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Abstract Background Fractures are the prevalent traumatic conditions encountered in orthopedic practices. The rising incidence of fractures has emerged as a pressing global health concern. Although the majority of individuals with fractures experience complete recovery of bone structure and function, approximately 10% of those with fractures exhibit delayed fracture healing (DFH). The objective of this investigation was to explore the function and underlying mechanisms of LINC00941 in the advancement of DFH, as well as its involvement in the regulation of osteoblastic differentiation by regulating the miR-335-5p/KAT7 axis. Methods The expression levels of LINC00941, miR-335-5p, KAT7 and osteoblast differentiation-related markers were assessed using RT-qPCR. The proliferation of MC3T3-E1 cells was evaluated through the CCK-8 assay, and cell apoptosis was analyzed via flow cytometry. The targeted regulatory relationships between LINC00941 and miR-335-5p, as well as between miR-335-5p and KAT7 were verified by a dual-luciferase reporter gene assay. Result The expression of LINC00941 was significantly up regulated, while miR-335-5p exhibited a notable downregulation in DFH patients, both of LINC00941 and miR-335-5p have been identified as potential predicted markers for DFH. Furthermore, LINC00941 has been demonstrated to inhibit osteoblast proliferation, promote apoptosis, and suppress osteoblast differentiation through the regulation of the miR-335-5p/KAT7 axis. Conclusion LINC00941/ miR-335-5p/KAT7 axis may be a therapeutic target for DFH.

Abstract Background The heterogeneity of cognitive impairments in schizophrenia has been widely observed. However, reliable cognitive boundaries to differentiate the subgroups remain elusive. The key challenge for cognitive subtyping is applying an integrated and standardized cognitive assessment and understanding the subgroup-specific neurobiological mechanisms. The present study endeavors to explore cognitive subgroups and identify their morphological features. Methods A total of 920 schizophrenia patients and 169 healthy controls were recruited. MATRICS Consensus Cognitive Battery was applied to assess cognitive performance and recognize cognitive subgroups through latent profile and latent transition analysis. Cortical thickness and gray matter volume were employed for the morphological features across subgroups. Results Four reproducible cognitive subgroups were identified, including multidomain-intact, executive-preserved, executive-deteriorated, and multidomain-deteriorated subgroup. After 12 weeks of follow-up, the cognitive characteristics of three out of the four subgroups kept stability, except for multidomain-deteriorated subgroup in which 48.8% of patients with improved cognition transited into the executive-deteriorated subgroup. Across subgroups, significant gradient features of brain structure were exhibited in fronto-temporal regions, hippocampus, and insula. Compared to healthy controls, multidomain-intact subgroup showed the most intact cognition and morphology, and multidomain-deteriorated subgroup with youngest age showed morphological decline in extensive regions. The remaining two subgroups showed intermediate cognitive performance, but could be distinguished by executive function and morphological differences in posterior cingulate cortex. Conclusions Our study provides novel insights into the heterogeneity of cognitive impairments in schizophrenia and the morphological features from cross-sectional and longitudinal levels, which could advance our understanding of complex cognition-morphology relationships and guide personalized interventions.

Abstract A non-invasive, accessible and effective biomarker is critical to the diagnosis, monitoring and treatment of age-related cognitive decline. Recent work has suggested a strong association between auditory brainstem responses (ABR) and cognitive function in aging macaques. Here we show in 118 human participants (66 females; age range=18-92 years; hearing loss = -5 to 70 dB HL) that cognition is associated with both age and hearing level, but this triad relationship is mainly driven by the age factor. After adjusting for age, cognition is still significantly associated with both the ABR wave V amplitude (B, 0.110, 95% CI, 0.018– 0.202; p = 0.020) and latency (B, -0.101, 95% CI, -0.186– -0.016; p = 0.021). Importantly, this age-adjusted ABR-cognition association is primarily driven by older individuals and language-dependent cognitive functions. We also perform the area under the curve (AUC) of the receiver-operating-characteristic analysis and find that the ABR wave V amplitude is best for detecting good cognitive performers (AUC = 0.96) whereas the wave V latency is best for detecting poor ones (AUC = 0.86). The present result not only confirms the previous animal work in humans but also shows the clinical potential of using auditory brainstem responses to improve diagnosis and treatment of age-related cognitive decline.

Abstract Atopic dermatitis (AD) is an immune-related skin disease with a genetic background. Numerous loci have been identified associated with AD to better comprehend its complicated genetic mechanisms by genome‑wide association studies (GWASs). However, current studies reveal the underlying mechanisms of these loci in the pathogenesis of AD inadequately. Therefore, we integrated the GWAS statistics of AD with plasma proteins to explore candidate proteins correlated with the pathogenesis of AD based on protein-centered omics studies. Herein, we adopted the updated AD GWAS statistics (N = 864,982) and the dataset of plasma protein quantitative trait loci (pQTLs), comprising 1,348 proteins from individuals of European descent. We first conducted the AD-related proteome-wide association studies (PWASs) (N = 7,213) by integrating pQTLs with the AD GWAS statistics and identified twenty-six significant plasma proteins by PWAS (FDR

Cochlear implantation (CI) offers a dependable treatment for sensorineural hearing loss, with precision electroacoustic stimulation parameters showing great potential in improving auditory outcomes in CI patients. Here, we report the attachment of MXene into CI systems which effectively mimic the neural electrode interface due to MXene's excellent electrical conductivity and biocompatibility. Low-frequency short-term biphasic electrical pulses emitted by the MXenes-based CI promoted the outgrowth of spiral ganglion neuron (SGN) neurites and growth cones, substantially boosting the calcium activity in SGNs. This study lays a theoretical foundation for the precision medicine approaches in CI patient care, and informs the selection of materials for cochlear implant electrode materials in the future.

Abstract Multiple myeloma (MM) is an incurable disease characterized by the abnormal expansion of plasma cells in the bone marrow (BM). Numerous studies have shown that BM tumor cells can influence the tumor microenvironment (TME) through communication with extracellular vesicle circular RNAs (circRNAs), a type of noncoding RNA. Our study revealed that a circular RNA, circRFWD2 (hsa_circ_0015361), is expressed by MM cells and translated into a new protein, circRFWD2_369aa. We found that elevated levels of circRFWD2_369aa in MM peripheral blood samples were closely associated with poor outcomes in MM patients. Further investigation revealed that circRFWD2 promoted the degradation of p27 through the ubiquitination pathway, leading to increased proliferation of MM cells. We also confirmed the interaction between circRFWD2 and its downstream genes DDB1 and CUL4A, indicating that circRFWD2 could form an E3 ligase complex with other genes to mediate the ubiquitination of p27. Notably, the protein translated by a circular RNA of RFWD2 can also function as an E3 ligase. Our study highlights the potential of circRFWD2 as a biomarker for MM, which may improve the sensitivity and specificity of diagnosis and efficacy analyses.

