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Abstract Background and Objective Mitochondria are crucial to the function of renal tubular cells, and their dynamic perturbation in many aspects is an important mechanism of diabetic kidney disease (DKD). Single-nucleus RNA sequencing (snRNA-seq) technology is a high-throughput sequencing analysis technique for RNA at the level of a single cell nucleus. Here, our DKD mouse kidney single-cell RNA sequencing conveys a more comprehensive mitochondrial profile, which helps us further understand the therapeutic response of this unique organelle family to drugs. Methods After high fat diet (HFD), mice were intraperitoneally injected with streptozotocin (STZ) to induce DKD, and then divided into three subsets: CON (healthy) subset, DKD (vehicle) subset, and LST (losartan; 25 mg/kg/day) subset. Divide HK-2 cell into LG (low glucose; 5 mM) and HG (high glucose; 30 mM) and HG + LST (losartan; 1 µ M) subsets. snRNA-seq was performed on the renal tissues of LST and DKD subset mice. To reveal the effects of losartan on gene function and pathway changes in renal tubular mitochondria, Gene Ontology (GO) enrichment analysis and GSEA/GSVA scoring were performed to analyze the specific response of proximal tubular (PT) cell mitochondria to losartan treatment, including key events in mitochondrial homeostasis such as mitochondrial morphology, dynamics, mitophagy, autophagic flux, mitochondrial respiratory chain, apoptosis, and ROS generation. Preliminary validation through in vitro and in vivo experiments, including observation of changes in mitochondrial morphology and dynamics using probes such as Mitotracker Red, and evaluation of the effect of losartan on key events of mitochondrial homeostasis perturbation using electron microscopy, laser confocal microscopy, immunofluorescence, and Western blotting. Detection of autophagic flux in cells by transfecting Ad-mCherry-GFP-LC3B dual fluorescence labeled adenovirus. Various fluorescent probes and energy detector are used to detect mitochondrial apoptosis, ROS, and respiration of mitochondrion. Results Through the single-cell atlas of DKD mouse kidneys, it was found that losartan treatment significantly increased the percentage of PT cells. Gene Ontology (GO) enrichment analysis of differentially expressed genes showed enrichment of autophagy of mitochondrion pathway. Further GSEA analysis and GSVA scoring revealed that mitophagy and other key mitochondrial perturbation events, such as ROS production, apoptosis, membrane potential, adenosine triphosphate (ATP) synthesis, and mitochondrial dynamics, were involved in the protective mechanism of losartan on PT cells, thereby improving mitochondrial homeostasis. Consistent results were also obtained in mice and cellular experiments. In addition, we highlighted a specific renal tubular subpopulation with mitophagy phenotype found in single-cell data, and preliminarily validated it with co-localization and increased expression of Pink1 and Gclc in kidney specimens of DKD patients treated with losartan. Conclusions Our research suggests that scRNA-seq can reflect the multifaceted mitochondrial landscape of DKD renal tubular cells after drug treatment, and these findings may provide new targets for DKD therapy at the organelle level.

[Objective] To perform genetic analysis on samples with weak agglutination and mixed agglutination of ABO blood group antigens in neonates, and to investigate the molecular biological characteristics of ABO subtypes in neonates. [Methods] Serological identification of ABO blood group was performed by tube method and microcolumn gel method. The ABO exons 2-7 were amplified by PCR, and the amplified products were sequenced by Sanger sequencing method to determine the genotype. [Results] Among the ABO blood group serological results of 14 neonates, 8 cases showed weakened A antigen, and 6 cases showed weakened B antigen. Seven samples were identified with ABO subtype alleles, with genotypes as A102/B101+c.538C>T, Aw26/B102, A205/O02, A205/B101(2 cases), Aw26/O02, B(A)06/O01, B101/O01(3 cases), A102/O01(2 cases), A102/B101 and B101/O02. Additionally, three other family members were also found to carry B(A)06 allele in a pedigree investigation. [Conclusion] For samples showing weakened antigens in ABO blood type identification of neonates, it is necessary to consider the possibility of ABO subtype in addition to age factors, and genetic testing can be used to prevent missed detection of ABO subtypes in neonates.

Abstract An innovative GaN trench MOSFET featuring an ultra-low gate-drain charge (Q gd ) is proposed, with its operational mechanisms thoroughly investigated using TCAD simulations. This novel MOSFET design introduces a triple-shield structure (BPSG-MOS) comprising three critical components: (1) a grounded split gate (SG), (2) a P+ shield region (PSR), and (3) a semi-wrapped BP layer that extends the P-shield beneath the gate and along the sidewalls of the trench gate. Both the SG and PSR effectively reduce gate-drain coupling, transforming most of the gate-drain capacitance (C gd ) into a series combination of gate-source capacitance (C gs ) and drain-source capacitance (C ds ). Furthermore, the BP layer refines the gate-drain capacitance by converting the C gd at the trench gate sidewalls into C gs . This configuration significantly lowers C gd , resulting in an ultra-low Q gd . Compared to the dual-shield MOSFET (PSGT-MOS) and the conventional trench MOSFET (TG-MOS), the BPSG-MOS achieves reductions in C gd by 81% and 98%, respectively.

Abstract Background Maize is a major feed and industrial crop and pivotal for ensuring global food security. In light of global warming and climate change, improving maize tolerance to water deficit is crucial. Identification and functional analysis of drought tolerance genes have potential practical importance in understanding the molecular mechanisms of drought stress. Results Here, we identified a maize Homeodomain-Leucine Zipper I, ZmHDZ4, in maize seedlings that is associated with drought tolerance. We demonstrated that ZmHDZ4 has transcriptional activation activity, exclusively localized in the nucleus. Several Cis-acting elements associated with abiotic stress have been identified in the core promoter region of ZmHDZ4. Under drought-stressed conditions, transgenic maize plants overexpressing ZmHDZ4 exhibited significantly higher relative water content and peroxidase (POD) and superoxidase dismutase (SOD) activities compared to wide-type plants, while displaying lower malondialdehyde (MAD) content. The expressions of ZmMFS1-88, ZmGPM573, and ZmPHD9 were significantly repressed in the ZmHDZ4-OE plants under drought-stressed conditions, indicating that ZmMFS1-88, ZmGPM573, and ZmPHD9 were the candidate target genes of ZmHDZ4. Conclusions ZmHDZ4 is involved in the regulation of drought stress tolerance in maize by participating in osmotic regulation, sugar metabolism pathways, and hormone regulation.

Abstract Background Zoledronic acid (ZA) is widely used for the treatment of osteolytic bone metastases in malignancies and osteoporosis, but it has been associated with renal impairment. In this study, we investigated adverse events (AEs) related to renal and urinary system diseases associated with ZA using the U. S. FDA’s Adverse Event Reporting System. Methods We collected FAERS data from Q1 2004 to Q1 2024 and used the reporting odds ratio to detect AEs related to renal and urinary system diseases associated with ZA. Additionally, we applied multiple algorithms, including ROR, proportional reporting ratio, bayesian confidence propagation neural network, and multi-item gamma poisson shrinker, to quantify renal and urinary AEs under different indications. Results A total of 52,495 AE reports involving ZA as the primary suspect drug were identified. Among renal and urinary system diseases, 25 distinct AEs were recognized, with renal tubular necrosis being the most frequently reported. For different indications, renal tubular necrosis was the most reported AE in breast cancer and osteoporosis; nephrogenic diabetes insipidus was both the most frequent and strongest signal in lung cancer; proteinuria was most common in multiple myeloma, and polyuria in prostate cancer. Furthermore, most AEs occurred in patients who had been on ZA for more than 360 days, followed by those within the first 30 days of use. Conclusion Based on pharmacovigilance data from FAERS, different renal and urinary system AEs should be closely monitored and addressed according to the specific indications for which ZA is used.

