Heat shock transcription factor 1 facilitates liver cancer progression by driving super-enhancer-mediated transcription of MYCN.

BACKGROUND: Heat shock transcription factors (HSFs) play crucial roles in the development of malignancies. However, the specific roles of HSFs in hepatocellular carcinoma (HCC) have yet to be fully elucidated. AIMS: To explore the involvement of the HSF family, particularly HSF1, in the progression and prognosis of HCC. MATERIALS & METHODS: We conducted a thorough analysis of HSF expression and copy number variations across various cancer datasets. Specifically focusing on HSF1, we examined its expression levels and prognostic implications in HCC. In vitro and in vivo experiments were carried out to evaluate the impact of HSF1 on liver cancer cell proliferation. Additionally, we utilized CUT&Tag, H3K27 acetylation enrichment, and RNA sequencing (RNA-seq) to investigate the super-enhancer (SE) regulatory landscapes of HSF1 in liver cancer cell lines. RESULTS: HSF1 expression is elevated in HCC and is linked to poor prognosis in several datasets. HSF1 stimulates liver cancer cell proliferation both in vitro and in vivo, partly through modulation of H3K27ac levels, influencing enhancer distribution. Mechanistically, our findings demonstrate that HSF1 transcriptionally activates MYCN expression by binding to its promoter and SE elements, thereby promoting liver cancer cell proliferation. Moreover, increased MYCN expression was detected in HCC tumors and correlated with unfavorable patient outcomes. DISCUSSION: Our study sheds light on previously unexplored aspects of HSF1 biology, identifying it as a transcription factor capable of shaping the epigenetic landscape in the context of HCC. Given HSF1's potential as an epigenetic regulator, targeting the HSF1-MYCN axis could open up new therapeutic possibilities for HCC treatment. CONCLUSION: The HSF1-MYCN axis constitutes a transcription-dependent regulatory mechanism that may function as both a prognostic indicator and a promising therapeutic target in liver cancer. Further exploration of this axis could yield valuable insights into novel treatment strategies for HCC.

Integrated network pharmacology and metabolomics to study the potential mechanism of Jiawei Yinchenhao decoction in chronic hepatitis B.

Chronic hepatitis B infection (CHB) is a major risk factor for the development of hepatocellular carcinoma (HCC) globally and continues to pose a significant global health challenge. Jiawei Yinchenhao decoction (JWYCH) is a modified version of Yinchenhao decoction (YCHD), which is widely used to treat liver diseases including icteric hepatitis, cholelithiasis, and hepatic ascites. However, the effectiveness and underlying mechanism of JWYCH on CHB are still unclear. This study aimed to investigate the impact of JWYCH on CHB and explore the underlying mechanism via network pharmacology and metabolomics. C57BL/6 mice were administered rAAV-HBV1.3 via hydrodynamic injection (HDI) to establish the CHB model. The infected mice were orally administered JWYCH for 4 weeks. HBsAg, HBeAg, HBV DNA, the serum liver function index, and histopathology were detected. In addition, network pharmacology was used to investigate potential targets, whereas untargeted metabolomics analysis was employed to explore the hepatic metabolic changes in JWYCH in CHB mice and identify relevant biomarkers and metabolic pathways. JWYCH was able to reduce HBeAg levels and improve liver pathological changes in mice with CHB. Additionally, metabolomics analysis indicated that JWYCH can influence 105 metabolites, including pipecolic acid, alpha-terpinene, adenosine, and L-phenylalanine, among others. Bile acid metabolism, arachidonic acid metabolism, and retinol metabolism are suggested to be potential targets of JWYCH in CHB. In conclusion, JWYCH demonstrated a hepatoprotective effect on a mouse model of CHB, suggesting a potential alternative therapeutic strategy for CHB. The effect of JWYCH is associated mainly with regulating the metabolism of bile acid, arachidonic acid, and retinol. These differentially abundant metabolites may serve as potential biomarkers and therapeutic targets for CHB.

Characterization and genome sequence of N,N-dimethylformamide degradation in Paracoccus sulfuroxidans DM175A1-1 isolated from activated sludge of wastewater.

