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AIM: To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD). METHODS: A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment. RESULTS: After three IPL treatments, both groups had significant improvement in MGYSS (both P

Abstract Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms.

Abstract Our study aimed to investigate the relationship between sleep–wake changes and depressive symptoms events among midlife women. We enrolled 1579 women aged 44–56 years who had no clinically relevant depressive symptoms at baseline. Depressive symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression scale. At the third and fourth follow-up visits, women reported their sleep habits. The sleep midpoint was defined as the time to fall asleep plus one-half of the sleep duration. Sleep–wake changes were determined by the difference in the midpoint of sleep between the third and fourth visits, which were 1 year apart. The median follow-up time was 7 years (range 1–7 years). Cox proportional hazard models were fitted to calculate hazard ratios and 95% confidence intervals for the incidence of depressive symptoms associated with sleep–wake changes. After adjusting for potential confounding factors, the hazard ratio (95% confidence interval) of depressive symptoms for severe sleep midpoint changes was 1.51 (1.12, 2.05) compared with mild sleep midpoint changes. This relationship remained statistically significant and changed little when additionally controlling for sleep duration, sleep quality, insomnia symptoms, use of sleep medications, use of nervous medications, glucose, insulin, lipids, dietary energy intake, and C-reactive protein. Our findings indicate that exposure to long-term severe sleep–wake changes increases the risk of depressive symptoms in midlife women.

Three new species of the genera Thiania C. L. Koch, 1846 and Yaginumaella Prószyński, 1979 are described and named as T. bamian sp. nov. (♂♀), T. flacata sp. nov. (♀) and Y. curvata sp. nov. (♂♀), from Hunan Province, China. Detailed descriptions, photos of somatic features and copulatory organs, as well as a distribution map are provided. Nucleotide data for the barcoding gene, cytochrome c oxidase subunit I (COI) of T. bamian sp. nov. (♂♀) and Y. curvata sp. nov. (♀) are provided.

Traditional Chinese Medicine (TCM) formulations serve as a multi-component pharmacological combination therapy with various potential targets and have collected extensive knowledge regarding the in vivo efficacy of treating cardiovascular disorders in clinical practice for thousands of years. However, the obscurity of the chemicals and the molecular mechanisms are impediments to their continued growth and globalization. Therefore, new modern medications based on the combination of beneficial TCM components with precise clinical efficacy are required. The goal of this study was to find the best combination of Achyranthes bidentata Blume (AB) and Paeonia lactiflora Pall. (PL) for hypertension with liver yang hyperactivity (HLYH). The integrated research consisting of principal component analysis (PCA), metabolomics, microbiology, and weighted correlation network analysis (WGCNA) were used to find the optimal combination of AB-PL combinations and reveal the mechanism of action. The result showed AB-PL (2:3) had a substantial protective impact on HLYH, as shown by lower blood pressure, improved liver yang hyperactivity, reduced cardiac remodeling and malondialdehyde (MDA), and increased NO content. Furthermore, the essential elements for AB-PL reducing hypertension may be related to 135 metabolites and 23 microorganisms. In conclusion, our findings support the efficacy of herbal remedies in the treatment of hypertension and provide some pharmacological evidence for the ongoing development of novel modern Chinese drugs for cardiovascular disorders.

Abstract Interactions between tumoral cells and tumor‐associated bacteria within the tumor microenvironment play a significant role in tumor survival and progression, potentially impacting cancer treatment outcomes. In lung cancer patients, the Gram‐negative pathogen Pseudomonas aeruginosa raises questions about its role in tumor survival. Here, a microfluidic‐based 3D‐human lung tumor spheroid‐P. aeruginosa model is developed to study the bacteria's impact on tumor survival. P. aeruginosa forms a tumor‐associated biofilm by producing Psl exopolysaccharide and secreting iron‐scavenging pyoverdine, which is critical for establishing a bacterial community in tumors. Consequently, pyoverdine promotes cancer progression by reducing susceptibility to iron‐induced death (ferroptosis), enhancing cell viability, and facilitating several cancer hallmarks, including epithelial–mesenchymal transition and metastasis. A promising combinatorial therapy approach using antimicrobial tobramycin, ferroptosis‐inducing thiostrepton, and anti‐cancer doxorubicin could eradicate biofilms and tumors. This work unveils a novel phenomenon of cross‐kingdom cooperation, where bacteria protect tumors from death, and it paves the way for future research in developing antibiofilm cancer therapies. Understanding these interactions offers potential new strategies for combatting cancer and enhancing treatment efficacy.

