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Abstract Background Per- and polyfluoroalkyl substances (PFAS) are commonly utilized in consumer products. While earlier studies have suggested potential impacts of certain PFAS on serum concentrations of vitamin D, these investigations were constrained to a limited set of conventional PFAS. Moreover, they did not specifically focus on populations with longer duration of PFAS exposure and potentially higher blood PFAS levels, such as older adults, and lacked adequate evidence to examine sex-related disparities. Methods This observational investigation utilized cross-sectional data obtained from the U.S. NHANES spanning the years 2003 to 2018. Survey-weighted multiple regression models were employed to evaluate the relationship between PFAS exposure and vitamin D concentrations. Multi-pollutant models were employed to evaluate the association between PFAS mixtures and vitamin D concentrations. Subsequently, environmental risk scores (ERS) were constructed to gauge associations with vitamin D concentrations. ERS was computed through a weighted linear combination of PFAS, utilizing calculations from ridge regression and adaptive elasticity network (adENET) methodologies. All analyses were stratified by sex. Results The study encompassed 3,853 older adults. Our analysis revealed a negative association between PFOA, PFOS, PFNA, and MeFOSAA and serum vitamin D concentrations. In analyses examining mixed exposures, various models consistently indicated an inverse association between PFAS mixed exposure and vitamin D concentrations. Moreover, an increase in ERS of PFAS across the interquartile range was associated with a decrease in vitamin D concentrations (Q4 vs. Q1, adENET: β: -0.083, 95% CI: -0.117, -0.048; ridge regression: β: -0.077, 95% CI: -0.111, -0.042). Notably, these associations were exclusively observed within the female population. Conclusions Our study indicates that heightened exposure to PFAS correlates with diminished serum vitamin D concentrations in females aged 60 years and older, evident in both single and mixed exposures. These findings find support in in vitro mechanistic studies, suggesting that PFAS may impact the metabolism of 25(OH)D, consequently affecting vitamin D concentrations.

Abstract Alzheimer’s disease (AD), an age-related neurodegenerative disorder, is characterized by irreversible brain tissue degeneration. The amyloid-β (Aβ) cascade hypothesis stands as the predominant paradigm explaining AD pathogenesis. This study aimed to elucidate the mechanisms underlying Aβ-induced pyroptosis in AD. AD models were established using amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice and Aβ-treated BV-2 cells (5 µM, 24 h). NEK7 expression was evaluated in vitro and in vivo. Cell pyroptosis was assessed before and after NEK7 expression was inhibited in BV-2 cells. Adeno-associated virus (AAV) vectors carrying short hairpin RNA (shRNA) against NEK7 (AAV-sh-NEK7) were administered to mice to knockdown NEK7 in vivo. Spatial learning and memory abilities were evaluated using the Morris water maze test. The interaction between NEK7 and histone H4 lysine 12 lactylation (H4K12la) were then investigated. The results suggested that NEK7 expression was markedly elevated in both in vitro and in vivo AD models. Treatment with Aβ significantly reduced cell viability and enhanced pyroptosis in BV-2 cells; these effects were reversed by inhibiting NEK7. Furthermore, AD mice with NEK7 knockdown exhibited shorter escape latencies and increased time spent in the target quadrant, suggesting that NEK7 inhibition improved cognitive function and memory retention. Mechanistically, Aβ treatment induced histone lactylation in BV-2 cells, and suppression of lactylation attenuated NEK7 transcriptional activity and mRNA levels. In summary, elevated NEK7 expression promoted histone lactylation in BV-2 cells, thereby facilitating pyroptosis. Inhibition of NEK7 conferred protection against Aβ-induced cellular damage and enhanced cognitive performance and memory retention in AD model mice. Collectively, targeting NEK7 represents a potential therapeutic strategy for alleviating AD symptoms. Graphical abstract

Named Entity Recognition (NER) in Chinese Electronic Medical Records (EMRs) is crucial for enhancing healthcare quality and efficiency. However, the unique complexity of the Chinese language and the unstructured format of medical texts create significant challenges. To address these issues, we propose MSCNER, a unified Multi-Scale Embedding Network designed specifically for NER in Chinese EMRs. MSCNER navigates linguistic and contextual challenges by employing a character relation classification scheme. The model first extracts detailed contextual information through an information extraction module and a context modeler. It then incorporates multi-scale feature extraction to gather comprehensive features across characters, words, and positions. Additionally, a weight allocation module based on an attention mechanism optimizes the recognition of complex and discontinuous entities. Experimental results on three benchmark Chinese EMR datasets demonstrate that MSCNER achieves state-of-the-art performance. It significantly surpasses existing models in terms of accuracy and reliability. These findings underscore the potential of MSCNER to improve NER in medical applications, paving the way for more effective and scalable healthcare data systems and broader applications in other language processing tasks.

Abstract Objective: To investigate the association between coal dust exposure and the occurrence of dyslipidemia in coal mine workers, and identify relevant risk factors. Methods: We selected a population who underwent occupational health examinations at Huainan Yangguang Xinkang Hospital from March 2020 to July 2022. Participants were divided into two groups based on the presence or absence of dyslipidemia, and their baseline information was collected, including records of coal dust exposure. We employed single-factor analysis to identify risk factors for dyslipidemia and adjusted for confounding factors in the adjusted models. Additionally, we explored the effects in different populations using stratified analysis, smooth curve fitting, and propensity score matching. Finally, we confirmed the causal relationship between coal dust exposure and dyslipidemia by examining tissue sections and lipid-related indicators in a mouse model of coal dust exposure. Results A total of 5,657 workers were included in the study, among whom 924 individuals had dyslipidemia and 4,743 individuals did not have dyslipidemia. The results of the single-factor analysis revealed that dust exposure, age, BMI, blood pressure, and smoking were statistically significant risk factors for dyslipidemia (p

Abstract Background Limited information is available regarding the impact of sarcopenia on the prognosis of antiangiogenic therapy in individuals with advanced non‐small cell lung cancer (NSCLC). This study primarily sought to examine the prognostic significance of sarcopenia in individuals with advanced NSCLC undergoing antiangiogenic therapy. Methods We retrospectively enrolled all patients who met the inclusion and exclusion criteria from 2019 to 2021 at Nantong University Hospital. Patients were grouped according to the presence or absence of sarcopenia. After propensity score matching (PSM), progression‐free survival (PFS), overall survival (OS), and adverse event rates were compared between the two groups. Factors associated with prognosis were screened using univariate and multivariate analyses. Results A total of 267 patients were included, with a total of 201 matched at baseline after PSM (77 in the sarcopenia group and 124 in the non‐sarcopenia group). The sarcopenia group had lower PFS (p = 0.043) and OS (p = 0.011) than the non‐sarcopenia group and a higher incidence of adverse events (p = 0.044). Multivariate analysis suggested that sarcopenia is an independent prognostic risk factor for OS in advanced NSCLC patients receiving antiangiogenic therapies (p = 0.009). Results of subgroup analyses showed some differences in the impact of sarcopenia on survival prognosis in populations with different characteristics. Conclusion Patients with advanced NSCLC with comorbid sarcopenia exhibit a worse prognosis when treated with antiangiogenic therapy, and preventing and ameliorating sarcopenia may lead to better survival outcomes in patients with advanced NSCLC.

