Succinate activates UCP2 to suppress neuroinflammation and confer protection following intracerebral hemorrhage.

AIMS: Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. RESULTS: We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxide, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophage, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream AMP-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I or AMPK abolished the therapeutic effects of succinate following ICH. INNOVATION AND CONCLUSION: We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate. KEY WORDS: succinate; uncoupling protein 2; microglia; neuroinflammation; intracerebral hemorrhage.

Revealing nutrient limitation status of microorganisms in the soil of Robinia pseudoacacia plantation through soil stoichiometry and enzyme metrology.

Exploring nutrient limitation in forest soil holds significant implications for forest tending and management. However, current research on nutrient limitation status of microorganisms in Robinia pseudoacacia plantations within the Loess Plateau remains insufficient. To investigate soil microbial nutrient limitation of R. pseu-doacacia plantations on the Loess Plateau, we selected R. pseudoacacia plantations with different afforestation time series (15, 25, 35, and 45 years) and a pile of barren slope cropland (control) in Yongshou County, Shaanxi Province as the research objects. We analyzed the contents of soil organic matter, total nitrogen, and total phosphorus, and the activities of ß-1,4-glucosidase (BG), cellobiose hydrolase (CBH), leucine aminopeptidase (LAP), ß-1,4-N-acetylglucoside (NAG) and phosphatase (AP). We analyzed the soil nutrient limitation by stoichiometry and enzyme metrology. The results showed a shift in soil pH from alkaline to acidic during vegetation restoration process, and that total phosphorus exhibited a gradual decrease over the course of 0 to 25 years. Soil orga-nic matter, total nitrogen and enzyme activities exhibited an increasing trend during the same time frame. However, between 25 and 45 years of age, soil total phosphorus, soil organic matter, total nitrogen, AP and LAP gradually declined while NAG, BG, and CBH initially increased and then decreased. Notably, the values of (BG+CBH)/(LAP+NAG), (BG+CBH)/AP and (LAP+NAG)/AP in R. pseudoacacia plantations were higher than the global average throughout the process of vegetation restoration. In the study area, the vector length was less than 1 and gradually increased, indicating that a progressive increase in microbial carbon limitation during the process of vegetation restoration. The vector angle exceeded 45° and exhibited an overall decreasing trend, suggesting that soil microorganisms were constrained by phosphorus (P) with a gradual deceleration of P limitation, without any nitrogen (N) limitation. The restoration of R. pseudoacacia plantation resulted in significant change in soil physical and chemical properties, while the time series of afforestation also influenced nutrient limitation of soil microorganisms.

Electrochemical lithium storage of a biactive organic molecule containing cyano and imine groups.

With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.

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Improving the availability of soil phosphorus (P) and promoting tree growth through tree species selection and assembly are the critical issue. We conducted an afforestation experiment following randomized block experimental design with 1, 2, 4, and 6 tree species richness in south subtropics, including Pinus massoniana, Mytilaria laosensis, Erythrophleum fordii, Castanopsis hystrix, Michelia macclurei, Manglietia glauca, Aquilaria sinensis, and Dalbergia odorifera. We measured the bioavailable P components (CaCl2-P, citrate-P, enzyme-P and HCl-P) and examined the effects of different tree species assembly on bioavailable P components and tree growth. The results showed that, compared with non-nitrogen-fixing tree species, the mixing of nitrogen-fixing tree species (E. fordii and D. odorifera) effectively increased the contents of soil water, total nitrogen, total phosphorus, and microbial biomass P (MBP). The assembly of specific tree species improved the accumulation of bioavailable P. Mixing of nitrogen-fixing tree species significantly increased CaCl2-P content by 46.2% to 160.3%, the enzyme-P content produced by microbial mineralization by 69.3% to 688.2%, and HCl-P by 31.5% to 81.3%, increased MBP by 81.8% to 149.4%, and microbial biomass N (MBN) by 88.1% to 160.6%, respectively. Redundancy and correlation analysis results showed that MBP, available P, total phosphorus, L-leucine aminopeptidase, cellobiose, acid phosphatase, MBN and soil organic carbon were key factors driving the variation of rhizosphere soil bioavailable P. Mixing of nitrogen-fixing tree species increased enzyme-P and citrate-P, and the availability of which were positively correlated to tree basal area. In this study, mixing of nitrogen-fixing tree species increased the rhizosphere soil bioavailable P content, which facilitates tree growth.

