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Microbial community and succession of 5-, 20-, and 50-year pit mud (PM) were uncovered in this study. The results showed that Bacteroidetes, Firmicutes and Ascomycota were dominant phyla in these PM samples. Interestingly, most sequences could not be classified into fungal taxa at the genus level by UNITE Database, the diversity and richness of bacteria in these PMs were higher than that of fungi. It was noteworthy that both 20-year and 50-year PMs exhibited higher abundances of Caproiciproducens and Petrimonas when compared with 5-year PM. While higher proportions of Lactobacillus and Acinetobacter were observed in the 5-year PM. Furfermore, these PMs microbiota mainly involved biosynthesis, degradation, and generation of precursor metabolites, which contributed to carbon cycling of Nong-xiang Baijiu anaerobic fermentation. Taken together, lactic acid bacteria depletion and caproic acid bacteria accumulation might be an important succession trend of PM microbiota during the long-term fermentation of Chinese Nong-xiang Baijiu. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01558-4.

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Objective: To identify factors that influence the severity of tinnitus via a hierarchical multiple linear regression model. Methods: The study was a retrospective cross-sectional analysis. The study included 331 patients experiencing tinnitus as their primary concern, who visited Shanghai Changzheng Hospital of the Navy Medical University between 2019 and 2021. Data on general health status and disease characteristics were collected from all patients. With their consent, participants underwent audiological evaluatons and completed questionnaires to analyze the characteristics of their tinnitus and the factors influencing its severity. Results: The correlation analysis showed a positive relationship between tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores with THI scores (P < 0.05) among nine examined variables (gender, handedness, employment status, age, BMI, tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores). The variables that were extracted from the multiple regression were; for the constant; ß = -51.797, t = -4.484, P < 0.001, variable is significant; for the tinnitus loudness; ß = 0.161, t = 2.604, P < 0.05, variable is significant; for the tinnitus frequency; ß = 0.000, t = 1.269, P = 0.206, variable is not significant; for the SAS scores; ß = 1.310, t = 7.685, P < 0.001, variable is significant; for the PSQI scores; ß = 1.680, t = 5.433, P < 0.001, variable is significant. Therefore, the most accurate model for predicting severity in tinnitus patients is a linear combination of the constant, tinnitus loudness, SAS scores, and PSQI scores, Y(Tinnitus severity) = ß 0 + ß 1 (Tinnitus loudness) + ß 2 (SAS scores) + ß 3 (PSQI scores). ß 0, ß 1, ß 2, and ß 3 are -51.797, 0.161, 1.310 and 1.680, respectively. Conclusion: Tinnitus severity is positively associated with loudness, anxiety levels, and sleep quality. To effectively manage tinnitus in patients, it is essential to promptly identify and address these accompanying factors and related symptoms.

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Agricultural systems significantly contribute to global N2O emissions, which is intensified by excessive fertilization and antibiotic residues, attracting global concerns. However, the dynamics and pathways of antibiotics-induced soil N2O production coupled with microbial metabolism remain controversial. Here, we explored the pathways of N2O production in agricultural soils exposed to ciprofloxacin (CIP), and revealed the underlying mechanisms of CIP degradation and the associated microbial metabolisms using 15N-isotope labeling and molecular techniques. CIP exposure significantly increases the total soil N2O production rate. This is attributed to an unexpected shift from heterotrophic and autotrophic nitrification to denitrification and an increased abundance of denitrifiers Methylobacillus members under CIP exposure. The most striking strain M. flagellatus KT is further discovered to harbor N2O-producing genes but lacks a N2O-reducing gene, thereby stimulating denitrification-based N2O production. Moreover, this denitrifying strain is probably capable of utilizing the byproducts of CIP as carbon sources, evidenced by genes associated with CIP resistance and degradation. Molecular docking further shows that CIP is well ordered in the catalytic active site of CotA laccase, thus affirming the potential for this strain to degrade CIP. These findings advance the mechanistic insights into N2O production within terrestrial ecosystems coupled with the organic contaminants degradation.

