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Ghrelin, an acylated peptide hormone of 28 amino acids, is an endogenous ligand of the released growth hormone secretagogue receptor (GHSR). Ghrelin has been isolated from human and rat stomach and is also detected in the hypothalamic arcuate nucleus. Ghrelin receptor is primarily located in the neuropeptide Y and agouti-related protein neurons. Many previous studies have shown that ghrelin and GHSR are involved in the regulation of energy homeostasis, and its administration can increase food intake and body weight gain. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acid level. Ghrelin appears to modulate the response to food cues via a neural network involved in the regulation of feeding and in the appetitive response to food cues. It also increases the response of brain areas involved in visual processing, attention, and memory to food pictures. Ghrelin is also an important factor linking the central nervous system with peripheral tissues that regulate lipid metabolism. It promotes adiposity by the activation of hypothalamic orexigenic neurons and stimulates the expression of fat storage-related proteins in adipocytes. Meanwhile, ghrelin exerts direct peripheral effects on lipid metabolism, including increase in white adipose tissue mass, stimulation of lipogenesis in the liver, and taste sensitivity modulation.

Bacterial biofilms, which consist of three-dimensional extracellular polymeric substance (EPS), not only function as signaling networks, provide nutritional support, and facilitate surface adhesion, but also serve as a protective shield for the residing bacterial inhabitants against external stress, such as antibiotics, antimicrobials, and host immune responses. Biofilm-associated infections account for 65-80% of all human microbial infections that lead to serious mortality and morbidity. Tremendous effort has been spent to address the problem by developing biofilm-dispersing agents to discharge colonized microbial cells to a more vulnerable planktonic state. Here, we discuss the recent progress of enzymatic eradicating strategies against medical biofilms, with a focus on dispersal mechanisms. Particularly, we review three enzyme classes that have been extensively investigated, namely glycoside hydrolases, proteases, and deoxyribonucleases.

Chrysanthemum is a globally popular ornamental crop. Seed propagation through hybridization is typically used for breeding new commercial cultivars. Achieving sufficient seed production is critical for the development and selection of new varieties. To date, research on chrysanthemum has mainly focused on studying the ornamental traits of plants, whereas morphological diversity research on the seed traits of the plants remains limited. In this study, we analyzed the phenotypic characteristics of four seed traits in seven chrysanthemum parent plants (designated C1–C7) and their progeny under open-pollination conditions. The traits examined included seed length (SL), seed width (SW), 100-seed weight (SWh) and the average number of seeds per inflorescence (ASPI). Among these, ASPI exhibited the highest coefficient of variation (CV) across both parent plants (0.41) and progeny generations (ranging from 0.32 to 0.62), indicating significant variability. By contrast, SL and SW displayed the lowest CVs (0.06 and 0.07, respectively) across all generations. According to correlation analyses, traits between parents were similar to those between progeny populations. SL highly significantly and positively correlated with SW (correlation coefficients: 0.97 in parents, 0.47 in progeny) and ASPI (0.91 in parents, 0.17 in progeny). ASPI emerged as the most variable and unstable trait under open-pollination conditions. This study provides valuable insights into the phenotypic variation of seed traits in chrysanthemums, offering a foundation for identifying high-seed set germplasm resources. These findings can support future research and innovation in chrysanthemum breeding techniques, accelerating the development of new cultivars with desirable traits.

Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), presents significant challenges in early diagnosis and personalized treatment. Recent research has focused on the role of the tumor microenvironment, particularly tumor-associated fibroblasts (CAFs), in tumor progression. This study systematically analyzed CAF immune infiltration-related genes to construct a prognostic model for LUAD, confirming its predictive value for patient outcomes. The risk score derived from CAF-related genes (CAFRGs) was negatively correlated with immune microenvironment scores and linked to the expression of immune checkpoint genes, indicating that high-risk patients may exhibit immune escape characteristics. Analysis via the TIDE tool revealed that low-risk patients had more active T-cell immune responses. The risk score also correlated with anti-tumor drug sensitivity, particularly to doramapimod. Notably, COX6A1 emerged as a key gene in the model, with its upregulation associated with immune cell infiltration and immune escape. Further in vitro experiments demonstrated that COX6A1 regulates LUAD cell migration, proliferation, and senescence, suggesting its role in tumor immune evasion. Additionally, further co-culture studies of lung cancer cells and fibroblasts revealed that COX6A1 knockdown promotes the expression of CAF-related cytokines, enhancing CAF infiltration. Overall, this study provides a foundation for personalized treatment of LUAD and highlights COX6A1 as a promising therapeutic target within the tumor immune microenvironment, guiding future clinical research.

