IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

The role of amino acid metabolism alterations in acute ischemic stroke: From mechanism to application.

Acute ischemic stroke (AIS) is the most prevalent type of stroke, and due to its high incidence, disability rate, and mortality rate, it imposes a significant burden on the health care system. Amino acids constitute one of the most crucial metabolic products within the human body, and alterations in their metabolic pathways have been identified in the microenvironment of AIS, thereby influencing the pathogenesis, severity, and prognosis of AIS. The amino acid metabolism characteristics in AIS are complex. On one hand, the dynamic progression of AIS continuously reshapes the amino acid metabolism pattern. Conversely, changes in the amino acid metabolism pattern also exert a double-edged effect on AIS. This interaction is bidirectional, dynamic, heterogeneous, and dose-specific. Therefore, the distinctive metabolic reprogramming features surrounding amino acids during the AIS process are systematically summarized in this paper, aiming to provide potential investigative strategies for the early diagnosis, treatment approaches, and prognostic enhancement of AIS.

Integrated biomarker profiling for predicting the response of type 2 diabetes to metformin.

AIM: To explore biomarkers that can predict the response of type 2 diabetes (T2D) patients to metformin at an early stage to provide better treatment for T2D. METHODS: T2D patients with (responders) or without response (non-responders) to metformin were recruited, and their serum samples were used for metabolomic analysis to identify candidate biomarkers. Moreover, the efficacy of metformin was verified by insulin-resistant mice, and the candidate biomarkers were verified to determine the biomarkers. Five different machine learning methods were used to construct the integrated biomarker profiling (IBP) with the biomarkers to predict the response of T2D patients to metformin. RESULTS: A total of 73 responders and 63 non-responders were recruited, and 88 differential metabolites were identified in the serum samples. After being verified in mice, 19 of the 88 were considered as candidate biomarkers. Next, after metformin regulation, nine candidate biomarkers were confirmed as the biomarkers. After comparing five machine learning models, the nine biomarkers were constructed into the IBP for predicting the response of T2D patients to metformin based on the Naïve Bayes classifier, which was verified with an accuracy of 89.70%. CONCLUSIONS: The IBP composed of nine biomarkers can be used to predict the response of T2D patients to metformin, enabling clinicians to start a combined medication strategy as soon as possible if T2D patients do not respond to metformin.

3D spheroid HepaRG and fluorescent biphasic tracer for CYP3A4-mediated antibiotic interaction monitoring in sepsis.

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme in the metabolism of xenobiotics, particularly in drug metabolism interactions (DDIs), making it a significant factor in clinical drug use. However, current assay techniques are both laborious and costly, making it difficult to construct a high-throughput monitoring method that can be used in conjunction with the clinic. This poses certain safety hazards for drug combination. Therefore, it is crucial to develop a synchronized monitoring method for the inhibition and induction of CYP3A4. In this study, we utilized 3D culture technology to develop a HepaRG cells spheroid model. The CYP450 and transporter expression, the albumin secretion, and urea synthesis capacity characteristics were analyzed. The NEN probe was utilized as a tracer molecule for CYP3A4. The fluorescence intensity of metabolites was characterized by laser confocal technique to determine the inhibition and expression of CYP3A4 in the HepaRG cell spheroid model by the antibiotics for sepsis. The results indicate that the HepaRG sphere model successfully possessed the physiological phenotype of the liver, which could be used for drug interaction monitoring. Through positive drug testing, NEN probe was able to achieve bidirectional characterization of CYP3A4 induction and inhibition. The monitoring method described in this paper was successfully applied to drug interaction monitoring of commonly used antibiotics in sepsis patients, which is a convenient and rapid monitoring method. The proposed method offers a new strategy for monitoring CYP3A4-mediated drug-drug interactions with a high-throughput assay, which will help to improve the safety of clinical drug combination.

