Protein-protein interactions in cGAS-STING pathway: a medicinal chemistry perspective.

Protein-protein interactions (PPIs) play pivotal roles in biological processes and are closely linked with human diseases. Research on small molecule inhibitors targeting PPIs provides valuable insights and guidance for novel drug development. The cGAS-STING pathway plays a crucial role in regulating human innate immunity and is implicated in various pathological conditions. Therefore, modulators of the cGAS-STING pathway have garnered extensive attention. Given that this pathway involves multiple PPIs, modulating PPIs associated with the cGAS-STING pathway has emerged as a promising strategy for modulating this pathway. In this review, we summarize an overview of recent advancements in medicinal chemistry insights into cGAS-STING PPI-based modulators and propose alternative strategies for further drug discovery based on the cGAS-STING pathway.

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The Association of Dietary Diversity with Hyperuricemia among Community Inhabitants in Shanghai, China: A Prospective Research.

Hyperuricemia, a major worldwide burden on public hygiene, is closely connected with dietary habits. However, few studies have evaluated the association of dietary diversity with hyperuricemia. To preliminarily reveal the status of a diversified diet in preventing hyperuricemia based on a neighborhood-based, massive-scale cohort in China, a total of 43,493 participants aged 20-74 years old, with no history of hyperuricemia at baseline, were enrolled in the research from April 2016 to December 2019. The Dietary Diversity Score (DDS) was utilized to evaluate the dietary variety and split the participants into the low-, medium-, and high-DDS groups. Information on participants was connected to regional health information systems that acquired data on hyperuricemia instances up to 28 February 2023. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox proportional hazards models. Restricted cubic splines (RCS) were implemented to analyze dose-response correlation. A total of 1460 individuals with newly diagnosed hyperuricemia were observed over a median follow-up period of 5.59 years. Compared to the low-DDS group, HRs for the medium- and high-DDS groups were 0.87 (95% CI 0.76-0.99) and 0.80 (95% CI 0.70-0.91) in the fully adjusted model, respectively. The risk of hyperuricemia incidence was reduced by 5% for each 1 unit of DDS increase. A linear correlation of DDS with hyperuricemia emerged and further revealed that the intake of 8-10 broad categories of food could decrease the incidence of hyperuricemia. Our results validate the dietary principle of "food diversification" recommended in guidelines. Conclusions should be applied with caution considering the paucity of related evidence in additional nations.

TRPS1, a sensitive marker for different histological and molecular types of breast cancer.

OBJECTIVES: We explored Trichorhinophalangeal syndrome type 1 (TRPS1) expression in special types of breast carcinoma, and analyzed the correlation between TRPS1 and androgen receptor (AR) expression in triple-negative breast cancer (TNBC). METHODS: TRPS1 expression was analyzed in 801 patients with special types of breast carcinoma. A total of 969 TNBC were used to analyze the correlation between the expression of TRPS1 and AR. TRPS1 expression was evaluated in 1975 cases of breast cancer with different molecular types. RESULTS: A total of 801 special types of breast cancers were stained with TRPS1.TRPS1 was positive in 100% (63/63) of mucinous carcinoma, 100% (7/7) adenoid cystic carcinomas (4 classic adenoid cystic carcinomas and 3 solid-basaloid adenoid cystic carcinomas), 100% (4/4) tubular carcinomas, 100% (2/2) secretory carcinomas, and 99.59% (243/244) invasive lobular carcinomas, 99.26% (267/269) invasive micropapillary carcinomas, 97.44% (38/39) ER-positive neuroendocrine tumors, 94.44% (34/36) metaplastic breast carcinomas (MBCs), 63.73% (65/102) apocrine carcinomas. TRPS1 was negative in all triple-negative neuroendocrine carcinomas (0/7).TRPS1 was positive in 92.86% (26/28) of metastatic special types of breast cancer. TRPS1 and AR expression were analyzed in 969 cases of TNBC. 90.40% were positive for TRPS1, and 42.41% were positive for AR. A significant inverse correlation between TRPS1 and AR expression was shown in TNBC (p < .001). TRPS1 showed a higher positive rate (93.13%) in TNBC compared to GATA binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP-15) and forkhead box transcription Factor C 1 (FOXC1). CONCLUSIONS: In conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

Prevalence and risk factors of hearing loss in the Chinese population aged 45 years and older: Findings from the CHARLS baseline survey.