Abstract Background In the process of education reform, carrying out continuous educational environment measurement is necessary. This study aimed to evaluate the perceptions of the medical education environment and learning autonomy in blended learning in pediatrics among clinical medicine students, as well as the relationship between these two constructs. Methods A cross-sectional study was conducted on clinical medical students from the First Clinical School of Wuhan University who had completed the blended learning courses of pediatrics. Perceptions of the medical education environment and learning autonomy were surveyed using the Dundee Ready Education Environment Measure (DREEM) and the Autonomy in Learning Rating Scale for college students (ALRS), respectively. Independent samples t-test, one-way ANOVA, correlation, and multiple linear regression analyses were conducted. Results A total of 487 students participated in the survey (valid response rate: 83.53%). Students’ perceptions of the current medical education environment and learning autonomy were generally positive. Among the average scoring rates of DREEM, students’ perception of teachers (SPT) > students’ perception of learning (SPL) > students’ perception of atmosphere (SPA) > students’ academic self-perceptions (SASP) > students’ social self-perception (SSSP), while learning strategies > learning motivation > self-regulation > content and environment among the average scoring rates of ALRS. Correlation analyses revealed that all subscales of the two were significantly associated with each other (P

Abstract Objective The global incidence of thyroid cancer (THCA) has significantly risen in recent years. This study aims to investigate the role and mechanisms of PTEN in epithelial mesenchymal transition (EMT), invasion and migration of THCA cells. Methods PTEN expression in THCA was analyzed through bioinformatics databases. RT-qPCR and Western blot analyses were performed to quantify PTEN levels in the Nthy-ori 3–1 cell line and three THCA cell types (TPC-1, B-CPAP, FTC-133). TPC-1 cells were transfected with a PTEN overexpression plasmid and treated with the Wnt activator. Cell viability and apoptosis were assessed via CCK-8 and flow cytometry, respectively. The expression levels of E-Cadherin, N-Cadherin, and Vimentin in TPC-1 cells were evaluated using Western blot. The invasive, migratory, and wound-healing abilities of the cells were examined using Transwell and scratch assays. Activation of the Wnt/β-catenin pathway was assessed through Western blot. Results PTEN expression was significantly lower in THCA cells, particularly in TPC-1 cells compared to other cell lines. PTEN overexpression led to decreased viability in TPC-1 cells, increased apoptosis, and a rise in E-Cadherin levels while reducing N-Cadherin and Vimentin levels, thereby inhibiting EMT. Furthermore, PTEN overexpression diminished the invasive, migratory and wound-healing capabilities of TPC-1 cells and suppressed activation of the Wnt/β-catenin pathway. Treatment with the Wnt activator partially counteracted the effects of PTEN overexpression on TPC-1 cells. Conclusion PTEN functions to inhibit EMT and the invasive and migratory characteristics of THCA cells by blocking the activation of the Wnt/β-catenin pathway.

Rhein is a natural anthraquinone substance extracted from Rheum palmatum L. This study aimed to evaluate Rhein’s protective effects against skin wound by in vivo and in vitro models and investigate whether its protective mechanism regulated the PI3K/AKT signaling pathway. The skin wound mice model was established and then treated with Rhein for 10 days. Hematoxylin and eosin staining and Masson’s trichrome staining were applied to assess histological changes and collagen maturity in the mice skin wound tissues. Human skin fibroblasts (HSFs) viability, migration, and invasion were detected by Cell counting kit-8 (CCK-8), scratch wound, and transwell assays respectively. Moreover, the protein expression of p-PI3K, PI3K, p-AKT, and AKT were determined by western blot assay. We found that local treatment with Rhein promoted skin wound healing and accelerated collagen maturation, compared with the Model group. In addition, Rhein promoted skin wound healing through accelerated HSF proliferation, migration, and invasion. Furthermore, Rhein remarkably enhanced p-PI3K and p-AKT expression, as well as p-PI3K/PI3K and p-AKT/AKT ratio in skin wound mice and HSF cells, suggesting that Rhein promoted skin wound healing by activating PI3K/AKT signaling pathway. In conclusion, Rhein is a promising agent for promoting wound healing of skin tissues.

In the context of achieving the “dual carbon” goal, the task of carbon emission reduction in the power industry urgently needs to be completed. Cross-regional electricity trading can facilitate the remote consumption of surplus renewable resources and contribute to the low-carbon transformation of the power system. Due to the inherent differences in power generation structures across interconnected regions, the impact of carbon costs on the clearing electricity prices within regions varies, leading to dynamic price differences between regions, which, in turn, affects the outcomes of cross-regional electricity trading, and further exacerbates the differences in power generation structures, thereby impacting interval electricity price differences. To address these complexities, this paper proposes an assessment model which considers both carbon costs and interval electricity price differences in evaluating cross-regional electricity trading volumes. The model aims to establish a coherent relationship between interval price differences and cross-regional electricity trading by incorporating carbon costs into the power system production process. It uses the dynamic interval price difference as a signal to determine the trading volume between regions in the evaluation of cross-regional electricity trading volumes. In assessing interval price differences, the model updates the intra-region power generation structure based on unit revenue rates, and contrasts the price differences before and after these structural iterations. Taking the cross-regional electricity trading between two interconnected areas as an example, the results of the computational simulations demonstrate that the proposed model effectively evaluates the dynamic price differences between regions and cross-regional electricity trading volumes. Additionally, it quantifies the impact of power generation structure evolution on interval price differences.

A new type of rotary reducer is urgently needed in engineering to improve the low efficiency of single point drive operation for flat single axis photovoltaic tracking brackets, in order to adapt to complex environments and reduce costs. For this purpose, a cylindrical worm helical gear toroidal worm multi-point drive rotary reducer was designed, and performance testing and analysis were conducted. Firstly, the installation position and transmission mechanism of the multi-point drive rotary reducer were analyzed and compared with that of the single point drive. Secondly, the performance of the rotary reducer under rated output torque and overturning torque was numerically simulated using Romax software, and a comprehensive performance testing platform for the rotary reducer was built to test the transmission performance of the prototype under rated output torque and overturning torque. The results show that multi-point drive can withstand larger loads compared to single point drive, and the overall stability of the tracking bracket is stronger; the larger the rated output torque value, the greater the stress value of the worm gear; the overall stress value and deformation of the secondary transmission mechanism under the overturning torque meet the actual working condition requirements; the test does not cause significant damage inside the reducer, and the simulation and test results are in good agreement. The design of the rotary reducer meets the practical working characteristics of the flat single axis photovoltaic tracking bracket under harsh working conditions, and can provide theoretical reference and support for improving the photovoltaic conversion efficiency construction of photovoltaic power stations.

Abstract Aims We aim to evaluate change in the use of prognostic guideline‐directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non‐cancer controls, including renin‐angiotensin‐system inhibitors (RASIs), beta‐blockers, and mineralocorticoid receptor antagonists (MRAs). Methods and results We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12 months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non‐cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR = 1.51, 95% CI = 1.35–1.68; beta‐blockers: OR = 1.22, 95% CI = 1.08–1.37; MRAs: OR = 1.31, 95% CI = 1.08–1.59) and poor persistence (RASIs: OR = 2.04, 95% CI = 1.75–2.37; beta‐blockers: OR = 1.35, 95% CI = 1.12–1.63; MRAs: OR = 1.49, 95% CI = 1.16–1.93), and higher risks for dose down‐titration for RASIs (OR = 1.69, 95% CI = 1.40–2.04) and beta‐blockers (OR = 1.31, 95% CI = 1.05–1.62). Cancer diagnosis was not associated with treatment initiation or dose up‐titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs. Conclusions Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF.

Abstract On‐chain sealed auctions represent a novel approach to electronic bidding auctions, wherein the introduction of zero‐knowledge proof technology has significantly enhanced the security of auctions. However, most mainstream on‐chain sealed auction schemes currently employ Bulletproofs to prove auction correctness, which leaves room for optimization in terms of verification time and inherent security. Addressing these issues, an on‐chain sealed auction scheme based on zero‐knowledge succinct non‐interactive argument of knowledge (zk‐STARK) is proposed. This scheme leverages the decentralization and immutability of blockchain and smart contracts to eliminate third‐party involvement while ensuring the security of the auction process. The Inter Planetary File System is utilized to provide a qualification review mechanism for the auctioneer, enabling the screening of unqualified bidders before the auction. Additionally, the scheme employs RSA encryption to conceal bidders' bids, Pedersen commitments to ensure the consistency of bidding information, and zk‐STARKs to verify the correctness of the winning bid. Security analysis and experimental results demonstrate that the proposed scheme meets the required security standards, with time consumption at various stages of the auction being within acceptable limits, and effectively reduces the time required for proof verification.