GLP-1 signaling-regulated SNAP25 is involved in improved insulin secretion in diabetic GK rats after Roux-en-Y gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved ß-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of ß-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND RESULTS: RYGB or sham surgery was conducted in GK rats. mRNA and protein expression of SNAP25 was assessed by qPCR and Western blot, respectively. Occupancy of CREB and acetyltransferase CBP and acetylation of histone H3 (ACH3) at the Snap25 promoter were determined using ChIP assay. RYGB led to increased SNAP25 expression and CREB phosphorylation in islets from GK rats. Increased SNAP25 improved GSIS in ß-cells cultured in high glucose conditions. Consistent with increased plasma GLP-1 after RYGB, GLP-1R agonist exendin4 increased SNAP25 expression and CREB phosphorylation in ß-cells. Mechanistically, exendin4 promoted the recruitment of CREB and CBP, thereby increasing ACH3 at the Snap25 promoter. Consistently, inhibition of CBP attenuated the effect of exendin4 on SNAP25 expression. Furthermore, the knockdown of SNAP25 diminished the increase of GSIS potentiated by chronic GLP-1 culture in INS-1 832/13 cells. CONCLUSIONS: Our findings unravel the novel mechanisms of RYGB-enhanced SNAP25 expression in ß-cells, and SNAP25 may contribute to the improved ß-cell secretory function induced by RYGB.

Gut microbiota and metabolic changes in children with idiopathic short stature.

BACKGROUND: Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown. METHODS: We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites. RESULTS: We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9-100%]) by receiver operating characteristic (ROC) analysis. CONCLUSION: Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children's growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.

A systematic review on the appropriate discounting rates for the economic evaluation of gene therapies: whether a specific approach is justified to tackle the challenges?

OBJECTIVES: Discounting the cost and effect for health intervention is a controversial topic over the last two decades. In particular, the cost-effectiveness of gene therapies is especially sensitive to the discount rate because of the substantial delay between the upfront cost incurred and long-lasing clinical benefits received. This study aims to investigate the influence of employing alternative discount rates on the incremental cost-effectiveness ratio (ICER) of gene therapies. METHODS: A systematic review was conducted to include health economic evaluations of gene therapies that were published until April 2023. RESULTS: Sensitivity or scenario analysis indicated that discount rate represented one of the most influential factors for the ICERs of gene therapies. Discount rate for cost and benefit was positively correlated with the cost-effectiveness of gene therapies, that is, a lower discount rate significantly improves the ICERs. The alternative discount rate employed in some cases could be powerful to alter the conclusion on whether gene therapies are cost-effective and acceptable for reimbursement. CONCLUSIONS: Although discount rate will have substantial influence on the ICERs of gene therapies, there lacks solid evidence to justify a different discounting rule for gene therapies. However, it is proposed that the discount rate in the reference case should be updated to reflect the real-time preference, which in turn will affect the ICERs and reimbursement of gene therapies more profoundly than conventional therapies.

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists.

The farnesoid X receptor (FXR) has been recognized as a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). FXR agonists benefit NAFLD by modulating bile acid synthesis and transport, lipid metabolism, inflammation, and fibrosis pathways. However, there are still great challenges involved in developing safe and effective FXR agonists. To investigate the critical factors contributing to their activity on the FXR, 3D-QSAR molecular modeling was applied to a series of isoxazole derivatives, using comparative molecular field analysis (CoMFA (q2 = 0.664, r2 = 0.960, r2pred = 0.872)) and comparative molecular similarity indices analysis (CoMSIA (q2 = 0.706, r2 = 0.969, r2pred = 0.866)) models, which demonstrated strong predictive ability in our study. The contour maps generated from molecular modeling showed that the presence of hydrophobicity at the R2 group and electronegativity group at the R3 group in these compounds is crucial to their agonistic activity. A molecular dynamics (MD) simulation was carried out to further understand the binding modes and interactions between the FXR and its agonists in preclinical or clinical studies. The conformational motions of loops L: H1/H2 and L: H5/H6 in FXR-ligand binding domain (LBD) were crucial to the protein stability and agonistic activity of ligands. Hydrophobic interactions were formed between residues (such as LEU287, MET290, ALA291, HIS294, and VAL297) in helix H3 and ligands. In particular, our study found that residue ARG331 participated in salt bridges, and HIS447 participated in salt bridges and hydrogen bonds with ligands; these interactions were significant to protein-ligand binding. Eight new potent FXR agonists were designed according to our results, and their activities were predicted to be better than that of the first synthetic FXR agonist, GW4064.