Background Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites interactively promote PMO remains unknown. Methods This study aimed to investigate changes in the intestinal flora and associated metabolites, and their role in PMO. 16S rRNA gene sequencing and metabolomics were performed to obtain postmenopausal women with osteopenia (lower bone mass, LBM), postmenopausal women with osteoporosis (OST), and healthy women as the control group. Results We identified taxa-specific and metabolite differences in the intestinal flora of the participants of this study. The pathogenic bacteria Klebsiella (0.59% and 0.71%, respectively) and Escherichia-Shigella (2.72% and 4.30%, respectively) were enriched in the LBM and OST groups ( p  < 0.05) . Some short-chain fatty acid (SCFAs) producing bacteria, Lactobacillus , Akkermansia , Prevotella , Alistipes , and Butyricicoccus , were reduced in patients with LBM and OST compared to the control. Moreover, fecal metabolomic analyses suggested that the metabolites of indole-3-acetic acid and 7-ketodeoxycholic acid were altered in the LBM and OST groups compared to the control ( p  < 0.05). Enrichment analysis suggested that valine, leucine, and isoleucine biosynthesis; aromatic amino acid biosynthesis; and phenylalanine metabolism were significantly associated with the identified microbiota biomarkers and OST. Moreover, metabolite marker signatures distinguished patients in the OST from those in the control group with an area under the curve (AUC) of 0.978 and 1.00 in the negative and positive ion modes, respectively. Finally, we also found that the fecal level of interleukin-10 (IL-10) in the OST group was significantly lower than that in the control group and LBM group ( p  < 0.05), while tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly higher in the OST group than that in the control group ( p  < 0.05). Conclusions This study provides robust evidence connecting the intestinal flora and fecal metabolomics with PMO. Integrated metabolite and microbiota analyses demonstrated that in addition to dysregulated bacteria, indole-3-acetic acid, 7-ketodeoxycholic acid, and other metabolites can be used for the distinguish of LBM and PMO.

Context: Selenium nanoparticles (SeNPs) have attracted worldwide attention due to their unique properties and potential bioactivities. Considering that hawthorn is both a traditional medicine and a common edible food, hawthorn fruit extract (HE) was chosen as a reductant to prepare SeNPs. Objective: SeNPs were synthesized by using an aqueous HE as a reductant and stabilizer. The antitumor activities and potential mechanisms of SeNPs were explored by using a series of cellular assays. Materials and methods: The HE mediated SeNPs (HE-SeNPs) were examined using various characterisation methods. The cytotoxicity was measured against HepG2 cells after treated with 0, 5, 10 and 20 μg/mL of HE-SeNPs for 24 h. Annexin V-FITC/PI staining analysis was performed to observe the apoptosis of HepG2 cells. Additionally, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels were evaluated. Finally, the protein expression levels of caspase-9 and Bcl-2 were identified by Western blot. Results: The mono-dispersed and stable SeNPs were prepared with an average size of 113 nm. HE-SeNPs showed obvious antitumor activities towards HepG2 cells with an IC 50 of 19.22 ± 5.3 μg/mL. Results from flow cytometry revealed that both early and total apoptosis rates increased after treating with HE-SeNPs. After cells were treated with various concentrations of HE-SeNPs (5, 10 and 20 μg/mL) for 24 h, the total rate increased to 7.3 ± 0.5, 9.7 ± 1.7 and 19.2 ± 1.6%, respectively. Meanwhile, treatment of HE-SeNPs up-regulated intracellular ROS levels and reduced the MMP. In addition, HE-SeNPs induced the up-regulation of caspase-9 and down-regulation of Bcl-2. Discussion and conclusions: HE-SeNPs induced intracellular oxidative stress and mitochondrial dysfunction to initiate HepG2 cell apoptosis through the mitochondrial pathway. Therefore, HE-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for human liver cancer.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based on their structural characteristics and origins. Furthermore, it explores proteolysis targeting chimers (PROTACs) targeting CDK4/6. We hope that this review could be of benefit for further research on CDK4/6 inhibitors and PROTACs.