Abstract Background The study aimed to investigate the predictive value of delta-radiomics derived from computed tomography (CT) for pathological complete response (pCR) to neoadjuvant immunochemotherapy (NICT) among patients with esophageal squamous cell carcinoma (ESCC), helping clinicians determine whether to modify the neoadjuvant treatment strategy, proceed to surgery, or forgo surgery altogether. Methods A total of 140 ESCC patients from two institutions (Database 1 = 93; Database 2 = 47) who underwent NICT and surgery were retrospectively included in the study. The training set consisted of patients from Database 1, while the testing set included patients from Database 2. All patients underwent contrast-enhanced CT scans before the start of the treatment and prior to the operation. The delta-radiomics features were calculated as the relative net change of radiomics features between the two-time points. Feature selection was conducted using Pearson correlation analysis, intraclass correlation coefficients, and the fivefold cross-validation with least absolute shrinkage and selection analysis. Four models were established, comprising a clinical model, a pre-treatment radiomics model, a delta-radiomics model, and a mixed model. Area under the curve (AUC) and decision curve analysis were used to assess the performance and the clinical value of the models. Results Less than half of the tumors (40/140, 28.6%) showed pCR following NICT. The delta-radiomics model displayed AUC of 0.827 and 0.790 in the training and testing set for predicting pCR, which was superior to the clinical model based on age and clinical tumor node metastasis (cTNM) stage (0.758 and 0.615) and the pre-treatment radiomics model (0.787 and 0.621). Furthermore, the delta-radiomics model demonstrated a more excellent AUC value in the testing set than the mixed model (0.847 and 0.719), which integrated clinical and delta-radiomics features. Conclusions The delta-radiomics model exhibited better diagnostic performance in preoperative prediction of pCR for NICT in ESCC patients compared to the clinical, pre-treatment radiomics, and mixed models.

Objective To investigate effect of Chinese herbal medicine pack hot compress on relieving skin itching symptom in diabetes patients. Methods From January 2024 to May 2024, 64 diabetes patients with deficiency of both Qi and Yin syndrome were divided into the control group and the intervention group according to the random number table grouping method, of 32 patients in each group, Both groups were administered the same basic treatment, The control group were given oral loratadine tablets, 10 mg orally once after a daily breakfast, 14 days; The intervention group was treated with Chinese herbal medicine pack hot compress. Using Traditional Chinese Medicine syndrome integral scale, Visual Analogue Scale(VAS) and Pittsburgh Sleep Quality Index (PSQI) to measure the degree of pruritus symptoms and sleep quality before enrollment and 14 days after treatment. Results The pruritus response rate in the intervention group was 96. 88% (31/32) and 75%(24/32) in the control group, with as significant difference (P＜0. 05). The total score of TCM integral scale was (16. 75 ± 4. 23) in the intervention group and (27. 94 ± 3. 29) in the control group, with as significant difference(t=11. 81, P＜0. 05); The VAS score of patients in intervention group was (2. 08 ± 0. 63), which was lower than (4. 55 ± 1. 21) of patients in the control group (t=10. 24, P＜0. 05); PSQI score of patients in the intervention group was (9. 06 ± 2. 75), which was lower than (10. 66 ± 2. 70) of patients in the control group (t= 2. 34, P＜0. 05). Conclusion The clinical effect of using Chinese herbal medicine pack hot compress to treat pruritus is remarkable, which can reduce the skin itching symptoms and improve the sleep quality of patients. (目的 探讨使用药包热敷器治疗糖尿病患者皮肤瘙痒的效果。方法 2024年1月—5月, 选取贵州中医药大学第一附属医院内分泌科住院的气阴两虚型糖尿病皮肤瘙痒患者64例为研究对象, 按照随机数字表分组法分为对照组和干预组, 每组32例。两组给予相同的基础治疗, 对照组均予口服氯雷他定片, 每日早餐后1次10 mg口服, 治疗14 d; 干预组给予中医特色技术药包热敷器治疗。利用中医证候总积分评估表、视觉模拟评分尺(VAS)、匹兹堡睡眠质量指数量表(PSQI), 在入组前和治疗后14 d分别进行患者瘙痒症状、瘙痒视觉感知、睡眠质量的测试, 评估患者皮肤瘙痒及睡眠改善情况。结果 干预组的瘙痒缓解率为96. 88%(31/32), 对照组为75%(24/32), 差异有统计学意义(P＜0. 05)。治疗后, 干预组中医证候总积分为(16. 75±4. 23)分, 对照组为(27. 94±3. 29)分, 干预组评分低于对照组(t=11. 81, P＜0. 05); 干预组患者瘙痒VAS评分为(2. 08±0. 63)分, 对照组为(4. 55±1. 21)分, 干预组评分低于对照组(t=10. 24, P＜0. 05); 干预组患者PSQI量表评分为(9. 06±2. 75)分, 对照组为(10. 66±2. 70)分, 干预组评分低于对照组(t=2. 34, P＜0. 05)。结论 临床使用药包热敷器治疗气阴两虚型糖尿病皮肤瘙痒效果明确, 能够减轻皮肤瘙痒症状, 改善患者睡眠质量, 提高生活质量, 具有推广价值。)

Objective·To investigate the expression of metastasis-associated protein 1 (MTA1) in placental tissues of preeclampsia (PE) patients and its impact on trophoblast cell function.Methods·Placental specimens were collected from pregnant women with PE (PE group, 20 cases) patients and healthy pregnant women as controls (control group, 35 cases). Western blotting and immunofluorescent double staining were performed to analyze the expression changes of MTA1. The human first-trimester placental trophoblast cell line HTR8/SVneo was cultured, and the cell migration ability was assessed through wound healing assay. The cell invasion ability was detected using Transwell invasion assay. Under hypoxic conditions simulating the invasion of extravillous trophoblasts into the uterus, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyze the mRNA expression of hypoxia-induced matrix metalloproteinases (MMP-2 and MMP-9), thus assessing their secretion levels. An extravillous trophoblast explant model was constructed to assess the overall villus outgrowth capacity of the explants. Immunohistochemistry (IHC) was performed to confirm the presence of the endothelial marker CD31 for placental angiogenesis analysis in mice. Fifteen Mta1-/- female mice and fifteen wild-type C57 female mice were mated with wild-type male C57 mice for fertility testing.Results·Western blotting revealed significantly decreased expression of MTA1 protein in placental tissues of the PE group compared to the control group. Immunofluorescent double staining showed that MTA1 was mainly localized in the nuclei of trophoblast cells. The wound healing assay demonstrated that HTR8/SVneo with stable MTA1 knockdown exhibited weaker cell migration ability compared to the control group (P=0.002). The Transwell invasion assay demonstrated a marked decrease in invasiveness in MTA1-knockdown cells, significantly lower than the control group (P=0.015). Hypoxia-induced expression levels of matrix metalloproteinases MMP-2 and MMP-9 were significantly reduced (P=0.020, P=0.003). After MTA1 knockdown, the overall villus outgrowth capacity of the explants was decreased compared to the control group (P=0.003). IHC results showed that CD31 expression in the placenta of Mta1-/- female mice was significantly lower than that of wild-type female mice (P=0.004). The litter size of Mta1-/- female mice was significantly reduced (P=0.000).Conclusion·The expression level of MTA1 is closely related to PE. Endogenous MTA1 may be involved in trophoblast invasion into the endometrium and villous capillary remodeling.

Abstract Background Soil microorganisms play a key role in nutrient cycling, carbon sequestration, and other important ecosystem processes, yet their response to seasonal dry–wet alternation remains poorly understood. Here, we collected 120 soil samples from dry-hot valleys (DHVs, ~ 1100 m a.s.l.), transition (~ 2000 m a.s.l.) and alpine zones (~ 3000 m a.s.l.) along the Jinsha River in southwest China during both wet and dry seasons. Our aims were to investigate the bacterial microbiome across these zones, with a specific focus on the difference between wet and dry seasons. Results Despite seasonal variations, bacterial communities in DHVs exhibit resilience, maintaining consistent community richness, diversity, and coverage. This suggests that the microbes inhabiting DHVs have evolved adaptive mechanisms to withstand the extreme dry and hot conditions. In addition, we observed season-specific microbial clades in all sampling areas, highlighting their resilience to environmental fluctuations. Notably, we found similarities in microbial clades between soils from DHVs and the transition zones, including the phyla Actinomycetota, Chloroflexota, and Pseudomonadota. The neutral community model respectively explained a substantial proportion of the community variation in DHVs (87.7%), transition (81.4%) and alpine zones (81%), indicating that those were predominantly driven by stochastic processes. Our results showed that migration rates were higher in the dry season than in the wet season in both DHVs and the alpine zones, suggesting fewer diffusion constraints. However, this trend was reversed in the transition zones. Conclusions Our findings contribute to a better understanding of how the soil microbiome responds to seasonal dry–wet alternation in the Jinsha River valley. These insights can be valuable for optimizing soil health and enhancing ecosystem resilience, particularly in dry-hot valleys, in the context of climate change.

