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Abstract A large scale of distributed photovoltaics is accessed through a low voltage distribution network in a single‐phase or two‐phase, which causes three‐phase unbalance and over‐voltage problems. These problems can be solved by using a voltage source converter to realize AC/DC interconnection and flexible power transfer between lines. How to utilize the characteristics of voltage source converters to optimize the power qualities, and fully promote distributed PV systems consumption in low voltage distribution network is an important research point. This paper proposes a power regulation model of VSC. The goal of this model is to adjust and optimize over‐voltage and three‐phase unbalance problems. By constructing a voltage‐power sensitivity calculation model for a three‐phase four‐wire system and integrating different control modes and adjustment capabilities of voltage source converters, a control strategy based on voltage source converters is proposed to address three‐phase unbalance and over‐voltage issues. Finally, the simulation results demonstrate the effectiveness of the proposed strategy.

Abstract Wetting behavior of droplets on a substrate with micro-grooves plays a key role in super-hydrophobicity. This paper aims to study the influence of groove width, droplet size, and surface tension on the anisotropic wetting behavior of droplets on micro-grooved PDMS membranes. Three types of PDMS membranes are made by mold replication. Profiles of droplets along the circumferential direction are observed by HD camera, and the 3D model of the droplet is reconstructed. Capillary forces at the three-phase contact line are obtained using the surface tension integration method. Additionally, liquid’s wetting depth within the micro-grooves is calculated using an interfacial free energy equilibrium approach. The experiment shows that the micro-grooved PDMS membrane has anisotropic constrain to droplets due to wetting depth change in micro-grooves. Meta-equilibrium states at the three-phase contact line are influenced not only by substrate free energy, but also by wetting depth, interface pressure, and substrate structure.

Abstract Objective Lymph node metastasis (LNM) is one of the most common pathways of metastasis in non-small cell lung cancer (NSCLC). Preoperative assessment of occult lymph node metastasis (OLNM) in NSCLC patients is beneficial for selecting appropriate treatment plans and improving patient prognosis. Method A total of 370 NSCLC patients were included in the study. Univariate and multivariate logistic regression analysis were used to screen potential risk factors for OLNM in preoperative NSCLC patients. And establish a nomogram for OLNM in NSCLC patients before surgery. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the established nomogram. Result Both univariate and multivariate logistic regression analyses suggested that multiple tumors, ERBB2 missense mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin are potential risk factors for OLNM in NSCLC patients. The constructed nomogram was evaluated, and the consistency index (C-index) and area under the ROC curve of the model were both 0.846. The calibration curve showed that the predicted values of the model had a high degree of fit with the actual observed values, and DCA suggested that the above indicators had good utility. Conclusion The personalized scoring prediction model constructed based on multiple tumors, ERBB2 miss mutation, CA125 levels, CA153 levels, tumor site, tumor length, and serum ferritin can screen NSCLC patients who may have OLNM.

Abstract Background Decision-making in the management of Crohn’s disease (CD)-related spontaneous intra-abdominal abscess (IAA) is challenging. This study aims to reveal predictive factors for percutaneous drainage and/or surgery in the treatment of CD-related spontaneous IAA through long-term follow-up. Methods Data were collected, including clinical manifestations, radiography and treatment strategies, in Chinese patients with CD-related IAA in a tertiary medical center. Univariate and Multivariate Cox analysis were conducted to identify predictors for invasive therapy. Results Altogether, 48 CD patients were identified as having IAA through enhanced CT scans. The median follow-up time was 45.0 (23.3, 58.0) months. 23 (47.9%) patients underwent conservative medical treatment, and 25 (52.1%) patients underwent percutaneous drainage and/or surgical intervention (invasive treatment group). The 1-, 2-, and 5-year overall survival rates without invasive treatment were 75.0%, 56.1%, and 46.1%, respectively. On univariate Cox analysis, the computerized tomography (CT) features including nonperienteric abscess (HR: 4.22, 95% CI: 1.81–9.86, p = 0.001), max abscess diameter (HR: 1.01, 95% CI: 1.00-1.02, p

Rice false smut, caused by Ustilaginoidea virens, is a devastating disease that greatly reduces rice yield and quality. However, controlling rice false smut disease is challenging due to the unique infection mode of U. virens. Therefore, there is a need for early diagnosis and monitoring techniques to prevent the spread of this disease. Lateral flow strip-based recombinase polymerase amplification (LF-RPA) overcomes the limitations of current U. virens detection technologies, which are time-consuming, require delicate equipment, and have a high false-positive rate. In this study, we used a comparative genomics approach to identify Uv_3611, a specific gene of U. virens, as the target for the LF-RPA assay. The designed primers and probe efffectively detected the genomic DNA (gDNA) of U. virens and demonstrated no cross-reactivity with related pathogens. Under optimal conditions, the LF-RPA assay demonstrated a sensitivity of 10 pg of U. virens gDNA. Additionally, by incorporating a simplified PEG-NaOH method for plant DNA extraction, the LF-RPA assay enabled the detection of U. virens in rice spikelets within 30 min, without the need for specialized equipment. Furthermore, the LF-RPA assay successfully detected U. virens in naturally infected rice and seed samples in the field. Therefore, the LF-RPA assay is sensitive, efficient, and convenient, and could be developed as a kit for monitoring rice false smut disease in the field.