Abstract The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.

The development of Si–HfO2/Yb2Si2O7/Yb2SiO5 environmental barrier coatings (EBCs) aims to improve the operational temperature and longevity of ceramic matrix composites (CMCs) in turbine environments. Nevertheless, several critical questions remain unanswered, including the oxidation mechanism of Si–HfO2 bond coating, the compatibility of its mixed thermally grown oxide (m-TGO) with adjacent layers during thermal cycling, and the evolution pattern of vertical mud-cracks that impact the overall performance in service. Using plasma spraying physical vapor deposition (PS-PVD), we fabricated these EBCs on a CMC substrate, and thermal cycling tests at 1400, 1450, and 1500 °C revealed that their durability reached 200 h. m-TGO growth followed a parabolic model, with the oxygen diffusion activation energy being 133.69 kJ/mol between 1400 and 1450 °C and 101.47 kJ/mol from 1450 to 1500 °C, emphasizing that the transport of molecular oxygen is key to controlling the oxidation of m-TGO in this EBC system. Although residual stresses and stored elastic strain energy build up between m-TGO and adjacent layers, especially around the cristobalite phase transition temperature, causing interlaminar crack formation in later thermal cycles, the stored elastic strain energy remains lower than that of the silicon oxide–thermally grown oxide (SiO2–TGO) formed in Si bond coating system. In addition to [110] dislocations, (001) twinning and interaction zones between twinning and dislocations were discovered for the first time, driving the bifurcation of mud cracks. Notably, controlling the mud-crack density is vital for protection of Yb2SiO5 layer, as bifurcated mud-crack tips may converge with adjacent mud-cracks.

Objective: This study examines the effect of music therapy on perioperative anxiety and postoperative satisfaction in elderly patients undergoing lower-limb fracture surgery with intravertebral anesthesia to address the increasing incidence of such fractures and related surgical stress. Methods: Conducted from February 2022 to June 2023, this prospective study involved 120 elderly patients at the People’s Liberation Army General Hospital of Southern Theatre Command. They were divided into the Music group (n = 60, receiving relaxing music during surgery) and the Control group (n = 60, no music). We measured preoperative and postoperative anxiety by using the Visual Analog Scale for Anxiety (VAS-A) along with intraoperative hemodynamic parameters and patient satisfaction postsurgery. Results: Both groups maintained stable heart rates, systolic and diastolic blood pressures, and mean arterial pressure. However, the Music group displayed significantly lower systolic blood pressure at the beginning of the operation (T5), 5 minutes after the operation (T6) and at the end of the operation (T9) than the Control group. After the surgery, the Music group had notably lower VAS-A scores and saliva cortisol levels, indicating reduced anxiety. Additionally, this group reported higher satisfaction levels. Conclusions: Music therapy notably reduced postoperative anxiety and improves patient satisfaction in elderly patients undergoing lower-limb fracture surgery with intravertebral anesthesia. These findings endorse music therapy as a beneficial, non-invasive, and cost-effective method to ameliorate perioperative stress and a complementary approach to traditional medical care in surgical settings.

Abstract Background Exposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown. Methods The cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models. Results Each 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively. Conclusion Blood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

Abstract Background Previous research has discovered that surfactant protein A (SP-A) is involved in the pathophysiology processes of certain lung illnesses. However, no definitive clinical studies have delved into the function of SP-A in individuals afflicted with community-acquired pneumonia (CAP). A prospective cohort study was used to investigate the relationships between blood SP-A levels and the severity and prognosis among CAP patients. Materials and methods This study included 260 patients with CAP. Clinical traits and demographic data were examined during hospitalization. The concentrations of serum SP-A and serum interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). In addition, to evaluate the severity of CAP, a variety of scores, including the CURB-65, PSI, SMART-COP, and APACHE II, were employed. Results The serum levels of SP-A at admission exhibited a gradual decline as the severity scores of CAP increased. Through Spearman correlation analysis, we observed an association between serum SP-A and some clinical indicators among CAP patients. Furthermore, results from a multiple linear regression model suggested changes in PSI scores (-17.868 scores, 95% CI: -32.743, -2.993) affect serum SP-A more than CURB-65 (-0.547 scores, 95% CI: -0.964, -0.131), SMART-COP (-1.097 scores, 95% CI: -1.889, -0.304) and APACHE II (-3.475 scores, 95% CI: -5.874, -1.075) with age, hypertension, diabetes mellitus, cerebral infarction, coronary heart disease, and bronchitis adjusted. In addition, the prognosis in CAP patients was monitored. Throughout their hospital stay, higher serum levels of SP-A decreased the risks of mechanical ventilation (RR: 0.315; 95% CI: 0.106, 0.937), vasoactive agents (RR: 0.165; 95% CI: 0.034, 0.790), intensive care unit (ICU) admissions (RR: 0.218; 95% CI: 0.066, 0.717) and longer hospital stays (RR: 0.397; 95% CI: 0.167, 0.945). Conclusion In CAP patients, inverse dose-response correlations exist between serum SP-A levels with severity scores as well as prognosis at admission, suggesting that SP-A may take part in the CAP pathophysiological processes. Moreover, lower serum SP-A on admission is associated with an elevated prognostic risk of mechanical ventilation, the use of vasoactive agents, longer hospital stays, ICU admission, and mortality. Therefore, as a biomarker, SP-A may have the potential to predict the severity and poor prognosis of CAP patients.

The gear friction pairs in RV reducer always withstand a broad range of temperature, sliding velocity and heavy load. In the research, three types of heat treatment methods (carburizing + quenching, nitrocarburizing and high concentration nitrocarburizing) are applied on the 20CrMo (cycloidal gear material) disc to study the tribological behavior and wear mechanism. The friction coefficient, wear depth and wear rate of the three types of friction pairs under various temperature (−20 °C, 25 °C, 50 °C, 100 °C) are measured and the microstructure characteristics are analyzed by SEM and EDS. The results reveal that high temperature can dramatically decrease the wear scar dimensions and wear rate due to the more active lubricant. Although the lubricant lost its activity at −20 °C, the friction coefficient and maximum wear depth for GCr15/20CrMo (carburizing + quenching) and GCr15/20CrMo (high concentration nitrocarburizing) are relatively less than 0.1 and 4 μm. The wear rate of GCr15/20CrMo (carburizing + quenching) and GCr15/20CrMo (high concentration nitrocarburizing) are 14.49 μm3/N·m and 17.20 μm3/N·m, which are only 28.7% and 34.1% of GCr15/20CrMo (nitrocarburizing). With the temperature increases to 25 °C, tribofilm is more likely to form on the 20CrMo specimen after nitrocarburizing, leading to better wear resistance. At high temperature (50 °C and 100 °C), GCr15/20CrMo (high concentration nitrocarburizing) system presents excellent tribological behavior by the combination of good lubricant activity, formation of tribofilm and refined nitrides. The wear rate even reaches 0.45 μm3/N·m and 0.43 μm3/N·m at the sliding velocity of 300 mm/s and 562 mm/s under 100 °C. Overall, specimen with high concentration nitrocarburizing process exhibits exceptional wear performance under full operating conditions of RV reducer.

