CD30 plays a role in T-dependent immune response and T cell proliferation.

CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily and expressed in both normal and malignant lymphoid cells. However, the role of CD30 in lymphopoiesis is not known. In this study, we showed CD30 was expressed both in T and B cells, but its deficiency in mice had no effect on T- and B-cell development. In fact, CD30 deficiency attenuated B-cell response to T-cell-dependent antigens. The impaired B cell response in CD30-deficient mice is caused by the reduction of activation-induced cytidine deaminase (AID) expression. Moreover, CD30-deficient mice exhibited decreased TCR-mediated T cell proliferation and slightly impaired TCR signaling. High-throughput RNA sequencing analysis revealed that CD30 deficiency led to a decrease of FOXO-autophagy axis in T cells upon TCR stimulation. Thus, CD30 positively regulates T-cell-dependent immune response and T cell proliferation.

In-Depth Proteomic Analysis Reveals Phenotypic Diversity of Macrophages in Liver Fibrosis.

Macrophages make up a heterogeneous population of immune cells that exhibit diverse phenotypes and functions in health and disease. Although macrophage epigenomic and transcriptomic profiles have been reported, the proteomes of distinct macrophage populations under various pathological conditions remain largely elusive. Here, we employed a label-free proteomic approach to characterize the diversity of the hepatic macrophage pool in an experimental model of CCl4-induced liver fibrosis. We found a decrease in the proportion of liver resident embryo-derived KCs (EmKCs), and a drastic increase in the proportion of monocyte-derived KCs (MoKCs) and CLEC2-Macs. Proteomic profiling revealed that MoKCs largely resembled EmKCs, whereas CLEC2-Macs exhibited greater proteomic alternations compared with EmKCs, suggesting two distinct destinations for monocyte differentiation during liver fibrosis. Furthermore, CLEC2-Macs were characterized by increased expression of proteins associated with inflammatory response, antigen processing and presentation processes, which may be involved in the pathogenesis of liver fibrosis. Collectively, our study provides insights into the considerable heterogeneity within the hepatic macrophage pool during liver fibrosis.

NONO regulates B-cell development and B-cell receptor signaling.

The paraspeckle protein NONO is a multifunctional nuclear protein participating in the regulation of transcriptional regulation, mRNA splicing and DNA repair. However, whether NONO plays a role in lymphopoiesis is not known. In this study, we generated mice with global deletion of NONO and bone marrow (BM) chimeric mice in which NONO is deleted in all of mature B cells. We found that the global deletion of NONO in mice did not affect T-cell development but impaired early B-cell development in BM at pro- to pre-B-cell transition stage and B-cell maturation in the spleen. Studies of BM chimeric mice demonstrated that the impaired B-cell development in NONO-deficient mice is B-cell-intrinsic. NONO-deficient B cells displayed normal BCR-induced cell proliferation but increased BCR-induced cell apoptosis. Moreover, we found that NONO deficiency impaired BCR-induced activation of ERK, AKT, and NF-κB pathways in B cells, and altered BCR-induced gene expression profile. Thus, NONO plays a critical role in B-cell development and BCR-induced B-cell activation.

Laboratory-Confirmed Influenza Hospitalizations During Pregnancy or the Early Postpartum Period - Suzhou City, Jiangsu Province, China, 2018-2023.

Pregnancy is associated with increased risk for severe illness and complications associated with influenza infection. Insufficient knowledge about the risk for influenza among pregnant women and their health care providers in China is an important barrier to increasing influenza vaccination coverage and treating influenza and its complications among pregnant women. Improved influenza incidence estimates might promote wider vaccine acceptance and higher vaccination coverage. In Suzhou, active population-based surveillance during October 2018-September 2023 estimated that the annual rate of hospitalization for acute respiratory or febrile illness (ARFI) among women who were pregnant or <2 weeks postpartum was 11.1 per 1,000 live births; the annual rate of laboratory-confirmed influenza-associated ARFI (influenza ARFI) hospitalization in this group was 2.1 per 1,000 live births. A majority of hospitalized pregnant or early postpartum patients with ARFI (82.6%; 2,588 of 3,133) or influenza ARFI (85.5%; 423 of 495) were admitted to obstetrics wards rather than respiratory medicine wards. Only one (0.03%) pregnant or postpartum ARFI patient had received influenza vaccination, and 31.3% of pregnant or postpartum women hospitalized for influenza ARFI received antiviral treatment; the lowest percentage of hospitalized women with influenza ARFI who received antiviral treatment was among women admitted to obstetrics and gynecology wards (29.6% and 23.1%, respectively), compared with 54.1% of those admitted to a respiratory medicine ward. These findings highlight the risk for influenza and its associated complications among pregnant and postpartum women, the low rates of influenza vaccination among pregnant women, and of antiviral treatment of women with ARFI admitted to obstetrics and gynecology wards. Increasing awareness of the prevalence of influenza ARFI among pregnant women, the use of empiric antiviral treatment for ARFI, and the infection control in obstetrics wards during influenza seasons might help reduce influenza-associated morbidity among pregnant and postpartum women.