In vitro silencing of RIP2 in naive CD4+ T cells from lupus-prone mice promotes pathogenic Th17 cell differentiation.

OBJECTIVE: This work aims to investigate whether RIP2 silencing in naive CD4+ T cells from lupus-prone mice impacts Th17 cell activity or differentiation in vitro. METHODS: Naive CD4+ T cells isolation from MRL/lpr mice's spleens. Three RNA interference target sequences of RIP2 were packaged with lentivirus and transfected into naive CD4+ T cells. The shRIP2 with the highest interference efficiency was selected and transfected into naive CD4+ T cells. Naive CD4+ T cells were cultured under conventional (TGF-ß1 and IL-6) and pathogenic (IL-6, IL-23, IL-1ß) differentiation environments, respectively. Then, RT-qPCR, Western blot or Flow Cytometry were used for measuring the amounts of RIP2 and IL-17 and the differentiation of Th17 cells in two settings. RESULTS: Under the conventional Th17 (cTh17) cell differentiation environment (TGF-ß1 and IL-6), RIP2 deficiency is linked to decreased IL-17A levels (1.00 ± 0.03 vs 0.80 ± 0.03) and attenuated cTh17 cell (2.46 ± 0.08 vs 0.78 ± 0.03) differentiation (all, P < 0.05). Under the pathogenic Th17 (pTh17) cell environment (IL-1ß, IL-23, IL-6), RIP2 deficiency is linked to elevated IL-17A levels (1.03 ± 0.05 vs 1.63 ± 0.07) and enhanced pTh17 cell (3.69 ± 0.19 vs 5.49 ± 0.10) differentiation (all, P < 0.05). CONCLUSION: Our data suggest that RIP2 inhibition induces preferential differentiation of naive CD4+ T cells to pathogenic Th17 cells, while being able to upregulate IL-17A levels in the context of pTh17 cell differentiation. Our study opens up new research areas to reveal the underlying mechanisms and potential therapeutic targets for the prevention and treatment of SLE patients. Key Points • Silencing of RIP2 in naive CD4+ T cells from lupus-prone mice promotes pathogenic Th17 (pTh17) cell differentiation and IL-17A production under pTh17 cell (IL-1ß, IL-23, and IL-6) conditions. • RIP2 deficiency in naive CD4+ T cells reduces conventional Th17 (cTh17) cell differentiation and IL-17A production under cTh17 cell (TGF-ß1 and IL-6) conditions. • RIP2-deficient naive CD4+ T cells preferentially differentiate towards pTh17 cells rather than cTh17 cells in vitro. • Inhibition of RIP2 may be involved in the development of SLE via effects on Th17/IL-17.

Nature of back slopping kombucha fermentation process: insights from the microbial succession, metabolites composition changes and their correlations.

Kombucha, a fermented tea prepared with a symbiotic culture of bacteria and yeast (SCOBY), offers a unique and unpredictable home-brewed fermentation process. Therefore, the need for a controlled kombucha fermentation process has become evident, which requiring a thorough understanding of the microbial composition and its relationship with the metabolites produced. In this study, we investigated the dynamics of microbial communities and metabolites over a 12-day fermentation period of a conventional kombucha-making process. Our findings revealed similarities between the microbial communities in the early (0-2 days) and late (10-12 days) fermentation periods, supporting the principle of back-slopping fermentation. Untargeted metabolite analysis unveiled the presence of harmful biogenic amines in the produced kombucha, with concentrations increasing progressively throughout fermentation, albeit showing relatively lower abundance on days 8 and 12. Additionally, a contrasting trend between ethanol and caffeine content was observed. Canonical correspondence analysis highlighted strong positive correlations between specific bacterial/yeast strains and identified metabolites. In conclusion, our study sheds light on the microbial and metabolite dynamics of kombucha fermentation, emphasizing the importance of microbial control and quality assurance measures in the production process.

Altered Brain Functional and Effective Connectivity Induced by Electroacupuncture in Rats Following Anterior Cruciate Ligament Transection.

Background: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.

Association between CYP3A5 Gene Polymorphism and Post-Transplant Acute Immune Rejection in Renal Transplant Recipients Receiving Tacrolimus Therapy: A Correlation Study.

