Canagliflozin alleviates pulmonary hypertension by activating PPARγ and inhibiting its S225 phosphorylation.

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.

Verbal memory network mapping in individual patients predicts postoperative functional impairments.

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals.

Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish.

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. Here, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-day time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds the molecular foundation and a comparative single-cell genomic framework to identify neutrophil markers of tissue damage using model organisms.

Exercise snacks are a time-efficient alternative to moderate-intensity continuous training for improving cardiorespiratory fitness but not maximal fat oxidation in inactive adults: a randomized controlled trial.

The aims of this study were (1) to determine how stair-climbing-based exercise snacks (ES) compared to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness (CRF), and (2) to explore whether ES could improve maximal fat oxidation rate (MFO) in inactive adults. Healthy, young, inactive adults (n: 42, age: 21.6 ± 2.3 years, BMI: 22.5 ± 3.6 kg·m-2, peak oxygen uptake (VO2peak): 33.6 ± 6.3 mL·kg-1·min-1) were randomly assigned to ES, MICT, or Control. ES (n = 14) and MICT (n = 13) groups performed three sessions per week over 6 weeks, while the control group (n = 15) maintained their habitual lifestyle. ES involved 3 × 30 s "all-out" stair-climbing (6 flight, 126 steps, and 18.9 m total height) bouts separated by >1 h rest, and MICT involved 40 min × 60%-70% HRmax stationary cycling. A significant group × time interaction was found for relative VO2peak (p < 0.05) with ES significantly increasing by 7% compared to baseline (MD = 2.5 mL·kg-1·min-1 (95% CI = 1.2, 3.7), Cohen's d = 0.44), while MICT had no significant effects (MD = 1.0 mL·kg-1·min-1 (-1.1, 3.2), Cohen's d = 0.17), and Control experienced a significant decrease (MD = -1.7 mL·kg-1·min-1 (-2.9, -0.4), Cohen's d = 0.26). MFO was unchanged among the three groups (group × time interaction, p > 0.05 for all). Stair climbing-based ES are a time-efficient alternative to MICT for improving CRF among inactive adults, but the tested ES intervention appears to have limited potential to increase MFO.

[Breast cancer lesion segmentation based on co-learning feature fusion and Transformer].

The PET/CT imaging technology combining positron emission tomography (PET) and computed tomography (CT) is the most advanced imaging examination method currently, and is mainly used for tumor screening, differential diagnosis of benign and malignant tumors, staging and grading. This paper proposes a method for breast cancer lesion segmentation based on PET/CT bimodal images, and designs a dual-path U-Net framework, which mainly includes three modules: encoder module, feature fusion module and decoder module. Among them, the encoder module uses traditional convolution for feature extraction of single mode image; The feature fusion module adopts collaborative learning feature fusion technology and uses Transformer to extract the global features of the fusion image; The decoder module mainly uses multi-layer perceptron to achieve lesion segmentation. This experiment uses actual clinical PET/CT data to evaluate the effectiveness of the algorithm. The experimental results show that the accuracy, recall and accuracy of breast cancer lesion segmentation are 95.67%, 97.58% and 96.16%, respectively, which are better than the baseline algorithm. Therefore, it proves the rationality of the single and bimodal feature extraction method combining convolution and Transformer in the experimental design of this article, and provides reference for feature extraction methods for tasks such as multimodal medical image segmentation or classification.

Right Sinus of Valsalva Aneurysm Rupturing into the Right Atrium and Dissecting into the Interventricular Septum.

The right sinus of the Valsalva aneurysm (SVA) rupturing into the right atrium (RA) and dissecting into the interventricular septum (IVS) is rare. The disease can be definitively diagnosed using two-dimensional (2D) echocardiography and color Doppler ultrasonography. Real-time biplane imaging and three-dimensional (3D) echocardiography offer new perspectives for viewing and diagnosing this disease.

Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials.

