Morroniside attenuates podocytes lipid deposition in diabetic nephropathy: A network pharmacology, molecular docking and experimental validation study.

BACKGROUND: Dysregulation of lipid metabolism is a key factor influencing the progression of diabetic nephropathy (DN). Morroniside (MOR) is a major active compound isolated from the traditional Chinese herb Cornus officinalis, our previous research found that it can improve the lipid deposition of renal tubular epithelial cells. The purpose of this study is to explore whether MOR can improve podocyte lipid deposition and its mechanism of reducing DN. METHODS: Initially, we used network pharmacology and bioinformatics techniques to predict the relationship between renal lipid metabolism of MOR and DN. Subsequently, the binding activity of MOR with lipid-related proteins was studied by molecular docking to determine how MOR acts through these proteins. After determining the target of MOR, animal experiments and cell tests were carried out to verify it. RESULTS: Using network pharmacology, bioinformatics, and molecular docking, target proteins for MOR treatment of DN were predicted and screened, including PGC-1α, LXRs, ABCA1, PPARY, CD36, and nephrin. It is particularly noted that MOR effectively binds to PGC-1α, while LXRs, ABCA1, PPARY and CD36 are downstream molecules of PGC-1α. Silencing the PGC-1α gene significantly reduced the therapeutic effects of MOR. Conversely, in groups without PGC-1α knockdown, MOR was able to increase the expression levels of PGC-1α and influence the expression of downstream proteins. Furthermore, through in vivo and in vitro experiments, utilizing techniques such as lipid droplet staining, PAS, MASSON staining, immunofluorescence, and Western blot, we found that MOR effectively elevated the expression levels of the podocyte protein nephrin and lipid metabolism-regulating proteins PGC-1α, PPARY, and ABCA1, while significantly inhibiting the expression of the lipid accumulation promoter CD36. CONCLUSION: MOR can regulate the cholesterol efflux in podocytes via the PGC-1α/LXRs/ABCA1 signaling pathway, and control cholesterol intake via the PGC-1α/PPARY/CD36 signaling pathway, thereby ameliorating lipid deposition in DN.

Se-dopant Modulated Selective Co-Insertion of H+ and Zn2+ in MnO2 for High-Capacity and Durable Aqueous Zn-Ion Batteries.

MnO2 is commonly used as the cathode material for aqueous zinc-ion batteries (AZIBs). The strong Coulombic interaction between Zn ions and the MnO2 lattice causes significant lattice distortion and, combined with the Jahn-Teller effect, results in Mn2+ dissolution and structural collapse. While proton intercalation can reduce lattice distortion, it changes the electrolyte pH, producing chemically inert byproducts. These issues greatly affect the reversibility of Zn2+ intercalation/extraction, leading to significant capacity degradation of MnO2. Herein, we propose a novel method to enhance the cycling stability of δ-MnO2 through selenium doping (Se-MnO2). Our work indicates that varying the selenium doping content can regulate the intercalation ratio of H+ in MnO2, thereby suppressing the formation of ZnMn2O4 by-products. Se doping mitigates the lattice strain of MnO2 during Zn2+ intercalation/deintercalation by reducing Mn-O octahedral distortion, modifying Mn-O bond length upon Zn2+ insertion, and alleviating Mn dissolution caused by the Jahn-Teller effect. The optimized Se-MnO2 (Se concentration of 0.8 at.%) deposited on carbon nanotube demonstrates a notable capacity of 386 mAh g-1 at 0.1 A g-1, with exceptional long-term cycle stability, retaining 102 mAh g-1 capacity after 5000 cycles at 3.0 A g-1.

Experiences of Chinese Rheumatoid Arthritis Patients Who Chose Western Medicine, Traditional Chinese Medicine, and a Combination of Treatments: A Study Based on Interviews and Thematic Analysis.

Background: This qualitative study, part of a prospective mixed-methods research, aimed to gain insights into the medical experiences and disease perceptions of Chinese patients living with rheumatoid arthritis (RA). Specifically, the study examined how RA patients' perceptions of their disease were influenced by the diagnosis and treatment they receive. Methods: RA patients undergoing treatment were invited to participate in this qualitative study. Face-to-face semi-structured interviews were conducted among 18 patients, and the collected data were analyzed using thematic analysis. Results: The 18 participants in this study had a mean (SD) age of 58, a median disease duration of 6.5 years, and a predominance of female subjects (17 out of 18). The qualitative analysis identified two themes with six sub-themes: 1. Patients' experiences of treatment: discovery of the disease, misdiagnosis and mistreatment, and patients' treatment choices; 2. Feelings about the disease: psychological impact, reflections on the disease, and expectations of treatment. Conclusion: This study provides valuable perspectives and data to enhance the understanding of the relationship between patients' illness perceptions and their healthcare choices.