Abstract Purpose The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P

Abstract With the increasing prevalence of diabetes mellitus worldwide, type 2 diabetes mellitus (T2D) combined with cognitive impairment and aging has become one of the common and important complications of diabetes mellitus, which seriously affects the quality of life of the patients, and imposes a heavy burden on the patients’ families and the society. Currently, there are no special measures for the treatment of cognitive impairment and aging in type 2 diabetes mellitus. Therefore, the search for potential biological markers of type 2 diabetes mellitus combined with cognitive impairment and aging is of great significance for future precisive treatment. We downloaded three gene expression datasets from the GEO database: GSE161355 (related to T2D with cognitive impairment and aging), GSE122063, and GSE5281 (related to Alzheimer’s disease). Differentially expressed genes (DEGs) were identified, followed by gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed using the STRING database, and the top 15 hub genes were identified using the CytoHubba plugin in Cytoscape. Core genes were ultimately determined using three machine learning methods: LASSO regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Linear Discriminant Analysis (LDA). The diagnostic performance of these genes was assessed using ROC curve analysis and validated in an independent dataset (GSE5281). Regulatory genes related to ferroptosis were screened from the FerrDb database, and their biological functions were further explored through GO and KEGG enrichment analyses. Finally, the CIBERSORT algorithm was used to analyze immune cell infiltration, and the correlation between core genes and immune cell infiltration levels was calculated, leading to the construction of an mRNA-miRNA regulatory network. In the GSE161355 and GSE122063 datasets, 217 common DEGs were identified. GSEA analysis revealed their enrichment in the PI3K-PLC-TRK signaling pathway, TP53 regulation of metabolic genes pathway, Notch signaling pathway, among others. PPI network analysis identified 15 candidate core genes, and further selection using LASSO, LDA, and SVM-RFE machine learning algorithms resulted in 6 core genes: BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1. ROC curve analysis indicated that these genes had good diagnostic performance in the GSE161355 dataset, with TP53 and IL1B achieving an AUC of 0.9, indicating the highest predictive accuracy. BCL6, HSP90AA1, CRYAB, and DNAJB1 also had AUCs greater than 0.8, demonstrating moderate predictive accuracy. Validation in the independent dataset GSE5281 showed that these core genes also had good diagnostic performance in Alzheimer’s disease samples (AUC > 0.6). Ferroptosis-related analysis revealed that IL1B and TP53 play significant roles in apoptosis and immune response. Immune cell infiltration analysis showed that IL1B is significantly positively correlated with infiltration levels of monocytes and NK cells, while TP53 is significantly negatively correlated with infiltration levels of follicular helper T cells. The construction of the miRNA-mRNA regulatory network suggested that miR-150a-5p might play a key role in the regulation of T2D-associated cognitive impairment and aging by TP53. This study, by integrating bioinformatics and machine learning methods, identified BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1 as potential diagnostic biomarkers for T2D with cognitive impairment and aging, with a particular emphasis on the significance of TP53 and IL1B in immune cell infiltration. These findings not only enhance our understanding of the molecular mechanisms linking type 2 diabetes to cognitive impairment and aging, providing new targets for early diagnosis and treatment, but also offer new directions and targets for basic research.

Abstract PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, the efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into their action sites. Herein, based on the ultra-pH-sensitive and enzyme-sensitive nanotechnology, a type of polymer PROTAC conjugated and pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following the construction of the PROTAC for Cyclin-dependent kinase 4 and 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds to many treatments even immune checkpoint blockades was selected as the tumor model in this study. As a result, PSRNs were found to maintain nanostructure (40 nm) in circulation and efficiently accumulated in tumors via enhanced permeation and retention effect. Then, they were dissociated into unimers (

Abstract Tumour detection with high selectivity and sensitivity is crucial for delineating tumour margins and identifying metastatic foci during image-guided surgery. Optical nanoprobes with preferential tumour accumulation is often limited by inefficient amplification of biological signals. Here, we report the design of a library of hydrophobic core-tunable ultra-pH-sensitive nanoprobes (HUNPs) for orthogonally amplifying tumour microenvironmental signals on multiple tumour models. We find that tuning the hydrophobicity of nanoparticle core composition with non-ionizable monomers can enhance cellular association of HUNPs by more than ten-fold, resulting in a high cellular internalization efficiency of HUNPs with up to 50% in tumours. Combining high tumour accumulation and high cell internalization efficiency, HUNPs show orthogonally amplified fluorescence signals, permitting the precise locating and delineating margins between malignant lesions and normal tissues with high contrast-to-noise ratio and resolution. Our study provides key strategies to design nanomedicines with high intracellular bioavailability for cancer detection, drug/gene delivery, and therapy.

Abstract This study aimed to investigate the advantages and applications of machine learning models in predicting the risk of allergic rhinitis (AR) in children aged 2–8, compared to traditional logistic regression. The study analyzed questionnaire data from 7131 children aged 2–8, which was randomly divided into training, validation, and testing sets in a ratio of 55:15:30, repeated 100 times. Predictor variables included parental allergy, medical history during the child’s first year (cfy), and early life environmental factors. The time of first onset of AR was restricted to after the age of 1 year to establish a clear temporal relationship between the predictor variables and the outcome. Feature engineering utilized the chi-square test and the Boruta algorithm, refining the dataset for analysis. The construction utilized Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and Extreme Gradient Boosting Tree (XGBoost) as the models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), and the optimal decision threshold was determined by weighing multiple metrics on the validation sets and reporting results on the testing set. Additionally, the strengths and limitations of the different models were comprehensively analyzed by stratifying gender, mode of birth, and age subgroups, as well as by varying the number of predictor variables. Furthermore, methods such as Shapley additive explanations (SHAP) and purity of node partition in Random Forest were employed to assess feature importance, along with exploring model stability through alterations in the number of features. In this study, 7131 children aged 2–8 were analyzed, with 524 (7.35%) diagnosed with AR, with an onset age ranging from 2 to 8 years. Optimal parameters were refined using the validation set, and a rigorous process of 100 random divisions and repeated training ensured robust evaluation of the models on the testing set. The model construction involved incorporating fourteen variables, including the history of allergy-related diseases during the child’s first year, familial genetic factors, and early-life indoor environmental factors. The performance of LR, SVM, RF, and XGBoost on the unstratified data test set was 0.715 (standard deviation = 0.023), 0.723 (0.022), 0.747 (0.015), and 0.733 (0.019), respectively; the performance of each model was stable on the stratified data, and the RF performance was significantly better than that of LR (paired samples t-test: p