The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world’s longevity town—Jiaoling, China, centenarians and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians. Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated 2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as antioxidant systems may contribute to health and longevity.

The worldwide distribution of Staphylococcus aureus across food types is an important food safety concern. This study aimed to estimate the prevalence of S. aureus in food products and its relationship with the occurrence and development of diabetes mellitus. A total of 55 articles were included. The pooled prevalence of S. aureus was 30.2%. The highest prevalence of S. aureus was observed in cereals, followed by meat and bean products, and the lowest in confectionery, egg products, and vegetables. The prevalence in dairy and seafood products was similar. Combinations of culture and molecular methods have been used for S. aureus detection. Furthermore, the prevalence of S. aureus in developed countries (Europe and North America) was higher than that in developing countries (Asia and Africa). In addition, the prevalence was higher in the provinces of Xinjiang and Shaanxi than that in Sichuan and Shandong in China, which may be due to the difference in climate and dietary habits. The results revealed that food type, bacterial detection methods, and location can influence the prevalence of S. aureus contamination. Resistance rates to preferred antibiotics against S. aureus were the highest for cephradine, polymyxin B, and penicillin at 82.9%, 82.0%, and 81.3%, respectively. In addition, 17 studies were system reviewed that the S. aureus infections are closely associated with the development of diabetes, and the treatment of probiotic, prebiotic, FMT, and bacteriophage can prevent and control S. aureus infections. This review emphasizes the high prevalence of S. aureus contamination in food, suggesting a potential diabetic infection risk and importance of observing principles of food safety and hygiene to reduce S. aureus. Map of countries and food type distribution involved in included studies in this meta‐analysis; meanwhile, suggesting that Staphylococcus aureus infection can result in the occurrence of diabetes.

Background Approximately 5.0–24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of SMAD4 gene mutation in CRC patients. Methods A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between SMAD4 mutations and the demographic and clinicopathological characteristics in CRC patients. The hazard ratios (HRs) with 95% confidence intervals (CI) were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS). Results Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from 5 studies and data on PFS/RFS were available from 3 studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% CI 1.28–1.67, P  = 0.001), the summary HR for PFS/RFS was 1.59 (95% CI 1.14–2.22, P  = 0.006). In terms of clinicopathology parameters, 9 studies have data that can be extracted, SMAD4 mutations were associated with tumor location (odds ratio [OR] = 1.15, colon/rectum, 95% CI 1.01–1.31, P  = 0.042), TNM stage (OR = 1.28, stage IV/I–III, 95% CI 1.03–1.58, P  = 0.025), lymph node metastasis (OR = 1.42, N1 + N2/N0, 95% CI 1.20–1.67, P  < 0.001), mucinous differentiation (OR = 2.23, 95% CI 1.85–2.70, P  < 0.001) and rat sarcoma viral oncogene homolog (RAS) mutation status (OR = 2.13, 95% CI 1.37–3.34, P  = 0.001). No connection was found with age, gender, tumor grade, microsatellite instability status and b-viral oncogene homolog B1 mutation status. Besides, publication bias was not observed in any study. Conclusions This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastasis and mucinous differentiation. Our meta-analysis indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies are needed to confirm this conclusion. Since SMAD4 mutations are closely related to RAS mutations, their relationship warrants further investigation.