Abstract Purpose This study aimed to examine the mechanisms influencing metacognitive awareness among nursing students, encompassing educational environment, learning motivation, emotional intelligence, and self-directed learning ability. These findings could be a theoretical reference for formulating metacognitive awareness intervention strategies specifically designed for nursing students. Method Through stratified sampling, 600 nursing students were recruited from two universities in China. Data collection involved five self-report instruments: the Metacognitive Awareness Inventory, Medical Education Environment Evaluation Scale, Learning Motivation Scale, Emotional Intelligence Scale, and Self-Directed Learning Ability Scale. Confirmatory factor analysis was utilized to test the measurement model, while structural equation modeling utilized multiple indices to assess model fit. Bootstrapping was conducted to analyze total, direct, and indirect effects. Results All study variables differed significantly according to age and year level (p

Abstract Classical gene-by-environment interaction (GxE) analysis can be used to characterize genetic effect heterogeneity but has a high multiple testing burden in the context of genome-wide association studies (GWAS). We adapt a colocalization method, SharePro, to account for effect heterogeneity in fine-mapping and identify candidates for GxE analysis with reduced multiple testing burden. SharePro demonstrates improved power for both fine-mapping and GxE analysis compared to existing methods as well as well-controlled false type I error in simulations. Using smoking status stratified GWAS summary statistics, we identify genetic effects on lung function modulated by smoking status that are not identified by existing methods. Additionally, using sex stratified GWAS summary statistics, we characterize sex differentiated genetic effects on fat distribution. In summary, we have developed an analytical framework to account for effect heterogeneity in fine-mapping and subsequently improve power for GxE analysis. The SharePro software for GxE analysis is openly available at https://github.com/zhwm/SharePro_gxe .

Objective: Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied. Methods: Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An in vivo assay was used to measure tumor growth. Results: It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1. Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC. In addition, SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an in vivo assay. Conclusions: The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.

Abstract Smooth metal microspheres with uniform sizes are ideal for constructing particle-arrayed anisotropic conductive films (ACF), but synthesis is hindered by challenges in controlling anisotropic metal growth. Here, we present a positioned transient-emulsion self-assembly and laser-irradiation strategy to fabricate pure gold microsphere arrays with smooth surfaces and uniform sizes. The fabrication involves assembling gold nanoparticles into uniform colloidosomes within a pre-designed microhole array, followed by rapid transformation into well-defined microspheres through laser heating. The gold nanoparticles melt and merge in a layer-by-layer manner due to the finite skin depth of the laser, leading to a localized photothermal effect. This strategy circumvents anisotropic growth, enables tunable control of microsphere size and positioning, and is compatible with conventional lithography. Importantly, these pure gold microspheres exhibit stable conductivity under deep compression, offering promising applications in soldering micro-sized chips onto integrated circuits.

Abstract Pulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease with an intricate etiology. Identifying biomarkers for early PAH lesions based on the exploration of subtle biological processes is significant for timely diagnosis and treatment. In the present study, nine distinct cell populations identified based on gene expression profiles revealed high heterogeneity in cell composition ratio, biological function, distribution preference, and communication patterns in PAH. Notably, compared to other cells, endothelial cells (ECs) showed prominent variation in multiple perspectives. Further analysis demonstrated the endothelial-to-mesenchymal transition (EndMT) in ECs and identified a subgroup exhibiting a contrasting phenotype. Based on these findings, a machine-learning integrated program consisting of nine learners was developed to create a PAH Endothelial-to-mesenchymal transition Signature (PETS). This study identified cell populations underlying EndMT and furnished a potential tool that might be valuable for PAH diagnosis and new precise therapies.

The choroid plexus (ChP) serves as the principal origin of cerebrospinal fluid (CSF). CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently. Nevertheless, the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined. In the present study, we elucidate the critical role of macrophages in the pathogenesis of ChP inflammation. Specifically, we identify the chemokine CCL2, released by ChP epithelial cells, recruits CCR2+ monocytes to the ChP thereby inciting hydrocephalus pathogenesis. The accumulated ChP macrophages increase the inflammation in ChP epithelial cells through TNF-α/TNFR1/NF-κB signaling cascade, thereby leading to CSF hypersecretion. Strikingly, augmentation of ChP‒CCL2 using an adeno-associated viral approach (AAV) exacerbates macrophage recruitment, activation, and ventriculomegaly in rat PHH models. Systemic application of Bindarit, a specific CCL2 inhibitor, significantly inhibits ChP macrophage infiltration and activation and reduces CSF secretion rate. Furthermore, the administration of CCR2 antagonist (INCB 3284) reduces ChP macrophage accumulation and ventriculomegaly. This study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus.

Abstract To understand the microbial diversity and community composition within the main constructive tree species, Picea crassifolia, Betula platyphylla, and Pinus tabuliformis, in Helan Mountain and their response to changes in soil physicochemical factors, a high throughput sequencing technology was used to analyze the bacterial and fungal diversity and community structure. RDA (Redundancy Analysis) and Pearson correlation analysis were used to explore the influence of soil physicochemical factors on microbial community construction, and co-occurrence network analysis was conducted on the microbial communities. The results showed that the fungal and bacterial diversity was highest in B. platyphylla, and lowest in P. crassifolia. Additionally, the fungal/bacterial richness was greatest in the rhizosphere soils of P. tabuliformis and B. platyphylla. RDA and Pearson correlation analysis revealed that NN (nitrate nitrogen) and AP (available phosphorus) were the main determining factors of the bacterial community, while NN and SOC (soil water content) were the main determining factors of the fungal community. Pearson correlation analysis between soil physicochemical factors and the alpha diversity of the microbial communities revealed a significant positive correlation between pH and the bacterial and fungal diversity, while SOC, TN (total nitrogen), AP, and AN (available nitrogen) were significantly negatively correlated with the bacterial and fungal diversity. Co-occurrence network analysis revealed that the soil bacterial communities exhibit richer network nodes, edges, greater diversity, and greater network connectivity. Indicating that bacterial communities exhibit more complex and stable interaction patterns in soil. This study reveals the complex interactive relationship between microbial communities and soil physicochemical factors in forest ecosystems. By analyzing the response of rhizosphere microbial communities of major tree species in Helan Mountain to nutrient dynamics and pH changes, we can deepen our understanding of the role of microorganisms in regulating ecosystem functions and provide theoretical basis for soil improvement and ecological restoration strategies.