Background/Aims: Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions: Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

ABSTRACT: Lactococcus lactis, widely used in the manufacture of dairy products, encounters various environmental stresses both in natural habitats and during industrial processes. It has evolved intricate machinery of stress sensing and defense to survive harsh stress conditions. Here, we identified a novel TetR/AcrR family transcription regulator, designated AcrR1, to be a repressor for acid and antibiotic tolerance that was derepressed in the presence of vancomycin or under acid stress. The survival rates of acrR1 deletion strain ΔAcrR1 under acid and vancomycin stresses were about 28.7-fold (pH 3.0, HCl), 8.57-fold (pH 4.0, lactic acid) and 2.73-fold (300 ng/mL vancomycin) greater than that of original strain F44. We also demonstrated that ΔAcrR1 was better able to maintain intracellular pH homeostasis and had a lower affinity to vancomycin. No evident effects of AcrR1 deletion on the growth and morphology of strain F44 were observed. Subsequently, we characterized that the transcription level of genes associated with amino acids biosynthesis, carbohydrate transport and metabolism, multidrug resistance, and DNA repair proteins significantly upregulated in ΔAcrR1 using transcriptome analysis and quantitative reverse transcription-PCR assays. Additionally, AcrR1 could repress the transcription of the nisin post-translational modification gene, nisC, leading to a 16.3% increase in nisin yield after AcrR1 deletion. Our results not only refined the knowledge of the regulatory mechanism of TetR/AcrR family regulator in L. lactis, but presented a potential strategy to enhance industrial production of nisin.

Sugars will eventually be exported transporter (SWEET) is a novel class of sugars transporter families which mainly mediate either sucrose or hexose translocation bidirectional across the cellular membranesfollowinga concentrating gradient with a passive diffusion patten. In higher plants, SWEET proteins commonly have seven transmembrane domains that form a pore in the membrane to allow the passage of sugars, containing two MtN3/Saliva domains. Phylogenetically, plant SWEETs are divided into four clades. SWEET transporters play important roles in diverse physiological and biochemical processes including phloem loading, plant hormone transportand vegetative growth. In this review, based on the current advance of the plant SWEET transporters, we summarized their discovery, structure characteristicsand biological functions, and pointed out current research problems. Finally,put forward several better future research directions and potential solutions for SWEET sugar transporters in plant from the following three aspects: 1) exploring the molecular mechanism of substrate recognition and selectivity of SWEET proteins; 2) mining and utilizing of key SWEET genes increasing crop yield and improving quality; 3) using gene editing technology and phosphorylation of SWEET transporters to engineer high-yielding and high-quality crops.

Abstract Twenty-four hours continuous intraocular pressure (IOP) monitoring is beneficial for glaucoma care. Contact lens sensors using LC technology can achieve non-invasive continuous IOP measuring around the clock and are relatively simple in principle and structure, thus dominating the mainstream. Among them, stretchable inductive LC contact lens sensors constructed with liquid metal have advantages in signal quality as well as wearing comfort, but currently its sensitivity is slightly insufficient. Here, we propose an LC sensor that constructed with liquid metal to form the stretchable inductance and capacitance further. The capacitive plate and inductive coil can response to IOP changes simultaneously, thus able to enhance the sensitivity in principle. We modeled the sensing mechanism and conducted design, fabrication, as well as various tests. The device exhibits good characteristics, including reliability, good signal quality, etc. Especially, it has a threefold increase in sensitivity, exceeding the current state-of-the-art contact lens sensors.

Abstract Background β-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the β-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. Results In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of β-catenin. Our analysis showed that a truncated β-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive β-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak β-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive β-catenin mutants activated mesoderm genes. Conclusion Our study uncovered an unconventional regulatory function of β-catenin through weak transactivation, indicating that the levels of β-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

Abstract Lumpy skin disease (LSD) is a highly contagious disease caused by lumpy skin disease virus (LSDV) in bovines. Rapid and accurate diagnosis is very important to controll it. However, current commercial detection kits need to be improved in terms of sensitivity or specificity. This study aimed to develop a novel diagnostic competitive enzyme-linked immunosorbent assay (cELISA) based on the newly identified antigen gene LSDV034. The rLSDV034 protein was identified as a potential diagnostic antigen, and it was expressed, purified, and used to immunize BALB/c mice. Using laboratory-prepared indirect ELISA (iELISA), the positive cell lines were screened, and their blocking activity was further verified by competitive ELISA (cELISA). The cell line, 1H7, was chosen to produce mouse ascites, which were purified for a monoclonal antibody (mAb, 5.395 mg/mL). The heavy chain type of the 1H7 mAb was identified as IgG1a, and its light chain subtype was identified as κ. Furthermore, cELISA was developed to detect bovine serum antibodies, with rLSDV034 (4 μg/mL) as the coating antigen and HRP-1H7 mAb (1:300) as the competitive antibody. The cutoff value of cELISA was 55%, based on 32 negative bovine serum samples. The analytical sensitivity was 1:8, and no cross-reaction was detected with bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitis virus (IBRV), Pasteurella multocida (P. multocida), or Mycoplasma bovis (M. bovis) from the serum samples. The diagnostic sensitivity and specificity of cELISA were 98.46% (95% confidence interval, CI: 91.7–100) and 100% (95% CI: 89.1–100), respectively, based on the analysis of 30 LSDV-infected bovine serum samples, 35 GTPV-vaccinated samples, and 32 negative samples. The overall coincidence of the cELISA with the virus neutralization test (VNT) reached 98.97% (95% CI: 94.4–100). Furthermore, we used cELISA to analyze 230 clinical bovine serum samples (including 59 infected and 171 vaccinated samples) and found that the serum positivity rates of the immunized samples (on d 60 postimmunization) and infected samples were 77.78% (95% CI: 70.8–83.8%) and 71.19% (95% CI: 57.9–82.2), respectively. These results indicate that the developed cELISA is promising for detecting serum antibodies in naturally infected or vaccinated cattle.

Abstract Background Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. Methods We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. Results A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. Conclusions This study constructed a cellular senescence-related signature that could be used to predict HCC patients’ responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.