N,N-dimethylformamide (DMF) is an organic solvent with stable chemical properties and high boiling point. Based on its good solubility, DMF is widely used in synthetic textile, leather, electronics, pharmaceutical and pesticide industries. However, the DMF pollutes the environment and does harm to human liver function, kidney function, and nerve function. Herein, an efficient DMF-degrading strain, DM175A1-1, was isolated and identified as Paracoccus sulfuroxidans. This strain can use DMF as the sole source of carbon and nitrogen. Whole-genome sequencing of strain DM175A1-1 revealed that it has a 3.99-Mbp chromosome a 120-kbp plasmid1 and a 40-kbp plasmid2. The chromosome specifically harbors the dmfA1 and dmfA2 essential for the initial steps of DMF degradation. And it also carries the some part of genes facilitating subsequent methylotrophic metabolism and glutathione-dependent pathway. Through further DMF tolerance degradation experiments, DM175A1-1 can tolerate DMF concentrations up to 10,000 mg/L, whereas the majority of Paracoccus strains could only show degradation activity below 1,000 mg/L. And the efficiency of organic nitrogen conversion to NH3-N in DMF can reach 99.0% when the hydraulic retention time (HRT) is controlled at 5 days. Meanwhile, it showed a significant degradation effect at a pharmaceutical enterprise in Zhejiang Province with high concentration of DMF wastewater. This study provides a new strain Paracoccus sulfuroxidans DM175A1-1 which shows a significant influence on DMF degradation, and reveals the characterization on its DMF degradation. It lays the foundation for the application of biological method in the efficient degradation of DMF in industrial wastewater.

Mass Spectrometry-Based Direct Sequencing of tRNAs De Novo and Quantitative Mapping of Multiple RNA Modifications.

Despite the extensive use of next-generation sequencing (NGS) of RNA, simultaneous direct sequencing and quantitative mapping of multiple RNA nucleotide modifications remains challenging. Mass spectrometry (MS)-based sequencing can directly sequence all RNA modifications without being limited to specific ones, but it requires a perfect MS ladder that few tRNAs can provide. Here, we describe an MS ladder complementation sequencing approach (MLC-Seq) that circumvents the perfect ladder requirement, allowing de novo MS sequencing of full-length heterogeneous cellular tRNAs with multiple nucleotide modifications at single-nucleotide precision. Unlike NGS-based methods, which lose RNA modification information, MLC-Seq preserves RNA sequence diversity and modification information, revealing new detailed stoichiometric tRNA modification profiles and their changes upon treatment with the dealkylating enzyme AlkB. It can also be combined with reference sequences to provide quantitative analysis of diverse tRNAs and modifications in total tRNA samples. MLC-Seq enables systematic, quantitative, and site-specific mapping of RNA modifications, revealing the truly complete informational content of tRNA.

Polyoxometalates and their composites for antimicrobial applications: Advances, mechanisms and future prospects.

The overuse of antibiotics can lead to the development of antibiotic-resistant bacteria, which can be even more difficult to treat and pose an even greater threat to public health. In order to address the issue of antibiotic-resistant bacteria, researchers currently are exploring alternative methods of sterilization that are both effective and sustainable. Polyoxometalates (POMs), as emerging transition metal oxide compounds, exhibit significant potential in various applications due to their remarkable tunable physical and chemical performance, especially in antibacterial fields. They constitute a diverse family of inorganic clusters, characterized by a wide array of composition, structures and charges. Presently, several studies indicated that POM-based composites have garnered extensive attention in the realms of the antibacterial field and may become promising materials for future medical applications. Moreover, this review will focus on exploring the antibacterial properties and mechanisms of different kinds of organic-inorganic hybrid POMs, POM-based composites, films and hydrogels with substantial bioactivity, while POM-based composites have the dual advantages of POMs and other materials. Additionally, the potential antimicrobial mechanisms have also been discussed, mainly encompassing cell wall/membrane disruption, intracellular material leakage, heightened intracellular reactive oxygen species (ROS) levels, and depletion of glutathione (GSH). These findings open up exciting possibilities for POMs as exemplary materials in the antibacterial arena and expand their prospective applications.

The molecular basis of flavonoid biosynthesis response to water, light, and temperature in grape berries.