Effects of chopping temperature on the gel quality of silver carp (Hypophthalmichthys molitrix) surimi: insight from gel-based proteomics.

BACKGROUND: Morden advanced analytical tools offer valuable information into the understanding of molecular mechanism of traditional food processing. Chopping temperature is well-known to affect the surimi gel quality of silver carp, but the detailed molecular mechanism is not very clear. In this study, a gel-based proteomics was performed on the extracted surimi proteins under different chopping temperatures (0, 5, 10, and 25 °C) along with other physicochemical characterization of surimi proteins and gels. RESULTS: With increased chopping temperature, protein extractability (in 3% sodium chloride) generally decreased, while the extracted protein generally exhibited larger surface hydrophobicity, reduced intrinsic fluorescence intensity, lower sulfhydryl content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profile of extracted protein showed a clear difference at 25 °C when compared with the other three temperatures, and more protein fragmentation occurred. Proteomic analysis of selected bands indicated that major myofibrillar proteins react differently with chopping temperatures, especially at 25 °C. The selected bands contained a variety of other proteins or their fragments, including adenosine triphosphate (ATP) synthase, glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate isomerase, heat shock protein, parvalbumin, collagen, and so forth. For the surimi gel, water-holding capacity and gel strength generally decreased with increased chopping temperature. CONCLUSION: Our results suggested that chopping at 0-10 °C is acceptable for the production of silver carp surimi in terms of gel strength and water-holding capacity. However, a chopping temperature near 0 °C led to less protein oxidation and denaturation. The inferior gel quality at 25 °C is linked to a decreased concentration of extracted protein and degradation of major myofibrillar protein, the latter is likely crosslinked with sarcoplasmic proteins. © 2024 Society of Chemical Industry.

The effect of fine particulate matter (PM2.5) pollution on health inequality: an intergenerational perspective.

Air pollution poses a serious challenge to public health and simultaneously exacerbating regional & intergenerational health inequality. This research introduces PM2.5 pollution into the intergenerational health transmission model, and estimates its impact on health inequality in China using Ordered Logit Regression (OLR) and Multi-scale Geographically Weighted Regression (MGWR) model. The results indicate that PM2.5 pollution exacerbate the intergenerational health inequality, and its impacts show inconsistency across family income levels, parental health insurance status, and area of residence. Specifically, it is more difficult for offspring in low-income families to escape from the influence of unhealthy family to become upwardly mobile. Additionally, this health inequality is more significant in households in which at least one parent does not have health insurance. Moreover, the intergenerational solidification caused by PM2.5 pollution is higher in the east and lower in the west. Both the PM2.5 level and solidification effect are high in Beijing-Tianjin-Hebei region, Yangtze River Delta region and central areas of China, which is the focus of air pollution management. These findings suggest that more emphasis should be placed on family-based health promotion. In areas with high PM2.5 pollution levels, resources, subsidies and air pollution protection should be provided for less healthy families with lower incomes and no health insurance.

Association between α-klotho levels and adults with COPD in the United States.