Abstract Despite a rapid expansion of Porcine reproductive and respiratory syndrome virus (PRRSV) sublineage 8.7 over recent years, very little is known about the patterns of virus evolution, dispersal, and the factors influencing this dispersal. Relying on a national PRRSV surveillance project established over 20 years ago, we expand the available genomic data of sublineage 8.7 from China. We perform independent interlineage and intralineage recombination analyses for the entire study period, which showed a heterogeneous recombination pattern. A series of Bayesian phylogeographic analyses uncover the role of Guangdong as an important infection hub within Asia. The spatial spread of PRRSV is highly linked with a composite of human activities and the heterogeneous provincial distribution of the swine industry, largely propelled by the smaller-scale Chinese rural farming systems in the past years. We sequence all four available modified live vaccines (MLVs) and perform genomic analyses with publicly available data, of which our results suggest a key “leaky” period spanning 2011–2017 with two concurrent amino acid mutations in ORF1a 957 and ORF2 250. Overall, our study provides an in-depth overview of the evolution, transmission dynamics, and potential leaky status of HP-PRRS MLVs, providing critical insights into new MLV development.

Abstract Background Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S. aureus pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin α5β1, thus effectively addressing S. aureus-induced pneumonia. Methods C57 mice (8 week-old females) infected with S. aureus via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses. Results LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of S. aureus-induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination. Conclusions Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin α5β1 significantly diminished the S. aureus-mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections.

Abstract Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with αPD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA) in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous H2O2. All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8+ T cells in tumor. At the same time, the combination with αPD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe3+, which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy.

Abstract There is limited research on the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) currently. The aim of this study is to summerize the clinicopathological factors and prognosis of cHCC-CCA, which could help us understand this disease. 72 cases of cHCC-CCA from West China Hospital of Sichuan University were collected. Tissue components were reviewed by pathologists. Immunohistochemistry was used to detect the status of mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) in cHCC-CCA, as well as the quantity and distribution of CD3+ T cells and CD8+ T cells. Fluorescence in situ hybridization was used to detect fibroblast growth factor receptor 2 (FGFR2) gene alteration. COX univariate and multivariate analyses were used to evaluate risk factors, and survival curves were plotted. 49 cases were classified as classic type cHCC-CCA and 23 cases as intermediate cell carcinoma. The cut-off value for diagnosing classic type was determined to be ≥ 30% for the cholangiocarcinoma component based on prognostic calculations. All tumors were MMR proficient. The rate of strong HER2 protein expression (3+) was 8.3%, and the frequency of FGFR2 gene alteration was 26.4%. CD3+ T cells and CD8+ T cells were mainly distributed at the tumor margin, and were protective factors for patients with cHCC-CCA. The overall survival of the 72 patients was 18.9 months, with a median survival of 12 months. Tumor size, TNM stage, and serum AFP level were prognostic factors for cHCC-CCA. The proportion of cholangiocarcinoma component reaching the threshold of 30%, may provide a reference for future pathology diagnosis. FGFR2 gene alteration was 26.4%, providing a clue for anti-FGFR2 therapy. However, more data is needed for further verification.

Abstract Many studies have focused on the effects of small molecules, such as amino acids, on metabolism under hypoxia. Recent findings have indicated that phenylalanine levels were markedly elevated in adaptation to chronic hypoxia. This raises the possibility that phenylalanine treatment could markedly improve the hypoxic endurance. However, the importance of hypoxia-regulated phenylalanine is still unclear. This study investigates the role of phenylalanine in hypoxia adaptation using a hypoxic zebrafish model and multi-omics analysis. We found that phenylalanine-related metabolic pathways are significantly up-regulated under hypoxia, contributing to enhanced hypoxic endurance. Phenylalanine treatment reduced ROS levels, improved mitochondrial oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) in hypoxic cells. Western blotting revealed increased phenylalanine uptake via L-type amino transporters (LAT1), activating the LKB1/AMPK signaling pathway. This activation up-regulated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and the Bcl-2/Bax ratio, while down-regulating uncoupling protein 2 (UCP2), thereby improving mitochondrial function under hypoxia. This is the first comprehensive multi-omics analysis to demonstrate phenylalanine’s crucial role in hypoxia adaptation, providing insights for the development of anti-hypoxic drugs. Graphical Abstract

Abstract Background Streptococcus pneumoniae (S. pneumoniae) is a major cause of morbidity and mortality in children worldwide, and its evolving serotype distribution and antibiotic resistance patterns are of global health concern. This meta-analysis aims to investigate the serotype distribution and antimicrobial resistance of S. pneumoniae after the introduction of pneumococcal conjugate vaccine 13-valent (PCV13) as a self-funded vaccine in Chinese pediatric populations. Methods We systematically reviewed studies published between 2017 and 2024 that focused on S. pneumoniae serotypes isolated from children under 14 years old in mainland China. Data sources included PubMed, Embase, Web of Science, CNKI, Wanfang, and SinoMed. The findings were synthesized using either a fixed-effects or random-effects model. Results Our meta-analysis included 12 studies, identifying the most common serotypes of S. pneumoniae were 19 F, 19 A, 23 F, 14, 6B and 6 A. Vaccine serotype coverage rates were 52.17% (95%CI: 44.91-59.42%) for PCV10, 74.77% (95%CI: 71.53-78.01%) for PCV13, 76.72% (95%CI: 75.37-78.07%) for PCV15 and 92.90% (95%CI: 92.09-93.71%) for PPSV23. Antimicrobial resistance was most pronounced for erythromycin at 93.73% (95%CI: 90.58-96.88%), followed by azithromycin, tetracycline, clindamycin, and sulfamethoxazole. Serotype prevalence and vaccine coverage varied regionally and by strain type. Conclusion The distribution of S. pneumoniae serotypes and their antibiotic resistance profiles in children under 14 years in mainland China have remained relatively stable post-PCV13 introduction as a self-funded vaccine. The results support continued use and possible expansion of PCV13 immunization and highlight the importance of ongoing surveillance and vaccine development to cover all prevalent serotypes in China.

