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Abstract Hepatocellular carcinoma (HCC) is a heterogeneous disease with high recurrence and mortality. It is well known that a large proportion of HCCs are caused by hepatitis B virus (HBV) infection. In particular, the HBV X protein (HBX), a multifunctional molecule produced by the virus, plays a leading role in hepatocarcinogenesis. However, the molecular mechanisms underlying HBX-mediated HCC remain not fully elucidated. Recently, liver cancer stem cells (LCSCs), a unique heterogeneous subpopulation of the malignancy, have received particular attention owing to their close association with tumorigenesis. Especially, the modulation of LCSCs by HBX by upregulating CD133, CD44, EpCAM, and CD90 plays a significant role in HBV-related HCC development. More importantly, not only multiple signaling pathways, including Wnt/β-catenin signaling, transforming growth factor-β (TGF-β) signaling, phosphatidylinositol-3-kinase (PI-3 K)/AKT signaling, and STAT3 signaling pathways, but also epigenetic regulation, such as DNA and histone methylation, and noncoding RNAs, including lncRNA and microRNA, are discovered to participate in regulating LCSCs mediated by HBX. Here, we summarized the mechanisms underlying different signaling pathways and epigenetic alterations that contribute to the modulation of HBX-induced LCSCs to facilitate hepatocarcinogenesis. Because LCSCs are important in hepatic carcinogenesis, understanding the regulatory factors controlled by HBX might open new avenues for HBV-associated liver cancer treatment.

Abstract Ghd7 is a central regulator to multiple growth and development processes in rice. While it is not clear how Ghd7 is regulated by upstream factors. To identify its upstream regulator, the truncated Ghd7 promoter fragments were used to screen cis elements binding to rice total nuclear proteins. Electrophoretic mobility shift assays screened one truncated fragment f3 binding to the proteins. Subsequently, the fragment f3 was employed to screen a yeast one-hybrid library, and a transcription factor OsIAA23 was screened as a direct upstream regulator of Ghd7. Dual-luciferase transient assay demonstrated the transcriptional repression effect of OsIAA23 on the activity of Ghd7, and the location of the cis elements binding to OsIAA23 in the region 1264 to 1255 bp upstream of ATG. Genetic analysis between the wild type Ghd7-OsIAA23 and single/double mutants further verified that OsIAA23 downregulated Ghd7 expression and led to a delayed heading under long day conditions. Moreover, natural variations in fragment f3 were associated with heading and geographic distribution in rice. This study sheds light on the direct regulatory mechanism of OsIAA23 on Ghd7, which enriches the understanding of the Ghd7 involved flowering regulatory network in rice.

Abstract Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

Abstract Autophagy has both protective and pathogenetic effects on injury caused by cerebral ischemia/reperfusion (I/R). Our previous research has indicated that stimulator of interferon genes (STING) could orchestrate microglia polarization following middle cerebral artery occlusion. However, it remains largely unexplored whether STING balances microglial polarization by regulating autophagy in brain I/R injury. Here, STING was observed to show an up-regulation in the microglia from mice subjected to experimental ischemic stroke. Strikingly, the deletion of STING led to the significant skewness of microglia activated by ischemia from a pro- to anti-inflammatory state and substantially alleviated ischemia-induced infarction and neuronal injury. In addition, STING-null mice can restore long-term neurobehavioral function. Then, the crosstalk between neuroinflammation and microglia autophagy was analyzed. The differential activity of autophagy in wild-type and STING-knockout (KO) mice or primary microglia was largely reversed when STING was restored in microglia. Irritating autophagy by rapamycin skewed the anti‑inflammatory state induced by STING-KO to a pro‑inflammatory state in microglia. Furthermore, microtubule-associated protein light-chain-3 (LC3) was identified as the key factor in the STING regulation of autophagy by glutathione-S-transferase (GST) pull-down analysis. Mechanically, STING can directly interact with LC3 through the STING transmembrane domain (1-139aa). Herein, current data determine the pivotal role of autophagy, specifically via LC3 protein, in the regulation of microglial phenotypic transformation by STING. These findings may provide a possible treatment target for delaying the progression of ischemic stroke.

Abstract Background Ticks are vectors of numerous pathogens, with their bacterial composition, abundance, diversity, and interaction influencing both their growth and disease transmission efficiency. Despite the abundance of ticks in Inner Mongolia, China, comprehensive data on their microbial communities are lacking. This study aims to analyze the microbial communities within ticks from Inner Mongolia to inform innovative control strategies for interrupting pathogen transmission. Methods Tick samples were collected from animals and vegetation in multiple locations across Inner Mongolia and stored at − 80 °C. Ticks were identified using morphological keys and molecular biology methods. Full-length 16S rRNA gene sequencing was performed on collected samples. Bacterial community composition and diversity were mainly analyzed using bioinformatic tools such as QIIME, phyloseq, and DESeq2. Alpha diversity was assessed using Chao1, ACE, and Shannon indices, while beta diversity was evaluated using Bray-Curtis dissimilarity matrices. LEfSe analysis was applied to identify taxa associated with ecological and biological variables. Results A total of 5,048,137 high-quality read counts were obtained, forming an average of 789.3 OTUs per sample. Proteobacteria, Firmicutes, and Bacteroidetes were the most dominant phyla. Bacterial community composition varied significantly with geography, with Dermacentor nuttalli showing a higher abundance of Rickettsia in Xilingol League, while other regions had different dominant genera. The microbial community also differed based on the feeding status of ticks. Additionally, the microbiota of engorged ticks showed organ specificity. Pathogen detection efforts revealed the presence of nine pathogens across all three tick species. D. nuttalli was found to carry a significantly higher burden of pathogenic bacteria, making it the most potentially threatening tick species in Inner Mongolia. Conclusions The study highlights significant variations in tick microbiomes influenced by geographic location, feeding status, and tick species. It underscores the importance of enhancing tick and tick-borne disease surveillance in Inner Mongolia for early detection and control of emerging pathogens. Graphical Abstract

Abstract Background Residual low back and leg pain can occur after percutaneous endoscopic interlaminar discectomy (PEID) and compromise early surgical outcomes. This study aimed to determine the efficacy of combining dexamethasone with vitamin B12 (VB12) via epidural injection in improving the symptoms of low back and leg pain after PEID, and the underlying mechanism of action. Methods Patients who underwent PEID for lumbar disc herniation (LDH) were enrolled and randomly assigned to the single surgery (SS) group, where disc removal was performed via PEID alone, or the combined treatment (CT) group, which received epidural injections of dexamethasone and VB12 alongside surgery. The outcome measures were the Visual Analog Scale (VAS), Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), serum inflammatory factor expression, adverse surgical events, duration of postoperative hospitalization, and modified MacNab criteria. Results Compared with the SS group, the CT group exhibited lower VAS scores for low back and leg pain at 1, 3, and 7 days post-surgery (P

