Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

The Association Between Intolerance of Uncertainty and Mobile Phone Addiction Among Overseas Chinese Students During COVID-19: The Mediating Roles of Perceived Stress and Rumination.

Purpose: This study investigated the mechanism underlying the association between intolerance of uncertainty and mobile phone addiction among Chinese overseas students during the COVID-19 pandemic by examining the mediating roles of perceived stress and rumination. Patients and Methods: An online questionnaire survey was distributed via social media platforms popular in mainland China. The items collected demographic information and assessed intolerance of uncertainty, perceived stress, rumination, and mobile phone addiction. A total of 249 respondents completed the questionnaire. Results: The findings suggest a considerably high risk of mobile phone addiction in the study period among overseas Chinese students, as three-fourths of the participants may have been susceptible to mobile phone addiction according to the suggested cut-off point of the Chinese version of the Smartphone Addiction Scale-Short Form. Intolerance of uncertainty showed a significant positive direct effect on mobile phone addiction. The mediation analyses suggest that intolerance of uncertainty affected mobile phone addiction mainly through three pathways: the mediating effect of perceived stress, the mediating effect of rumination, and the chain mediating effect of perceived stress and rumination. Conclusion: This study enhances understanding of mobile phone addiction among Chinese overseas students and suggests the mediating roles of rumination and perceived stress in the relationship between intolerance of uncertainty and mobile phone addiction. The study also provides suggestions for interventions among Chinese students overseas.

Sealing the Breach: A Surgical Solution for Tracheoesophageal Fistula With a Simple Two-Layer Closure.

Tracheoesophageal puncture (TEP) followed by voice prosthesis placement stands as the primary method for voice rehabilitation after laryngectomy, heralded for its effectiveness. While generally well-tolerated, the procedure does pose potential long-term complications. These include prosthesis valve leakage, scarring, and prosthesis displacement, all of which can impede phonation capabilities. Of these, prosthesis leakage emerges as the most critical concern, precipitated by the progressive widening of the fistula. This complication can precipitate aspiration pneumonitis, stemming from the loss of physical separation between the esophagus and trachea. This case series details three instances where persistent tracheoesophageal fistula arose following TEP, necessitating surgical intervention. Herein, we present the clinical manifestations, surgical approach employing a simple two-layer closure, and ensuing outcomes.

Effect analysis of applying high-quality service model to surgical nursing.

BACKGROUND: Surgical care of the hand plays a crucial role in the medical field, as problems with the hand can profoundly affect a patient's quality of life and function. In order to meet the needs of patients, improve patient satisfaction and improve treatment outcomes, high-quality service models have been introduced in the field of nursing. AIM: To explore the effect analysis of applying high-quality service model to surgical nursing. METHODS: We conducted a retrospective study of patients who underwent hand surgery at our hospital between 2019 and 2022, using a quality service model that included improved patient education, pain management, care team collaboration, and effective communication. Another group of patients received traditional care as a control group. We compared postoperative recovery, satisfaction, complication rate, and length of hospital stay between the two groups. Inferential statistics were used to compare the difference between the two groups by independent sample t test, Chi-square test and other methods to evaluate the effect of intervention measures. RESULTS: Postoperative recovery time decreased from 17.8 ± 2.3 d to 14.5 ± 2.1 d, pain score decreased from 4.7 ± 1.9 to 3.2 ± 1.4, and hand function score increased from 78.4 ± 7.1 to 88.5 ± 6.2. In terms of patient satisfaction, the quality service model group scored 87.3 ± 5.6 points, which was significantly higher than that of the traditional care group (74.6 ± 6.3 points). At the same time, patients' understanding of medical information also improved from 6.9 ± 1.4 to 8.6 ± 1.2. In terms of postoperative complications, the application of the quality service model reduced the incidence of postoperative complications from 26% to 10%, the incidence of infection from 12% to 5%, and the incidence of bleeding from 10% to 3%. The reduction in these data indicates that the quality service model plays a positive role in reducing the risk of complications. In addition, the average hospital stay of patients in the quality service model group was shortened from 6.8 ± 1.5 d to 5.2 ± 1.3 d, and the hospitalization cost was also reduced from 2800 ± 600 yuan to 2500 ± 500 yuan. CONCLUSION: Applying a quality service model to hand surgery care can significantly improve patient clinical outcomes, including faster recovery, less pain, greater satisfaction, and reduced complication rates.