Abstract The orbital Hall effect in light materials has attracted considerable attention for developing orbitronic devices. Here we investigate the orbital torque efficiency and demonstrate the switching of the perpendicularly magnetized materials through the orbital Hall material, i.e., Zr. The orbital torque efficiency of approximately 0.78 is achieved in the Zr orbital Hall material with the perpendicularly magnetized [Co/Pt]3 sample, which significantly surpasses that of the perpendicularly magnetized CoFeB/Gd/CoFeB sample (approximately 0.04). Such a notable difference is attributed to the different spin-orbit correlation strength between the [Co/Pt]3 sample and the CoFeB/Gd/CoFeB sample, confirmed through theoretical calculations. Furthermore, the full magnetization switching of the [Co/Pt]3 samples with a switching current density of approximately 2.6×106 A/cm2 has been realized through Zr, which even outperforms that of the W spin Hall material. Our finding provides a guideline to understand orbital torque efficiency and paves the way for developing energy-efficient orbitronic devices.

Abstract Signaling systems of microorganisms are responsible for regulating the physiological and metabolic processes and also play vital roles in the communications of cells. Identifying signaling molecules mediating the cross-talks is challenging yet highly desirable for comprehending the microbial interactions. Here, we demonstrate that a pathogenic Gram-negative Chromobacterium violaceum exerts significant influence on the morphological differentiation and secondary metabolism of Gram-positive Streptomyces. The physiological metabolisms are directly modulated by three novel cinnamoyl lipids (CVCL1, 2, and 3) from C. violaceum CV12472, whose biosynthesis is under the control of N-acylhomoserine lactone signaling system. Furthermore, a receptor of CVCLs in Streptomyces ansochromogenes 7100 is determined to be SabR1, the cognate receptor of γ-butenolide signaling molecules. This study reveals an unprecedented mode of microbial interactions, and the quorum sensing signaling systems in these two groups of bacteria can be bridged via CVCLs, suggesting that CVCLs can modulate the physiological metabolism of cross-phylum microorganisms.

Abstract Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained‐release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady‐state trough concentrations (Ctrough) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20–50 kg. As a result, the PK characteristics of VPA were described using a one‐compartment model with first‐order absorption. The absorption rate constant (ka) was set at 2.64 and 0.46 h−1 for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target Ctrough, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.

Abstract Background Portal vein tumor thrombosis (PVTT) commonly occurs in patients with primary liver cancer (PLC). Transarterial chemoembolization (TACE) is a treatment for patients with PLC and PVTT. Some studies have shown that combining TACE therapy with hepatic arterial infusion chemotherapy (HAIC) might improve the survival rate of PLC patients with PVTT. However, few studies have compared the different regimens of PLC with PVTT. We aimed to compare the differences between the oxaliplatin + raltetrexed regimen and FOLFOX regimen. Methods We divided the 248 patients into two groups. There were 60 patients in the oxaliplatin + ratitetrexed group and 74 patients in the FOLFOX group. The primary endpoints were OS and PFS. The secondary endpoints were ORR and adverse events. We used SPSS software, the Kaplan–Meier method, the t test, and the rank sum test to compare the differences between the two groups. Results The median OS was 10.82 months in the oxaliplatin + raltitrexed group and 8.67 months in the FOLFOX group. The median PFS time was greater in the oxaliplatin + raltitrexed group (10.0 months) than that in the FOLFOX group (7.1 months). The ORR was greater in the oxaliplatin + raltitrexed group than that in the FOLFOX group (18.3% vs. 13.5%; P = 0.445). The DCR in the oxaliplatin + raltitrexed group was higher than that in the FOLFOX group (70.0% vs. 64.8%; P = 0.529). However, in the subgroup analysis, the difference between them was more significant in the type II PVTT subgroup. The OS was 12.08 months in the oxaliplatin + raltitrexed group and 7.26 months in the FOLFOX group (P = 0.008). The PFS was 11.68 months in the oxaliplatin + raltitrexed group and 6.26 months in the FOLFOX group (P = 0.014). In the right branch of type II PVTT, the OS was 13.54 months in the oxaliplatin + raltitrexed group and 6.89 months in the FOLFOX group (P = 0.015), and the PFS was 13.35 months in the oxaliplatin + raltitrexed group and 6.27 months in the FOLFOX group (P = 0.030). The incidence of adverse reactions was similar between the two groups. Conclusions Compared with the FOLFOX regimen, the oxaliplatin + raltitrexed chemoembolization regimen had longer OS, PFS time and ORR and DCR and it was safe and tolerable.

Abstract Objective To analyze the degree, evolution and causes of socioeconomic inequality in perceived access to health services among the older adults in China. Methods The data used in this study were drawn from the 4 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2008, 2011, 2014, 2018. Erreygers index (EI) was used to measure socioeconomic inequality in perceived access to health services in each survey wave. A panel logit regression model was used to examine the impact of socioeconomic status on perceived access to health services. The recentered influence function (RIF) regression decomposition method was used to explore the causes of socioeconomic inequality in perceived access to health services. Inverse probability weighting (IPW) was employed to adjust estimates for missing responses and loss to follow-up. Results “Pro-rich” socioeconomic inequality in perceived access to health services in China was found with inequality falling through time. The older adults with higher incomes, who had adequate financial support, and those who were wealthier compared with other residents reported lower socioeconomic inequality in perceived access to health services. Having basic health insurance and access to care resources when ill can help alleviate such inequalities. Conclusions Socioeconomic inequality in perceived access to health services was shown to be responsive to policies that enhance health insurance coverage and support the provision of (paid and unpaid) caregiving for the older adults.

Abstract Background Pharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China. Methods A survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made. Results Questionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost. Conclusion Although GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.