Abstract Background Manual placement of cervical pedicle screws is risky, and robot-assisted placement of atlantoaxial pedicle screws has not been reported. Case report We describe a 74-year-old female patient with atlantoaxial fracture and dislocation combined with spinal cord injury caused by a car accident. The left lower limb muscle strength was grade 0, the right upper limb muscle strength was grade 1, and the right lower limb muscle strength was grade 2. Loss of sensation below the clavicle level, decreased superficial sensation in the extremities, loss of deep sensation in the left lower extremity, and incontinence were observed. We successfully placed atlas pedicle screws with the assistance of the Mazor X robot. One week after the operation, radiological imaging revealed that the reduction effect was good, the placement of the pedicle screws was satisfactory, the left upper limb and left lower limb muscle strength was level 2, the right upper limb and the muscle strength of the right lower limb were grade 3, and the sensory function was partially restored. No complications related to screw placement were found at the 3-month postoperative follow-up. Conclusions Mazor X robot-assisted descending pedicle screw fixation of the atlas is feasible and safe.

Abstract To examine the association and modifiable risk factors between grip strength (GS) and Parkinson’s disease (PD) incidence considering genetic factors, a total of 411,648 individuals without PD at baseline from the UK Biobank were included. GS was measured by a hydraulic dynamometer. The polygenic risk score assessed the genetic predisposition. Multivariable Cox regression models were performed. During a median follow-up of 12.3 years, 2409 individuals developed PD. Compared with those with high GS, low-GS individuals had a 58.5% increased risk of PD (42.7%–76.1%), and 16.3% of this excess risk could be explained by adjusted risk factors. Low GS and high genetic predisposition contribute to the highest PD risk in an additive interaction. We observed that low GS was associated with higher PD incidence, particularly among individuals with high genetic predisposition. In addition to enhancing GS, interventions targeting risk factors (e.g., unhealthy lifestyles) might also reduce the excess risk.

Abstract Post-cardiac arrest brain (PCABI) is a severe medical condition characterized by a significant risk of neurological impairment and death. Nevertheless, the specific process and essential molecules responsible for its development are not fully understood. Profiling based on competing endogenous RNAs (ceRNA) has been implicated in the onset and progression of neurological disorders, yet its role in PCABI remains unclear. In this study, we performed RNA transcriptome sequencing analysis to identify differentially expressed genes in the rat model for cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A hub ceRNA regulatory network was constructed using miRWalk 2.0 and Cytohubba plug-in in Cytoscape. Subsequently, real-time quantitative reverse transcription-polymerase chain reaction and dual-luciferase activity assays validated MSTRG.13,871, miR-155-5p, and Grip1 as differentially expressed in CA/CPR group, with MSTRG.13,871 capable of targeting both miR-155-5p and Grip1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the ceRNA network enrichment in immunoregulation mechanisms such as mitochondrion, apoptotic process, and negative regulation cell death. Our research highlights the mechanism of PCABI by revealing a critical regulatory axis involving MSTRG.13,871-miR-155-5p-Grip1 in the hippocampus CA1 region after CA/CPR in rats, proposing a feasible controlled mechanism, which may serve as a theoretical basis for designing innovative therapies.

Abstract Sepsis-associated encephalopathy (SAE) is a frequent and severe complication in septic patients, characterized by diffuse brain dysfunction resulting from systemic inflammation. Accurate prediction of long-term mortality in these patients is critical for improving clinical outcomes and guiding treatment strategies. We conducted a retrospective cohort study using the MIMIC IV database to identify adult patients diagnosed with SAE. Patients were randomly divided into a training set (70%) and a validation set (30%). Least absolute shrinkage and selection operator regression and multivariate logistic regression were employed to identify significant predictors of 1-year mortality, which were then used to develop a prognostic nomogram. The model’s discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. A total of 3,882 SAE patients were included in the analysis. The nomogram demonstrated strong predictive performance with AUCs of 0.881 (95% CI: 0.865, 0.896) in the training set and 0.859 (95% CI: 0.830, 0.888) in the validation set. Calibration plots indicated good agreement between predicted and observed 1-year mortality rates. The decision curve analysis showed that the nomogram provided greater net benefit across a range of threshold probabilities compared to traditional scoring systems such as Glasgow Coma Scale and Sequential Organ Failure Assessment. Our study presents a robust and clinically applicable nomogram for predicting 1-year mortality in SAE patients. This tool offers superior predictive performance compared to existing severity scoring systems and has significant potential to enhance clinical decision-making and patient management in critical care settings.

Abstract Colonizing in the gastrointestinal tract, Escherichia coli confronts diverse acidic challenges and evolves intricate acid resistance strategies for its survival. The lysine-mediated decarboxylation (Cad) system, featuring lysine decarboxylase CadA, lysine/cadaverine antiporter CadB, and transcriptional activator CadC, plays a crucial role in E. coli’s adaptation to moderate acidic stress. While the activation of the one-component system CadC and subsequent upregulation of cadBA operon in response to acid and lysine presence have been proposed, the molecular mechanisms governing the transition of CadC from an inactive to an active state remain elusive. Under neutral conditions, CadC is inhibited by forming a complex with lysine-specific permease LysP, stabilized in this inactive state by a disulfide bond. Our study unveils that, in an acidic environment, the disulfide bond in CadC is reduced by the disulfide bond isomerase DsbC, exposing R184 to periplasmic proteases, namely DegQ and DegP. Cleavage at R184 by DegQ and DegP generates an active N-terminal DNA-binding domain of CadC, which binds to the cadBA promoter, resulting in the upregulated transcription of the cadA and cadB genes. Upon activation, CadA decarboxylates lysine, producing cadaverine, subsequently transported extracellularly by CadB. We propose that accumulating cadaverine gradually binds to the CadC pH-sensing domain, preventing cleavage and activation of CadC as a feedback mechanism. The identification of DegP, DegQ, and DsbC completes a comprehensive roadmap for the activation and regulation of the Cad system in response to moderate acidic stress in E. coli.

Abstract Background SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects. Methods Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18–45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55–80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg). Results Sixty-two (part 1/2, n = 50/12; age range, 18–42/55–63 years) and 30 subjects (age range, 18–42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2–60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed. Conclusions A single intravenous dose of SHR-1707 at 2–60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development. Trial registration NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov.