The Epidemic Characteristics of Stroke Death from 2012 to 2021 in Chongqing, China.

INTRODUCTION: Stroke has become a major disease that threatens the global population's health and is a major public health problem that needs to be solved in China. Therefore, it is essential to analyze the trend of the mortality of stroke and its epidemic characteristic of stroke death. METHODS: Death cases of stroke were reported to the national death registry system by the medical staff of all medical institutions, and the population data every year were obtained from District or County's Statistic Bureau in Chongqing. They were analyzed to calculate the mortality, age-standardized mortality rate by Chinese standardization population (ASMRC), age-specific mortality, proportion, and annual percent of change (APC) according to the ICD-10 code. ASMRC was based on the standard population of the 6th census in China, 2010. The stroke mortality of each subgroup was compared using the χ2 test. Trend analysis was presented by APC. RESULTS: The crude mortality of stroke increased from 96.29 per 100,000 in 2012 to 115.93 per 100,000 significantly, with the APC of 2.02% (t = 2.82, p = 0.022) in Chongqing. ASMRC of stroke was 56.47 per 100,000 in 2012 and 54.70 per 100,000 in 2021, and its trend change was stable (APC = -0.01, t = 0.07, p = 0.947). The crude mortality of stroke in males was higher than that in females every year (p < 0.05). The death proportion of intracerebral hemorrhage dwindled from 60.53% in 2012 to 49.88% in 2021, whereas the death proportion of ischemic stroke increased from 20.92% in 2012 to 39.96% in 2021. The average age of stroke death was delayed from 73.43 years old in 2012 to 76.52 years old in 2021 significantly (t = 18.12, p < 0.001). The percentage of stroke death at home increased from 75.23% in 2012 to 79.23% in 2021, while the percentage of stroke death at hospitals decreased from 17.89% in 2012 to 15.89% in 2021. CONCLUSION: The crude mortality of stroke surged, and intracerebral hemorrhage was the main death cause of all subtypes. The mortality of stroke in males and rural residents was higher than that in females and urban residents. Most stroke deaths occurred at home. Male and rural residents were crucial populations for stroke prevention and control. There should be improved medical resources in rural areas and enhanced capability of stroke diagnosis and treatment.

Associations of various healthy dietary patterns with biological age acceleration and the mediating role of gut microbiota: results from the China Multi-Ethnic Cohort study.

To investigate the associations between dietary patterns and biological aging, identify the most recommended dietary pattern for coping with biological aging and explore the potential mediating role of gut microbiota in less-developed ethnic minority regions (LEMRs). This prospective cohort study included 8288 participants aged 30-79 years from the China Multi-Ethnic Cohort study (CMEC). Anthropometric measurements and clinical biomarkers were utilized to construct biological age based on Klemera and Doubal's method (KDM-BA) and KDM-BA acceleration (KDM-AA). Dietary information was obtained through the baseline food frequency questionnaire (FFQ). Six dietary patterns were constructed: plant-based diet index (PDI), healthful plant-based diet index (hPDI), unhealthful plant-based diet index (uPDI), healthy diet score (HDS), Dietary Approaches to Stop Hypertension (DASH), and alternative Mediterranean diets (aMED). Follow-up adjusted for baseline analysis were employed to assess the associations between dietary patterns and KDM-AA. Additionally, quantile G-computation was utilized to evaluate the significant beneficial and harmful food groups. In the subsample of 764 participants with gut microbiota data obtained through 16S rRNA gene sequencing, we used causal mediation model to explore the mediating role of gut microbiota in the associations between dietary patterns and KDM-AA. The results showed that all dietary patterns were associated with KDM-AA. Transitioning from non-compliance to compliance, DASH exhibited the strongest negative association with KDM-AA [ß = -0.91, 95%CI (-1.19, -0.63)]. The component analyses revealed that tea and soybean products were the significant beneficial food groups, while salt, preserved vegetables, red and processed meats were identified as the major harmful food groups. In mediation analysis, the decreased abundance of Synergistetes phylum and Pyramidobacter genus possibly mediated the negative associations between plant-based diets and KDM-AA (5.61%-9.19%). Overall, healthy dietary patterns, especially DASH, are negatively associated with biological aging in LEMRs. The Synergistetes and Pyramidobacter may mediate the associations between plant-based diets and biological aging. Developing appropriate strategies may promote healthy aging in LEMRs.

Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China.

AIM: This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients. METHODS: Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies-vaccination without screening, screening-based vaccination, and no vaccination-among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties. RESULTS: It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. CONCLUSIONS: The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.

Effect of vegetable consumption on risk of gastric cancer: a systematic review and multi-level meta-analysis of prospective studies.

Vegetables are known to be beneficial to human health, but the association between vegetable consumption and gastric cancer remains uncertain. To synthesise knowledge about the relationship between vegetable group consumption and gastric cancer risk, update present meta-analyses and estimate associations between vegetable consumption and gastric cancer risk based solely on prospective studies, we perform a PRISMA-compliant three-level meta-analysis. Systematic search identified thirteen prospective studies with fifty-two effect sizes that met all inclusion criteria and no exclusion criteria for our meta-analysis. Pooled risk ratios (RRs) showed a positive association between high vegetable consumption and low gastric cancer risk (pooled RR 0·93, 95% confidence interval 0·90-0·97, P = 0·06). In moderator analyses for indicators of gender, region and quantity of vegetable intake, there was no significant difference between subgroups. However, the effect became significant in populations with lower than the minimum risk exposure level (TMREL) of vegetable consumption (P < 0·05). Higher vegetable intake is associated with a decreased risk of gastric cancer. This effect may be limited to specific populations, such as ones with lower vegetable consumption. Evidence from our study has important public health implications for dietary recommendations.

Effect of health lifestyle on the risk of stroke: A prospective cohort study from Chongqing, China.

OBJECTIVE: To prospectively investigate the associations of healthy lifestyle factors on the risk of stroke and stroke subtypes, as studies exploring this relationship are limited in China. METHODS: The 22,661 participants in the prospective cohort study in Chongqing, China, aged 30-79 years and stroke-free at baseline completed follow-up from 2018 to 2022. We included seven healthy lifestyle factors, including non-smoking, non-excessive drinking, sufficient physical activity, healthy diet, sleep duration of 7-9 h/d, and standard range of body mass index and waist-to-hip ratio. The healthy lifestyle score was calculated based on the number of healthy lifestyle factors. RESULTS: Compared with participants who had scores ≤2, participants with scores ≥6 had an HRs (95 % CIs) of 0.56 (0.34, 0.92) for total stroke and 0.53 (0.30, 0.93) for ischemic stroke. For every 1-point increase in healthy lifestyle scores, the HRs (95 % CIs) for total stroke and ischemic stroke was 0.86 (0.78, 0.95) and 0.86 (0.77, 0.96), respectively. CONCLUSIONS: Maintaining multiple healthy lifestyle factors can significantly reduce the risk of stroke. As the number of healthy lifestyle factors increased, the stroke risk gradually decreased. Our findings emphasize the significance of comprehensive lifestyle interventions.

Long-term exposure to fine particulate matter constituents in relation to chronic kidney disease: evidence from a large population-based study in China.

