Structural characteristics and in vitro starch digestibility of oil-modified cooked rice with varied addition manipulations.

Lipid has crucial applications in improving the quality of starchy products during heat processing. Herein, the influence of lipid modification and thermal treatment on the physicochemical properties and starch digestibility of cooked rice prepared with varied addition manipulations was investigated. Rice bran oil (RO) and medium chain triglyceride oil (MO) manipulations were performed either before (BC) or after cooking (AC). GC-MS was applied to determine the fatty acid profiles. Nutritional quality was analyzed by quantifying total phenolics, atherogenic, and thrombogenic indices. All complexes exhibited higher surface firmness, a soft core, and less adhesive. FTIR spectrum demonstrated that the guest component affected some of the dense structural attributes of V-amylose. The kinetic constant was in the range between 0.47 and 0.86 min-1 wherein before mode presented a higher value. The lowest glucose release was observed in the RO_BC sample, whereas the highest complexing index was observed in the RO_AC sample, indicating that the dense molecular configuration of complexes that could resist enzymatic digestion was more critical than the quantity of complex formation. Despite the damage caused by mass and heat transfer, physical barrier, intact granule forms, and strengthened dense structure were the central contributors affecting the digestion characteristics of lipid-starch complexes.

BCR::ABL1 Kinase N-lobe Mutants Confer Moderate to High Degrees of Resistance to Asciminib.

Secondary kinase domain mutations in BCR::ABL1 represent the most common cause of resistance to tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia patients. The first five approved BCR::ABL1 TKIs target the ATP-binding pocket. Mutations confer resistance to these ATP-competitive TKIs and those approved for other malignancies by decreasing TKI affinity and/or increasing ATP affinity. Asciminib, the first highly active allosteric TKI approved for any malignancy, targets an allosteric regulatory pocket in the BCR::ABL1 kinase C-lobe. As a non-ATP-competitive inhibitor, the activity of asciminib is predicted to be impervious to increases in ATP affinity. Here we report several known mutations that confer resistance to ATP-competitive TKIs in the BCR::ABL1 kinase N-lobe that are distant from the asciminib binding pocket yet unexpectedly confer in vitro resistance to asciminib. Among these is BCR::ABL1 M244V, which confers clinical resistance even to escalated asciminib doses. We demonstrate that BCR::ABL1 M244V does not impair asciminib binding, thereby invoking a novel mechanism of resistance. Molecular dynamics simulations of the M244V substitution implicate stabilization of an active kinase conformation through impact on the -C helix as a mechanism of resistance. These N-lobe mutations may compromise the clinical activity of ongoing combination studies of asciminib with ATP-competitive TKIs.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Effects of Matrix Structure on Protein Digestibility and Antioxidant Property of Different Soybean Curds During In Vitro Digestion.

This study compared the three most common types of tofu (soybean curd), which were prepared by using magnesium chloride (MgCl2 tofu), calcium sulfate (CaSO4 tofu), and glucono-δ-lactone (GDL tofu) coagulants. The results showed that GDL tofu had a higher water holding capacity than MgCl2 tofu and CaSO4 tofu, which was attributed to its high surface hydrophobicity and disulfide bond content. GDL tofu possessed the lowest firmness, gumminess, and chewiness, along with a uniform network structure and a thin protein matrix. In contrast, MgCl2 tofu exhibited an inhomogeneous network structure with a thick protein matrix. Combining the results of protein hydrolysis degree, SDS-PAGE, and free amino acids during in vitro digestion, it was indicated that the degree of protein digestion in GDL tofu was the highest. After intestinal digestion, GDL tofu had the highest total phenolic content, ferric reducing antioxidant power, and DPPH value. These results demonstrated the superior protein digestibility and antioxidant property of GDL tofu during in vitro digestion due to its structural characteristics that facilitate enzyme diffusion in the matrix. The findings offer insight into the protein digestibility and antioxidant properties of different types of tofu during digestion from structural characteristic perspective and valuable reference information for consumer dietary nutrition.

To What Extent Do Low-Voltage Electrostatic Fields Play a Role in the Physicochemical Properties of Pork during Freezing and Storage?

Low-voltage electrostatic fields (LVEF) are recognized as a new technology that can improve the quality of frozen meat. To determine the extent to which LVEF assistance affects the quality of frozen pork for long-term storage, pork was frozen and stored at -18 and -38 °C for up to 5 months. Water-holding capacity, muscle microstructure, and protein properties were investigated after up to 5 months of frozen storage with and without LVEF assistance. In comparison to traditional -18 and -38 °C frozen storage, LVEF treatment inhibited water migration during frozen storage and thawing. As a result, thawing losses were reduced by 15.97% (-18 °C) and 3.38% (-38 °C) in LVEF-assisted compared to conventional freezing methods. LVEF helped to maintain the muscle fiber microstructure and reduce muscle protein denaturation by miniaturizing ice crystal formation by freezing. As a result of this study, LVEF is more suitable for freezing or short-term frozen storage, while a lower temperature plays a more significant role in long-term frozen storage.

