The Impact of DAZZEON αSleep® Far-Infrared Blanket on Sleep, Blood Pressure, Vascular Health, Muscle Function, Inflammation, and Fatigue.

The application of far-infrared blankets has shown certain benefits in health promotion and therapy, such as improving blood circulation and alleviating muscle pain. However, the effects of such blankets on increasing deep sleep, reducing blood pressure, enhancing memory, dilating microvessels for blood flow, reducing chronic inflammation, and decreasing fatigue remain to be studied. We aim to investigate the effects of the DAZZEON αSleep® far-infrared blanket on these indicators. This study adopted a double-blind design, recruiting 24 male participants aged over 45 years, divided into two groups of 12 each: (A) a placebo group and (B) a DAZZEON αSleep® group. The participants used the blanket every night for two weeks, with sleep records taken using a wearable device and blood pressure, blood oxygen levels, arterial stiffness, and surface temperature measured before and after the intervention. Blood samples were collected for an analysis of inflammation and sleep-related blood indicators (serotonin and melatonin), and exercise tests were conducted to assess fatigue improvement. Compared with before the intervention, the blanket significantly increased changes in grip strength and reaction time. Additionally, it significantly increased blood serotonin, melatonin, and nitric oxide concentrations (p < 0.05), thus significantly increasing deep sleep and REM sleep durations (p < 0.05) and improving subjective sleep quality (p < 0.05). This study confirmed that using the DAZZEON αSleep® far-infrared blanket for 14 consecutive days helps to improve blood circulation, reduce vascular age and arterial stiffness, increase serotonin and melatonin levels, and improve sleep quality, as well as enhances muscle strength and reaction time.

Large-scale whole-exome sequencing analyses identified protein-coding variants associated with immune-mediated diseases in 350,770 adults.

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.

Exome sequencing identifies novel genetic variants associated with varicose veins.

BACKGROUND: Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood. METHODS: We conducted an exome-wide association study of VV using whole-exome sequencing data from the UK Biobank, and focused on common and rare variants using single-variant association analysis and gene-level collapsing analysis. FINDINGS: A total of 13,823,269 autosomal genetic variants were obtained after quality control. We identified 36 VV-related independent common variants mapping to 34 genes by single-variant analysis and three rare variant genes (PIEZO1, ECE1, FBLN7) by collapsing analysis, and most associations between genes and VV were replicated in FinnGen. PIEZO1 was the closest gene associated with VV (P = 5.05 × 10-31), and it was found to reach exome-wide significance in both single-variant and collapsing analyses. Two novel rare variant genes (ECE1 and METTL21A) associated with VV were identified, of which METTL21A was associated only with females. The pleiotropic effects of VV-related genes suggested that body size, inflammation, and pulmonary function are strongly associated with the development of VV. CONCLUSIONS: Our findings highlight the importance of causal genes for VV and provide new directions for treatment.

Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study.

Context: Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD. Methods: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy. Results: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It's worth noting that 20 phenotypes exist where ADHD's appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (ß= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (ß= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (ß=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (ß= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (ß=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (ß= -0.255, 95% CI: 0.621~0.967, P=0.234), among others. Conclusion: Studies indicate that the immune system's response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

[Effects and Mechanisms of Polystyrene Microplastics on Extracellular Antibiotic Resistance Genes in Wastewater].