Abstract Background In recent years, mobile medical technology has made great progress in chronic disease management, but its application in patients with atrial fibrillation (AF) still needs to be clarified. Objective This study aims to determine whether the newly developed smartphone app for patients with AF (Alfalfa App) can improve anticoagulation knowledge, drug treatment compliance, and satisfaction of AF patients. Methods Alfalfa App integrates the functions of patient education, remote consultation, and medication reminder through a simple user interface. From June 2020 to December 2020, patients with AF were recruited in five large tertiary hospitals in China. Patients were randomly divided into the Alfalfa App or routine nursing groups. Patients’ knowledge, medication adherence, and satisfaction with anticoagulation were assessed using validated questionnaires at baseline, 1 month, and 3 months. Results In this randomized controlled trial, 113 patients with AF were included, 57 patients were randomly assigned to the Alfalfa App group, and 56 patients were randomly assigned to the routine nursing group. Forty-eight patients in the Alfalfa App group completed a three-month follow-up, and 48 patients in the routine nursing group completed a three-month follow-up. Basic demographic data were comparable between the two groups. The average age of AF patients was 61.65 ± 11.01 years old, and 61.5% of them were male. With time (baseline to 3 months), the knowledge scores of the Alfalfa App group (P

Abstract Background Quantifying the professional ethical challenges that nurses encounter is crucial for both theoretical insights and practical outcomes. The objective of this research is to assess the psychometric properties of the Chinese adaptation of the Moral Distress Scale for Healthcare Professionals (MD-APPS). Methods In 2024, a survey approach was utilized to engage with several tertiary-level healthcare institutions throughout China. A cohort of 448 nursing professionals who satisfied the specified selection benchmarks was consequently incorporated into the study. To evaluate the scale's reliability and validity, methods including the Content Validity Index (CVI), Factor Analysis—both Exploratory (EFA) and Confirmatory (CFA)—alongside assessments of internal consistency and test-retest reliability were employed. Results Expert evaluations yielded an I-CVI of 0.90, suggesting good content validity for the MD-APPS's Chinese adaptation. Exploratory Factor Analysis (EFA) revealed a bi-dimensional framework with 7 components, explaining 56.34% of the cumulative variance. Confirmatory Factor Analysis (CFA) outcomes displayed a χ-square/df ratio of 1.542. The estimate for Robust RMSEA was 0.054, and the SRMR was ascertained to be 0.041. Indices for both Robust TLI and Robust CFI surpassed the 0.9 threshold, indicating an acceptable fit; this aspect was supported by a P-value (Chi-square) of 0.094. The internal consistency, measured by Cronbach's α, was found to be 0.74, while the test-retest reliability over a two-week period reached 0.964. These findings provide initial evidence for the psychometric properties of the Chinese MD-APPS. Conclusion The Chinese adaptation of the MD-APPS demonstrates promising initial psychometric properties, suggesting its potential suitability for exploring nurses' professional ethical challenges within the Chinese cultural context. This scale may facilitate the identification of diverse elements influencing nurses' professional ethics and the assessment of the ethical climate in nursing practices. However, further validation studies are needed to fully establish its psychometric robustness across various healthcare settings in China.

EPSPS is a key gene in the shikimic acid synthesis pathway that has been widely used in breeding crops with herbicide resistance. However, its role in regulating cell elongation is poorly understood. Through the overexpression of EPSPS genes, we generated lines resistant to glyphosate that exhibit an unexpected dwarf phenotype. A representative line, DHR1, exhibits a stable dwarf phenotype throughout its entire growth period. Except for plant height, the other agronomic traits of DHR1 are similar to its transgenic explants ZM24. Paraffin section observations showed that DHR1 internodes are shortened due to reduced elongation and division of the internode cells. Exogenous hormones confirmed that DHR1 is not a classical brassinolide (BR)- or gibberellin (GA)-related dwarfing mutant. Hybridization analysis and fine mapping confirmed that the EPSPS gene is the causal gene for dwarfism, and the phenotype can be inherited in different genotypes. Transcriptome and metabolome analyses showed that genes associated with the phenylpropanoid synthesis pathway are enriched in DHR1 compared with ZM24. Flavonoid metabolites are enriched in DHR1, whereas lignin metabolites are reduced. The enhancement of flavonoids likely results in differential expression of auxin signal pathway genes and alters the auxin response, subsequently affecting cell elongation. This study provides a new strategy for generating dwarfs and will accelerate advancements in light simplification in the cultivation and mechanized harvesting of cotton.

Abstract Objective Premenstrual Syndrome is also known as premenstrual tension syndrome because of the pronounced premenstrual mental and emotional anomalies. This study focuses on the association between occupational stress, sleep quality and premenstrual syndrome in clinical nurses and the mediating role of sleep quality. Methods A cross-sectional study was conducted to measure occupational stress, sleep quality and premenstrual syndrome in 415 clinical nurses using the Chinese Nurses Stressor Scale, the Pittsburgh Sleep Quality Index Scale, and the Premenstrual Syndrome Scale. SPSS was used to explore the relationship between the variables, and AMOS was used to explore the mediating role between the variables. Results Nurses’ occupational stress positively predicted PMS (β = 0.176, p

Abstract Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints. Graphical Abstract

Methane is one of the long-lived greenhouse gases, with a global warming potential 28 times that of carbon dioxide, accounting for about 16% of the global warming effect. Coal production activities are one of the main sources of methane emissions in China. As one of the main coal production bases in China, Shanxi Province’s coal industry emits a large amount of methane. Using the high-resolution remote sensing data to estimate the methane emission from the coal industry in Shanxi Province can lay a data foundation for establishing a refined methane emission inventory of the coal industry and provide scientific basis for formulating effective emission reduction measures. Using the Advanced Hyperspectral Imager (AHSI) carried by China’s GF–5–02 satellite, 838 methane plumes from 408 factories and mines in Shanxi Province’s coal mining areas were detected and their emission rates were calculated using data from October 2021 to March 2023. The results show that: ① the methane plume emission rate in Shanxi Province’s coal mining areas shows asymmetry, with 84% of the plumes having emission rates between 0.5−3.0 t/h, but there are also a few extreme cases, with the highest emission rate exceeding 10.0 t/h.② Shanxi Province has six dense areas of point source emissions of methane, five of which correspond to the high-value areas of XCH4. ③ Methane emission point sources are detected, with coal mines and coking enterprises being the majority of emission sources. The average emission rate of different types of emission sources differs greatly, and the emission rate fluctuates with time and source changes. Methane emissions may occur in all stages of the coal mining. ④ Highly persistent emission sources account for only 13% of all point sources, but contribute 41% of the total emission rate. Conversely, highly intermittent emission sources account for 59%, but contribute only 25% of the total emission rate. The comprehensive methane emission rate of the coal industry in Shanxi Province is 177.17±56.35 t/h, mainly contributed by the methane emissions from coal mines, coking and thermal power enterprises.

Abstract Background Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. Results In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients’ survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. Conclusions Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.