Abstract Background Preoperative frailty is a risk factor associated with postoperative delirium (POD), which has attracted more attention from clinicians, but no research has shown that it is related to elderly patients undergoing craniotomy. Therefore, the aim of this study was to determine the effect of preoperative frailty on POD in older patients, especially those who underwent craniotomy. Methods From October 2022 to May 2023, older patients who underwent elective craniotomy were collected. Assess the occurrence of frailty using the FRAIL scale one day before surgery. Evaluate the occurrence of POD using the Confusion Assessment Method (CAM) within three days after surgery. Participants were divided into two groups, one group being POD, Logistic regression analysis was used to find the risk variables for POD, and the predictive value of preoperative frailty to POD was determined by using the operating characteristic curve of the subjects. Results A total of 300 patients were included in this study, among whom 83 patients (27.7%) exhibited preoperative frailty and 69 patients (23.0%) experienced POD. The results of the multivariate logistic regression analysis indicate that preoperative frailty (OR: 8.816, 95% CI: 3.972–19.572), preoperative hypoalbuminemia (OR: 0.893, 95% CI: 0.811–0.984), low BMI (OR: 0.793, 95% CI: 0.698–0.901), and prolonged operative duration (OR: 1.007, 95% CI: 1.004–1.010) are independent risk factors for POD in older patients who underwent craniotomy. We constructed a risk prediction model using these factors, which had an area under the ROC curve of 0.908 (95% CI: 0.869–0.947, P

Abstract Epithelial ovarian carcinoma (EOC) is the most fatal among female reproductive system tumors. The immune tumor microenvironment and ubiquitin-proteasome pathway are closely related to the proliferation, invasion, and response to chemotherapy in EOC. However, their specific roles in EOC have not been fully elucidated. Therefore, we aimed to recognize potential prognostic markers and novel therapeutic targets for EOC. We constructed the ubiquitin-related signature risk model comprising HSP90AB1, FBXO9, SIGMAR1, STAT1, SH3KBP1, EPB41L2, DNAJB6, VPS18, PPM1G, AKAP12, FRK, and PYGB, specifically for patients with EOC. The high-risk model presented a worse prognosis, primarily associated with the B-cell receptor signaling pathway, ECM receptor interaction, focal adhesion, and actin cytoskeleton regulations. Analysis of the immune landscape revealed a higher abundance of B cells, M2 macrophages, neutrophil CD4 T cells, cancer-associated fibroblasts, macrophage neutrophils, and fibroblasts in the high-risk group. It also exhibited lower tumor mutation burden, mRNAsi, and EREG-mRNAsi and reduced sensitivity to other chemotherapy drugs, except dasatinib. These findings serve as a valuable indicator for personalized treatment strategies and clinical stratification in managing patients with EOC. Additionally, our study will serve as a foundation for future mechanistic research to explore the association between the ubiquitin-proteasome pathway and EOC.

Abstract Phototherapy can offer a safe and non-invasive solution against infections, while promoting wound healing. Conventional phototherapeutic devices are bulky and limited to hospital use. To overcome these challenges, we developed a wearable, flexible red and blue LED (r&bLED) patch controlled by a mobile-connected system, enabling safe self-application at home. The patch exhibits excellent skin compatibility, flexibility, and comfort, with high safety under system supervision. Additionally, we synthesized a sprayable fibrin gel (F-gel) containing blue light-sensitive thymoquinone and red light-synergistic NADH. Combined with bLED, thymoquinone eradicated microbes and biofilms within minutes, regardless of antibiotic resistance. Furthermore, NADH and rLED synergistically improved macrophage and endothelial cell mitochondrial function, promoting wound healing, reducing inflammation, and enhancing angiogenesis, as validated in infected diabetic wounds in mice and minipigs. This innovative technology holds great promise for revolutionizing at-home phototherapy for chronic infected wounds.

Objective: To evaluate the capability of wrist pulse analysis in distinguishing three physiological and pathological conditions: healthy individuals, coronary heart disease (CHD) patients without a history of ischemic stroke, and CHD patients with a history of ischemic stroke. Methods: Study participants were recruited from Shuguang East Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, and Shanghai Municipal Hospital of Traditional Chinese Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, from April 15 to September 15, 2021. They were categorized into three groups: healthy controls (Group 1), CHD patients without a history of ischemic stroke (Group 2), and CHD patients with a history of ischemic stroke (Group 3). The wrist pulse signals of the study participants were non-invasively collected using a pulse diagnosis instrument. The linear time-domain features and nonlinear time-series multiscale entropy (MSE) features of the pulse signals were extracted using time-domain analysis and the MSE methods, which were subsequently compared between groups. Based on these extracted features, a recognition model was developed using a random forest (RF) algorithm. The classification performance of the models was evaluated using metrics, including accuracy, precision, recall, and F1-score derived from confusion matrix as well as the area under the receiver operating characteristics (ROC) curve (AUC). Results: A total of 189 participants were enrolled, with 63 in Group 1, 61 in Group 2, and 65 in Group 3. Compared with Group 1, Group 2 showed significant increases in pulse features H2/H1, H3/H1, W1, W2, and W2/T, and decreased in MSE1 – MSE7 (P < 0.05), while Group 3 showed significant increases in pulse features T5/T4, T, H1/T1, W1, W2, AS, and Ad, and decreased in MSE1 – MSE20 (P < 0.05). Compared with Group 2, Group 3 demonstrated notable increases in H1/T1 and As (P < 0.05). The RF model achieved precision of 80.00%, 61.54%, and 61.54%, recall of 74.29%, 60.00%, and 68.97%, F1-scores of 70.04%, 60.76%, and 65.04%, and AUC values of 0.92, 0.74, and 0.81 for Groups 1, 2, and 3, respectively. The overall accuracy was 67.69%, with micro-average AUC of 0.83 and macro-average AUC of 0.82. Conclusion: Differences in pulse features reflect variations in arterial compliance, peripheral resistance, cardiac afterload, and pulse signal complexity among healthy individuals, CHD patients without a history of ischemic stroke, and those with such a history. The developed pulse-based recognition model holds the potential in distinguishing between these three groups, offering a novel diagnostic reference for clinical practice.

Under hydrothermal conditions, two novel Zn(ii)/Cd(ii) complexes [Cd2(L)4(Cl)2]·(SO4) (1) and {[Zn2(L)2(Sip)(OH)]·H2O}n (2) (L = 2-(2,6-dichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, NaH2Sip = 5-sulfoisophthalic acid monosodium salt) were successfully synthesized and characterized by elemental analysis, single-crystal X-ray diffraction, and Hirshfeld surface analysis. The study reveals that complex 1 is constructed from the binuclear [Cd2L4Cl2] unit, and the [Cd2L4Cl2] units are linked via C–H⋯π and C–Cl⋯π interactions into 2D supramolecular layers. These 2D layers are further connected to generate 3D structures by N–H⋯O and N–H⋯S hydrogen bonds. Complex 2 exhibits a 1D double-chain structure consisting of a binuclear [Zn2L2(OH)] unit, which is further connected by π–π interaction to shape a 2D supramolecular structure.

In view of the geological characteristics and development contradictions of different types of heavy oil reservoirs in Shengli Oilfield， a set of development technologies for heavy oil reservoirs have been developed， and remarkable development achievements have been obtained. In this paper， the progress of development technologies for different types of heavy oil reservoirs was summarized in the theoretical basis and the field application. For heavy oil reservoirs after many rounds of huffing and puffing， the well pattern infilling technology was formed based on the non-Darcy flow theory. For sensitive heavy oil reservoirs， the adverse impact of water sensitivity on development was reduced based on the proposed theory of near heat and remote prevention. For extra-heavy oil reservoirs， HDCS technology was applied through the synergistic viscosity reduction and energy enhancement due to the expansion to solve the development problem of difficult injection and production. For inefficient water-flooding heavy oil reservoirs， the flow lines of infilled corner wells and water wells were changed by turning to steam flooding to enhance oil recovery. For deep heavy oil reservoirs， the multi-thermal composite oil displacement theory was formed， and deep heavy oil reservoirs were effectively produced based on the understanding of the synergistic interaction mechanism of gas-heat synergy for heat retention and enhancing steam chamber， heat-agent synergy for replacing viscosity reduction and improving flooding， and gas-agent synergy for thermal front equilibrium. For thin heavy oil reservoirsthe steam absorption capacity and production ranges were improved through the thermal and horizontal well composite development model. For shallow extra-heavy oil reservoirs， HDNS technology was used to enhance the energy， reduce viscosity， and expand the spread， realizing efficient development. The application of development technologies for heavy oil reservoirs in Shengli Oilfield provides technical support for the beneficial development and green development of heavy oil in Shengli Oilfield.