Enhanced Thermostability of Nattokinase by Computation-Based Rational Redesign of Flexible Regions.

Nattokinase is a nutrient in healthy food natto that has the function of preventing and treating blood thrombus. However, its low thermostability and fibrinolytic activity limit its application in food and pharmaceuticals. In this study, we used bioinformatics analysis to identify two loops (loop10 and loop12) in the flexible region of nattokinase rAprY. Using this basis, we screened the G131S-S161T variant, which showed a 2.38-fold increase in half-life at 55 °C, and the M3 variant, which showed a 2.01-fold increase in activity, by using a thermostability prediction algorithm. Bioinformatics analysis revealed that the enhanced thermostability of the G131S-S161T variant was due to the increased rigidity and structural shrinkage of the overall structure. Additionally, the increased rigidity of the local region surrounding the active center and its mutated sites helps maintain its normal conformation in high-temperature environments. The increased catalytic activity of the M3 variant may be due to its more efficient substrate binding mechanism. We investigated strategies to improve the thermostability and fibrinolytic activity of nattokinase, and the resulting variants show promise for industrial production and application.

A novel approach for anterior cruciate ligament tibial avulsion fracture: arthroscopic modified suture bridge fixation technique.

INTRODUCTION: Anterior cruciate ligament (ACL) tibial avulsion fracture is a rare injury, which usually happens in adults with traffic accidents or sports injuries. Surgery interventions are common treatment methods, they can restore knee function and help to return to normal life. In this study, we described an arthroscopic modified suture bridge fixation technique for ACL tibial avulsion fractures and explored the feasibility and therapeutic effects. MATERIALS AND METHODS: This retrospective study reviewed data from January 2020 to May 2022. Data were collected on 18 patients (10 males and 8 females) with ACL tibial avulsion fractures and underwent arthroscopic modified suture bridge fixation technique. The study analyzed surgical data about intraoperative blood loss, operation time, hospital stay, fracture healing time, and visual analog scale (VAS). Functional evaluation of the knee joint was performed using the anterior drawer test, Lysholm knee scoring scale, International Knee Documentation Committee (IKDC), and knee range of motion (ROM). RESULTS: All 18 patients were followed up between 12 and 20 months, with an average of 15.22 ± 1.96 months. The intraoperative blood loss was approximately 15-40 mL, averaging 25.78 ± 6.19 mL. The operation time was 65-85 min, with a mean of 74.89 ± 4.86 min. The hospital stay of patients was 3-5 days, with a mean of 3.89 ± 0.76 days. The mean fracture healing time was 8-12 weeks after surgery, with a mean of 9.22 ± 1.7 weeks. All incisions healed grade I without infection. There were no internal fixation failures, neurovascular injuries, and lower extremity deep venous thrombosis. The anterior drawer test was negative in all patients. At the final follow-up, the mean VAS score was 0-3, averaging 1.56 ± 0.71. The Lysholm score of the injured knee was 89-96, with an average of 92.50 ± 2.50; the IKDC score was 88-93, with an average of 90.44 ± 1.89; the knee ROM was 110-126°, with an average of 120.67° ± 4.31°. CONCLUSION: Results demonstrated that the modified suture bridge fixation technique under arthroscope could provide reliable fixation and favorable clinical effects for ACL tibial avulsion fractures. This is a simple, minimally invasive, effective, and clinically applicable surgical method for ACL tibial avulsion fracture.

Graphene Oxide-Silver-Coated Sulfonated Polyetheretherketone (Ag/GO-SPEEK): A Broad-Spectrum Antibacterial Artificial Bone Implants.