Abstract Extracranial metastasis of glioma is extremely rare. Herein, we report a case of glioblastoma that originated and showed stepwise malignant transformation from a low‐grade glioma (LGG) along with the presence of lung and mediastinal lymph node metastases after repeated craniotomy. A 30‐year‐old man presented with hemoptysis. Thoracic computed tomography revealed a space‐occupying lesion in the right upper lung with mediastinal nodal and metastases in both lungs; lung cancer was suspected. The patient's medical history showed that he had undergone craniotomy three times in 7 years for a primary LGG disease relapse, and stepwise malignant‐transformed high‐grade glioma (HGG). However, brain magnetic resonance imaging did not reveal any relapse of intracranial tumors. The diagnosis of extracranial metastatic glioblastoma was confirmed using the morphology and staining results for specific immunohistochemistry markers using the specimen obtained via endobronchial ultrasound transbronchial needle aspiration. Subsequently, the patient received a combination of systemic and local treatments; however, he died of massive hemoptysis after 6 months. The survival time of this glioma patient improved after transformation and metastasis. Detailed descriptions will help us understand the biological behavior of glioma, but more studies are needed to confirm the complex mechanism of extracranial metastasis.

Abstract Background To mitigate hospital-acquired transmission of coronavirus disease 2019 (COVID-19), various prevention and control measures have been strictly implemented in medical institutions. These stringent measures can potentially reduce the incidence of hospital-acquired respiratory infections. This study aimed to assess if there were changes in the prevalence of hospital-acquired respiratory infections during a period of national attention focused on COVID-19 prevention. Methods A retrospective analysis of the clinical data from adult patients with hospital-acquired respiratory infections admitted between October and December 2019 and during the same period in 2020 was performed. All patients were referred from a general hospital in Beijing China and COVID-19 patients were not treated at the hospital. Hospital-acquired respiratory infections were diagnosed based on the criteria of the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN). A comparison of the incidence and mortality rate of hospital-acquired respiratory infections between the two selected time periods was conducted. Additionally, multivariate logistics regression analysis was used to identify mortality-associated risk factors. Results This study included 2,211 patients from October to December 2019 (pre-COVID-19 pandemic) and 2,921 patients from October to December 2020 (during the COVID-19 pandemic). The incidence of hospital-acquired respiratory infections in 2019 and 2020 was 4.7% and 2.9%, respectively, with odds ratio (OR): 0.61, 95% confidence interval (CI): 0.46–0.81, and P = 0.001. In-hospital mortality of hospital-acquired respiratory infections in 2019 and 2020 was 30.5% and 38.4%, respectively, with OR: 1.42, 95%CI: 0.78–2.59, and P = 0.25. Multivariate logistics regression analysis revealed that a history of previous malignancy (OR: 2.50, 95%CI: 1.16–5.35, P = 0.02), was associated with in-hospital mortality. Conclusions The incidence of hospital-acquired respiratory infections was significantly decreased following the implementation of various prevention and control measures during the COVID-19 pandemic. A history of previous malignancy was associated with higher in-hospital mortality in older inpatients with hospital-acquired respiratory infections.

Abstract Spiral phase contrast imaging alleviates the information load by extracting the geometric features of objects and is one of the most representative branches of instant imaging processing. The self-healing capacity of edge detectors can enhance their robustness to obstacles in practical applications. Here, a self-healing spiral phase contrast imaging scheme is proposed and experimentally demonstrated by a liquid crystal edge detector combining a spiral phase, an axicon phase, and a lens phase. The spiral phase is encoded into a liquid crystal by photopatterning. Self-healing contrast imaging is characterized by a series of edge images of both high-contrast amplitude-type and low-contrast phase-type objects. This work extends the self-healing capacity of these detectors to instant imaging processing and paves the way for optical applications with self-healing features.

Introduction: Global warming is increasing interest in how aquatic animals can adjust their physiological performance and cope with temperature changes. Therefore, understanding the behavioral changes and molecular underpinnings in fish under warming is crucial for both the individual and groups survival. This could provide experimental evidence and resource for evaluating the impact of global warming. Objective: Three genetic families of common carp (Cyprinus carpio) were generated. These juveniles were constructed short-term (4 days) and long-term (30 days) warming groups to investigate the effects of warming on behavioral responses and to elucidate the potential underlying mechanisms of warming-driven behavior. Methods: Behavioral tests were used to explore the effects of short- and long-term exposure to warming on the swimming behavior of C. carpio. Brain transcriptome combined with measurement of nervous system activity was used to further investigated the comprehensive neuromolecular mechanisms under warming. Results: Long-term warming groups had a more significant impact on the decline of swimming behavior in juvenile C. carpio. Furthermore, brain comparative transcriptomic analysis combined with measurement of nervous system activity revealed that genes involved in cytoskeletal organization, mitochondrial regulation, and energy metabolism are major regulators of behavior in the juvenile under warming. Importantly, especially in the long-term warming groups, enrichment analysis of associated gene expression suggested functional alterations of synaptic transmission and signal transduction leading to swimming function impairment in the central nervous system, as revealed by behavioral tests. Conclusions: Our study provides evidence of the neurogenomic mechanism underlying the decreased swimming activity in juvenile C. carpio under warming. These findings have important implications for understanding the impacts of climate change on aquatic ecosystems and the organisms that inhabit them.

Pressure ulcers (PUs) are common skin injuries known for their high morbidity, rapid onset, susceptibility to infection, and challenging healing process. One potential therapy for PUs is cell-based therapy using mesenchymal stem cells (MSCs). However, poor survival and low cell retention of MSCs on skin lesions limit their therapeutic effects and applications. In this study, we prepared an extracellular matrix (dECM) hydrogel decellularized from the human umbilical cord (UC). A patch composed of UC-dECM and UC-MSCs was employed in the treatment of PUs in C57BL/6 mice. Our results indicate that the UC-dECM hydrogel effectively sustains cell viability, enhances the stemness-related gene expression in UC-MSCs, and promotes human umbilical vein endothelial cells (HUVECs) migration and angiogenesis. Compared to the groups treated with the patch containing only UC-dECM, injection of UC-MSCs or gauze dressing, the patch combining UC-dECM hydrogel with UC-MSCs significantly accelerated PU healing. This positive outcome can be attributed to the promotion of tissue re-epithelialization, collagen deposition, angiogenesis, and inflammation inhibition. Our results suggest that the composite patch, comprised of UC-dECM hydrogel and UC-MSCs, may be a promising therapeutic approach for PU treatment.