Microplastics (MPs) and antibiotic resistance genes (ARGs) are typical co-existing emerging pollutants in wastewater treatment plants. MPs have been shown to alter the distribution pattern of ARGs in sludge, but their effects on free extracellular ARGs (feARGs) in wastewater remain unclear. In this study, we used fluorescence quantitative PCR to investigate the dynamics of feARGs (including tetC, tetO, sul1, and sul2) in wastewater and their transition mechanisms after 60 d of exposure to typical MPs (polystyrene, PS). The results showed that the absolute abundance of tetracycline feARGs decreased by 28.4 %-76.0 % and 35.2 %-96.2 %, respectively, under nm-level and mm-level PS exposure and changed by -55.4 %-122.4 % under µm-level PS exposure. The abundance of sul1 showed a trend of nm-level > µm-level > mm-level upon PS exposure, and the changes in sul1 abundance was greater with ρ(PS)=50 mg·L-1 exposure. The relative abundance of sul2 was reduced by 25.4 %-42.6 % and 46.1 %-90.3 % after µm-level and mm-level PS exposure, respectively, and increased by 1.9-3.9 times after nm-level PS exposure, and the sul2 showed a higher reduction at ρ (PS)=50 mg·L-1 exposure than that at ρ (PS)=0.5 mg·L-1. The Pearson correlation analysis showed that the relative abundance of feARGs during PS exposure was positively correlated with cell membrane permeability and typical mobile genetic elements (intI1) abundance and negatively correlated with reactive oxygen species level. Our findings elucidated the effects and corresponding mechanisms of PS on the growth and mobility of feARGs in wastewater, providing a scientific basis for the control of the combined MPs and ARGs pollution in wastewater.

Dynamic observation and risk factors analysis of deep vein thrombosis after hip fracture.

OBJECTIVE: To dynamically observe the occurrence of deep vein thrombosis (DVT) after a hip fracture and analyze of the risk factors affecting the dynamic alteration of DVT. METHODS: Data of patients with hip fractures from January 1, 2017 to August 31, 2021 were collected. Patients were divided into DVT and non-DVT groups according to their daily Doppler ultrasonography findings. Survival analysis was used to describe dynamic changes in DVT occurrence with time. Log-rank tests were used to compare the influence of individual factors of patients with DVT occurrence, and a Cox proportional hazards regression model was used to identify the risk factors affecting the dynamic alteration of DVT occurrence. RESULTS: A total of 331 patients were included: 148(44.7%) had preoperative DVT, and 143 (96.6%) had DVT in the first 3days after admission. The probability of DVT was 0.42 on Day 1, 0.11 on Day 2, 0.10 on Day 3, 0.08 on Day 4, 0.20 on Day 5, and 0.00 on Day 6-7, with a median survival time of 3.30 d. Age>70 years, intertrochanteric fracture, admission hemoglobin<130g/L, and admission hematocrit<40% had a significantly higher occurrence rate of DVT. A hematocrit level of <40% (Hazard Ratio 2.079, 95% Confidence Interval:1.148-3.764, P = 0.016) was an independent risk factor for DVT. CONCLUSION: DVT after hip fractures mainly occurred in the first three days after admission, the trend was stabilized within one week, and day 1 had the highest rate of DVT incidence. Age, fracture type, HGB level, and Hct level affected dynamic occurrence of DVT. At constant other factors, Hct<40% was 2.079-fold incidence in the risk of preoperative DVT formation than those with Hct≥40% after hip fracture.

Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.

A novel Burkholderia pyrrocinia strain effectively inhibits Fusarium graminearum growth and deoxynivalenol (DON) production.

BACKGROUND: Fusarium graminearum is a devastating fungal pathogen that poses a significant threat to global wheat production and quality. Control of this toxin-producing pathogen remains a major challenge. This study aimed to isolate strains with antagonistic activity against F. graminearum and at the same time to analyze the synthesis of deoxynivalenol (DON), in order to provide a new basis for the biological control of FHB. RESULTS: Total of 69 microorganisms were isolated from the soil of a wheat-corn crop rotation field, and an antagonistic bacterial strain F12 was identified as Burkholderia pyrrocinia by molecular biology and carbon source utilization. F. graminearum control by strain F12 showed excellent biological activities under laboratory conditions (95.8%) and field testing (63.09%). Meanwhile, the DON content of field-treated wheat grains was detected the results showed that F12 have significantly inhibited of DON, which was further verified by qPCR that F12 produces secondary metabolites that inhibit the expression of DON and pigment-related genes. In addition, the sterile fermentation broth of F12 not only inhibited mycelial growth and spore germination, but also prevented mycelia from producing spores. CONCLUSION: In this study B. pyrrocinia was reported to have good control of FHB and inhibition of DON synthesis. This novel B. pyrrocinia F12 is a promising biological inoculant, providing possibilities for controlling FHB, and a theoretical basis for the development of potential biocontrol agents and biofertilizers for agricultural use. © 2024 Society of Chemical Industry.