BACKGROUND: Acute immune rejection remains a challenge in the post-transplant period, with approximately 7.8% of renal transplant recipients experiencing rejection episodes within the first year. Genetic polymorphisms in the CYP3A5 gene, which influences tacrolimus metabolism, have garnered interest regarding their association with clinical outcomes in renal transplantation. METHODS: This retrospective correlation study analysed clinical data from kidney transplant patients who received tacrolimus treatment at our hospital from June 2015 to June 2023. The presence of CYP3A5 gene polymorphisms, tacrolimus trough levels, and demographic and clinical data were collected and analysed. RESULTS: A total of 105 kidney transplant patients were included. Patients were divided into acute immune rejection (n = 56) and non-acute immune rejection (n = 49) groups. The distribution of CYP3A5 gene polymorphisms differed significantly between the acute rejection and non-acute rejection groups (p = 0.037). The acute rejection group exhibited a higher frequency of CYP3A5 *1/*1 or *1/*3 genotypes than the non-acute rejection group. No statistically significant differences were found in the tacrolimus trough levels between the two groups. Correlation analysis revealed a statistically significant correlation between CYP3A5 gene polymorphism and post-transplant acute immune rejection (r = 0.223, p < 0.05). CONCLUSIONS: This study demonstrated a significant association between CYP3A5 gene polymorphism and the risk of post-transplant acute immune rejection in renal transplant recipients receiving tacrolimus therapy. These findings highlighted the importance of genetic variability in tacrolimus metabolism when managing immunosuppressive therapy in transplant recipients.

Application of fecal immunochemical test in colorectal cancer screening: A community-based, cross-sectional study in average-risk individuals in Hainan.

BACKGROUND: The incidence of colorectal cancer (CRC) in China is steadily rising, with a high proportion of advanced-stage diagnoses. This highlights the significance of early detection and prevention measures to enhance survival rates. Fecal immunochemical testing (FIT) is a globally recommended CRC screening method; however, limited research has been conducted on its application in Hainan. AIM: To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan, while also examining the risk factors associated with positive FIT results. METHODS: This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province. The study was conducted from August 2022 to April 2023, employing a stratified sampling method to select participants. Individuals with positive FIT results subsequently underwent colonoscopy. Positive predictive values for confirmed CRC and advanced adenoma were calculated, and the relationship between relevant variables and positive FIT results was analyzed using χ 2 tests and multivariate logistic regression. RESULTS: A total of 1788 participants completed the FIT screening, with a median age of 57 years (interquartile range: 40-75). Among them, 503 (28.1%) were males, and 1285 (71.9%) were females, resulting in an 89.4% compliance rate for FIT screening. The overall positivity rate of FIT was 4.4% [79 out of 1788; 95% confidence interval (CI): 3%-5%]. The specific positivity rates for Haikou, Sanya, Orient City, Qionghai City, and Wuzhishan City were 9.6% (45 of 468; 95%CI: 8%-11%), 1.3% (6 of 445; 95%CI: 0.1%-3.1%), 2.7% (8 of 293; 95%CI: 1.2%-4.3%), 3.3% (9 of 276; 95%CI: 1.0%-6.3%), and 4.2% (11 of 406; 95%CI: 1.2%-7.3%), respectively. Significant associations were found between age, dietary habits, and positive FIT results. Out of the 79 participants with positive FIT results, 55 underwent colonoscopy, demonstrating an 82.2% compliance rate. Among them, 10 had a clean gastrointestinal tract, 43 had polyps or adenomas, and 2 were confirmed to have CRC, yielding a positive predictive value of 3.6% (95%CI: 0.9%-4.2%). Among the 43 participants with polyps or adenomas, 8 were diagnosed with advanced adenomas, resulting in an advanced adenoma rate of 14.5% (95%CI: 10.1%-17.7%). CONCLUSION: In the Hainan region, FIT screening for CRC among asymptomatic individuals at average risk is feasible and well-received.

Associations of neutrophil-percentage-to-albumin ratio level with all-cause mortality and cardiovascular disease-cause mortality among patients with hypertension: evidence from NHANES 1999-2010.