Flavonoids, including proanthocyanidins (PAs), anthocyanins and flavonols are essential secondary metabolites that contribute to the nutritional value and sensory quality of grape berry and red wine. Advances in molecular biology technology have led to substantial progress in understanding the regulation of flavonoid biosynthesis. The influence of terroir on grape berries and wine has garnered increasing attention, yet its comprehensive regulatory network remains underexplored. In terms of application, environmental factors such as water, light, and temperature are more easily regulated in grapevines compared to soil conditions. Therefore, we summarize their effects on flavonoid content and composition, constructing a network that links environmental factors, hormones, and metabolites to provide a deeper understanding of the underlying mechanisms. This review enriches the knowledge of the regulatory network mechanisms governing flavonoid responses to environmental factors in grapes.

The growth-promoting effects of protein hydrolysates and their derived peptides on probiotics: structure-activity relationships, mechanisms and future perspectives.

Lactic acid bacteria (LAB) are the main probiotics currently available in the markets and are essential for maintaining gut health. To guarantee probiotic function, it is imperative to boost the culture yield of probiotic organisms, ensure the sufficient viable cells in commercial products, or develop effective prebiotics. Recent studies have shown that protein hydrolysates and their derived peptides promote the proliferation of probiotic in vitro and the abundance of gut flora. This article comprehensively reviews different sources of protein hydrolysates and their derived peptides as growth-promoting factors for probiotics including Lactobacillus, Bifidobacterium, and Saccharomyces. We also provide a preliminary analysis of the characteristics of LAB proteolytic systems focusing on the correlation between their elements and growth-promoting activities. The structure-activity relationship and underlying mechanisms of growth-promoting peptides and their research perspectives are thoroughly discussed. Overall, this review provides valuable insights into growth-promoting protein hydrolysates and their derived peptides for proliferating probiotics in vivo or in vitro, which may inspire researchers to explore new options for industrial probiotics proliferation, dairy products fermentation, and novel prebiotics development in the future.

A novel scoring system based on sIL-2R for predicting IVIG resistance in Chinese children with KD.

OBJECTIVE: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. METHODS: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. RESULTS: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. CONCLUSION: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

A comparative evaluation of bioequivalence of Gan & Lee glargine U300 and Toujeo® in Chinese healthy male participants.

Background: To assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants. Methods: A single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax). Results: GL Glargine U300 demonstrated comparable PK parameters (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of M1) and PD responses [AUCGIR.0-24h, GIRmax, AUCGIR.0-12h, and AUCGIR.12-24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events. Conclusion: The PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®. Clinical trial registration: https://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Sequence-encoded bioactive protein-multiblock polymer conjugates via quantitative one-pot iterative living polymerization.

Protein therapeutics are essential in treating various diseases, but their inherent biological instability and short circulatory half-lives in vivo pose challenges. Herein, a quantitative one-pot iterative living polymerization technique is reported towards precision control over the molecular structure and monomer sequence of protein-polymer conjugates, aiming to maximize physicochemical properties and biological functions of proteins. Using this quantitative one-pot iterative living polymerization technique, we successfully develop a series of sequence-controlled protein-multiblock polymer conjugates, enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations are performed to disclose the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution in mice. Overall, this work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions as a promising candidate in disease treatment.

TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway.

BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC. METHODS: Bioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC. RESULTS: GRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/ß-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/ß-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing. CONCLUSIONS: Our work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target.

The impact of NUMB on chicken abdominal adipogenesis: A comprehensive analysis.

Excessive abdominal fat deposition negatively impacts poultry meat production and carcass yield. Identification of novel adipogenesis regulators may help improve production performance declines caused by excessive fat deposition. NUMB Endocytic Adaptor Protein (NUMB) typically functions as a cell fate determinant and plays a significant role in cell development and various diseases. Here, we found that NUMB is abundantly expressed in chicken abdominal fat depots and is induced in cultured adipocytes following adipogenic treatment. The gain- and loss-of-function experiments demonstrated that NUMB promotes the proliferation and G1/S transition of chicken adipocytes, enhances adipocyte differentiation, and increases the expression of PPARγ1 transcript. Through mRNA-seq analysis and molecular experiments, we further confirmed that NUMB inhibits the transcriptional activation of the NOTCH1 pathway and the expression of the downstream transcription factor HES1 by inducing NOTCH1 degradation. Nevertheless, the inhibition of the NOTCH1/HES1 axis alone cannot fully explain NUMB's role in adipogenesis, as NUMB also regulates the expression of multiple adipogenic transcription factors such as E2F1, EGR2, and NR4A3. Our data suggest that NUMB is a potent activator of adipogenesis and enhances our understanding of its regulatory mechanisms in chicken abdominal fat deposition.