The random forest algorithm， known for its robustness against noise and powerful computational capabilities， is widely employed in diagnosing vibration faults in rotating machinery. However， when applied in industrial settings， the algorithm encounters challenges such as limited sample sizes， the inability to integrate prior knowledge， and comparatively lower accuracy. To tackle these issues， a method for diagnosing vibration faults in steam turbines using an improved random forest （IRF） algorithm is proposed. This approach incorporates prior knowledge to optimize decision trees， utilizing analytical hierarchy process （AHP） and information entropy. Genuine operational datasets from the data center of a million-kW thermal power plant are utilized to validate the efficacy and reliability of the proposed method. Computational findings indicate that， in comparison to the traditional random forest algorithm， IRF achieves higher accuracy and a reduced miss rate， with a 33% decrease in the number of decision trees. Moreover， the operational time is slashed to just 11.4% of that taken by the traditional random forest algorithm. These results suggest that IRF holds significant practical value for real-time， precise vibration fault diagnosis in thermal power units.

【Objective】 This paper is to propose a method to optimize ecological space zoning and develop scientific management strategies for watersheds. The focus is on clarifying the synergies and trade-offs among mountains, waters, forests, farmlands, lakes, and grasslands. 【Method】 The study takes the Hongfeng Lake watershed as a case study. It is a typical watershed consisting of mountains, water, forests, fields, lakes and grasses. Quantitative and qualitative methods were used to calculates synergies and trade-offs between these sub-ecosystems at both basin scale and local scale. The ecological zoning in the watershed was analyzed by considering the synergistic relationships between mountains, waters, forests, farmlands, lakes and grasslands. 【Result】 The study revealed significant spatial variation in ecological zones within the studied areas. It identified contrasting spatial relationships in the distribution of synergies and trade-offs, particularly between water and other subsystems, as defined by the water intersection line. Key findings include differentiated ecological protection roles of forests and grasslands, high pollution risks facing lakes, and the reliance on rainfall for agriculture outside regions where lakes effectively manage water storage. The watershed was classified into nine ecological control zones, including urban water source protection zones and ecological agricultural zones along the lake and its tributaries. Additionally, mountain areas were designated as ecological industrial development and conservation zones, water source conservation zones, and geo-hazard risk zones. 【Conclusion】 By analyzing the coordination and trade-offs among various ecological components, this study ensures the maximization of ecological diversity within each zoning type. The findings highlight the need for tailored management strategies across different zones to address their unique ecological needs and challenges.

ABSTRACT Serratia and Acinetobacter are recognized as significant opportunistic pathogens affecting aquatic animals and humans. However, their infections in amphibians are poorly documented, and their pathogenicity to the Chinese spiny frog (Quasipaa spinosa) remains unexplored. This study investigated an outbreak of putrid-skin disease among Q. spinosa on a farm in Lishui City, Zhejiang Province, China. Two pathogenic strains, GL-XJ7 and GL-XJ11, were isolated from disease lesions and identified as Serratia nematophila and Acinetobacter guillouiae, respectively, through morphological, physiological, biochemical, and molecular analyses including 16S rDNA sequencing and phylogenetic tree construction. Experimental infections revealed median lethal concentrations (LD50) over 72 h of 3.98×107 CFU/mL for S. nematophila strain GL-XJ7 and 3.16 × 106 CFU/mL for A. guillouiae strain GL-XJ11. Infected frogs exhibited symptoms consistent with natural infections, including reduced vitality, skin shedding, and ulceration. Histopathological examinations demonstrated that both strains induced hepatocellular damage, nuclear alterations, muscular atrophy, myofibrillar degeneration, and intestinal necrosis. Antibiotic susceptibility tests showed that S. nematophila strain GL-XJ7 was highly susceptible to ceftazidime and gentamicin, while A. guillouiae strain GL-XJ11 exhibited high susceptibilities to tetracycline, ceftazidime, and gentamicin. Both strains demonstrated resistance to penicillin, ampicillin, bacitracin, and clindamycin. This study provides the first description of natural S. nematophila strain GL-XJ7 and A. guillouiae strain GL-XJ11 infections and their pathogenesis in Q. spinosa, highlighting potential risks to other animals and human health. These findings establish a theoretical foundation for the clinical management and prevention of putrid-skin disease in artificially bred frogs.IMPORTANCEFrogs are among the most widely distributed amphibians globally. The Chinese spiny frog (Quasipaa spinosa) is a unique amphibious species endemic to China and holds significant economic value in aquaculture. Effective disease prevention and control are crucial for the sustainable development of frog breeding industries and the conservation of genetic resources. In this study, we investigated a putrid-skin disease outbreak at a frog farm in Lishui City, Zhejiang Province, Eastern China. We isolated and identified the causative pathogenic bacteria and analyzed their pathogenicity through artificial infection experiments and histopathological examinations. This research provides the first data on the pathogenic characteristics of Serratia nematophila and Acinetobacter guillouiae in Q. spinosa. Furthermore, we assessed the antibiotic susceptibility of these two pathogens, revealing their multidrug resistance. Our findings offer a scientific foundation for the accurate diagnosis and control of putrid-skin disease in frogs, contributing to the preservation of Q. spinosa genetic resources.

ABSTRACT Estimating the impacts of anthropogenic activities and climate change on species' spatial distributions is crucial for conservation. In this study, based on 62 valid occurrence records of Sphenomorphus incognitus and 24 environmental factors (19 climate factors, 4 topographic factors, and 1 human activity factor), we utilized the biomod2 combined model platform to predict suitable habitats for S. incognitus under two current scenarios (Scenario 1: natural state; Scenario 2: human interference state) and two future climate scenarios (SSP1‐2.6 and SSP5‐8.5) in 2050s and 2090s. The mean true skill statistic (TSS) and the area under the receiver operating characteristic curve (AUC) suggested that the ensemble model yield more precise predictions than those of individual models. Rainfall and slope were identified as the most important factors influencing S. incognitus distribution. Human disturbance has significantly reduced suitable habitat by 44.13 × 104 km2, which is a decrease in 23.95% compared to natural conditions. Spatial analysis revealed substantial fragmentation of suitable habitat due to human activities. The incorporation of anthropogenic factors into the analysis of future climate scenarios has revealed that the area of suitable habitat exhibits divergent trends. Two distinct scenarios have been identified, each of which results in a reduction in the area of the region by 29.58 × 104 km2 and an increase by 27.04 × 104 km2, respectively, by the year 2090. The primary influence persists in human activities. The centroid of suitable habitat shifted toward the southeast under SSP1‐2.6 and toward the northwest under SSP5‐8.5. Our findings highlight the significant impact of anthropogenic factors on S. incognitus habitat and emphasize the need for conservation measures. Future research should incorporate additional socioeconomic data to further investigate the effects of human disturbance on this species.

With the rapid development of urbanization, urban wetlands have been severely damaged by human activities and natural factors, leading to problems such as reduced area and decreased connectivity between wetlands. Constructing wetland ecological networks is an effective approach to alleviating urban wetland landscape fragmentation and enhancing wetland connectivity. However, research on constructing, analyzing, and optimizing wetland ecological networks in highly urbanized areas remains limited. This study used landscape ecology, topology, and spatial analyses techniques to build a wetland ecological network for Haidian District, a rapidly urbanizing area. A complex network model was used to conduct in-depth analysis and optimization of the network. The results show that the wetland ecological network in Haidian District identified 25 wetland ecological sources and 45 wetland stepping-stone patches. The network established 64 wetland ecological corridors and 87 wetland stepping-stone corridors. Additionally, 21 ecological fracture points and 15 high ecological barriers were detected in the network. Topological analysis revealed that removing key nodes would significantly reduce the stability of the network. To address this issue, a simulation was performed that added eight new corridors, resulting in improved overall connectivity and stability of the optimized wetland ecological network. Specific conservation and restoration strategies were proposed based on the existing issues of wetlands in Haidian District. The findings of this study provide important references for the sustainable development of the wetland ecosystem in Haidian District and offer methodological support for the conservation and restoration of wetlands in other highly urbanized areas.

