High body mass index is associated with elevated risk of perioperative ischemic stroke in patients who underwent noncardiac surgery: A retrospective cohort study.

BACKGROUND: Body mass index (BMI) serves as a global metric for assessing obesity and overall health status. However, the impact of BMI, treated as a continuous variable, on the risk of perioperative stroke remains poorly understood. This retrospective cohort study aimed to elucidate the association between BMI and the risk of perioperative ischemic stroke in patients undergoing non-cardiovascular surgery. METHODS: A cohort of 223,415 patients undergoing noncardiac surgery at the First Medical Center of Chinese PLA General Hospital between January 1, 2008 and August 31, 2019 was screened. Preoperative high BMI, defined as BMI >22.64 kg/m2, was the primary exposure, and the outcome of interest was the new diagnosis of perioperative ischemic stroke within 30 days post-surgery. Robust controls for patient and intraoperative factors were implemented to minimize residual confounding. Logistic regression and propensity score matching were employed, and patients were stratified into subgroups for further investigation. RESULTS: The overall incidence of perioperative ischemic stroke was 0.23% (n = 525) in the cohort. After adjusting for patient-related variables (OR 1.283; 95% CI, 1.04-1.594; p < 0.05), surgery-related variables (OR 1.484; 95% CI, 1.2-1.849; p < 0.001), and all confounding variables (OR 1.279; 95% CI, 1.025-1.607; p < 0.05), patients with BMI >22.64 kg/m2 exhibited a significantly increased risk of perioperative ischemic stroke. This association persisted in the propensity score matched cohort (OR 1.577; 95% CI, 1.203-2.073; p < 0.01). Subgroup analyses indicated that preoperative BMI >22.64 kg/m2 correlated with an elevated risk of perioperative ischemic stroke in female patients, those with coronary heart disease, peripheral vascular diseases, and individuals undergoing neurosurgery. CONCLUSION: We first identified BMI >22.64 kg/m2 as a substantial and independent risk factor for perioperative ischemic stroke in Chinese noncardiac surgery patients. Normal BMI may not suffice as a universal preventive standard. Instead, a more stringent perioperative weight management approach is recommended, particularly for specific subgroups such as female patients, those with coronary heart disease and peripheral vascular disease, and individuals scheduled for neurosurgery.

The Association Between Personality Traits and Health-Related Quality of Life and the Mediating Role of Smoking: Nationwide Cross-Sectional Study.

Background: There are positive and negative correlations in different directions between smoking, personality traits, and health-related quality of life (HRQOL), where smoking may mask the pathway between personality traits and HRQOL. Understanding the masking pathway of smoking between personality traits and HRQOL can elucidate the mechanisms of smoking's psychosocial effects and provide new ideas for developing tobacco control strategies. Objective: The purpose of this study was to investigate the correlation between Big Five personality traits and HRQOL and whether smoking mediates the relationship between them. Methods: This was a cross-sectional study using data from 21,916 respondents from the 2022 Psychology and Behavior Investigation of Chinese Residents survey. Linear regression models were used to analyze the correlations between smoking, Big Five personality traits, and HRQOL while controlling for potential confounders. The mediating role of smoking on the association between Big Five Personality traits and HRQOL was analyzed using the Sobel-Goodman mediation test. Results: Extraversion (ß=.001; P=.04), agreeableness (ß=.003; P<.001), and neuroticism (ß=.003; P<.001) were positively correlated with HRQOL, whereas openness was negatively correlated with HRQOL (ß=-.001; P=.003). Smoking was associated with a decrease in HRQOL and mediated the positive effect of HRQOL on extraversion (z=-2.482; P=.004), agreeableness (z=-2.264; P=.02), and neuroticism (z=-3.230; P=.001). Subgroup analyses further showed that smoking mediated the effect of neuroticism on HRQOL in the population with chronic illnesses (z=-2.724; P=.006), and in the population without chronic illnesses, smoking contributed to the effect of HRQOL on extraversion (z=-2.299; P=.02), agreeableness (z=-2.382; P=.02), and neuroticism (z=-2.213; P=.03). Conclusions: This study provided evidence that there is a correlation between personality traits and HRQOL. It also found that smoking plays a role in mediating the connection between personality traits and HRQOL. The development of future tobacco control strategies should consider the unique traits of each individual's personality, highlighting the significance of extraversion, agreeableness, and neuroticism.