Advances in oligosaccharides and polysaccharides with different structures as wall materials for probiotics delivery: A review.

Probiotics are active microorganisms that are beneficial to the health of the host. However, probiotics are highly sensitive to the external environment, and are susceptible to a variety of factors that reduce their activity during production, storage, and use. Microencapsulation is an effective method that enhances probiotic activity. Macromolecules like polysaccharides, who classified as biologically active prebiotics, have attracted significant attention for their utility in probiotic microencapsulation. This article summarized the types of commonly used microencapsulation materials and their structural characteristics from the perspective of polysaccharides prebiotics. It also discussed recent advancements, probiotic-prebiotic microcapsule-based modulation of the immune system, as well as the associated limitations. Furthermore, the advantages and disadvantages of eight prebiotics as microencapsulation wall materials. The honeycomb structure of ß-glucan enhances the bioavailability of probiotics, while, fructooligosaccharide and galactooligosaccharides improve microbead structure to tightly encapsulate probiotics. The terminal reducing groups of isomaltooligosaccharides and the free hydroxyl groups in xylooligosaccharides also positively affect the structure of microcapsules. Prebiotics not only enhance the survival rate and biological activity of probiotics as embedding materials during storage, but also exert their own probiotic effects. Collectively, prebiotics holds great promise as microencapsulation materials for probiotics delivery.

Effects of vegetation cover and aquaculture pollution on viral assemblages in mangroves sediments.

Mangrove forests, a critical coastal ecosystem, face numerous anthropogenic threats, particularly from aquaculture activities. Despite the acknowledged significance of viruses in local and global biogeochemical cycles, there is limited knowledge regarding the community structure, genomic diversity, and ecological roles of viruses in mangrove forests ecosystems, especially regarding their responses to aquaculture. In this study, we identified 17,755 viral operational taxonomic units (vOTUs) from nine sediments viromes across three distinct ecological regions of the mangrove forests ecosystem: mangrove, bare flat, and aquaculture regions. Viral assemblages varied among three regions, and the pathogenic viruses associated with marine animals, such as the white spot syndrome virus (WSSV) from Nimaviridae, were identified in this study. The relative abundance of Nimaviridae in the bare flat region was higher than in other regions. Furthermore, viruses in distinct mangrove forests sediments regions have adapted to their environments by adopting distinct survival strategies and encoding various auxiliary metabolic genes involved in carbon metabolism and antibiotic resistance. These adaptations may have profound impacts on biogeochemical cycles. This study provides the first insights into the effects of vegetation cover and aquaculture on the community structure and ecological roles of viruses in mangrove forests sediments. These findings are crucial for understanding the risks posed by anthropogenic threats to mangrove forests ecosystems and informing effective management strategies.

Effects of physical processing on food protein allergenicity: A focus on differences between animal and alternative proteins.

In recent years, physical technologies have been widely employed to reduce food protein allergenicity due to their simplicity and stability. This paper summarizes recent research advances in these technologies, focusing on differences in their effects on allergenicity between animal and alternative proteins. The mechanisms of allergenicity reduction and the advantages and disadvantages of these technologies were compared. It was found that heating, although affording better allergenicity reduction than non-thermal treatment technologies, affects other properties of the food. Because of their higher molecular weights and more complex structures, animal proteins are less affected by physical technologies than alternative proteins. It is worth noting that there is a scarcity of existing technology to reduce the allergenicity of food proteins, and more technologies should be explored for this purpose. In addition, better allergenicity-reducing processing technologies should be designed from the perspectives of processing conditions, technological innovations, and combined processing technologies in the future.

Mitochondrial dysfunction and NLRP3 inflammasome: key players in kidney stone formation.