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Background: Growing evidence suggests that endometriosis (EMs) is a risk factor for endometriosis-associated ovarian cancer (EAOC). The aim was to identify and validate gene signatures associated with EMs that may serve as potential biomarkers for evaluating the prognosis of patients with EAOC. Methods: The data of EMs and control samples was obtained from GEO database. The weighted gene co-expression network analysis (WGCNA) identified modular genes significantly associated with EMs. The KEGG pathway and GO functional enrichment analyses were also performed. Univariate Cox regression analysis was conducted to screen marker genes associated with the prognosis of EAOC patients. Finally, RT-qPCR and immunohistochemical verified the expression of ADAMTS19 and TUBB in normal ovarian and EAOC tissues, and the biological functions of ADAMTS19 and TUBB were preliminarily explored by CCK8 and Transwell assays. Results: The WGCNA identified 2 co-expression modules, which in total included 615 genes, and 7642 differentially expressed genes (DEGs) were detected thorough analysis of the EAOC dataset. After taking the intersection of 615 modular genes and 7642 DEGs, 214 shared genes were obtained, and univariate COX regression analysis pointed 10 genes associated with the prognosis of EAOC. Moreover, it was demonstrated by RT-qPCR and immunohistochemical staining experiments that ADAMTS19 expression was elevated, while TUBB expression was reduced in EAOC compared with normal ovarian cells and tissues. Finally, cell experiments revealed that ADAMTS19 promoted the proliferation and invasion in EAOC cells, while overexpression of TUBB inhibited these processes. Conclusions: The present study identified and validated new EMs-associated gene markers, which could serve as potential biomarkers for assessing the prognostic risk of EAOC patients. In addition, some of these genes may have significance as novel therapeutic targets and could be used to guide clinical applications.

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INTRODUCTION: The heritability of Alzheimer's disease (AD) is estimated to be 58%-79%. However, known genes can only partially explain the heritability. METHODS: Here, we conducted gene-based exome-wide association study (ExWAS) of rare variants and single-variant ExWAS of common variants, utilizing data of 54,569 clinically diagnosed/proxy AD and related dementia (ADRD) and 295,421 controls from the UK Biobank. RESULTS: Gene-based ExWAS identified 11 genes predicting a higher ADRD risk, including five novel ones, namely FRMD8, DDX1, DNMT3L, MORC1, and TGM2, along with six previously reported ones, SORL1, GRN, PSEN1, ABCA7, GBA, and ADAM10. Single-variant ExWAS identified two ADRD-associated novel genes, SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. The druggability evidence suggests that DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets. DISCUSSION: Our study contributes to the current body of evidence on the genetic etiology of ADRD. HIGHLIGHTS: Gene-based analyses of rare variants identified five novel genes for Alzheimer's disease and related dementia (ADRD), including FRMD8, DDX1, DNMT3L, MORC1, and TGM2. Single-variant analyses of common variants identified two novel genes for ADRD, including SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets.

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Jamming is an athermal transition between flowing and rigid states in amorphous systems such as granular matter, colloidal suspensions, complex fluids and cells. The jamming transition seems to display mixed aspects of a first-order transition, evidenced by a discontinuity in the coordination number, and a second-order transition, indicated by power-law scalings and diverging lengths. Here we demonstrate that jamming is a first-order transition with quenched disorder in cyclically sheared systems with quasistatic deformations, in two and three dimensions. Based on scaling analyses, we show that fluctuations of the jamming density in finite-sized systems have important consequences on the finite-size effects of various quantities, resulting in a square relationship between disconnected and connected susceptibilities, a key signature of the first-order transition with quenched disorder. This study puts the jamming transition into the category of a broad class of transitions in disordered systems where sample-to-sample fluctuations dominate over thermal fluctuations, suggesting that the nature and behavior of the jamming transition might be better understood within the developed theoretical framework of the athermally driven random-field Ising model.

