Adaptive truncation of the S gene in IBV during chicken embryo passaging plays a crucial role in its attenuation.

Like all coronaviruses, infectious bronchitis virus, the causative agent of infectious bronchitis in chickens, exhibits a high mutation rate. Adaptive mutations that arise during the production of live attenuated vaccines against IBV often decrease virulence. The specific impact of these mutations on viral pathogenicity, however, has not been fully elucidated. In this study, we identified a mutation at the 3' end of the S gene in an IBV strain that was serially passaged in chicken embryos, and showed that this mutation resulted in a 9-aa truncation of the cytoplasmic tail (CT) of the S protein. This phenomenon of CT truncation has previously been observed in the production of attenuated vaccines against other coronaviruses such as the porcine epidemic diarrhea virus. We next discovered that the 9-aa truncation in the S protein CT resulted in the loss of the endoplasmic-reticulum-retention signal (KKSV). Rescue experiments with recombinant viruses confirmed that the deletion of the KKSV motif impaired the localization of the S protein to the endoplasmic-reticulum-Golgi intermediate compartment (ERGIC) and increased its expression on the cell surface. This significantly reduced the incorporation of the S protein into viral particles, impaired early subgenomic RNA and protein synthesis, and ultimately reduced viral invasion efficiency in CEK cells. In vivo experiments in chickens confirmed the reduced pathogenicity of the mutant IBV strains. Additionally, we showed that the adaptive mutation altered the TRS-B of ORF3 and impacted the transcriptional regulation of this gene. Our findings underscore the significance of this adaptive mutation in the attenuation of IBV infection and provide a novel strategy for the development of live attenuated IBV vaccines.

Identification and Comparison of the Sialic Acid-Binding Domain Characteristics of Avian Coronavirus Infectious Bronchitis Virus Spike Protein.

Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and GD (GI-7), and the corresponding region of M41 (GI-1), as the minimal SABD using truncated protein histochemistry and neuraminidase assays. Both α-2,3- and α-2,6-linked sialic acids on the surfaces of CEK cells can be used as attachment receptors by IBV, leading to increased infection efficiency. However, 9-O acetylation of the sialic acid glycerol side chain inhibits IBV S1 and SABD protein binding. We further constructed recombinant strains in which the S1 gene or the SABD in the GD and SD genomes were replaced with the corresponding region from M41 by reverse genetics. Infecting chickens with these viruses revealed that the virulence and nephrotropism of rSDM41-S1, rSDM41-206, rGDM41-S1, and rGDM41-206 strains were decreased to various degrees compared to their parental strains. A positive sera cross-neutralization test showed that the serotypes were changed for the recombinant viruses. Our results provide insight into IBV infection of host cells that may aid vaccine design. IMPORTANCE To date, only α-2,3-linked sialic acid has been identified as a potential host binding receptor for IBV. Here, we show the minimum region constituting the sialic acid binding domain (SABD) and the binding characteristics of the S1 subunit of spike (S) protein of IBV strains SD (GI-19), GD (GI-7), and M41 (GI-1) to various sialic acids. The 9-O acetylation modification partially inhibits IBV from binding to sialic acid, while the virus can also bind to sialic acid molecules linked to host cells through an α-2,6 linkage, serving as another receptor determinant. Substitution of the putative SABD from strain M41 into strains SD and GD resulted in reduced virulence, nephrotropism, and a serotype switch. These findings suggest that sialic acid binding has diversified during the evolution of γ-coronaviruses, impacting the biological properties of IBV strains. Our results offer insight into the mechanisms by which IBV invades host cells.

Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

Integrating intratumoral and peritumoral radiomics with clinical risk factors for prognostic prediction in pancreatic ductal adenocarcinoma patients undergoing combined chemotherapy and HIFU ablation.