Background: The associations of neutrophil-percentage-to-albumin ratio (NPAR) level with all-cause and cardiovascular disease (CVD)-cause mortality among patients with hypertension remain unclear. This study aims to investigate the associations of NPAR level with all-cause and CVD-cause mortality among patients with hypertension. Methods: This prospective cohort study included 8,990 patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of NPAR level with all-cause mortality and CVD-cause mortality. Restricted cubic spline analyses were used to examine the nonlinear association of NPAR level with all-cause mortality and CVD-cause mortality. Results: This cohort study included data from 8,990 participants in analysis. During 104,474 person-years of follow-up, 3,069 all-cause deaths and 1,449 CVD-cause deaths were documented. Nonlinear associations were observed for NPAR levels with risk of all-cause mortality and CVD-cause mortality among patients with hypertension. Compared with participants in T1 of NPAR, there was a significantly increased risk of all-cause mortality and CVD-cause mortality for participants in both T2 and T3 in the fully adjusted model (model 3). The corresponding HRs for all-cause mortality were 1.10 (95% CI, 0.98-1.22) and 1.63 (95% CI, 1.45-1.82). The corresponding HRs for CVD-cause mortality were 1.10 (95% CI, 0.99-1.23) and 1.63 (95% CI, 1.46-1.81). Conclusions: Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in adults with hypertension. NPAR may be clinically useful for predicting long-term health outcomes and mortality in hypertensive population.

An asymmetric nautilus-like HflK/C assembly controls FtsH proteolysis of membrane proteins.

FtsH, a AAA protease, associates with HflK/C subunits to form a megadalton complex that spans the inner membrane and extends into the periplasm of E. coli. How this complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following overproduction of protein components, recent cryo-EM structures reveal symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit degradation of membrane-embedded substrates. Here, we present structures of native complexes in which HflK/C instead forms an asymmetric nautilus-like assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. Consistent with this nautilus-like structure, proteomic assays suggest that HflK/C enhances FtsH degradation of certain membrane-embedded substrates. The membrane curvature in our FtsH•HflK/C complexes is opposite that of surrounding membrane regions, a property that correlates with lipid-scramblase activity and possibly with FtsH's function in the degradation of membrane-embedded proteins.

Current investigation of the high prevalence of sexual dysfunction in female patients with systemic lupus erythematosus: a cross-sectional study.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects women of childbearing age and has been reported to cause sexual dysfunction in women. Although there are articles on sexual function in women with SLE, the number of articles is small, and the factors affecting sexual function in women with SLE are controversial. Based on this, this study aimed to investigate the prevalence of sexual dysfunction in Chinese female SLE patients and to explore the factors that influence it. The study design was a cross-sectional study conducted from December 2023 to April 2024 in the Department of Rheumatology and Immunology of a tertiary hospital in Hefei, Anhui Province. A total of 293 female patients diagnosed with SLE were enrolled using face-to-face questionnaires and online questionnaires. The questionnaire consisted of four parts: general information questionnaire, fatigue severity scale (FSS), depression-anxiety-stress scale (DASS-21), and female sexual functioning index (FSFI) scale. A total of 173 (59.04%) patients had sexual dysfunction, including 251 (85.67%) with decreased libido and 186 (63.46%) with difficulty in sexual arousal. There was a correlation between the patients' total FSFI scores and age (p = 0.028), marital satisfaction (p < 0.001), own education level (p = 0.008), partner's education level (p = 0.003), place of residence (p = 0.039), monthly household income (p < 0.001), family financial satisfaction(p < 0.001), menstrual status (p = 0.003), hormone use (p = 0.021),immunosuppressant use (p = 0.042), disease activity (p = 0.016), FSS score (p < 0.001), stress score (p < 0.001), anxiety score (p < 0.001) and depression score (p < 0.001)were correlated. The results of stepwise regression analysis showed that marital satisfaction (b = 2.011, t = 3.797, p < 0.001), monthly household income (b = 0.854, t = 2.316, p = 0.021), menstrual status (b = 1.218, t = 2.350, p = 0.019), fatigue scale score (b = - 0.069, t = - 2.302, p = 0.022), and depression score (b = - 0.117, t = - 2.910, p = 0.004) were the influencing factors of FSFI total score, and the difference was statistically significant. The incidence of sexual dysfunction in Chinese female SLE patients is high, and medical personnel should pay more attention to patients' sexual problems, to provide theoretical and practical bases for further prevention, treatment, and care of sexual dysfunction in female SLE patients.

Revealing and reconstructing the 3D Li-ion transportation network for superionic poly(ethylene) oxide conductor.