Purpose: Chronic obstructive pulmonary disease (COPD) is accompanied by increased inflammation, persistent lung function decline, and extensive lung injury. Klotho, a well-known antiaging protein, has anti-inflammatory and antioxidative effects. However, the effects of klotho on COPD have yet to be thoroughly elucidated. This study examined the association among COPD adults and their α-klotho level. Patients and methods: Data were collected from the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES). A total of 676 participants were analyzed and divided into COPD (n = 403) and non-COPD (n = 273) groups. The two groups were compared with respect to clinical characteristics. Logistic regression analysis and a generalized additive model were used to estimate the association between COPD incidence and serum α-klotho concentration. All COPD participants were stratified according to the levels of α-klotho (Q1: <687 pg./mL; Q2: 687-900 pg./mL; Q3: ≥900 pg./mL), and clinical characteristics were compared. Results: Non-COPD individuals had higher α-klotho levels than did COPD individuals (863.09 ± 267.13 vs. 817.51 ± 302.20, p < 0.05). Logistic regression analysis revealed that the Q2 and Q3 layers had a lower risk of COPD than did the Q1 layer, with odds ratios (ORs) of 0.73 (0.50, 0.99) for Q2 and 0.58 (0.41, 0.86) for Q3 (p < 0.001). The generalized additive model showed that the risk of COPD gradually decreased with increasing α-klotho concentration when the α-klotho concentration < 1,500 pg./mL, while the risk of COPD increased as the α-klotho concentration increased to ≥1,500 pg./mL. Compared with individuals in the Q2 or Q3 groups, individuals with COPD in the Q1 group were more likely to be current smokers, have lower levels of erythrocytes, and have higher levels of creatinine and leukocytes. Conclusion: Increased α-klotho levels were negatively correlated with the risk of COPD in participants over 40 years old with α-klotho <1,500 pg./mL. When α-klotho was ≥1,500 pg./mL, the risk of COPD increased as α-klotho levels increased. Pulmonary ventilation function and the number of hemocytes differed among COPD patients with different levels of α-klotho.

Progranulin Facilitates Corneal Repair Through Dual Mechanisms of Inflammation Suppression and Regeneration Promotion.

The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects modulating Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs.

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

Structural characterization of Astragalus polysaccharide-D1 and its improvement of low-dose metformin effect by enriching Staphylococcus lentus.

To explore the adjuvant therapy drugs of low-dose metformin, one homogeneous polysaccharide named APS-D1 was purified from Astragalus membranaceus by DEAE-52 cellulose and Sephadex G-100 column chromatography. Its chemical structure was characterized by molecular weight distribution, monosaccharide composition, infrared spectrum, methylation analysis, and NMR. The results revealed that APS-D1 (7.36 kDa) consisted of glucose, galactose, and arabinose (97.51 %:1.56 %:0.93 %). It consisted of →4)-α-D-Glcp-(1→ residue backbone with →3)-ß-D-Galp-(1→ residue and terminal-α/ß-D-Glcp-(1→ side chains. APS-D1 could significantly improve inflammation (TNF-α, LPS, and IL-10) in vivo. Moreover, APS-D1 improved the curative effect of low-dose metformin without adverse events. APS-D1 combined with low-dose metformin regulated several gut bacteria, in which APS-D1 enriched Staphylococcus lentus to produce l-carnitine (one of 136 metabolites of S. lentus). S. lentus and l-carnitine could improve diabetes, and reduction of S. lentusl-carnitine production impaired diabetes improvement. The combination, S. lentus, and l-carnitine could promote fatty acid oxidation (CPT1) and inhibit gluconeogenesis (PCK and G6Pase). The results indicated that APS-D1 enhanced the curative effect of low-dose metformin to improve diabetes by enriching S. lentus, in which the effect of S. lentus was mediated by l-carnitine. Collectively, these findings support that low-dose metformin supplemented with APS-D1 may be a favorable therapeutic strategy for type 2 diabetes.

Research on Evolution of Relevant Defects in Heavily Mg-Doped GaN by H Ion Implantation Followed by Thermal Annealing.

This study focuses on the heavily Mg-doped GaN in which the passivation effect of hydrogen and the compensation effect of nitrogen vacancies (VN) impede its further development. To investigate those two factors, H ion implantation followed by thermal annealing was performed on the material. The evolution of relevant defects (H and VN) was revealed, and their distinct behaviors during thermal annealing were compared between different atmospheres (N2/NH3). The concentration of H and its associated yellow luminescence (YL) band intensity decrease as the thermal annealing temperature rises, regardless of the atmosphere being N2 or NH3. However, during thermal annealing in NH3, the decrease in H concentration is notably faster compared to N2. Furthermore, a distinct trend is observed in the behavior of the blue luminescence (BL) band under N2 and NH3. Through a comprehensive analysis of surface properties, we deduce that the decomposition of NH3 during thermal annealing not only promotes the out-diffusion of H ions from the material, but also facilitates the repair of VN on the surface of heavily Mg-doped GaN. This research could provide crucial insights into the post-growth process of heavily Mg-doped GaN.

