The effectiveness and feasibility of ball-milled powdered activated carbon (BPAC) for removal of organic pesticides in conventional drinking water treatment process.

In the conventional drinking water treatment process (CDWTP), powdered activated carbon (PAC) is commonly used for removing organic pesticides, or other organic contaminants. However, the hydraulic retention time (HRT) in CDWTP is insufficient for fulfilling PAC adsorption equilibrium to realize its full capacity. This study examined the adsorption kinetics, adsorption thermal dynamics, and removal efficiency for six organic pesticides using the ball-milled PAC (BPAC) with varying particle sizes in CDWTP. Based on the experiments with the pesticides of atrazine, diazinon, dimethoate, fenitrothion, isoproturon and thiometon, the results indicated that as the particle size reduced from around 38 µm for the commercial PAC to 1 µm for the BPAC, the adsorption rates for hydrophobic pesticides increased up to twentyfold. Diffusional adsorption from the bulk solution to the external PAC surface is the most likely predominant mechanism. This could allow a sufficient pesticides' adsorption within the limited HRT and to achieve a great depth removal of these toxic compounds. However, the addition of BPAC with a diameter of 1 µm was observed to significantly increase residual particles in treated water after the conventional treatment process. With a further systematic evaluation of both adsorption rate and particle penetration, a particle size of around 6 µm BPAC was considered a practical compromise between the adsorption rate and particle penetration for real application. Results from five surface waters of different water quality indicated that, compared to commercial PAC, application of 6 µm BPAC could achieve up to a 75% reduction in adsorbent dosage while maintaining around the same pesticide removal efficiencies. Additionally, thermodynamic analyses suggest that adsorption of these pesticides could be enthalpically or entropically driven depending on the degree of pesticide hydrophobicity.

Unraveling the role of low-density lipoprotein-related genes in lung adenocarcinoma: Insights into tumor microenvironment and clinical prognosis.

BACKGROUND: The hypothesized link between low-density lipoprotein (LDL) and oncogenesis has garnered significant interest, yet its explicit impact on lung adenocarcinoma (LUAD) remains to be elucidated. This investigation aims to demystify the function of LDL-related genes (LRGs) within LUAD, endeavoring to shed light on the complex interplay between LDL and carcinogenesis. METHODS: Leveraging single-cell transcriptomics, we examined the role of LRGs within the tumor microenvironment (TME). The expression patterns of LRGs across diverse cellular phenotypes were delineated using an array of computational methodologies, including AUCell, UCell, singscore, ssGSEA, and AddModuleScore. CellChat facilitated the exploration of distinct cellular interactions within LDL_low and LDL_high groups. The findmarker utility, coupled with Pearson correlation analysis, facilitated the identification of pivotal genes correlated with LDL indices. An integrative approach to transcriptomic data analysis was adopted, utilizing a machine learning framework to devise an LDL-associated signature (LAS). This enabled the delineation of genomic disparities, pathway enrichments, immune cell dynamics, and pharmacological sensitivities between LAS stratifications. RESULTS: Enhanced cellular crosstalk was observed in the LDL_high group, with the CoxBoost+Ridge algorithm achieving the apex c-index for LAS formulation. Benchmarking against 144 extant LUAD models underscored the superior prognostic acuity of LAS. Elevated LAS indices were synonymous with adverse outcomes, diminished immune surveillance, and an upsurge in pathways conducive to neoplastic proliferation. Notably, a pronounced susceptibility to paclitaxel and gemcitabine was discerned within the high-LAS cohort, delineating prospective therapeutic corridors. CONCLUSION: This study elucidates the significance of LRGs within the TME and introduces an LAS for prognostication in LUAD patients. Our findings accentuate putative therapeutic targets and elucidate the clinical ramifications of LAS deployment.

TRPV4 antagonist suppresses retinal ganglion cell apoptosis by regulating the activation of CaMKII and TNF-α expression in a chronic ocular hypertension rat model.

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.

Cardiac Resolvin D2 ameliorates sepsis-induced cardiomyopathy via inhibiting Caspase-11/GSDMD dependent pyroptosis.

BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is common complication in septic patients with a high mortality and is characterized by an abnormal inflammation response, which was precisely regulated by endogenous specialized pro-resolving mediators (SPMs). However, the metabolic changes of cardiac SPMs during SICM and the roles of SPMs subset in the development of SICM remain unknown. METHODS: In this work, the SPMs concentration was assessed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) of SICM mice and SICM patients. The cardiac function was measured by echocardiography after the treatment of a SPMs subset, termed Resolvin D2 (RvD2). Caspase-11-/-, GSDMD-/- and double deficient (Caspase-11-/-GSDMD-/-) mice were used to clarify the mechanisms of RvD2 in SICM. RESULTS: We found that endogenous cardiac SPMs were disorders and RvD2 was decreased significantly and correlated with left ventricular ejection fraction (LVEF) and ß-BNP, cTnT in Lipopolysaccharide/Cecum ligation and puncture (CLP) induced SICM models. Treatment with RvD2 attenuated lethality, cardiac dysfunction and cardiomyocytes death during SICM. Mechanistically, RvD2 alleviated SICM via inhibiting Caspase-11/GSDMD-mediated cardiomyocytes pyroptosis. Finally, the plasma levels of RvD2 were also decreased and significantly correlated with IL-1ß, ß-BNP, cTnT and LVEF in patients with SICM. Of note, plasma RvD2 level is indicator of SICM patients from healthy controls or sepsis patients. CONCLUSION: These findings suggest that decreased cardiac RvD2 may involve in the pathogenesis of SICM. In addition, treatment with RvD2 represents a novel therapeutic strategy for SICM by inhibiting cardiomyocytes pyroptosis.

Deep learning for advancing peptide drug development: Tools and methods in structure prediction and design.

Peptides can bind challenging disease targets with high affinity and specificity, offering enormous opportunities for addressing unmet medical needs. However, peptides' unique features, including smaller size, increased structural flexibility, and limited data availability, pose additional challenges to the design process compared to proteins. This review explores the dynamic field of peptide therapeutics, leveraging deep learning to enhance structure prediction and design. Our exploration encompasses various facets of peptide research, ranging from dataset curation handling to model development. As deep learning technologies become more refined, we channel our efforts into peptide structure prediction and design, aligning with the fundamental principles of structure-activity relationships in drug development. To guide researchers in harnessing the potential of deep learning to advance peptide drug development, our insights comprehensively explore current challenges and future directions of peptide therapeutics.

Targeting NEDD8 suppresses surgical stress-facilitated metastasis of colon cancer via restraining regulatory T cells.

Regulatory T cells (Tregs) are a key determinant for the immunosuppressive and premetastatic niche for cancer progression after surgery resection. However, the precise mechanisms regulating Tregs function during surgical stress-facilitated cancer metastasis remain unknown. This study aims to unravel the mechanisms and explore potential strategies for preventing surgical stress-induced metastasis by targeting NEDD8. Using a surgical stress mouse model, we found that surgical stress results in the increased expression of NEDD8 in Tregs. NEDD8 depletion abrogates postoperative lung metastasis of colon cancer cells by inhibiting Treg immunosuppression and thereby partially recovering CD8+T cell and NK cell-mediated anti-tumor immunity. Furthermore, Treg mitophagy and mitochondrial respiration exacerbated in surgically stressed mice were attenuated by NEDD8 depletion. Our observations suggest that cancer progression may result from surgery-induced enhancement of NEDD8 expression and the subsequent immunosuppressive function of Tregs. More importantly, depleting or inhibiting NEDD8 can be an efficient strategy to reduce cancer metastasis after surgery resection by regulating the function of Tregs.

Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS.

The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.

Efficient Computational Framework for Target-Specific Active Peptide Discovery: A Case Study on IL-17C Targeting Cyclic Peptides.