OBJECTIVE: This study aimed to determine the prevalence of hearing loss and identify associated risk factors in a Chinese population aged 45 years and older. STUDY DESIGN: This study employed a cross-sectional research design. Data from the 4th wave survey of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2018 were utilized. Participants were assessed using self-reported questionnaires, and various demographic and comorbidity factors were analyzed to elucidate the risk factors associated with hearing loss. METHODS: A total of 17,695 individuals from 10,257 households in 450 villages and urban settlements were included in the study. Hearing loss was assessed through self-reported questionnaires. Risk factors, including demographic characteristics and comorbidities, were analyzed to identify associations with hearing loss. RESULTS: The study population had a hearing loss prevalence rate of 17.9% (n = 3,179). Regional variations were observed, with highest rates in Chongqing (28.67%), Yunnan (25.12%), and Qinghai (24.36%), and lowest rates in Zhejiang (17.71%), Tianjin (10.56%), and Shanghai (9.26%). Age ≥70 was associated with higher risk (OR = 3, p<0.05), while being female was associated with reduced risk (OR = 0.81, p<0.05). Higher education level showed lower risk (OR<1, p<0.05). Non-agricultural workers had lower risk (OR = 0.67, p<0.05). Fewer social activities were correlated with decreased risk (OR = 0.89, p = 0.024). Ethnic minorities had slightly higher risk (OR = 1.23, p<0.05). CONCLUSION: This study provides valuable insights into the prevalence and risk factors associated with hearing loss in the Chinese population aged 45 years and older. The findings emphasize the importance of early detection and intervention, particularly among older individuals and those residing in specific regions, for effective hearing loss management.

The association between serum soluble α-Klotho and thyroid profile among adults from NHANES 2007-2012.

BACKGROUND: Thyroid hormone is the key endocrine regulator of growth, development, metabolism, and other bodily functions. α-Klotho has been involved in the aging process and acts as an endocrine factor involved in the regulation of various metabolic processes in humans. However, the relationship between α-Klotho and thyroid profile has not been uniformly recognize. OBJECTIVE: To determine the relationship between α-Klotho and thyroid profile in adult individuals. METHODS: Population data of 4614 adult individuals were obtained from the NHANES database during the period of 2007-2012. Weighted multivariable regression analysis was performed using a general linear model with serum α-Klotho as the independent variable and thyroid profile as the dependent variables, respectively. The generalized additive model was used for smoothing curve fitting and threshold effect analysis. RESULTS: α-Klotho was associated with a slightly higher FT3, TT3 and TT4 level in unadjusted and adjusted regression models. However, a higher α-Klotho level was associated with a lower TSH level. After α-Klotho was grouped as quantiles with reference (Q1), α-Klotho still showed a statistically significant positive correlation with FT3 and TT3 levels in Q2, Q3 and Q4. In addition, α-Klotho was positively corrected with TT4, but negatively associated with TSH in Q4. CONCLUSIONS: Serum soluble α-Klotho was positively associated with FT3, TT3 and TT4, but negatively correlated with TSH. The significant effect of α-Klotho on thyroid profile suggests its potential as a predictive marker of thyroid functions, indicating its possible involvement in the regulation of thyroid hormone secretion.

N, N'-bidentate ligand anchored palladium catalysts on MOFs for efficient Heck reaction.

Metal-organic frameworks (MOFs), recognized as advanced catalyst carriers due to their adjustable porous, diverse structure and highly exposed active sites, have earned increasing attention for their potential to address the longevity of catalytic centers. In this manuscript, we have devised and synthesized a multifunctional amino-pyridine benzoic acid (APBA) ligand to replace the modulator ligand of the MOF-808 and disperse the palladium catalytic centers atomically on the MOF-APBA. The resulting single-site catalytic system, Pd@MOF-APBA, demonstrates preeminent efficiency and stability, as evidenced by a high average turnover number (95000) and a low metal residue (4.8 ppm) in the Heck reaction. This catalyst has exhibited recyclability for multiple runs without significant loss of reactivity for gram-scale reactions. The catalyst's high activity and efficiency can be attributed to the suitable electrical properties and structures of the N, N'-bidentate ligand for the catalytic palladium ions, postponing their deactivations, including leaching and agglomeration.

[Comparison study of food, energy and nutrient intake by 24-hour dietary recall method on two consecutive days versus three consecutive days].