Purpose: Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in under-foot impact loading environments. Methods: The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures. Results: The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model. Conclusion: Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Age-related macular degeneration (AMD) is a complicated disease that causes irreversible visual impairment. Increasing evidences pointed retinal pigment epithelia (RPE) cells as the decisive cell involved in the progress of AMD, and the function of anti-oxidant capacity of PRE plays a fundamental physiological role. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes. Its functions of protecting RPE cells against oxidative stress (OS) and ensuing physiological changes, including inflammation, mitochondrial damage and autophagy dysregulation, have already been elucidated. Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis. For the first time, this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis, including proteins and miRNAs, and their underlying molecular mechanisms, which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

Diabetic wounds pose an enduring clinical hurdle, marked by delayed recovery, persistent inflammation, and an elevated susceptibility to infections. Conventional treatment approaches often fall short of delivering optimal outcomes, prompting the exploration of innovative methods to enhance the healing process. Electrospun wound dressings offer superior healing, controlled drug release, enhanced cell proliferation, biocompatibility, high surface area, and antimicrobial properties. In the current study, polycaprolactone/gelatin-based nanofibrous wound dressings were developed for the delivery of Wharton's jelly stem cells and curcumin into the diabetic wounds bed. Curcumin was loaded into the polycaprolactone/gelatin solution and electrospun to produce curcumin-loaded scaffolds. In vitro experiments including scanning electron microscopy, cell viability assay, release assay, hemocompatibility assay, cell proliferation assay, and antibacterial assay were utilized to characterize the delivery system. Then, curcumin-loaded scaffolds were seeded with 30,000 Wharton's jelly stem cells and implanted into a rat model of diabetic wounds. Study showed that the scaffolds containing both Wharton's jelly stem cells and curcumin significantly improved diabetic wound closure (86.32 3.88% at the end of 14th day), augmented collagen deposition, and improved epithelial tissue formation. Gene expression studies showed that VEGF and IGF genes were significantly upregulated by the co-delivery system. Our developed system may have augmented diabetic wound healing via upregulating pro-healing genes.

Abstract Background Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co‐differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Methods Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real‐time polymerase chain reaction, Cell Counting Kit‐8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. Results PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA‐432‐5p (miR‐432‐5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR‐433‐3p in PMECs, and upregulate zinc finger AN1‐type containing 5 (ZFAND5) expression by targeting miR‐3613‐5p in PCs. Conclusions Our results suggest that circPMS1 promotes cell proliferation through the miR‐432‐5p/DEPDC1 or miR‐432‐5p/POL2D axis in PASMCs, through the miR‐433‐3p/MXI1 axis in PMECs, and through the miR‐3613‐5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

Abstract Background Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs). Results We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4−/− mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice. Conclusions Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.

Abstract Circumventing the conventional two-electron oxygen reduction pathway remains a great problem in enhancing the efficiency of H2O2 photosynthesis. A promising approach to achieve outstanding photocatalytic activity involves the utilization of redox intermediates. Here, we engineer a polyimide aerogel photocatalyst with photoreductive carbonyl groups for non-sacrificial H2O2 production. Under photoexcitation, carbonyl groups on the photocatalyst surface are reduced, forming an anion radical intermediate. The produced intermediate is oxidized by O2 to produce H2O2 and subsequently restores the carbonyl group. The high catalytic efficiency is ascribed to a photocatalytic redox cycle mediated by the radical anion, which not only promotes oxygen adsorption but also lowers the energy barrier of O2 reduction reaction for H2O2 generation. An apparent quantum yield of 14.28% at 420 ± 10 nm with a solar-to-chemical conversion efficiency of 0.92% is achieved. Moreover, we demonstrate that a mere 0.5 m2 self-supported polyimide aerogel exposed to natural sunlight for 6 h yields significant H2O2 production of 34.3 mmol m−2.

Abstract Background Flavivirus is a challenge all over the world. The replication of flavivirus takes place within membranous replication compartments (RCs) derived from endoplasmic reticulum (ER). Flavivirus NS1 proteins have been proven essential for the formation of viral RCs by remodeling the ER. The glycosylation of flavivirus NS1 proteins is important for viral replication, yet the underlying mechanism remains unclear. Methods HeLa cells were used to visualize the ER remodeling effects induced by NS1 expression. ZIKV replicon luciferase assay was performed with BHK-21 cells. rZIKV was generated from BHK-21 cells and the plaque assay was done with Vero Cells. Liposome co-floating assay was performed with purified NS1 proteins from 293T cells. Results We found that the glycosylation of flavivirus NS1 contributes to its ER remodeling activity. Glycosylation deficiency of NS1, either through N-glycosylation sites mutations or tunicamycin treatment, compromises its ER remodeling activity and interferes with viral RCs formation. Disruption of NS1 glycosylation results in abnormal aggregation of NS1, rather than reducing its membrane-binding activity. Consequently, deficiency in NS1 glycosylation impairs virus replication. Conclusions In summary, our results highlight the significance of NS1 glycosylation in flavivirus replication and elucidate the underlying mechanism. This provides a new strategy for combating flavivirus infections.

Abstract Background Few studies have simultaneously focused on the associations of vegetable and fruit intake, physical activity, school bullying, and Internet addiction (IA) with depressive symptoms. This study aimed to explore the direct and indirect effects of the above factors on depressive symptoms in adolescents by constructing a structural equation model (SEM). Methods This study was conducted in Qingdao from September to November 2021. A total of 6195 secondary school students aged 10–19 years were included in the analysis. Information on all variables was assessed using a self-administered questionnaire. An SEM was constructed with depressive symptoms as the endogenous latent variable, IA as the mediating variable, and vegetable and fruit intake, physical activity, and school bullying as the exogenous latent variables. The standardized path coefficients (β) were the direct effects between the latent variables, and the indirect effects were obtained by the product of direct effects between relevant latent variables. Results The median value with the interquartile range of depressive symptom scores was 7 (3,12). Vegetable and fruit intake (β=-0.100, P

Abstract The diversity of secondary metabolites is an important means for plants to cope with the complex and ever‐changing terrestrial environment. Plant biosynthetic gene clusters (BGCs) are crucial for the biosynthesis of secondary metabolites. The domestication and evolution of BGCs and how they affect plant secondary metabolites biosynthesis and environmental adaptation are still not fully understood. Buckwheat exhibits strong resistance and abundant secondary metabolites, especially flavonoids, allowing it to thrive in harsh environments. A non‐canonical BGC named UFGT3 cluster is identified, which comprises a phosphorylase kinase (PAK), two transcription factors (MADS1/2), and a glycosyltransferase (UFGT3), forming a complete molecular regulatory module involved in flavonoid biosynthesis. This cluster is selected during Tartary buckwheat domestication and is widely present in species of the Fagopyrum genus. In wild relatives of cultivated buckwheat, a gene encoding anthocyanin glycosyltransferase (AGT), which glycosylates pelargonidin into pelargonidin‐3‐O‐glucoside, is found inserted into this cluster. The pelargonidin‐3‐O‐glucoside can help plants resist UV stress, endowing wild relatives with stronger high‐altitude adaptability. This study provides a new research paradigm for the evolutionary dynamics of plant BGCs, and offers new perspectives for exploring the mechanism of plant ecological adaptability driven by environmental stress through the synthesis of secondary metabolites.

Colistin (CT) is the last-resort of antibiotic against multidrug-resistance (MDR) Acinetobacter baumannii (A. baumannii) infection. However, colistin resistance is increasingly reported in A. baumannii isolates partially due to the global emergence and dissemination of plasmid-borne mobile colistin resistance (mcr) gene and is a threat to human health. Thus, available treatment strategies urgently required in the fight against colistin-resistant A. baumannii. Here, we showed that mcr confers damaged outer membrane (OM) permeability in A. baumannii, which could compromise the viability of A. baumannii. Consistently, A. baumannii with colistin resistance exhibits increased susceptibility to macromolecular antibiotics such as rifampicin (RIF) and erythromycin (ERY). Moreover, the combination therapy of colistin and rifampicin demonstrates efficacy against colistin-resistant A. baumannii, regardless of the presence of mcr. Altogether, our data suggest that the synergy of colistin in combination with macromolecular hydrophobic antibiotics poses a promising therapeutic alternative for colistin-resistant A. baumannii.

ObjectivesMetagenomic next-generation sequencing (mNGS) is emerging as a novel diagnostic technology for various infectious diseases; however, limited studies have investigated its application in etiological diagnosis of early onset pneumonia (EOP) among patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital cardiac arrest (IHCA), The clinical significance of early mNGS in predicting short-term prognosis of IHCA patients after ECPR remains unclear.MethodsThis retrospective study included 76 patients with IHCA who underwent ECPR at the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022. Baseline characteristics and etiological data of all patients during their hospitalization were collected and statistically analyzed. The primary outcome of this study was the diagnosis of EOP, while the secondary outcomes included successful extracorporeal membrane oxygenation (ECMO) weaning and survival at discharge. Additionally, the characteristics of bronchoalveolar lavage fluid (BALF) flora in these patients were compared by analyzing both mNGS results and culture results.ResultsMultivariate logistic regression were employed to analyze the predictors of ECMO weaning failure, mortality at discharge, and the incidence of EOP. Ultimately, patients with lower SOFA scores on admission [OR (95%CI): 1.447 (1.107-1.890), p=0.007] and those who underwent early mNGS testing within 48 hours after ECPR [OR (95%CI): 0.273 (0.086-0.865), p=0.027] demonstrated a higher probability of successful weaning from ECMO. Patients with higher SOFA scores on admission [OR (95%CI): 2.404 (1.422-4.064), p=0.001], and elevated lactate levels [OR (95%CI): 1.176 (1.017-1.361), p=0.029] exhibited an increased likelihood of mortality at discharge. Furthermore, early mNGS detection [OR (95%CI): 0.186 (0.035-0.979), p=0.047], and lower CRP levels (48h-7d after ECMO) [OR (95%CI):1.011 (1.003-1.019), p=0.006] were associated with a reduced incidence of EOP. In addition, the pathogens detected by mNGS within 48 hours after ECPR were mainly oral colonizing bacteria and viruses, and viruses were in the majority, while all BALF cultures were negative. In contrast, between 48 hours and 7 days after ECPR, BALF cultures were positive in all EOP patients.ConclusionsEarly mNGS testing to identify microbial flora facilitates timely adjustment of antibiotic regimens, thereby reducing the incidence of EOP and improving short-term prognosis in patients undergoing ECPR following IHCA.

BackgroundInterleukin (IL)-38 is a newly discovered anti-inflammatory cytokine. However, its concentration and clinical significance in patients with gout remain unclear. This study aimed to investigate the levels of IL-38 in patients with gout and evaluate their clinical significance.MethodsThirty-two patients with active gout, 27 patients with inactive gout, and 20 negative controls (NCs) were included in the study. Clinical parameters, including white blood cell count, C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, uric acid, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, and glycoserated serum protein, were obtained from laboratory tests of blood samples. The serum concentration of IL-38 was determined using enzyme-linked immunosorbent assay. Spearman’s correlation analysis and receiver operating characteristic curve assessments were used to investigate the role and diagnostic value of IL-38 in gout.ResultsPatients with active and inactive gout exhibited significantly lower serum IL-38 levels than NCs. No significant differences were observed between the two gout groups. A negative correlation was observed between IL-38 and white blood cell counts, whereas a positive correlation was found between IL-38 and creatinine levels. Furthermore, IL-38, either alone or in combination with uric acid, demonstrated substantial diagnostic potential.ConclusionThe findings suggest that the decreased serum levels of IL-38 in patients with gout compared to that in NCs indicates that IL-38 may have immunomodulatory effects on gout inflammation and possesses clinical application value.

ObjectiveTo systematically review the literature on radiomics for predicting intracranial aneurysm rupture and conduct a meta-analysis to obtain evidence confirming the value of radiomics in this prediction.MethodsA systematic literature search was conducted in PubMed, Web of Science, Embase, and The Cochrane Library databases up to March 2024. The QUADAS-2 tool was used to assess study quality. Stata 15.0 and Review Manager 5.4.1 were used for statistical analysis. Outcomes included combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CI), as well as pre-test and post-test probabilities. The SROC curve was plotted, and the area under the curve (AUC) was calculated. Publication bias and small-study effects were assessed using the Deeks’ funnel plot.ResultsThe 9 included studies reported 4,284 patients, with 1,411 patients with intracranial aneurysm rupture (prevalence 32.9%). The overall performance of radiomics for predicting intracranial aneurysm rupture showed a combined Sen of 0.78 (95% CI: 0.74–0.82), Spe of 0.74 (95% CI: 0.70–0.78), +LR of 3.0 (95% CI: 2.7–3.4), −LR of 0.29 (95% CI: 0.25–0.35), DOR of 10 (95% CI: 9–12), and AUC of 0.83 (95% CI: 0.79–0.86). Significant heterogeneity was observed in both Sen (I2 = 90.93, 95% CI: 89.00–92.87%) and Spe (I2 = 94.28, 95% CI: 93.21–95.34%).ConclusionRadiomics can improve the diagnostic efficacy of intracranial aneurysm rupture. More large-sample, prospective, multicenter clinical studies are needed to further evaluate its predictive value.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

The medium-entropy perovskite oxide Bi0.5Sr0.5Fe0.85Nb0.05Ta0.05Sb0.05O3–δ (BSFNTS) is evaluated as a potential cathode catalyst for solid oxide fuel cells (SOFCs). The crystal structure, electrocatalytic activity, oxygen reduction kinetics, and CO2 tolerance are systematically investigated. At 700 °C, the BSFNTS cathode exhibits excellent electrochemical performance with a polarization resistance as low as 0.095 Ω cm2. The maximal power density of the fuel cell with the BSFNTS cathode is 900 mW cm−2. Furthermore, the rate control step for the oxygen reduction reaction (ORR) of the electrode is primarily identified as the adsorbed and diffusion process of the molecule oxygen. The BSFNTS electrode presents excellent CO2 tolerance and durability in a CO2-containing atmosphere, which is related to the high acidity of Bi, Nb, Ta, and Sb cations and the larger average bonding energy of BSFNTS. The preliminary results indicate that BSFNTS medium-entropy oxide is an attractive cathode electrocatalyst for SOFCs.