OBJECTIVE: A radiomics nomogram will be created utilizing MRI data from intratumoral and peritumoral areas to forecast survival outcomes in patients who have had treatment for pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 87 individuals diagnosed with PDAC were included in the study, with 60 patients in the training cohort and 27 patients in the validation cohort. A grand total of 2395 radiomics characteristics were extracted from the tumor region and the peritumoral region. The least absolute shrinkage and selection operator (LASSO) method was used to select features and create a radiomics score, also known as the Rad-score. A multivariate regression analysis was then conducted to build the radiomics nomogram. The evaluation of the nomogram included discrimination, calibration, and clinical utility assessments. RESULTS: Based on the conclusions derived from the multivariate Cox model, Rad-Score, jaundice, and tumor size were identified as independent risk factors for overall survival (OS). The inclusion of the Rad-score in the radiomics nomogram led to improved accuracy in predicting survival compared to the clinical model. Patients were categorized into high-risk and low-risk groups based on their Rad-Score. Kaplan-Meier analysis revealed a statistically significant difference between the two groups (p < 0.05). Furthermore, the radiomics nomogram demonstrated excellent ability to differentiate, calibrate, and provide clinical utility in both the training and validation groups. CONCLUSIONS: The MRI-based intratumoral and peritumoral radiomics nomogram, integrating the Rad-score and clinical data, provided better prognostic prediction for PDAC patients after HIFU treatment, which may hold great potential for guiding personalized care for these patients.

Discovery of a novel DYRK1A inhibitor with neuroprotective activity by virtual screening and in vitro biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is implicated in accumulation of amyloid ß-protein (Aß) and phosphorylation of Tau proteins, and thus represents an important therapeutic target for neurodegenerative diseases. Though many DYRK1A inhibitors have been discovered, there is still no marketed drug targeting DYRK1A. This is partly due to the lack of effective and safe chemotypes. Therefore, it is still necessary to identify new classes of DYRK1A inhibitors. By performing virtual screening with the workflow mainly composed of pharmacophore modeling and molecular docking as well as the following DYRK1A inhibition assay, we identified compound L9, ((Z)-1-(((5-phenyl-1H-pyrazol-4-yl)methylene)-amino)-1H-tetrazol-5-amine), as a moderately active DYRK1A inhibitor (IC50: 1.67 µM). This compound was structurally different from the known DYRK1A inhibitors, showed a unique binding mode to DYRK1A. Furthermore, compound L9 showed neuroprotective activity against okadaic acid (OA)-induced injury in the human neuroblastoma cell line SH-SY5Y by regulating the expression of Aß and phosphorylation of Tau protein. This compound was neither toxic to the SH-SY5Y cells nor to the human normal liver cell line HL-7702 (IC50: >100 µM). In conclusion, we have identified a novel DYRK1A inhibitor with neuroprotective activity through virtual screening and in vitro biological evaluation, which holds the promise for further study.

Sequential mediation model of social support, care burden, and internalized stigma among family function and depression in caregivers of patients with schizophrenia: evidence from a cross-sectional study in southwest China.

PURPOSE: There is a lack of comprehensive measurements and systematic evaluations of the depression in caregivers of patients with psychiatric disorders and the factors influencing them in China. This study aims to explore the relationship between family function and depression in caregivers of patients with schizophrenia at the individual, family, and social levels according to the ecological system theory and attachment theory. METHODS: In this study, multi-stage, stratified cluster sampling was adopted to sample caregivers of patients with schizophrenia as subjects from one to three counties of four counties in Yunnan, from September 2022 to March 2023. Collecting the current caregiver's demographic data, family functions, social support, care burden, depression and internalized stigma. RESULTS: The results of single-factor analysis show that age, education level, relationship with patients, and the degree of self-care of patients are the influencing factors of depression of people living with schizophrenia (p < 0.05). The scores of self-rating depression scale are higher for caregivers who have not received formal education, caregivers who cannot take care of themselves and the parents, spouses and children of patients. The results of Pearson correlation analysis show that depression is positively associated with internalized stigma and care burden, and negatively associated with social support and family function (p < 0.05). The results of multiple linear regression show that after controlling age, education level, the patient's self-care capacity, and relationship with patient, the internalized stigma (ß = 0.184, p = 0.01) is positively correlated with depression. The mediation effect route of family function → social support → care burden → internalized stigma → depression was significant with 95% confidence interval [-0.150, -0.01], and the chained mediation effect was 5.904%. CONCLUSIONS: To reduce the depression level in family caregivers of schizophrenia, apart from taking measures to improve the caregiver's family function, enhancing social support, decreasing care burden, and reducing internalized stigma are suggested.

Mediation of metabolic syndrome in the association between long-term exposure to particulate matter and incident cardiovascular disease: Evidence from a population-based cohort in Chengdu.

BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Out-of-pocket medical expenditures, remittances and health outcomes in China.