Background and objectiveRelevant research has provided valuable insights into risk factors for bicycle crashes at intersections. However, few studies have focused explicitly on three common types of bicycle crashes on road segments: overtaking, rear-end, and door crashes. This study aims to identify risk factors for overtaking, rear-end, and door crashes that occur on road segments.Material and methodsWe analysed British STATS19 accident records from 1991 to 2020. Using multivariate logistic regression models, we estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for multiple risk factors. The analysis included 127,637 bicycle crashes, categorised into 18,350 overtaking, 44,962 rear-end, 6,363 door, and 57,962 other crashes.ResultsSignificant risk factors for overtaking crashes included heavy goods vehicles (HGVs) as crash partners (AOR = 1.30, 95% CI 1.27-1.33), and elderly crash partners (AOR = 2.01, 95% CI = 1.94-2.09), and decreased risk in rural area with speed limits of 20-30 miles per hour (AOR = 0.45, 95% CI = 0.43-0.47). For rear-end crashes, noteworthy risk factors included unlit darkness (AOR = 1.49, 95% CI = 1.40-1.57) and midnight hours (AOR = 1.28, 95% CI = 1.21-1.40). Factors associated with door crashes included urban areas (AOR = 16.2, 95% CI = 13.5-19.4) and taxi or private hire cars (AOR = 1.61, 95% CI = 1.57-1.69). Our joint-effect analysis revealed additional interesting results; for example, there were elevated risks for overtaking crashes in rural areas with elderly drivers as crash partners (AOR = 2.93, 95% CI = 2.79-3.08) and with HGVs as crash partners (AOR = 2.62, 95% CI = 2.46-2.78).ConclusionsThe aforementioned risk factors remained largely unchanged since 2011, when we conducted our previous study. However, the present study concluded that the detrimental effects of certain variables became more pronounced in certain situations. For example, cyclists in rural settings exhibited an elevated risk of overtaking crashes involving HGVs as crash partners.

Abstract Current research efforts in polymer and nanotechnology applications are primarily focused on cargo delivery to enhance the therapeutic index, with limited attention being paid to self‐molecularly targeted nanoparticles, which may also exhibit significant therapeutic potential. Long‐term and anomalous lipid accumulation in the liver is a highly relevant factor contributing to liver diseases. However, the development of the reliable medications and their pharmacological mechanisms remain insufficient. Herein, a polyguanide nanoinhibitors (PGNI) depot is constructed by copolymerizing biguanide derivatives in different proportions onto prepolymers. The nanoinhibitors for their ability to ameliorate lipid accumulation in vitro and in vivo is screened, and subsequently demonstrated that covalently polymeric guanidine chains exhibit superior efficacy in ameliorating hepatic lipid accumulation via heterogeneous mechanisms compared to small‐molecule guanidine. It is found that PGNIs stabilize guanidine metabolism in the liver, preferably for biosafety. More importantly, PGNI is ingested and localized in hepatocyte lysosomes and is locked to interact with vesicular adenosine triphosphatase (V‐ATPase) on lysosomes, leading to the inhibition of V‐ATPase and lysosomal acidification, thereby activating the AMPK pathway, reducing fatty acid synthesis, and enhancing lipolysis and fatty acid oxidation. These results imply that polymer‐formed nanoparticles can serve as targeted inhibitors, offering a novel approach for therapeutic applications.

Avian reovirus (ARV) is highly prevalent in healthy poultry flocks and has been linked to viral arthritis/tendonitis, dwarf syndrome, chronic respiratory disease, and immunosuppression in avian species, resulting in significant economic losses within the poultry industry. The non-structural protein p17 encoded by ARV induces cellular autophagy and facilitates viral proliferation, playing a pivotal role in viral pathogenesis. To further elucidate the pathogenic mechanism basis of ARV p17 protein function, we employed a yeast two-hybrid system to identify Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) as an interacting host protein with p17. In this study, we validated the interaction between PRPS2 and p17 using laser confocal microscopy, coimmunoprecipitation, and GST-Pulldown assays. Moreover, our findings demonstrate that the C-terminal region of PRPS2 is responsible for its binding to the p17 protein. Intriguingly, ARV infection significantly upregulated PRPS2 expression levels. Additionally, PRPS2 was shown to have a substantial impact on ARV replication; overexpression of PRPS2 increased ARV replication while knockdown of PRPS2 resulted in decreased quantities of ARV particles. Furthermore, our findings suggest that this process involves cellular apoptosis as a potential mechanism underlying these observations. Overall, this research provides valuable insights into elucidating the function of the p17 protein and sheds light on the pathogenic mechanism involving ARV-induced cellular apoptosis while offering novel perspectives for exploring therapeutic targets against ARV.

Abstract Zinc ion hybrid capacitors (ZIHCs) with Zn metal faradic and carbon capacitive electrodes have potential applications in grid‐scale energy storage systems and wearable devices. However, the high specific energy density reported in many recent studies is based on the mass of active carbon materials alone, with deficient device energy density. This perspective article discusses how four crucial parameters influence the device energy density of ZIHCs, including areal mass loading (mc) and specific capacity (Qg,c) of active carbon materials in cathodes, negative‐to‐positive electrode capacity ratio (N/P), and electrolyte‐to‐active carbon materials mass ratio (E/C). Using a representative device model, how the device energy density varies when these four parameters change is shown. Detailed analysis indicates that specific parameter windows with the four parameters within narrow ranges (e.g., mc = 10–20 mg cm−2, Qg,c > 100 mAh g−1, N/P < 20, and E/C < 5) need to be achieved simultaneously to deliver application‐relevant energy density (e.g., >30 Wh kg−1) in ZIHCs. It is hoped that these findings assist in objectively evaluating reported performance data and identifying essential issues for future research development to realize practical applications.

Eva-1 Homolog B (EVA1B) has been preliminarily found to be associated with prognostic outcomes and immune microenvironment in several human cancer types, but the implications of EVA1B in ESCC remain unclear. Human ESCC and paracancerous tissues were gathered in this study, and EVA1B expression was measured via immunoblotting. EC109 and KYSE-180 ESCC cells were stably infected by sh-EVA1B lentivirus, and functional experiments were subsequently implemented. Syngeneic mouse models were built, and the expansion and recruitment of myeloid-derived suppressor cells (MDSCs) were then evaluated. The results showed that EVA1B presented the notable up-regulation in clinical ESCC tissues versus controls, and was connected to more advanced stages and the abundance of MDSCs. Silencing EVA1B notably attenuated proliferation of ESCC cells and tumor growth in syngeneic mouse models. Moreover, EVA1B suppression resulted in apoptosis and cell cycle arrest, and impaired ESCC cell aggressiveness. Among ESCC patients, EVA1B was strongly correlated to EMT pathway activity. Targeted suppression of EVA1B mitigated the expression of Wnt3a, β-catenin and LRP6 in ESCC cells and tumor xenografts. Additionally, inhibition of EVA1B attenuated the expansion and recruitment of MDSCs within the immune microenvironment based upon the reduction in the percentage of CD11b+Gr-1+ immunosuppressive MDSCs as well as the expression of MDSC expansion stimulators (S100A8, S100A9, Arg-1, and VEGF). Collectively, our findings unveiled the contribution of high expression of EVA1B to ESCC progression and MDSCs expansion and recruitment, indicating that targeted suppression of EVA1B may be a potential treatment choice for ESCC patients.

A M8.5 earthquake struck the Haiyuan area in 1920 and resulted in a 240-km long surface rupture zone along the Haiyuan fault (HYF). In this study, to determine the spatial relationship between soil gases and fault activity on a regional scale, radon (Rn) and carbon dioxide (CO2) concentrations in soil gas were measured in situ with a grid spacing of 5 ∼ 10 km along the Haiyuan surface rupture zone (HYSRZ). Ordinary Kriging (OK) and Inverse Distance Weight (IDW) interpolation were used to investigate spatial variations in Rn and CO2 concentrations. Synchronous soil gas anomalies were identified in southern Haiyuan County and at the southern end of the HYSRZ, and were correlated with higher slip rate, larger deformation, and larger degree rupture size than other segments. Moreover, soil gas anomalies were spatially highly coupled with seismically active zones and low b value areas, suggesting that the permeability and porosity of gas emissions are enhanced by higher stress. Two seismic velocity profiles across the gas anomaly area confirmed that low-velocity bodies exist at 0 ∼ 10 km below the surface, as revealed by magnetotelluric (MT) sounding results, indicating that gas emissions are associated with the migration of deep fluids. Our results provide new insight into the source of fluids in the HYSRZ and offer support for the design of a continuous geochemical measurement network in this area.