Genetic associations of protein-coding variants in venous thromboembolism.

Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.

Machine learning developed a CD8+ exhausted T cells signature for predicting prognosis, immune infiltration and drug sensitivity in ovarian cancer.

CD8+ exhausted T cells (CD8+ Tex) played a vital role in the progression and therapeutic response of cancer. However, few studies have fully clarified the characters of CD8+ Tex related genes in ovarian cancer (OC). The CD8+ Tex related prognostic signature (TRPS) was constructed with integrative machine learning procedure including 10 methods using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 dataset. Several immunotherapy benefits indicators, including Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore (IPS), TMB score and tumor escape score, were used to explore performance of TRPS in predicting immunotherapy benefits of OC. The TRPS constructed by Enet (alpha = 0.3) method acted as an independent risk factor for OC and showed stable and powerful performance in predicting clinical outcome of patients. The C-index of the TRPS was higher than that of tumor grade, clinical stage, and many developed signatures. Low TRPS score indicated a higher level of CD8+ T cell, B cell, macrophage M1, and NK cells, representing a relative immunoactivated ecosystem in OC. OC patients with low risk score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, suggesting a better immunotherapy response. Moreover, higher TRPS score indicated a higher score of cancer-related hallmarks, including angiogenesis, EMT, hypoxia, glycolysis, and notch signaling. Vitro experiment showed that ARL6IP5 was downregulated in OC tissues and inhibited tumor cell proliferation. The current study constructed a novel TRPS for OC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy benefits for OC patients.

Nurses' perspectives on child-friendly care needs in emergency departments: A qualitative study.

BACKGROUND: Children can become anxious when undergoing emergency medical treatment. Therefore, emergency departments should be child friendly. This study explored emergency nurses' perspectives on children's needs during emergency care. METHOD: This qualitative study employed purposive sampling to recruit 17 emergency nurses from 3 medical centers in northern and central Taiwan. Individual interviews were conducted between January and August 2021. Data were analyzed through qualitative content analysis. RESULTS: The participants had 2-23 years of experience in caring for children in emergency departments. We identified 208 unique meaning units in the interview data, 79 of which were related to child-friendly emergency care. These were classified into 42 codes across 6 categories and 27 subcategories. The six categories were timely comfort, emotional care, frontline safety, emergency response, human resources support, and treatment efficiency. CONCLUSION: Emergency nurses have professional competencies, play a crucial role as care providers for children in the emergency department, and ensure the comfort and safety of children seeking treatment. The categories related to child-friendly emergency care identified in this study can serve as a basis for developing child-friendly care emergency guidelines.

Exome sequencing identifies genes associated with sleep-related traits.

Sleep is vital for human health and has a moderate heritability. Previous genome-wide association studies have limitations in capturing the role of rare genetic variants in sleep-related traits. Here we conducted a large-scale exome-wide association study of eight sleep-related traits (sleep duration, insomnia symptoms, chronotype, daytime sleepiness, daytime napping, ease of getting up in the morning, snoring and sleep apnoea) among 450,000 participants from UK Biobank. We identified 22 new genes associated with chronotype (ADGRL4, COL6A3, CLK4 and KRTAP3-3), daytime sleepiness (ST3GAL1 and ANKRD12), daytime napping (PLEKHM1, ANKRD12 and ZBTB21), snoring (WDR59) and sleep apnoea (13 genes). Notably, 20 of these genes were confirmed to be significantly associated with sleep disorders in the FinnGen cohort. Enrichment analysis revealed that these discovered genes were enriched in circadian rhythm and central nervous system neurons. Phenotypic association analysis showed that ANKRD12 was associated with cognition and inflammatory traits. Our results demonstrate the value of large-scale whole-exome analysis in understanding the genetic architecture of sleep-related traits and potential biological mechanisms.

Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

Suboptimal Use of DOACs Post-Discharge for Geriatric Hip Fractures with Isolated Calf Deep Vein Thrombosis: Do Clinician Prescribing Preferences and Patient Compliance Alters Clinical Outcomes?

Introduction: This study aimed to examine the impacts of DOACs compliance and prescribing preferences on clinical outcomes in elderly hip fracture patients with isolated calf deep vein thrombosis (ICDVT). Methods: We conducted a retrospective cohort study that evaluated 702 patients who underwent surgical treatment combined with ICDVT in an academic university hospital between January 2016 and October 2021. DOACs compliance was investigated through telephone and outpatient follow-up, and ICDVT clinical outcomes were collected 30 and 90 days post-discharge, respectively. Variables of interest were collected through the electronic medical record system, and data were analyzed after adjusting for predictors of non-completely dissolved (CD) of ICDVT. Results: The DOACs compliance survey revealed that 375 (53.42%) patients were fully adherent, 270 (38.46%) were fairly adherent, and 57 (8.12%) were poorly adherent. Approximately 62% of patients had ICDVT dissipation within 30 days after discharge, reaching 94% within 90 days. DOACs QD/BID regimen is often based on economic status, activity capacity, discharge destination and post-operative weight-bearing activities (p<0.05).The mechanism of injury, ASA classification, surgical technique and timing of ICDVT formation were significantly correlated with DOACs 14/28 days regimen (p<0.05).Multivariate analysis revealed that rural patients [OR 1.518 (95% CI, 1.117-2.236)], pre-operative ICDVT[OR 2.816 (95% CI, 1.862-4.259)] and thrombus length [OR 1.157 (95% CI, 1.263-1.821)] were ICDVT risk factors for non-CD. Furthermore, DOACs fair compliance [OR 0.087 (95% CI, 0.042-0.178)], DOACs full compliance [OR 0.283 (95% CI, 0.139-0.579)], and hospitalization duration [OR 0.793 (95% CI, 0.694-0.907)] were ICDVT protective factors for CD. Conclusion: Better compliance with DOACs benefits early ICDVT dissipation, but final clinical outcomes have to be validated with longer follow-up periods. When managing elderly patients with hip fractures, indications for anticoagulation should be considered and individualized protocols should be used.

Transcription factor E4F1 dictates spermatogonial stem cell fate decisions by regulating mitochondrial functions and cell cycle progression.

BACKGROUND: Spermatogonial stem cells (SSCs) provide a foundation for robust and continual spermatogenesis in mammals. SSCs self-renew to maintain a functional stem cell pool and differentiate to supply committed progenitors. Metabolism acts as a crucial determinant of stem cell fates; however, factors linking metabolic programs to SSC development and maintenance are poorly understood. RESULTS: We analyzed the chromatin accessibility of undifferentiated spermatogonia at the single-cell level and identified 37 positive TF regulators that may have potential roles in dictating SSC fates. The transcription factor E4F1 is expressed in spermatogonia, and its conditional deletion in mouse germ cells results in progressive loss of the entire undifferentiated spermatogonial pool. Single-cell RNA-seq analysis of control and E4f1-deficient spermatogonia revealed that E4F1 acts as a key regulator of mitochondrial function. E4F1 binds to promotors of genes that encode components of the mitochondrial respiratory chain, including Ndufs5, Cox7a2, Cox6c, and Dnajc19. Loss of E4f1 function caused abnormal mitochondrial morphology and defects in fatty acid metabolism; as a result, undifferentiated spermatogonia were gradually lost due to cell cycle arrest and elevated apoptosis. Deletion of p53 in E4f1-deficient germ cells only temporarily prevented spermatogonial loss but did not rescue the defects in SSC maintenance. CONCLUSIONS: Emerging evidence indicates that metabolic signals dictate stem cell fate decisions. In this study, we identified a list of transcription regulators that have potential roles in the fate transitions of undifferentiated spermatogonia in mice. Functional experiments demonstrated that the E4F1-mediated transcription program is a crucial regulator of metabolism and SSC fate decisions in mammals.

