Comprehensive evaluation and screening of phytochemical compounds and their hypolipidemic activities of lotus leaf based on HPLC-Q-TOF-MS and spectral-effect analysis.

This study aimed to identify and quantify the primary components in lotus leaf and to explore the hypolipidemic components through spectral-effect relationships and chemometric methods. Utilizing a data-dependent acquisition-diagnostic fragment ion/characteristic neutral loss screening strategy (DFI-NLS), a reliable HPLC-Q-TOF-MS analysis was conducted, identifying 77 compounds, including 36 flavonoids, 21 alkaloids, 3 terpenoids, 11 organic acids, 4 phenols, 1 lignin and 1 unsaturated hydrocarbon. A straightforward HPLC-DAD method was developed for the simultaneous determination of seven major components in lotus leaf, and quercetin-3-O-glucuronide (Q3GA) was identified as the most abundant component. The HPLC fingerprints of 36 lotus leaf sample batches were assessed using chemometric approaches such as principal component analysis and hierarchical cluster analysis. The hypolipidemic effect of these samples was analyzed by measuring total cholesterol (TC) and total triglycerides (TG) levels in palmitic acid (PA) and oleic acid (OA)-induced lipid modeling in HepG-2 cells, employing partial least squares regression and grey relation analysis to investigate the spectral-effect relationship of the lotus leaf. The in vivo hypolipidemic effect of these compounds was assessed using an egg yolk powder-induced high-fat zebrafish model. The findings indicated that peak No.11 (Q3GA) in the chemical fingerprint was significantly associated with hypolipidemic activity, suggesting it as a potential hypolipidemic compound in lotus leaf. In summary, this study facilitates the exploration of the phytochemical compounds and their bioactive properties in the lotus leaf.

Engineering the surface roughness of the gold nanoparticles for the modulation of LSPR and SERS.

In this work, we reported that by using a strong thiol ligand as the morphology-directing reagent, a series of Au nanoparticles with plate-like surface sub-structures could be successfully obtained via a one-pot seedless synthesis. The size and the density of the plates on the surface of Au can be readily tuned with the amount of the thiol ligand, resembling different roughness of the surface. Arising from the different surface roughness, the localized surface plasmon resonance (LSPR) of these shape and morphological alike Au nanoparticles can be continuously tuned within the visible-NIR region. The broad LSPR absorptions and feasible tunability make the Au nanoparticles suitable candidate for plasmonic-related applications. Interestingly, huge SERS enhancement was simultaneously achieved based on the specific surface roughness. Our results demonstrate the great potentials for tuning the LSPR and SERS of Au nanostructures through the engineering of the surface morphologies, which would assist for the design, synthesis, and applications of Au-based plasmonic nanomaterials in various fields.

The bimolecular reactive transport in heterogeneous porous media: Sub-diffusion in interpretation of laboratory experiment.

This present work consists of investigating the effects of particle size heterogeneity and flow rates on transport-reaction kinetics of CuSO4 and Na2EDTA2- in porous media, via the combination of a bimolecular reaction experiment and model simulations. In the early stages of transport, a peak is observed in the concentration breakthrough curve of the reactant CuSO4, related to the delayed mixing and reaction of the reactants. The numerical results show that an increase in flow rate promotes the mixing processes between the reactants, resulting in a larger peak concentration and a slighter tail of breakthrough curves, while an increase in medium heterogeneity leads to a more significant heavy tail. The apparent anomalous diffusion and heavy-tailing behavior can be effectively quantified by a novel truncated fractional derivative bimolecular reaction model. The truncated fractional-order model, taking into account the incomplete mixing, offers a satisfactory reproduction of the experimental data.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated. METHODS: The target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug-disease-target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS. RESULTS: A total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened. CONCLUSION: Res has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

H/D Exchange of Aromatic Sulfones via Base Promotion and Silver Catalysis.

Aromatic sulfones are the prevailing scaffolds in pharmaceutical and material sciences. However, compared to their widespread application, the selective deuterium labeling of these structures is restricted due to their electron-deficient properties. This study presents two comprehensive strategies for the deuteration of aromatic sulfones. The base-promoted deuteration uses DMSO-d6 as the deuterium source, resulting in a rapid H/D exchange within 2 h. Meanwhile, a silver-catalyzed protocol offers a much milder option by using economical D2O to furnish the labeled sulfones.

[Pedigree Analysis of Hereditary Coagulation Factor XII Deficiency Caused by Compound Heterozygous Mutation p.Gly175Cys and p.Gly542Ser of F12 Gene].

OBJECTIVE: To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis. METHODS: The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of F12 gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure. RESULTS: The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of F12 gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband's father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure. CONCLUSION: The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.

Trajectories of Perceived Parental Psychological Control and the Longitudinal Associations with Chinese Adolescents' School Adjustment across High School Years.

Past research supports the detrimental effects of parental psychological control on adolescent school adjustment in both emotional and academic domains. However, how psychological control changes during adolescence, and how such developmental course is related to adolescent psychological well-being and academic functioning are unclear. The direction of effects between parenting and child behaviors is also inconclusive. This 3-year longitudinal study addressed these research gaps by using five waves of survey data on 710 Chinese adolescents of high school ages (Mean age at T1 = 15.54 years, SD = 0.45, 50% males). Using latent growth curve models and latent class growth analysis, the majority of adolescents (about 63%) reported gradual increases of parental psychological control in the first 2 years of high school but a slight decline afterwards, while the other 37% perceived low and stable levels. Results from parallel latent growth modeling suggested that trajectories of psychological control were positively related to developmental trends of internalizing problems (i.e., depression and anxiety) and maladaptive academic functioning, but negatively associated with the trajectory of adaptive academic functioning, as indexed by intercept-intercept and slope-slope associations. The random-intercept cross-lagged models further revealed that psychological control was predictive of adolescent anxiety and lower adaptive academic functioning, and bidirectionally associated with maladaptive academic-related beliefs and behaviors at the within-person level. Taken together, these findings highlight the crucial role of parental psychological control on adolescent school adjustment in the Chinese cultural context and support the reciprocal model of parent-child interactions.

Niche convergence and biogeographic history shape elevational tree community assembly in a subtropical mountain forest.

Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.

[Research progress in treatment of chronic prostatitis/chronic pelvic pain syndrome with traditional Chinese medicine].

Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) is a common urological disease with complex etiology. The treatment effect of western medicine is not satisfactory, and the course of the disease is protracted, which brings great trouble to patients. Traditional Chinese medicine(TCM) has a variety of treatment methods based on syndrome differentiation and treatment, including internal treatment with TCM, acupuncture and massage, and other external treatment methods for comprehensive treatment, with significant effect. This study summarized the etiology and pathogenesis of CP/CPPS and found that western medicine cannot fully explain the etiology and pathogenesis of CP/CPPS. It was believed that CP/CPPS was mainly related to many factors such as special pathogen infection, voiding dysfunction, mental and psychological abnormalities, neuroendocrine abnormalities, immune abnormalities, excessive oxidative stress, pelvic diseases, and heredity. TCM believed that CP/CPPS was caused by damp heat, blood stasis, Qi stagnation, and poisoning and was closely related to the organs of the liver, spleen, kidney, lung, stomach, bladder, and meridians of Chong and Ren channels and three yin channels of the foot. In the treatment of TCM, multiple comprehensive treatment plans are currently used, including internal treatment with TCM(decoction, proprietary Chinese medicine, and unique therapies of famous doctors), acupuncture and massage treatment, and other external treatment methods(rectal administration, topical application of TCM, and ear acupoint pressure). Comprehensive regulation has significant clinical efficacy and prominent characteristics of TCM, and it is worth clinical promotion. This study aims to provide a reference for clinical prevention and treatment of CP/CPPS and points out potential directions for future research in this field.

Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Psychological Aspects of Facial Palsy.

This article discusses the psychological effects of facial palsy (FP) in adults. FP is the abnormal functioning of facial muscles resulting from temporary or permanent damage of the facial nerves. Following facial paralysis, patients can develop motor and psychosocial functioning issues impacting quality of life. In addition, real or perceived judgment in social settings of those with FP increases the risk of low self-esteem, anxiety, and depression. Currently, most available research focuses on surgical patients and suggests a lack of psychological support throughout the affliction. A multidisciplinary approach when treating patients with FP can help improve the patient's quality of life.

Characteristics of the time processing of adults' strongest sustained attentional bias toward neutral infant faces.

Previous studies have shown that adults exhibit the strongest attentional bias toward neutral infant faces when viewing faces with different expressions at different attentional processing stages due to different stimulus presentation times. However, it is not clear how the characteristics of the temporal processing associated with the strongest effect change over time. Thus, we combined a free-viewing task with eye-tracking technology to measure adults' attentional bias toward infant and adult faces with happy, neutral, and sad expressions of the same face. The results of the analysis of the total time course indicated that the strongest effect occurred during the strategic processing stage. However, the results of the analysis of the split time course revealed that sad infant faces first elicited adults' attentional bias at 0 to 500 ms, whereas the strongest effect of attentional bias toward neutral infant faces was observed at 1000 to 3000 ms, peaking at 1500 to 2000 ms. In addition, women and men had no differences in their responses to different expressions. In summary, this study provides further evidence that adults' attentional bias toward infant faces across stages of attention processing is modulated by expressions. Specifically, during automatic processing adults' attentional bias was directed toward sad infant faces, followed by a shift to the processing of neutral infant faces during strategic processing, which ultimately resulted in the strongest effect. These findings highlight that this strongest effect is dynamic and associated with a specific time window in the strategic process.

The simultaneous removal of methylene blue (MB) and Ca2+ by recyclable adsorbents based the scales derived from coal gasification system.

The transformation of solid wastes from industrial production into effective adsorbents could significantly contribute to wastewater treatment. In this study, after acidizing and burning soft scale (SS) from coal gasification system, two magnetic adsorbents (mag-ASS and mag-BASS) were prepared via the combination of magnetite with ultrasonic, respectively. The treatment effects of mag-ASS and mag-BASS were then investigated for simulated wastewater containing macromolecular organic matter [i.e., methylene blue (MB)] and Ca2+. The results indicated that the pseudo second order kinetic, Elovich, Freundlich, Langmuir and Temkin model could well describe the adsorption behavior of MB and Ca2+ onto mag-ASS and mag-BASS. The maximum adsorption capacities of mag-ASS for MB and mag-BASS for Ca2+ were 600.53 mg/g and 102.54 mg/g, respectively. Surprisingly, the adsorption abilities of mag-ASS for MB and mag-BASS for Ca2+ show significantly higher than the others. The adsorption mechanisms of MB mainly included electrostatic interaction, π-π conjugate interaction and cation exchange, while those of Ca2+ were mainly electrostatic interaction and cation exchange. The diffusion of MB and Ca2+ onto the magnetic adsorbents might be controlled by the combined effects of intraparticle and liquid film diffusion. There was no significant reduction in adsorption capacity after 8 cycles of adsorption and desorption, indicating that SS-based magnetic adsorbents had good recyclability and stability. Moreover, the removal efficiency of mag-BASS for total hardness and total organic carbon in real coal gasification gray water (CGGW) was 82.60 and 64.10%, respectively. The treatment of CGGW and the resource of wastes would significantly promote the reasonable disposal of coal gasification scales.

Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry.

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy. However, the mechanisms controlling its protein turnover remain elusive. Through proteomic screens and structural characterizations, we identify a reciprocal antagonism of PIN1-APC/CCDH1 mediated by domain-oriented phosphorylation-dependent dual interactions as a fundamental mechanism governing mitotic protein stability and cell-cycle entry. Remarkably, combined PIN1 and cyclin-dependent protein kinases (CDKs) inhibition creates a positive feedback loop of PIN1 inhibition and APC/CCDH1 activation to irreversibly degrade PIN1 and other crucial mitotic proteins, which force permanent cell-cycle exit and trigger anti-tumor immunity, translating into synergistic efficacy against triple-negative breast cancer.

3M syndrome patient with a novel mutation: A case report.

BACKGROUND: A rare autosomal recessive genetic disorder, 3M syndrome, is characterized by severe intrauterine and postnatal growth retardation. Children with 3M syndrome typically exhibit short stature, facial deformities, long tubular bones, and high vertebral bodies but generally lack mental abnormalities or other organ damage. Pathogenic genes associated with 3M syndrome include CUL7, OBSL1 and CCDC8. The clinical and molecular characteristics of patient with 3M syndrome are unique and serve as important diagnostic indicators. CASE SUMMARY: In this case, the patient displayed square shoulders, scoliosis, long slender tubular bones, and normal neurological development. Notably, the patient did not exhibit the typical dysmorphic facial features, relative macrocephaly, or growth retardation commonly observed in individuals with 3M syndrome. Whole exon sequencing revealed a novel heterozygous c.56681+1G>C (Splice-3) variant and a previously reported nonsense heterozygous c.3341G>A (p.Trp1114Ter) variant of OBSL1. Therefore, it is important to note that the clinical features of 3M syndrome may not always be observable, and genetic confirmation is often required. Additionally, the identification of the c.5683+1G>C variant in OBSL1 is noteworthy because it has not been previously reported in public databases. CONCLUSION: Our study identified a new variant (c.5683+1G>C) of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.

Group A Streptococcus Pili-Roles in Pathogenesis and Potential for Vaccine Development.

The Gram-positive human pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) employs an arsenal of virulence factors that contribute to its pathogenesis. The pilus is an important factor that enables the pathogen to adhere to and colonize host tissues. Emerging research in pilus function shows that pili's involvement in establishing infection extends beyond host adhesion. The diversity of GAS pilus types reflect the varying characteristics identified in different pili. With the development of new experimental systems and animal models, a wider range of biological functions have been explored. This brief review summarizes recent reports of new functions in different GAS pilus types and the methodologies that contributed to the findings. The established importance of the pilus in GAS pathogenesis makes this surface structure a promising vaccine target. This article also reviews recent advancements in pilus-based vaccine strategies and discusses certain aspects that should be considered in vaccine development according to the newly defined properties of pili.

