A positive association between BMI and kidney stones among the diabetic population: a cross-sectional study from NHANES.

BACKGROUND: In the past, research has shown that a higher body mass index (BMI) is one of the variables that increase the likelihood of kidney stones; however, no studies have found a connection between the two in the type II diabetic population. The purpose of this research is to reveal the association between BMI and kidney stones in the type II diabetic population. METHODS: We selected demographic data, laboratory data, lifestyle, and medical history from the NHANES. Specifically includes age, gender, systemic immune-inflammation index (SII), poverty income rate (PIR), body mass index (BMI), kidney stones, education, coronary artery disease, smoking, and drinking. RESULTS: BMI and kidney stones were shown to have a positive association in type II diabetics (blood sugar level > 7.0 mmol/L or diagnosed by a doctor) (OR = 1.021, 95% CI 1.008-1.033, P = 0.001), even after controlling for factors, such as age, gender, race, education level, coronary heart disease, smoking, and drinking. The subgroup analysis revealed a more significant positive association among the 67-80 years, female and Non-Hispanic White population. CONCLUSIONS: There is a positive correlation between BMI and kidney stones among the type II diabetic population.

Causal relationship between gut microbiota and prostate cancer contributes to the gut-prostate axis: insights from a Mendelian randomization study.

BACKGROUND: Changes in gut microbiota abundance have been linked to prostate cancer development. However, the causality of the gut-prostate axis remains unclear. METHODS: The genome-wide association study (GWAS) data for gut microbiota sourced from MiBioGen (n = 14,306), alongside prostate cancer summary data from PRACTICAL (n = 140,254) and FinnGen Consortium (n = 133,164). Inverse-variance-weighted (IVW) was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl), after diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. We used meta-analysis methods in random effects to combine the Mendelian randomization (MR) estimates from the two sources. RESULTS: The pooled analyses of MR results show that genus Eubacterium fissicatena (OR = 1.07, 95% CI 1.01 to 1.13, P = 0.011) and genus Odoribacter (OR = 1.14, 95% CI 1.01 to 1.27, P = 0.025) were positively associated with prostate cancer. However, genus Adlercreutzia (OR = 0.89, 95% CI 0.83 to 0.96, P = 0.002), Roseburia (OR = 0.90, 95% CI 0.83 to 0.99, P = 0.03), Holdemania (OR = 0.92, 95% CI 0.86 to 0.97, P = 0.005), Flavonifractor (OR = 0.85, 95% CI 0.74 to 0.98, P = 0.024) and Allisonella (OR = 0.93, 95% CI 0.89 to 0.98, P = 0.011) seems to be a protective factor for prostate cancer. Sensitivity analysis found no significant heterogeneity, horizontal pleiotropy, or reverse causal links in all causal associations. CONCLUSION: This MR study lends support to a causal relationship between genetically predicted gut microbiota and prostate cancer. Research on the gut-prostate axis, along with further multi-omics analyses, holds significant implications for the prevention and treatment of prostate cancer.

The Causal Relationships Between Gut Microbiota, Brain Volume, and Intelligence: A Two-Step Mendelian Randomization Analysis.

BACKGROUND: Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence. METHODS: We performed a 2-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota (N = 18,340) and intelligence (N = 269,867). The inverse-variance weighted method was used to conduct the MR analyses complemented by a range of sensitivity analyses to validate the robustness of the results. Considering the close relationship between brain volume and intelligence, we applied 2-step MR to evaluate whether the identified effect was mediated by regulating brain volume (N = 47,316). RESULTS: We found a risk effect of the genus Oxalobacter on intelligence (odds ratio = 0.968 change in intelligence per standard deviation increase in taxa; 95% CI, 0.952-0.985; p = 1.88 × 10-4) and a protective effect of the genus Fusicatenibacter on intelligence (odds ratio = 1.053; 95% CI, 1.024-1.082; p = 3.03 × 10-4). The 2-step MR analysis further showed that the effect of genus Fusicatenibacter on intelligence was partially mediated by regulating brain volume, with a mediated proportion of 33.6% (95% CI, 6.8%-60.4%; p = .014). CONCLUSIONS: Our results provide causal evidence indicating the role of the microbiome in intelligence. Our findings may help reshape our understanding of the microbiota-gut-brain axis and development of novel intervention approaches for preventing cognitive impairment.