Polyetheretherketone (PEEK), particularly its sulfonated form (SPEEK), has emerged as a promising synthetic biomaterial for artificial bone implants, providing an alternative to conventional titanium metal. However, postoperative infections pose a critical challenge, driven by diverse and antibiotic-resistant bacteria. To address this issue, we propose the modification of the SPEEK surface using a thin graphene oxide (GO) film containing silver (Ag) ions. The resulting coating exhibits substantial antibacterial effects against various pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. Experimental assessments elucidate the coating's impact on bacterial adhesion, biofilm formation, and morphology. The results suggest that hindered bacterial growth stems from reduced biofilm production and the controlled release of Ag ions facilitated by the GO coating. The Ag/GO-SPEEK material holds promise as a bioactive implant, addressing the challenges associated with bacterial targeting in bone tissue engineering applications.

Advancing vaccine development: Evaluation of a mannose-modified lipid nanoparticle-based candidate for African swine fever p30 mRNA vaccine eliciting robust immune response in mice.

The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4+ and CD8+ T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).

Light-Induced Conductance Potentiation and Depression in an All-Optically Controlled Memristor.

Optoelectronic memristors are new multifunctional devices with both electrically tunable and light-tunable synaptic plasticity, attracting great attention as key promising devices for optoelectronic neuromorphic computing systems. At present, the conductance modulation in most optoelectronic memristors is conducted in a hybrid photoelectric mode, suffering some problems such as heat generation and control complexity. Here, an optoelectronic memristor based on the p+-Si/n-ZnO heterojunction is proposed where the conductance can be reversibly modulated in an all-optically controlled mode. The electron detrapping/trapping mechanism at the p+-Si/n-ZnO interface barrier region is presented to explain the light-induced conductance potentiation/depression behavior. Furthermore, some synaptic functions, including excitatory postsynaptic current (EPSC), inhibitory postsynaptic current (IPSC), and paired-pulse facilitation (PPF), are successfully mimicked in the p+-Si/n-ZnO heterojunction memristor, instructing its application potential for optoelectronic neuromorphic computing.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion.

AIM: To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy (NAION) and central retinal artery occlusion (CRAO) and develop a predictive diagnostic nomogram. METHODS: The study included 37 patients with monocular NAION, 20 with monocular CRAO, and 24 with hypertension. Gender, age, and systemic diseases were recorded. Blood routine, lipids, hemorheology, carotid and brachial artery doppler ultrasound, and echocardiography were collected. The optic disc area, cup area, and cup-to-disc ratio (C/D) of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured. RESULTS: The carotid artery intimal medial thickness (C-IMT) of the affected side of the CRAO group was thicker (P=0.039) and its flow-mediated dilation (FMD) was lower (P=0.049) than the NAION group. Compared with hypertension patients, NAION patients had higher whole blood reduced viscosity low-shear (WBRV-L) and erythrocyte aggregation index (EAI; P=0.045, 0.037), and CRAO patients had higher index of rigidity of erythrocyte (IR) and erythrocyte deformation index (EDI; P=0.004, 0.001). The optic cup and the C/D of the NAION group were smaller than the other two groups (P<0.0001). The diagnostic prediction model showed high diagnostic specificity (83.7%) and sensitivity (85.6%), which was highly related to hypertension, the C-IMT of the affected side, FMD, platelet (PLT), EAI, and C/D. CONCLUSION: CRAO patients show thicker C-IMT and worse endothelial function than NAION. NAION and CRAO may be related to abnormal hemorheology. A small cup and small C/D may be involved in NAION. The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.

Integrated anatomical structure, physiological, and transcriptomic analyses to identify differential cold tolerance responses of Ziziphus jujuba mill. 'Yueguang' and its autotetraploid 'Hongguang'.

Cold stress is a limiting stress factor that limits plant distribution and development; however, polyploid plants have specific characteristics such as higher resistance to abiotic stress, especially cold stress, that allow them to overcome this challenge. The cultivated cultivar Ziziphus jujuba Mill. 'Yueguang' (YG) and its autotetraploid counterpart 'Hongguang' (HG) exhibit differential cold tolerance. However, the underlying molecular mechanism and methods to enhance their cold tolerance remain unknown. Anatomical structure and physiological analysis indicated YG had a higher wood bark ratio, and xylem ratio under cold treatment compared to HG. However, the half-lethal temperature (LT50), cortex ratio, and malondialdehyde (MDA) content were significantly decreased in YG than HG, which indicated YG was cold tolerant than HG. Transcriptome analysis showed that 2084, 1725, 2888, and 2934 differentially expressed genes (DEGs) were identified in HC vs YC, H20 vs Y20, Y20 vs YC, and H20 vs HC treatment, respectively. Meanwhile, KEGG enrichment analysis of DEGs showed that several metabolic pathways, primarily plant hormone signal transduction and the MAPK signaling pathway, were involved in the differential regulation of cold tolerance between YG and HG. Furthermore, exogenous abscisic acid (ABA) and brassinolide (BR) treatments could improve their cold tolerance through increased SOD and POD activities, decreased relative electrical conductivity, and MDA content. All of these findings suggested that plant hormone signal transduction, particularly ABA and BR, might have an important role in the regulation of differential cold tolerance between YG and HG, laying the foundation for further improving cold tolerance in jujube and examining the molecular mechanisms underlying differences in cold tolerance among different ploidy cultivars.