A-to-I RNA co-editing predicts clinical outcomes and is associated with immune cells infiltration in hepatocellular carcinoma.

Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.

SABA prescriptions and asthma management practices in Singapore: results from a cross-sectional, observational SABINA III study.

OBJECTIVES: To evaluate asthma characteristics and treatment patterns, including short-acting ß2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study. DESIGN: Cross-sectional, observational study. SETTING: Multicentre study conducted at five sites across Singapore. METHODS: In patients with asthma (aged ≥12 years), data on demographics, disease characteristics and asthma treatment prescriptions were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by 2017 Global Initiative for Asthma recommendations) and practice type (primary/specialist care). RESULTS: Of the 205 patients analysed (mean (SD) age, 53.6 (16.8) years; female, 62%), 55.9% were enrolled by specialists and 44.1% by primary care physicians. Most study patients (80.5%) had moderate-to-severe asthma (86.0% in specialist care and 74.4% in primary care). In the 12 months before study enrolment, 18.0% of patients experienced ≥1 severe exacerbation. Asthma was well or partly controlled in 78.0% of patients. Overall, 17.1% of all patients were overprescribed SABA (≥3 SABA canisters/year) in the preceding 12 months, and overprescription was greater in specialist versus primary care (26.3% vs 5.6%). Only 2.9% of patients were prescribed SABA monotherapy, while 41.0% received SABA in addition to maintenance therapy. Among the latter, 40.5% were overprescribed SABA. Overall, a higher percentage of patients prescribed ≥3 SABA canisters (vs 0-2 SABA canisters) were assessed as having uncontrolled asthma during the study visit (42.9% vs 17.6%). Maintenance therapy in the form of inhaled corticosteroids (ICS) or ICS/long-acting ß2 agonist fixed-dose combinations were prescribed to 14.1% and 84.9% of patients, respectively, in the 12 months before enrolment. CONCLUSIONS: In this Singapore cohort, ~17% of all patients and more than 40% of patients prescribed SABA in addition to maintenance therapy were overprescribed SABA. These findings emphasise the need to align clinical practices with the latest evidence-based treatment recommendations. TRIAL REGISTRATION: NCT03857178.

Metered-Dose Inhaler Spacer with Integrated Spirometer for Home-Based Asthma Monitoring and Drug Uptake.

This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring device (EMD), and a spirometer. While there are devices made to individually address the issues of technique, adherence and monitoring, respectively, for asthma patients as laid out in the Global Initiative for Asthma's (GINA) global strategy for asthma management and prevention, Spiromni was designed to address all three issues using a single, combination device. Spiromni addresses the key challenge of measuring both inhalation and exhalation profiles, which are different by an order of magnitude. Moreover, the innovative design prevents exhalation from entering the spacer chamber and prevents medication loss during inhalation using umbrella valves without a loss in flow velocity. Apart from recording the peak exhalation flow rate, data from the sensors allow us to extract other key lung volume and capacities measures similar to a medical pulmonary function test. We believe this low-cost portable multi-functional device will benefit both asthma patients and clinicians in the management of the disease.