BackgroundThe aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed.MethodsThe expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. In vitro experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings in vivo using xenograft tumors. Tumor cell lines were developed to study AEG-1’s effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns.ResultsOur analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis.ConclusionIn conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy.

Abstract Background The rarity of primary central nervous system lymphoma (PCNSL) and treatment heterogeneity contributes to a lack of prognostic models for evaluating posttreatment remission. This study aimed to develop and validate radiomic‐based models to predict the durable response (DR) to high‐dose methotrexate (HD‐MTX)‐based chemotherapy in PCNSL patients. Methods A total of 159 patients pathologically diagnosed with PCNSL between 2011 and 2021 across two institutions were enrolled. According to the NCCN guidelines, the DR was defined as the remission lasting ≥1 year after receiving HD‐MTX‐based chemotherapy. For each patient, a total of 1218 radiomic features were extracted from prebiopsy T1 contrast‐enhanced MR images. Multiple machine‐learning algorithms were utilized for feature selection and classification to build a radiomic signature. The radiomic‐clinical integrated models were developed using the random forest method. Model performance was externally validated to verify its clinical utility. Results A total of 105 PCNSL patients were enrolled after excluding 54 cases with ineligibility. The training and validation cohorts comprised 76 and 29 individuals, respectively. Among them, 65 patients achieved DR. The radiomic signature, consisting of 8 selected features, demonstrated strong predictive performance, with area under the curves of 0.994 in training cohort and 0.913 in validation cohort. This signature was independently associated with the DR in both cohorts. Both the radiomic signature and integrated models significantly outperformed the clinical models in two cohorts. Decision curve analysis underscored the clinical utility of the established models. Conclusions This radiomic signature and integrated models have the potential to accurately predict the DR to HD‐MTX‐based chemotherapy in PCNSL patients, providing valuable therapeutic insights.

PurposeNeurofilament-light chain (NfL) is associated with neurodegenerative diseases, which are increasingly prevalent with aging. Vitamin K has been shown a neuroprotective effect. Therefore, we aimed to explore the potential relationship between dietary vitamin K intake and serum NfL.MethodsThis study was conducted on the 2013–2014 cycles of the National Health and Nutrition Examination Survey, a multi-site population-based study of the US general population. Serum NfL level was measured using a highly sensitive immunoassay. Dietary vitamin K intake was estimated from two-day dietary recall interviews, and its relationship with NfL was determined using linear regression models.ResultsThe study included a total of 1,533 participants with a median age of 46 years, comprising 801 women (52.2%) and 732 men (47.8%). The median dietary intake of vitamin K was 81.6 μg/d, and the median serum NfL was 12 pg./mL. After adjusting for potential confounding factors in the full model, individuals with higher dietary vitamin K intake had lower serum NfL levels (Q4 vs. Q1, β = −4.92, 95%CI: −7.66, −2.19, p = 0.002). A non-linear negative dose–response association is found between dietary vitamin K intake and serum NfL levels (P for non-linearity = 0.008); this association reaches a plateau when the dietary vitamin K intake is higher than 200 μg/d. According to the results of stratified analysis, the relationship between dietary vitamin K intake and serum NfL levels was stronger in the population of middle-aged and older adults.ConclusionThe present study suggested a negative association between dietary vitamin K intake and serum NfL levels in the general US population, especially in middle-aged and older adults. This study might offer a novel nutritional idea for the primary prevention and mechanism exploration of neurodegenerative diseases.

Since the p53 protein is an important promising biomarker of lung tumor and colorectal tumor, it is very essential to design a highly effective mean to monitor the degree of p53 for the early clinical analysis/therapy of the related tumors. In this work, a sandwich-type electrochemical immunosensing (SES) platform is proposed for the first time to detect p53 via synthesizing Ti3C2Tx MXene nanoribbons (Ti3C2Tx Nb) and ferrocene/gold nanoparticles (Fc/Au) respectively as the sensing substrate and signal-amplifier. The superior electrical property and large surface area of Ti3C2Tx Nb are beneficial to assemble the initial p53-antibodies (Ab1), while the synthesized Fc/Au is devoted to assemble the secondary p53 antibodies (Ab2) and gives a magnified signal. By adopting the Fc molecules as the probes, the experiments reveal the response current of Fc resulted from the SES structure increases along with the p53 increase from 1.0 to 200.0 pg mL−1. A considerable low detection limit (1.0 pg mL−1) is achieved after optimizing several key conditions, it is thus confirmed the as-proposed SES mean exhibits significant application in the detection of p53 protein and other targets.