ObjectiveThis study aims to investigate the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and sex hormones and sex hormone-binding globulin (SHBG) in boys with obesity.MethodsRetrospective analysis of metabolic indicators and sex hormone levels in boys with obesity who sought medical attention at the First People’s Hospital of Lianyungang City from January 2020 to December 2023. Based on abdominal ultrasound results, they were categorized into a simple obesity group and MAFLD group, and differences between the two groups were compared. Utilizing logistic regression analysis to explore the risk factors for developing MAFLD, and through the construction of Receiver Operating Characteristic (ROC) curves, conducting a preliminary assessment of the diagnostic value for MAFLD.ResultsA total of 155 male children with obesity were included in the study, mean age of 11.07 ± 1.53 years. Children in the MAFLD group had higher levels of height[(159.49 ± 12.73)cm vs.(155.55 ± 10.50)cm], weight[(82.32 ± 18.75)kg vs.(68.28 ± 15.00)kg], BMI[(32.08 ± 4.49)kg/m2 vs.(27.85 ± 4.21)kg/m2],fasting insulin[33.42(24.07,43.93)uIU/ml vs.23.91(15.72,31.52)uIU/ml],HOMA-IR[7.27(5.26,10.71) vs.4.87(3.27,6.86)],fastingC-peptide[1409.00(1175.00,1668.00)pmol/L vs.1020.00(849.05,1303.00)pmol/L], WBC[(7.85 ± 1.80)×109/L vs.(7.15 ± 1.42)×109/L], HbA1c[5.40(5.30,5.70)% vs.(5.30(5.20,5.60)%],ALT[48.00(27.00,80.00)U/L vs.19.00(15.00,26.50)U/L], and AST[31.00(24.00,60.00)U/L vs.21.00(18.50, 26.00)U/L] compared to the simple obesity group (P

Abstract Multiple myeloma (MM) is a cancer of plasma cells caused by abnormal gene expression and interactions within the bone marrow (BM) niche. The BM environment significantly influences the progression of MM. Celastrol, a natural compound derived from traditional Chinese medicine, exhibits significant anticancer effects. This study aimed to identify specific targets of celastrol and develop more effective and less toxic treatment options for MM. Celastrol is used as a probe to determine its specific target, pyridoxine‐5′‐phosphate oxidase (PNPO). Increased levels of PNPO are associated with poor outcomes in MM patients, and PNPO promotes MM cell proliferation and induces osteoclast differentiation through exosomes. Mechanistically, PNPO oxidizes disheveled 3M282 (DVL3), leading to abnormal activation of the Wnt/β‐catenin pathway. Based on the critical sites of PNPOR95/K117, Eltrombopag is identified as a potential therapeutic candidate for MM. In addition, the experiments showed its efficacy in mouse models. Eltrombopag inhibited the growth of MM cells and reduced bone lesions by disrupting the interaction between PNPO and DVL3, as supported by preliminary clinical trials. The study highlights the importance of PNPO as a high‐risk gene in the development of MM and suggests that Eltrombopag may be a promising treatment option.

Microplastics (MPs) have been identified in various human tissues and organs. This study aims to evaluate the presence of MPs in human follicular fluid (hFF) and their potential impact on oocyte maturation. Laser direct infrared spectroscopy of 19 hFF samples identified 7956 particles, including 1739 microplastics (21.9 %) from 30 types. Of these, 923 particles had matching degrees > 0.8, and 7033 had matching degrees between 0.65 and 0.8. The most abundant MPs were Chlorinated Polyethylene (CPE), Fluorosilicone rubber, Polyvinyl chloride (PVC), Butadiene rubber (BR), and Styrene-butadiene-styrene (SBS), with diameters ranging from 20 to 100 μm. Five random samples were analyzed by pyrolysis-gas chromatography-mass spectrometry, which detected four types of microplastics—Polyethylene (PE), Polypropylene (PP), Polystyrene (PS), and PVC—at varying concentrations. PE was the most abundant (22.284 mg/kg), followed by PVC (1.061 mg/kg), PP (0.837 mg/kg), and PS (0.600 mg/kg). Based on the diameter and concentration ranges of MPs in hFF, we used seven types of fluorescence-labeled MP beads—PE, PVC, PP, PS, CPE, Polymethylmethacrylate (PMMA), and Polytetrafluoroethylene (PTFE)—to assess their impact on mouse oocyte in vitro maturation. The results showed that smaller MP beads (e.g., 50 μm PE) were more likely to penetrate the zona pellucida and enter the oocyte, while larger beads (e.g., 500 nm PMMA) tended to adhere to the zona and remain outside the oocyte. All seven types of MP beads hindered oocyte maturation, resulting in varying reductions in maturation rates compared to the control group. Our findings suggest that MPs contaminate hFF and may impair oocyte maturation.

Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine. Phase III involved 320 patients with similar groupings, including a placebo group. The primary outcome was the resting summed pain intensity difference over 24 hours (rSPID24). Secondary outcomes included rSPID and active-SPID (aSPID) at other time points, rescue analgesia received, cumulative dose of analgesics, and satisfaction scores. Safety endpoints included treatment-emergent adverse events (TEAEs) and AE of special interest (AESIs). In both phases, SHR8554 demonstrated significant analgesic efficacy. In Phase II, the least squares (LS) mean differences in rSPID24 compared to morphine for the 0.05 mg,0.1 mg, and 0.2 mg SHR8554 groups were 16.8 (p = 0.01), 7.4 (p = 0.27), and 0.2 (p = 0.98), respectively. Phase III confirmed the efficacy of the 0.05 mg and 0.1 mg SHR8554 doses compared to placebo, with LS mean differences of 15.4 (p = 0.0001) and −19.8 (p