Carbon tetrachloride (CCl4) is a potent chemical compound that can induce liver cells necrosis. The purpose of this study was to evaluate the hepatic toxicity of CCl4 exposure in Macaca fascicularis to explore the liver toxicity mechanism using a proteomic approach. One animal (no.F6) was intoxicated by oral gavage with 15 % CCl4 solution (10 mL/kg, dissolved in edible peanut oil), and was sacrificed at 48 h after CCl4 administration. Another blank control animal (no.F4) was sacrificed at the same time. The liver cells of the blank control animal showed normal hepatocyte morphology. However, the hepatocytes at 48 h time point after CCl4 administration showed necrosis and vacuolation histopathologically. The animal No.F7∼F12 and no.M7∼M12 were administrated by gavage with 15 % CCl4 solution (10 mL/kg, dissolved in edible peanut oil). Blood samples were collected before gavage administration, and served as the 0 h blank control samples. Then, blood samples were collected at 2 h, 48 h, 72 h and 168 h after CCl4 exposure, and served as the test samples. Routine biochemistry and immunical parameters were performed using biochemistry analyzer for all serum. Then the serum from male and female animals at 0 h, 2 h, 48 h, and 72 h was mixed, respectively. The peripheral serum proteins at 0 h, 2 h, 48 h, and 72 h were extracted, then the proteins were enzymatically hydrolyzed and the peptides were isotopic labeled by isobaric tags for relative and absolute quantification (iTRAQ). Finally, the UniProt Protein Sequence Library of Macaca fascicularis was queried to identify and compare the differential proteins between different time points. The results showed that, as traditional biomarkers of liver injury, alanine aminotransferases (ALT) and aspartate aminotransferases (AST) showed a typical time-effect curve. Compared with 0 h, there were totally 55, 323, and 158 differential proteins (P value 1.5, FDR

Background Esophageal squamous cell carcinoma (ESCC) is a primary histological type of esophageal carcinoma with high morbidity. Aryl hydrocarbon receptor nuclear translocator-like (ARNTL) is a circadian clock gene associated with the progression of multiple tumors. However, its roles and mechanisms in ESCC remain unknown.Methods ARNTL expression was analyzed using TCGA database and detected using qRT-PCR, and ARNTL-related pathways were analyzed through GSEA. Cell functional behaviors were assessed in vitro by measuring cell viability, proliferation, and apoptosis. Cell growth in the murine model was investigated through xenograft model and immunofluorescence assays of PCNA and Ki67. The downstream targets of ARNTL were analyzed through sequencing and identified via luciferase report, ChIP, and RNA pull-down analyses. Dual-specificity protein phosphatase-1 (DUSP1) expression was analyzed using GEO datasets and measured using qRT-PCR and western blotting. Protein expression was examined via western blotting.Results ARNTL expression was decreased in esophageal carcinoma and associated with histological types, and elevated expression of ARNTL repressed ESCC cell viability and proliferation and facilitated cell apoptosis. ARNTL upregulation reduced tumor cell growth in murine models and decreased PCNA and Ki67 levels. Furthermore, DUSP1 was downregulated upon ARNTL silencing in ESCC. ARNTL could bind and positively regulate DUSP1 transcription. Additionally, DUSP1 silencing reversed the influences of ARNTL upregulation on cell viability, proliferation, and apoptosis in ESCC cells. ARNTL attenuated the activation of the ERK signaling by decreasing ERK phosphorylation through upregulation of DUSP1.Conclusion ARNTL hinders cell growth and contributes to cell apoptosis by inactivating ERK signaling through transcriptional upregulation of DUSP1 in ESCC.

The existing intelligent anti-jamming methods based on deep reinforcement learning are applied to space-ground TT&C and communication links, in which the deep neural network used for decision-making has a complex structure, and the resources of satellites and other vehicles are limited, making it difficult to independently complete the timely training of complex neural network under the constraints of limited complexity, and the decision-making of anti-jamming cannot converge. Aiming at the above problems, an intelligent anti-jamming decision algorithm based on proximal policy optimization was proposed, which deployed the decision-making neural network and the training neural network in the vehicles and the ground station, respectively. The ground station conducted the optimal offline training based on the empirical information feedback from the vehicles, and assisted the decision-making neural network in parameter updating, thereby achieving the effective selection of anti-jamming strategies while satisfying the resource constraints of the vehicles. The simulation results demonstrate that the convergence speed of the proposed algorithm is increased by 37%, and the system capacity after convergence is increased by 25%, compared with the decision algorithms of policy gradient and deep Q-learning.

Abstract Polycystic ovary syndrome (PCOS), which is the most prevalent endocrine disorder among women in their reproductive years, is linked to a higher occurrence and severity of atherosclerosis (AS). Nevertheless, the precise manner in which PCOS impacts the cardiovascular well-being of women remains ambiguous. The Gene Expression Omnibus database provided four PCOS datasets and two AS datasets for this study. Through the examination of genes originating from differentially expressed (DEGs) and critical modules utilizing functional enrichment analyses, weighted gene co-expression network (WGCNA), and machine learning algorithm, the research attempted to discover potential diagnostic genes. Additionally, the study investigated immune infiltration and conducted gene set enrichment analysis (GSEA) to examine the potential mechanism of the simultaneous occurrence of PCOS and AS. Two verification datasets and cell experiments were performed to assess biomarkers' reliability. The PCOS group identified 53 genes and AS group identified 175 genes by intersecting DEGs and key modules of WGCNA. Then, 18 genes from two groups were analyzed by machine learning algorithm. Death Associated Protein Kinase 1 (DAPK1) was recognized as an essential gene. Immune infiltration and single-gene GSEA results suggest that DAPK1 is associated with T cell-mediated immune responses. The mRNA expression of DAPK1 was upregulated in ox-LDL stimulated RAW264.7 cells and in granulosa cells. Our research discovered the close association between AS and PCOS, and identified DAPK1 as a crucial diagnostic biomarker for AS in PCOS.

In this article, we focus on the global regularity of n-dimensional liquid crystal equations with fractional dissipation terms (−Δ)αu{\left(-\Delta )}^{\alpha }u and (−Δ)βd{\left(-\Delta )}^{\beta }d. We show that the equations have a unique global smooth solution if α≥12+n4\alpha \ge \frac{1}{2}+\frac{n}{4} and β≥12+n4\beta \ge \frac{1}{2}+\frac{n}{4}.

It is of great significant for prop-fan engine under medium to high Mach number to evaluate the propulsive efficiency of turbofan, turboprop and prop-fan engines. The mathematical model for propulsive efficiency analysis is established by using energy-momentum method based on the model of separate exhaust turbofan engines, and a unified propulsive efficiency analysis method is formed for turbofan, prop-fan and propeller fan engines. Different external fan pressure ratios, equivalent bypass ratios and different flight Mach number are selected for calculation. The results show that the propulsion efficiency of turboprop engine is higher at medium to low flight Mach number, the propulsion efficiency of prop-fan engine is higher at medium to high flight Mach number, and the propulsion efficiency of turbofan engine is higher at high subsonic flight Mach number. The existing flight Mach number interval distribution law of the superior propulsion efficiency of turboprop, prop-fan and turbofan engines is conformed. The study can provide a method for the research and analysis of the propulsion efficiency of turbofan, turboprop and prop-fan engines.

Abstract Background Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC. Methods Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity. Results We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan–Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores. Conclusions Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.

The transmission tower and tower line coupling system is an important carrier of the power system transmission process. Strong winds in coastal areas have a significant impact on the transmission tower and tower line system. To study the dynamic response characteristics of tower line system under the action of random fluctuating wind fields, the 1W2C9 drum-type self-supporting transmission tower in Guangdong is taken as the research object. Finite element models for the single tower and one tower two-line tower line coupling system are established. By combining the Davenport wind speed spectrum with the fourth order autoregressive method, the fluctuating wind fieldswith spatial correlation are simulated for a single tower with 9 nodes and tower line system with 49 nodes. The dynamic response of a single tower and tower line system under this fluctuating wind field is studied, and the influence of different wind direction angles on theirdynamic response is explored. The results indicate that the maximum dynamic response of both the single tower and tower line system is greater than their pseudo-static response. The existence of transmission lines enhances the stability of the transmission tower line system, reducing its dynamic response. A wind direction angle of 90° proves to be the most unfavorable for the dynamic response of the single tower and tower line system.

Abstract We present a case of a 21‐year‐old woman with fever (>38.0°C) for 5 days, mucocutaneous lesions and refractory hypotension requiring dual inotropic support. The only significant past medical history was an episode of COVID infection 4 months before admission. She was diagnosed to have multisystem inflammatory syndrome in adult (MIS‐A)—a relatively new entity which occurs as a severe complication in patients post‐COVID‐19 infection. This condition can present remarkably similarly to Kawasaki disease. Although the paediatric counterpart of MIS‐A typically occurs within 2–6 weeks post COVID‐19 infection, MIS‐A may occur up to 4 months post‐COVID‐19 infection. We wish to raise awareness of this rare entity, their similarities with Kawasaki disease and the importance of early initiation of intravenous immunoglobulin and high‐dose aspirin.