Background/Aims: As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Materials and Methods: Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Results: Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Conclusion: Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Abstract Spinal cord injury (SCI) results in irreversible neurological impairment. After SCI, Ferritinophagy-induced free iron released from ferritin can lead to extensive lipid peroxidation and aggravate neurological damage. NRF2/HO-1 pathway is to endow cells with a protective effect against oxidative stress, and it plays an important role in the transcriptional activation of a series of antioxidant and detoxification genes. UAMC-3203 is a ferrostatin-1(Fer-1) analogue with better solubility and stability, which can more effectively inhibit ferroptosis after SCI. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with UAMC-3203. ELISA was employed to assess the impact of UAMC-3203 on inflammation-related factors, while immunofluorescence was utilized to investigate the influence of UAMC-3203 on neuronal count as well as the activation of astrocytes and microglia/macrophages. Malondialdehyde (MDA) were detected to reflect the level of oxidation products. Western blot analysis was used to measure the level of ferroptosis markers and the expression of NRF2/HO-1. Our findings demonstrate that UAMC-3203 inhibits the production of reactive oxygen species (ROS) and lipid peroxides, preventing ferroptosis and reducing neuronal degeneration. Additionally, UAMC-3203 suppresses astrocyte proliferation and microglia/macrophage activation, as well as the release of ferroptosis-related inflammatory factors. These combined effects contribute to the preservation of spinal cord tissue and the facilitation of motor function recovery. UAMC-3203 maybe inhibit ferroptosis after SCI to promote functional recovery.

Abstract This study sought to elucidate the mechanisms underlying the impact of the interferon signaling pathway on Ferroptosis in tumor cells and its correlation with CD8 + T cell exhaustion. Using mouse models and single-cell sequencing, the researchers studied the interaction between CD8 + T cells and the interferon signaling pathway. Differential gene analysis revealed key genes involved in CD8 + T cell exhaustion, and their downstream factors were explored using bioinformatics tools. The expression levels of interferon-related genes associated with Ferroptosis were analyzed using data from the TCGA database, and their relevance to tumor tissue Ferroptosis and patients’ prognosis was determined. In vitro experiments were conducted to measure the levels of IFN-γ, MDA, and LPO, as well as tumor cell viability and apoptosis. In vivo validation using a mouse tumor model confirmed the results obtained from the in vitro experiments, highlighting the potential of silencing HSPA6 or DNAJB1 in enhancing the efficacy of PD-1 therapy and inhibiting tumor growth and migration.

A novel coupled model integrating Elman-AdaBoost with adaptive mutation sparrow search algorithm (AM-SSA), called AMSSA-Elman-AdaBoost, is proposed for predicting the existing metro tunnel deformation induced by adjacent deep excavations in soft ground. The novelty is that the modified SSA proposes adaptive adjustment strategy to create a balance between the capacity of exploitation and exploration. In AM-SSA, firstly, the population is initialized by cat mapping chaotic sequences to improve the ergodicity and randomness of the individual sparrow, enhancing the global search ability. Then the individuals are adjusted by Tent chaotic disturbance and Cauchy mutation to avoid the population being too concentrated or scattered, expanding the local search ability. Finally, the adaptive producer-scrounger number adjustment formula is introduced to balance the ability to seek the global and local optimal. In addition, it leads to the improved algorithm achieving a better accuracy level and convergence speed compared with the original SSA. To demonstrate the effectiveness and reliability of AM-SSA, 23 classical benchmark functions and 25 IEEE Congress on Evolutionary Computation benchmark test functions (CEC2005), are employed as the numerical examples and investigated in comparison with some well-known optimization algorithms. The statistical results indicate the promising performance of AM-SSA in a variety of optimization with constrained and unknown search spaces. By utilizing the AdaBoost algorithm, multiple sets of weak AMSSA-Elman predictor functions are restructured into one strong predictor by successive iterations for the tunnel deformation prediction output. Additionally, the on-site monitoring data acquired from a deep excavation project in Ningbo, China, were selected as the training and testing sample. Meanwhile, the predictive outcomes are compared with those of other different optimization and machine learning techniques. In the end, the obtained results in this real-world geotechnical engineering field reveal the feasibility of the proposed hybrid algorithm model, illustrating its power and superiority in terms of computational efficiency, accuracy, stability, and robustness. More critically, by observing data in real time on daily basis, the structural safety associated with metro tunnels could be supervised, which enables decision-makers to take concrete control and protection measures.

BACKGROUND: Diabetic retinopathy (DR) is one of the serious complications of diabetes mellitus (DM). Many studies have identified the risk factors associated with DR, but there is not much evidence on the importance of these factors for DR. This study aimed to investigate the associated factors for patients with type 2 DM (T2DM) and calculate the importance of the identified factors. MATERIALS AND METHODS: Using probability proportionate to size sampling method in this community-based cross-sectional study, 22 community health service centers were selected from 10 administrative districts in Shenzhen, China. Approximately 60 T2DM patients were recruited from each center. The participants completed a structural questionnaire, had their venous blood collected, and underwent medical examinations and fundus photography. Logistic regression models were used to identify the risk factors of DR. The classification and regression tree (CART) model was used to calculate the importance of the identified risk factors. RESULTS: This study recruited 1097 T2DM patients, 266 of whom were identified as having DR, yielding a prevalence rate of 24.3% (95% confidence interval [CI]: 21.7%–26.9%). Results showed that a longer duration of DM, indoor-type lifestyle, and higher levels of hemoglobin A1c (HbA1c) or urea increased the risk of DR. Patients with HbA1c values ≥7% were about 2.45 times (odds ratio: 2.45; 95% CI: 1.83–3.29) more likely to have DR than their counterparts. The CART model found that the values of variable importance for HbA1c, DM duration, lifestyle (i.e., indoor type), and urea were 48%, 37%, 10%, and 4%, respectively. CONCLUSION: The prevalence of DR is high for T2DM patients who receive DM health management services from the primary healthcare system. HbA1c is the most important risk factor for DR. Integration of DR screening and HbA1c testing into the healthcare services for T2DM to reduce vision impairment and blindness is urgently warranted.

Abstract Background Pyrethroid chemicals are one of the main acaricides used against ticks. Resistance to these chemicals has been reported to be associated with mutations in the voltage-gated sodium channel (VGSC) gene of the Rhipicephalus microplus. This study investigates R. microplus resistance to pyrethroids in Guangxi region of China, marking one of the first research efforts in this area. The findings are intended to provide vital baseline for the effective implementation of localized tick control strategies. Methods From March to July 2021, 447 R. microplus tick samples were collected from five prefecture-level cities in Guangxi. Allele-specific polymerase chain reaction (AS-PCR) was used to amplify segments C190A and G215T of the domain II S4-5 linker and T2134A of domain III S6 in the VGSC, to detect nucleotide mutations associated with resistance to pyrethroid acaricides. Subsequent analyses were conducted to ascertain the prevalence, types of mutations, and genotypic distributions within the sampled populations. Results Mutations within VGSC gene were identified across all five studied populations of R. microplus, although the mutation rates remained generally low. Specifically, the most prevalent mutation was C190A, observed in 4.9% of the samples (22/447), followed by G215T at 4.0% (18/447), and T2134A at 1.3% (6/447). The distribution of mutations across three critical sites of the VGSC gene revealed four distinct mutation types: C190A, G215T, C190A + G215T, and T2134A. Notably, the single mutation C190A had the highest mutation frequency, accounting for 4.3%, and the C190A + G215T combination had the lowest, at only 0.7%. The analysis further identified seven genotypic combinations, with the wild-type combination C/C + G/G + T/T predominating at a frequency of 90.4%. Subsequently, the C/A + G/G + T/T combination was observed at a frequency of 4.3%, whereas the C/C + T/T + T/T combination exhibited the lowest frequency (0.2%). Additionally, no instances of simultaneous mutations at all three sites were detected. Geographical differences in mutation types were apparent. Both samples from Hechi to Chongzuo cities exhibited the same three mutation types; however, C190A was the most prevalent in Hechi, while G215T dominated in Chongzuo. In contrast, samples from Beihai to Guilin each exhibited only one mutation type: G215T occurred in 12.5% (4/32) of Beihai samples, and C190A in 7.5% (4/53) of Guilin samples. Conclusions These findings underscore the relatively low frequency of VGSC gene mutations in R. microplus associated with pyrethroid resistance in the Guangxi, China. Moreover, the variation in mutation types and genotypic distributions across different locales highlights the need for regionalized strategies in monitoring and managing pyrethroid resistance in tick populations. This molecular surveillance is crucial for informing targeted control measures and mitigating the risk of widespread resistance emergence. Graphical Abstract

Abstract Renal tumors are one of the common diseases of urology, and precise segmentation of these tumors plays a crucial role in aiding physicians to improve diagnostic accuracy and treatment effectiveness. Nevertheless, inherent challenges associated with renal tumors, such as indistinct boundaries, morphological variations, and uncertainties in size and location, segmenting renal tumors accurately remains a significant challenge in the field of medical image segmentation. With the development of deep learning, substantial achievements have been made in the domain of medical image segmentation. However, existing models lack specificity in extracting features of renal tumors across different network hierarchies, which results in insufficient extraction of renal tumor features and subsequently affects the accuracy of renal tumor segmentation. To address this issue, we propose the Selective Kernel, Vision Transformer, and Coordinate Attention Enhanced U-Net (STC-UNet). This model aims to enhance feature extraction, adapting to the distinctive characteristics of renal tumors across various network levels. Specifically, the Selective Kernel modules are introduced in the shallow layers of the U-Net, where detailed features are more abundant. By selectively employing convolutional kernels of different scales, the model enhances its capability to extract detailed features of renal tumors across multiple scales. Subsequently, in the deeper layers of the network, where feature maps are smaller yet contain rich semantic information, the Vision Transformer modules are integrated in a non-patch manner. These assist the model in capturing long-range contextual information globally. Their non-patch implementation facilitates the capture of fine-grained features, thereby achieving collaborative enhancement of global–local information and ultimately strengthening the model’s extraction of semantic features of renal tumors. Finally, in the decoder segment, the Coordinate Attention modules embedding positional information are proposed aiming to enhance the model’s feature recovery and tumor region localization capabilities. Our model is validated on the KiTS19 dataset, and experimental results indicate that compared to the baseline model, STC-UNet shows improvements of 1.60%, 2.02%, 2.27%, 1.18%, 1.52%, and 1.35% in IoU, Dice, Accuracy, Precision, Recall, and F1-score, respectively. Furthermore, the experimental results demonstrate that the proposed STC-UNet method surpasses other advanced algorithms in both visual effectiveness and objective evaluation metrics.

Abstract A simple and flexible mass balance approach was applied to observations of XCH4 from TROPOMI to estimate CH4 emissions over Shanxi Province, including the impacts of advective transport, pressure transport, and atmospheric diffusion. High-frequency eddy-covariance flux observations were used to constrain the driving terms of the mass balance equation. This equation was then used to calculate day-to-day and 5 km × 5 km grided CH4 emissions from May 2018 to July 2022 based on TROPOMI RPRO column CH4 observations. The Shanxi-wide emissions of CH4, 126 ± 58.8 ug/m2/s, shows a fat tail distribution and high variability on a daily time scale (the 90th percentile is 2.14 times the mean and 2.74 times the median). As the number of days in the rolling average increases, the change in the variation decreases to 128 ± 35.7 ug/m2/s at 10-day, 128 ± 19.8 ug/m2/s at 30-day and 127 ± 13.9 ug/m2/s at 90-day. The range of values of the annual mean emissions on coal mine grids within Shanxi for the years 2018 to 2022 was 122 ± 58.2, 131 ± 71.2, 111 ± 63.6, 129 ± 87.1, and 138 ± 63.4 ug/m2/s, respectively. The 5-year average emissions from TROPOMI are 131 ± 68.0 ug/m2/s versus 125 ± 94.6 ug/m2/s on the grids where the EDGAR bottom-up database also has data, indicating that those pixels with mines dominate the overall emissions in terms of both magnitude and variability. The results show that high-frequency observation-based campaigns can produce a less biased result in terms of both the spatial and temporal distribution of CH4 emissions as compared with approaches using either low-frequency data or bottom-up databases, that coal mines dominate the sources of CH4 in Shanxi, and that the observed fat tail distribution can be accounted for using this approach.

Abstract Background Despite adequate transurethral resection of the bladder tumor (TURBT) followed by intravesical bacillus-calmette guérin (BCG), high-risk non-muscle-invasive bladder cancer (HR-NMIBC) is associated with high rates of recurrence and progression. Immune checkpoint inhibitors can improve antitumor activity in bladder cancer, but relevant evidence in HR-NMIBC is limited. Thus, we evaluated the efficacy and safety of the tislelizumab-based combination regimen in HR-NMIBC. Methods A retrospective study included 21 patients diagnosed with HR-NMIBC between July 2020 and September 2022. All patients underwent TURBT followed by combination regimens of tislelizumab plus BCG with or without gemcitabine/cisplatin (GC) chemotherapy. Clinical Data on demographics and characteristics, treatment information, outcomes, and safety were collected and analyzed. Results Among the 21 patients with HR-NMIBC, the median age was 63 years (range 39–85), with the majority of patients with stage T1 (16/21, 76.19%). The median treatment of tislelizumab was 5 cycles (range 1–12) and the median number of BCG instillations was 12 times (range 2–19). Of the 21 patients, 15 (71.43%) received combination chemotherapy with GC, with a median treatment of 2 cycles (range 0–7); others did not. Overall, after the median follow-up of 25 months (range 7–31), the estimated 2-year bladder recurrence-free survival rate was 78.64% (95% confidence intervals [CIs], 50.79–91.83%), 2-year cystectomy-free survival rate was 83.00% (95% CI 53.53–94.59%), and 2-year disease-free survival rate was 73.39% (95% CI 46.14–88.36%). Sixteen stage T1 patients achieved a distant metastasis-free survival rate of 95.45% (95% CI 71.87–99.34%) at 2 years. Fourteen (66.67%) patients experienced at least one treatment related-AEs (TRAEs), with 9.52% (2/21) of grade 3–4. Grade ≥ 3 TRAEs were hypophysitis (1/21, 4.76%) and myasthenia (1/21, 4.76%). No treatment-related deaths were observed. Conclusions The study demonstrated promising clinical benefits and a manageable safety profile of tislelizumab-based combination regimen as a bladder-sparing treatment of HR-NMIBC.

Abstract Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan–Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis.

This study investigated the effect of magnesium application on peanut growth and yield under two nitrogen (N) application rates in acidic soil in southern China. The chlorophyll content, net photosynthetic rate and dry matter accumulation of the N-sensitive cultivar decreased under reduced N treatments, whereas no effect was observed on the relevant indicators in the N-insensitive variety GH1026. Mg application increased the net photosynthetic rate by increasing the expression of genes involved in chlorophyll synthesis and Rubisco activity in the leaves during the pegging stage under 50%N treatment, while no effect on the net photosynthetic rate was observed under the 100%N treatment. The rate of dry matter accumulation at the early growth stage, total dry matter accumulation and pod yield at harvest increased after Mg application under 50%N treatment by increasing the transportation of assimilates from stems and leaves to pods in both peanut varieties, whereas no effect was found under 100%N treatment. Moreover, Mg application increased the NUE under 50%N treatment. No improvement of NUE in either peanut variety was found under 100%N treatment, while Mg application under the 50%N treatment can obtain a higher economic benefit than the 100%N treatment. In acidic soil, application of 307.5 kg ha−1 of Mg sulfate fertilizer under 50% reduced nitrogen application is a suitable fertilizer management measure for improving carbon assimilation, NUE and achieve high peanut yields in southern China.

Abstract Objective This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS). Methods A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded. Results The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P 0.05). Conclusion The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS.

Abstract The greater amberjack is a very important fishery species with high commercial value, and it is distributed worldwide. Transcriptome-based studies on S. dumerili have been limited by an inadequate reference genome and a lack of well-annotated full-length transcripts. In this study, a total of 12 tissues from juvenile and adult fish both sexes were collected for next-generation RNA sequencing (RNA-seq) and full-length isoform sequencing (Iso-seq). For Iso-seq, a total of 163,218, 149,716, and 189,169 high-quality unique transcript sequences were obtained, with an N50 of 5,441, 5,255, and 5,939, from juvenile, adult male and adult female S. dumerili, respectively. We integrated the Iso-seq and RNA-seq data to construct a comprehensive gene annotation and systematically profiled the dynamics of gene expression across the 12 tissues. Our gene models had greater detail and accuracy than those from NCBI and Ensembl, with more precise polyA locations. These resources serve as a foundation for functional genomic studies and provide valuable insights into the molecular mechanisms underlying the development, reproduction and commercial traits of amberjack.

IntroductionThe Bovine Viral Diarrhea Virus 1 (BVDV1) and HoBi-like virus (BVDV3), both within the same genus, share genomic homology and exhibit low antigenic cross-reactivity despite presenting similar clinical manifestations. In 2021, a bovine respiratory disease complex (BRDC) outbreak on two cattle farms in the Inner Mongolia Autonomous Region of China resulted in ten fatalities.MethodsMetagenomic and metatranscriptomic analyses were used to identify viral agents, including a co-infection case. A genetic evolution analysis assessed the relationships with related strains. Experimental infections in guinea pigs and calves evaluated the pathogenicity of the virusesResultsPhylogenetic analysis of the BVDV3 isolate IM2201 revealed close relatedness to Brazilian strains, with 97.06% nucleotide homology to the highly virulent strain SV478/07. Experimental co-infection in guinea pigs resulted in more severe clinical signs, including fever, cough, diarrhea, and significant pathological changes, and led to a higher mortality rate (40%) compared to no mortality from single-virus infections with BVDV1 or BVDV3. Similarly, co-infected cattle exhibited more severe clinical signs, including bloody diarrhea and rectal temperatures exceeding 40°C, along with persistent viremia and nasal viral shedding from 7 to 21 days post-infection. Blood analysis revealed significant reductions in white blood cell counts, particularly in co-infected cattle.DiscussionThis study highlights the enhanced pathogenicity and synergistic effects of BVDV1 and BVDV3 co-infection, exacerbating disease severity.

Background First‐pass successful reperfusion (FPSR), defined as a successful/complete reperfusion achieved after a single thrombectomy pass, is predictive of favorable outcome in patients with acute ischemic stroke with large‐vessel occlusion. It is unknown whether intravenous tirofiban is effective in increasing the rate of FPSR in acute anterior large‐vessel occlusion stroke. Methods and Results Patients who had acute large‐vessel occlusion stroke presenting within 24 hours and underwent endovascular thrombectomy were analyzed from the RESCUE BT (Intravenous Tirofiban for Patients With Large Vessel Occlusion Stroke) clinical trial, of which the main analysis was neutral. The RESCUE BT trial randomized patients to receive either intravenous tirofiban or placebo before endovascular thrombectomy. The primary end point was FPSR, defined as successful reperfusion (extended thrombolysis in cerebral infarction scale 2b50, 2c, or 3) at first thrombectomy attempt. A modified Poisson regression analysis assessed the association between intravenous tirofiban treatment and FPSR. Of 948 enrolled patients, 463 patients were randomized to the tirofiban group and 485 to the placebo group. The mean age was 67 years, and 41.0% of the patients were women. FPSR was achieved more often in the tirofiban group (30.5% versus 23.5%; adjusted risk ratio, 1.24 [95% CI, 1.01–1.51]; P=0.04). FPSR was associated with a favorable shift to lower modified Rankin Scale disability levels at 90 days (common odds ratio, 1.42 [95% CI, 1.08–1.86]; P=0.01). Conclusions In this post hoc analysis of the RESCUE BT trial, treatment with intravenous tirofiban before endovascular thrombectomy was associated with increased FPSR in patients with acute ischemic stroke due to large‐vessel occlusion in the anterior circulation. FPSR was associated with reduced 90‐day levels of disability. Registration URL: http://chictr.org; Unique Identifier: ChiCTR‐INR‐17014167.