DNA nanoassembly based turn-on amplification probe for sensitive colorimetric CRISPR/Cas12a-mediated detection of pathogen DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR) system has been explored as an efficient tool for nucleic acid diagnostics. However, it normally needs instrumentation or produces turn-off signals. Herein, a bulged Y-shape DNA (Y-DNA) nanoassembly was designed and synthesized as a novel turn-on probe. A CRISPR/Cas12a and Y-DNA probe mediated colorimetric assay (named as CYMCOA) strategy was developed for visual detection of pathogen DNA. Upon activating Cas12a with pathogen DNA, the Y-DNA bulge is catalytically trans-cleaved, releasing the G-quadruplex sequence embedded in the Y-DNA nanoassembly as a peroxidase-like DNAzyme. Visible signals with chromogen substrates are thus produced. The CYMCOA strategy was combined with recombinase polymerase amplification (RPA), an isothermal amplification technique, in detecting Helicobacter pylori (Hp) bacteria and SARS-CoV-2 N plasmids as two model pathogens. The bioassay has very excellent detection sensitivity and specificity, owing to the triple cascade amplification reactions and the very low mismatch tolerance. The lower limit of detection values were 0.16 cfu⋅mL-1, 1.5 copies⋅µL-1, and 0.17 copies⋅µL-1 for Hp bacteria, Hp plasmids, and SARS-CoV-2 N plasmids respectively. The detection is fast and accurate. The colorimetric bioassay strategy provides to be a simple, accurate, fast and instrumentation-free platform for nucleic acids detections in various settings, including crude and emergent situations.

LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to suppress colorectal cancer metastasis and chemoresistance.

Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC). Metastatic CRC frequently develops resistance to chemotherapeutic agents. This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance. Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models. Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain- and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L-CHEK2. RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance. An oxaliplatin-resistant CRC cell line was established by in vivo selection. WST-1, colony formation, invasion, migration, Biacore technology, gain- and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results: The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor. The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients. Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2, resulting in the formation of long CHEK2 (L-CHEK2), subsequently promoting E-cadherin secretion. PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion. Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance. Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC. Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance.

The effect of different times of day for exercise on blood glucose fluctuations.

AIMS: This study aims to explore blood glucose variations before and after short-term intensive exercise in the morning or afternoon of a day and the trend of blood glucose fluctuations during exercise in patients with T2DM (type 2 diabetes, T2DM). METHODS: Blood glucose variations of Fouty during morning exercise 8:00-12:00 hours and twenty during afternoon exercise 14:30-18:30 hours). Patients with T2DM discharged from the hospital were analyzed retrospectively, with the baseline data checked through the medical record system before intervention. We were asked to perform seven times of treadmill aerobic exercise, which lasted for 30 minutes with incremental intensity for each time, for two weeks under the supervision of the Continuous Glucose Monitor (CGM) and the heart rate armband. The exercise intensity has been adjusted by the clinicians and specialist nurses from the Department of Diabetes Mellitus according to the blood glucose levels and heart rate curves during exercise; data including the height, weight, body mass index (BMI), waist-to-hip ratio, fasting blood glucose, glycosylated hemoglobin, in-exercise CGM-measured blood glucose value/min, and after-exercise fingertip blood glucose value of patients with T2DM were collected after the intensive exercise (2 weeks). SPSS 22.0 and GraphPad Prism 7 were adopted for statistical analysis using the T-test and ANOVA. RESULT: No difference was observed in the baseline data between the morning and afternoon exercise groups before intervention; compared to the morning exercise group, the fasting C-peptide value (2.15±0.97 vs. 1.53±0.46) in the afternoon exercise group was higher than that in the morning exercise group, with a superior (p=0.029) effect after two weeks of intervention, exhibiting a significant difference in the results. According to the results of repeated variance ANOVA analysis, the time for the appearance of significant improvement in blood glucose in the afternoon exercise group was 5 minutes earlier (11th minute vs 1 minute)than that in the morning exercise group (15th minute vs 1 min); significant differences were observed in both time (p=0.048 vs p<0.01) between the two groups on exercise days, as revealed by the results of bivariate ANOVA; in comparison to the morning exercise group (7.42±1.68), there was a significant difference (p=0.049)in the mean blood glucose between the two groups 25 min after patients with T2DM in the afternoon exercise group (6.25±1.53) started to exercise; in addition, a significant statistical difference (p=0.021) was revealed in the CGM-measured hourly the mean blood glucose on exercise days between the morning(8.18±1.88) and afternoon exercise (6.75±1.40)groups at 4:00 pm in week one and two w. CONCLUSIONS: Glycaemic improvement in the short-term intensive afternoon exercise group may be superior to that of the morning exercise group, which may be related to greater fasting C-peptide secretion and longer effective exercise duration. The time to exercise is a factor affecting blood glucose variations during exercise. However, significant variations in the level of blood glucose during exercise must be further observed through exercise intervention over a more extended period.