Abstract Background Type 2 diabetes mellitus (T2DM) is associated with decreased heart rate variability (HRV) with an unclear intermediate mechanism. This study aimed to conduct mediation analysis to explore the impact of various adipose tissues on the relationship between T2DM and HRV. Methods A total of 380 participants were enrolled for analysis, including 249 patients with T2DM and 131 non-diabetic controls. The thicknesses of four adipose tissues (subcutaneous, extraperitoneal, intraperitoneal, and epicardial) were measured by abdominal ultrasound or echocardiography respectively. HRV was assessed by 24-hour Holter for monitoring both frequency domain indices (LF, HF, and LF/HF) and time domain indices (SDNN, SDANN, SDNN index, rMSSD and pNN50). Mediation analysis was used toexamine whether adipose tissues mediated the relationship between T2DM and each index of HRV. Then, a latent variable - HRV burden - was constructed by structural equation model with selected HRV indices to comprehensively assess the whole HRV. Results Compared to non-diabetic controls, patients with T2DM exhibited a significant reduction in indices of HRV, and a remarkable increase in the thicknesses of extraperitoneal, intraperitoneal, and epicardial adipose tissues. Mediation analysis found significant indirect effects of T2DM on six indices of HRV, including HF, SDNN, SDANN, SDNN index, rMSSD, and pNN50, which was mediated by epicardial adipose tissue rather than other adipose tissues, with the mediation proportions of 64.21%, 16.38%, 68.33%, 24.34%, 24.10% and 30.51%, respectively. Additionally, epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV burden (24.26%), which composed by SDNN, SDNN index, rMSSD, and pNN50. Conclusion Epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV, which reinforces the value of targeting heart-specific visceral fat to prevent cardiac autonomic neuropathy in diabetes.

Abstract Early social isolation (SI) leads to various abnormalities in emotion and behavior during adulthood. However, the negative impact of SI on offspring remains unclear. This study has discovered that paternal early SI causes social memory deficits and anxiety-like behavior in F1 young adult mice, with alterations of myelin and synapses in the medial prefrontal cortex (mPFC). The 2-week SI in the F1 progeny exacerbates social memory impairment and hypomyelination in the mPFC. Furthermore, the down-regulation of miR-124, a key inhibitor of myelinogenesis, or over-expression of its target gene Nr4a1 in the mPFC of the F1 mice improves social interaction ability and enhances oligodendrocyte maturation and myelin formation. Mechanistically, elevated levels of miR-124 in the sperm of paternal SI mice are transmitted epigenetically to offspring, altering the expression levels of miR-124/Nr4a1/glucocorticoid receptors in mPFC oligodendrocytes. This, in turn, impedes the establishment of myelinogenesis-dependent social behavior. This study unveils a novel mechanism through which miR-124 mediates the intergenerational effects of early isolation stress, ultimately impairing the establishment of social behavior and neurodevelopment.

Abstract Cytokine storm (CS) emerges as an exacerbated inflammatory response triggered by various factors such as pathogens and excessive immunotherapy, posing a significant threat to life if left unchecked. Quercetin, a monomer found in traditional Chinese medicine, exhibits notable anti-inflammatory and antiviral properties. This study endeavors to explore whether quercetin intervention could mitigate CS through a combination of network pharmacology analysis and experimental validation. First, common target genes and potential mechanisms affected by quercetin and CS were identified through network pharmacology, and molecular docking experiments confirmed quercetin and core targets. Subsequently, in vitro experiments of Raw264.7 cells stimulated by lipopolysaccharide (LPS) showed that quercetin could effectively inhibit the overexpression of pro-inflammatory mediators and regulate the AKT1-FoxO1 signaling pathway. At the same time, quercetin can reduce ROS through the Keap1-Nrf2 signaling pathway. In addition, in vivo studies of C57BL/6 mice injected with LPS further confirmed quercetin's inhibitory effect on CS. In conclusion, this investigation elucidated novel target genes and signaling pathways implicated in the therapeutic effects of quercetin on CS. Moreover, it provided compelling evidence supporting the efficacy of quercetin in reversing LPS-induced CS, primarily through the regulation of the AKT1-FoxO1 and Keap1-Nrf2 signaling pathways.

Abstract Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3β/β-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.

Abstract The movement towards electrification is entailing deep changes in power systems. On the demand side, the adoption of electric heating (EH) has grown rapidly in recent years. To eliminate the voltage fluctuations caused by the random switching‐on/‐off behaviors of EHs in some application scenes with special‐power‐line in low voltage distribution networks (LVDNs), a swarm‐intelligence‐based coordinated control approach of EHs for voltage stabilization with zero communication burden while guaranteeing the users’ thermal comforts is researched. A novel bird‐perch‐on‐branch (BPB) ‐based swarm intelligence theory is proposed, which reveals the mapping relation between local observations and global states. On this theoretical basis, a multi‐agent reinforcement learning (MARL) framework is developed for the coordinated dispatch of EHs, where the deep‐Q‐network (DQN) algorithm is adopted to learn and generate the optimal control policy for each EH. The implementation of the proposed MADQN‐BPB approach is described based on the principle of centralized‐training and decentralized‐execution. Comparative control performances of MADQN‐BPB with a commercially available approach, and the global optimal solution are evaluated. Simulation results verify the capability of MADQN‐BPB in voltage stabilization with zero communication burden. Its control performance is close to that of the global optimal solution, and is scalable to the variations of environment.

Objectives: Studies have increasingly focussed on the relationship between periodontitis (PD) and preeclampsia (PE). However, conclusions have not been consistent, and it is unclear whether any causal relationship exists between them and whether causality is bidirectional. This study employed Mendelian randomisation (MR) analysis to investigate the potential bidirectional causal relationship between PD and PE. Methods: Genetic variants strongly linked to PD (17,353 cases and 28,210 controls), chronic periodontitis (CP; 1817 cases and 2215 controls), aggressive periodontitis (AgP; 851 cases and 6580 controls), and PE (7212 cases and 194,266 controls) in the genome-wide association study (GWAS) of European ancestry were used as instrumental variables (IVs). Inverse variance weighting (IVW) served as the primary method for causal inference. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was utilised to analyse horizontal pleiotropy. Cochrane Q tests and leave-one-out analyses were used to assess heterogeneity and stability amongst IVs. Results: The MR analysis revealed no causal impacts of PD or its 2 subtypes—CP and AgP—on PE. Similarly, no significant causal effect of PE on PD was found in the reverse-MR analysis (IVW odds ratio, 0.97; 95% confidence interval, 0.91–1.05; P = .58). The findings from MR–Egger, weighted median, weighted mode, and the simple modelling approaches, as well as the pleiotropy and sensitivity analyses, aligned with those of the IVW method. Conclusions: The MR analysis suggests no bidirectional causal relationship between PD and PE; hence, PD and PE might not increase or prevent the risk of one other. Clinical Relevance: Genetically, periodontitis or its subtypes chronic periodontitis and aggressive periodontitis may not require specific clinical attention to prevent the development of preeclampsia.