Neutrophil-derived migrasomes are an essential part of the coagulation system.

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.

The relationship of intimate partner violence on depression: the mediating role of perceived social support and the moderating role of the Big Five personality.

Introduction: This study aimed to explore the influence of Intimate Partner Violence (IPV) on depression, the mediating role of social support, and the moderating role of the Big Five personality traits in the relationship between social support and depression. Methods: Participants were recruited from Mainland China, using a stratified random sampling and quota sampling method. From June to August 2022, a diverse group of 21,916 participants (ranging from 12 to 100 years old) completed the Intimate Partner Violence Scale, Patient Health Questionnaire, Perceived Social Support Scale, and Big Five Inventory-Short Version. Results: IPV was significantly positively correlated with depression and significantly negatively correlated with perceived social support. Perceived social support plays a mediating role in the link between IPV and depression. Discussion: Healthcare workers should assess social support and provide adequate care or recommendations for increasing social support when patients with IPV report depressive symptoms. Patients can be coached by professionals to improve their resiliency by developing or nurturing more optimistic personality traits.

The role of sleep quality and anxiety symptoms in the association between childhood trauma and self-harm attempt: A chain-mediated analysis in the UK Biobank.

BACKGROUND: Childhood trauma is a risk factor for self-harm/suicidal behavior, but research on the potential association linking sleep quality and anxiety symptoms to childhood trauma and self-harm attempt is limited. The aim of this study was to describe the mediating role of sleep quality and anxiety symptoms between childhood trauma and self-harm attempt, and to provide a scientific basis for the prevention of self-harm behaviors. METHODS: This study ultimately included 11,063 study participants who participated in the baseline survey of this large prospective cohort study of the UK Biobank. We used structural equation modeling (SEM) to analyze the chain mediating role of sleep quality and anxiety symptoms in childhood trauma and self-harm attempt while controlling for covariates. RESULTS: A total of 19.58 % of study participants self-reported self-harm attempt. Sleep quality was negatively correlated with childhood trauma, anxiety symptoms, and self-harm attempt (p < 0.01). Childhood trauma, anxiety symptoms, and self-harm attempt were positively correlated (p < 0.01). In addition, after adjusting for confounders, anxiety symptoms were able to partially mediate the association between childhood trauma and self-harm attempt (effect value: 0.042, p < 0.01), and sleep quality and anxiety symptoms can chain mediate the association between childhood trauma and self-harm attempt (effect value:0.002, p < 0.01), with a total mediating effect of 65.67 % of the total effect. Subgroup analyses further showed that the mediating effects of sleep quality and anxiety symptoms on childhood trauma and self-harm attempt differed across age, gender, ethnicity, and smoking and drinking subgroups. CONCLUSIONS: This study found a complex relationship between childhood trauma, sleep quality, anxiety symptoms, and self-harm attempt, with sleep quality and anxiety symptoms mediating the relationship between childhood trauma and self-harm attempt. Multiple avenues of intervention, such as the provision of professional psychological interventions and timely monitoring, should be used to improve the sleep quality and mental health of individuals with traumatic childhood experiences and to prevent the occurrence of emotionally harmful behaviors such as self-harm/suicide.

In-situ construction of iron-modified nickel nanoparticles assisted by hexamethylenetetramine with the internal and external collaboration for highly selective electrocatalytic carbon dioxide reduction.

