cells in PMO. The elevated LPS levels of osteoporosis patients which not only indicate a breach in intestinal integrity but also suggest a novel biomarker for assessing osteoporosis risk linked to gut health.