Dangui Huoxue Preparation (DHP) Ameliorates Skin Fibrosis, Inflammation, and Vasculopathy in the Bleomycin-Induced Murine Model of Systemic Sclerosis.

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy with poor prognosis. Dangui Huoxue Preparation (DHP) is a clinically effective traditional Chinese herbal formula for the treatment of SSc in the hospital. This study aims to investigate the therapeutic effects and underlying molecular mechanisms of DHP in the treatment of SSc. SSc mice models are induced by bleomycin (BLM). Tissues of DHP group, normal control group, and positive control drug Sanqi Tongshu Capsule (STC) group are collected for inflammation, fibrosis, and vasculopathy. Also, the human dermal fibroblasts (HDF) stimulated with TGF-ß1 are analyzed for in vitro study. The expression levels of MCP-1, IFN-γ, IL-1ß, IL-10, Fizz1, iNOS, and IL12p40, and the mRNA levels of Col1a1, Col1a2, Col3a1, and Col5a1 are significantly decreased in all DHP groups and STC group compare with those in the BLM group. The main drug of DHP inhibits the proliferation and migration of HDF, reduces Ctgf, Itgb3, Itgb5 expression, and also inhibits the Smad3 pathway. In conclusion, DHP can ameliorate SSc skin inflammation, fibrosis, and vasculopathy, possibly suppressing the TGF-ß1/Smad3 signaling pathway through extracellular and intracellular mechanisms.

Tanshinone IIA ameliorates the development of dermal fibrosis in systemic sclerosis.

OBJECTIVES: We previously revealed the role of tanshinone IIA (TAN IIA) on endothelial cells and the impact of TAN IIA on the endothelial-to-mesenchymal transition in systemic sclerosis (SSc). In this study, we sought to further determine whether TAN IIA can directly act on the skin fibroblasts of scleroderma and look into its underlying anti-fibrotic mechanisms. METHODS: Bleomycin was used to establish the SSc mouse model. After TAN IIA treatment, dermal thickness, type I collagen and hydroxyproline content were measured. Primary fibroblasts were acquired from SSc patients and cultured in vitro, and the effects of TAN IIA on proliferation, apoptosis and the cell cycle of fibroblasts were detected. RESULTS: In a bleomycin-induced SSc model, we discovered that TAN IIA significantly improved skin thickness and collagen deposition, demonstrating a potent anti-fibrotic action. TAN IIA inhibits the proliferation of skin fibroblasts derived from SSc patients by causing G2/M cell cycle arrest and promoting apoptosis. Additionally, TAN IIA downregulated extracellular matrix gene transcription and collagen protein expression in skin fibroblasts in a dose-gradient-dependent manner. Furthermore, we showed how TAN IIA can reduce the activation of the transforming growth factor-ß (TGF-ß)/Smad and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways, which are important factors in SSc. CONCLUSIONS: In summary, these data suggest that TAN IIA can reduce SSc-related skin fibrosis by modulating the TGF-ß/Smad and MAPK/ERK signalling pathways. More importantly, our results imply that TAN IIA can directly act on the skin fibroblasts of SSc, therefore, inhibiting fibrosis.

The Dynamic Changes in the Composition and Diversity of Vaginal Microbiota in Women of Different Pregnancy Periods.

The vaginal microbiota undergoes subtle changes during pregnancy, which may affect different pregnancy responses. This study used the Illumina MiSeq high-throughput sequencing method to analyze the 16S rRNA gene amplicons of pregnant women and the vaginal microbiota structure of pregnant women at different pregnancy periods. There were a total of 15 pregnant women, with 45 samples were taken from these women, within half a year before becoming pregnant, in the last trimester, and 42 days postpartum. Before and after pregnancy, the female vaginal microbiota was mainly composed of Firmicutes, followed by Actinobacteriota and Proteobacteria. The abundance of Lactobacillus was relatively high. The α-diversity and microbial abundance were relatively low, and there was no significant difference in microbial composition between the two. After childbirth, the diversity and abundance of women's vaginal bacterial communities were higher, with a decrease in the number of Firmicutes and a higher abundance of Actinobacteria, Proteobacteria, and Bacteroidota. There was a significant difference in the microbial community structure before and after pregnancy. This study showed that the microbiota structure of the vagina of pregnant women was similar to before pregnancy, but after childbirth, there were significant changes in the microbiota of the vagina, with a decrease in the number of probiotics and an increase in the number of harmful bacteria, increasing the risk of illness.

[Identification of Peripheral Blood GZMK + CD8 + T Cells As Biomarkers of Alzheimer's Disease Based on Single-Cell Transcriptome].

Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the peripheral blood of patients with Alzheimer's disease (AD) as biomarkers. Methods: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells, was downloaded from the Gene Expression Omnibus (GEO) database and was analyzed in the RAD-Blood web server (http://www.bioinform.cn/RAD-Blood/). The changes in blood cell composition in AD patients were analyzed. The abnormal communications between different types of cells in AD patients were investigated by the CellChat R package. Results: There were two kinds of CD8 + T cells in the blood of AD patients and healthy individuals, one of which highly expressed granzyme K ( GZMK) (false discovery rate [FDR]<0.05), and the other highly expressed GZMA, GZMB, and GZMH (FDR<0.05). In the blood of AD patients, the content of GZMK + CD8 + T cells was increased by 32.9% ( P=5.15E-21), their interactions with other cell types were increased, and they might be associated with AD through the abnormal signal transduction of major histocompatibility complex class Ⅰ (MHC-Ⅰ). Erythrocyte provided the main ligands, that are, human leukocyte antigen (HLA) class Ⅰ molecules, including HLA- A, HLA- B, HLA- C, and HLA- E, for the abnormal MHC-Ⅰ signaling pathway of GZMK + CD8 + T cells. The RESISTIN signaling pathway was specifically enriched in the blood of AD patients. Conclusion: The increased content of peripheral blood GZMK + CD8 + T cells, the increased interaction between GZMK + CD8 + T cells and erythrocytes, and the enhanced RESISTIN pathway are potential blood biomarkers of AD.

Associations among multidomain lifestyles, chronic diseases, and dementia in older adults: a cross-sectional analysis of a cohort study.

Background: Unhealthy lifestyles and chronic diseases are commonly seen and treatable factors in older adults and are both associated with dementia. However, the synergistic effect of the interaction of lifestyles and chronic diseases on dementia is unknown. Methods: We determined independent associations of multidomain lifestyles and chronic diseases (cerebrovascular disease, diabetes, and hypertension) with dementia and examined their synergistic impact on dementia among older adults. The data were drawn from the Hubei Memory and Aging Cohort Study. We created a summary score of six factors for multidomain lifestyles. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV. Logistic regression and multiple correspondence analyses were used to explore the relationships among multidomain lifestyles, chronic diseases, and dementia. A sensitivity analysis was performed to minimize the interference of reverse causality and potential confounders. Results: Independent associations with dementia were found in unhealthy (OR = 1.90, 95% CI: 1.38-2.61) and intermediate healthy lifestyles (OR, 3.29, 2.32-4.68), hypertension (OR, 1.21, 1.01-1.46), diabetes (OR, 1.30, 1.04-1.63), and cerebrovascular disease (OR, 1.39, 1.12-1.72). Interactions of diabetes (p = 0.004), hypertension (p = 0.004), and lifestyles were significant, suggesting a combined impact on dementia. Sensitivity analysis supported the strong association among multidomain lifestyles, chronic diseases, and dementia prevalence. Conclusion: An unhealthy lifestyle was associated with a higher prevalence of dementia, regardless of whether the participants had chronic diseases; however, this association was stronger in individuals with chronic diseases. Multidomain lifestyles and chronic diseases may have an enhanced impact on dementia.

Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis.

Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc. Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration. Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-ß receptor inhibitor (SB-525334), and so on. Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies.

Prevalence and risk factors for subjective cognitive decline and the correlation with objective cognition among community-dwelling older adults in China: Results from the Hubei memory and aging cohort study.

INTRODUCTION: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent. METHODS: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses. RESULTS: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD. DISCUSSION: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia. HIGHLIGHTS: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.

Meta-analysis of the characteristic expression of circulating microRNA in type 2 diabetes mellitus with acute ischemic cerebrovascular disease.

Objective: To comprehensively evaluate the characteristics of the circulating microRNA expression profile in type 2 diabetic patients with acute ischemic cerebrovascular disease by systematic evaluation and meta-analysis. Methods: The literatures up to March 2022 related to circulating microRNA and acute ischemic cerebrovascular disease in type 2 diabetes mellitus were searched and screened from multiple databases. The NOS quality assessment scale was used to evaluate methodological quality. Heterogeneity tests and statistical analyses of all data were performed by Stata 16.0. The differences in microRNA levels between groups were illustrated by the standardized mean difference (SMD) and 95% confidence interval (95% CI). Results: A total of 49 studies on 12 circulating miRNAs were included in this study, including 486 cases of type 2 diabetes complicated with acute ischemic cerebrovascular disease and 855 controls. Compared with the control group (T2DM group), miR-200a, miR-144, and miR-503 were upregulated and positively correlated with acute ischemic cerebrovascular disease in type 2 diabetes mellitus patients. Their comprehensive SMD and 95% CI were 2.71 (1.64~3.77), 5.77 (4.28~7.26) and 0.73 (0.27~1.19), respectively. MiR-126 was downregulated and negatively correlated with acute ischemic cerebrovascular disease in type 2 diabetes mellitus patients, its comprehensive SMD and 95% CI were -3.64 (-5.56~-1.72). Conclusion: In type 2 diabetes mellitus patients with acute ischemic cerebrovascular disease, the expression of serum miR-200a, miR-503, plasma and platelet miR-144 was upregulated and the expression of serum miR-126 was downregulated. It may have diagnostic value in the early identification of type 2 diabetes mellitus with acute ischemic cerebrovascular disease.

