Associations of five dietary indices with metabolic dysfunction-associated steatotic liver disease and liver fibrosis among the United States population.

Background and aims: The role of dietary factors in metabolic dysfunction-associated steatotic liver disease (MASLD)-which represents a new definition of liver steatosis and metabolic dysfunction- remains unclear. This study aimed to explore the relationships between dietary indices and MASLD. Methods: We analyzed data from the United States National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycle, including 4,690 participants with complete vibration-controlled transient elastography (VCTE) data. Multivariate logistic regression models adjusted for covariates were used to assess the association between dietary indices, MASLD, and MASLD-associated liver fibrosis (MASLD-LF). Restricted cubic spline (RCS) models and subgroup analyses were also performed. Results: The Alternative Healthy Eating Index (AHEI), Healthy Eating Index-2020 (HEI-2020), Dietary Approaches to Stop Hypertension Index (DASHI), and Mediterranean Diet Index (MEDI) were found to be negatively associated with MASLD risk, while the Dietary Inflammatory Index (DII) had a positive association. The highest quartile of MEDI was linked to a 44% reduction in MASLD risk [Q1 vs. Q4 odds ratio (OR): 0.56; 95% confidence interval (CI): 0.34-0.94, P for trend: 0.012]. DASHI was uniquely associated with a reduced risk of MASLD-LF (continuous OR: 0.79; 95% CI: 0.64-0.97; p for trend: 0.003). Our RCS curves indicated a nonlinear association with DASHI-MASLD (p-overall: 0.0001, p-nonlinear: 0.0066). Subgroup analyses showed robust associations among the non-Hispanic White and highly educated populations. Conclusion: Specific dietary patterns were associated with reduced risks of MASLD and MASLD-LF. The DASHI, in particular, showed a significant protective effect against MASLD-LF. These findings suggest potential dietary interventions for managing MASLD and MASLD-LF, although large-scale randomized controlled trials are warranted to validate these findings.

Enhancing Two-Photon Excited Fluorescence of Metal-Organic Framework Single Crystals through Modulation of Inorganic Nodes.

Regulation of the two-photon excited fluorescence (TPEF) emission intensity and wavelength of metal-organic framework (MOF) crystals with similar constitutions presents a significant challenge. In this study, two MOFs, Zn-BTPPA and Cd3-BTPPA, were constructed using tetrakis(1,1'-biphenyl-4-carboxylic acid)-1,4-benzenediamine (H4BTPPA) as the organic ligand and mononuclear Zn and trinuclear Cd3 inorganic nodes, respectively. The incorporation of H4BTPPA within the MOF structures enables effective TPEF emission in both Zn-BTPPA and Cd3-BTPPA. The TPEF results show that Zn-BTPPA and Cd3-BTPPA exhibited strong emissions at 523 and 463 nm, respectively, when excited with a 780 nm laser. Moreover, Zn-BTPPA and Cd3-BTPPA exhibited much higher two-photon absorption cross sections, approximately 4.9 and 5.2 times higher than that of the reported dinuclear MOF, Cd2-BTPPA, with a similar composition, respectively. With different inorganic nodes, the stacking of chromophores, π···π interactions, and ligand geometry were found to correlate with the enhanced TPEF in Cd3-BTPPA and the blue-shifted TPEF in Zn-BTPPA. This work serves as an inspiration for designing efficient TPEF MOF materials based on the structure-property relationship.

GOLM1 dictates acquired Lenvatinib resistance by a GOLM1-CSN5 positive feedback loop upon EGFR signaling activation in hepatocellular carcinoma.

Lenvatinib is a multiple receptor tyrosine kinases inhibitor (TKI) authorized for first-line treatment of hepatocellular carcinoma (HCC). However, Lenvatinib resistance is common in HCC clinical treatment, highlighting the urgent need to understand mechanisms of resistance. Here, we identified Golgi membrane protein 1 (GOLM1), a type II transmembrane protein originally located in the Golgi apparatus, as a novel regulator of Lenvatinib resistance. We found GOLM1 was overexpressed in Lenvatinib resistant human HCC cell lines, blood and HCC samples. Additionally, GOLM1 overexpression contributes to Lenvatinib resistance and HCC progression in vitro and in vivo. Mechanistically, GOLM1 upregulates CSN5 expression through EGFR-STAT3 pathway. Reversely, CSN5 deubiquitinates and stabilizes GOLM1 protein by inhibiting ubiquitin-proteasome pathway of GOLM1. Furthermore, clinical specimens of HCC showed a positive correlation between the activation of the GOLM1-EGFR-STAT3-CSN5 axis. Finally, GOLM1 knockdown was found to act in synergy with Lenvatinib in subcutaneous and orthotopic mouse model. Overall, these findings identify a mechanism of resistance to Lenvatinib treatment for HCC, highlight an effective predictive biomarker of Lenvatinib response in HCC and show that targeting GOLM1 may improve the clinical benefit of Lenvatinib.