In view of the problem of floor water inrush in the process of deep coal seam mining, propose to establish a risk assessment model for coal seam floor water inrush using GIS and combined weight TOPSIS method. Take coal 12-1 of level −950 in Donghuantuo Coal Mine as an example, the coal seam hosting thickness, coal seam burial depth, fault intensity index, aquifer thickness, water-rich aquifer thickness, first aquiclude thickness and second aquiclude thickness are taken as decisive indexes. Based on actual engineering exploration, the entropy weighted AHP weighted TOPSIS method is used to determine the partition threshold and classification level, analyse the risk of water inrush from coal seam floor, and visualise it based on GIS platform. The results show that the combined weight values of coal seam burial depth and fault scale index are 0.4008 and 0.2201, which have a significant impact on water inrush from the coal seam floor. The zoning threshold for the risk coefficient of water inrush from the 12–1 coal seam floor is 0.478, The overall water inrush risk of the mine field is less. Only a few areas in the southwest of the mine field are water inrush risk areas.

Research on megaplasmids that contribute to the spread of antimicrobial resistance (AMR) in Pseudomonas aeruginosa strains has grown in recent years due to the now widely used technologies allowing long-read sequencing. Here, we systematically analyzed distinct and consistent genetic characteristics of megaplasmids found in P. aeruginosa. Our data provide information on their phylogenetic distribution and hypotheses tracing the potential evolutionary paths of megaplasmids. Most of the megaplasmids we found belong to the IncP-2-type, with conserved and syntenic genetic backbones carrying modules of genes associated with chemotaxis apparatus, tellurite resistance and plasmid replication, segregation, and transmission. Extensively variable regions harbor abundant AMR genes, especially those encoding β-lactamases such as VIM-2, IMP-45, and KPC variants, which are high-risk elements in nosocomial infection. IncP-2 megaplasmids act as effective vehicles transmitting AMR genes to diverse regions. One evolutionary model of the origin of megaplasmids claims that chromids can develop from megaplasmids. These chromids have been characterized as an intermediate between a megaplasmid and a chromosome, also containing core genes that can be found on the chromosome but not on the megaplasmid. Using in silico prediction, we identified the “PABCH45 unnamed replicon” as a putative chromid in P. aeruginosa, which shows a much higher similarity and closer phylogenetic relationship to chromosomes than to megaplasmids while also encoding plasmid-like partition genes. We propose that such a chromid could facilitate genome expansion, allowing for more rapid adaptations to novel ecological niches or selective conditions, in comparison to megaplasmids.

To equip data-driven dynamic chemical process models with strong interpretability, we develop a light attention–convolution–gate recurrent unit (LACG) architecture with three sub-modules—a basic module, a brand-new light attention module, and a residue module—that are specially designed to learn the general dynamic behavior, transient disturbances, and other input factors of chemical processes, respectively. Combined with a hyperparameter optimization framework, Optuna, the effectiveness of the proposed LACG is tested by distributed control system data-driven modeling experiments on the discharge flowrate of an actual deethanization process. The LACG model provides significant advantages in prediction accuracy and model generalization compared with other models, including the feedforward neural network, convolution neural network, long short-term memory (LSTM), and attention-LSTM. Moreover, compared with the simulation results of a deethanization model built using Aspen Plus Dynamics V12.1, the LACG parameters are demonstrated to be interpretable, and more details on the variable interactions can be observed from the model parameters in comparison with the traditional interpretable model attention-LSTM. This contribution enriches interpretable machine learning knowledge and provides a reliable method with high accuracy for actual chemical process modeling, paving a route to intelligent manufacturing.

Abstract Osteoblasts and osteoclasts play an important role in maintaining the structural integrity of bone tissue, in which osteoclasts degrade bone structure and osteoblasts restore bone tissue. The imbalance of osteoblast and osteoclast function can lead to many bone-related diseases, such as osteoporosis and inflammatory osteolysis. The drug that can both promote bone formation and inhibit bone loss will be able to treat those diseases. In this study, it was found that LMK-235, an selective HDAC4/5 inhibitor, inhibited the differentiation and maturation of osteoclasts by regulating NF-κB and p-Smad2/3 signaling pathways via inhibition of HDAC4. At the same time, we found that LMK-235 promoted osteoblast mineralization by upregulating Runx2 expression via inhibition of HDAC4. In vivo, LMK-235 was able to alleviate lipopolysaccharide (LPS)-induced calvarial osteolysis and promote the repair of bone defects. Taken together, LMK-235 suppresses osteoclast differentiation and promotes osteoblast formation by inhibiting HDAC4. This may provide a valuable treatment for bone diseases caused by abnormal osteoclast bone resorption and osteoblast bone regeneration.

Abstract Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = −0.73, 95% CI: −1.09 to −0.37) and general anxiety symptoms (SMD = −0.75; 95% CI: −1.23 to −0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

Abstract This study explores aerosol direct, indirect, and feedback effects on meteorology and fine particulate matter during heat waves of August 2022 over eastern China by using an online coupled regional climate–chemistry–aerosol model. In this period, aerosols exerted mean direct (DRE) and indirect (IRE) radiative effects of −3.9 Wm−2 and −2.4 Wm−2 at TOA, which totally caused a decrease in average surface air temperature by 0.3 °C over east China, accompanied by decreases in PBLH (planetary boundary layer height) and precipitation and an increase in PM2.5 concentration. With the anthropogenic emission reduction from 2013 to 2022, DRE apparently decreased while IRE changed little, leading to a decrease in total aerosol radiative effect (TRE) by 27% at TOA. The weakened TRE resulted in increases in surface air temperature and precipitation by 0.14 °C and 2.7 mm, respectively, on average over east China, with the maximum warming exceeding 0.5 °C in BTH (Beijing–Tianjin–Hebei province). This study highlights a warming trend due to weakened TRE, which may exacerbate heat wave, and an increasing importance of aerosol IRE relative to DRE due to weak sensitivity of cloud properties to aerosol change during the emission reduction.