Lithium Exposure and Risk of Major Neurocognitive Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). CONCLUSION: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

Optimization and mechanisms of proteolytic enzyme immobilization onto large-pore mesoporous silica nanoparticles: Enhanced tumor penetration.

Immobilization of proteolytic enzymes onto nanocarriers is effective to improve drug diffusion in tumors through degrading the dense extracellular matrix (ECM). Herein, immobilization and release behaviors of hyaluronidase, bromelain, and collagenase (Coll) on mesoporous silica nanoparticles (MSNs) were explored. A series of cationic MSNs (CMSNs) with large and adjustable pore sizes were synthesized, and investigated together with two anionic MSNs of different pore sizes. CMSNs4.0 exhibited the highest enzyme loading capacity for hyaluronidase and bromelain, and CMSNs4.5 was the best for Coll. High electrostatic interaction, matched pore size, and large pore volume and surface area favor the immobilization. Changes of the enzyme conformations and surface charges with pH, existence of a space around the immobilized enzymes, and the depth of the pore structures, affect the release ratio and tunability. The optimal CMSNs-enzyme complexes exhibited deep and homogeneous penetration into pancreatic tumors, a tumor model with the densest ECM, with CMSNs4.5-Coll as the best. Upon loading with doxorubicin (DOX), the CMSNs-enzyme complexes induced high anti-tumor efficiencies. Conceivably, the DOX/CMSNs4.5-NH2-Coll nanodrug exhibited the most effective tumor therapy, with a tumor growth inhibition ratio of 86.1 %. The study provides excellent nanocarrier-enzyme complexes, and offers instructive theories for enhanced tumor penetration and therapy.

High salt diet inhibits the expression of Bmal1 and promotes atrial fibrosis and vulnerability to atrial fibrillation in Dahl salt sensitive rats.

BACKGROUND: Hypertension is a risk factor for atrial fibrillation (AF), and brain and muscle arnt-like protein 1 (Bmal1) regulate circadian blood pressure and is implicated in several fibrotic disorders. Our hypothesis that Bmal1 inhibits atrial fibrosis and susceptibility to AF in salt-sensitive hypertension (SSHT) and our study provide a new target for the pathogenesis of AF induced by hypertension. METHODS: The study involved 7-week-old male Dahl salt-sensitive that were fed either a high-salt diet (8% NaCl; DSH group) or a normal diet (0.3% NaCl; DSN group). An experimental model was used to measure systolic blood pressure (SBP), left atrial ejection fraction (LAEF), left atrial end-volume index (LAEVI), left atrial index (LAFI), AF inducibility, AF duration, and atrial fibrosis pathological examination and the expression of Baml1 and fibrosis-related proteins (TNF-α and α-SMA) in left atrial tissue. RESULTS: DSH increased TNF-α and α-SMA expression in atrial tissue, level of SBP and LAESVI, atrial fibrosis, AF induction rate and AF duration, and decreased Bmal1 expression in atrial tissue, circadian rhythm of hypertension and level of LAEF and LAFI. Our results also showed that the degree of atrial fibrosis was negatively correlated with Bmal1 expression, but positively correlated with the expression of TNF-α and α-SMA. CONCLUSIONS: We demonstrated that a high-salt diet leads to circadian changes in hypertension due to reduction Bmal1 expression, which plays a crucial role in atrial fibrosis and increased susceptibility to AF in SSHT rats.

Relationship between Circulating 25-Hydroxyvitamin D and Metabolic Syndrome in Chinese Adults: A Large Nationwide Longitudinal Study.

OBJECTIVE: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. METHODS: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). CONCLUSIONS: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.

Moonlighting glyceraldehyde-3-phosphate dehydrogenase of Lactobacillus gasseri inhibits keratinocyte apoptosis and skin inflammation in experimental atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. OBJECTIVE: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. METHODS: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. RESULTS: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. CONCLUSION: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice.

Introduction: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR. Methods: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition. Results: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group. Discussion: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

TGF-ß downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.