Drugging p53: Barriers, Criteria, and Prospects.

Pharmacologically targeting tumor suppressors necessitates an unprecedented strategy of restoring, rather than conventionally inhibiting, protein function, and p53, the most commonly mutated protein in cancer, has thus remained undruggable. In this study, we address long-standing misconceptions in the field and gaps in the scientific logic for a p53 function-restoration strategy, identify four barriers for drugging mutant p53, and accordingly propose effectiveness evaluation criteria, clinical-translating norms, and prospects for mutant p53 rescue compounds.

Integrated volatile metabolome and transcriptome analyses provide insights into the warm aroma formation elicited by methyl jasmonate in carrot root.

Carrot is a highly significant vegetable cultivated worldwide and possesses a unique aroma with abundant edible and medicinal values. However, it remains largely unknown whether jasmonic acid could regulate aroma formation in carrot. Here, an integrated analysis of the volatile metabolome and transcriptome of carrot roots exposed to different concentrations of methyl jasmonate (MeJA) was performed. The results revealed 1,227 volatile organic compounds and 972 differential accumulated metabolites, with terpenes representing the largest portion. MeJA treatment evidently increased the relative odor activity values as well as the accumulation of most volatile compounds. In addition, 4,787 differentially expressed genes were identified and subjected to function enrichment analysis, indicating a role of terpene biosynthesis and metabolism in response to MeJA application. A network consisting of 4,680 transcription factor-structural pairs that showed highly significant positive correlations was constructed, which may be utilized as genetic targets for examining terpene accumulation and aroma formation elicited by methyl jasmonate. The results from the present work substantially improved our understanding of MeJA-mediated aroma formation in carrot.

Advances in conjugate drug delivery System: Opportunities and challenges.

Ideal drug delivery system is designed to accurately deliver the drug to its intended site. The development of conjugate drug delivery system introduces a novel pathway to precise drug delivery with advantages over traditional methods. The core of a conjugate drug delivery system comprises a molecule with two functional components, bounded by a linker structure. One component is responsible for delivering or stabilizing the conjugate, while the other is used to provide the therapeutic or diagnostic effects of the bioactivity. Conjugate drug delivery system improves patient health by maintaining the structural stability of drugs in molecular form, delivering therapeutics or diagnostic material to the target site, minimising off-target accumulation and promoting patient compliance. This system includes various types of drug conjugates that modulate drug pharmacokinetics, stability, absorption, and exposure in lesions and healthy tissues. In this review, we focus on the key characteristics and recent advances of various conjugate drug delivery systems and explore their mechanisms. We also point out the current challenges faced by conjugate drug delivery system and look forward to the future prospects.

Comparative study of polysaccharide metabolites in purple, orange, and white Ipomoea batatas tubers.

We employed LC-MS/MS to investigate the metabolic profiles of polysaccharide compounds in white, orange, and purple sweet potato flesh. Comparisons between Orange vs White, Purple vs Orange, and Purple vs White identified 69 polysaccharide metabolites, including 23, 36, and 44 differential metabolites, respectively, with distinct differentiation. Among the three sample groups, 14 polysaccharide compounds and 2 anthocyanins exhibited significant differences. Our further analysis indicated that anthocyanins occupy a central position in the related network diagram and are interconnected with polysaccharides. In metabolic pathways, sucrose and the anthocyanin precursor UDP-glucose were upregulated in purple sweet potatoes, along with elevated levels of pelargonidin 3-O-ß-D-sambubioside and delphinidin 3,5-diglucoside. Conversely, sucrose was downregulated in purple sweet potatoes while increasing in white and orange varieties. Therefore, we hypothesize that the competition between sugars and anthocyanins for shared biosynthesis precursors is attributed to differential polysaccharide metabolites among sweet potato tubers of three colors.

Transcriptome analysis reveals the importance of phototransduction during the first-feeding in mandarin fish (Siniperca chuatsi).