Background: The influence of air pollution on osteoarthritis (OA) remains underexplored. Methods: We conducted a prospective cohort study in the UK Biobank, estimating exposure levels of particulate matter (PM2.5, PM10, PM2.5–10), nitrogen oxides (NO2, NOx), and air pollutants exposure score (APES). Cox models assessed associations between air pollution exposure and OA incidence, joint replacement, and survival. Additionally, using genome-wide association statistics, we examined the potential causal associations between air pollution-related DNA methylation (DNAm) and OA risk. Gene-environment interaction analyses were conducted to explore the potential modification effect of DNA methylation-related genetic variants on the impact of air pollution on OA risk. Results: Individual exposure to each air pollutant was associated with an increased risk of developing OA, but not with progression from OA to joint replacement. For APES, the hazard ratio for incident OA was 1.09 (95 % CI = 1.04–1.13), and the hazard ratio of progression from OA to death was 1.16 (95 % CI = 1.00–1.35) in the highest quartile group compared to the lowest quartile group. Moreover, genetically predicted methylation at the PM2.5-related CpG site cg04027612 near the GDF5 gene was associated with a lower risk of OA. A potential epigenetic modification effect of cg04027612 near GDF5 on OA risk was observed. Conclusion: Long-term exposure to air pollution was associated with an increased risk of OA in the population and poorer survival outcomes for OA patients, with epigenetic changes in GDF5 potentially playing a role in the underlying mechanisms.

PurposeThe aim of the present study was to investigate the cardiovascular mortality risk among lung cancer patients compared to the general population.MethodsUsing data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, we conducted a population-based cohort study including 278,418 lung cancer patients aged over 30 years between 1 January 1990 and 31 December 2020 as well as the general population. Poisson regression was employed to calculate incidence rate ratios (IRRs) for cardiovascular mortality.ResultsPatients exhibited a significantly higher IRR of cardiovascular mortality risk compared to the general population [IRR 1.74, 95% confidence interval (CI) 1.71–1.77]. The risk was most pronounced in patients aged 30–79 years (IRR 2.61, 95% CI 2.55–2.66), peaking at ages 30–34 years (IRR 48.93, 95% CI 21.98–108.92). Elevated cardiovascular mortality risks were observed across all subgroups, including diseases of the heart (IRR 1.79, 95% CI 1.75–1.82), cerebrovascular diseases (IRR 1.52, 95% CI 1.45–1.59), and other cardiovascular diseases (IRR 1.78, 95% CI 1.67–1.90). The first month after diagnosis presented the highest risk for patients aged 30–79 years (IRR 12.08, 95% CI 11.49–12.70) and ≥80 years (IRR 4.03, 95% CI 3.70–4.39). Clinical characteristics significantly modified cardiovascular mortality.ConclusionsIntegrating cardiovascular disease monitoring and proactive management into lung cancer treatment protocols is essential to the improvement of overall survival and quality of life for lung cancer patients, particularly those who were young or with advanced tumor stage.

ObjectivesThe increasing prevalence of obesity underscores the need to explore its impact on assisted reproductive technology (ART) outcomes. This study aims to evaluate the association between visceral fat area (VFA), measured by bioelectrical impedance analysis (BIA), and pregnancy outcomes following frozen embryo transfer (FET).MethodsIn this retrospective clinical study, the data of 1,510 patients who underwent FET between April 2022 and April 2023 were analyzed. The VFA was measured by BIA, and patients were categorized into low and high VFA groups based on a threshold of 65 cm². Pregnancy outcomes were compared between the two groups. Univariable and multivariate logistic regression analyses, along with restricted cubic spline (RCS) modeling, were used to adjust for age, body mass index (BMI), and basal estradiol (E2) levels to determine the relationship between VFA and FET outcomes.ResultsThere were significant differences in baseline characteristics and outcomes between the two groups. The high VFA group was characterized by older age and a lower basal estradiol (E2) level. The biochemical pregnancy rate, implantation rate, clinical pregnancy rate (CPR), and live birth rate (LBR) were significantly lower in the high VFA group. Logistic regression revealed a significant negative correlation between the high VFA group and both CPR and LBR. The RCS model demonstrated that the VFA was nonlinearly correlated with CPR and LBR. Subgroup analysis showed that among individuals under 35 years of age or with a BMI < 24, high VFA was significantly associated with poorer CPR and LBR.ConclusionsHigh VFA is associated with poorer pregnancy outcomes after FET in female patients with infertility, with both CPR and LBR decreasing as VFA increases. Clinicians should consider VFA as an important reference for targeted fat management interventions to optimize reproductive success, especially when VFA exceeds 65 cm².

IntroductionGastrodiae Rhizoma (referred to Tianma in Chinese), the dried tuber of Gastrodia elata Bl. (Orchidaceae), is utilized as a medicine-food homology product. Sulfur fumigation is commonly employed in the processing of Gastrodiae Rhizoma (GR). Polysaccharides are a crucial active substance produced in GR, yet the impacts of sulfur fumigation on them remain unelucidated.MethodsThis study aimed to optimize the hot water extraction conditions of polysaccharides from sulfur-fumigated GR (SGCPs) and nonsulfur-fumigated GR (NGCPs). The research explored the effects of sulfur fumigation on the structure and antioxidant activity of GR polysaccharides.Results and discussionThe results showed that the optimal extraction conditions for SGCPs and NGCPs were 67°C for 31 min with a liquid-to-material ratio of 15 mL/g and 64°C for 32 min with a liquid-to-material ratio of 17 mL/g, respectively. Compared with NGCPs, SGCPs exhibited significantly reduced DPPH radical, hydroxyl radical, ABTS+ radical scavenging activity, and Fe2+ chelating ability. Moreover, both NGCPs and SGCPs offered significant protective effects against H2O2−induced oxidative damage in RAW264.7 cells, but the protective effect of SGCPs was significantly lower than that of NGCPs. NMR analyses revealed that the main chain connections of SGCP3 and NGCP3 were both →4)-α-D-Glcp-(1→, and sulfur fumigation increased the number of repeating unit structures →4)-D-Glcp-(1 → in GR polysaccharides. SGCP3 and NGCP3 had the same monosaccharides composition but different molar ratios, with molecular weights of 727,650 and 39,991 Da, respectively. In general, sulfur fumigation reduced the antioxidant activities of GR polysaccharides by altering their structure and composition.