Perioperative, functional, and oncological outcomes after cryoablation or partial nephrectomy for small renal masses in solitary kidneys: a systematic review and meta-analysis.

AIM: This study aims to compare the perioperative, functional, and oncological outcomes of cryoablation (CA) and partial nephrectomy (PN) for managing small renal masses in patients with solitary kidneys. The study seeks to assess the efficacy and safety of both interventions, evaluating their impact on kidney function and their ability to mitigate cancer recurrence. METHODS: Searches were systematically conducted on PubMed, Scopus, EMBASE, SinoMed, and Google Scholar, identifying seven observational studies. Statistical analysis was performed using Stata v.12.0 and Review Manager version 5.2. Results for dichotomous variables are expressed using odds ratios, and weighted mean differences are used for continuous variables. RESULTS: Our findings revealed that patients undergoing CA experienced significantly shorter operative time (p < 0.0001), reduced estimated blood loss (p < 0.00001), a shorter length of stay (p = 0.0001), and fewer postoperative complications (p = 0.02) compared to those undergoing PN. Although the CA group exhibited a lower transfusion rate (p = 0.69) compared with the PN group, the difference was not statistically significant. The combined data analysis demonstrated a significantly lower increase in serum creatinine levels after surgery in the CA group compared with the PN group (p = 0.003). Similarly, there was a noteworthy decrease in the estimated glomerular filtration rate after surgery in the PN group compared with the CA group (p < 0.0001). While not statistically significant, the CA group showed a lower postoperative dialysis rate (p = 0.11). Regarding oncological outcomes, the analysis revealed no significant differences between CA and PN concerning local recurrence (p = 0.2) and distant metastasis (p = 0.12), respectively. CONCLUSIONS: Our analysis indicates comparable efficacy between PN and CA in controlling tumour recurrence and metastasis. However, CA is associated with superior preservation of renal function, significantly enhanced perioperative outcomes, and fewer postoperative complications. Based on our data, it can be inferred that the scope for applying CA might be expanded to encompass more patients seeking a less invasive treatment option.

Multi-tissue transcriptome-wide association study reveals susceptibility genes and drug targets for insulin resistance-relevant phenotypes.

AIM: Genome-wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)-relevant phenotypes. However, the genes responsible for these associations remain largely unknown. We aim to identify susceptibility genes for IR-relevant phenotypes via a transcriptome-wide association study. MATERIALS AND METHODS: We conducted a large-scale multi-tissue transcriptome-wide association study for IR (Insulin Sensitivity Index, homeostasis model assessment-IR, fasting insulin) and lipid-relevant traits (high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol and total cholesterol) using the largest GWAS summary statistics and precomputed gene expression weights of 49 human tissues. Conditional and joint analyses were implemented to identify significantly independent genes. Furthermore, we estimated the causal effects of independent genes by Mendelian randomization causal inference analysis. RESULTS: We identified 1190 susceptibility genes causally associated with IR-relevant phenotypes, including 58 genes that were not implicated in the original GWAS. Among them, 11 genes were further supported in differential expression analyses or a gene knockout mice database, such as KRIT1 showed both significantly differential expression and IR-related phenotypic effects in knockout mice. Meanwhile, seven proteins encoded by susceptibility genes were targeted by clinically approved drugs, and three of these genes (H6PD, CACNB2 and DRD2) have been served as drug targets for IR-related diseases/traits. Moreover, drug repurposing analysis identified four compounds with profiles opposing the expression of genes associated with IR risk. CONCLUSIONS: Our study provided new insights into IR aetiology and avenues for therapeutic development.

Sleep and circadian rhythm disturbance in kidney stone disease: a narrative review.