Carbon dioxide (CO2) electroreduction provides a sustainable route for realizing carbon neutrality and energy supply. Up to now, challenges remain in employing abundant and inexpensive nickel materials as candidates for CO2 reduction due to their low activity and favorable hydrogen evolution. Here, the representative iron-modified nickel nanoparticles embedded in nitrogen-doped carbon (Ni1-Fe0.125-NC) with the porous botryoid morphology were successfully developed. Hexamethylenetetramine is used as nitrogen-doped carbon source. The collaboration of internal lattice expansion with electron effect and external confinement effect with size effect endows the significant enhancement in electrocatalytic CO2 reduction. The optimized Ni1-Fe0.125-NC exhibits broad potential ranges for continuous carbon monoxide (CO) production. A superb CO Faradaic efficiency (FECO) of 85.0 % realized at -1.1 V maintains a longtime durability over 35 h, which exceeds many state-of-the-art metal catalysts. Theoretical calculations further confirm that electron redistribution promotes the desorption of CO in the process for favorable CO production. This work opens a new avenue to design efficient nickel-based materials by considering the intrinsic structure and external confinement for CO2 reduction.

Rapid and accurate quantification of viable Bifidobacterium cells in milk powder with a propidium monoazide - antibiotic fluorescence in situ hybridization - flow cytometry method.

Due to its beneficial effects on human health, Bifidobacterium is commonly added to milk powder. Accurate quantification of viable Bifidobacterium is essential for assessing the therapeutic efficacy of milk powder. In this study, we introduced a novel propidium monoazide (PMA) - antibiotic fluorescence in situ hybridization (AFISH) - flow cytometry (FCM) method to rapidly and accurately quantify viable Bifidobacterium cells in milk powder. Briefly, Bifidobacterium cells were treated with chloramphenicol (CM) to increase their rRNA content, followed by staining with RNA-binding oligonucleotide probes, based on the AFISH technique. Then, the DNA-binding dye PMA was used to differentiate between viable and non-viable cells. The PMA-AFISH-FCM method, including sample pretreatment, CM treatment, dual staining, and FCM analysis, required around 2 h and was found to be better than the current methods. This is the first study to implement FCM combined with PMA and oligonucleotide probe for detecting Bifidobacterium.

Developing a Differentiable Long-Range Force Field for Proteins with E(3) Neural Network-Predicted Asymptotic Parameters.

Accurately describing long-range interactions is a significant challenge in molecular dynamics (MD) simulations of proteins. High-quality long-range potential is also an important component of the range-separated machine learning force field. This study introduces a comprehensive asymptotic parameter database encompassing atomic multipole moments, polarizabilities, and dispersion coefficients. Leveraging active learning, our database comprehensively represents protein fragments with up to 8 heavy atoms, capturing their conformational diversity with merely 78,000 data points. Additionally, the E(3) neural network (E3NN) is employed to predict the asymptotic parameters directly from the local geometry. The E3NN models demonstrate exceptional accuracy and transferability across all asymptotic parameters, achieving an R2 of 0.999 for both protein fragments and 20 amino acid dipeptide test sets. The long-range electrostatic and dispersion energies can be obtained using the E3NN-predicted parameters, with an error of 0.07 and 0.02 kcal/mol, respectively, when compared to symmetry-adapted perturbation theory (SAPT). Therefore, our force fields demonstrate the capability to accurately describe long-range interactions in proteins, paving the way for next-generation protein force fields.

Effects of dietary supplementation with alkaline mineral complex on in vitro ruminal fermentation and bacterial composition.