This study examines the relationship between out-of-pocket medical expenditures, remittances and health outcomes in China using Ordinary Least Squares (OLS) and Propensity Score Matching (PSM) methods. The analysis is based on data from the Global Financial Inclusion database by the World Bank (2021), encompassing a sample of 3,446 individuals. The results indicate that out of-pocket expenditure has a negative impact on health outcomes, while remittance shows a positive association across all age groups, including reproductive and non-reproductive populations. These findings suggest that high out-of-pocket medical costs may hinder access to healthcare services and lead to poorer health outcomes. Conversely, remittance plays a beneficial role in improving health outcomes, highlighting the potential of financial support to positively impact the well-being of individuals.

Cette étude examine la relation entre les dépenses médicales directes, les envois de fonds et les résultats de santé en Chine à l'aide des méthodes des moindres carrés ordinaires (OLS) et de l'appariement des scores de propension (PSM). L'analyse est basée sur les données de la base de données Global Financial Inclusion de la Banque mondiale (2021), portant sur un échantillon de 3 446 personnes. Les résultats indiquent que les dépenses directes ont un impact négatif sur les résultats en matière de santé, tandis que les envois de fonds montrent une association positive dans tous les groupes d'âge, y compris les populations reproductrices et non reproductrices. Ces résultats suggèrent que des frais médicaux élevés peuvent entraver l'accès aux services de santé et conduire à de moins bons résultats en matière de santé. À l'inverse, les envois de fonds jouent un rôle bénéfique dans l'amélioration des résultats en matière de santé, soulignant le potentiel du soutien financier à avoir un impact positif sur le bien-être des individus.

[Bionic design, preparation and clinical translation of oral hard tissue restorative materials].

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

Role of Stress Granules in Suppressing Viral Replication by the Infectious Bronchitis Virus Endoribonuclease.

Infectious bronchitis virus (IBV), a γ-coronavirus, causes the economically important poultry disease infectious bronchitis. Cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation. Previous studies suggested that SGs were involved in the antiviral activity of host cells to limit viral propagation. Here, we aimed to delineate the molecular mechanisms regulating the SG response to pathogenic IBV strain infection. We found that most chicken embryo kidney (CEK) cells formed no SGs during IBV infection and IBV replication inhibited arsenite-induced SG formation. This inhibition was not caused by changes in the integrity or abundance of SG proteins during infection. IBV nonstructural protein 15 (Nsp15) endoribonuclease activity suppressed SG formation. Regardless of whether Nsp15 was expressed alone, with recombinant viral infection with Newcastle disease virus as a vector, or with EndoU-deficient IBV, the Nsp15 endoribonuclease activity was the main factor inhibiting SG formation. Importantly, uridine-specific endoribonuclease (EndoU)-deficient IBV infection induced colocalization of IBV N protein/dsRNA and SG-associated protein TIA1 in infected cells. Additionally, overexpressing TIA1 in CEK cells suppressed IBV replication and may be a potential antiviral factor for impairing viral replication. These data provide a novel foundation for future investigations of the mechanisms by which coronavirus endoribonuclease activity affects viral replication. IMPORTANCE Endoribonuclease is conserved in coronaviruses and affects viral replication and pathogenicity. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal, and reproductive systems, causing millions of dollars in lost revenue to the poultry industry worldwide annually. Mutating the viral endoribonuclease poly(U) resulted in SG formation, and TIA1 protein colocalized with the viral N protein and dsRNA, thus damaging IBV replication. These results suggest a new antiviral target design strategy for coronaviruses.

Catalpol modulating the crosstalking between mesenchymal stromal cells and macrophages via paracrine to enhance angiogenesis and osteogenesis.

Due to the inflammatory responses associated with defect occurrence and materials implantation, immunoregulation has emerged as a promising strategy to enhance bone regeneration. It has been widely reported that a material could facilitate osteogenesis if it can guide macrophages to anti-inflammatory M2 phenotype, vice versa, a substrate will influence macrophage phenotype if it is osteoinductive. However, few studies have looked into the intercellular crosstalking directly. Herein, the compound catalpol was selected for its multiple functions to study the interactions between bone marrow mesenchymal stromal cells (BMSCs) and macrophages. This iridoid glucoside exhibits excellent anti-inflammatory and osteoinductive activities. The effects of catalpol on mediating M1/M2 polarization of macrophages, inhibiting osteoclast differentiation, promoting osteogenesis and angiogenesis were systematically investigated to correlate the biological responses of BMSCs and macrophages. To extend its in vivo application, the catalpol was then loaded onto an electrospun polylactide/gelatin composite fibrous mesh and subcutaneously implanted to evaluate the local inflammation and ectopic osteogenesis. The results revealed that the functions of catalpol displayed in modulating cellular behaviors are via cell paracrine to strengthen intercellular crosstalking, hence demonstrating that catalpol itself could serve as a promising bioactive stimulator for bone tissue engineering.