BACKGROUND AND STUDY AIMS: Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE) and is highly prevalent. The efficacy of L-ornithine L-aspartate (LOLA) for the treatment of HE is well known but its role in MHE remains uncertain. The objectives of the current study were to evaluate the efficacy of LOLA for the treatment of MHE in patients with cirrhosis. METHODS: The Cochrane Library, PubMed, EMBASE, Web of Science and Ovid databases were searched. Only randomized controlled trials (RCTs) that compared the efficacy of LOLA with placebo or no intervention for the treatment of MHE in patients with cirrhosis were included from inception to January 2023. The primary outcomes were reversal of MHE and development of overt hepatic encephalopathy (OHE). RESULTS: Overall, six RCTs comprising 292 patients were included. Compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95 % CI = 1.528, 3.352, P = 0.000, I2 = 0.0 %) and preventing progression of OHE (RR = 0.220, 95 % CI = 0.076, 0.637, P = 0.005, I2 = 0.0 %). Based on subgroup analyses, oral LOLA treatment appeared more likely to reverse MHE (RR = 2.648, 95 % CI = 1.593, 4.402, P = 0.000, I2 = 0.0 %), intravenous LOLA treatment yielded a similar probability of reversing MHE (RR = 1.669, 95 % CI = 0.904, 3.084, P = 0.102, I2 = 0.0 %). LOLA did not show a superior possibility in reducing mortality (RR = 0.422, 95 % CI = 0.064, 2.768, P = 0.368, I2 = 0.0 %) and ammonia levels (SMD = 0.044, 95 % CI = -0.290, 0.379, P = 0.795, I2 = 0.0 %) compared with placebo or no intervention. CONCLUSIONS: LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.

The Chimeric Chaoyang-Zika Vaccine Candidate Is Safe and Protective in Mice.

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

Update on the STING Signaling Pathway in Developing Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

Is low-volume high-intensity interval training a time-efficient strategy to improve cardiometabolic health and body composition? A meta-analysis.

The present meta-analysis aimed to assess the effects of low-volume high-intensity interval training (LV-HIIT; i.e., ≤5 min high-intensity exercise within a ≤15 min session) on cardiometabolic health and body composition. A systematic search was performed in accordance with PRISMA guidelines to assess the effect of LV-HIIT on cardiometabolic health and body composition. Twenty-one studies (moderate to high quality) with a total of 849 participants were included in this meta-analysis. LV-HIIT increased cardiorespiratory fitness (CRF, SMD = 1.19 [0.87, 1.50]) while lowering systolic blood pressure (SMD = -1.44 [-1.68, -1.20]), diastolic blood pressure (SMD = -1.51 [-1.75, -1.27]), mean arterial pressure (SMD = -1.55 [-1.80, -1.30]), MetS z-score (SMD = -0.76 [-1.02, -0.49]), fat mass (kg) (SMD = -0.22 [-0.44, 0.00]), fat mass (%) (SMD = -0.22 [-0.41, -0.02]), and waist circumference (SMD = -0.53 [-0.75, -0.31]) compared to untrained control (CONTROL). Despite a total time-commitment of LV-HIIT of only 14%-47% and 45%-94% compared to moderate-intensity continuous training and HV-HIIT, respectively, there were no statistically significant differences observed for any outcomes in comparisons between LV-HIIT and moderate-intensity continuous training (MICT) or high-volume HIIT. Significant inverse dose-responses were observed between the change in CRF with LV-HIIT and sprint repetitions (ß = -0.52 [-0.76, -0.28]), high-intensity duration (ß = -0.21 [-0.39, -0.02]), and total duration (ß = -0.19 [-0.36, -0.02]), while higher intensity significantly improved CRF gains. LV-HIIT can improve cardiometabolic health and body composition and represent a time-efficient alternative to MICT and HV-HIIT. Performing LV-HIIT at a higher intensity drives higher CRF gains. More repetitions, longer time at high intensity, and total session duration did not augment gains in CRF.

Association Between Bariatric Surgery and Breastfeeding Outcomes in Women: a Retrospective Case-Control Study.

BACKGROUND AND OBJECTIVE: Bariatric surgery (BS) has shown promise in enhancing exclusive breastfeeding practices among women with obesity. Nevertheless, there remains a dearth of research exploring the intricate relationship between BS and breastfeeding outcomes. This study aims to investigate the potential association between bariatric surgery and exclusive breastfeeding outcomes. METHODS: Employing a retrospective case-control design, this study undertook a comprehensive comparison of women who had undergone BS and subsequently gave birth during the study period. By meticulously matching the control group (No-BS group) based on key preoperative variables such as body mass index, age, parity, and delivery year, a robust comparative analysis was established. RESULTS: Participants in the BS group exhibited a significantly extended duration of exclusive breastfeeding in comparison to the No-BS group (p < 0.001). However, there were no noteworthy disparities observed in terms of breast milk production between the two groups (p > 0.05). Notably, an independent risk factor associated with diminished exclusive breastfeeding duration was identified: gastroesophageal reflux symptoms (p = 0.003). CONCLUSION: This study furnishes valuable insights into the efficacy of bariatric surgery in extending the duration of exclusive breastfeeding among pregnant women grappling with obesity. Furthermore, our findings underscore the discernible impact of postoperative gastroesophageal reflux symptoms on the duration of exclusive breastfeeding.