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

Radiological Features of Primary Pulmonary Invasive Mucinous Adenocarcinoma Based on 312 Consecutive Patients.

BACKGROUND: The aim of this study is to investigate the radiological features of primary pulmonary invasive mucinous adenocarcinoma (IMA) in a relatively large population to help improve its further understanding and its accuracy of initial diagnosis. METHODS: This retrospective study included consecutive patients with pathologically confirmed primary pulmonary IMA from January 2019 to December 2021. According to tumor morphology, IMAs were divided into regular nodule/mass, irregular, and large consolidative types. According to tumor density, IMAs were divided into solid, halo, part-solid, pure ground-glass, and cystic types. ANOVA, chi-square, or Fisher exact tests were used to analyze the differences in radiological and clinicopathological characteristics of IMA according to morphological and density subtypes. RESULTS: We analyzed 312 patients. Pulmonary IMA tended to occur in the elderly, with a slightly higher number of women than men. IMA showed a predominance in the lower lobe and adjacent to pleura. IMA of regular nodule/mass, irregular, and large consolidative types accounted for 80.8% (252/312), 13.8% (43/312), and 5.4% (17/312), respectively. Solid, halo, part-solid, pure ground-glass, and cystic IMAs accounted for 55.8% (174/312), 28.2% (88/312), 11.2% (35/312), 1.3% (4/312), and 3.5% (11/312), respectively. The lobulated (76.9%), spiculated (63.5%), and air bronchogram (56.7%) signs were common in IMA. Dead branch sign (88.2%), angiogram sign (88.2%), and satellite nodules/skipping lesions (47.1%) were common in large-consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations were common (56.1%), whereas epidermal growth factor receptor mutations were relatively rare (2.3%). CONCLUSIONS: Pulmonary IMA of regular nodule/mass type and solid type were the most common at the initial diagnosis. Detailed radiological features can aid in the differential diagnosis of IMA.

Evaluating perceived technology self-efficacy and telehealth acceptance in optometry students.

CLINICAL RELEVANCE: Constant technological improvements require practitioners to be open to adopting technologies such as telehealth for enhanced patient care. Understanding the barriers and facilitators of telehealth adoption will guide stakeholders in making decisions for safe and effective implementation of telehealth. BACKGROUND: Effective use of telehealth improves patient outcomes. It is unclear if optometry students feel supported in using and/or are accepting of telehealth. This study evaluated telehealth acceptance of optometry students, its association with their technology self-efficacy, and whether telehealth training alters this relationship. METHODS: Final-year optometry students at the University of Melbourne were invited to participate in a telehealth course. A 22-item online survey adapted from the Technology Proficiency Self-Assessment for twenty-first Century Learning was used to evaluate technology self-efficacy pre- and post-learning. Telehealth acceptance was evaluated using a 34-item survey according to the Unified Theory of Acceptance and Use of Technology-2. A 5-point Likert scale was used for each item, yielding two total scores. Respondent demographics, frequency of usage and number of devices were recorded. Descriptive statistics, ANOVA and Pearson correlation were used to analyse demographic variables and relationship between technology self-efficacy and telehealth acceptance. RESULTS: 58 (68%) and 49 (58%) students participated in the pre- and post-learning surveys. Majority were 20-29-year-old females. Students used between two and four devices for online activities, with 62% being online at least hourly. Technology self-efficacy scores (average ± SD) pre- and post-learning were 83.8% ± 8.2 and 87.8% ± 7.1. Telehealth acceptance scores pre- and post-learning were 66.1% ± 9.6 and 73.98% ± 9.9. There was no association with gender, number of devices and frequency of online use for all scores. Correlation between technology self-efficacy and telehealth acceptance was insignificant pre-learning (p = 0.3) but was significant post-learning (p = 0.04). CONCLUSION: Optometry students demonstrated high technology self-efficacy compared to telehealth acceptance. Telehealth training resulted in marked improvement in telehealth acceptance.

Association between blood mitochondrial DNA copy number and mental disorders: A bidirectional two-sample mendelian randomization study.