The mitochondrion serves as a critical intracellular organelle, engaging in essential roles in the regulation of energy production, oxidative stress management, calcium homeostasis, and apoptosis. One such disease that has been particularly associated with these functions is kidney stone disease (KSD), specifically calcium oxalate (CaOx). It is underpinned by oxidative stress and tissue inflammation. Recent studies have shed light on the vital involvement of mitochondrial dysfunction, the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome, endoplasmic reticulum stress and subsequent cell death in CaOx crystal retention and aggregation. These processes are pivotal in the pathogenesis of kidney stone formation. This review focuses on the pivotal roles of mitochondria in renal cell functions and provides an overview of the intricate interconnectedness between mitochondrial dysfunction and NLRP3 inflammasome activation in the context of KSD. It is essential to recognise the utmost significance of gaining a comprehensive understanding of the mechanisms that safeguard mitochondrial function and regulate the NLRP3 inflammasome. Such knowledge carries significant scientific implications and opens up promising avenues for the development of innovative strategies to prevent the formation of kidney stones.

Experimental study on migration characteristics of LNAPL in the aquitard under pumping conditions.

Research on the migration behaviors of contaminants in the aquitard has been deficient for an extended period. Clay is commonly employed as an impermeable layer or barrier to stop the migration of contaminants. However, under certain conditions, the clay layer may exhibit permeability to water, thereby allowing contaminants to infiltrate and potentially contaminate adjacent aquifers. Consequently, it holds immense importance to scrutinize and investigate the migration characteristics of light non-aqueous phase liquid (LNAPL) within the aquitard for the purposes of groundwater pollution control and remediation. To evaluate the environmental risk posed by organic contaminants in the aquitard, an experimental model was formulated and devised to monitor the LNAPL concentration in the aquitard under pumping conditions. The correlation between pumping rate and LNAPL concentration was investigated. A self-developed plexiglass sandbox model was used to simulate the migration characteristics of LNAPL in the aquitard under pumping conditions. Four experimental scenarios were designed, varying pumping rates, aquitard thicknesses, and groundwater level changes. The LNAPL concentration curve was derived by systematically tracking and analyzing LNAPL levels at various locations within the aquitard. The results indicated that higher pumping rates corresponded to increased migration of LNAPL, resulting in greater LNAPL ingress into the pumping well during extraction. A thicker aquitard demonstrated a more pronounced inhibitory effect on LNAPL, leading to an extended penetration time of LNAPL within the aquitard. The drawdown within the aquitard exerted a discernible influence on LNAPL migration, with the LNAPL concentration continuing to decrease in tandem with declining water levels during pumping. These research findings can establish a scientific foundation for the control and remediation of contaminants within aquitards.

The Relationship of Waist Circumference with the Morbidity of Cardiovascular Diseases and All-Cause Mortality in Metabolically Healthy Individuals: A Population-Based Cohort Study.

Background: This study explores the relationship between waist circumference and morbidity of cardiovascular diseases (CVD) and all-cause mortality in metabolically healthy individuals. Methods: A cohort of 5775 metabolically healthy participants from the 2001-2014 US National Health and Nutrition Examination Survey and National Death Index database was tracked over a median period of 81 months. These participants were divided into quartiles (Q1, Q2, Q3, Q4) based on increasing waist circumference. To compensate for missing covariates, multivariate multiple imputation methods were used. Adjusted logistic regression models were employed to examine the correlation between waist circumference and cardiovascular disease prevalence. Furthermore, Kaplan-Meier curves and multivariable Cox regression analysis were utilized to evaluate the association between waist circumference and all-cause mortality, both qualitatively and quantitatively. Results: The adjusted logistic regression model indicated that a 10 cm increase in waist circumference was associated with a 1.45 times higher prevalence of CVD. As a categorical variable, there was a significant upward trend in CVD incidence across quartiles of waist circumference. The adjusted odds ratios (95% confidence intervals) were 2.41 (1.13-5.53) for Q2, 2.65 (1.18-6.39) for Q3, and 2.53 (0.9-7.44) for Q4, compared to Q1. Notably, individuals with high waist circumference showed significantly poorer survival compared to those with low waist circumference (p = 0.008). The Cox regression analysis revealed that each 10 cm increase in waist circumference contributed to an ~8% increase in all-cause mortality. Conclusions: This study underscores a positive correlation between waist circumference and both CVD morbidity and all-cause mortality in metabolically healthy individuals. The findings highlight the significance of routinely monitoring waist circumference for effective CVD risk management, regardless of metabolic health status.

Effect of dietary supplementation with sanguinarine on meat quality and lipid metabolism of broilers.

Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.