Clinicopathological characteristics, prognostic factors, and outcomes of elderly patients with lymphoma-associated hemophagocytic lymphohistiocytosis: A multicenter analysis.

BACKGROUND: Lymphoma is the most common secondary cause of hemophagocytic lymphohistiocytosis (HLH) in adults. Lymphoma-associated HLH (LA-HLH) in the elderly population is not rare, however, little has been reported regarding clinicopathological characteristics, prognostic factors, and outcomes of LA-HLH in the elderly population. METHODS: We retrospectively analyzed a multicenter cohort of elderly patients with LA-HLH. Clinicopathological features and treatment information were collected. The impacts of baseline characteristics and treatments on survival outcomes were analyzed. RESULTS: A total of 173 elderly patients with LA-HLH were included. Compared with young patients, elderly patients showed different clinical and laboratory features. Regarding lymphoma subtypes, B-cell lymphoma was more common in elderly patients (elderly 61.3% vs. young 32.3%, p < 0.001) while T/NK-cell lymphoma was more common in young patients (65.3% vs. 35.3%, p < 0.001). The median survival of elderly patients with LA-HLH was only 92 days. The prior use of HLH therapy or etoposide-containing HLH therapy was not associated with improved overall survival. T/NK-cell subtype, a lower platelet count (≤53 × 109/L), a lower albumin level (≤32.1 g/L), a higher LDH level (>1407 U/L), and a higher creatinine level (>96.8 µmol/L) were independent predictors of decreased overall survival and 60-day survival. A prognostic index was established and demonstrated to be robust in predicting the overall survival and 60-day survival of elderly patients with LA-HLH. CONCLUSIONS: LA-HLH in elderly patients displayed heterogeneous clinicopathological features and survival outcomes. Treatments need to be optimized to improve the outcomes of elderly patients with LA-HLH.

Association between the C-reactive protein to albumin ratio with asthma and mortality in adult: a population-based study.

Asthma is a prevalent chronic disease characterized by airflow obstruction, causing breathing difficulties and wheezing. This study investigates the association between the C-reactive protein to albumin ratio (CAR) and asthma prevalence, as well as all-cause and respiratory mortality among asthma patients, using data from the 2001-2018 National Health and Nutrition Examination Survey. We included participants aged 20 years and older with complete CAR data, excluding those who were pregnant or lost to follow-up. The analysis employed weighted logistic regression and Cox proportional hazards models with stepwise adjustment, restricted cubic spline analysis for nonlinear relationships, and time-dependent ROC curves for predictive accuracy. Results showed that the highest CAR quartile significantly increased the risk of asthma (OR 1.56, 95% CI 1.38-1.78), all-cause mortality (HR 2.20, 95% CI 1.67-2.89), and respiratory mortality (HR 2.56, 95% CI 1.30-5.38). The impact of CAR on all-cause mortality was particularly significant in hypertensive patients. These findings highlight CAR's potential as a valuable biomarker for predicting asthma prevalence and mortality, underscoring its role in asthma management and prognostication.

ATP11A Promotes Epithelial-mesenchymal Transition in Gastric Cancer Cells via the Hippo Pathway.

Background: ATP11A, a P-type ATPase, functions as flippases at the plasma membrane to maintain cellular function and vitality in several cancers. However, the role of ATP11A in gastric cancer remains unknown. This study aimed to identify ATP11A related to the biological behavior of gastric cancer, and elucidate the underlying mechanism. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression and prognosis of ATP11A. The biofunctions of ATP11A were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The expression of ATP11A were validated by immunohistochemistry (IHC), qRT-PCR and Western blotting. Transwell, wound healing, CCK8 and colony-formation were to detected the migration, invasion and proliferation of gastric cancer cells. The epithelial-mesenchymal transition (EMT) and Hippo pathway markers were examined by Western blotting. Results: The expression of ATP11A was higher in gastric cancer tissues than in normal tissues, and high ATP11A levels were related to worse prognosis of gastric cancer patients. Additionally, we proved that ATP11A promoted the migration, invasion and proliferation in gastric cancer cells. Furthermore, ATP11A was found to promote EMT by devitalizing the Hippo pathway. Conclusion: ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

Exploring the Birthday Week Effect on Hand, Foot, and Mouth Disease in Yunnan Province, China, From 2008 to 2022: Surveillance Data Analysis.