BACKGROUND: Mitochondria is essential for cellular energy production, oxidative stress, and apoptosis. Mitochondrial DNA (mtDNA) encodes essential proteins for mitochondrial function. Although several studies have explored the association between changes in mtDNA copy number (mtDNA-CN) and risk of mental disorders, the results remain debated. This study used a bidirectional two-sample Mendelian randomization (MR) analysis to examine the genetic causality between mtDNA-CN and mental disorders. METHODS: Genome-wide association study (GWAS) data for mtDNA-CN were sourced from UK biobank, involving 383,476 European cases. GWAS data for seven mental disorders-attention deficit/hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia, bipolar disorder, major depressive disorder, anxiety, and obsessive-compulsive disorder-were primarily obtained from the Psychiatric Genomics Consortium. Causal associations were assessed using inverse variance weighting, with sensitivity analyses via the weighted median and MR-Egger methods. Reverse MR considered the seven mental disorders as exposures. All analyses were replicated with additional mtDNA-CN GWAS data from 465,809 individuals in the Heart and Ageing Research in Genomic Epidemiology consortium and the UK Biobank. RESULTS: Forward MR observed a 27 % decrease in the risk of ASD per standard deviation increase in genetically determined blood mtDNA-CN (OR = 0.73, 95%CI: 0.58-0.92, p = 0.002), with no causal effects on other disorders. Additionally, reverse MR did not indicate a causal association between any of the mental disorders and mtDNA-CN. Validation analyses corroborated these findings, indicating their robustness. CONCLUSIONS: Our study supports the potential causal association between mtDNA-CN and the risk of ASD, suggesting that mtDNA-CN could serve as a promising biomarker for early screening of ASD.

Oleanolic acid improves the in vitro developmental competence of early porcine embryos by reducing oxidative stress and ameliorating mitochondrial function.

Objective: Oleanolic acid (OA) is a pentacyclic triterpenoid with antioxidant activity that can be an effective scavenger of free radicals in cells. This study was designed to investigate the effects of OA on porcine early embryo developmental competence in vitro and its possible mechanisms of action. Methods: In the present study, parthenogenetically activated porcine embryos were used as models to assess the effect of OA on the in vitro developmental capacity of early porcine embryos in vitro. Zygotic genome activation, mitochondrial function, oxidative stress, cell proliferation and apoptosis in early porcine embryos were examined after supplementing the culture medium with 5 µM OA. Results: The results showed that 5 µM OA supplementation not only significantly increased the blastocyst diameter in early porcine embryos on day 6 but also increased the total number of blastocysts. Furthermore, OA supplementation increased the blastocyst proliferation rate and decreased blastocyst apoptosis. Moreover, OA supplementation significantly increased the proportion of embryos that developed to the 4-cell stage after 48 h of in vitro culture and upregulated the expression of genes associated with zygotic genome activation (DPPA2 and ZSCAN4). Notably, OA alleviated oxidative stress by reducing the intracellular levels of reactive oxygen species and increasing the intracellular levels of reduced glutathione at the 4-cell stage and increased the activities of superoxide dismutase and catalase. Concurrently, OA significantly increased the mitochondrial membrane potential and intracellular ATP content. Conclusion: These results suggest that OA promotes the in vitro developmental competence of parthenogenetically activated porcine embryos by reducing oxidative stress and improving mitochondrial function during in vitro culture and that OA may contribute to the efficiency of in vitro embryo production.

The moderating role of information processing speed in the relationship between brain remodeling and episodic memory in amnestic mild cognitive impairment.

INTRODUCTION: The role of information processing speed (IPS) on relationships between episodic memory (EM) and central remodeling features in amnestic mild cognitive impairment (aMCI) was investigated. METHODS: Neuropsychological evaluations and multimodal magnetic resonance imaging were performed on 48 patients diagnosed with aMCI and 50 healthy controls (HC). Moderation models explored the moderating effect of IPS on associations between EM and imaging features at single-region, connectivity, and network levels. RESULTS: IPS significantly enhanced the positive correlations between recall and cortical thickness of left inferior temporal gyrus. IPS also notably amplified negative correlations between recognition and functional connectivity (FC) of left inferior parietal lobe and right occipital, as well as between recall/recognition and nodal clustering coefficient of left anterior cingulate cortex. DISCUSSION: IPS functioned as a moderator of associations between recall and neuroimaging metrics at the "single region-connectivity-network" level, providing new insights for cognitive rehabilitation in aMCI patients. HIGHLIGHTS: aMCI patients exhibited brain functional and structural remodeling alterations. IPS moderated relations between episodic memory and brain remodeling metrics. Therapy targeted at IPS can be considered for improving episodic memory in aMCI.

Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure.

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.