Extracellular perception of multiple novel core effectors from the broad host-range pear anthracnose pathogen Colletotrichum fructicola in the nonhost Nicotiana benthamiana.

Colletotrichum fructicola is emerging as a devastating pathogenic fungus causing anthracnose in a wide range of horticultural crops, particularly fruits. Exploitation of nonhost resistance (NHR) represents a robust strategy for plant disease management. Perception of core effectors from phytopathogens frequently leads to hypersensitive cell death and resistance in nonhost plants; however, such core effectors in C. fructicola and their signaling components in non-hosts remain elusive. Here, we found a virulent C. fructicola strain isolated from pear exhibits non-adaptation in the model plant Nicotiana benthamiana. Perception of secreted molecules from C. fructicola appears to be a dominant factor in NHR, and four novel core effectors-CfCE4, CfCE25, CfCE61, and CfCE66-detected by N. benthamiana were, accordingly, identified. These core effectors exhibit cell death-inducing activity in N. benthamiana and accumulate in the apoplast. With a series of CRISPR/Cas9-edited mutants or gene-silenced plants, we found the coreceptor BAK1 and helper NLRs including ADR1, NRG1, and NRCs mediate perceptions of these core effectors in N. benthamiana. Concurrently, multiple N. benthamiana genes encoding cell surface immune receptors and intracellular immune receptors were greatly induced by C. fructicola. This work represents the first characterization of the repertoire of C. fructicola core effectors responsible for NHR. Significantly, the novel core effectors and their signaling components unveiled in this study offered insights into a continuum of layered immunity during NHR and will be helpful for anthracnose disease management in diverse horticultural crops.

AMPA receptor potentiation alleviates NLRP3 knockout-induced fear generalization in mice.

Genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome enhances the extinction of contextual fear memory, which is attributed to its role in neuronal and synaptic dysregulation, concurrent with neurotransmitter function disturbances. This study aimed to determine whether NLRP3 plays a role in generalizing fear via the inflammatory axis. We established the NLRP3 KO mice model, followed by behavioral and biochemical analyses. The NLRP3 KO mice displayed impaired fear generalization, lower neuroinflammation levels, and dysregulated neurotransmitter function. Additionally, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not the inhibition of NMDA or 5-HT2C receptors, resulted in fear generalization in NLRP3 KO mice because TAT-GluA2 3Y, but not SB242084 and D-cycloserine, treated blocked NLRP3 deprivation effects on fear generalization. Thus, global knockout of NLRP3 is associated with aberrant fear generalization, possibly through AMPA receptor signaling.

Effects of plasma-activated slightly acidic electrolyzed water on salmon myofibrillar protein: Insights from structure and molecular docking.

The present study investigated the impact of plasma-activated water (PAW), slightly acidic electrolytic water (SAEW) and plasma-activated slightly acidic electrolytic water (PASW) treatment on myofibrillar protein (MP) in salmon fillets. Additionally, the interaction mechanism between myosin and reactive oxygen species was explored by molecular docking. Compared with the control group (719.26 nm), PASW treatment group exhibited the smallest particle size (408.97 nm). The PASW treatment exhibited efficacy in reducing MP aggregation and inhibiting protein oxidation. In comparison with other treatments, PASW treatment demonstrated a greater ability to mitigate damage to the secondary and tertiary structures of MP. O3 and H2O2 interact with myosin through hydrogen bonding. Specifically, O3 interacts with Lys676, Gly677, and Met678 of myosin while H2O2 binds to Thr681, Asp626, Arg680, and Met678. This study offers novel insights into the impact of PASW on MP, and provides a theoretical foundation for its application in aquatic product processing.