Fine particulate matter (PM2.5) may disrupt women's reproductive hormones, posing potential reproductive risks. However, the exact compositions of PM2.5 responsible for these effects remain unclear. Our investigation explored the long-term impacts of PM2.5 constituents on reproductive hormones, based on a large longitudinal assisted reproductive cohort study in Anhui, China. We included 24,396 reproductive hormone samples from 19,845 women attending assisted reproductive technologies (ART) between 2014 and 2020. Using high-resolution gridded data (1-km resolution), we calculated the residence-specified PM2.5 constituents during the year before the month of hormone testing. Relationships between PM2.5 constituents [organic matter (OM), chloride (Cl-), sulfate (SO42-), ammonium (NH4+), black carbon, and nitrate] and reproductive hormones were investigated using the linear mixed model with subject-specific intercepts. The constituent-proportion model and the constituent-residual model were also constructed. Additionally, cubic spline analysis was used to examine the potential non-linear exposure-response relationship. We found that per interquartile range (IQR) increment in OM was associated with a 5.31 % (3.74 %, 6.89 %) increase in estradiol, and per IQR increment in Cl- and NH4+ were associated with 13.56 % (7.63 %, 19.82 %) and 9.07 % (4.35 %, 14.01 %) increases in luteinizing hormone. Conversely, per IQR increment in OM and Cl- were associated with −7.27 % (-9.34 %, −5.16 %) and −8.52 % (-10.99 %, −5.98 %) decreases in progesterone, and per IQR increment in SO42- was associated with a −9.15 % (-10.31 %, −7.98 %) decrease in testosterone. These associations were held in both proportional and residual models. Moreover, exposure-response curves for estradiol and progesterone with PM2.5 constituents exhibited approximately U-shaped. These results suggested that specific PM2.5 constituents might disrupt reproductive hormone homeostasis in women attending ART, providing new evidence for formulating PM2.5 pollution reduction strategies that could benefit women's reproductive health.

The clock synchronization is a key technology for the reliability of wireless sensor networks (WSN). To reduce the communication burden and address the challenge of clock synchronization for high-precise clock systems in WSN with switching topologies, this paper proposes an event-triggered synchronization strategy for high-precise clock systems. Firstly, based on the concept of offset and skew, the model of whole clock systems is investigated and an event-triggered strategy is proposed for high-precise clock systems with switching topologies. Then, a synchronization strategy for clock systems is presented to achieve clock synchronization with the convergence of clock offset and clock skew. The sufficient condition for the synchronization of high-precise clock systems with switching topologies is obtained. Afterwards, the optimal event-triggered weighting matrices and controller gains are calculated by converting the clock synchronization problem as a solvable optimization problem. Finally, the performance of the proposed clock synchronization method is evaluated by simulations.

Introduction: Road traffic injuries stands as a major concern globally, as they result in significant loss of life, economic impact, and erode trust in government and societal safety. The influence of weather on road traffic safety is undeniable, impacting road conditions, individuals, and vehicles. However, the specific influence of weather on road traffic casualties has seldom been explored. Method: This study assesses the effect of weather factors on road traffic casualties in China from 2006 to 2021. Vector error correction models (VECM) were utilized to determine the Granger causality between weather factors and covariates. Furthermore, panel autoregressive distribution lag models (ARDL) were applied to quantify the association between weather factors and road traffic casualties. Results: The findings indicate that rainfall and temperature exert a short-term negative impact on casualty risk, which intriguingly becomes positive in the long term. A standout discovery is the significant role of health investments, which are shown to reduce casualty numbers in both the short and long-terms. In the long run, the gross domestic product significantly enhances casualties, while expressway mileage notably decreases them. Conclusions: These results demonstrate the significant influence of weather on road traffic casualties and highlight the critical roles played by factors such as gross domestic product, health investment, and expressway mileage. The evidence presented in the study underscores the urgent need for more effective strategies to mitigate road traffic casualties. Thus, some effective measures are proposed to reduce road traffic casualties. This study is conducive to the improvement of traffic in severe weather in China and provides guidance for traffic management departments.

BackgroundCurrently, there remains substantial controversy in research regarding whether the concomitant use of colchicine and statins increases the occurrence of rhabdomyolysis, warranting further substantiation.ObjectiveThis study aimed to identify the likelihood drug-drug interactions (DDIs) for the co-administration of colchicine and statins resulting in rhabdomyolysis.MethodsA disproportionality analysis was conducted by using data sourced from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to detect rhabdomyolysis signals associated with the combined use of colchicine and statins. The association between (colchicine/statins/colchicine and statins) and rhabdomyolysis were evaluated using information component (IC). DDI signals were calculated based on the Ω shrinkage measure and Bayesian confidence propagation neural network (BCPNN) method. Furthermore, stratification was performed based on colchicine and individual statins agents.ResultsIn total, 11,119 reports of rhabdomyolysis were identified in the FAERS database, 255 (2.29%) involved both colchicine and statins. Our analysis showed potential DDI signals of rhabdomyolysis (Ω025 = 1.17) among individuals concurrent use of colchicine and statins. Moreover, further drug-specific analysis suggests DDI signals in the colchicine-atorvastatin pair (Ω025 = 1.12), and colchicine-rosuvastatin pair (Ω025 = 1.05), along with a higher proportion of rhabdomyolysis (IC025 = 5.20) and (IC025 = 4.26), respectively.ConclusionThe findings suggest that concomitant use of colchicine and statins may increase the risk of rhabdomyolysis, particularly when combined with atorvastatin or rosuvastatin. Therefore, healthcare professionals should pay special attention to life-threatening AE such as rhabdomyolysis, when co-prescribing colchicine statins.