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Educational attainment (EA), socioeconomic status (SES) and cognition are phenotypically and genetically linked to health outcomes. However, the role of copy number variations (CNVs) in influencing EA/SES/cognition remains unclear. Using a large-scale (n = 305,401) genome-wide CNV-level association analysis, we discovered 33 CNV loci significantly associated with EA/SES/cognition, 20 of which were novel (deletions at 2p22.2, 2p16.2, 2p12, 3p25.3, 4p15.2, 5p15.33, 5q21.1, 8p21.3, 9p21.1, 11p14.3, 13q12.13, 17q21.31, and 20q13.33, as well as duplications at 3q12.2, 3q23, 7p22.3, 8p23.1, 8p23.2, 17q12 (105 kb), and 19q13.32). The genes identified in gene-level tests were enriched in biological pathways such as neurodegeneration, telomere maintenance and axon guidance. Phenome-wide association studies further identified novel associations of EA/SES/cognition-associated CNVs with mental and physical diseases, such as 6q27 duplication with upper respiratory disease and 17q12 (105 kb) duplication with mood disorders. Our findings provide a genome-wide CNV profile for EA/SES/cognition and bridge their connections to health. The expanded candidate CNVs database and the residing genes would be a valuable resource for future studies aimed at uncovering the biological mechanisms underlying cognitive function and related clinical phenotypes.

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Radiotherapy (RT) serves as the primary treatment for solid tumors. Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes. However, RT may also promote the accumulation of immunosuppressive cytokines and immunosuppressive cells, greatly impeding the activation of antitumor immune responses and substantially limiting the effectiveness of RT. Therefore, regulating post-RT immunosuppression to steer the immune milieu toward heightened activation potentially enhances RT's therapeutic potential. Cytokines, potent orchestrators of diverse cellular responses, play a pivotal role in regulating this immunosuppressive response. Identifying and promptly neutralizing early released immunosuppressive cytokines are a crucial development in augmenting RT's immunomodulatory effects. To this end, we conducted a screen of immunosuppressive cytokines following RT and identified macrophage colony-stimulating factor (MCSF) as an early up-regulated and persistent immune suppressor. Single-cell sequencing revealed that the main source of up-regulated MCSF derived from tumor cells. Mechanistic exploration revealed that irradiation-dependent phosphorylation of the p65 protein facilitated its binding to the MCSF gene promoter, enhancing transcription. Knockdown and chemical inhibitor experiments conclusively demonstrated that suppressing tumor cell-derived MCSF amplifies RT's immune-activating effects, with optimal results achieved by early MCSF blockade after irradiation. Additionally, we validated that MCSF acted on macrophages, inducing the secretion of a large number of inhibitory cytokines. In summary, we propose a novel approach to enhance the immune activation effects of RT by blocking the MCSF-CSF1R signaling pathway early after irradiation.

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The concentrations of atmospheric pollutants PM2.5, O3, SO2, NO2, and CO together with the meteorological factors of temperature （T）, relative humidity （RH）, wind speed, and other relevant data in Tangshan from 2015 to 2021 were collected to study the variation characteristics of PM2.5 and O3 at different periods in Tangshan City in the past seven years and their influencing factors, to discuss the contributions of air mass transport to PM2.5 and O3 pollution, and to reveal the synergistic influence mechanism of PM2.5 and O3 on atmospheric compound pollution by using correlation analysis and backward trajectory cluster analysis techniques. The results showed that PM2.5 concentrations in Tangshan decreased year by year from 2015 to 2021, whereas O3 concentration showed a unimodal trend, with the peak appearing in 2017. Both PM2.5 and O3 concentrations showed obvious seasonal variation trends； PM2.5 was characterized by the highest concentration in winter and the lowest concentration in summer, whereas O3 was characterized by the highest concentration in summer and the lowest concentration in winter. In addition, the diurnal variation in PM2.5 showed a bimodal distribution, with the peak occurring during the morning and evening on weekdays, and O3 showed a unimodal distribution, with the peak value appearing during the period with strong ultraviolet radiation in the afternoon. PM2.5 had a significant positive correlation with SO2, NO2, and CO, whereas O3 had a significant positive correlation with radiation and temperature. Under the different pollution conditions, PM2.5 and O3 were affected by air mass transports from different directions. Being impacted by various factors, the synergistic effect of PM2.5 and O3 on atmospheric compound pollution showed an obvious negative effect in winter, whereas there was an obvious positive effect in spring, summer, and autumn. Under the backgrounds of different pollutions, when the concentration of PM2.5 exceeded 150 µg·m-3, the synergistic effect of PM2.5 and O3 showed an obvious negative effect.