Background Endometriosis (EM) is a major cause of infertility, but the pathogenesis and mechanisms are not yet fully elucidated. MiR-19b-3p is involved in many diseases, but its functional role in EM-associated infertility remains unexplored. This study aimed to examine miR-19b-3p abundance and IGF1 concentration in cumulus cells (CCs) and follicular fluid of EM-associated infertility patients, and to investigate the potential role of miR-19b-3p in KGN cells by identifying its target and elucidating the underlying mechanisms.Results The results from the case-control study indicated that, compared to the control group consisting of patients with tubal infertility, patients with EM-associated infertility exhibited a lower percentage of mature oocytes. MiR-19b-3p level was elevated in CCs from EM-associated infertility patients. IGF1 was identified as a direct target of miR-19b-3p and was negatively regulated by miR-19b-3p in KGN cells. Overexpression of miR-19b-3p significantly inhibited cell viability and proliferation, promoted apoptosis, and arrested the cell cycle at G0/G1 phase in KGN cells. The effects of miR-19b-3p were reversed by co-transfection of IGF1, and the biological effects of miR-19b-3p in KGN cells were mediated by IGF1. Additionally, miR-19b-3p targeted IGF1 to down-regulate AKT phosphorylation and participate in the apoptotic pathway in KGN cells.Conclusions This study demonstrates that miR-19b-3p level is elevated in CCs and IGF1 concentration is decreased in follicular fluid in patients with EM-associated infertility. MiR-19b-3p regulates the biological effects of KGN cells by targeting IGF1.

Objective The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique—“the medially pedicled IPFP flap”—for reducing postoperative pain, wound complications, and improving functional recovery after TKA. Methods A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C‐reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow‐up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t‐tests were used to compare continuous data and chi‐squared tests were used to compare categorical data between groups. Results Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p

Abstract The resistance of cancer cells to treatment significantly impedes the success of therapy, leading to the recurrence of various types of cancers. Understanding the specific mechanisms of therapy resistance may offer novel approaches for alleviating drug resistance in cancer. Recent research has shown a reciprocal relationship between circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification, and their interaction can affect the resistance and sensitivity of cancer therapy. This review aims to summarize the latest developments in the m6A modification of circRNAs and their importance in regulating therapy resistance in cancer. Furthermore, we explore their mutual interaction and exact mechanisms and provide insights into potential future approaches for reversing cancer resistance.

Abstract Purpose To investigate the correlation between whole eye movement (WEM) parameters measured using Corvis ST and axial length (AL) to explore whether AL affects WEMs. Methods This single-center, cross-sectional study included data from healthy subjects and patients preparing for refractive surgery at the Qingdao Eye Hospital of Shandong First Medical University. Data were collected from July 2021 to April 2022. We first determined the correlations of WEMs at the time of corneal first applanation (A1_WEM), highest concavity (HC_WEM), and second applanation (A2_WEM), as well as the maximum value of WEM (WEM_Max) with AL. Subsequently, we established a series of regression models to analyze the relationships between different WEM values and AL. Results AL was negatively correlated with HC_WEM, A2_WEM, and WEM_Max (r = − 0.28, − 0.23, and − 0.22, respectively; P

Abstract Purpose This study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing. Methods A retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes. Results Demographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4. Conclusion For patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

AIM: To determine the factors related to preoperative ocular characters that are predictive of insufficient vault (

Abstract Background Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. Methods Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. Results Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. Conclusions These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. Trial registration ClinicalTrials.gov NCT03451734.

Abstract Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.

Abstract The term “geographical synthetic thinking” is taken from the latest Chinese version of the “Geography Curriculum Standards” (General High School 2017 edition, Compulsory Education 2022 edition) and is one of the four core competencies prioritized in the teaching of geography at the secondary-school level. This study proposes that using geographic subject mind maps improves students’ geographical synthetic thinking and develops a set of geographic subject mind map (GSMM) drawing standards for teachers and matching standards and suggestions for teaching applications. Seven geography teachers and their students from eight class sections in seven provinces and cities in China were recruited to participate in the study. The teachers taught students how to use geographic subject mind maps designed to develop students’ geographical synthetic thinking in the geography classroom. After 4–5 experimental lessons, the geographical synthetic thinking level of the 267 valid student participants showed a significant improvement, with a statistically significant difference between pretest and posttest scores. The teachers’ level of application of geographic subject mind maps in teaching was significantly and positively correlated with the students’ improvements in geographical synthetic thinking, demonstrating that the standardized use of geographic subject mind maps in accordance with teaching application standards can effectively improve students’ geographical synthetic thinking levels.

Abstract Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein–Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM–receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P

Osteoarthritis (OA) is a chronic joint disease affecting millions of adults worldwide, characterized by degeneration of articular cartilage. Many environmental risk factors contribute to OA development. Benzophenone-3 (BP-3), a commonly used ultraviolet filter in personal care products, has been positively associated with OA risk. However, it remains unclear whether and how BP-3 induces toxic effects on articular chondrocytes and promote OA development. This study aims to investigate the damage of BP-3 at environmentally relevant concentrations to human chondrocytes, as well as potential mechanisms linking BP-3 with injury of chondrocytes. Notably, BP-3 significantly inhibited cell viability, induced apoptosis, and up-regulated matrix metalloproteinase (MMP) 1 and 13 which mediated cartilage degradation in C28/I2 human normal chondrocytes. Moreover, the function of mitochondria was impaired and oxidative stress occurred in BP-3 exposure groups, evidenced by elevation of reactive oxygen species (ROS) generation, reduction of mitochondrial membrane potential, decrease of ATP production and inhibition of mitochondrial respiratory chain complex I, II, III and IV. Meanwhile, BP-3 caused mitochondrial cristae vague and formation of autophagosomes. PTEN induced putative kinase 1/E3 ubiquitin protein ligase (PINK1/Parkin) pathway was also activated by BP-3. Addition of autophagy inhibitor, 3-Methyladenine (3-MA), suppressed PINK1/Parkin-mediated mitophagy, but increased BP-3-induced expression of MMP1 and 13, as well as exacerbated BP-3-induced apoptosis, suggesting mitophagy may exert a chondroprotective effect and partially alleviate apoptosis induced by this compound. In brief, BP-3 exposure may increase OA risk via inducing apoptosis and increasing breakdown of extracellular matrix in chondrocytes, and mitochondrial dysfunction and mitophagy may play a crucial role in the mechanisms of BP-3-induced toxicity to articular chondrocytes.