A bidirectional Mendelian randomization study about the role of morning plasma cortisol in attention deficit hyperactivity disorder.

Context: Cortisol, a hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, has been linked to attention deficit hyperactivity disorder (ADHD). The nature of the relationship between cortisol and ADHD, and whether it is causal or explained by reverse causality, remains a matter of debate. Objective: This study aims to evaluate the bidirectional causal relationship between morning plasma cortisol levels and ADHD. Methods: This study used a bidirectional 2-sample Mendelian randomization (MR) design to analyze the association between morning plasma cortisol levels and ADHD using genetic information from the authoritative Psychiatric Genomics Collaboration (PGC) database (n = 55,347) and the ADHD Working Group of the CORtisol NETwork (CORNET) Consortium (n = 12,597). MR analyses were employed: inverse variance weighting (IVW), MR-Egger regression, and weighted medians. OR values and 95% CI were used to evaluate whether there was a causal association between morning plasma cortisol levels on ADHD and ADHD on morning plasma cortisol levels. The Egger-intercept method was employed to test for level pleiotropy. Sensitivity analysis was performed using the "leave-one-out" method, MR pleiotropy residual sum, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results: Findings from bidirectional MR demonstrated that lower morning plasma cortisol levels were associated with ADHD (ADHD-cortisol OR = 0.857; 95% CI, 0.755-0.974; P = 0.018), suggesting there is a reverse causal relationship between cortisol and ADHD. However, morning plasma cortisol levels were not found to have a causal effect on the risk of ADHD (OR = 1.006; 95% CI, 0.909-1.113; P = 0.907), despite the lack of genetic evidence. The MR-Egger method revealed intercepts close to zero, indicating that the selected instrumental variables had no horizontal multiplicity. The "leave-one-out" sensitivity analysis revealed stable results, with no instrumental variables significantly affecting the results. Heterogeneity tests were insignificant, and MR-PRESSO did not detect any significant outliers. The selected single-nucleotide polymorphisms (SNPs) F were all >10, indicating no weak instrumental variables. Thus, the overall MR analysis results were reliable. Conclusion: The study findings suggest a reverse causal relationship between morning plasma cortisol levels and ADHD, with low cortisol levels associated with ADHD. No genetic evidence was found to support a causal relationship between morning plasma cortisol levels and the risk of ADHD. These results suggest that ADHD may lead to a significant reduction in morning plasma cortisol secretion.

Molecular characterization and antimicrobial activity of NK-lysin in black scraper (Thamnaconus modestus).

NK-lysin (NKL) is a positively charged antimicrobial peptide with broad-spectrum bactericidal activities. In this study, the cDNA sequence of NKL (TmNKL) from black scraper (Thamnaconus modestus) was cloned, which encodes a predicted polypeptide of 150 amino acids that contains a surfactant protein B domain with three disulfide bonds. Phylogenetically, TmNKL was most closely related to its teleost counterpart from tiger puffer (Takifugu rubripes). Expression analysis demonstrated that TmNKL transcripts were constitutively expressed in all tested tissues, with the highest expression levels in the gills. Its expression was significantly upregulated in the gills, head kidney, and spleen after infection with Vibrio parahaemolyticus. A linear peptide (TmNKLP40L) and a disulfide-type peptide (TmNKLP40O) were further synthesized and results showed that disulfide bonds are not essential for bactericidal activities of TmNKL, and that both forms of TmNKL exhibited potent bactericidal activities against 4 gram- negative bacteria, including V. parahaemolyticus, V. alginolyticus, Edwardsiella tarda, and V. harveyi. Observed antimicrobial activities are likely due to the effects of TmNKLP40L and TmNKLP40O treatment on disrupting the integrity of both inner and outer membrane of V. parahaemolyticus, resulting in hydrolysis of bacterial genomic DNA. Damaged cell membranes and leakage of intracellular contents were further confirmed using scanning and transmission microscopy. Moreover, administration of 1.0 µg/g TmNKLP40L or TmNKLP40O significantly decreased bacterial load in tissues and thus, pronouncedly enhanced the survival of V. parahaemolyticus-infected fish. Overall, our results demonstrated that TmNKL is a potent innate effector and provides protective effects against bacterial infection.

Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.

The innate immune system protects the host from external pathogens and internal damage in various ways. The cGAS-STING signaling pathway, comprised of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and downstream signaling adaptors, plays an essential role in protective immune defense against microbial DNA and internal damaged-associated DNA and is responsible for various immune-related diseases. After binding with DNA, cytosolic cGAS undergoes conformational change and DNA-linked liquid-liquid phase separation to produce 2'3'-cGAMP for the activation of endoplasmic reticulum (ER)-localized STING. However, further studies revealed that cGAS is predominantly expressed in the nucleus and strictly tethered to chromatin to prevent binding with nuclear DNA, and functions differently from cytosolic-localized cGAS. Detailed delineation of this pathway, including its structure, signaling, and regulatory mechanisms, is of great significance to fully understand the diversity of cGAS-STING activation and signaling and will be of benefit for the treatment of inflammatory diseases and cancer. Here, we review recent progress on the above-mentioned perspectives of the cGAS-STING signaling pathway and discuss new avenues for further study.

Taxifolin Inhibits WSSV Infection and Transmission by Increasing the Innate Immune Response in Litopenaeus vannamei.

An outbreak of white spot syndrome virus (WSSV) can hit shrimp culture with a devastating blow, and there are no suitable measures to prevent infection with the virus. In this study, the activity of active molecules from Chinese herbs against WSSV was evaluated and screened. Taxifolin had the highest rate (84%) of inhibition of the WSSV infection. The viral infectivity and genome copy number were reduced by 41% when WSSV virion was pretreated with taxifolin prior to shrimp infection. A continuous exchange of taxifolin significantly reduced the mortality of shrimp infected with WSSV. Due to the WSSV virion infectivity being affected by taxifolin, the horizontal transmission of the virus was blocked with an inhibition rate of up to 30%, which would further reduce the cost of a viral outbreak. Additionally, the viral genome copy number was also reduced by up to 63% in shrimp preincubated in taxifolin for 8 h. There may be a connection to the enhancement of innate immunity in shrimp that resulted in a 15% reduction in mortality for taxifolin-fed shrimp after the WSSV challenge. After dietary supplementation with taxifolin, the resistance of larvae to WSSV was improved, indicating that taxifolin may be a potential immunostimulant for shrimp to prevent WSD. Therefore, the results indicate that taxifolin has application potential for blocking a WSSV outbreak and reducing the loss of shrimp culture.

Incidence and risk factors of clinically important venous thromboembolism in tibial plateau fractures.

While there are multiple reports on venous thromboembolism (VTE) associated with several orthopedic procedures, the knowledge regarding incidence and risk factors of VTE in tibial plateau fractures is limited. This study aimed to investigate the incidence and risk factors of clinically important venous thromboembolism (CIVTE) in patients with tibial plateau fractures. All adult patients who underwent surgical treatment of tibia plateau fractures between 2003 and 2018 in our level 1 trauma center were included in the study. All patients suspected CIVTE were assessed by the ultrasonography and/or CT scan. Univariate and multivariate analysis were used to evaluate the association between potential risk factors and CIVTE Variables. Thirty-nine of 462 patients (8.4%) developed clinically important venous thromboembolism, in which pulmonary embolism (PE) and deep vein thrombosis (DVT) were observed in 18 (3.9%) and 21 (4.54%) patients, respectively. Male gender (OR 9.75; 95% CI 2.34-40.66), spine injury (OR 9.51; 95% CI 3.39-26.64), other extremity injury (OR 3.7; 95% CI 1.58-8.66), length of stay in ICU (OR 1.14; 95% CI 1.09-1.2) were all risk factors for CIVTE. The incidence of CIVTE in tibial plateau fracture was relatively high (8.4%); The male gender, spine injury, other extremity injury, length of stay in ICU were the independent risk factors.