Background: Hand, foot, and mouth disease (HFMD) is a notable infectious disease predominantly affecting infants and children worldwide. Previous studies on HFMD have primarily focused on natural patterns, such as seasonality, but research on the influence of important social time points is lacking. Several studies have indicated correlations between birthdays and certain disease outcomes. Objective: This study aimed to explore the association between birthdays and HFMD. Methods: Surveillance data on HFMD from 2008 to 2022 in Yunnan Province, China, were collected. We defined the period from 6 days before the birthday to the exact birthday as the "birthday week." The effect of the birthday week was measured by the proportion of cases occurring during this period, termed the "birthday week proportion." We conducted subgroup analyses to present the birthday week proportions across sexes, age groups, months of birth, and reporting years. Additionally, we used a modified Poisson regression model to identify conditional subgroups more likely to contract HFMD during the birthday week. Results: Among the 973,410 cases in total, 116,976 (12.02%) occurred during the birthday week, which is 6.27 times the average weekly proportion (7/365, 1.92%). While the birthday week proportions were similar between male and female individuals (68,849/564,725, 12.19% vs 48,127/408,685, 11.78%; χ21=153.25, P<.001), significant differences were observed among different age groups (χ23=47,145, P<.001) and months of birth (χ211=16,942, P<.001). Compared to other age groups, infants aged 0-1 year had the highest birthday week proportion (30,539/90,709, 33.67%), which is 17.57 times the average weekly proportion. Compared to other months, patients born from April to July and from October to December, the peak months of the HFMD epidemic, had higher birthday week proportions. Additionally, a decreasing trend in birthday week proportions from 2008 to 2022 was observed, dropping from 33.74% (3914/11,600) to 2.77% (2254/81,372; Cochran-Armitage trend test: Z=-102.53, P<.001). The results of the modified Poisson regression model further supported the subgroup analyses findings. Compared with children aged >7 years, infants aged 0-1 year were more likely to contract HFMD during the birthday week (relative risk 1.182, 95% CI 1.177-1.185; P<.001). Those born during peak epidemic months exhibited a higher propensity for contracting HFMD during their birthday week. Compared with January, the highest relative risk was observed in May (1.087, 95% CI 1.084-1.090; P<.001). Conclusions: This study identified a novel "birthday week effect" of HFMD, particularly notable for infants approaching their first birthday and those born during peak epidemic months. Improvements in surveillance quality may explain the declining trend of the birthday week effect over the years. Higher exposure risk during the birthday period and potential biological mechanisms might also account for this phenomenon. Raising public awareness of the heightened risk during the birthday week could benefit HFMD prevention and control.

The impact of social network use on adolescent depression: the chain mediation between self-objectification and body satisfaction.

Introduction: Adolescents are in the transitional stage from childhood to adulthood, a critical period for individual physical and mental development. With the rapid development of the Internet, social networking has become an integral part of adolescents' daily lives. However, the information that adolescents are exposed to on social networks is often processed and embellished, which may cause them to become physically dissatisfied and lead to emotional problems, such as depression. We investigated the chain-mediating effects of self-objectification and body satisfaction on the relationship between social network use and depression. Methods: We utilized questionnaire data of 2025 adolescents from two secondary schools and one high school in China. Results: Our results demonstrated that (1) there are obvious sex differences in the intensity of social network use and active and passive social network use among adolescents, with usage higher among girls than for boys; (2) self-objectification and body satisfaction play a mediating role in the relationship between the intensity of social network use and adolescent depression, as well as the presence of chain-mediating roles; and (3) self-objectification and body satisfaction play an intermediary role in the relationship between active and passive social network use and adolescent depression; there is further a chain intermediary role. The findings suggest that social network use affects adolescents' depression through self-objectification and body satisfaction, which is not only manifested in the general use intensity of social networks but also in their active and passive use modes of social networks. Conclusion: This study provides theoretical support for the causes and mechanisms behind the influence of social network use on adolescent depression and has practical implications for the prevention and intervention of adolescent emotional problems.