Forensic Identification and Evaluation of 25 Obstetric Brachial Plexus Palsy Medical Damage Cases.

OBJECTIVES: To analyze the high risk factors of obstetric brachial plexus palsy (OBPP), and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification. METHODS: A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center. The shortcomings of hospitals in birth weight assessment, delivery mode selection, labor process observation and shoulder dystocia management, and the causal relationship between them and the damage consequences of the children were summarized. RESULTS: Fault medical behavior was assessed as the primary cause in 2 cases, equal cause in 10 cases, secondary cause in 8 cases, minor cause in 1 case, no causal relationship in 1 case, and unclear causal force in 3 cases. CONCLUSIONS: In the process of forensic identification of OBPP, whether medical behaviors fulfill diagnosis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation, delivery mode notification, standardized use of oxytocin, standard operation of shoulder dystocia, etc. Meanwhile, it is necessary to fully consider the objective risk of different risk factors and the difficulty of injury prevention, and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

ADAR2 deficiency ameliorates non-alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine-to-inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post-transcriptional modification of genome-encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity-associated NAFLD and sarcopenia remains unclear. METHODS: ADAR2+/+/GluR-BR/R mice (wild type [WT]) and ADAR2-/-/GluR-BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high-fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross-sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. RESULTS: ADAR2 KO mice fed with HFD exhibited lower body weight (-7.7%, P < 0.05), lower liver tissue weight (-20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (-24%, P < 0.001) and liver injury (P < 0.01). ADAR2 KO mice displayed protection against HFD-induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA; P < 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy-associated transcripts, such as forkhead box protein O1, muscle atrophy F-box/atrogin-1 and muscle RING finger 1/tripartite motif-containing 63, were decreased in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. ADAR2 deficiency attenuates HFD-induced local liver and skeletal muscle tissue inflammation. ADAR2 deficiency abolished HFD-induced systemic (P < 0.01), hepatic (P < 0.0001) and muscular (P < 0.001) SAA1 levels. C2C12 myotubes treated with recombinant SAA1 displayed a decrease in myotube length (-37%, P < 0.001), diameter (-20%, P < 0.01), number (-39%, P < 0.001) and fusion index (-46%, P < 0.01). Myogenic markers (myosin heavy chain and myogenin) were decreased in SAA1-treated myoblast C2C12 cells. CONCLUSIONS: These results provide novel evidence that ADAR2 deficiency may be important in obesity-associated sarcopenia and NAFLD. Increased SAA1 might be involved as a regulatory factor in developing sarcopenia in NAFLD.

Prediction of body mass index and skeletal maturity for early menarche risk at menarche onset: a cross-sectional study of Chinese girls.

BACKGROUND: This study aimed to assess the predictive value of body mass index (BMI) and skeletal maturity for the occurrence of early menarche in Chinese girls. METHODS: A cross-sectional analysis was conducted on 785 girls aged 8.1-14.6 years who visited our hospital within 3 months of menarche onset. Early menarche was defined as menarche age (MA) <10 years. Skeletal maturity was classified based on the difference between bone age (BA) and chronological age (CA), termed BA-CA; advanced BA was defined as BA-CA>2 years. RESULTS: The average MA was 10.7 (SD: 1.1) years, with a prevalence of early menarche of 23.3%. BA exhibited relative stability compared with MA, with an average of 12.8 (SD: 0.5) years at menarche onset. At menarche onset, the average height, weight and BMI were 149.1 (SD: 5.1) cm, 43.3 (SD: 7.2) kg and 19.4 (SD: 2.8) kg/m², respectively. Logistic regression analyses indicated that every 1-year increment in BA-CA was independently associated with a 18.90-fold higher risk of early menarche (95% CI 11.77 to 30.32), respectively, and remained statistically significant even after adjusting for height or mid-parental height. Furthermore, the prediction of BA-CA for early menarche demonstrated a dose-dependent pattern across BMI categories, with the greatest risk observed in normal-weight girls, the lowest risk in obese girls and an intermediate risk in overweight girls at the same degree of BA advancement. CONCLUSIONS: Our findings provide evidence supporting the significant contributions of BMI and skeletal maturity in predicting early menarche among Chinese girls at menarche onset. Additionally, the results suggest a dose-dependent relationship between skeletal maturity and BMI categories, with normal-weight girls displaying a higher risk of early menarche compared to overweight and obese girls with the same degree of BA advancement.