Predicting risk on cardiovascular or cerebrovascular disease based on a physical activity cohort: Results from APAC study.

Commonly used prediction models have been primarily constructed without taking physical activity into account. Using the Kailuan physical activity cohorts from Asymptomatic Polyvascular Abnormalities in Community (APAC) study, we developed a 9-year cardiovascular or cerebrovascular disease (CVD) risk prediction equation. Participants in this study were included from APAC cohort, which included 5440 participants from the Kailuan cohort in China. Cox proportional hazard regression model was applied to construct sex-specific risk prediction equations for the physical activity cohort (PA equation). Proposed equations were compared with the 10-year risk prediction model, which is developed for atherosclerotic cardiovascular disease risk in Chinese cohorts (China-PAR equation). C statistics of PA equations were 0.755 (95% confidence interval, 0.750-0.758) for men and 0.801 (95% confidence interval, 0.790-0.813) for women. The estimated area under the receiver operating characteristic curves in the validation set shows that the PA equations perform as good as the China-PAR. From calibration among four categories of predicted risks, the predicted risk rates by PA equations were almost identical to the Kaplan-Meier observed rates. Therefore, our developed sex-specific PA equations have effective performance for predicting CVD for physically active cohorts in the physical activity cohort in Kailuan.

Chlorogenic acid ameliorated non-alcoholic steatohepatitis via alleviating hepatic inflammation initiated by LPS/TLR4/MyD88 signaling pathway.

Non-alcoholic steatohepatitis (NASH) is a severe pathological stage in non-alcoholic fatty liver disease (NAFLD) and is generally recognized to be induced by chronic inflammation. Natural compound chlorogenic acid (CGA) is well-known for its anti-inflammatory capacity. This study aimed at evaluating the alleviation of CGA on NASH and further exploring its engaged mechanism via focusing on abrogating hepatic inflammation. Our results showed that CGA had a good amelioration on NASH in vivo. CGA alleviated liver oxidative injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) activation and reduced liver steatosis via up-regulating peroxisome proliferator-activated receptor-alpha (PPARα). CGA attenuated hepatic inflammation in vivo, but didn't decrease the elevated lipopolysaccharide (LPS) content. CGA blocked the activation of nuclear factor kappa-B (NFκB) or inflammasome both in MCDD-fed mice and in LPS-stimulated macrophages. CGA was found to directly bind to myeloid differentiation primary response 88 (MyD88), and thus competitively blocked the interaction between toll-like receptor 4 (TLR4) and MyD88, thereby abrogating hepatic inflammation initiated by LPS-TLR4-MyD88. Moreover, the CGA-provided anti-inflammatory effect was obviously disappeared in macrophages overexpressed MyD88. Hence, CGA has an excellent efficacy in improving NASH. CGA alleviated liver inflammation during NASH progression through blocking LPS-TLR4-MyD88 signaling pathway via directly binding to MyD88.

Comparing diversity patterns and processes of microbial community assembly in water column and sediment in Lake Wuchang, China.

The study compare the diversity patterns and processes of microbial community assembly in the water and sediment of Lake Wuchang (China) using high-throughput sequencing of 16S rRNA gene amplicons. A higher microbial α-diversity in the sediment was revealed (P < 0.01), and the most common bacterial phyla in water column were Proteobacteria, Cyanobacteria and Actinobacteria, while Proteobacteria, Acidobacteria, Chloroflexi and Nitrospirae were dominant in sediment. Functions related to phototrophy and nitrogen metabolism primarily occurred in the water column and sediment, respectively. The microbial communities in water column from different seasons were divided into three groups, while no such dispersion in sediment based on PCoA and ANOSIM. According to Pearson correlation analysis, water temperature, dissolved oxygen, water depth, total nitrogen, ammonium, and nitrite were key factors in determining microbial community structure in water column, while TN in sediment, conductivity, and organic matter were key factors in sediment. However, the stochastic processes (|ßNTI| < 2) dominated community assembly in both the water column and sediment of Lake Wuchang. These data will provide a foundation for microbial development and utilization in lake water column and sediment under the circumstances of increasing tendency of lake ecological fishery in China.

GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels.

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.