Development and Validation of the Healthcare-Seeking Intention Questionnaire in Patients with Diabetic High-Risk Foot.

Objective: Timely screening and intervention can prevent the development of the diabetic foot. However, delayed visits to the clinic are common among diabetic foot patients. The study aimed to develop and validate a questionnaire to assess healthcare-seeking behavior among patients with diabetic high-risk foot. Methods: The questionnaire of healthcare-seeking intention for patients with diabetic high-risk foot was developed in two phases: (1) Developing the questionnaire: 1) questionnaire items were formulated after literature review, group discussion and semi-qualitative interview; 2) a two-round modified Delphi method was to examine the content validity and the degree of consistency in questionnaire items; 3) conducting pre-survey to revise the questionnaire items. (2) Assessing the internal reliability and construct validity. Results: The final questionnaire consisted of five main themes and 28 items with a five-point rating. Cronbach's alpha coefficients for the five dimensions were respectively 0.937 (relevant knowledge of diabetic foot), 0.669 (attitudes toward seeking care), 0.896 (social support for seeking care), 0.621 (efficacy in coping with foot symptoms), 0.871 (intention to seek care). The Scale-level Content Validity Index of the five parts was 1.00, 0.80, 1.00, 1.00, and 1.00, respectively. The Kaiser-Meyer-Olkin values for each dimension was greater than 0.7, and the p-value for Bartlett's test of sphericity was less than 0.05. Conclusion: This questionnaire showed good validity, internal consistency, and reliability. It provided a potentially useful instrument to evaluate healthcare-seeking intention among patients with diabetic high-risk foot.

Prenatal exposure to PM2.5 and its composition on child growth trajectories in the first two years: A prospective birth cohort study.

The findings on the relationship between prenatal exposure to particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) and its constituent and children's growth trajectories are inconsistent. This association's sensitive exposure time window and possible gender differences remain unclear. Our aim was to determine the association between prenatal exposure to PM2.5 and its component and children's growth trajectories by the age of two. From 2015 to 2021, 6407 mother-infant pairs were enrolled in the study. The PM2.5 include sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), organic matter (OM), and black carbon (BC), from the ChinaHighAirPollutants (CHAP) datasets. Children were followed at birth, 1, 3, 6, 9, 12, 18, and 24 months. Population-based and individual-based methods were used to simulate child growth trajectories: slow growth, normal growth, and rapid growth. The distributed lags modeling was used to identify sensitive time windows for the effects of prenatal exposure to PM2.5 and its components on child growth. Sex-stratified analyses estimated sex differences. Median concentrations [interquartile ranges (IQRs)] were 57.46(17.3), 10.59(3.8), 14.26(4.4), 8.69(2.8), 13.05(3.4), and 2.53(0.7) µg/m3 for PM2.5, SO42-, NO3-, NH4+, OM, and BC, respectively. Compared with the normal growth trajectory group, exposure to PM2.5 was significantly associated with a higher risk of rapid growth trajectory in boys (ORs with 95% CI for the entire, first trimester, and second trimester of pregnancy, respectively: 1.016[1.006,1.025], 1.007[1.002,1.011], 1.007[1.002,1.011]). Exposure to PM2.5 was significantly associated with a higher risk of slow growth trajectory in girls (ORs with 95% CI for the entire, second trimester, and third trimester of pregnancy, respectively: 1.010 [1.001,1.018], 1.006 [1.001,1.011], 1.007 [1.002,1.012]). Prenatal PM2.5 and its composition exposure was positively associated with BMI peak in boys (ßs with 95% CI for PM2.5, SO42-, NO3-, NH4+, OM, BC: 0.004[0.000,0.007], 0.025[0.006,0.044], 0.012[0.002,0.023], 0.022[0.004,0.039], 0.016[0.001,0.031], 0.082[0.005,0.159]), and not statistically significant in girls. We observed a more pronounced BC effect in our cohort. Prenatal exposure to PM2.5 and its component, especially at 10-22 weeks of gestation, is associated with a higher risk of rapid growth in boys and a risk of slow growth in girls.

JuA alleviates liver ischemia-reperfusion injury by activating AKT/NRF2/HO-1 pathways.