Abstract The EphA family belongs to a large group of membrane receptor tyrosine kinases. Emerging evidence indicates that the EphA family participates in tumour occurrence and progression. Nonetheless, the expression patterns and prognostic values of the nine EphAs in non-small cell lung cancer (NSCLC) have rarely been studied before. In the current study, we comprehensively analysed the expression and prognostic role of EphA family members by different means. The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases were used to investigate the expression of EphAs in NSCLC. The cBioPortal database was applied to analyse the prognostic values and genetic mutations of EphAs.We discovered that the expression of EphA10 was significantly higher in NSCLC tissues than in adjacent noncancerous tissues, and survival analyses showed that a higher level of EphA10 predicted poor prognosis. Further exploration into the role of EphA10 by ESTIMATE, CIBERSORT, and ssGSEA analysis found that it was also related to immune infiltration and higher expression of targets of ICI targets. In conclusion, this study revealed that among the EphA family members, EphA10 played an oncogenic role and was a promising biomarker for poor prognosis and better immunotherapy response in NSCLC.

To solve the spectrum scarcity problem, dynamic spectrum access (DSA) technology has emerged as a promising solution. Effectively implementing DSA demands accurate and efficient spectrum prediction. However, complex spatiotemporal correlation and heterogeneity in spectrum observations usually make spectral prediction arduous and even ambiguous. In this letter, we propose a spectrum prediction method based on an attention-aided graph convolutional neural network (AttGCN) to capture features in both spatial and temporal dimensions. By leveraging the attention mechanism, the AttGCN adapts its attention weights at different time steps and spatial positions, thus enabling itself to seize changes in spatiotemporal correlations dynamically. Simulation results show that the proposed spectrum prediction method performs better than baseline algorithms in long-term forecasting tasks.

Abstract Spatial accurate mapping of land susceptibility to wind erosion is necessary to mitigate its destructive consequences. In this research, for the first time, we developed a novel methodology based on deep learning (DL) and active learning (AL) models, their combination (e.g., recurrent neural network (RNN), RNN-AL, gated recurrent units (GRU), and GRU-AL) and three interpretation techniques (e.g., synergy matrix, SHapley Additive exPlanations (SHAP) decision plot, and accumulated local effects (ALE) plot) to map global land susceptibility to wind erosion. In this respect, 13 variables were explored as controlling factors to wind erosion, and eight of them (e.g., wind speed, topsoil carbon content, topsoil clay content, elevation, topsoil gravel fragment, precipitation, topsoil sand content and soil moisture) were selected as important factors via the Harris Hawk Optimization (HHO) feature selection algorithm. The four models were applied to map land susceptibility to wind erosion, and their performance was assessed by three measures consisting of area under of receiver operating characteristic (AUROC) curve, cumulative gain and Kolmogorov Smirnov (KS) statistic plots. The results revealed that GRU-AL model was considered as the most accurate, revealing that 38.5%, 12.6%, 10.3%, 12.5% and 26.1% of the global lands are grouped at very low, low, moderate, high and very high susceptibility classes to wind erosion hazard, respectively. Interpretation techniques were applied to interpret the contribution and impact of the eight input variables on the model’s output. Synergy plot revealed that the soil carbon content exhibited high synergy with DEM and soil moisture on the model’s predictions. ALE plot showed that soil carbon content and precipitation had negative feedback on the prediction of land susceptibility to wind erosion. Based on SHAP decision plot, soil moisture and DEM presented the highest contribution on the model’s output. Results highlighted new regions at high latitudes (southern Greenland coast, hotspots in Alaska and Siberia), which exhibited high and very high land susceptibility to wind erosion.

Abstract This review explores the intricate roles of metal ions—iron, copper, zinc, and selenium—in glioma pathogenesis and immune evasion. Dysregulated metal ion metabolism significantly contributes to glioma progression by inducing oxidative stress, promoting angiogenesis, and modulating immune cell functions. Iron accumulation enhances oxidative DNA damage, copper activates hypoxia-inducible factors to stimulate angiogenesis, zinc influences cell proliferation and apoptosis, and selenium modulates the tumor microenvironment through its antioxidant properties. These metal ions also facilitate immune escape by upregulating immune checkpoints and secreting immunosuppressive cytokines. Targeting metal ion pathways with therapeutic strategies such as chelating agents and metalloproteinase inhibitors, particularly in combination with conventional treatments like chemotherapy and immunotherapy, shows promise in improving treatment efficacy and overcoming resistance. Future research should leverage advanced bioinformatics and integrative methodologies to deepen the understanding of metal ion-immune interactions, ultimately identifying novel biomarkers and therapeutic targets to enhance glioma management and patient outcomes.

Abstract TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Abstract Background The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. Methods We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3 −/− and Cxcl10 −/− ) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3 −/− and Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3 −/− or Cxcl10 −/− recipient mice (CD45.2) and examined donor-contributed hematopoiesis. Results Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10 −/− donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. Conclusions The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.

Abstract Humic acid (HA) can substantially enhance plant growth and improve soil health. Currently, the impacts of HA concentrations variation on the development and soil quality of Panax notoginseng (Sanqi) from the forest understorey are still unclear. In this study, exogenous HA was administered to the roots of Sanqi at varying concentrations (2, 4, and 6 ml/L). Subsequently, the diversity and community structure of bacteria and fungi were assessed through high-throughput sequencing technology. The investigation further involved analyzing the interplay among the growth of sanqi, soil edaphic factors, and the microbial network stability. Our finding revealed that moderate concentrations (4 ml/L) of HA improved the fresh/dry weight of Sanqi and NO3 -−N levels. Compared with control, the moderate concentrations of HA had a notable impact on the bacterial and fungal communities compositions. However, there was no significant difference in the α and β diversity of bacteria and fungi. Moreover, the abundance of beneficial bacteria (Bradyrhizobium) and harmful bacteria (Xanthobacteraceae) increased and decreased at 4 ml/L HA, respectively, while the bacterial and fungal network stability were enhanced. Structural equation model (SEM) revealed that the fresh weight of Sanqi and bacterial and fungal communities were the factors that directly affected the microbial network stability at moderate concentrations of HA. In conclusion, 4 ml/L of HA is beneficial for promoting Sanqi growth and soil quality. Our study provides a reference for increasing the yield of Sanqi and sustainable development of the Sanqi-pine agroforestry system.