Two-component room temperature vulcanizing silicone adhesive RTV566 with a lower elastic modulus has been widely used in precision optomechanical products such as remote sensors and aerospace infrared cameras. However, the silicone adhesive is of poor manufacturability due to its extremely high viscosity, and the bonded joint usually exhibits low bonding strength and requires a long curing time. This paper investigates a way to improve both the adhesion strength and curing efficiency of Invar alloy and optical glass with RTV566 through single-lap experiments. It is found that adding small amounts of acetone and water can significantly reduce the viscosity, enhance the bonding strength, and shorten the curing time. The viscosity can be reduced by 63.4 % and the bonding strength can be improved by 136.4 % with the weight ratio of adhesive to acetone being 20:2. Moreover, a little amount of water in the weight ratio of 100:10:0.1 (adhesive: acetone: water) can shorten the curing time from 7 days to 4 days without harms to the bonding strength and elastic modulus. As to the mechanism, the silicone adhesive can be dissolved by acetone and its sulfuration reaction can be enhanced by water, resulting in good manufacturability and high curing efficiency. This work contributes a novel and easy-to-use method to greatly improve the performances of the bonding process of precision optical structures.

ABSTRACT: The current study investigated the effects of dietary crude protein (CP) level on the liver lipid metabolism, gut microbiota, and bile acids (BA) profiles of growing pullets. Roman growing pullets (N = 180, 13-wk-old) were divided into 3 treatments groups with 6 replicates in each group and 10 hens in each replicate and provided 3 different dietary CP level diet treatments. The diet treatments included: a high-protein diet (15.5% CP, HP group), a medium-protein diet (14.5% CP, MP group), and a low-protein diet (13.5% CP, LP group). Compared with HP group, LP group significantly increased the lipid contents in the body (such as Breast intramuscular fat [BIMF], Leg intramuscular fat [LIMF], Percentage of abdominal fat [PAF], liver triglyceride [TG] and liver cholesterol [TC]), and the lipid metabolism-related parameters in serum (such as cholesterol (TC), high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low density lipoprotein [VLDL]), and the mRNA expression of lipid metabolism-related genes (such as fatty acid synthase [FAS], CCAAT/enhancer binding protein β [C/EBPβ], and fatty acid translocase [FAT/CD6]) (P < 0.05). In addition, LP group significantly reduced the contents of lithocholic acid (LCA), isoLCA, and ursodesoxycholic acid (UDCA), and increased the deoxycholic acid (DCA) content compared with HP group (P < 0.05). The effects of LCA on lipid deposition were confirmed in chicken preadipocyte cell line (CPI), in which LCA supplementation significantly decreased the relative expression of PPARγ, FAS, acyl-CoA carboxylase (ACC) and SREBP-1c (P < 0.05). Correlation analysis further revealed a significant association between BA profiles and lipid metabolism-related parameters. Furthermore, 16S rRNA gene sequencing indicated that dietary protein level can significantly affect the richness, diversity, and composition of cecal microbiota in growing pullets. LP group significantly increased the abundance of Bacteroidetes and significantly decreased the abundance of Firmicutesa compared with the HP group. In summary, low protein diet in growing pullets influence the liver lipid metabolism through changing the gut microbiota and liver BA metabolism.

Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions.

BackgroundMorganella morganii is an emerging nosocomial opportunistic pathogen with increasing multidrug resistance. Antibiotic resistance, driven primarily by the horizontal transfer of resistance genes, has become a global health crisis. Integrons, mobile genetic elements, are now understood to facilitate the transfer of these genes, contributing to the rapid proliferation of resistant strains. Understanding the regulatory role of integrons in drug resistance gene expression is crucial for developing novel strategies to combat this pressing public health issue.ObjectiveTo investigate the distribution of promoter types in the variable regions of class 1 integrons isolated from clinical isolates of M. morganii and their regulatory role in the expression of downstream drug resistance gene cassettes.MethodsNinety seven clinical isolates of M. morganii were screened for the presence of class 1 integrons (intI1) using polymerase chain reaction (PCR). Gene cassettes within the variable regions of positive isolates were characterized, and the gene cassette promoter Pc variants and downstream auxiliary promoter P2 were identified. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was employed for homology analysis. Recombinant plasmids containing different variable region promoters and gene cassettes were constructed to evaluate drug resistance genes and integrase (intI1) expression levels using reverse transcription-quantitative PCR (RT-qPCR) and antimicrobial susceptibility testing.ResultsOf the clinical isolates, 28.9% (n = 28/97) were positive for class 1 integrons. 24.7% (n = 24/97) of these isolates carried gene cassettes encoding resistance to aminoglycosides and trimethoprim. Three Pc promoter types (PcH1, PcS, and PcW) were identified, while all P2 promoters were inactive with a 14-base pair spacing between the −35 and −10 regions. ERIC-PCR analysis classified the integron-positive strains into 6 genotypes, with high consistency in promoter types and gene cassettes within each genotype. RT-qPCR and antimicrobial susceptibility testing demonstrated that strong promoters significantly enhanced the expression of downstream drug resistance gene cassettes compared to weak promoters. Additionally, RT-qPCR revealed a negative correlation between intI1 expression and Pc promoter strength.ConclusionClass 1 integrons are prevalent in M. morganii. The promoter types within these integrons are diverse, and promoter strength is closely linked to downstream gene cassette expression. Integron-positive strains exhibit high homology, suggesting horizontal gene transfer and dissemination in clinical settings.

Abstract Spin‐orbit coupling (SOC) has significant effects on the superconductivity and magnetism of transition metal dichalcogenides (TMDs) at the 2D limit. Although 2D TMD samples possess many exotic properties different from those of bulk samples, experimental characterization in this field is still limited, especially for magnetism. Recent studies have revealed that bulk misfit layer compounds (MLCs) with (LaSe)1.14(NbSe2)n = 1,2 exhibit an Ising superconductivity similar to that of heavily electron‐doped NbSe2 monolayers. This offers an opportunity to study the effect of SOC on the magnetism of 2D TMDs. Here, the possible SOC effect in (LaSe)1.14(NbSe2) is investigated by measuring nuclear magnetic resonance (NMR) and electrical transport. It is found that the LaSe layer not only functions as a charge reservoir for transferring electrons into the NbSe2 layer but also remarkably influences the local electronic environment around the 93Nb nuclei. More importantly, the significant SOC induces both a weak antilocalization (WAL) effect and anisotropic spin fluctuations in noncentrosymmetric NbSe2 layers. The present work contributes to a deep understanding of the role of the SOC effect in 2D TMDs and supports MCLs as an intriguing platform for exploring exotic physical properties within the 2D limit.