The association between chemical constituents of ambient fine particulate matter and obesity in adults: A large population-based cohort study.

OBJECTIVES: Current evidence demonstrated that ambient fine particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and its constituents may be obesogenic in children, but evidence from adults is lacking. Our aim was to characterize the association between PM2.5 and its constituents and obesity in adults. METHODS: We included 68,914 participants from the China Multi-Ethnic Cohort (CMEC) baseline survey. Three-year average concentrations of PM2.5 and its constituents were evaluated by linking pollutant estimates to the geocoded residential addresses. Obesity was defined as body mass index (BMI) ≥ 28 kg/m2. Logistic regression was used to examine the relationship between PM2.5 and its constituents and obesity. We performed weighed quantile sum (WQS) regression to get the overall effect of PM2.5 and its constituents and the relative contribution of each constituent. RESULTS: Per-SD increase in PM2.5 (odds ratio [OR] = 1.43, 95% confidence interval [CI]: 1.37-1.49), black carbon (BC) (1.42, 1.36-1.48), ammonium (1.43, 1.37-1.49), nitrate (1.44, 1.38-1.50), organic matter (OM) (1.45, 1.39-1.51), sulfate (1.42, 1.35-1.48), and soil particles (SOIL) (1.31, 1.27-1.36) were positively associated with obesity, and SS (0.60, 0.55-0.65) was negatively associated with obesity. The overall effect (OR = 1.34, 95% CI: 1.29-1.41) of the PM2.5 and its constituents was positively associated with obesity, and ammonium made the most contribution to this relationship. Participants who were older, female, never smoked, lived in urban areas, had lower income or higher levels of physical activity were more significantly adversely affected by PM2.5, BC, ammonium, nitrate, OM, sulfate and SOIL compared to other individuals. CONCLUSION: Our study revealed that PM2.5 constituents except SS were positively associated with obesity, and ammonium played the most important role. These findings provided new evidence for public health interventions, especially the precise prevention and control of obesity.

Associations between major dietary patterns and blood pressure among Southwest Chinese: A cross-sectional analysis based on the China Multi-Ethnic Cohort (CMEC) study.

BACKGROUND AND AIMS: In the less developed multi-ethnic regions (LEMRs) of Southwest China, the associations between dietary patterns and blood pressure (BP) values remain unclear. We aimed to investigate such associations and related effect modifiers. METHODS AND RESULTS: This study included 81,433 participants from the China Multi-Ethnic Cohort Study. Dietary intakes during the year before the interview were measured with the Quantitative Food Frequency Questionnaire. Three major dietary patterns that were highly in line with geographical and ethnic distributions of the study population, i.e., "Sichuan Basin," "Yunnan-Guizhou Plateau," and "Qinghai-Tibet Plateau," were derived using principal component factor analysis. The multilinear regression model combined with inverse probability of exposure weighting was used to estimate the associations between dietary patterns and BP values. Comparing the highest with the lowest quintiles, the Sichuan Basin dietary pattern (characterized by urban lifestyles) was associated with 2.67 mmHg lower systolic blood pressure (SBP) (95% CI: -3.07 to -2.27) and 0.89 mmHg lower diastolic blood pressure (95% CI: -1.12 to -0.65). In contrast, both the Yunnan-Guizhou Plateau (characterized by agricultural lifestyles) and the Qinghai-Tibet Plateau dietary patterns (characterized by nomadic lifestyles) showed positive associations with BP. In the stratified analysis, the associations between dietary patterns and SBP were significantly stronger in women than in men for all three kinds of dietary patterns. CONCLUSION: Both major dietary patterns and their associations with BP showed a substantial disparity in LEMRs of Southwest China. Dietary patterns in regions of higher socioeconomic status are more conducive to reducing the rising of BP, especially for women and urban residents, which might provide insights into the BP control in LEMRs of Southwest China.

Asymptomatic hyperuricemia associated with increased risk of nephrolithiasis: a cross-sectional study.