Abstract Objectives To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC’s etiology and further support the development of therapeutic strategies. Methods A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results UC patients demonstrated significantly higher native T1 (p

Colitis is an inflammatory intestinal disease that lasts for a long time, has an unknown cause, and occurs repeatedly. It is usually accompanied by symptoms such as intestinal cell damage, intestinal immunity, and abnormal intestinal flora. Numerous studies have shown that dietary fiber, as a prebiotic, its metabolites can selectively improve the composition of the intestinal flora, which in turn improves the level of intestinal short-chain fatty acids, reduces the expression of inflammatory factors, and enhances the function of the intestinal immune barrier, thereby improving the inflammatory response of the organism. This anti-inflammatory effect of dietary fiber through its metabolites provides new research ideas to assist in the treatment of colitis. This paper outlines the pathogenesis of colitis, and the mechanism of interaction between dietary fiber and its metabolites with intestinal flora, inflammatory factors and immune cells, aiming to provide theoretical basis for the alleviation of colitis by dietary fiber and the development of functional foods.

Solid polymer electrolytes (SPEs) are highly promising for realizing high-capacity, low-cost, and safe Li metal batteries. However, the Li dendritic growth and side reactions between Li and SPEs also plague these systems. Herein, a fluorinated lithium salt coating (FC) with organic-inorganic gradient and soft–rigid feature is introduced on Li surface as an artificial protective layer by the in-situ reaction between Li metal and fluorinated carboxylic acid. The FC layer can improve the interface stability and wettability between Li and SPEs, assist the transport of Li ions, and guide Li nucleation, contributing to a dendrite-free Li deposition and long-lifespan Li metal batteries. The symmetric cell with FC-Li anodes exhibits a high areal capacity of 1 mAh cm−2 at 0.5 mA cm−2, and an ultra-long lifespan of 2000 h at a current density of 0.1 mA cm−2. Moreover, the full cell paired with the LiFePO4 cathode exhibits improved cycling stability, remaining 83.7% capacity after 500 cycles at 1 C. When matching with the S cathode, the FC layer can prevent the shuttle effect, contributing to stable and high-capacity Li–S battery. This work provided a promising way for the construction of stable all-solid-state lithium metal batteries with prolonged lifespan.

Abstract The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P

Abstract Background HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. Methods Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. Results A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p

Abstract Calculus equations serve as fundamental frameworks in mathematics, enabling describing an extensive range of natural phenomena and scientific principles, such as thermodynamics and electromagnetics. Analog computing with electromagnetic waves presents an intriguing opportunity to solve calculus equations with unparalleled speed, while facing an inevitable tradeoff in computing density and equation reconfigurability. Here, we propose a reconfigurable metamaterial processing unit (MPU) that solves arbitrary linear calculus equations at a very fast speed. Subwavelength kernels based on inverse-designed pixel metamaterials are used to perform calculus operations on time-domain signals. In addition, feedback mechanisms and reconfigurable components are used to formulate and solve calculus equations with different orders and coefficients. A prototype of this MPU with a compact planar size of 0.93λ0×0.93λ0 (λ0 is the free-space wavelength) is constructed and evaluated in microwave frequencies. Experimental results demonstrate the MPU’s ability to successfully solve arbitrary linear calculus equations. With the merits of compactness, easy integration, reconfigurability, and reusability, the proposed MPU provides a potential route for integrated analog computing with high speed of signal processing.

Abstract Non-alcoholic steatohepatitis (NASH) is a hepatocyte inflammation based on hepatocellular steatosis, yet there is no effective drug treatment. Atherosclerosis (AS) is caused by lipid deposition in the endothelium, which can lead to various cardiovascular diseases. NASH and AS share common risk factors, and NASH can also elevate the risk of AS, causing a higher morbidity and mortality rate for atherosclerotic heart disease. Therefore, timely detection and diagnosis of NASH and AS are particularly important. In this study, differential gene expression analysis and weighted gene co-expression network analysis were performed on the AS (GSE100927) and NASH (GSE89632) datasets to obtain common crosstalk genes, respectively. Then, candidate Hub genes were screened using four topological algorithms and externally validated in the GSE43292 and GSE63067 datasets to obtain Hub genes. Furthermore, immune infiltration analysis and gene set variation analysis were performed on the Hub genes to explore the underlying mechanisms. The DGIbd database was used to screen candidate drugs for AS and NASH. Finally, a NASH model was constructed using free fatty acid-induced human L02 cells, an AS model was constructed using lipopolysaccharide-induced HUVECs, and a co-morbidity model was constructed using L02 cells and HUVECs to verify Hub gene expression. The result showed that a total of 113 genes common to both AS and NASH were identified as crosstalk genes, and enrichment analysis indicated that these genes were mainly involved in the regulation of immune and metabolism-related pathways. 28 candidate Hub genes were screened according to four topological algorithms, and CXCL9, IL2RB, and SPP1 were identified as Hub genes after in vitro experiments and external dataset validation. The ROC curves and SVM modeling demonstrated the good diagnostic efficacy of these three Hub genes. In addition, the Hub genes are strongly associated with immune cell infiltration, especially macrophages and γ–δ T cell infiltration. Finally, five potential therapeutic drugs were identified. has-miR-185 and hsa-miR-335 were closely related to AS and NASH. This study demonstrates that CXCL9, IL2RB, and SPP1 may serve as potential biomarkers for the diagnosis of the co-morbidity patterns of AS and NASH and as potential targets for drug therapy.