The effects of long-term exposure to fine particulate matter (PM2.5) constituents on chronic kidney disease (CKD) are not fully known. This study sought to examine the association between long-term exposure to major PM2.5 constituents and CKD and look for potential constituents contributing substantially to CKD. This study included 81,137 adults from the 2018 to 2019 baseline survey of China Multi-Ethnic Cohort. CKD was defined by the estimated glomerular filtration rate. Exposure concentration data of 7 major PM2.5 constituents were assessed by satellite remote sensing. Logistic regression models were used to estimate the effect of each PM2.5 constituent exposure on CKD. The weighted quantile sum regression was used to estimate the effect of mixed exposure to all constituents. PM2.5 constituents had positive correlations with CKD (per standard deviation increase), with ORs (95% CIs) of 1.20 (1.02-1.41) for black carbon, 1.27 (1.07-1.51) for ammonium, 1.29 (1.08-1.55) for nitrate, 1.20 (1.01-1.43) for organic matter, 1.25 (1.06-1.46) for sulfate, 1.30 (1.11-1.54) for soil particles, and 1.63 (1.39-1.91) for sea salt. Mixed exposure to all constituents was positively associated with CKD (1.68, 1.32-2.11). Sea salt was the constituent with the largest weight (0.36), which suggested its importance in the PM2.5-CKD association, followed by nitrate (0.32), organic matter (0.18), soil particles (0.10), ammonium (0.03), BC (0.01). Sulfate had the least weight (< 0.01). Long-term exposure to PM2.5 sea salt and nitrate may contribute more than other constituents in increasing CKD risk, providing new evidence and insights for PM2.5-CKD mechanism research and air pollution control strategy.

Elevated urine albumin creatinine ratio increases cardiovascular mortality in coronary artery disease patients with or without type 2 diabetes mellitus: a multicenter retrospective study.

BACKGROUND: Albuminuria has been suggested as an atherosclerotic risk factor among the general population. However, whether this association will be amplified in patients with coronary artery disease (CAD) is unknown. It is also unknown whether diabetes mellitus confounds the association. We aim to analyse the prognosis of elevated urine albumin creatinine ratio (uACR) in the CAD population with or without type 2 diabetes mellitus (T2DM). METHODS: This multi-center registry cohort study included 5,960 patients with CAD. Patients were divided into T2DM and non-T2DM group, and baseline uACR levels were assessed on three grades (low: uACR < 10 mg/g, middle: 10 mg/g ≤ uACR < 30 mg/g, and high: uACR ≥ 30 mg/g). The study endpoints were cardiovascular mortality and all-cause mortality. RESULTS: During the median follow-up of 2.2 [1.2-3.1] years, 310 (5.2%) patients died, of which 236 (4.0%) patients died of cardiovascular disease. CAD patients with elevated uACR had a higher risk of cardiovascular mortality (middle: HR, 2.32; high: HR, 3.22) than those with low uACR, as well as all-cause mortality. Elevated uACR increased nearly 1.5-fold risk of cardiovascular mortality (middle: HR, 2.33; high: HR, 2.34) among patients without T2DM, and increased 1.5- fold to 3- fold risk of cardiovascular mortality in T2DM patients (middle: HR, 2.49; high: HR, 3.98). CONCLUSIONS: Even mildly increased uACR could increase the risk of cardiovascular mortality in patients with CAD, especially when combined with T2DM.

Association between Nocturnal Sleep Duration and Insomnia symptoms with depressive symptoms among 44,900 Chinese Han adults aged 30-79 in Southwest China.

BACKGROUND: Although there are several cross-sectional and prospective studies on the relationship between sleep duration /insomnia symptoms and depression symptoms, the results of these studies are still not conclusive, and few studies have further analyzed the association between sleep duration and depressive symptoms in adults by gender and age. Thus, this study aimed to investigate the relationship between nocturnal sleep duration and insomnia symptoms with depression symptoms, and further examine whether the association was impacted by age and gender in a large-scale Han Chinese population in southwest China. METHODS: A cross-sectional study was performed that included 44,900 participants from 18 districts in southwest China from September 2018 to January 2019. The study comprised 42,242 individuals in the final analysis. Depressive symptoms were investigated using the PHQ-2 questionnaires. Multivariate logistic regression analysis was performed to investigate the relationship between nocturnal sleep duration and insomnia symptoms with depression symptoms as well as the influence of age and gender. RESULTS: After adjusting for multiple variables, those with nocturnal sleep duration < 7 h had a higher odds ratio for depression (OR:1.47, 95%CI 1.31-1.65) compared to participants whose nocturnal sleep duration was in the range of 7-8 h. Notably, there is a higher association in those aged below 45 years (OR:1.91, 95%CI 1.52-2.41) and in female participants (OR:1.57, 95%CI 1.35-1.82). However, nocturnal sleep duration longer than 9 h was not associated with depression symptoms in either the whole population analysis or the subgroup analysis. Insomniacs had a higher odds ratio for depression(OR:1.87, 95%CI 1.84-2.36, respectively) compared to non-insomniacs. There is a higher association in those aged 45-60 years (OR:2.23, 95%CI 1.82-2.73) and in female participants (OR:2.17, 95%CI 1.84-2.56). Further subgroup analysis by age and gender at the same time showed the association between sleep deprivation and depression was highest among women aged below 45 years, while the association between insomnia and depression was the highest among men aged 45-59 years. CONCLUSION: Short nocturnal sleep duration and insomnia symptoms were positively associated with the risk of depressive symptoms among Chinese Han adults aged 30-79 in Southwest China, especially the middle-aged population and females should be more concerned.