OBJECTIVE: To compare the differences in estimated food, energy, and nutrient intakes between the consecutive 3 days 24-hour dietary recall(24HR)(referred to as the 3-day method) and consecutive 2 days 24HR(referred to as the 2-day method) to provide a basis for the use of consecutive 2 days 24HR in China nutrition surveillance. METHODS: Using objective sampling to select participants in northern and southern provinces, dietary data were obtained through consecutive 3 days 24HR, and the average intakes of food, energy and nutrients were calculated for three days from Thursday to Saturday and two days on Friday and Saturday, respectively. The 3-day method was considered as the reference standard method to evaluate the performance of the 2-day method for estimating food, energy and nutrient intakes. RESULTS: Among 778 participants aged 18-60 years in urban and rural areas of two provinces, the errors of the mean and median of 2-day method for estimating the intake of four major food categories less than 6% compared with the 3-day method, and there were significant equivalencies(P<0.025) and no significant differences in four major food categories group(P>0.05). Of the 24 food groups estimated by the 2-day method, 17 had mean errors within 5%, the largest error was in animal offal(13.45%) and the smallest in fruit(0.15%), and there were significant equivalencies(P<0.025) and no significant differences in seven food groups(P>0.05). For energy and nutrients, the mean and median errors of energy were less than 0.5% and there were significant equivalencies(P<0.025) and no significant differences for energy(P>0.05). Among the 25 nutrients, except sodium, iodine and vitamin E, the mean and median errors of the other 22 nutrients were less than 5%, and there were significant equivalencies(P<0.025) and no significant differences in 16 nutrients(P>0.05). CONCLUSION: There was little difference between the two survey method in assessing the intake of high consumption frequency foods, energy and most nutrients at group level, the 2-day method can be used as an alternative to the 3-day method to collect dietary intake data with high consumption rates in the population.

Transcriptomic and Metabolomic Analyses Reveal Molecular Regulatory Networks for Pigmentation Deposition in Sheep.

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin-eosin (HE) and Masson-Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep.

Gender Disparities in the Association Between Educational Attainment and Cardiovascular-Kidney-Metabolic Syndrome: Cross-Sectional Study.

Background: Cardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. Objective: We aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life's Essential 8 construct. Methods: This study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. Results: Among 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. Conclusions: Low education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

Association between dietary niacin intake and lung function among American adults: A cross-sectional analysis from national health and nutrition examination survey, 2007-2012.

Background: The pathogenesis of pulmonary senescence involves immune system dysregulation, oxidative stress, and mitochondrial dysfunction. The effects on lung function of niacin, an essential coenzyme involved in mitochondrial energy metabolism with known antioxidant properties, are poorly understood. Methods: This cross-sectional study used data from the 2007-2012 National Health and Nutrition Examination Survey, including spirometry data and niacin intake information of 9706 adults. This study investigated various spirometry measures, such as forced expiratory volume in 1 s, forced vital capacity, pulse expiratory flow, (forced expiratory volume in 1 s)/(forced vital capacity)ratio, and predicted forced expiratory volume in 1 s and forced vital capacity percentages. Additionally, a secondary analysis was conducted using Global Initiative for Chronic Obstructive Lung Disease and chronic obstructive pulmonary disease. Foundation Spirometry Grade criteria to assess the relationship between niacin intake, airflow limitation, and obstruction. Multivariate regression models were used to adjust for relevant covariates. Results: The study included 9706 U S. adults (4788 men and 4918 women) with a median age of 46.2 years. After adjusting for relevant factors, a positive correlation was observed between niacin intake and lung function. Compared to the lowest quintile of niacin intake (Q1, ≤14.5 mg/day), individuals in the highest quintile (Q5, >34.5 mg/day) exhibited significant increases in lung function parameters, including forced expiratory volume in 1s (69.84 mL, p = 0.003), pulse expiratory flow (254.48 mL, p < 0.001), (forced expiratory volume in 1 s)/(forced vital capacity)(0.01, p = 0.041), percent predicted forced expiratory volume in 1 s(2.05, p = 0.002), and percent predicted forced vital capacity(1.29, p = 0.042).Subset analyses of individuals with spirometry-defined airflow obstruction showed associations of high niacin intake with significantly improved forced expiratory volume, pulse expiratory flow, and percent predicted pulse expiratory flow and an interaction among race, education, and smoking status with respect to the relationship between niacin intake and lung function parameters. Conclusions: Higher niacin intake was associated with increased measures of lung function. A diet rich in niacin-containing foods may play a role in improving lung health.