The circadian rhythm generated by circadian clock genes functions as an internal timing system. Since the circadian rhythm controls abundant physiological processes, the circadian rhythm evolved in organisms is salient for adaptation to environmental change. A disturbed circadian rhythm is a trigger for numerous pathological events. Recently, accumulated data have indicated that kidney stone disease (KSD) is related to circadian rhythm disturbance. However, the mechanism between them has not been fully elucidated. In this narrative review, we summarized existing evidence to illustrate the possible association between circadian rhythm disturbance and KSD based on the epidemiological studies and risk factors that are linked to circadian rhythm disturbance and discuss some chronotherapies for KSD. In summary, KSD is associated with systemic disorders. Metabolic syndrome, inflammatory bowel disease, and microbiome dysbiosis are the major risk factors supported by sufficient data to cause KSD in patients with circadian rhythm disturbance, while others including hypertension, vitamin D deficiency, parathyroid gland dysfunction, and renal tubular damage/dysfunction need further investigation. Then, some chronotherapies for KSD were confirmed to be effective, but the molecular mechanism is still unclear.

The causal association between smoking, alcohol consumption and risk of upper urinary calculi: insights from a Mendelian randomization study.

Background: The causal link between smoking, alcohol consumption, and upper urinary calculi remains uncertain in observational studies due to confounding factors. To uncover potential causal associations, we utilized two-sample univariable and multivariable Mendelian randomization (MR) methods. Methods: Five risk factors related to lifestyles (cigarettes per day, lifetime smoking index, smoking initiation, drinks per week and alcohol intake frequency) were chosen from the Genome-Wide Association Study (GWAS). Upper urinary calculi were obtained from the FinnGen and United Kingdom Biobank consortium. Inverse-variance-weighted (IVW) was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). While diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. Results: The summary OR for upper urinary calculi was 0.6 (IVW 95% CI: 0.49-0.74; p = 1.31 × 10-06) per standard deviation decrease in drinks per week. Interestingly, the genetically predicted alcohol intake frequency was associated with a significantly increased risk upper urinary calculi (OR = 1.27; 95% CI: 1.11-1.45; p = 0.0005). Our study found no association between smoking initiation, the number of cigarettes per day, and the lifetime smoking index and the risk of upper urinary calculi. By adjusting for body mass index and education, estimates of drinks per week remained consistent in multivariate MR analyses, while alcohol intake frequency became non-significant. Conclusion: MR analysis showed that drinks per week was negatively associated with upper urinary calculi, whereas the effect of tobacco on upper urinary calculi was not significant and the detrimental effect of alcohol intake frequency on upper urinary calculi became non-significant after adjusting for BMI and education.

Dose dependent effect of nitrogen on the phyto extractability of Cd in metal contaminated soil using Wedelia trilobata.

Cadmium (Cd) is one of the toxic heavy metal that negatively affect plant growth and compromise food safety for human consumption. Nitrogen (N) is an essential macronutrient for plant growth and development. It may enhance Cd tolerance of invasive plant species by maintaining biochemical and physiological characteristics during phytoextraction of Cd. A comparative study was conducted to evaluate the phenotypical and physiological responses of invasive W. trilobata and native W. chinensis under low Cd (10 µM) and high Cd (80 µM) stress, along with different N levels (i.e., normal 91.05 mg kg-1 and low 0.9105 mg kg-1). Under low-N and Cd stress, the growth of leaves, stem and roots in W. trilobata was significantly increased by 35-23%, 25-28%, and 35-35%, respectively, compared to W. chinensis. Wedelia trilobata exhibited heightened antioxidant activities of catalase and peroxidase were significantly increased under Cd stress to alleviate oxidative stress. Similarly, flavonoid content was significantly increased by 40-50% in W. trilobata to promote Cd tolerance via activation of the secondary metabolites. An adverse effect of Cd in the leaves of W. chinensis was further verified by a novel hyperspectral imaging technology in the form of normalized differential vegetation index (NDVI) and photochemical reflectance index (PRI) compared to W. trilobata. Additionally, W. trilobata increased the Cd tolerance by regulating Cd accumulation in the shoots and roots, bolstering its potential for phytoextraction potential. This study demonstrated that W. trilobata positively responds to Cd with enhanced growth and antioxidant capabilities, providing a new platform for phytoremediation in agricultural lands to protect the environment from heavy metals pollution.

Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to new-generation ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. RESULTS: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide. CONCLUSION: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further.

Improving the Efficiency of Precise Genome Editing with CRISPR/Cas9 to Generate Goats Overexpressing Human Butyrylcholinesterase.