Liver ischemia-reperfusion (I/R) injury is a detrimental complication of organ transplantation, shock, and sepsis. However, the available drugs to mitigate I/R injury remain limited. Jujuboside A (JuA) is renowned for its antioxidant, anti-inflammatory, and anti-apoptotic properties; nevertheless, its potential in liver I/R injury remains unknown. Thus, this study aimed to explore the role and underlying mechanisms of JuA in liver I/R injury. Mouse models of I/R and AML12 cell models of hypoxia/reoxygenation (H/R) were constructed. Haematoxylin and eosin staining, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) detection, and cell viability analysis were used to assess liver injury. To evaluate oxidative stress, inflammation, apoptosis, and mitochondrial damage, immunofluorescence staining, transmission electron microscopy analysis, enzyme-linked immunosorbent assay, and flow cytometry were conducted. Moreover, molecular docking techniques and western blot were employed to identify downstream target molecules and pathways affected by JuA. The results showed that JuA pretreatment effectively attenuated liver necrosis and ALT and AST level elevations induced by I/R while enhancing AML12 cell viability following H/R. Furthermore, JuA pretreatment suppressed oxidative stress triggered by I/R and H/R, thereby inhibiting the level of pro-inflammatory factors and NLRP3 inflammasome activation. Notably, JuA pretreatment alleviated mitochondrial damage and apoptosis. Mechanistically, JuA pretreatment resulted in the activation of the AKT/NRF2/HO-1 signalling pathways, whereas MK2206, the inhibitor of AKT, partially reversed the hepatoprotective effects of JuA during liver I/R. Collectively, our findings illustrated that JuA mitigated oxidative stress, inflammation, apoptosis, and mitochondrial damage by facilitating the AKT/NRF2/HO-1 signalling pathway, thereby alleviating liver I/R injury.

Design of Mixed-Metal MOF-74-MgNi for Water Adsorption-Driven Solar Thermal Energy Storage and Heat Transformation Applications.

Adsorption solar thermal energy storage and heat transformation are ecologically benign and energy-efficient technologies. Efficient adsorbents are the key to this technology. In this paper, two metal ions, Mg2+ and Ni2+, were introduced into the metal-organic framework MOF-74. The synthesis conditions were adjusted to obtain MOF-74 with a high water adsorption capacity and stability. The results show that MOF-74-MgNi-2 has the maximum water adsorption capacity. At a low moisture pressure P/P0 = 0.1, its water adsorption capacity is 0.44 g/g, 0.12 g/g, and 0.10 g/g greater than that of MOF-74-Mg and MOF-74-Ni, respectively. Its saturated water adsorption capacity at P/P0 = 0.9 is as high as 0.62 g/g, which is 1.3 times that of MOF-74-Ni and 1.1 times that of MOF-74-Mg, respectively. Its superior water adsorption capacity is explained by the combination of experiment and molecular simulation, which takes into account the pore structure and electrostatic potential energy distribution. Its thermal breakdown temperature is greater than 250 °C. Its water adsorption capacity decreases by only 9.0% in the 10th cycle. Under conventional refrigeration conditions, its refrigeration coefficient and working capacity are 0.75 and 0.43 cm3/cm3, respectively, which are greater than those of the majority of the regularly used adsorbents. In addition, it satisfies the primary technological goals of adsorption-based thermal batteries with a heat storage capacity of up to 1394 kJ/kg. The mixed-metal method is shown to be useful in the design of high-performance MOF-74 for solar thermal energy storage and heat transformation.

Influencing factors for postpartum depression in women with gestational diabetes mellitus.

Objective: It remains undefined about the association between gestational diabetes mellitus (GDM) and postpartum depression (PPD). Hence, a cross-sectional study was conducted to evaluate the association between GDM and PPD among pregnant women and to investigate the influencing factors for PPD. Methods: From June 2021 to June 2022, 205 parturients with GDM and 201 without GDM were included in the study as the GDM group and the control group, respectively. The collected data from the general information questionnaire and Self Rating Depression Scale (SDS) were statistically analyzed based on binomial logistic regression analyses and generalized linear mixed models (GLMMs). Results: Age at delivery, gestational age, glycosylated hemoglobin, triglyceride, SDS, and proportions of women who had a history of induced abortion or GDM were significantly different between the GDM group and control group (P<0.05). The incidence of PPD in the GDM group was significantly higher than that in the control group. The neonatal body weight and triglyceride in GDM women with PPD were significantly lower than those in GDM women without PPD (P<0.001). The univariate logistic regression analysis demonstrated that educational age was a protective factor, while glycosylated hemoglobin and GDM were risk factors for PPD. The multiple linear regression analysis revealed that neonatal body weight (OR=-0.904, 95%CI: -1.657 to -0.152, P=0.019) and educational age (OR=-0.166, 95%CI: -0.306 to -0.025, P=0.021) were protective factor, while GDM (OR=1.854, 95%CI: 1.027-2.681, P<0.0001) was a risk factor for PPD. Conclusion: GDM may be associated with PPD. Neonatal body weight and educational age were protective factors for PPD, and GDM was a risk factor for PPD. Therefore, more attention should be paid to the mental health status of women with GDM, especially those with lesser educational age and lower neonatal body weight.

Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids.

Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study. These vessels made of photoresist with densely distributed micropores with a diameter of 20 µm on the sidewall, are cocultured with brain organoids to facilitate the diffusion of culture medium into the organoids. The vascularized organoids exhibit dimensional breaking growth and enhanced proliferation, reduced hypoxia and apoptosis, suggesting that the 3D-printed meshed vessels partially mimic vascular function to promote the culture of organoids. Furthermore, cortical, striatal and medial ganglionic eminence (MGE) organoids are respectively differentiated to generate Cortico-Striatal-MGE assembloids by 3D-printed vessels. The enhanced migration, projection and excitatory signaling transduction are observed between different brain regional organoids in the assembloids. This study presents an approach using TPP 3D printing to construct vascularized brain organoids and assembloids for enhancing the development and assembly, offering a research model and platform for neurological diseases.

The effect of SGLT2 inhibition on brain-related phenotypes and aging: a drug target Mendelian randomization study.

INTRODUCTION: Observational study suggested SGLT2 inhibitors might promote healthy aging. However, whether brain-related phenotypes mediate this association. We applied Mendelian randomization (MR) to investigate the effect of SGLT2 inhibition on chronological, biological age and cognition and explore the mediation effects of brain imaging-derived phenotypes (IDPs). METHODS: We selected genetic variants associated with both expression levels of SLC5A2 (GTEx and eQTLGen data; N=129 to 31,684) and HbA1c levels (UK Biobank; N=344,182) and used them to proxy the effect of SGLT2 inhibition. Aging related outcomes, including parental longevity (N=389,166) and epigenetic clocks (N=34,710), and cognitive phenotypes, including cognitive function (N=300,486) and intelligence (N= 269,867) were derived from genome-wide association studies. Two-step MR were conducted to explore the associations between SGLT2 inhibition, IDPs, and aging outcomes, cognition. RESULTS: SGLT2 inhibition was associated with longer father's attained age (years of life increase per SD (6.75 mmol/mol) reduction in HbA1c levels = 6.21, 95%CI 1.95 to 11.15), better cognitive function (beta = 0.17, 95%CI 0.03 to 0.31) and higher intelligence (beta = 0.47, 95%CI 0.19 to 0.75). Two-step MR identified two IDPs as mediators linking SGLT2 inhibition with chronological age (total proportion of mediation = 22.6%), where four and five IDPs were mediators for SGLT2 inhibition on cognitive function and intelligence respectively (total proportion of mediation = 61.6% and 68.6% respectively). CONCLUSIONS: Our study supported that SGLT2 inhibition increases father's attained age, cognitive function and intelligence, which was mediated through brain images of different brain regions. Future studies are needed to investigate whether similar effect could be observed for users of SGLT2 inhibitors.

Research on a new type of ureteral stent material Zn-2Cu-0.5Fe-xMn with controllable degradation rate.

The placement of ureteral stents plays a crucial role in the treatment of ureteral strictures, therefore requiring high material performance standards. In addition, depending on the etiology of ureteral strictures, there are significant differences in the retention time of ureteral stents, thus requiring different degradation rates for the stents. Therefore, it is crucial to develop stent materials with high performance and controllable degradation rates. This study explores the potential of Zn-2Cu-0.5Fe-xMn alloy as a ureteral stent material, utilizing the antibacterial effect of copper ions, the strengthening effect of Fe element on Zn-based alloys, and the accelerated degradation effect of Mn element. The research found that with the increase in Mn content, the average grain size of the alloy and the size of (Fe, Mn)Zn13 phase gradually increased, leading to a decrease in hardness. The corrosion rate of the alloy increased with the increase in Mn content, attributed to changes in grain size and standard electrode potential differences between elements. Due to the antibacterial effects of Zn ions and Cu ions, the Zn-2Cu-0.5Fe-xMn alloy exhibits good anti-stone formation capabilities. Furthermore, the alloy also demonstrates acceptable cytotoxicity. Therefore, the Zn-2Cu-0.5Fe-xMn alloy is expected to become an important implant material in urological surgery.