The development of potentially active peptides for specific targets is critical for the modern pharmaceutical industry's growth. In this study, we present an efficient computational framework for the discovery of active peptides targeting a specific pharmacological target, which combines a conditional variational autoencoder (CVAE) and a classifier named TCPP based on the Transformer and convolutional neural network. In our example scenario, we constructed an active cyclic peptide library targeting interleukin-17C (IL-17C) through a library-based in vitro selection strategy. The CVAE model is trained on the preprocessed peptide data sets to generate potentially active peptides and the TCPP further screens the generated peptides. Ultimately, six candidate peptides predicted by the model were synthesized and assayed for their activity, and four of them exhibited promising binding affinity to IL-17C. Our study provides a one-stop-shop for target-specific active peptide discovery, which is expected to boost up the process of peptide drug development.

Multiple roles of LncRNA-BMNCR on cell proliferation and apoptosis by targeting miR-145/CBFB axis in BMECs.

Bovine mastitis is one of the most serious and costly disease affecting dairy cattle production. The present study explored the inflammatory response and autoprotective mechanism of a novel specific high expression BMNCR (bovine mastitis related long non-coding RNA) in S. aureus induced mastitis by miR-145/CBFB axis in dairy cows from the perspective of molecular genetics. In bovine mammary epithelial cells, we preformed loss of function experiments to detect changes in cytokine, proliferation and apoptosis by qRT-PCR, western blot, flow cytometry and EdU staining. The results demonstrated that BMNCR significantly increased cell apoptosis, and inhibited cell proliferation. However, the secretion of IL-1α, IL-2, IL-6, IL-8 and IL-12 were enhanced after knock-down BMNCR. Bioinformatics analysis demonstrated that BMNCR could target 8 miRNAs, in-depth analyses indicated that BMNCR acts as a molecular sponge for bta-miR-145 and CBFB was one of 23 target gene of bta-miR-145 . The results of the present study demonstrated that the role of BMNCR in S. aureus induced mastitis can be mediated by sponge bta-miR-145 activating CBFB expression. BMNCR could be a potential target for mastitis diagnosis and therapy, which may enrich the theoretical research of therapeutic intervention, and further increase milk yield and improve milk quality.

Toxicity effects of pesticides based on zebrafish (Danio rerio) models: Advances and perspectives.

Pesticides inevitably enter aquatic environments, posing potential risks to organisms. The common aquatic model organism, zebrafish (Danio rerio), are widely used to evaluate the toxicity of pesticides. In this review, we searched the Web of Science database for articles published between 2012 and 2022, using the keywords "pesticide", "zebrafish", and "toxicity", retrieving 618 publications. Furthermore, we described the main pathways by which pesticides enter aquatic environments and the fate of their residues in these environments. We systematically reviewed the toxicity effects of pesticides on zebrafish, including developmental toxicity, endocrine-disrupting effects, reproductive toxicity, neurotoxicity, immunotoxicity, and genotoxicity. Importantly, we summarized the latest research progress on the toxicity mechanism of pesticides to zebrafish based on omics technologies, including transcriptomics, metabolomics, and microbiomics. Finally, we discussed future research prospects, focusing on the combined exposure of multiple pollutants including pesticides, the risk of multigenerational exposure to pesticides, and the chronic toxicity of aquatic nanopesticides. This review provides essential data support for ecological risk assessments of pesticides in aquatic environments, and has implications for water management in the context of pesticide pollution.

Identification cloning and functional analysis of novel natural antisense lncRNA CFL1-AS1 in cattle.

Long noncoding RNAs have been identified as important regulators of gene expression and animal development. The expression of natural antisense transcripts (NATs) transcribed in the opposite direction to protein-coding genes is usually positively correlated with the expression of homologous sense genes and is the key factor for expression. Here, we identified a conserved noncoding antisense transcript, CFL1-AS1, that plays an important role in muscle growth and development. CFL1-AS1 overexpression and knockout vectors were constructed and transfected into 293T and C2C12 cells. CFL1-AS1 positively regulated CFL1 gene expression, and the expression of CFL2 was also downregulated when CFL1-AS1 was knocked down. CFL1-AS1 promoted cell proliferation, inhibited apoptosis and participated in autophagy. This study expands the research on NATs in cattle and lays a foundation for the study of the biological function of bovine CFL1 and its natural antisense chain transcript CFL1-AS1 in bovine skeletal muscle development. The discovery of this NAT can provide a reference for subsequent genetic breeding and data on the characteristics and functional mechanisms of NATs.