Prognostic Differences Between Surveillance and Active Treatment After Initial Orchiectomy in Patients With Stage I Mixed Germ Cell Tumors of the Testis: A Propensity Score Matching Analysis.

INTRODUCTION: The prognosis and optimal treatment approach for stage I mixed germ cell cancers of the testis are not well-established. This study aimed to assess contemporary treatment rates and their correlation with the cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients with stage I testicular mixed germ cell tumors (TMGCT) who underwent orchiectomy, comparing surveillance with active treatment, including chemotherapy (CHT) and retroperitoneal lymph node dissection (RPLND). METHODS: Retrospective analysis of clinical data from stage I TMGCT patients who underwent orchiectomy was conducted using the Surveillance, Epidemiology, and End Results database from 2004 to 2019. The annual percentage change (APC) in the use of surveillance, postoperative CHT, and RPLND was examined. Propensity score matching (PSM) and cumulative incidence, analyses were employed to compare differences in CSM and OCM between surveillance and active treatment, as well as between CHT and RPLND. Multivariate competing-risks regression models were utilized to investigate independent factors affecting CSM and OCM among stage I TMGCT patients. RESULTS: The study included 5743 individuals with stage I TMGCT that underwent surveillance (61.6%), CHT(27.2%), or RPLND (11.2%). Among them, 82 deaths were attributed to TMGCT, and 82 deaths resulted from other causes. Surveillance rates increased over time (APC: 0.635%, P = 0.008), as did CHT rates (APC: 0.863%, P < 0.001), while RPLND rates declined (APC: -0.96%, P < 0.001). After PSM, multivariate competing-risks regression analysis showed that, active treatment, compared to surveillance, was not an independent factor for CSM and OCM. In contrast, when compared to CHT, RPLND was an independent factor associated with lower CSM (hazard ratio = 0.247, 95% confidence interval: 0.08-0.761; P = 0.015), but not OCM (hazard ratio = 0.946, 95% confidence interval: 0.377-2.37; P = 0.91). CONCLUSIONS: Surveillance and CHT rates have increased over time for patients with stage I TMGCT following initial orchiectomy, while RPLND utilization has decreased. There was no significant difference in CSM between surveillance and active treatment groups, but RPLND demonstrated significantly lower CSM than CHT in active treatment. Our findings suggest that the usage of RPLND in patients with stage I TMGCT should be reconsidered.

An Improved YOLOv5-Based Lightweight Submarine Target Detection Algorithm.

Submarine recognition plays a critical role in maritime security and military defense. However, traditional submarine recognition algorithms face limitations in feature representation capability and robustness. Additionally, deploying deep learning methods on embedded and mobile platforms presents a bottleneck. To address these challenges, we propose an innovative and practical approach-an improved YOLOv5-based lightweight submarine automatic recognition detection algorithm. Our method leverages the Feature Pyramid based on MobileNetV3 and the C3_DS module to reduce computation and parameter complexity while ensuring high precision in submarine recognition. The integration of the adaptive neck from the SA-net strategy further mitigates missed detections, significantly enhancing the accuracy of submarine target detection and recognition. We evaluated our improved model on a submarine dataset, and the results demonstrate remarkable advancements in Precision, Recall, and mAP0.5, with respective increases of 8.54%, 6.02%, and 3.36%. Moreover, we achieved a notable reduction of 34.1% in parameter quantity and 67.9% in computational complexity, showcasing its lightweight effects. Overall, our proposed method introduces novel improvements to submarine recognition, addressing existing limitations and offering practical benefits for real-world deployment on embedded and mobile platforms. The enhanced performance in precision and recall metrics, coupled with reduced computational requirements, emphasizes the significance of our approach in enhancing maritime security and military applications.