Abstract Background Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). Methods We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. Results In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5–148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). Conclusion Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. Registry and registry number for systematic reviews or meta-analyses We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.

Abstract The anomalous Hall effect (AHE) and its thermoelectric counterpart, the anomalous Nernst effect (ANE), are two transverse transport coefficients that are intensely studied in condensed matter physics. While conventional wisdom links AHE and ANE to ferromagnetism, recent achievements reveal that they can emerge in nonmagnetic and antiferromagnetic topological materials with a diversity of mechanisms—many of which await further elucidation. Here, both an unconventional AHE (UAHE) that does not scale with the magnetization and a sizable ANE ( ≈ 1.8 μV K−1) are shown to be possessed by the metallic tetragonal antiferromagnet SmMnBi2. Electronic band structure of SmMnBi2 is investigated by angle-resolved photoemission spectroscopy and first-principles calculations. It is demonstrated that the UAHE reflects the intrinsic Berry curvature contribution stemming from the spin-canted antiferromagnetism, whereas the ANE is possibly further amplified by extrinsic mechanisms. These results identify SmMnBi2 as a promising candidate for exploring unusual transverse transport effects and the extremely rich underlying physics.

Abstract Background Postoperative performance, including best corrected distance visual acuity (BCDVA) and optical metrics (from the OQAS and iTrace devices), was compared among 4 different intraocular lenses (IOLs). Methods This prospective observational study included 104 eyes from 104 subjects who underwent cataract surgery combined with implantation of 4 different IOLs: monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs and extended depth of focus (EDoF) IOLs. Postoperative BCDVA and optical metrics were collected at the 6th month. The OQAS optical metrics included the objective scattering index (OSI), Strehl ratio (SR), modulation transfer function (MTF) cut-off frequency, and predicted visual acuity (PVA); the iTrace optical metrics included blur/double vision, glare/halo, starburst, mixed focus, night myopia, and night hyperopia. Results There was no significant difference in BCDVA among the 4 groups (P = 0.059; power = 70.3%). Differences were observed in all OQAS optical metrics among the groups (all P

A production technique with the high yield and environmentally friendly process need be developed for ε-Caprolactam (CPL) in the chemical industry. This technology is highly desired to design and synthesize high−performance catalysts for liquid phase Beckmann rearrangement of cyclohexanone oxime (CHO) to CPL. In this work, 3-methyl-1-(propyl-4-sulfonyl) imidazolium methanesulfonate ([PHSO3MIM][MSA]) with highly efficient and excellent yield is synthesized successfully. When the optimum molar ratio of ZnCl2 over [PHSO3MIM][MSA] was 0.02, it exhibits the high selectivity (94%) of CPL at 90 °C for 1 h. Interestingly, Fourier-transform infrared (FT-IR) investigations show that the functional Brønsted−Lewis acidic types of ionic liquids (ILs) are formed by the uniformly distributed ZnCl2 and [PHSO3MIM][MSA]. In addition, the hydrogen bond (H-bond) is formed between CHO and ILs. After ten reaction cycles, no significant structure changes are observed in the recovered [PHSO3MIM][MSA]·ZnCl2. The solubilities of ILs are predicted by using COSMO-RS model, the results show that [PHSO3MIM][MSA] is a promising candidate for the liquid phase Beckmann rearrangement of CHO into CPL. Finally, a theoretical model of the H-bond interactions between ILs and CHO is further confirmed to support the advance of reaction mechanism. A feasible way is provided for the CPL production technique in the liquid phase Beckmann rearrangement reaction.

Aeromonas hydrophila is an opportunistic pathogen of fishes and aquatic animals. A. hydrophila has a strong ability to disrupt gut integrity and cause inflammation and septicemia in fish, however, the mechanism is not fully understood. In this study, we identified the function of a galactosaminogalactan (GAG) synthase (named WbuB) in the pathogenic A. hydrophila CCL1. WbuB belongs to the family 4 of glycosyltransferases (GT4) and is composed of 407 amino acids (aa). For virulence analysis, the mutant which has an in-frame deletion of the WbuB gene in CCL1 was created (named ΔWbuB). ΔWbuB had the decreased biofilm formation, as well as adhesion ability and cytotoxicity. Animal infection study in crucian carps showed that, compared to CCL1, ΔWbuB caused the decreased expression levels of ASC, NLRP3, caspase-1 and IL-1β in gut. Moreover, the expression levels of ZO-1 and Occludin were increased by ΔWbuB infection. In line with the results, the intestinal permeability and tissue dissemination capacity of ΔWbuB were attenuated significantly. These lost virulence capacities of ΔWbuB were restored by complementation with the WbuB gene. Taken together, these results indicate that WbuB is essential for the activation of NLRP3 inflammasome and is a novel virulent factor for tight junction barrier during A. hydrophila infection.

Microbially mediated arsenic methylation, remains understudied in subgeothermal environments. This study aimed to investigate the activity and diversity of arsM-carrying microorganisms in sediment samples (termed YC1, YC2, and YC5) from a low-temperature hot spring. Microcosm assays revealed that only YC1 and YC2 exhibited limited As-methylating activities, generating a maximum of 2.3–3.5 μg/L methylarsenate (MMA) and 2.2–2.8 μg/L dimethylarsenate (DMA). The addition of lactate and arsenite significantly promoted these activities, increasing the concentrations to 26.1–184.0 μg/L MMA and 38.1–204.0 μg/L DMA. The arsM gene abundance also increased by 46–276%, indicating that lactate can activate arsenite methylation. YC1 and YC2, which were closer to the hot spring hole than YC5 was, had similar patterns, and shared a similar arsM community structure, dominated by Actinobacteriota, Firmicutes, and Proteobacteriota on days 7 and 21. In contrast, at YC5, the sampling site far from the spring hole, representatives of Acidobacteriota were dominant on day 7, whereas those of Actinobacteriota were prevalent on day 21. Acidobacteriota co-occurred with dimethylarsenate production, and Mycobacterium co-occurred with DMA demethylation. These findings suggested that the low-temperature arsenic hot spring possessed diverse arsenic-methylating species, whereas demethylating bacteria preferred to inhabit niches farther from the hot spring. HIGHLIGHTS Lactate stimulates methyl arsenic formation from subgeothermal sediments.; The arsM-carrying bacterial species composition differed with distance to the hot spring.; Demethylation occurred more often in the downstream sediment samples.;

Pressure-induced nitrogen-rich compounds hold significant application prospects in high-energy-density materials. Utilizing first-principles calculations and swarm-intelligence structure search methods, we have identified ten new types of Gd-N compounds with different configurations, such as one-dimensional N-chains composed of N6 rings or N8 rings, and two-dimensional N-layers constructed of N14 rings, N18 rings, or N18 + N6 rings. Moreover, the predicted Gd-N compounds exhibit different magnetic properties, and a magnetic phase diagram is constructed in the pressure range of 0 to 200 GPa. Remarkably, the volumetric energy density (11.58–17.79 kJ/cm3) of Gd polynitrides with high nitrogen content, including P-1(I)-GdN6, P-1(II)-GdN6, R-3-GdN8, C2mm-GdN9, and P1-GdN10, surpassed that of TNT (7.05 kJ/cm3), making them promising candidates for energetic materials. The discovery of diverse chain-like and layered structures in the GdNx compounds highlights the role of gadolinium in inducing the diversity and complexity of nitrogen arrangements.

The aim of this study was to investigate the effects and potential mechanisms of 8-week transcranial direct-current stimulation (tDCS) combined with resistance training (RT) on pull-up performance in male college students. Twenty-five male college students were randomly assigned to either RT combined with anodal tDCS stimulation (RT + tDCS) or RT alone (RT). Participants of both groups engaged in lat pull-down training programs for 8 weeks, with the RT + tDCS group receiving 20 min tDCS before each RT session. Pre- and post-intervention tests included pull-up endurance (number of repetitions), flexed arm circumference (FAC), and lat pull-down maximal voluntary isometric contraction (MVIC) peak force. During the pull-up endurance test, surface electromyography (sEMG) was recorded for the bicep brachii (BB), tricep brachii (TB), brachioradialis (BR), anterior deltoid (AD), middle deltoid (MD), posterior deltoid (PD), pectoralis major (PM), and latissimus dorsi (LD) muscles. Both groups demonstrated significant improvements in pull-up endurance and lat pull-down MVIC peak force after training, but no significant difference between the two groups was observed in the post-training test. Additionally, muscle activation of BR, PD, and PM decreased significantly in both groups, while the RT + tDCS group also demonstrated a significant reduction in TB coactivation after training. These findings suggest that eight weeks of tDCS combined with lat pull-down training and lat pull-down training alone can both significantly improve pull-up performance, which may be attributed to enhanced muscle contraction capacity. Although no significant training gains were found between the two training groups, the RT + tDCS group showed a significant decrease in TB coactivation and the enhancement of elbow flexion muscle contraction efficiency after training.

The TiSiN/NiTiAl _x CrCoN nanomultilayer films were grown on 304 stainless steels through magnetron sputtering system. The microstructure and cross-sectional and surface images, mechanical and cavitation erosion properties of the prepared films were explored in detail. The results of the study reveal that all TiSiN/NiTiAl _x CrCoN nanomultilayer films exhibit a face-centered cubic structure with a preferential orientation in (200) plane. The cross-sectional images of films show the columnar structure. The values of elastic modulus, hardness, and adhesive strength for the TiSiN/NiTiAl _x CrCoN nanomultilayer films initially increase and later decrease as the Al content is increased, whereas the mass loss for the TiSiN/NiTiAl _x CrCoN nanomultilayer films initially decrease and later increase during the cavitation erosion experiment. The TiSiN/NiTiAl _0.8 CrCoN nanomultilayer film provides a maximum hardness value equal to 31.3 GPa, a maximum elastic modulus equal to 218.9 GPa, a highest adhesive strength equal to 38.8 N and a least mass loss equal to 0.8 mg. The study showed that the solid solution strength and the alternating stress field enhance the properties of the TiSiN/NiTiAl _x CrCoN nanomultilayer films.

Flexible perovskite solar cells (F-PSCs) have the advantages of high power-per-weight, solution processability, and bending durability and have emerged as a competitive photovoltaic technology for various applications. As the core electron transport layer (ETL) in n-i-p-type device configurations, the solution-processed SnO2 generally suffers from serious defect stacking on films, compromising the charge transport properties and the performance of resulting devices. Herein, we proposed a media-filling strategy to optimize the contact quality at the buried interface by introducing Al2O3 nanoparticles on the SnO2 surface. Rather than forming a compact insulating layer, the Al2O3 can fill the grain boundaries of SnO2 and smooth the substrate surface. Optimized interfacial contact under careful concentration control can rationally minimize the contact area of the perovskite with the surface imperfections of SnO2 to mitigate trap-assisted charge recombination. Furthermore, the reduced surface roughness of SnO2 facilitates the uniform deposition and oriented growth of upper perovskite film. As a result, the target F-PSCs achieved an impressive efficiency of 23.83% and retained 80% of the initial performance after 5000 bending cycles at a radius of four mm.

The net primary productivity (NPP) of vegetation is the key indicator for assessing ecosystem productivity and carbon cycling. The Ulan Mulun River Basin (UMRB) in Northwest China is a typical coal mining area, including open-pit mining (OPM) and underground coal mining (UGM). There are limited studies utilizing long-term, high-resolution data to investigate the spatiotemporal and driving mechanisms of NPP in different types of mining and non-coal mining (NCM) areas. In this study, NPP was estimated using high-resolution Landsat data (30 m) and an improved CASA model for the period 1987–2022. The spatiotemporal variations in NPP across the basin were systematically investigated using Theil–Sen–MK trend analysis, partial derivatives, and multivariate regression residual to explore and quantify the impacts of climate variability (CV) and human activities (HAs) on the different coal mining and NCM areas. The research results show that the overall fluctuating upward trend of vegetation cover in the country is 64.84% during the period from 1987 to 2022. However, there is a decreasing trend of NPP in the coal mining areas. Precipitation was the major factor influencing the change in NPP (21.835 gC/m2/a), while HAs had a lesser effect (4.667 gC/m2/a). In addition, UGM and NCM were more positively affected by HAs than OPM, while OPM was more positively affected by CV than UGM and NCM. These findings can guide scientific ecological restoration strategies, assess carbon balance impacts, and optimize land management and planning in mining areas to achieve a balance between resource development and environmental protection.