Introduction: Dairy industry growth faces challenges in China due to inadequate forage, leading to high-concentrate diets and potential rumen issues. Buffering agents, like sodium bicarbonate, play a crucial role in stabilizing rumen pH. Alkaline Mineral Complex (AMC), a liquid additive with a pH of 14, shows promise in supporting dairy cow health and mitigating heat stress through ionization. Methods: This experiment was aimed to study the effect of adding AMC to total mixed ration (TMR) on in vitro ruminal fermentation and bacterial composition. AMCat 1, 2, 4, and 8 mL/kg was added to the substrate (0.5 g TMR). Nutrient digestibility was measured after 48 h fermentation, and fermentation parameters and microbial composition were measured after 48 h fermentation. Results and discussion: The results of the experiment indicated that: The different concentrations of AMC showed a significant impact on time taken for gas production to reach 1/2 of the total gas production (HT) parameters (p < 0.05). Linear pH increase occurs at 6 and 24 h with rising AMC concentration (p < 0.05), showing a quadratic trend at 12 h (p < 0.05). The optimal buffering effect on rumen acid-base balance was observed at a 2 mL/kg concentration of AMC. Microbial diversity analysis indicated that there was no significant change in α-diversity with different AMC concentrations (p > 0.05). The microbial level demonstrated no significant difference in species diversity of rumen fluid bacteria among the various AMC concentration treatment groups compared to the control group, further supporting that the advantage of adding AMC in stabilizing the rumen environment without altering the structure of the rumen microbiota. Besides, the addition of AMC significantly increased the concentrations of acetate, propionate, total fatty acids (TVFA), and NH3-N, suggesting that AMC contributed to enhancing the energy and nitrogen utilization efficiency in ruminants. Based on the above detection indicators, we recommend that the most favorable concentration is 2 mL/kg.

Branched-Chain Amino Acid Degradation Pathway was Inactivated in Colorectal Cancer: Results from a Proteomics Study.

Background: Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is crucial for treatment and drug development. Methods: In this study, we established a C57B/6N mouse model of colon carcinogenesis using azoxymethane-dextran sodium sulfate (AOM-DSS) treatment for 14 weeks to identify proteins associated with colon cancer. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted on the cell membrane components enriched in the colonic mucosa. Additionally, tumor tissues and adjacent normal colon tissues were collected from patients with colon cancer for comparative protein and metabolite analyses. Results: In total, 74 differentially expressed proteins were identified in the tumor tissue samples from AOM/DSS-treated mice compared to both the adjacent tissue samples from AOM/DSS-treated mice and tissue samples from saline-treated control mice. Bioinformatics analysis revealed eight downregulated proteins enriched in the branched-chain amino acids pathway (valine, leucine, and isoleucine degradation). Moreover, these proteins are already known to be associated with the survival rate of patients with cancer. Targeted metabolomics showed increased levels of valine, leucine, and isoleucine in tumor tissues compared to those in adjacent normal tissues in patients with colon cancer. Furthermore, a real-time PCR experiment demonstrated that Aldehyde dehydrogenase, mitochondrial (short protein name ALDH2, gene name Aldh2) and Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (short protein name HCDH, gene name Hadh) (two genes) in the pathway of branched-chain amino acids) were downregulated in patients with colon cancer (colon tumor tissues vs. their adjacent colon tissues). ALDH2 expression was further validated by western blotting in AOM/DSS-treated mouse model and in clinical samples. Conclusion: This study highlighted the inactivation of the branched-chain amino acid degradation pathway in colon cancer and identified ALDH2 and HCDH as potential biomarkers for diagnosing colon cancer and developing new therapeutic strategies.

Evaluating the mosquito vector range for two orthobunyaviruses: Oya virus and Ebinur Lake virus.