Chronic high-intensity interval training and moderate-intensity continuous training are both effective in increasing maximum fat oxidation during exercise in overweight and obese adults: A meta-analysis.

Objective: to (1) systematically review the chronic effect of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on maximal fat oxidation (MFO) in overweight and obese adults, and (2) explore MFO influencing factors and its dose-response relationships with HIIT and MICT. Methods: Studies using a between-group design involving overweight and obese adults and assessing the effect of HIIT and MICT on MFO were included. A meta-analysis on MFO indices was conducted, and the observed heterogeneities were explored through subgroup, regression, and sensitivity analyses. Results: Thirteen studies of moderate to high quality with a total of 519 overweight and obese subjects were included in this meta-analysis (HIIT, n = 136; MICT, n = 235; Control, n = 148). HIIT displayed a statistically significant favorable effect on MFO compared to no-training (MD = 0.07; 95%CI [0.03 to 0.11]; I2 = 0%). Likewise, MICT displayed a statistically significant favorable effect on MFO compared to no-training (MD = 0.10; 95%CI [0.06 to 0.15]; I2 = 95%). Subgroup and regression analyses revealed that exercise intensity (Fatmax vs. non-Fatmax; %VO2peak), exercise mode, BMI, and VO2peak all significantly moderated MICT on MFO. When analyzing studies that have directly compared HIIT and MCIT in obese people, it seems there is no difference in the MFO change (MD = 0.01; 95%CI [-0.02 to 0.04]; I2 = 64%). No publication bias was found in any of the above meta-analyses (Egger's test p > 0.05 for all). Conclusion: Both HIIT and MICT are effective in improving MFO in overweight and obese adults, and they have similar effects. MCIT with an intensity of 65-70% VO2peak, performed 3 times per week for 60 min per session, will optimize MFO increases in overweight and obese adults. Given the lack of studies examining the effect of HIIT on MFO in overweight and obese adults and the great diversity in the training protocols in the existing studies, we were unable to make sound recommendations for training.

Short-term effects of SARS-CoV-2 infection and return to sport on neuromuscular performance, body composition, and mental health - A case series of well-trained young kayakers.

Purpose: This study aimed to examine the short-term effects of SARS-CoV-2 infection and return to sport (RTS) on neuromuscular performance, body composition, and mental health in well-trained young kayakers. Methods: 17 vaccinated kayakers (8 male, 9 female) underwent body composition assessment, peak power output bench press (BP), and 40-s maximum repetition BP tests 23.9 ± 1.6 days before and 22.5 ± 1.6 days after a SARS-CoV-2 infection. A linear transducer was used to examine the BP performance. The perception of training load and mental health were quantified with Borg's CR-10 scale and the Hooper questionnaire before and after infection. The difference and relationship of variables were used Wilcoxon test, Student t-test, Pearson's, and Spearman's r correlation coefficients. Results: There was a significant increase in body mass, fat-free mass, and skeletal muscle mass, but no significant changes in body fat, fat mass, and all BP performance after infection (p < 0.05). There was a significant reduction in training hours per week, session rating of perceived exertion (sRPE), internal training load (sRPE-TL), fatigue, muscle soreness levels, and Hooper index, but no changes in sleep quality and stress levels after infection (p < 0.05). The training and mental health during the RTS period was significantly correlated (r = -0.85 to 0.70) with physical performance after infection. Conclusion: A SARS-CoV-2 infection did not appear to impair the upper-body neuromuscular performance and mental health of vaccinated well-trained young kayakers after a short-term RTS period. These findings can assist coaches, and medical and club staff when guiding RTS strategies after other acute infections or similar restrictions.

Repetition velocity as a measure of loading intensity in the free weight and Smith machine Bulgarian split squat.

This study investigated the grouped and individualized load-velocity profile (GLVP vs. ILVP) in Bulgarian split squat using Smith machine and free weight. Seventy five recreational male lifters completed two incremental loading tests of Bulgarian split squat. Mean velocity was measured by a linear-position transducer (GymAware). Linear regression equation was applied to construct the GLVP and ILVP. The agreement of predicted %1RM and measured %1RM was assessed by a combination of intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of measurement (SEM) and Bland-Altman analysis. Acceptable validity was defined as ICC > 0.75, CV ≤ 10% and p ≥ 0.05 (a paired Wilcoxon signed-rank test). A very high level of inverse load-velocity relationships were demonstrated in Bulgarian split squat (r =  - 0.92) with free weights and a Smith machine. ILVP (ICC ≥ 0.98, CV ≤ 8.73%, p ≥ 0.56) was valid enough to predict the %1RM, but GLVP of both limbs revealed large CVs in free weights (CV: 15.4%,15.63%) and a Smith machine (CV: 11.24%, 12.25%). Cross-validation between the actual %1RM and predicted %1RM using free weights and a Smith machine ILVP was not acceptable (p ≤ 0.03, CV ≥ 14.07%). A very high level of inverse relationship were observed between %1RM and MV in Bulgarian split squat using free weights and a Smith machine, indicating individualized load velocity properties, and the ILVP showed high between-devices variability in both scenarios. Using velocity as a measure of loading intensity in Bulgarian split squat needs to consider the individualized load velocity properties, and difference between free weights and a Smith machine.

Rapid Generation of Recombinant Flaviviruses Using Circular Polymerase Extension Reaction.

The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

Chemically induced reprogramming to reverse cellular aging.

A hallmark of eukaryotic aging is a loss of epigenetic information, a process that can be reversed. We have previously shown that the ectopic induction of the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals can restore youthful DNA methylation patterns, transcript profiles, and tissue function, without erasing cellular identity, a process that requires active DNA demethylation. To screen for molecules that reverse cellular aging and rejuvenate human cells without altering the genome, we developed high-throughput cell-based assays that distinguish young from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic compartmentalization (NCC) assay. We identify six chemical cocktails, which, in less than a week and without compromising cellular identity, restore a youthful genome-wide transcript profile and reverse transcriptomic age. Thus, rejuvenation by age reversal can be achieved, not only by genetic, but also chemical means.

Trichlorfon blocks androgen synthesis and metabolism in rat immature Leydig cells.

Trichlorfon is a widely used organophosphorus insecticide. It has been reported that it has reproductive toxicity to animal models. However, whether trichlorfon affects testosterone biosynthesis and metabolism remains unclear. In this study, we explored the effects of trichlorfon on the steroidogenesis and the expression of genes in androgen biosynthetic and metabolic cascades in immature Leydig cells isolated from pubertal male rats. Immature Leydig cells were treated with trichlorfon (0.5-50 µM) for 3 h. Trichlorfon significantly inhibited total androgen output under basal condition at 5 and 50 µM, and under LH- and cAMP-stimulated conditions at 50 µM. Trichlorfon also downregulated the expression of Star, Sod2, and Gpx1 and their proteins at 5 and 50 µM and the expression of Cyp11a1, Hsd3b1, Cyp17a1, and Srd5a1 at 50 µM. Trichlorfon significantly inhibited total androgen output at 50 µM, which was partially reversed by 400 µg/ml vitamin E, which alone had no effects on androgen output. In conclusion, trichlorfon downregulates the expression of steroidogenesis-related genes and antioxidants, which leads to a decrease in androgen production in rat immature Leydig cells.

Association between Lower Body Qualities and Change-of-Direction Performance: A Meta-Analysis.

The aim of the present study is to determine the associations between lower body muscle strength qualities and change of direction (CoD) performance. Three databases were used to perform a systematic literature search up to September 30, 2022. Based on the studies that met the inclusion criteria, we calculated Pearson's r correlation coefficient to examine the relationships between muscle strength qualities and CoD performance. The quality of the studies included was evaluated by the modified version of the Downs and Black Quality Index Tool. Heterogeneity was determined via the Q statistic and I 2, and Egger's test was used to assess small study bias. The results revealed that lower body maximal strength (pooled: r=- 0.54, dynamic: r=- 0.60, static: r=- 0.41), joint strength (pooled: r=- 0.59, EXT-ecc: r=- 0.63, FLEX-ecc: r=- 0.59), reactive strength (r=- 0.42) and power (pooled: r=- 0.45, jump height: r=- 0.41, jump distance: r=- 0.60, peak power: r=- 0.41) were negatively and moderately related to CoD performance. To conclude, the results highlight that a number of muscle strength qualities are associated with CoD performance and are pertinent to specific phases of a directional change. It should be noted that the conclusions of this study do not establish causality, and further research is needed to better understand their training effects and underlying mechanisms.