Study on the interaction mechanism between (-)-epigallocatechin-3-gallate and myoglobin: Multi-spectroscopies and molecular simulation.

(-)-Epigallocatechin-3-gallate (EGCG) is remarkably efficacious in inhibiting the browning of red meat. We therefore propose a hypothesis that EGCG forms complexes with myoglobin, thereby stabilizing its structure and thus preventing browning. This study investigated the interaction mechanism between EGCG and myoglobin. EGCG induced static quenching of myoglobin. Noncovalent forces, including hydrogen bonds and van der Waals, primarily governing the interactions between myoglobin and EGCG. The interactions primarily disrupted myoglobin's secondary structure, thus significantly reducing surface hydrophobicity by 53% (P < 0.05). The modification augmented the solubility and thermal stability of myoglobin. The radius of gyration (Rg) value fluctuated between 1.47 and 1.54 nm, and the hydroxyl groups in EGCG formed an average of 2.93 hydrogen bonds with myoglobin. Our findings elucidated the formation of stable myoglobin-EGCG complexes and the myoglobin-EGCG interaction, thus confirming our initial hypothesis.

The potential causal relationship between various lifestyles and depression: a univariable and multivariable Mendelian randomization study.

Background: Previous studies have shown that lifestyle was associated with depression. Thus, the aim of this study was to examine the causality between multiple lifestyles and depression by Mendelian randomization (MR) analysis. Methods: The single-nucleotide polymorphisms (SNPs) of depression, alcoholic drinks per week, sleeplessness or insomnia, body mass index (BMI), mood swings, weekly usage of mobile phone in the last 3 months, beef intake, cooked vegetable intake, and "smoking status: never" were acquired from the Integrative Epidemiology Unit Open genome-wide association study database. Causal effects of eight exposure factors and depression were investigated using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, and results were primarily referred to IVW. Subsequently, univariable MR (UVMR) analysis was performed on eight exposure factors and depression, separately. In addition, sensitivity analysis, including heterogeneity test, horizontal pleiotropy, and leave-one-out (LOO) methods, was conducted to evaluate the stability of MR results. Furthermore, multivariable MR (MVMR) analysis was carried out. Results: UVMR analysis revealed that all eight exposure factors were causally associated with depression; alcoholic drinks per week, sleeplessness or insomnia, BMI, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake were risk factors, and beef intake and "smoking status: never" were protection factors. Heterogeneity tests revealed no heterogeneity for alcoholic drinks per week, sleeplessness or insomnia, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake. Meanwhile, there was no horizontal pleiotropy in UVMR, and LOO analysis verified that univariable analysis results were reliable. Moreover, MVMR analysis indicated that mood swings and weekly usage of mobile phone in the last 3 months were risk factors, and beef intake was a protection factor for depression when multiple factors occurred at the same time. Conclusion: Alcoholic drinks per week, sleeplessness or insomnia, BMI, mood swings, weekly usage of mobile phone in the last 3 months, and cooked vegetable intake were risk factors, and beef intake and "smoking status: never" were protection factors. In addition, mood swings, weekly usage of mobile phone in the last 3 months, and beef intake had a direct effect on depression when multiple factors occurred simultaneously.

How does the SARS-CoV-2 reinfection rate change over time? The global evidence from systematic review and meta-analysis.

BACKGROUND: There is a significant increase in the number of SARS-CoV-2 reinfection reports in various countries. However, the trend of reinfection rate over time is not clear. METHODS: We searched PubMed, Web of Science, Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang for cohort studies, case-control studies, and cross-sectional studies up to March 16, 2023, to conduct a meta-analysis of global SARS-CoV-2 reinfection rate. Subgroup analyses were performed for age, country, study type, and study population, and time-varying reinfection rates of SARS-CoV-2 were estimated using meta-regression. The risk of bias was assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute critical appraisal tool. RESULT: A total of 55 studies involving 111,846 cases of SARS-CoV-2 reinfection were included. The pooled SARS-CoV-2 reinfection rate was 0.94% (95% CI: 0.65 -1.35%). In the subgroup analyses, there were statistically significant differences in the pooled reinfection rates by reinfection variant, and study type (P < 0.05). Based on meta-regression, the reinfection rate fluctuated with time. CONCLUSION: Meta-regression analysis found that the overall reinfection rate increased and then decreased over time, followed by a period of plateauing and then a trend of increasing and then decreasing, but the peak of the second wave of reinfection rate was lower than the first wave. SARS-CoV-2 is at risk of reinfection and the Omicron variant has a higher reinfection rate than other currently known variants. The results of this study could help guide public health measures and vaccination strategies in response to the Coronavirus Disease 2019 (COVID-19) pandemic.