Coal-water slurry gasification is one of advanced coal gasification technologies. The improvement on the efficiency of coal-water slurry gasification is helpful to promote the clean and efficient utilization of coal. Coal-water slurry preheating technology is considered as one of the key technologies to improve the energy utilization efficiency of coal gasification. At present, the variation pattern and intrinsic mechanism of thermal conductivity of complex liquid-solid suspensions are still not fully understood. The thermal conductivity is an important basic parameter of the medium flow heat transfer, characterizing its thermal conductivity in the steady-state thermal conductivity process. The transient hot wire method is used to measure the thermal conductivity of the same concentration coal-water slurry at different temperatures. The experimental results show that the higher the temperature, the higher the thermal conductivity. The thermal conductivity of coal-water slurry is determined at different mass concentrations with a room temperature. The experimental results show that it can be divided into two stages: the mass concentration increases from 51% to 58% in a drop zone, and the thermal conductivity decreases rapidly, its value decreases from 0.401 W/(m·K) to 0.358 W/(m·K); and the mass concentration continues to increase from 58% to 67% in a constant zone, and the thermal conductivity basically remains at 0.358 W/(m·K). Based on the experimental results, the parallel prediction model of thermal conductivity of coal-water slurry with coal particle-bonded water composite is proposed by considering the parallel model, Maxwell model, generalized self-consistent model and other composite models. The water in coal-water slurry contains free water and bound water, and the bound water will form a coal particle-bound water composite phase with coal particles, and the coal-water slurry is regarded as a two-phase composite composed of the composite phase and the free water phase. In the drop zone, with the increase of coal particle concentration, the free water phase decreases, the composite phase remains basically unchanged, and the thermal conductivity of coal-water slurry decreases rapidly. In the constant zone, the amount of bound water in the composite phase decreases with further increase in coal particle concentration, but the thermal conductivity of the composite phase remains basically stable. The model prediction results agree well with the experimental data.

Purpose: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. Methods: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 − 25.42, p = 0.002), 2.85 (95% CI: 1.11 − 7.31, p = 0.030), 2.62 (95% CI: 1.12 − 6.13, p = 0.027), 2.44 (95% CI: 1.25 − 4.76, p = 0.009), and 1.5 (95% CI: 1.10 − 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Abstract In recent years, the combined pollution of PM2.5 and O3 in China, particularly in economically developed regions such as the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), has garnered significant attention due to its potential implications. This study systematically investigated the changes of PM2.5 and O3 and their associated human health effects in the GBA, utilizing observational data spanning from 2015 to 2019. The findings revealed a spatial trend indicating a gradual decrease in PM2.5 levels from the northwest to the southeast, while the spatial distribution of MDA8 O3 demonstrated an opposing pattern to that of PM2.5. The monthly fluctuations of PM2.5 and MDA8 O3 exhibited V-shaped and M-shaped patterns, respectively. Higher MDA8 O3 concentrations were observed in autumn, followed by summer and spring. Over the five-year period, PM2.5 concentrations exhibited a general decline, with an annual reduction rate of 1.7 μg m−3/year, while MDA8 O3 concentrations displayed an annual increase of 3.2 μg m−3. Among the GBA regions, Macao, Foshan, Guangzhou, and Jiangmen demonstrated notable decreases in PM2.5, whereas Jiangmen, Zhongshan, and Guangzhou experienced substantial increases in MDA8 O3 levels. Long-term exposure to PM2.5 in 2019 was associated with 21,113 (95% CI 4968–31,048) all-cause deaths (AD), 1333 (95% CI 762–1714) cardiovascular deaths (CD), and 1424 (95% CI 0–2848) respiratory deaths (RD), respectively, reflecting declines of 27.6%, 28.0%, and 28.4%, respectively, compared to 2015. Conversely, in 2019, estimated AD, CD, and RD attributable to O3 were 16,286 (95% CI 8143–32,572), 7321 (95% CI 2440–14,155), and 6314 (95% CI 0–13,576), respectively, representing increases of 45.9%, 46.2%, and 44.2% over 2015, respectively. Taken together, these findings underscored a shifting focus in air pollution control in the GBA, emphasizing the imperative for coordinated control strategies targeting both PM2.5 and O3.

The effects of different cooking methods (raw, microwave, steaming and frying) on the volatile components of Ctenopharyngodon idella were analyzed by gas chromatography-mass spectrometry, electronic nose technique and sensory evaluation. The results of gas chromatography-mass spectrometry showed that 78 volatiles were detected in 4 cooking methods, mainly olefin, alkanes, aldehydes, esters and other volatile compounds, and the number and content of components in frying methods were higher than those in other processing groups. The electronic nose and principal component analysis showed that, compared with raw fish, the volatiles of fish was closer between steaming and microwave, and fried one had a greater effect on the volatiles. The results of sensory evaluation showed that the fish smell in four treatments all had a certain fishy and grassy taste, but the fried one was mainly manifested in burnt and greasy taste. In addition, the special volatile compounds such as trans, trans-2,4-decenal, 2-furanaldehyde and 2-amyl furan produced during frying give the smell of roast meat, which could cover the off-odor such as fishy and grassy. In summary, the volatiles of Ctenopharyngodon idella were mainly aldehydes and esters, and compared with raw fish, frying had the greatest impact on the volatile components, which could better reduce the fishy off-flavor, the results would provide a theoretical basis for the development of deep processing technology for Ctenopharyngodon idella meat.

The different generations of bearing steel are designed to withstand high temperatures, quick speeds, and heavy loads and meet the requirements of aviation, aerospace, and advanced equipment production. In this study, three generation bearing systems (Si3N4/GCr15, Si3N4/M50, and Si3N4/CSS-42L) with pentaerythritol ester lubricants were selected to investigate their friction behavior and evolutionary mechanisms from room temperature to 350 °C. The results indicate that the coefficient of friction (COF) values for all three systems initially decreased and then increased as the temperature increased. The COF of Si3N4/GCr15 was not more than 0.170 when the temperature did not exceed 150 °C. Furthermore, the wear rate of Si3N4/M50 and Si3N4/CSS-42L are 2.67 × 10−4 mm3·N−1·m−1 and 2.04 × 10−4 mm3·N−1·m−1 at 260 °C, which are only 15.4% and 11.8% of Si3N4/GCr15. This discrepancy can be attributed to the formation of metal oxides on the worn surface of Si3N4/M50 and Si3N4/CSS-42L, and was easier to form on the worn surface of CSS-42L. Therefore, the applicable temperature range for GCr15 usually below 150 °C and for Si3N4/M50 and Si3N4/CSS-42L, it was from 150 to 260 °C. These results disclose the friction behavior and mechanism of these three generation bearing steel are different, and can be a guideline to choose proper bearing steel in future situation.

Constructed wetland systems have been widely used in China due to their advantages of good treatment effect, low cost and environmental friendliness. However, traditional constructed wetlands have challenges in application such as deactivation due to filler clogging, difficulty in filler replacement and low adaptability. To address the above problems, this research proposes a modular filler design constructed wetland based on the concept of assembly construction, which can quickly replace the clogged filler without destroying the overall structure of the wetland. Four commonly used fillers were selected and applied to the pilot system of the assembled constructed wetland in this study, in order to investigate the purification effect of the constructed wetland system with different filler module combinations (CW1, CW2, CW3) on the simulated wastewater. The results showed that the filler combination CW1 was the best for the removal of NH4+-N, and for TP and COD, CW2 has the best removal effect. Therefore, the assembled constructed wetland is adjustable and substantially reduces the maintenance cost, which provides technical guidance for its application in engineering. HIGHLIGHTS Proposed a pilot system for the prefabricated constructed wetland.; Explored the purification effects of different combinations of fillers.; Analyzed concentration changes of pollutants along the route.; Conducted cost analysis for replacing fill in two types of wetlands.;