Pre-rigor salting improves gel strength and water-holding of surimi gel made from snakehead fish (Channa argus): The role of protein oxidation.

The purpose of this study was to determine the effect of pre-rigor salting on the quality characteristics of surimi gels prepared from snakehead fish muscle. Pre-rigor and post-rigor muscle were mixed with 0.3% or 3% NaCl (w/w) and made into surimi gels, respectively. Results showed that pre-rigor muscle had a higher content of ATP, longer sarcomere, higher pH and greater protein solubility. Metabolic profile suggested that pre-rigor muscle had higher content (a 28-fold increase) of antioxidants such as butyryl-l-carnitine. Transmission electron microscopy showed more damage of mitochondria in post-rigor muscle. Surimi paste from pre-rigor meat chopped with 3% NaCl generally showed greater radical scavenging ability and had higher content of free sulfhydryl. Surimi gel made from pre-rigor muscle salted with 3% NaCl showed a larger gel strength (3.18 kg*mm vs. 2.22 kg*mm) and better water-holding (86% vs. 80%) than that of post-rigor group. Based on these findings, we hypothesized that: In addition to other factors such as pH, degree of denaturation, etc., less protein oxidation in pre-rigor salted surimi also contributes to the improved gel properties.

Effect of Helicobacter pylori infection on body fat percentage in middle-aged and elderly populations.

Obesity, which is associated with excessive accumulation of body fat, is emerging as a new public health problem. Bioelectrical impedance analysis (BIA) is a non-invasive and straightforward method to analyze body composition, providing a more accurate estimate of obesity than the commonly used body mass index. The primary objective of this study was to examine the potential impact of Helicobacter pylori (H. pylori) infection on body fat percentage in a population using cross-sectional and cohort studies. METHODS: A population of people who underwent physical examinations at Taizhou Hospital between 2017 and 2022 was included. The participants underwent various tests, including urea breath test, hematological examination, and anthropometric measurement, in addition, their body fat percentage was determined through the use of BIA. Univariate and multifactorial regression analyses were conducted to identify factors associated with excess body fat. RESULTS: There was a difference in body fat percentage between H. pylori positive and negative populations. The population was divided into young and middle-aged and elderly according to age, and H. pylori infection was found to differ only in the middle-aged and elderly population. Multifactorial logistic regression showed that H. pylori infection remained associated with excess body fat in the middle-aged and elderly population. A subsequent cohort study confirmed the association of persistent H. pylori infection with excess body fat in the population. CONCLUSION: H. pylori was negatively associated with excess body fat in middle-aged and elderly populations, and long-term H. pylori infection has a negative effect on body fat in people.

Unleashing Novel Therapeutic Strategies for Dry Eye: Targeting ROS and the cGAS-STING Signaling Pathway with Tetrahedral Framework Nucleic Acids.

Dry eye affects majority of the global population, causing significant discomfort or even visual impairment, of which inflammation plays a crucial role in the deterioration process. This highlights the need for effective and safe anti-inflammatory treatments to achieve satisfactory therapeutic outcomes. This study focuses on the potential of tetrahedral framework nucleic acids (tFNA), a self-assembled nucleic acid material, as a simple and rapid treatment for oxidative stress and inflammation-induced disorders associated with dry eye. Mechanistically, tFNA is found to effectively alleviate dry eye damage by promoting corneal epithelial healing, restoring goblet cell function, and facilitating tear secretion recovery. Through RNA-seq analysis, it is observed that tFNA treatment normalizes the expression levels of most genes. Further exploration of the mechanism reveals that tFNA reduces excessive production of reactive oxygen species and modulates the inflammatory microenvironment, especially through cGAS-STING pathway thereby levels of inflammatory cytokines, including MMP9 and IL-6, are reduced. Additionally, tFNA demonstrates excellent safety performance without causing damage to the eye. Importantly, this study represents a successful application of nanophase materials with nucleic acid biological features for the effective treatment of dry eye, highlighting the potential clinical use of tFNA in the treatment of dry eye.