The CRISPR/Cas9 system is widely used for genome editing in livestock production, although off-target effects can occur. It is the main method to produce genome-edited goats by somatic cell nuclear transfer (SCNT) of CRISPR/Cas9-mediated genome-edited primary goat fetal fibroblast cells (GFFs). Improving the double-strand break (DSB) efficiency of Cas9 in primary cells would improve the homologous repair (HR) efficiency. The low efficiency of HR remains a major hurdle in CRISPR/Cas9-mediated precise genome editing, increasing the work required to screen the genome-edited primary cell clones. In this study, we modified several essential parameters that affect the efficiency of the CRISPR/Cas9-mediated knock-in GFF cloning system, including establishing a high-efficiency transfection system for primary cells via nucleofection and optimizing homology arm (HA) length during HR. Here, we specifically inserted a recombinant human butyrylcholinesterase gene (rhBChE) into the goat fibroblast growth factor (FGF)-5 locus through the CRISPR/Cas9 system, thereby achieving simultaneous rhBChE insertion and FGF5 knock-out. First, this study introduced the Cas9, FGF5 knock-out small guide RNA, and rhBChE knock-in donors into GFFs by electroporation and obtained positive cell clones without off-target effects. Then, we demonstrated the expression of rhBChE in GFF clones and verified its function. Finally, we obtained a CRISPR/Cas9-mediated rhBChE-overexpression goat.

Tensor Network Efficiently Representing Schmidt Decomposition of Quantum Many-Body States.

Efficient methods to access the entanglement of a quantum many-body state, where the complexity generally scales exponentially with the system size N, have long been a concern. Here we propose the Schmidt tensor network state (Schmidt TNS) that efficiently represents the Schmidt decomposition of finite- and even infinite-size quantum states with nontrivial bipartition boundary. The key idea is to represent the Schmidt coefficients (i.e., entanglement spectrum) and transformations in the decomposition to tensor networks (TNs) with linearly scaled complexity versus N. Specifically, the transformations are written as the TNs formed by local unitary tensors, and the Schmidt coefficients are encoded in a positive-definite matrix product state (MPS). Translational invariance can be imposed on the TNs and MPS for the infinite-size cases. The validity of Schmidt TNS is demonstrated by simulating the ground state of the quasi-one-dimensional spin model with geometrical frustration. Our results show that the MPS encoding the Schmidt coefficients is weakly entangled even when the entanglement entropy of the decomposed state is strong. This justifies the efficiency of using MPS to encode the Schmidt coefficients, and promises an exponential speedup on the full-state sampling tasks.

Erectile function, urinary continence and oncologic outcomes of neurovascular bundle sparing robot-assisted radical prostatectomy for high-risk prostate cancer: A systematic review and meta-analysis.

Background: The nerve-sparing (NS) effect of robot-assisted radical prostatectomy (RARP) on patients with a high-risk prostate cancer remains unclear. The objective of this study was to compare the urinary continence, erectile function and oncology outcomes of the nerve-sparing and non-nerve-sparing (NNS) group during RARP surgeries. Methods: We systematically searched databases including PubMed, Embase, Cochrane Library and Web of Science to identify relevant studies published in English up to December 2022. Newcastle-Ottawa Scale (NOS) was used as a quality evaluation tool to evaluate the quality of the literature parameters involved, including urinary continence, erectile function and oncologic outcomes, which were compared using the Stata 15.1 software (StataSE, USA). Results: A total of 8 cohort studies involving 2499 patients were included. A meta-analysis of results showed that the NS group was beneficial to the recovery of urinary continence (RR 0.46, 95%CI 0.22, 0.96; p=0.045<0.05) and erectile function (RR 0.32, 95%CI 0.16, 0.63; p=0.001<0.05) 12 months after surgeries, which showed a better oncological outcome (RR 1.31, 95%CI 1.01, 1.69; p=0.01<0.05). Conclusions: The current study results indicate that intraoperative NS during RARP is beneficial to long-term postoperative functional recovery and tumor prognosis of patients with high-risk prostate cancers. Due to interstudy interferences, the results should be interpreted with caution. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022384647.

Correlation of the spin state and catalytic property of M-N4 single-atom catalysts in oxygen reduction reactions.