[Herbal cake-partitioned moxibustion regulates M1 and M2 macrophage polarization of colonic mucosa in rats with Crohn's disease].

OBJECTIVE: To observe the effect of herbal cake-partitioned moxibustion (Moxi) on the expressions of inflammatory factors and M1/M2 polarization in colonic mucosal macrophages in Crohn's disease (CD) rats, so as to explore its underlying mechanisms in the treatment of CD. METHODS: Forty male SD rats were randomly divided into normal, model, Moxi and medication groups (n=10). The CD model was established by enema of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) solution (5%TNBS∶50% alcohol=2∶1, 3 mL/kg), once every 7 days, 4 times altogether. For rats of the Moxi group, cake-partitioned moxibustion was given to "Tianshu" (ST25) and "Qihai" (CV6), two moxa-cones for each acupoint every time, once daily for 10 days. For rats of the medication group, intragastric perfusion of mesalazine solution was given twice daily for 10 days. After the treatment, the colonic mucosa tissue was sampled, and the macrophages were isolated, purified and cultured. The pathological changes of colon tissues were observed by H.E. staining. The ultrastructure of colon tissue was observed by transmission electron microscopy. The expression levels of α7nAChR, NF-κB p65 and TNF-α in colon mucosal macrophages were detected by Western blot. The number of M1 and M2 macrophages in colon mucosa was detected by flow cytometry and immunofluorescence assay. RESULTS: Compared with the normal group, the colon tissue of rats presented huge ulceration and inflammatory manifestations, the junction of colon epithelial cells was loose, the structure of organelles was damaged; the expression level of α7nAChR in macrophages of colon mucosa was significantly decreased (P<0.01), while the expression levels of NF-κB p65 and TNF-α, and the number of M1 and M2 macrophages were increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the morphology and structure of colon mucosa tissues of rats in Moxi and medication groups were improved; the expression level of α7nAChR, the number of M2 macrophage in colon mucosa were significantly increased (P<0.01, P<0.05), while the expression levels of NF-κB p65 and TNF-α, and the number of M1 macrophage were significantly decreased (P<0.01, P<0.05) in both the Moxi and medication groups. CONCLUSION: Herbal cake-partitioned moxibustion may inhibit NF-κB activation by up-regulating the expression level of α7nAChR to promote the polarization of macrophages from M1 to M2 type, and reduce the proportion of M1 macrophages, inhibit the expression of TNF-α in colonic mucosa of CD rats, so as to relieve the intestinal inflammation.

Effect of Conbercept on Corneal Neovascularization in a Rabbit Model.

OBJECTIVE: To study the efficacy of Conbercept for the treatment of corneal neovascularization (NV) in a rabbit model. METHODS: NV was induced by placing sutures. Eight rabbits were used as a control. The other 136 rabbits were randomly divided into two equal groups, and 68 rabbits in each group were divided into four subgroups and given different treatments. Time-course photographs, histological examination, and enzyme-linked immunoassay ELISA analysis for vascular endothelial growth factor were performed at weeks 1, 2, and 3 after injection placement. RESULTS: At weeks 1, 2, and 3 after injection placement, there was less expression of corneal NV and VEGF in the conbercept-treated groups than in the saline-treated control groups and less corneal NV and VEGF were expressed in the early treatment group than in the late treatment group. At weeks 2 and 3 after injection, there were fewer corneal NV (length and area) in the early intrastromal injection group with conbercept than in the early subconjunctival injection group with conbercept and a smaller diameter of corneal NV than in the late intrastromal injection group treated with conbercept. Histological examination showed a smaller diameter of corneal NV in all eyes in conbercept-treated groups 1 w after injection than before injection. Treatment with subconjunctival injection with conbercept led to a larger diameter at weeks 2 and 3 than at week 1. CONCLUSIONS: Subconjunctival and intrastromal administrations of conbercept effectively inhibit corneal NV in rabbits, and the latter has the better effect. The effect is the best in the group with cornea intrastromal injection of conbercept 1 w after suture. Early administration of conbercept may successfully inhibit corneal NV in an animal model.