Effect of the intraoperative head hypsokinesis on sore throat after thyroid surgery: a randomized controlled trial.

PURPOSE: Postoperative sore throat (POST) after thyroidectomy is a major concern.A roll is typically inserted under the shoulder to achieve head hypsokinesis and neck extension to better expose the surgical site during thyroid surgery. However, POST and impaired voice function have been attributed to neck overextension. This study aimed to explore the rational angle of head hypsokinesis that both reduced sore throat intensity and protects voice function after thyroid surgery. METHODS: A total of 210 patients who underwent thyroidectomy were enrolled and randomized into high-tilt (Group H) and low-tilt angle groups (Group L). The primary outcome was the incidence of POST 6 h after surgery. Secondary outcomes included the severity of postoperative pharyngeal pain, voice function, swallowing pain, and coughing. RESULTS: The incidence of POST 6 h after thyroidectomy was significantly lower in Group L than that in Group H. In addition, the intensity of postoperative sore throat and swallowing pain was more severe in Group H. A lower degree of head hypsokinesis in Group L prevented transient postoperative voice injury. CONCLUSIONS: A lower degree of head hypsokinesis effectively mitigated sore throat severity after thyroidectomy and improved postoperative voice function. REGISTER INFORMATION: The trial was registered in the Chinese Clinical Trial Registry on 21 June 2022 (ChiCTR2200061329). The trial is registered at https://www.chictr.org.cn/showproj.html?proj=166254 .

The Landscape of Smart Biomaterial-Based Hydrogen Therapy.

Hydrogen (H2) therapy is an emerging, novel, and safe therapeutic modality that uses molecular hydrogen for effective treatment. However, the impact of H2 therapy is limited because hydrogen molecules predominantly depend on the systemic administration of H2 gas, which cannot accumulate at the lesion site with high concentration, thus leading to limited targeting and utilization. Biomaterials are developed to specifically deliver H2 and control its release. In this review, the development process, stimuli-responsive release strategies, and potential therapeutic mechanisms of biomaterial-based H2 therapy are summarized. H2 therapy. Specifically, the produced H2 from biomaterials not only can scavenge free radicals, such as reactive oxygen species (ROS) and lipid peroxidation (LPO), but also can inhibit the danger factors of initiating diseases, including pro-inflammatory cytokines, adenosine triphosphate (ATP), and heat shock protein (HSP). In addition, the released H2 can further act as signal molecules to regulate key pathways for disease treatment. The current opportunities and challenges of H2-based therapy are discussed, and the future research directions of biomaterial-based H2 therapy for clinical applications are emphasized.

Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes.

BACKGROUND: Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear. METHODS: We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables. FINDINGS: The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: -1.51 [-2.01, -1.01] mmol/L) compared to the corn oil group (-0.66 [-1.15, -0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation. CONCLUSIONS: Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO. FUNDING: This study was funded by the National Nature Science Foundation.

Machine learning risk prediction model for bloodstream infections related to totally implantable venous access ports in patients with cancer.

Objective: This study aimed to develop and validate a machine learning-based risk prediction model for catheter-related bloodstream infection (CRBSI) following implantation of totally implantable venous access ports (TIVAPs) in patients. Methods: A retrospective cohort study design was employed, utilizing the R software package mlr3. Various algorithms including logistic regression, naive Bayes, K nearest neighbor, classification tree, and random forest were applied. Addressing class imbalance, benchmarks were used, and model performance was assessed using the area under the curve (AUC). The final model, chosen for its superior performance, was interpreted using variable importance scores. Additionally, a nomogram was developed to calculate individualized risk probabilities, enhancing clinical utility. Results: The study involved 755 patients across both development and validation cohorts, with a TIVAP-CRBSI rate of 14.17%. The random forest model demonstrated the highest discrimination ability, achieving a validated AUC of 0.94, which was consistent in the validation cohort. Conclusions: This study successfully developed a robust predictive model for TIVAP-CRBSI risk post-implantation. Implementation of this model may aid healthcare providers in making informed decisions, thereby potentially improving patient outcomes.