BACKGROUND: Existing evidence shows that there is an independent correlation between nephrolithiasis and gout, and hyperuricemia is the most important risk factor for gout. However, hyperuricemia was often used as an accompanying symptom of gout to explore its association with nephrolithiasis, there were few studies to explore whether hyperuricemia itself or serum uric acid (SUA) is related to the risk of nephrolithiasis. Evidence on the relationship between hyperuricemia and nephrolithiasis is still insufficient. METHODS: A total of 22,303 participants aged 30 to 79 years who participated in the China Multi-Ethnic Cohort (CMEC) study in Yunnan Province from May 2018 to September 2019 were included in the study. All participants received standardized face-to-face interviews, medical examinations, and biochemical examinations. Logistic regression was used to estimate the association between hyperuricemia and nephrolithiasis, and a restricted cubic spline (RCS) model was used to explore the dose-response relationship between SUA and the risk of nephrolithiasis. RESULTS: 14.5% of all participants were diagnosed with hyperuricemia, and 12.1% were diagnosed with nephrolithiasis. After adjusting for all potential confounders, the OR (95%CI) for nephrolithiasis in participants with hyperuricemia compared with participants without hyperuricemia was 1.464 (1.312,1.633), p < 0.001. Restricted cubic spline regression analysis showed that the risk of nephrolithiasis increased with the increase of SUA, and when the level of SUA is higher than 356 µmol/L in males and higher than 265 µmol/L in females, there is a dose-response relationship between the increase of SUA and the risk of nephrolithiasis in both males and females (p for nonlinearity = 0.1668, p for nonlinearity = 0.0667). CONCLUSION: Asymptomatic hyperuricemia is associated with an increased risk of developing nephrolithiasis. Before reaching the diagnostic criteria for hyperuricemia, the risk of nephrolithiasis rises with the increase in SUA. This suggests that controlling SUA levels may be significant for the prevention of nephrolithiasis.

The association between tea consumption and blood pressure in the adult population in Southwest China.

OBJECTIVES: Prior research on the effect of tea consumption on blood pressure (BP) generated inconsistent findings. The objective of this study was to explore the effects of different types of tea consumption on BP. METHODS: We included 76,673 participants aged 30-79 from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Binary logistic regression was used to analyze the influences of different types of tea consumption on the risk of hypertensive BP. Moreover, multiple linear regression was used to examine the association between tea drinking and BP. RESULTS: Tea consumption was associated with a reduced risk of hypertensive BP by 10% (AOR: 0.90, 95%CI: 0.86-0.94). While dark tea was related to a 1.79-5.31 mmHg reduction in systolic blood pressure (SBP) and a 0.47-1.02 mmHg reduction in diastolic blood pressure (DBP), sweet tea, regardless of the duration, frequency, or amount of consumption, significantly was associated with a reduced SBP by 3.19-7.18 mmHg. Green tea also was associated with a reduced SBP by 1.21-2.98 mmHg. Although scented tea was related to reduced SBP by 1.26-2.48 mmHg, the greatest effect came from the long duration (> 40 years:ß=-2.17 mmHg, 95%CI=-3.47 mmHg --0.87 mmHg), low frequency (1-2 d/w: ß = -2.48 mmHg, 95%CI=-3.76 mmHg--1.20 mmHg), and low amount (≤ 2 g/d: ß=-2.21 mmHg, 95%CI=-3.01 mmHg--1.40 mmHg). Additionally, scented tea was correlated to a decrease in DBP at the frequency of 1-2 d/w (ß=-0.84 mmHg, 95%CI=-1.65 mmHg--0.02 mmHg). Drinking black tea only was associated with lowered SBP. The protective effect of black tea on SBP was characterized by the long-duration (> 15 years, -2.63--5.76 mmHg), high frequency (6-7 d/w, -2.43 mmHg), and medium amount (2.1-4.0 g/d, -3.06 mmHg). CONCLUSION: Tea consumption was associated with lower SBP and a reduced risk of hypertensive BP. The antihypertensive effect varies across types of tea consumed.

Combination of mineral protection and molecular characteristics rather than alone to govern soil organic carbon stability in Qinghai-Tibetan plateau wetlands.