BACKGROUND: Mosquito-borne viruses cause various infectious diseases in humans and animals. Oya virus (OYAV) and Ebinur Lake virus (EBIV), belonging to the genus Orthobunyavirus within the family Peribunyaviridae, are recognized as neglected viruses with the potential to pose threats to animal or public health. The evaluation of vector competence is essential for predicting the arbovirus transmission risk. METHODS: To investigate the range of mosquito vectors for OYAV (strain SZC50) and EBIV (strain Cu20-XJ), the susceptibility of four mosquito species (Culex pipiens pallens, Cx. quinquefasciatus, Aedes albopictus, and Ae. aegypti) was measured through artificial oral infection. Then, mosquito species with a high infection rate (IR) were chosen to further evaluate the dissemination rate (DR), transmission rate (TR), and transmission efficiency. The viral RNA in each mosquito sample was determined by RT-qPCR. RESULTS: The results revealed that for OYAV, Cx. pipiens pallens had the highest IR (up to 40.0%) among the four species, but the DR and TR were 4.8% and 0.0%, respectively. For EBIV, Cx. pipiens pallens and Cx. quinquefasciatus had higher IR compared to Ae. albopictus (1.7%). However, the EBIV RNA and infectious virus were detected in Cx. pipiens pallens, with a TR of up to 15.4% and a transmission efficiency of 3.3%. CONCLUSIONS: The findings indicate that Cx. pipiens pallens was susceptible to OYAV but had an extremely low risk of transmitting the virus. Culex pipiens pallens and Cx. quinquefasciatus were susceptible to EBIV, and Cx. pipiens pallens had a higher transmission risk to EBIV than Cx. quinquefasciatus.

Comprehensive data mining reveals RTK/RAS signaling pathway as a promoter of prostate cancer lineage plasticity through transcription factors and CNV.

Prostate cancer lineage plasticity is a key driver in the transition to neuroendocrine prostate cancer (NEPC), and the RTK/RAS signaling pathway is a well-established cancer pathway. Nevertheless, the comprehensive link between the RTK/RAS signaling pathway and lineage plasticity has received limited investigation. In particular, the intricate regulatory network governing the interplay between RTK/RAS and lineage plasticity remains largely unexplored. The multi-omics data were clustered with the coefficient of argument and neighbor joining algorithm. Subsequently, the clustered results were analyzed utilizing the GSEA, gene sets related to stemness, multi-lineage state datasets, and canonical cancer pathway gene sets. Finally, a comprehensive exploration of the data based on the ssGSEA, WGCNA, GSEA, VIPER, prostate cancer scRNA-seq data, and the GPSAdb database was conducted. Among the six modules in the clustering results, there are 300 overlapping genes, including 3 previously unreported prostate cancer genes that were validated to be upregulated in prostate cancer through RT-qPCR. Function Module 6 shows a positive correlation with prostate cancer cell stemness, multi-lineage states, and the RTK/RAS signaling pathway. Additionally, the 19 leading-edge genes of the RTK/RAS signaling pathway promote prostate cancer lineage plasticity through a complex network of transcriptional regulation and copy number variations. In the transcriptional regulation network, TP63 and FOXO1 act as suppressors of prostate cancer lineage plasticity, whereas RORC exerts a promoting effect. This study provides a comprehensive perspective on the role of the RTK/RAS pathway in prostate cancer lineage plasticity and offers new clues for the treatment of NEPC.

iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency.

BACKGROUND: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. METHODS: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. RESULTS: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. CONCLUSIONS: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.

Accurate Protein pKa Prediction with Physical Organic Chemistry Guided 3D Protein Representation.

Protein pKa is a fundamental physicochemical parameter that dictates protein structure and function. However, accurately determining protein site-pKa values remains a substantial challenge, both experimentally and theoretically. In this study, we introduce a physical organic approach, leveraging a protein structural and physical-organic-parameter-based representation (P-SPOC), to develop a rapid and intuitive model for protein pKa prediction. Our P-SPOC model achieves state-of-the-art predictive accuracy, with a mean absolute error (MAE) of 0.33 pKa units. Furthermore, we have incorporated advanced protein structure prediction models, like AlphaFold2, to approximate structures for proteins lacking three-dimensional representations, which enhances the applicability of our model in the context of structure-undetermined protein research. To promote broader accessibility within the research community, an online prediction interface was also established at isyn.luoszgroup.com.

Bi-directional charge transfer channels in highly crystalline carbon nitride enabling superior photocatalytic hydrogen evolution.