The mandarin fish (Siniperca chuatsi), as a typical freshwater carnivorous fish, has high economic value. Mandarin fish have a peculiar feeding habit of feeding on other live fry during the first-feeding period, while rejecting zooplankton or particulate feed, which may be attributed to the low expression of zooplankton-associated gene sws1 in mandarin fish. The domesticated strain of mandarin fish could feed on Artemia at 3 days post hatching (dph). However, the mechanism of mandarin fish larvae recognize and forage Artemia as food is still unclear. In this study, we employed transcriptional analysis to identify the representative differential pathways between mandarin fish larvae unfed and fed with Artemia at 3 dph. The comparative transcriptome analysis has unveiled a tapestry of genetic expression, highlighting 403 genes that have been up-regulated and 259 that have been down-regulated, all of which constitute the differentially expressed genes (DEGs). KEGG pathway analysis revealed that the number of differentially expressed genes in the photoconductive signaling pathway was the largest. Next, the Vorinostat (suberoylanilide hydroxamic acid, SAHA) was used to assess whether sws1 induced ingestion of Artemia in mandarin fish larvae. We discovered that SAHA-treated larvae had more food intake of Artemia and up-regulated the transcription level of npy, which might have been associated with the up-regulated of sws1 opsin. Additionally, exposure to 0.5 µM SAHA increased the expression of genes involved in phototransduction pathway. These findings would provide insights on the molecular processes involved in mandarin fish larvae feeding on Artemia at the first-feeding stage.

Inequalities changes in health services utilization among middle-aged and older adult disabled people in China: based on CHARLS 2011-2018.

Background: Multiple intersections, including socioeconomic inequalities, influence health equity for disabled people and sub-populations. However, this association has not been sufficiently analyzed among Chinese-impaired persons. This study aimed to investigate the health services utilization and inequalities in middle and older adult persons with disabilities and subgroups. Methods: The China Health and Retirement Longitudinal Study (CHARLS) database in 2011, 2013, 2015, and 2018 were used. Health services utilization was measured by outpatient, inpatient, and self-treatment service utilization. Types of disabilities were classified into six categories. The pooled cross-section regression, concentration index, horizontal inequity index, and concentration index decomposition were used to evaluate inequalities and explore their main contributing factor. Results: The utilization and non-utilization of healthcare services showed variations across years (p < 0.05). The CIs and HIs for inpatient health service utilization were positive for all years and disability types. The total CIs of inpatient utilization were the highest (0.248). The highest disparities in utilization of inpatient services were for physical disabilities (0.4515 for CI in 2011), and the highest in self-treatment services were for intellectual disability (0.1538 for CI in 2011). The expenditure factor was the main contributor to inequalities. Chronic disease, educational level, and health insurance factors also contribute to the utilization inequalities. Conclusion: Policies should promote medical insurance and assistance for disabled people with serious impairment and poor. It is crucial to improve the provision of basic medical services, including meeting the demand for varied disabilities and the accessibility of facilities and equipment to enhance the access and well-being of people with disabilities.

Comparative analysis of codon usage bias in the chloroplast genomes of eighteen Ampelopsideae species (Vitaceae).

BACKGROUND: The tribe Ampelopsideae plants are important garden plants with both medicinal and ornamental values. The study of codon usage bias (CUB) facilitates a deeper comprehension of the molecular genetic evolution of species and their adaptive strategies. The joint analysis of CUB in chloroplast genomes (cpDNA) offers valuable insights for in-depth research on molecular genetic evolution, biological resource conservation, and elite breeding within this plant family. RESULTS: The base composition and codon usage preferences of the eighteen chloroplast genomes were highly similar, with the GC content of bases at all positions of their codons being less than 50%. This indicates that they preferred A/T bases. Their effective codon numbers were all in the range of 35-61, which indicates that the codon preferences of the chloroplast genomes of the 18 Ampelopsideae plants were relatively weak. A series of analyses indicated that the codon preference of the chloroplast genomes of the 18 Ampelopsideae plants was influenced by a combination of multiple factors, with natural selection being the primary influence. The clustering tree generated based on the relative usage of synonymous codons is consistent with some of the results obtained from the phylogenetic tree of chloroplast genomes, which indicates that the clustering tree based on the relative usage of synonymous codons can be an important supplement to the results of the sequence-based phylogenetic analysis. Eventually, 10 shared best codons were screened on the basis of the chloroplast genomes of 18 species. CONCLUSION: The codon preferences of the chloroplast genome in Ampelopsideae plants are relatively weak and are primarily influenced by natural selection. The codon composition of the chloroplast genomes of the eighteen Ampelopsideae plants and their usage preferences were sufficiently similar to demonstrate that the chloroplast genomes of Ampelopsideae plants are highly conserved. This study provides a scientific basis for the genetic evolution of chloroplast genes in Ampelopsideae species and their suitable strategies.

Long non-coding ribonucleic acid SNHG18 induced human granulosa cell apoptosis via disruption of glycolysis in ovarian aging.

BACKGROUND: In-depth understanding of dynamic expression profiles of human granulosa cells (GCs) during follicular development will contribute to the diagnostic and targeted interventions for female infertility. However, genome-scale analysis of long non-coding ribonucleic acid (lncRNA) in GCs across diverse developmental stages is challenging. Meanwhile, further research is needed to determine how aberrant lncRNA expression participates in ovarian diseases. METHODS: Granulosa cell-related lncRNAs data spanning five follicular development stages were retrieved and filtered from the NCBI dataset (GSE107746). Stage-specific lncRNA expression patterns and mRNA-lncRNA co-expression networks were identified with bioinformatic approaches. Subsequently, the expression pattern of SNHG18 was detected in GCs during ovarian aging. And SNHG18 siRNA or overexpression plasmids were transfected to SVOG cells in examining the regulatory roles of SNHG18 in GC proliferation and apoptosis. Moreover, whether PKCɛ/SNHG18 signaling take part in GC glycolysis via ENO1 were verified in SVOG cells. RESULTS: We demonstrated that GC-related lncRNAs were specifically expressed across different developmental stages, and coordinated crucial biological functions like mitotic cell cycle and metabolic processes in the folliculogenesis. Thereafter, we noticed a strong correlation of PRKCE and SNHG18 expression in our analysis. With downregulated SNHG18 of GCs identified in the context of ovarian aging, SNHG18 knockdown could further induce cell apoptosis, retard cell proliferation and exacerbate DNA damage in SVOG cell. Moreover, downregulated PKCɛ/SNHG18 pathway interrupted the SVOG cell glycolysis by lowering the ENO1 expression. CONCLUSIONS: Altogether, our results revealed that folliculogenesis-related lncRNA SNHG18 participated in the pathogenesis of ovarian aging, which may provide novel biomarkers for ovarian function and new insights for the infertility treatment.

Investigating thermal properties of 2D non-layered material using a NEMS-based 2-DOF approach towards ultrahigh-performance bolometer.

Two-dimensional (2D) non-layered materials in many aspects differ from their layered counterparts, and the exploration of their physical properties has produced many intriguing findings. However, due to challenges in applying existing experimental techniques to such nanoscale samples, their thermal properties have remained largely uncharacterized, hindering further exploration and device application using this promising material system. Here, we demonstrate an experimental study of thermal conduction in ß-In2S3, a typical non-layered 2D material, using a resonant nanoelectromechanical systems (NEMS) platform. We devise a new two-degrees-of-freedom technique, more responsive and sensitive than Raman spectroscopy, to simultaneously determine both the thermal conductivity to be 3.7 W m-1 K-1 and its interfacial thermal conductance with SiO2 as 6.4 MW m-2 K-1. Leveraging such unique thermal properties, we further demonstrate a record-high power-to-frequency responsivity of -447 ppm/µW in ß-In2S3 NEMS sensors, the best among drumhead NEMS-based bolometers. Our findings offer an effective approach for studying thermal properties and exploring potential thermal applications of 2D non-layered materials.

The role of quercetin in NLRP3-associated inflammation.

Quercetin is a natural flavonoid that is widely found in fruits and vegetables. As an important flavonoid, it exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, antiviral, immunomodulatory, and analgesic activities. Quercetin exerts powerful antioxidant activity by regulating glutathione, enzyme activity, and the production of reactive oxygen species (ROS). Quercetin exerts powerful anti-inflammatory effects by acting on the Nod-like receptor protein 3 (NLRP3) inflammasome. In diabetes, quercetin has been shown to improve insulin sensitivity and reduce high blood sugar level, while, in neurological diseases, it potentially prevents neuronal degeneration and cognitive decline by regulating neuroinflammation. In addition, in liver diseases, quercetin may improve liver inflammation and fibrosis by regulating the NLRP3 activity. In addition, quercetin may improve inflammation in other diseases based on the NLRP3 inflammasome. With this background, in this review, we have discussed the progress in the study on the mechanism of quercetin toward improving inflammation via NLRP3 inflammasome in the past decade. In addition, from the perspective of quercetin glycoside derivatives, the anti-inflammatory mechanism of hyperoside, rutin, and isoquercetin based on NLRP3 inflammasome has been discussed. Moreover, we have discussed the pharmacokinetics of quercetin and its nanoformulation application, with the aim to provide new ideas for further research on the anti-inflammatory effect of quercetin and its glycoside derivatives based on NLRP3 inflammasome, as well as in drug development and application.

Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment.

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. STATEMENT OF SIGNIFICANCE: Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.

A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.

The gastrointestinal tract is where the majority of gut microbiota settles; therefore, the composition of the gut microbiota and the changes in metabolites, as well as their modulatory effects on the immune system, have a very important impact on the development of gastrointestinal diseases. The purpose of this article was to review the role of the gut microbiota in the host environment and immunometabolic system and to summarize the beneficial effects of botanical active ingredients on gastrointestinal cancer, so as to provide prospective insights for the prevention and treatment of gastrointestinal diseases. A literature search was performed on the PubMed database with the keywords "gastrointestinal cancer", "gut microbiota", "immunometabolism", "SCFAs", "bile acids", "polyamines", "tryptophan", "bacteriocins", "immune cells", "energy metabolism", "polyphenols", "polysaccharides", "alkaloids", and "triterpenes". The changes in the composition of the gut microbiota influenced gastrointestinal disorders, whereas their metabolites, such as SCFAs, bacteriocins, and botanical metabolites, could impede gastrointestinal cancers and polyamine-, tryptophan-, and bile acid-induced carcinogenic mechanisms. GPRCs, HDACs, FXRs, and AHRs were important receptor signals for the gut microbial metabolites in influencing the development of gastrointestinal cancer. Botanical active ingredients exerted positive effects on gastrointestinal cancer by influencing the composition of gut microbes and modulating immune metabolism. Gastrointestinal cancer could be ameliorated by altering the gut microbial environment, administering botanical active ingredients for treatment, and stimulating or blocking the immune metabolism signaling molecules. Despite extensive and growing research on the microbiota, it appeared to represent more of an indicator of the gut health status associated with adequate fiber intake than an autonomous causative factor in the prevention of gastrointestinal diseases. This study detailed the pathogenesis of gastrointestinal cancers and the botanical active ingredients used for their treatment in the hope of providing inspiration for research into simpler, safer, and more effective treatment pathways or therapeutic agents in the field.

Role perceptions and experiences of adult children in remote glucose management for older parents with type 2 diabetes mellitus: a qualitative study.

BACKGROUND: With the advent of the smart phone era, managing blood glucose at home through apps will become more common for older individuals with diabetes. Adult children play important roles in glucose management of older parents. Few studies have explored how adult children really feel about engaging in the glucose management of their older parents with type 2 diabetes mellitus (T2DM) through mobile apps. This study provides insights into the role perceptions and experiences of adult children of older parents with T2DM participating in glucose management through mobile apps. METHODS: In this qualitative study, 16 adult children of older parents with T2DM, who had used mobile apps to manage blood glucose for 6 months, were recruited through purposive sampling. Semi-structured, in-depth, face-to-face interviews to explore their role perceptions and experiences in remotely managing their older parents' blood glucose were conducted. The Consolidated Criteria for Reporting Qualitative Research (COREQ) were followed to ensure rigor in the study. The data collected were analyzed by applying Colaizzi's seven-step qualitative analysis method. RESULTS: Six themes and eight sub-themes were identified in this study. Adult children's perceived roles in glucose management of older parents with T2DM through mobile apps could be categorized into four themes: health decision-maker, remote supervisor, health educator and emotional supporter. The experiences of participation could be categorized into two themes: facilitators to participation and barriers to participation. CONCLUSION: Some barriers existed for adult children of older parents with T2DM participating in glucose management through mobile apps; however, the findings of this study were generally positive. It was beneficial and feasible for adult children to co-manage the blood glucose of older parents. Co-managing blood glucose levels in older parents with T2DM can enhance both adherence rates and confidence in managing blood glucose effectively.

Performance of radiomics in the differential diagnosis of parotid tumors: a systematic review.

Purpose: A systematic review and meta-analysis were conducted to evaluate the diagnostic precision of radiomics in the differential diagnosis of parotid tumors, considering the increasing utilization of radiomics in tumor diagnosis. Although some researchers have attempted to apply radiomics in this context, there is ongoing debate regarding its accuracy. Methods: Databases of PubMed, Cochrane, EMBASE, and Web of Science up to May 29, 2024 were systematically searched. The quality of included primary studies was assessed using the Radiomics Quality Score (RQS) checklist. The meta-analysis was performed utilizing a bivariate mixed-effects model. Results: A total of 39 primary studies were incorporated. The machine learning model relying on MRI radiomics for diagnosis malignant tumors of the parotid gland, demonstrated a sensitivity of 0.80 [95% CI: 0.74, 0.86], SROC of 0.89 [95% CI: 0.27-0.99] in the validation set. The machine learning model based on MRI radiomics for diagnosis malignant tumors of the parotid gland, exhibited a sensitivity of 0.83[95% CI: 0.76, 0.88], SROC of 0.89 [95% CI: 0.17-1.00] in the validation set. The models also demonstrated high predictive accuracy for benign lesions. Conclusion: There is great potential for radiomics-based models to improve the accuracy of diagnosing benign and malignant tumors of the parotid gland. To further enhance this potential, future studies should consider implementing standardized radiomics-based features, adopting more robust feature selection methods, and utilizing advanced model development tools. These measures can significantly improve the diagnostic accuracy of artificial intelligence algorithms in distinguishing between benign and malignant tumors of the parotid gland. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023434931.

Catalytic elevation effect of methylglyoxal on invertase and characterization of MGO modification products.

Reactive carbonyl species can modify digestive enzymes upon intake due to their electrophilic nature. This study evaluated the effects of methylglyoxal (MGO), glyoxal, acrolein, and formaldehyde on invertase, an enzyme presents in digestive tract. Unexpectedly, MGO enhanced, rather than inhibited, invertase activity. Moreover, MGO counteracted the inhibitory effects of the other three carbonyls on invertase activity. Kinetic analyses revealed that 150 mmolLexp.-1 MGO resulted in a 2-fold increase in the Km and a 3.3-fold increase in Vmax, indicating that MGO increased the turnover rate of sucrose while reducing the substrate binding affinity of invertase. Additionally, MGO induced dynamic quenching of fluorescence, reduced free amino groups, increased hydrophobicity, the content of Amadori products, fluorescent and nonfluorescent AGEs, and amyloid fibrils of invertase. The specific modifications responsible for the elevated activity of MGO on invertase require further investigation.

Changes in the serum metabolomics of polycystic ovary syndrome before and after compound oral contraceptive treatment.

Background: Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism. This study aimed to investigate differences in the serum metabolic profiles of patients with PCOS compared with healthy controls, in addition to investigating the effects of compound oral contraceptive (COC) treatment in patients with PCOS. Materials and methods: 50 patients with PCOS and 50 sex-matched healthy controls were recruited. Patients with PCOS received three cycles of self-administered COC treatment. Clinical characteristics were recorded, and the laboratory biochemical data were detected. We utilized ultra-performance liquid chromatography-high-resolution mass spectrometry to study the serum metabolic changes between patients with PCOS, patients with PCOS following COC treatment, and healthy controls. Result: Patients with PCOS who received COC treatment showed significant improvements in serum sex hormone levels, a reduction in luteinising hormone levels, and a significant reduction in the levels of biologically active free testosterone in the blood. Differential metabolite correlation analysis revealed differences between PCOS and healthy control groups in N-tetradecanamide, hexadecanamide, 10E,12Z-octadecadienoic acid, and 13-HOTrE(r); after 3 months of COC treatment, there were significant differences in benzoic acid, organic acid, and phenolamides. Using gas chromatography-mass spectrometry to analyse blood serum in each group, the characteristic changes in PCOS were metabolic disorders of amino acids, carbohydrates, and purines, with significant changes in the levels of total cholesterol, uric acid, phenylalanine, aspartic acid, and glutamate. Conclusion: Following COC treatment, improvements in sex hormone levels, endocrine factor levels, and metabolic levels were better than in the group of PCOS patients receiving no COC treatment, indicating that COC treatment for PCOS could effectively regulate the levels of sex hormones, endocrine factors, and serum metabolic profiles.

Transient Pressure Behavior of CBM Wells during the Injection Fall-Off Test Considering the Quadratic Pressure Gradient.

Conventional coalbed methane (CBM) reservoir models for injection fall-off testing often disregard the quadratic pressure gradient's impact. This omission leads to discrepancies in simulating the transient behavior of formation fluids and extracting critical reservoir properties. Accurate determination of permeability, storability, and other properties is crucial for effective reservoir characterization and production forecasting. Inaccurate estimations can lead to suboptimal well placement, ineffective production strategies, and ultimately, missed economic opportunities. To address this shortcoming, we present a novel analytical model that explicitly incorporates the complexities of the quadratic pressure gradient and dual-permeability flow mechanisms, prevalent in many CBM formations where nanopores are rich, presenting a kind of natural nanomaterial. This model offers significant advantages over traditional approaches. By leveraging variable substitution, it facilitates the derivation of analytical solutions in the Laplace domain, subsequently converted to real-space solutions for practical application. These solutions empower reservoir engineers to generate novel type curves, a valuable tool for analyzing wellbore pressure responses during injection fall-off tests. By identifying distinct flow regimes within the reservoir based on these type curves, engineers gain valuable insights into the dynamic behavior of formation fluids. This model goes beyond traditional approaches by investigating the influence of the quadratic pressure gradient coefficient, inter-porosity flow coefficient, and storability ratio on the pressure response. A quantitative comparison with traditional models further elucidates the key discrepancies caused by neglecting the quadratic pressure gradient. The results demonstrate the proposed model's ability to accurately depict the non-linear flow behavior observed in CBM wells. This translates to more reliable pressure and pressure derivative curves that account for the impact of the quadratic pressure gradient.

Accumulation patterns of flavonoids and phenolic acids in different colored sweet potato flesh revealed based on untargeted metabolomics.

Sweet potatoes are rich in flavonoids and phenolic acids, showing incomparable nutritional and health value. In this investigation, we comprehensively analyzed the secondary metabolite profiles in the flesh of different-colored sweet potato flesh. We determined the metabolomic profiles of white sweet potato flesh (BS), orange sweet potato flesh (CS), and purple sweet potato flesh (ZS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CS vs. BS, ZS vs. BS, and ZS vs. CS comparisons identified a total of 4447 secondary metabolites, including 1540, 1949, and 1931 differentially accumulated metabolites. Among them, there were significant differences in flavonoids and phenolic acids. There were 20 flavonoids and 13 phenolic acids that were common differential metabolites among the three comparison groups. The accumulation of paeoniflorin-like and delphinidin-like compounds may be responsible for the purple coloration of sweet potato flesh. These findings provide new rationale and insights for the development of functional foods for sweet potatoes. List of compounds: Kaempferol (PubChem CID: 5280863); Peonidin 3-(6"-p-coumarylglucoside) (PubChem CID: 44256849); Swerchirin (PubChem CID: 5281660); Trilobatin (PubChem CID: 6451798); 3-Geranyl-4-hydroxybenzoate (PubChem CID: 54730540); Eupatorin (PubChem CID: 97214); Icaritin (PubChem CID: 5318980); Isorhamnetin (PubChem CID: 5281654); Glucoliquiritin apioside (PubChem CID: 74819335); Brazilin (PubChem CID: 73384).

Carnosic Acid: A Novel Selective Inhibitor of ERAP1 by Direct Binding and Its Modulation of Antigen Processing and Presentation.

ERAP1 is an emerging target for a large subclass of severe autoimmune diseases known as "MHC-I-opathy", together with tumor immunity. Nevertheless, effective inhibitors targeting ERAP1 remain a challenge. In this study, a novel food-derived natural product ERAP1-targeting inhibitor, carnosic acid, was identified, and to our knowledge, it is one of the best active compounds among the highly selective inhibitors targeting the orthosteric site of ERAP1. The results reveal that carnosic acid could bind strongly, like a key to the ERAP1 active site in the biased S1' pocket, which is different from the binding mode of the existing orthosteric site inhibitors. HLA-B27-mediated cell modeling validated that carnosic acid has the activity to reverse the AS-associated cellular phenotype brought on by ERAP1 through inhibition. Our findings provide insights into the design of potent inhibitors against the ERAP1 orthosteric site and the discovery of a key direct target of carnosic acid.

An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation.

Alzheimer's disease (AD), the most common form of dementia, has a complex pathogenesis. The number of AD patients has increased in recent years due to population aging, while a trend toward a younger age of onset has arisen, imposing a substantial burden on society and families, and garnering extensive attention. DNA methylation has recently been revealed to play an important role in AD onset and progression. DNA methylation is a critical mechanism regulating gene expression, and alterations in this mechanism dysregulate gene expression and disrupt important pathways, including oxidative stress responses, inflammatory reactions, and protein degradation processes, eventually resulting in disease. Studies have revealed widespread changes in AD patients' DNA methylation in the peripheral blood and brain tissues, affecting multiple signaling pathways and severely impacting neuronal cell and synaptic functions. This review summarizes the role of DNA methylation in the pathogenesis of AD, aiming to provide a theoretical basis for its early prevention and treatment.