Abstract Acute thrombosis secondary to atherosclerotic plaque rupture is the main cause of acute cardiac and cerebral ischemia. An animal model of unstable atherosclerotic plaques is highly important for investigating the mechanism of plaque rupture and thrombosis. However, current animal models involve complex operations, are costly, and have plaque morphologies that are different from those of humans. We aimed to establish a simple animal model of vulnerable plaques similar to those of humans. Rabbits were randomly divided into three groups. Group A was given a normal formula diet for 13 weeks. Group C underwent surgery on the intima of the right carotid artery with – 80 °C cryofluid-induced injury after 1 week of a high-fat diet and further feeding a 12-week high-fat diet. Group B underwent the same procedure as Group C but without the – 80 °C cryofluid. Serum lipid levels were detected via ELISA. The plaque morphology, stability and degree of stenosis were evaluated through hematoxylin–eosin (HE) staining, Masson trichrome staining, Elastica van Gieson staining (EVG), and oil red O staining. Macrophages and inflammatory factors in the plaques were assessed via immunohistochemical analysis. The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels in groups B and C were significantly greater than those in group A. No plaque formation was observed in group A. The plaques in group B were very small. In group C, obvious plaques were observed in the blood vessels, and the plaques exhibited a thin fibrous cap, a large lipid core, and partially visible neovascularization, which is consistent with the characteristics of vulnerable plaques. In the plaques of group C, a large number of macrophages were present, and matrix metalloproteinase 9 (MMP-9) and lectin-like oxidized LDL receptor 1 (LOX-1) were abundantly expressed. We successfully established a rabbit model of vulnerable carotid plaque similar to that of humans through the combination of cryofluid-induced endothelial injury and a high-fat diet, which is feasible and cost effective.

Abstract The traffic in developing countries presents its own specificity, notably due to the heterogeneous traffic and a weak-lane discipline. This leads to differences in driver behavior between these countries and developed countries. Knowing that the analysis of the drivers from developed countries leads the design of the majority of driver models, it is not surprising that the simulations performed using these models do not match the field data of the developing countries. This article presents a systematic review of the literature on modeling driving behaviors in the context of developing countries. The study focuses on the microsimulation approaches, and specifically on the multiagent paradigm, that are considered suitable for reproducing driving behaviors with accuracy. The major contributions from the recent literature are analyzed. Three major scientific challenges and related minor research directions are described.

Abstract In terms of the collaborative optimization of CO2 flooding for Enhanced Oil Recovery (EOR) and CO2 sequestration, previous studies have co-optimized both cumulative oil production and CO2 sequestration by various algorithms. However, these solutions fail to optimize the CO2 injection schemes for high-water cut oil reservoirs. This paper presents an optimization methodology for CO2 flooding and sequestration in high-water cut oil reservoirs. The production optimization was carried out by adjusting the injection and production rate. To solve the proposed objective functions, the simultaneous perturbation stochastic approximation (SPSA) algorithm is applied in this paper, and the CMG-GEM module is utilized to simulate the reservoir production performance. A typical high-water cut reservoir in the Shengli oilfield was used to verify the feasibility of the presented methodology. In this paper, the production performance and net present value (NPV) for continuous gas injection under different water cuts were analyzed. The optimal timing of transforming from water flooding to gas displacement for the high-water cut reservoir was optimized. In addition, the optimal water–gas ratios for Water-Alternating-Gas (WAG) flooding were determined. The sensitivity of NPV to gas injection price and carbon subsidy was analyzed. The results show that when the gas price is 0.178 $/m3 and the carbon subsidy is 0.0169 $/m3, the optimal timing of transforming from water flooding to gas injection should be earlier than the time when the water cut is 0.82. Through the combination of NPV, cumulative oil production rate, and CO2 sequestration volume for WAG flooding, the optimal WAG ratio should be 1:2. The presented method in this paper considers various economic indicators and can optimize CO2 flooding and sequestration in high-water cut oil reservoirs efficiently, which can provide some guidance for the design of CO2 flooding schemes in high-water cut oil reservoirs.

Abstract Dysregulated activation of Wnt/β-catenin signaling pathway is a frequent or common event during advanced progression of multiple cancers. With this signaling activation, it enhances their tumorigenic growth and facilitates metastasis and therapy resistance. Advances show that this signaling pathway can play dual regulatory roles in the control of cellular processes epithelial-mesenchymal transition (EMT) and cancer stemness in cancer progression. Aberrant activation of Wnt/β-catenin signaling pathway is shown to be common in prostate cancer and also castration-resistant prostate cancer (CRPC). However, the transcriptional regulators of this pathway in prostate cancer are still not well characterized. NURR1 (NR4A2) is an orphan nuclear receptor and plays an important role in the development of dopaminergic neurons. Previously, we have shown that NURR1 exhibits an upregulation in isolated prostate cancer stem-like cells (PCSCs) and a xenograft model of CRPC. In this study, we further confirmed that NURR1 exhibited an upregulation in prostate cancer and also enhanced expression in prostate cancer cell lines. Functional and molecular analyses showed that NURR1 could act to promote both in vitro (cancer stemness and EMT) and also in vivo oncogenic growth of prostate cancer cells (metastasis and castration resistance) via its direct transactivation of CTNNB1 (β-catenin) and activation of β-catenin to mediate the activation of Wnt/β-catenin signaling pathway. Moreover, we also demonstrated that NURR1 activity in prostate cancer cells could be modulated by small molecules, implicating that NURR1 could be a potential therapeutic target for advanced prostate cancer management.

Abstract The elevation gradient has long been known to be vital in shaping the structure and function of terrestrial ecosystems, but little is known about the elevation-dependent pattern of net CO2 uptake, denoted by net ecosystem productivity (NEP). Here, by analyzing data from 203 eddy covariance sites across China, we report a negative linear elevation-dependent pattern of NEP, collectively shaped by varying hydrothermal factors, nutrient supply, and ecosystem types. Furthermore, the NEP shows a higher temperature sensitivity in high-elevation environments (3000–5000 m) compared with the lower-elevation environments (

Abstract Site selection for building solar farms in deserts is crucial and must consider the dune threats associated with sand flux, such as sand burial and dust contamination. Understanding changes in sand flux can optimize the site selection of desert solar farms. Here we use the ERA5-Land hourly wind data with 0.1° × 0.1° resolution to calculate the yearly sand flux from 1950 to 2022. The mean of sand flux is used to score the suitability of global deserts for building solar farms. We find that the majority of global deserts have low flux potential (≤ 40 m3 m-1 yr-1) and resultant flux potential (≤ 2.0 m3 m-1 yr-1) for the period 1950–2022. The scoring result demonstrates that global deserts have obvious patchy distribution of site suitability for building solar farms. Our study contributes to optimizing the site selection of desert solar farms, which aligns with the United Nations sustainability development goals for achieving affordable and clean energy target by 2030.