Hybrid weakness and continuous flowering caused by compound expression of FTLs in Chrysanthemum morifolium × Leucanthemum paludosum intergeneric hybridization.

Hybridization is an important evolutionary mechanism ubiquitous to plants. Previous studies have shown that hybrid polyploidization of cultivated chrysanthemum, 'Zhongshanzigui', and Leucanthemum paludosum exhibit spring-flowering traits. This study explores the function of the LpFTLs gene via the phenotype of A. thaliana after heterologous transformation of the LpFTLs gene, and analyzes the mechanism ofthe continuous flowering phenotype and heterosis of hybrid offspring. The results suggest that the flowering phenotype of hybrid offspring in spring may be related to the expression of the LpFTLs gene. Ectopic expression of Leucanthemum paludosumLpFTLs in Arabidopsis thaliana resulted in earlier flowering, indicating that the LpFTLs gene also affects the flowering time in L. paludosum. Compound expression of FTLs in C. morifolium × L. paludosum intergeneric hybridization directly leads to serious heterosis in the hybrid offspring. Moreover, continuous flowering appears to be accompanied by hybrid weakness under the balance of vegetative and reproductive growth. Therefore, in future studies on chrysanthemum breeding, a suitable balance point must be established to ensure the target flowering time under normal growth.

Ampelopsin induces MDA-MB-231 cell cycle arrest through cyclin B1-mediated PI3K/AKT/mTOR pathway in vitro and in vivo.

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.

Physiologically-based pharmacokinetic modeling to predict drug-drug interactions of dabigatran etexilate and rivaroxaban in the Chinese older adults.

INTRODUCTION: Drug-drug interaction (DDI) is one of the major concerns for the clinical use of NOACs in the older adults considering that coexistence of multiple diseases and comorbidity were common. Current guidelines on the DDI management were established based on clinical studies conducted in healthy adults and mainly focus on the Caucasians, whereas systemic and ethnic differences may lead to distinct management in the Chinese older adults. OBJECTIVES: To investigate the impact of aging on the DDI magnitude between P-gp and/or CYP3A4 inhibitors with dabigatran etexilate and rivaroxaban in older adults, providing additional information for the use in clinical practice. RESULTS: Compared with the simulated adult, the AUC of the simulated older adults increased by 42-88% (DABE) and 21-60% (rivaroxaban), respectively, during NOACs monotherapy. Simulation on DDIs predicted that verapamil and clarithromycin further increase the exposure of dabigatran by 29-72% and 40-47%, whereas clarithromycin, fluconazole, and ketoconazole increase the exposure of rivaroxaban by 21-30%, 16-24%, and 194-247% in the older adults. Overall, our simulation result demonstrated that aging and DDIs both increased the exposure of NOACs. However, aging does not have a drastic impact on the extent of DDIs. The DDI ratios of young and old older adults were similar to the adults and were also similar between Caucasians and Chinese. DISCUSSION: We further simulated the interactions under steady-state based on the EHRA guideline (2021). Our simulation results revealed that recommended reduced dosing regimen of dabigatran etexilate during comedication with verapamil and clarithromycin (110 and 75 mg BID for Chinese young and old older adults) will result in exposure (trough concentration) that was either slightly higher or similar to the trough concentration of patients with any bleeding events. Routine monitoring of bleeding risk is encouraged. Further studies on the use of rivaroxaban in Chinese older adults are warranted. CONCLUSION: Aging and DDI increases exposure of drug in Chinese older adults. However, aging does not have a drastic impact on the extent of DDIs. Clinical management of DDIs in Chinese older adults in the absence of complex polypharmacy can a priori be similar to the EHRA guideline but routine monitoring of bleeding risk is encouraged when dabigatran etexilate given with verapamil and clarithromycin.