The gut metabolite indole-3-propionic acid activates ERK1 to restore social function and hippocampal inhibitory synaptic transmission in a 16p11.2 microdeletion mouse model.

BACKGROUND: Microdeletion of the human chromosomal region 16p11.2 (16p11.2 + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 + / -  syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 + / -  are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 + / - , as well as the underlying molecular mechanisms. RESULTS: Mice with the 16p11.2 + / -  showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. CONCLUSIONS: Our study reveals that 16p11.2 + / -  leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 + / -  mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract.

A cross-sectional study of factors influencing left ventricular myocardial work in peritoneal dialysis patients.

Objectives: To evaluate myocardial work in peritoneal dialysis patients by pressure-strain loop. To analyze the factors influencing myocardial work in peritoneal dialysis patients with preserved ejection fraction. Methods: We collected clinical data on possible effects on myocardial work in 105 maintenance peritoneal dialysis patients with preserved ejection fraction and applied ultrasonic pressure-strain loops to obtain the left ventricular global constructive work (GCW), Global work index (GWI), global work waste (GWW), and global work efficiency (GWE) of the patients. Then, the clinical data and myocardial work indices were statistically described and correlated. Results: Left ventricular hypertrophy was observed in 78 % of peritoneal dialysis patients with left ventricular ejection fraction preservation. There is a correlation between the left ventricular mass index and myocardial work indices (P < 0.05). On multiple linear regression analysis, systolic blood pressure (SBP), IL-6, and hemoglobin correlated with GCW(P < 0.05); SBP and IL-6 correlated with GWI(P < 0.05); homocysteine, SBP, TNF-α, and hemoglobin correlated with GWW(P < 0.05); homocysteine, TNF-α and hemoglobin correlated with GWE (P < 0.05). Conclusions: Using noninvasive pressure-strain loops to assess left ventricular myocardial work can provide information on cardiac function more consistent with pathophysiological changes than conventional ejection fraction. Hypertension, anemia, hyperhomocysteinemia, and inflammation influence left ventricular myocardial work in peritoneal dialysis patients, and they selectively affect one or more myocardial work indices.

mm9_circ_014683 regulates microglia polarization through canonical NFκB signaling pathway in diabetic retinopathy.

Diabetic retinopathy (DR) is still the major cause of visual loss in working-aged people, one of the critical pathological processes are retinal microglia-mediated inflammation. Our previous study demonstrated that enhanced M1 microglial polarization was involved in retinal inflammation in DR, but the detailed mechanism needs further investigation. Circular RNAs (circRNAs) are important kind of noncoding RNAs involved in the regulation of various cell biological processes. Herein, the circRNA expression profiles of BV2 mouse microglia treated with or without glucose were detected, and a total of 347 differentially expressed circRNAs were identified in glucose-treated BV2 cells. The key circRNA mm9_circ_014683 increased after glucose stimulation. Inhibiting or overexpressing mm9_circ_014683 showed no effect on the proliferation and apoptosis of microglia. Inhibiting mm9_circ_014683 impeded M1 polarization and promoted M2 polarization, and overexpressing mm9_circ_014683 showed the opposite effect. A total of 216 differentially expressed genes were identified in mm9_circ_014683-knockdown BV2 cells, which were enriched in several signaling pathways, including the NFκB signaling pathway. Moreover, mm9_circ_014683 positively regulated the canonical, NFκB signaling pathway. Besides, mm9_circ_014683 was highly expressed in the retinal microglia of diabetic mice, and intraocular injection of Lv-circRNA inhibited M1 but enhanced M2 retinal microglial polarization. In conclusion, mm9_circ_014683 regulates microglial polarization through the canonical NFκB signaling pathway in diabetic retinopathy. This study may provide insight into the pathogenesis and treatment of DR.

Research progress on the treatment of diabetic nephropathy with leech and its active ingredients.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy.