Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.

Wilms tumor-1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single-cell chromatin accessibility and gene expression maps of foetal kidneys and kidney organoids are generated. Functional implications of WT1-targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1-mediated transcriptional regulation during podocyte development, cultured and implanted patient-derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single-cell RNA sequencing (scRNA-seq) and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR-Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1-related epigenomic landscape with respect to human podocyte development and identifies the disease-causing role of a WT1 mutation.

CDDO-Me ameliorates podocyte injury through anti-oxidative stress and regulation of actin cytoskeleton in adriamycin nephropathy.

Podocyte injury is the common initiating event in focal segmental glomerulosclerosis (FSGS). Oxidative stress and inflammation mediate podocyte injury in FSGS. NRF2 pathway regulates the constitutive and inducible transcription of various genes that encode antioxidant proteins and anti-inflammatory proteins and have pivotal roles in the defense against cellular oxidative stress. In this study, we used adriamycin-induced nephropathy (ADR) in mice as a model of FSGS to confirm that CDDO-Me treatment ameliorated adriamycin-induced kidney damage by improving renal function and kidney histology. CDDO-Me inhibited the level of oxidative stress, inflammation, and apoptosis in adriamycin-induced podocyte injury by activating NRF2 pathway in vivo and in vitro. Furthermore, CDDO-Me stabled the cytoskeleton by regulating NRF2/srGAP2a pathway. Together, these findings show that by activating NRF2 pathway, CDDO-Me could be a therapeutic strategy to prevent the adverse effects of adriamycin-induced podocyte injury.

Effect of core training on athletic and skill performance of basketball players: A systematic review.

A limited number of studies focus on the effect of core training on basketball players' athletic performance and skills. This systematic reviewaimed to comprehensively and critically review the available studies in the literature that investigate the impact of core training on basketball players' physical and skill performance, and then offer valuable recommendations for both coaches and researchers. Thedata collection, selection, and analysis adhered to the PRISMA protocol. English databases, including Ebscohost, Scopus, PubMed, Web of Science, and Google Scholar,were searched until September 2022. A total of eight articles were included, with four studies comparing the effects of core training versus traditional strength training or usual basketball training. All studies investigated the impact of core training on athletic performance. The findings revealed that core training can help players improve their overall athletic and skill performance, particularly in the areas of strength, sprinting,jumping, balance, agility, shooting, dribbling, passing, rebounding, and stepping. In addition, core training, particularly on unstable surfaces,as well as combining static and dynamic core training,improvebasketball players' athletic and skill performance. Despite the relativelylittle evidence demonstrating the effect of core training on endurance, flexibility, and defensive skills, this review demonstrates that it should be incorporated into basketball training sessions.

TYRO3 protects podocyte via JNK/c-jun-P53 pathway.

Podocyte injury plays a critical role in diabetic kidney disease (DKD). Our previous work demonstrated a protective role of tyrosine-protein kinase receptor TYRO3 in glomerular disease; However, the downstream signaling of TYRO3 remains unclear. Our data showed that genetic ablation of tyro3 in zebrafish recapitulated a nephrotic syndrome phenotype. TYRO3 expression was suppressed by high glucose and TGF-ß, which may contribute to the decreased TYRO3 expression in progressive DKD. Moreover, knockdown of TYRO3 expression with siRNA induced podocytes apoptosis and cytoskeleton rearrangement. Further study revealed that TYRO3 conferred antiapoptotic effects through the activation of JNK/c-jun-P53 in podocytes. Our results revealed a novel signaling module of TYRO3 in podocyte homeostasis, which provides a new molecular insight of TYRO3 effect in podocyte protection.

Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation.

The parathyroid hormone type 1 receptor (PTH1R), a class B1 G protein-coupled receptor, plays critical roles in bone turnover and Ca2+ homeostasis. Teriparatide (PTH) and Abaloparatide (ABL) are terms as long-acting and short-acting peptide, respectively, regarding their marked duration distinctions of the downstream signaling. However, the mechanistic details remain obscure. Here, we report the cryo-electron microscopy structures of PTH- and ABL-bound PTH1R-Gs complexes, adapting similar overall conformations yet with notable differences in the receptor ECD regions and the peptide C-terminal portions. 3D variability analysis and site-directed mutagenesis studies uncovered that PTH-bound PTH1R-Gs complexes display less motions and are more tolerant of mutations in affecting the receptor signaling than ABL-bound complexes. Furthermore, we combined the structural analysis and signaling assays to delineate the molecular basis of the differential signaling durations induced by these peptides. Our study deepens the mechanistic understanding of ligand-mediated prolonged or transient signaling.

Development of a Check-All-That-Apply (CATA) Ballot and Machine Learning for Generation Z Consumers for Innovative Traditional Food.

Generation Z (Gen Z) consumers account for an increasing proportion of the food market. The aim of this study took lamb shashliks as an example and developed novel products from the perspective of cooking methods in order to develop a traditional food suitable for Gen Z consumers. The sensory characterization of electric heating air (EH), microwave heating (MH), air frying (AF), and control (traditional burning charcoal (BC) of lamb shashliks) was performed using the CATA methodology with 120 Gen Z consumers as assessors. A 9-point hedonic scale was used to evaluate Gen Z consumers' preferences for the cooking method, as well as a CATA ballot with 46 attributes which described the sensory characteristics of lamb shashliks. The machine learning algorithms were used to identify consumer preferences for different cooking methods of lamb shashliks as a function of sensory attributes and assessed the relationship between products and attributes present in the perceptual map for the degree of association. Meanwhile, sensory attributes as important variables play a relatively more important role in each cooking method. The most important variables for sensory attributes of lamb shashliks using BC are char-grilled aroma and smoky flavor. Similarly, the most important variables for AF samples are butter aroma, intensity aroma, and intensity aftertaste, the most important variables for EH samples are dry texture and hard texture, and the most important variables for MH samples are light color regarding external appearance and lumpy on chewing texture. The interviews were conducted with Gen Z consumers to investigate why they prefer innovative products-AF. Grounded theory and the social network analysis (SNA) method were utilized to explore why consumers chose AF, demonstrating that Gen Z consumers who had previously tasted AF lamb shashliks could easily perceive the buttery aroma. This study provides a theoretical and practical basis for developing lamb shashliks tailored to Gen Z consumers.

Effect of Core Training on Skill Performance Among Athletes: A Systematic Review.

Background: This study aims to present a critical review of the existing literature on the effect of core training on athletes' skill performance, and to provide recommendations and suggest future research directions for both coaches and researchers. Methods: The data in this study were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We collected studies in the literature using prominent academic and scientific databases such as Ebscohost, Scopus, PubMed, Web of Science, and Google Scholar. Only 16 of the 119 studies met all of the inclusion criteria, and were thus included in the systematic review. Each study's quality was determined using the PEDro scale. The scoring of 16 studies ranges from 2 to 5. Results: Core training could potentially improve skill performance among football, handball, basketball, swimming, dancing, Karate, Muay Thai, gymnasts, volleyball, badminton, and golf players. Conclusion: Compared with the traditional training methods, core training is a new strength training method. Strong core muscles function as hubs in the biological motor chain, which create a fulcrum for the four limbs' strength and establish a channel for the cohesion, transmission, and integration of the upper and lower limbs. In other words, core training optimizes the transfer and overall control of motion and force to the terminal segment within athletic actions. Meanwhile, core training could increase stability and stiffness in the spine to reduce unrequired "energy leaks" and torso movement during the exertion of external loads. This mechanism could help athletes achieve better skill performance. Therefore, this review suggests that core training should be considered integrated into athletes' daily training routines. Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021100013].

Effect of core training on skill-related physical fitness performance among soccer players: A systematic review.

Aims: This study aims to present an in-depth review of the available literature on the effect of core training on skill-related physical fitness performance among soccer players, as well as to offer suggestions for researchers and coaches. Methods: The data in this study were presented based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Using scientific databases and web search engines including Scopus, Ebscohost, Web of Science, PubMed, and Google Scholar, researchers collected studies from the published literature. Only 26 of the 84 articles satisfied all the inclusion criteria and were thus included in the systematic review. The quality of each study was determined using the PEDro scale. The scores for 26 studies range between three and six. Results: Core training can improve soccer players' skill-related physical fitness, including their power, speed, balance, and agility. Conclusion: The core is the anatomic and functional center of the body as well as its "engine." All movements emanate from the center of the body and are transmitted to the extremities. The core muscles differ from the limb muscles because they frequently cocontract, thus making the torso hard to the point whereby all the muscles work together to become synergists. Theoretically, a strong core permits the passage of force from the lower body to the upper body with minimal energy loss in the torso. Based on the 26 studies, this review suggests that core training should be incorporated into the daily training sessions of soccer players, with a minimum frequency and length of 15 min per training session, twice per week, for 4 weeks. Systematic review registration: https://inplasy.com, identifier INPLASY202290045.

Triptolide preserves glomerular barrier function via the inhibition of p53-mediated increase of GADD45B.

Podocytes are important to glomerular filtration barrier integrity and maintenance of size selectivity in protein filtration in the kidney. Although there is evidence to suggest that triptolide has direct protective effects on podocyte injuries, the mechanism mediating this process remains largely unexplored. In this study, we found triptolide suppresses podocyte p53 and GADD45B expression in vivo and in vitro. We used our previously developed in vivo zebrafish model of inducible podocyte-targeted injury and found that triptolide or the inhibition of p53 and gadd45ba with morpholino (MO) alleviated metronidazole (MTZ) induced edema in zebrafish, while the overexpression of gadd45ba in podocytes blocked the protective effect of triptolide and p53 MO on podocyte injury in zebrafish. Further study showed that p53 directly transactivated GADD45B. Triptolide inhibited p53 binding to the GADD45B promoter and subsequent GADD45B transcription. We further demonstrated that p53 may indirectly regulate GADD45B expression via NF-κB signaling. Taken together, our findings demonstrated that triptolide maintained glomerular barrier function via the inhibition of p53-NF-κB-GADD45B signaling, which provides a new understanding of the antiproteinuric effects of triptolide in glomerular diseases.