The rational design of high-performance catalysts for oxygen reduction reactions (ORRs) is of great importance for large-scale applications in the field of proton-exchange membrane fuel cells and the green synthesis of H2O2. The effect of spin states of paramagnetic metal ions on the selectivity of ORRs is significant for single-atom catalysts (SACs). In this work, via spin-polarization density functional theory (DFT) calculations, we systematically investigated the popular paramagnetic metal-nitrogen graphene (M-N4-C, M = Mn, Fe, and Co) SACs to mainly focus on the correlation of spin states and catalytic performance (e.g. activity and selectivity). Both thermodynamically and kinetically, it was found that Co-N4-C (S = 1/2) has excellent 2e- oxygen reduction performance (hydrogen peroxide production) with an ultralow overpotential of 0.03 V, and the hydrogenation of OOH* is the rate-determining step (RDS) with an energy barrier of 1.20 eV. The 4e- ORR tends to occur along the OOH dissociation pathway (O* + OH*) on Co-N4-C (S = 3/2), in which OOH* decomposition is the RDS with an energy barrier of 1.01 eV. It is proved that the spin magnetic moment is the key factor to regulate the ORR property via multi-angle electronic analysis. The spin states of catalysts play a crucial role in the activity and selectivity of ORRs mainly by manipulating the bond strength between OOH and catalysts. This will provide new insights for the rational design of ORR catalysts with magnetic metals.

Perioperative, functional, and oncologic outcomes in patients undergoing robot-assisted radical prostatectomy previous transurethral resection of prostate: a systematic review and meta-analysis of comparative trials.

The influence of robot-assisted radical prostatectomy (RARP) on patients who have previously undergone transurethral resection of the prostate (TURP) versus TURP-naive patients is still debatable. The present study aimed to compare perioperative, functional, and oncologic outcomes of RARP between TURP and Non-TURP groups. We systematically searched the databases such as Science, PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies published in English up to August 2022. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42022378126). Eight comparative trials with a total of 4186 participants were conducted. The TURP group had a longer operative time (WMD 22.22 min, 95% CI 8.48, 35.95; p = 0.002), a longer catheterization time (WMD 1.32 day, 95% CI 0.37, 2.26; p = 0.006), a higher estimated blood loss (WMD 23.86 mL, 95% CI 2.81, 44.90; p = 0.03), and higher bladder neck reconstruction rate (OR 8.02, 95% CI 3.07, 20.93; p < 0.0001). Moreover, the positive surgical margin (PSM) was higher in the TURP group (OR 1.49, 95% CI 1.12, 1.98 p = 0.007). However, there was no difference between the two groups regarding the length of hospital stay, transfusion rates, nerve-sparing status, complication rates, long-term continence, potency rates and biochemical recurrence (BCR). Performing RARP on patients who have previously undergone TURP is a safe procedure. Furthermore, the current findings demonstrated that the TURP group had comparable oncologic and long-term functional outcomes to the Non-TURP group.

Reproductive behaviour and longevity: Evidence from Chinese centenarians.

With the implementation of the three-child policy in China, the debate between fertility and health and longevity has again become a hot topic in the era of increasing ageing. This study aimed to explore the association between reproductive behaviour and longevity of older women and men in China. Based on data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2014 to 2018, a total of 1428 deceased older people were enrolled in the study, including 421 centenarians and 1007 non-centenarians. The analysis of the association between fertility and longevity was conducted in the multivariate logistic regression. Compared to women aged 99 years and below, centenarian women had significantly fewer children (p < 0.01), fewer sons (p < 0.01) and fewer daughters. Centenarian men had more children, more daughters and fewer sons. For both men and women, centenarians were significantly characterized by later age at first birth (p < 0.01) and later age at last birth (p < 0.01). Centenarians were significantly characterized by having children and having a daughter, however, non-centenarians were significantly characterized by having a son (p < 0.01). The association between fertility and health of both men and women should be taken into account in the development of fertility policies and supporting policies. Fertility levels should be increased without compromising the health benefits of individuals in their later years.

Rational design of bimetallic MXene solid solution with High-Performance electrocatalytic N2 reduction.

Electrocatalytic N2 reduction reaction (eNRR) was an effective alternative method for green synthesis of NH3. By combining the first-principal Density functional theory (DFT) calculations and Monte Carlo (MC) simulation, we systematacially investigated 24 types equal-ratio bimetallic MXene solid solution, involving 88 different catalysts. Our focus was on the catalytic performance of these materials in eNRR. The computational result indicate that MoW(3Mo) has high stability, selectivity (93.8 % against the hydrogen evolution reaction (HER)) and activity (UL = -0.26 V), which is significantly better than that of monometal Mo2CO2 and W2CO2. This improvement in catalytic properties is attributed to the unique electronic structure (e.g. d-band center, charge) of bimetallic MXene solid solution. In explicit solvent conditions, the microenvironment of hydrogen bond in aqueous liquid thermodynamically promotes the catalytic property for eNRR and reduce the catalytic property of HER side reaction, but the kinetic barrier is also increased due to the effect of the hydrogen-bond microenvironment on proton migration. Overall, the obtained bimetallic MXene solid solution MoW(3Mo) exhibits excellent catalytic performance in eNRR.

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of vascular cell adhesion molecule-1 (VCAM-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF), causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.

Efficacy of pantoprazole plus perforation repair for peptic ulcer and its effect on the stress response.

BACKGROUND: Peptic ulcer (PU) is an abnormal phenomenon in which there is rupture of the mucosa of the digestive tract, which not only affects patients' normal life but also causes an economic burden due to its high medical costs. AIM: To investigate the efficacy of pantoprazole (PPZ) plus perforation repair in patients with PU and its effect on the stress response. METHODS: The study subjects were 108 PU patients admitted between July 2018 and July 2022, including 58 patients receiving PPZ plus perforation repair [research group (RG)] and 50 patients given simple perforation repair [control group (CG)]. The efficacy, somatostatin (SS) concentration, stress reaction [malondialdehyde (MDA), lipid peroxide (LPO)], inflammatory indices [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-1ß], recurrence, and complications (perforation, hemorrhage, and pyloric obstruction) were compared. RESULTS: The overall response rate was higher in the RG than in the CG. Patients in the RG had markedly elevated SS after treatment, which was higher than that of the CG, while MDA, LPO, TNF-, CRP, and IL-1ß were significantly reduced to lower levels than those in the CG. Lower recurrence and complication rates were identified in the RG group. CONCLUSION: Therefore, PPZ plus perforation repair is conducive to enhancing treatment outcomes in PU patients, reducing oxidative stress injury and excessive inflammatory reactions, and contributing to low recurrence and complication rates.

A study on the impact of Internet use on depression among Chinese older people under the perspective of social participation.

PURPOSE: This study aimed to evaluate the role of social participation in the relationship between internet use and depressive symptoms among Chinese older adults and investigate how the internet use interact with social participation to reduce the risk of depressive symptoms. METHODS: Based on the survey from the China Health and Retirement Longitudinal Study (CHARLS) in 2018, we identified 4645 subjects and used the Ordinary Least Square method (OLS) and Propensity Score Matching method (PSM) to identify the association between Internet use and depression of older people, and further test how social participation played a role in the relationship. RESULTS: The level of depression of older people was significantly reduced in those who using internet in China, and the effect was still robust under different identification methods. The mental health was improved when using internet because of the increase of social participation and social capital. Further, The positive effect was stronger especially in those who were female, living in rural areas, has low education attainments and were 70-79 years old. CONCLUSIONS: The popularity of internet use has a positive effect on the depressive symptoms of Chinese older adults. Effective measures were encouraged to improve the friendliness of internet for older people and promote the popularization of the Internet and older group, achieving the spiritual well-being of them in the Internet society.

Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression.

Growing evidence suggests that relative carbohydrate intake affects depression; however, the association between carbohydrates and depression remains controversial. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using genetic variants associated with relative carbohydrate intake (N = 268,922) and major depressive disorder (N = 143,265) from the largest available genome-wide association studies. MR evidence suggested a causal relationship between higher relative carbohydrate intake and lower depression risk (odds ratio, 0.42 for depression per one-standard-deviation increment in relative carbohydrate intake; 95% confidence interval, 0.28 to 0.62; P = 1.49 × 10-5). Multivariable MR indicated that the protective effect of relative carbohydrate intake on depression persisted after conditioning on other diet compositions. The mediation analysis via two-step MR showed that this effect was partly mediated by body mass index, with a mediated proportion of 15.4% (95% confidence interval, 6.7% to 24.1%). These findings may inform prevention strategies and interventions directed towards relative carbohydrate intake and depression.