Abstract Background The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. Methods OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. Results Pla-Exos derived from active TAO patients (Pla-ExosTAO−A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO−A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO−A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. Conclusion Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.

The carbon fiber triaxial woven fabric has good application prospects in the field of space deployment devices because of its advantages of stable structure， light density and quasi-isotropic. In order to study the deformation properties of carbon fiber triaxial woven fabric/thermoplastic polyurethanes （TPU） flexible composite， TPU and carbon fibertriaxial woven fabric were composited by hot pressing. The unit cell model of triaxial woven fabric was established by metallographic microscope and SEM.The moment of inertia of different sections was calculated by the model， the moment of inertia of the weft section is greater than that of the warp， and the triaxial woven fabric is more difficult to deform in the weft direction. Drape experiments were performed on carbon fiber plain fabric and triaxial woven fabric.The results show that the deformation ability of the triaxial woven fabric is stronger than plain fabric， and the warp direction deformation of triaxial woven fabric is greater than the weft when it is draped， which is consistent with the calculation result of the moment of inertia of the model section； triaxial woven fabric is subjected to tensile tests in the 0°，15°and 30°directions， the load curve changes and ultimate loads of the three angles are analyzed at different strain stages.

Macrophages play a key role in wound healing. Dysfunction of their M0 polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation, which affects wound healing. Regulating the polarization of M0 macrophages to M2 macrophages is an effective strategy for treating wound healing. Mesenchymal stem cells (MSCs) deliver endogenous regulatory factors via paracrine extracellular vesicles, which may play a key role in wound healing, and previous studies have shown that apoptotic bodies (ABs) are closely associated with inflammation regression and macrophage polarization. However, the specific regulatory mechanisms involved in ABs remain unknown. In the present study, we designed an MSC-AB (MSC-derived AB)-loaded polycaprolactone (PCL) scaffold, evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro, and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing. Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs, and drives M0 macrophages to program M2 macrophages to regulate inflammation and angiogenesis, thereby synergistically promoting wound healing. This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immune responses.

Context: There is a significant challenge associated with the co-morbidity of mental and physical illnesses throughout the world. A classic example of mental/physical co-morbidity is diabetes-related depression (DD). Objective: DD is treated with Zuogui Jiangtang Jieyu prescription (ZJJ). Diabetes and psychiatric disorders are associated with dysbiosis of the gut microbiota. In this study, the aim is to examine the effects of ZJJ on gut microbiota and neuroinflammation in DD. Methods: A model of DD was established and treated with medium and high doses of ZJJ as well as Metformin & Fluoxetine. A detection of depressive-like behavior was then conducted on the rats. Proinflammatory cytokines were measured in cerebrospinal fluid, and HPA axis-related proteins, glucose metabolism, and lipopolysaccharide (LPS) were measured in serum. Fecal samples from each group were collected and analyzed by 16S rRNA sequencing; TLR4 and MyD88 levels were detected by Western blot and immunohistochemistry (IHC) in the hippocampus. Results: High doses of ZJJ (ZJJ-H) were found to alleviate HPA axis hyperactivity and improve gut microbiota in rats with DD. Additionally, ZJJ treatment attenuated the inflammatory response in cerebrospinal fluid, e.g. a significant reduction in proinflammatory factors, a decrease in serum LPS levels, and an inhibition of TLR4/MyD88-related pathways in the hippocampus. Discussion and conclusion: ZJJ improved DD glucose metabolism and alleviated depression-like behaviors by improving gut microbiota and inhibiting hippocampal TLR4/Myd88 signaling pathways.

Background: Tacrolimus is regarded as a cornerstone of immunosuppressive therapy after lung transplantation. Tacrolimus-induced neurotoxicity is common, while late-onset severe encephalopathy is rare. Case presentation: We report a case of a 61-year-old woman who presented with confusion and limb stiffness 29 months after undergoing bilateral lung transplantation for bronchiectasis. She received immunosuppressive regimen consisting of low-dose tacrolimus, sirolimus, mycophenolate mofetil, and prednisone due to renal insufficiency. Neurological examination revealed gaze deviation towards the right side in both eyes, as well as nuchal rigidity. The muscle strength of her extremities was at grade 1–2, and muscle tone was increased, with a bilateral positive Babinski sign. Blood tests revealed that tacrolimus and sirolimus levels were within the therapeutic range. Brain magnetic resonance imaging revealed that periventricular white matter lesions were slightly more extensive than those observed prior to transplantation. Lumbar puncture showed that cerebrospinal fluid pressure and composition were normal. A diagnosis of tacrolimus-induced encephalopathy was made after a thorough clinical examination. Subsequently, cyclosporine was administered instead of tacrolimus for anti-rejection therapy, and she has remained free of neurological symptoms since then. The improvement of clinical symptoms following the withdrawal of tacrolimus supports the drug-induced etiology of this neurological disorder. Conclusions: We highlight that tacrolimus-induced encephalopathy can occur in a late stage after lung transplantation and may occur with tacrolimus whole blood concentrations within the therapeutic range.

To effectively utilize dust suppression measures in fully mechanized excavation faces, this study proposed a rapid prediction algorithm for the flow field based on proper orthogonal decomposition (POD) and machine learning. First, computational fluid dynamics (CFD) technology was used to simulate the air flow field and dust concentration field under various conditions, generating high-dimensional flow field data. Then, the POD method was applied to reduce the dimensionality of this data, extracting core modes that captured the main characteristics of the flow field and producing basis function modes and mode coefficients. Machine learning techniques were subsequently used to predict the mode coefficients that accounted for over 90% of the total energy under different conditions, enabling predictions of mode coefficients for unknown conditions. Finally, by reconstructing the flow or dust concentration field data using the predicted mode coefficients and basis function modes, rapid and accurate predictions for the flow field in excavation faces were achieved. The results showed that the numerical simulation model for the excavation face had a relative error within 3%, accurately reflecting the actual air flow and dust distribution. Selecting the first five modes for the flow field and the first seven modes for the dust concentration field balanced the accuracy and efficiency of POD reconstruction. The support vector machine (SVM) model outperformed the Random Forest and Neural Network models in predicting mode coefficients. For 60 different conditions, the relative errors between the POD and SVM-predicted flow velocity and dust concentration, and the CFD results, were 0.36 m/s and 86.24 mg/m³, respectively. The average prediction time for the flow and dust concentration fields was 73 seconds, achieving high-precision, rapid predictions for airflow and dust concentration in mine excavation faces.

Accumulating studies have highlighted the great potential of postbiotics in alleviating diseases and protecting host health. Compared with traditional functional foods (such as probiotics and prebiotics), postbiotics have the advantages of a single composition, high physiological activity, long shelf life, easy absorption, and high targeting, etc. The development of postbiotics has led to a wide range of potential applications in functional food and drug development. However, the lack of clinical trial data, mechanism analyses, safety evaluations, and effective regulatory frameworks has limited the application of postbiotic products. This review describes the definition, classification, sources, and preparation methods of postbiotics, the progress and mechanism of preclinical and clinical research in improving host diseases, and their application in food. Strengthen understanding of the recognition and development of related products to lay a theoretical foundation.

IntroductionThe extent to which sinks are contaminated by carbapenem-resistant Acinetobacter baumannii (CRAB) in intensive care units (ICUs) and the association between these contaminated sinks and hospital-acquired CRAB infections during the non-cluster period remains largely unknown. Here, we performed a prospective multicenter study in 16 ICUs at 11 tertiary hospitals in Chengdu, China.MethodsWe sampled sinks, collected CRAB clinical isolates, and conducted whole-genome sequencing and analysis.ResultsA total of 789 swabs were collected from 158 sinks, and 16 CRAB isolates were recovered from 16 sinks, resulting in a contamination rate of 10.16%. Twenty-seven clinical isolates were collected during the study period. The majority (97.67%, 42/43) of the CRAB isolates belonged to ST2, and 36 (83.72%) of them had both blaOXA-23 and blaOXA-66. The 43 strains belonged to 12 clones. One certain clone caused multiple contaminations of seven sinks in one GICU. Two clones of ST2 blaOXA-23 and blaOXA-66-carrying sink strains were likely the sources of the two clusters in the two GICUs, respectively. Five ST2 blaOXA-23-carrying isolates were found to be common clones but were recovered from two hospitals.ConclusionThe contamination rate of CRAB in handwashing sinks is high in some local ICUs, and the contaminated sinks can serve as environmental reservoirs for CRAB clusters.