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Recent advances in spatial omics have expanded the spectrum of profiled molecular categories beyond transcriptomics. However, many of these technologies are constrained by limited spatial resolution, hindering our ability to deeply characterize intricate tissue architectures. Existing computational methods primarily focus on the resolution enhancement of transcriptomics data, lacking the adaptability to address the emerging spatial omics technologies that profile various omics types. Here, we introduce soScope, a unified generative framework designed to enhance data quality and spatial resolution for molecular profiles obtained from diverse spatial technologies. soScope aggregates multimodal tissue information from omics, spatial relations and images, and jointly infers omics profiles at enhanced resolutions with omics-specific modeling through distribution priors. With comprehensive evaluations on diverse spatial omics platforms, including Visium, Xenium, spatial-CUT&Tag, and slide-DNA/RNA-seq, soScope improves performances in identifying biologically meaningful intestine and kidney architectures, revealing embryonic heart structure that cannot be resolved at the original resolution and correcting sample and technical biases arising from sequencing and sample processing. Furthermore, soScope extends to spatial multiomics technology spatial-CITE-seq and spatial ATAC-RNA-seq, leveraging cross-omics reference for simultaneous multiomics enhancement. soScope provides a versatile tool to improve the utilization of continually expanding spatial omics technologies and resources.

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Background: This study aims to elucidate the association between glycemia and the occurrence of multi-vessel lesions in participants undergoing coronary angiography. Methods: We analyzed 2,533 patients with coronary artery disease who underwent coronary angiography. Of these, 1,973 patients, identified by the endpoint of multi-vessel lesions, were examined using univariate and multivariate logistic regression analyses to determine the relationship between glycemia levels and multi-vessel lesion occurrence. Results: The analysis included 1,973 participants, among whom 474 patients were identified with coronary multi-vessel lesions. Univariate logistic regression analysis demonstrated a positive correlation between glycemia and the occurrence of coronary multi-vessel lesions (OR 1.04; 95% CI 1.01-1.08; p = 0.02). The adjusted model indicated that for each unit increase in glycemia, the risk of developing coronary multi-vessel lesions increased by 4%, showing a significant correlation (p < 0.05). Subgroup analyses revealed that the impact of glycemia on multi-vessel lesions in patients with PCI varied according to gender, age, and smoking status, with the effect being more pronounced in men, older patients, and smokers. Conclusion: Our findings establish a significant association between glycemia and the incidence of multi-vessel lesions, particularly pronounced in male patients, individuals over 45, and smokers.

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BACKGROUND: Shift work is associated with susceptibility to several neuropsychiatric disorders. This study aims to investigate the effect of shift work on the incidence of neuropsychiatric disorders, and highlighting how individual variability may influence the association. METHODS: UK Biobank participants with employment information were included. Cox survival was conducted in main and subgroup analyses. Correlation analyses explored the impact of shift work on brain structures, and mediation analyses were performed to elucidate the shared underlying mechanisms. Shift work tolerance was evaluated through survival analyses contrasting the risks associated with five neuropsychiatric disorders in shift versus non-shift workers across different demographic or occupational strata. RESULTS: The analysis encompassed 254,646 participants. Shift work was associated with higher risk of dementia (HR 1.29, 95 % CI 1.10-1.52), anxiety (1.08, 1.01-1.15), depression (1.29, 1.22-1.36), and sleep disorders (1.18, 1.09-1.28), but not stroke (p = 0.20). Shift work was correlated with decreasing volume of various brain regions, particularly in thalamus, lateral orbitofrontal, and middle temporal. Mediation analysis revealed that increased immune response and glucose levels are common pathways linking shift work to these disorders. We observed diversity in shift work tolerance across different individual characteristics, among which socioeconomic status and length of working hours were the most essential. LIMITATIONS: Self-reported employment information may cause misclassification and recall bias. And since we focused on the middle-aged population, the conclusions may not be representative of younger or older populations. CONCLUSIONS: Our findings indicated the need to monitor shift worker health and provide personalized management to help adapt to shift work.

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BACKGROUND: The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment. METHODS: From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model. RESULTS: The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05). CONCLUSIONS: Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

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Solid-state electrolytes (SSEs) are challenged by complex interfacial chemistry and poor ion transport through the interfaces they form with battery electrodes. Here, we investigate a class of SSE composed of micrometer-sized lithium oxide (Li2O) particles dispersed in a polymerizable 1,3-dioxolane (DOL) liquid. Ring-opening polymerization (ROP) of the DOL by Lewis acid salts inside a battery cell produces polymer-inorganic hybrid electrolytes with gradient properties on both the particle and battery cell length scales. These electrolytes sustain stable charge-discharge behavior in Li||NCM811 and anode-free Cu||NCM811 electrochemical cells. On the particle length scale, Li2O retards ROP, facilitating efficient ion transport in a fluid-like region near the particle surface. On battery cell length scales, gravity-assisted settling creates physical and electrochemical gradients in the hybrid electrolytes. By means of electrochemical and spectroscopic analyses, we find that Li2O particles participate in a reversible redox reaction that increases the effective CE in anode-free cells to values approaching 100%, enhancing battery cycle life.

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Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

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RATIONALE: Rectal cavernous hemangioma is a rare, benign vascular disease that seldom causes lower gastrointestinal bleeding, characterized by a high rate of misdiagnosis and missed diagnoses. Surgical treatment is considered to be relatively effective; however, it is accompanied by certain employed in the treatment of superficial hemangioma, boasting the advantages of minimally invasive surgery, including safety, effectiveness, reduced trauma, and rapid recovery. However, there is a lack of literature regarding the application of foam sclerosing agents for gastrointestinal hemangiomas. CASE CONCERNS: We present a case of a 60-year-old male who was admitted to our hospital with a history of recurrent hematochezia for >1 year and worsening symptoms for 1 week. The patient's medical history was unremarkable. DIAGNOSES: Following colonoscopy, nuclear magnetic resonance imaging, computed tomography, and other examinations, the final diagnosis was rectal cavernous hemangioma. INTERVENTIONS: Due to the patient's refusal of surgery, endoscopic foam sclerotherapy using a lauromacrogol injection was performed after obtaining informed consent from the patient and their relatives. OUTCOMES: Post-sclerotherapy, hematochezia symptoms ceased, and no adverse reactions were observed. Two months later, colonoscopy and nuclear magnetic resonance imaging showed that the hemangioma had almost completely disappeared, with only a small amount of tumor remnants, yielding a satisfactory curative effect. CONCLUSION: Our findings indicate that endoscopic injection of a lauromacrogol foam sclerosing agent is a safe, effective, and minimally invasive treatment option for gastrointestinal cavernous hemangiomas.

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Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.

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This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway.

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The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves' disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.

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Phototherapy has been extensively used to prevent and treat signs of aging and stimulate wound healing, and phototherapy through light-emitting diodes (LEDs). In contrast to LED, organic LED (OLED) devices are composed of organic semiconductors that possess novel characteristics. We investigated the regenerative potential of OLED for restoring cellular potential from senescence and thus delaying animal aging. Bone marrow-derived stem cells (BMSCs) and adipose-derived stem cells (ADSCs) were isolated from the control and OLED- treated groups to evaluate their proliferation, migration, and differentiation potentials. Cellular senescence was evaluated using a senescence-associated ß-galactosidase (SA-ß-gal) activity assay and gene expression biomarker assessment. OLED treatment significantly increased the cell proliferation, colony formation, and migration abilities of stem cells. SA-ß-gal activity was significantly decreased in both ADSCs and BMSCs in the OLED-treated group. Gene expression biomarkers from treated mice indicated a significant upregulation of IGF-1 (insulin growthfactor-1). The upregulation of the SIRT1 gene inhibited the p16 and p19 genes then to downregulate the p53 expressions for regeneration of stem cells in the OLED-treated group. Our findings indicated that the survival rates of 10-month aging senescence-accelerated mouse prone 8 mice were prolonged and that their gross appearance improved markedly after OLED treatment. Histological analysis of skin and brain tissue also indicated significantly greater collagen fibers density, which prevents ocular abnormalities and ß-amyloid accumulation. Lordokyphosis and bone characteristics were observed to resemble those of younger mice after OLED treatment. In conclusion, OLED therapy reduced the signs of aging and enhanced stem-cell senescence recovery and then could be used for tissue regeneration.

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