Introducing a donor-acceptor (D-A) unit is an effective approach to facilitate charge transfer in polymeric carbon nitride (PCN) and enhance photocatalytic performance. However, the introduction of hetero-molecules can lead to a decrease in crystallinity, limiting interlayer charge transfer and inhibiting further improvement. In this study, we constructed a novel D-A type carbon nitride with significantly higher crystallinity and a bi-directional charge transfer channel, which was achieved through 2,5-thiophenedicarboxylic acid (2,5-TDCA)-assisted self-assembly followed by KCl-templated calcination. The thiophene and cyano groups introduced serve as the electron donor and acceptor, respectively, enhancing in-plane electron delocalization. Additionally, introduced potassium ions are intercalated among the adjacent layers of carbon nitride, creating an interlayer charge transfer channel. Moreover, the highly ordered structure and improved crystallinity further facilitate charge transfer. As a result, the as-prepared photocatalyst exhibits superior photocatalytic hydrogen evolution (PHE) activity of 7.449 mmol h-1 g-1, which is 6.03 times higher than that of pure carbon nitride. The strategy of developing crystalline D-A-structured carbon nitride with controlled in-plane and interlayer charge transfer opens new avenues for the design of carbon nitride with enhanced properties for PHE.

Changes in corneal endothelial cells after scleral-sutured fixation of intraocular lens in children with congenital ectopia lentis: a 2-year follow-up.

PURPOSE: To investigate the changing patterns of corneal endothelial cells and the associated factors in children with congenital ectopia lentis (CEL) after scleral-sutured fixation of intraocular lens (SSFIOL). SETTING: Zhongshan ophthalmic center, Guangzhou, China. DESIGN: Retrospective study. METHODS: Patients were divided into the surgery group and the control group. Central endothelial cell density (ECD), coefficient of variation in cell size (CV), the percentage of hexagonal cells (hexagonality, HEX), average cell size (AVG) and central corneal thickness (CCT) were analyzed for both group at baseline and each follow-up visit. Clinic characteristic, ocular parameters, IOL decentration and IOL tilt of patients in the surgery group were collected. Multiple linear regression was performed to assess the potential associated factors for the postoperative changes in corneal endothelial cells in the surgery group. RESULTS: After 2-year follow-up, the decline of ECD was 17.8% (95%CI: -21.8 to -13.9) in the surgery group and -3.1% (95%CI: -5.2 to -1.0) in the control group(P<0.001), while the increase of AVG was 24.3%(17.1to 31.6) in the surgery group and 2.7%(1.0 to 4.5) in the control group (P<0.001). Multivariate analysis showed that AL≥24mm and WTW<12.2mm were significantly associated with greater loss of ECD (ß=-241.41, 95% CI: -457.91 to -24.91, P=0.030 and ß=251.63, 95% CI: 42.10 to 461.17,P=0.020, respectively) and AL≥ 24mm was significantly positively associated with the increase of AVG (ß=34.81, 95% CI: 0.90 to 68.71, P=0.044). CONCLUSIONS: SSFIOL has a significant impact on corneal endothelium in children with CEL. More attention should be paid to monitor postoperative corneal endothelium change during long-term follow-up in CEL children, especially for those with longer AL and smaller WTW.

Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy.

BACKGROUND: Retinitis pigmentosa (RP) is a genetically heterogeneous group of degenerative disorders causing progressive vision loss due to photoreceptor death. RP affects other retinal cells, including the retinal pigment epithelium (RPE). MicroRNAs (miRs) are implicated in RP pathogenesis, and downregulating miR-181a/b has shown therapeutic benefit in RP mouse models by improving mitochondrial function. This study investigates the expression profile of miR-181a/b in RPE cells and the neural retina during RP disease progression. We also evaluate how miR-181a/b downregulation, by knocking out miR-181a/b-1 cluster in RPE cells, confers therapeutic efficacy in an RP mouse model and explore the mechanisms underlying this process. RESULTS: Our findings reveal distinct expression profiles, with downregulated miR-181a/b in RPE cells suggesting a protective response and upregulated miR-181a/b in the neural retina indicating a role in disease progression. We found that miR-181a/b-2, encoded in a separate genomic cluster, compensates for miR-181a/b-1 ablation in RPE cells at late time points. The transient downregulation of miR-181a/b in RPE cells at post-natal week 6 (PW6) led to improved RPE morphology, retarded photoreceptor degeneration and decreased RPE aerobic glycolysis. CONCLUSIONS: Our study elucidates the underlying mechanisms associated with the therapeutic modulation of miR-181a/b, providing insights into the metabolic processes linked to its RPE-specific downregulation. Our data further highlights the impact of compensatory regulation between miR clusters with implications for the development of miR-based therapeutics.

The New Challenge of Obesity - Obesity-Associated Nephropathy.

In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no "point-to-point" treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease.

Improvement in the Sustained-Release Performance of Electrospun Zein Nanofibers via Crosslinking Using Glutaraldehyde Vapors.

Volatile active ingredients in biopolymer nanofibers are prone to burst and uncontrolled release. In this study, we used electrospinning and crosslinking to design a new sustained-release active packaging containing zein and eugenol (EU). Vapor-phase glutaraldehyde (GTA) was used as the crosslinker. Characterization of the crosslinked zein nanofibers was conducted via scanning electron microscopy (SEM), mechanical properties, water resistance, and Fourier transform infrared (FT-IR) spectroscopy. It was observed that crosslinked zein nanofibers did not lose their fiber shape, but the diameter of the fibers increased. By increasing the crosslink time, the mechanical properties and water resistance of the crosslinked zein nanofibers were greatly improved. The FT-IR results demonstrated the formation of chemical bonds between free amino groups in zein molecules and aldehyde groups in GTA molecules. EU was added to the zein nanofibers, and the corresponding release behavior in PBS was investigated using the dialysis membrane method. With an increase in crosslink time, the release rate of EU from crosslinked zein nanofibers decreased. This study demonstrates the potential of crosslinking by GTA vapors on the controlled release of the zein encapsulation structure containing EU. Such sustainable-release nanofibers have promising potential for the design of fortified foods or as active and smart food packaging.

An Integrated Approach of Bioassays and Non-Target Screening for the Assessment of Endocrine-Disrupting Activities in Tap Water and Identification of Novel Endocrine-Disrupting Chemicals.

The safety of drinking water is a significant environmental issue of great concern for human health since numerous contaminants are often detected in drinking water and its sources. Boiling is a common household method used to produce relatively high-quality drinking water in some countries and regions. In this study, with the aid of an integrated approach of in vitro bioassays and non-target analysis based on high-resolution mass spectrometry coupled with liquid chromatography, alterations in endocrine-disrupting activities in tap water samples without and with boiling were revealed, as well as the potential endocrine-disrupting chemicals (EDCs) contributing to these alterations were identified. The organic extracts of tap water had no significant (ant)agonistic activities against an estrogen receptor (ER), progesterone receptor (PR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) at enrichment concentrations of ≤10 times, posing no immediate or acute health risk to humans. However, the presence of agonistic activities against PR and MR and antagonistic activities against ER, PR, GR, and MR in OEs of tap water at relatively higher enrichment concentrations still raise potential health concerns. Boiling effectively reduced antagonistic activities against these steroid hormone receptors (SHRs) but increased estrogenic and glucocorticoid activities in drinking water. Four novel potential EDCs, including one UV filter (phenylbenzimidazole sulfonic acid, PBSA) and three natural metabolites of organisms (beta-hydroxymyristic acid, 12-hydroxyoctadecanoic acid, and isorosmanol) were identified in drinking water samples, each of which showed (ant)agonistic activities against different SHRs. Given the widespread use of UV filters in sunscreens to prevent skin cancer, the health risks posed by PBSA as an identified novel EDC are of concern. Although boiling has been thought to reduce the health risk of drinking water contamination, our findings suggest that boiling may have a more complex effect on the endocrine-disrupting activities of drinking water and, therefore, a more comprehensive assessment is needed.