The hotspot temperature of the reactor is one of the important indices in reactor design, and the appropriate hotspot value can ensure that the reactor will not overheat failure and threaten the safety of the power system. In this paper, the temperature field simulation model of a 500 kV dry-type air-core shunt reactor is established, and the hotspot temperature of the reactor is obtained by COMSOL software. Then, the radial basis function response surface function is used to construct the response surface function of the hotspot temperature and its related variables, and the applicability of the response surface function is tested to analyze the rationality and accuracy of the response surface function. Finally, the optimal solution of the response surface function under the coordination of variables and related constraints is obtained by using the constrained simulated annealing algorithm. The results show that the hotspot temperature of the reactor envelope winding decreases obviously after optimization.

The large-scale integration of distributed energy sources and power electronic devices results in the DC microgrid exhibiting significant low inertia and weak damping characteristics. This, in turn, leads to inevitable fluctuations in the DC bus voltage, which endanger the stable operation of the DC system. Energy storage devices can provide equivalent inertia. To enhance the inertia and response speed of the DC bus interface converter, this paper proposes a power allocation parameter adaptive virtual DC motor control strategy based on a hybrid energy storage unit. The strategy introduces power allocation control to regulate the energy storage converter on the basis of virtual inertia parameter adaptive control, thereby enabling the energy storage converter to simulate the inertia and damping characteristics of a DC generator. The small-signal stability of the system is analyzed by establishing a small-signal model of the photovoltaic energy storage system and utilizing the impedance ratio criterion. Finally, the proposed control strategy is validated through simulation. The results demonstrate that the strategy effectively mitigates the fluctuations in bus voltage under varying photovoltaic power and sudden load changes, ensures the power distribution in the hybrid energy storage system, and enhances the dynamic response of the system.

IntroductionAn innovative methodology is proposed to delve into the pivotal role of regional distribution networks (RDNs) in fostering low-carbon development.MethodsThe methodology first constructs an evaluation framework encompassing various dimensions and then integrates spherical fuzzy sets (SFSs) with the best-worst method (BWM), enabling the precise calculation of indicator weight parameters. Subsequently, we employ the measurement of alternatives and ranking according to compromise solution (MARCOS) with SFSs to process and synthesize decision making information.ResultsTake the Shanghai region as an example, results show that C4 has the highest performance and C10 has the lowest.DiscussionIn conclusion, this research presents a significant step forward in understanding the importance of RDNs in promoting low-carbon development and offers a practical approach for decision-makers to assess and enhance the performance of RDNs.

Abstract SMYD3 (SET and MYND domain‐containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor‐bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA‐seq and chip‐seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway.

In air-assisted spraying, pesticide droplet retention on crop leaves is key to evaluating spray effectiveness. However, airflow can deform leaves, reducing droplet retention and affecting spray performance. This study used wind tunnels and high-speed cameras to capture leaf deformation at different airflow speeds and the motion of droplets on curved leaf surfaces. The results showed that leaf curvature during bending deformation is generally less than 0.05 mm-1. Critical wind speed for droplet movement is negatively correlated with droplet size and leaf curvature, with a 24.8% difference between different leaf curvatures and a 17.5% difference between droplet sizes. The droplet’s dimensionless shape variable is positively correlated with both droplet size and leaf curvature. The maximum shape variable on curved leaves reaches 0.24, with acceleration differences of about 30%, while droplets of different sizes show a maximum shape variable of 0.18 and an acceleration difference of up to 68%. These findings enhance understanding of droplet-leaf interactions and provide insights for improving pesticide efficiency.

This study explored the unique role of collaborative teaching among ultrasonographers, anesthesiologists, and vascular surgeons in the training of vascular surgeons in developing countries. Using qualitative research methods, data were collected through in-depth interviews and observations to analyze the improvement in ultrasound operational skills and basic anesthesia skills among trainees, as well as their satisfaction with collaborative teaching. The results indicate that collaborative teaching significantly enhances trainees’ professional skills and interdisciplinary collaboration abilities, gaining widespread recognition from trainees. This teaching model provides trainees with a comprehensive learning experience through interdisciplinary cooperation, hands-on practice, contributing to the cultivation of vascular surgeons with comprehensive qualities and professional competencies. This study offers new ideas and methods for the training of vascular surgeons in developing countries, holding significant implications for the development of medical education.

ObjectiveThe limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury.MethodsA rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation.ResultsThe CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus.ConclusionIcariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

Abstract Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration‐resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron‐dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate‐specific membrane antigen (PSMA)‐targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane‐coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M‐gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA‐specific, CRPC‐targeting platform for ferroptosis induction with increased efficacy and safety.

Abstract Objective To examine the relationship between C‐reactive protein (CRP) and knee pain, and further explore whether this association is mediated by obesity. Methods The population was derived from 1999 to 2004 National Health and Nutrition Examination Survey. Logistic regression was used to analyze the relationship between CRP and knee pain in three different models, and the linear trend was analyzed. A restricted cubic spline model to assess the nonlinear dose−response relationship between CRP and knee pain. Mediation analyses were used to assess the potential mediating role of obesity. Subgroup analyses and sensitivity analyses were performed to ensure robustness. Results Compared with adults with lower CRP (first quartile), those with higher CRP had higher risks of knee pain (odds ratio 1.39, 95% confidence interval 1.12−1.72 in third quartile; 1.56, 1.25−1.95 in fourth quartile) after adjusting for covariates (except body mass index [BMI]), and the proportion mediated by BMI was 76.10% (p

This study aimed to investigate the effects of Miao medicinal Canna edulis RS3-resistant starch on behavioral performance and substantia nigra neuron apoptosis-related indicators in a rat model of Parkinson's disease (PD). Among the experimental groups, except for the control group, we induced PD rat models by subcutaneous injection of rotenone in the neck and back. After model induction, a 28-day drug intervention was conducted. Various techniques have been employed, including behavioral analysis, Real-time Polymerase Chain Reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and terminal deoxynucleotidyltransferase-mediated UTP nick-ends. labeling (TUNEL) and Nissl staining to investigate the effect of Canna edulis RS3-resistant starch on the substantia nigra and neuronal apoptosis-related markers in the brains of PD model rats. Our study revealed that Canna edulis RS3, a resistant starch, significantly reduced the climbing time of PD model rats, prolonged their hanging time, lowered the expression levels of the inflammatory factors IL-1β, IL-6, and TNF-α, increased the number of TH-positive neurons in the substantia nigra, and decreased the levels of IL-1β, IL-6, and TNF-α. Furthermore, Canna edulis RS3 elevated the protein expression levels of tyrosine hydroxylase (TH) and Bcl-2 while reducing those of Bax, TLR4, NLRP3,and p-P65, and mitigated apoptosis and morphological changes in dopaminergic neurons in the substantia nigra region. Our results suggest that Canna edulis RS3-resistant starch may offer therapeutic benefits for PD patients with PD by potentially influencing inflammation and apoptosis in the dopaminergic system.