Wetlands in the Yarlung Tsangpo River Basin (YTR) on the Qinghai-Tibet Plateau provide immense soil organic carbon (SOC) storage, which is highly susceptible to climate warming and requires urgent deciphering SOC stabilization mechanisms of long-term protection of SOC against decomposition. Conflicting views exist regarding whether persistent SOC is controlled by molecular features or by mineral protection. As such, this study quantified SOC stability using two thermal indices (TG-T50, and DSC), described molecular features of SOC using pyrolysis-gas chromatography-mass spectrometry, and measured SOC protection by minerals using a chemical extraction method. Results indicated SOC of topsoils had higher thermal stability, with TG-T50 and DSC-T50 of 337.61 °C and 384.58 °C, than that of subsoils with TG-T50 and DSC-T50 of 337.32 and 382.67 °C, respectively. We found subsoils had significantly higher proportions of aliphatic and aromatic compounds, while existed higher SOC associated with minerals. It seemed SOC stabilization differed with soil depths, in which mineral protection dictated SOC thermal stability in topsoils while molecular features posed a more important constraint on SOC stabilization in subsoils. Overall, our findings support the hypothesis of physical and chemical protection but emphasized that SOC thermal stability largely depended on to extent of the combination between molecular features and mineral protection, which explained 55% in topsoils and 73% in subsoils, respectively.

Impacts of spectral characteristics of dissolved organic matter on methylmercury contents in peatlands, Northeast China.

Dissolved organic matter (DOM) plays an important role in promoting or suppressing methylmercury (MeHg) production in wetlands. However, the effects of DOM spectral characteristics on MeHg levels remain poorly understood in boreal peatlands in Northeast China, where is undergoing remarkable climate warming. In the present work, soil samples were collected from 22 peatlands in the Greater Khingan Mountains (GKM) to test the hypothesis that DOM spectral properties control MeHg levels. DOM was characterized by UV-Vis absorption and fluorescence spectroscopy; the three-dimensional fluorescence excitation-emission matrix (EEM) was used to unveil the origin of DOM. The average total mercury (THg) and MeHg contents were 112.76 µg/kg and 12.43 µg/kg across all peatlands, respectively. There was a significantly positive correlation between MeHg and the longitude spanning the range from 120 to 123°E (p < 0.05). Proportions of MeHg to THg (%MeHg), 12.3% on average, were positively correlated with DOM humification degree at p < 0.05 level. Protein-like components of DOM (P-like) were negatively related to %MeHg. DOM had positive effects on THg, and P-like components, HIX and BIX can negatively affect THg as well as MeHg. Our findings demonstrate that the spectral characteristics of DOM in soil are crucial to the content of methyl mercury in the GKM soil.

Hydrogen Bonding Enables Polymer Hydrogels with pH-Induced Reversible Dynamic Responsive Behaviors.

Poly(acrylic acid-co-N-vinylcaprolactam) (PAN) hydrogels containing multiple hydrogen bonds can exhibit pH-induced reversible dynamic responsive behaviors. When placing a transparent hydrogel in an acid bath, as hydrogen bonds between comonomer units involving protonated COOH groups are formed faster than water diffusion, a nonequilibrium light-scattering state is formed to turn the hydrogel opaque, while as the swelling equilibrium is reached over time, the hydrogel regains its transparency. Likewise, when the transparent, hydrogen-bonded hydrogel is subsequently immersed in DI water, faster water absorption occurs in where more COOH groups are deprotonated, which also generates a light-scattering state leading to opacity, while the transparency is slowly recovered after equilibrium. Using such two-way dynamic transparency evolution, a PAN-based hydrogel material is prepared to demonstrate a dynamic memory system for information memorizing-forgetting and recalling-forgetting.

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways.

BACKGROUND: Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts. METHODS: A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin-Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting. RESULTS: After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability. CONCLUSIONS: Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

An overview of signaling pathways regulating YAP/TAZ activity.

YAP and TAZ are ubiquitously expressed homologous proteins originally identified as penultimate effectors of the Hippo signaling pathway, which plays a key role in maintaining mammalian tissue/organ size. Presently, it is known that YAP/TAZ also interact with various non-Hippo signaling pathways, and have diverse roles in multiple biological processes, including cell proliferation, tissue regeneration, cell lineage fate determination, tumorigenesis, and mechanosensing. In this review, we first examine the various microenvironmental cues and signaling pathways that regulate YAP/TAZ activation, through the Hippo and non-Hippo signaling pathways. This is followed by a brief summary of the interactions of YAP/TAZ with TEAD1-4 and a diverse array of other non-TEAD transcription factors. Finally, we offer a critical perspective on how increasing knowledge of the regulatory mechanisms of YAP/TAZ signaling might open the door to novel therapeutic applications in the interrelated fields of biomaterials, tissue engineering, regenerative medicine and synthetic biology.