Association between alcohol consumption and risk of stroke among adults: results from a prospective cohort study in Chongqing, China.

BACKGROUND: The incidence of stroke in China is increasing, along with a clear trend in the prevalence of risk factors. Alcohol consumption is also a risk factor for stroke. Many cohort studies have explored the relationship between alcohol consumption and stroke risk. However, findings have been inconsistent. METHODS: We used cluster sampling to select 13 districts and counties (at the same level) in Chongqing, China. Then, we used stratified random sampling to distribute the number of people in each district and county. 23,308 adults aged 30-79 were recruited between October 2018 and February 2019. Follow-up was conducted through a monitoring system and questionnaires until September 2022. Information on alcohol consumption and other covariates was collected using a standardized questionnaire. Participants were asked to report their weekly frequency of drinking over the past year and weekly intake of various alcoholic beverages in general. The frequency of drinking was divided into three categories: 1-2 d/week, 3-5 d/week, and 6-7 d/week. The average daily alcohol consumption is calculated based on the amount of alcohol contained in different alcoholic beverages. It is classified as nondrinker (0 g/day), light (0 to 12 g/day), moderate (13 to 36 g/day), and high (> 36 g/day). Cox proportional hazard regression models were used to estimate the association between alcohol consumption and stroke risk. Results are shown as multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: With an average follow-up of 3.80 years, there were 310 new stroke events. The incidence of total stroke was 368.69 per 100,000 person-years. Overall, after adjusting for covariates, moderate alcohol consumption (average daily alcohol consumption 13-36 g/d) was associated with a lower risk of total stroke (HR: 0.48; 95% CI: 0.25-0.92) compared with nondrinkers. The adjusted HR and 95% CI for total stroke and ischemic stroke for those who drank alcohol 6-7 days per week were 0.60(0.37, 0.96) and 0.53(0.30, 0.94), respectively. The risk of total stroke (HR: 0.39; 95% CI: 0.17-0.89) was reduced in a pattern of drinking 6-7 days per week but with a mean alcohol consumption of less than 36 g/d. There was no significant association between alcohol consumption and hemorrhagic stroke. CONCLUSION: This study suggests moderate alcohol consumption is associated with a lower risk of total stroke. And healthy drinking patterns should be of more significant concern.

Association between spicy food and hypertension among Han Chinese aged 30-79 years in Sichuan Basin: a population-based cross-sectional study.

BACKGROUND: While spicy food is believed to have cardiovascular-protective effects, its impact on hypertension remains uncertain due to conflicting findings from previous studies. This study aimed to explore the association between spicy food and hypertension in Sichuan Basin, China. METHODS: The baseline data of 43,657 residents aged 30-79 in the Sichuan Basin were analyzed including a questionnaire survey (e.g., sociodemographics, diet and lifestyle, medical history), medical examinations (e.g., height, body weight, and blood pressure), and clinical laboratory tests (e.g., blood and urine specimens). Participants were recruited by multi-stage, stratified cluster sampling in consideration of both sex ratio and age ratio between June 2018 and February 2019. Multivariable logistic regression was performed to explore the effect of spicy food on hypertension and multivariable linear regression was applied to estimate the effect of spicy food on systolic and diastolic blood pressure (SBP/DBP). RESULTS: Concerning hypertension, negative associations with spicy food consumption were observed only in females: compared to those who do not eat spicy food, the odds ratios of consuming spicy food 6-7 days/week, consuming spicy food with strong strength, and years of eating spicy food-to-age ratio were 0.886 (0.799, 0.982), 0.757 (0.587, 0.977), 0.632 (0.505, 0.792), respectively. No significant association was found in males (All P trends > 0.05). In the stratified analyses, participants in the subgroup who were 50 to 79 years old (OR, 95%CI: 0.814, 0.763, 0.869), habitually snored (OR, 95%CI: 0.899, 0.829, 0.976), had a BMI < 24 kg/m2 (OR, 95%CI: 0.886, 0.810, 0.969), had a normal waist circumference (OR, 95%CI: 0.898, 0.810, 0.997), and had no dyslipidemia (OR, 95%CI: 0.897, 0.835, 0.964) showed a significantly stronger association. For SBP, consuming spicy food had negative effects in both genders, but the effect was smaller in males compared to females: among males, the ß coefficients for consuming spicy food 1-2 days/week, weak strength, and years of eating spicy food-to-age ratio were 0.931 (-1.832, -0.030), -0.639 (-1.247, -0.032), and - 2.952 (-4.413, -1.492), respectively; among females, the ß coefficients for consuming spicy food 3-5 days/week, 6-7 days/week, weak strength, moderate strength, and years of eating spicy food-to-age ratio were - 1.251 (-2.115, -0.388), -1.215 (-1.897, -0.534), -0.788 (-1.313, -0.263), -1.807 (-2.542, -1.072), and - 5.853 (-7.195, -4.512), respectively. For DBP, only a positive association between the years of eating spicy food-to-age ratio and DBP was found in males with ß coefficient (95%CI ) of 1.300 (0.338, 2.263); Little association was found in females (all P trends > 0.05), except for a decrease of 0.591 mmHg ( 95%CI: -1.078, -0.105) in DBP among participants who consumed spicy food 1-2 days/week, compared to those who did not consume spicy food. CONCLUSION: Spicy food may lower SBP and has an antihypertensive effect, particularly beneficial for women and individuals with fewer risk factors in the Sichuan Basin. Spicy food consumption may decrease DBP in women but increase it in men. Further multicenter prospective cohort studies are needed to confirm these findings.

Bioinspired Robust Keratin Hydrogels for Biomedical Applications.

Although keratins are robust in nature, hydrogels producing their extracts exhibit poor mechanical properties due to the complicated composition and ineffective self-assembly. Here we report a bioinspired strategy to fabricate robust keratin hydrogels based on mechanism study through recombinant proteins. Homotypic and heterotypic self-assembly of selected type I and type II keratins in different combinations was conducted to identify crucial domain structures for the process, their kinetics, and relationship with the mechanical strength of hydrogels. Segments with best performance were isolated and used to construct novel assembling units. The new design outperformed combinations of native proteins in mechanical properties and in biomedical applications such as controlled drug release and skin regeneration. Our approach not only elucidated the critical structural domains and underlying mechanisms for keratin self-assembly but also opens an avenue toward the rational design of robust keratin hydrogels for biomedical applications.

Circ_0006667 contributes to high glucose-induced retinal pigment epithelial cell dysfunction by mediating miR-7-5p/TGFA axis in diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes mellitus and it can lead to visual impairment and blindness. The loss of retinal pigment epithelial (RPE) cells is associated with the etiology of DR. Moreover, dysregulated circular RNAs (circRNAs) are implicated in DR progression. Therefore, this project aims to explore the role and potential mechanism of circ_0006667 in DR. METHODS: RPE cells (ARPE-19) were stimulated with high glucose (33 mM; HG group) for 24 h to establish the DR cell model. Circ_0006667, microRNA-7-5p (miR-7-5p), and transforming growth factor alpha (TGFA) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, and apoptosis were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry. CyclinD1, Cleaved-caspase-3, and TGFA protein levels were detected using western blot. Using Circinteractome and starBase analysis, the binding miR-7-5p and circ_0006667 or TGFA was predicted, and then validated using dual-luciferase reporter and RNA Immunoprecipitation (RIP). RESULTS: Circ_0006667 expression was up-regulated in DR patients and HG-induced ARPE-19 cells. HG stimulation suppressed ARPE-19 cell proliferation and promoted cell apoptosis and inflammation, which were alleviated via circ_0006667 silence. Circ_0006667 acted as a molecular sponge for miR-7-5p, and circ_0006667 absence-mediated protective effects in HG-induced ARPE-19 cells were largely overturned by the interference of miR-7-5p. miR-7-5p directly targeted TGFA, and miR-7-5p overexpression protected ARPE-19 cells from HG-induced dysfunction largely by down-regulating TGFA. Circ_0006667 can up-regulate the expression of TGFA by sponging miR-7-5p in ARPE-19 cells. CONCLUSION: Circ_0006667 silencing protected ARPE-19 cells from HG-induced dysfunction by mediating miR-7-5p/TGFA axis.

LncRNA00492 is required for marginal zone B-cell development.

B-cell development undergoes a series of steps from the bone marrow to the secondary lymphoid organs. A defect in B-cell development can lead to immunodeficiency or malignant disorders, such as leukaemia or lymphoma. Long non-coding RNAs have been reported to act as important regulators of many pathological processes. However, very little is known regarding the role of lncRNAs during B-cell development and the regulation of their expression. In this study, we explored the expression and role of lncRNA Gme00492 in B-cell development. We observed that lnc00492 was highly expressed in B-cell development and primarily expressed in the nucleus. Lnc00492-deficient mice had fewer marginal zone B cells in the spleen, likely due to a developmental block. Importantly, lnc00492 interacts with CTBP1 and targets it for ubiquitination and degradation during B-cell development, whereas the transcriptional corepressor factor CTBP1 plays a critical role in Notch2 signalling. Thus, we identified a novel regulatory axis between lnc00492 and CTBP1 in B cells, suggesting that lnc00492 is essential for marginal zone B-cell development.

A Bioinspired Hemostatic Powder Derived from the Skin Secretion of Andrias davidianus for Rapid Hemostasis and Intraoral Wound Healing.

High-performance hemostasis has become increasingly essential in treating various traumas. However, available topical hemostats still have various drawbacks and side-effects. Herein, hemostatic powders derived from the skin secretion of Andrias davidianus (SSAD) with controllable particle size are prepared using feasible frozen-ball milling following lyophilization for hemorrhage-control. Scanning electron microscopy, rheometry, and Brunauer-Emmett-Teller test are used to characterize the coagulation-promoting surface topography, rheological properties, and porous structure of the SSAD particles. The blood-coagulation assays showed that the SSAD powders can induce blood-absorption in a particle size-dependent manner. Particle sizes of the SSAD powders larger than 200 µm and smaller than 800 µm greatly affect the blood-clotting rate. Associated with the thromboelastography (TEG) and amino acid/protein composition analyses, the accessibility and diffusion of blood are mainly dependent on the wettability, adhesivity, and clotting factors of the SSAD particles. Rapid hemostasis in vivo further involves three hemorrhage models (liver, femoral artery, and tail) as well as an oral wound model, which suggest favorable hemostatic and simultaneous regenerative effects of the SSAD hemostatic powder. Considering its degradability and good biocompatibility, SSAD can be an optimal candidate for a new class of inexpensive, natural, and promising hemostatic and wound-dressing agent.

A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration.

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD-derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD-derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague-Dawley rats without suturing. The intimal SSAD-derived hydrogel, with a pore size of 241.7 ± 21.0 µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD-derived hydrogel, with a pore size of 3.3 ± 1.4 µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD-derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD-derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD-derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

Triglyceride-glucose index linked to all-cause mortality in critically ill patients: a cohort of 3026 patients.

BACKGROUND: Triglyceride-glucose (TyG) index as a reliable surrogate of insulin resistance (IR) has been shown to be related to adverse clinical outcomes in patients with acute coronary syndrome, heart failure, ischemic stroke and so on. However, the relationship between TyG index and all-cause mortality in intensive care unit (ICU) patients remains unknown. The purpose of this study was to investigate the correlation between TyG index and all-cause mortality to evaluate the impact of IR on the prognosis of this population. METHODS: This was a retrospective observational study that included 3026 patients who had an initial triglyceride and glucose data on the first day of ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. These patients were grouped into quartiles (Q1-Q4) according to TyG index. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality. RESULTS: During 10.46 years of follow-up, 1148 (37.9%) patients died, of which 350 (11.6%) occurred during the hospital stay and 258 (8.5%) occurred during the ICU stay. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with higher TyG index (log-rank P = 0.021). Multivariable Cox proportional hazards analyses showed that the TyG index was an independent risk predictor of ICU death (HR: 1.72, 95% CI 1.18-2.52, P = 0.005) and hospital death (HR: 2.19, 95% CI 1.59-3.03, P < 0.001), and each 1-unit increased in the TyG index, a 1.19-fold increase in the risk of death during the hospital stay. CONCLUSIONS: TyG index is strongly related to the all-cause mortality increasing in critically ill patients. This finding indicates that the TyG index might be useful in identifying people at high risk of ICU death and hospital death.