Background: Although cadmium exposure had been demonstrated to be toxic to the nervous system, little was known about the link between cadmium exposure and axonal injury. Therefore, the present study aimed to reveal whether there was any correlation between blood cadmium and serum neurofilament light chain (NfL) levels in the general population. Methods: This study included 1040 participants with a median (IQR) age of 47 (35−60) years from the 2013–2014 National Health and Nutrition Examination Survey. Serum NfL levels were measured through immunoassay, and whole blood cadmium concentrations were detected by means of inductively coupled plasma mass spectrometry. Linear regression and restricted cubic spline model was applied to analyze the significance of relationship between blood cadmium and serum NfL levels. Results: In the full adjusted model, blood cadmium levels were found to be positively associated with serum NfL levels (Q4 vs Q1, β = 3.35, 95 %CI: 0.41, 6.30, p for trend = 0.014). A potential linear positive dose-effect relationship was discovered between blood cadmium and serum NfL levels (p for non-linearity = 0.15). According to the result of stratified analysis, the significant positive relationship between blood cadmium and serum NfL levels was present only in the population of middle-aged and older adults. Conclusion: The present study suggested a positive association between blood cadmium and serum NfL levels in the general US population.

Abstract Introduction Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. Methods We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. Results Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362–0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. Conclusion The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.

Based on the principle of D’Alembert, the nonlinear vibration equation of cylindrical membrane is established, and the analysis and experimental verification of it are conducted. The control equation system for cylindrical membrane vibration problems is established, and the equation system according to the physical equations and boundary conditions of thin diaphragms is simplified and solved, the analytical solution of nonlinear vibration frequency of cylindrical membrane is obtained, and the linear analytical solution is verified by finite element simulation, which shows that the error between theoretical calculation and numerical simulation is small, and the applicability of finite element method to the modal analysis of flexible membrane structure is verified. A 3D laser scanning vibration measurement system is used to test the vibration frequency of cylindrical membranes in the air environment. The finite element analysis software is used to obtain the dry mode and wet mode vibration frequencies of cylindrical membranes and extract the additional mass coefficients of air. The results showed that the test results of the vibration in wet mode have a good consistency with the numerical analysis results, and the influence of the additional quality of the ground air on the cylindrical membrane is in the same order of magnitude as its own mass.

Abstract Background The evidence regarding the association of reproductive factors with cardiovascular diseases (CVDs) is limited. Aims To investigate the relationship of reproductive factors with the risk of CVDs, as well as all-cause and cardiovascular mortality. Methods This study included 16,404 adults with reproductive factors from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2019. Logistic models and restricted cubic spline models were used to assess the association of reproductive factors with CVDs. COX proportional hazards models and restricted cubic spline models, with adjustment for potential confounding, were employed to analyze the relation between reproductive factors and cardiovascular and all-cause death. Results There is a nonlinear relationship between age at menarche and CVDs. Age at menopause ≤ 11(OR 1.36, 95% CI 1.10–1.69) was associated with an increased risk of CVDs compared to ages 12–13 years. Age at Menopause ≤ 44 (OR 1.69, 95% CI 1.40–2.03) was associated with increased CVDs compared to age 35–49 years. Number of pregnancies ≥ 5(OR 1.26, 95% CI 1.02–1.55) was associated with an increased risk of CVDs compared to one pregnancy. In continuous variable COX regression models, a later age at menopause (HR 0.98, 95% CI 0.97–0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97–0.99) were associated with a decreased risk of all-cause death. A later age at menopause (HR 0.98, 95% CI 0.97–0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97–0.99) were associated with a decreased risk of cardiac death. Conclusions Female reproductive factors are significant risk factors for CVDs American women.

Abstract Background Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. Methods The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. Results DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, l-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. Conclusion DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.