Electroacupuncture improves follicular development and metabolism and regulates the expression of adiponectin, AMPK and ACC in an obese rat model of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and follicular arrest. Electroacupuncture (EA) has been shown to be effective at improving hyperandrogenism and follicular arrest in PCOS; however, its mechanism of action remains to be deciphered. OBJECTIVE: In this study, we investigated whether EA improved follicular development in an obese rat model of PCOS and regulated the expression of adiponectin, AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). METHODS: EA was administered at CV3, CV4 and ST40. Changes in body weight, paraovarian fat, estrus cycle, ovarian morphology, levels of related hormones, and glucose and lipid metabolism were evaluated. In addition, protein and mRNA expression of adiponectin, AMPK and ACC was measured. RESULTS: The body weight and paraovarian fat of rats in the EA group were reduced, while estrus cyclicity and ovarian morphology improved. Levels of free fatty acids, triglycerides, total cholesterol and low-density lipoprotein cholesterol were significantly reduced in the EA group, as well as blood glucose levels. Furthermore, levels of testosterone and luteinizing hormone were reduced in the EA group, while estradiol levels were increased. Protein and mRNA expression of adiponectin, AMPKα1 and liver kinase B1 (LKB1) was found to be increased in the EA group, while protein and mRNA expression of ACC were significantly reduced.Conclusion: Our findings suggest that EA improved follicular development and metabolism and regulated expression levels of adiponectin, AMPKα1, LKB1 and ACC in our obese rat model of PCOS.

Compressed variance component mixed model reveals epistasis associated with flowering in Arabidopsis.

Introduction: Epistasis is currently a topic of great interest in molecular and quantitative genetics. Arabidopsis thaliana, as a model organism, plays a crucial role in studying the fundamental biology of diverse plant species. However, there have been limited reports about identification of epistasis related to flowering in genome-wide association studies (GWAS). Therefore, it is of utmost importance to conduct epistasis in Arabidopsis. Method: In this study, we employed Levene's test and compressed variance component mixed model in GWAS to detect quantitative trait nucleotides (QTNs) and QTN-by-QTN interactions (QQIs) for 11 flowering-related traits of 199 Arabidopsis accessions with 216,130 markers. Results: Our analysis detected 89 QTNs and 130 pairs of QQIs. Around these loci, 34 known genes previously reported in Arabidopsis were confirmed to be associated with flowering-related traits, such as SPA4, which is involved in regulating photoperiodic flowering, and interacts with PAP1 and PAP2, affecting growth of Arabidopsis under light conditions. Then, we observed significant and differential expression of 35 genes in response to variations in temperature, photoperiod, and vernalization treatments out of unreported genes. Functional enrichment analysis revealed that 26 of these genes were associated with various biological processes. Finally, the haplotype and phenotypic difference analysis revealed 20 candidate genes exhibiting significant phenotypic variations across gene haplotypes, of which the candidate genes AT1G12990 and AT1G09950 around QQIs might have interaction effect to flowering time regulation in Arabidopsis. Discussion: These findings may offer valuable insights for the identification and exploration of genes and gene-by-gene interactions associated with flowering-related traits in Arabidopsis, that may even provide valuable reference and guidance for the research of epistasis in other species.

Revitalizing Skin Repair: Unveiling the Healing Power of Livisin, a Natural Peptide Calcium Mimetic.

When the skin is damaged, accelerating the repair of skin trauma and promoting the recovery of tissue function are crucial considerations in clinical treatment. Previously, we isolated and identified an active peptide (livisin) from the skin secretion of the frog Odorrana livida. Livisin exhibited strong protease inhibitory activity, water solubility, and stability, yet its wound-healing properties have not yet been studied. In this study, we assessed the impact of livisin on wound healing and investigated the underlying mechanism contributing to its effect. Our findings revealed livisin effectively stimulated the migration of keratinocytes, with the underlying mechanisms involved the activation of CaSR as a peptide calcium mimetic. This activation resulted in the stimulation of the CaSR/E-cadherin/EGFR/ERK signaling pathways. Moreover, the therapeutic effects of livisin were partially reduced by blocking the CaSR/E-cadherin/EGFR/ERK signaling pathway. The interaction between livisin and CaSR was further investigated by molecular docking. Additionally, studies using a mouse full-thickness wound model demonstrated livisin could accelerate skin wound healing by promoting re-epithelialization and collagen deposition. In conclusion, our study provides experimental evidence supporting the use of livisin in skin wound healing, highlighting its potential as an effective therapeutic option.

New Insight into Muscle-Type Cofilin (CFL2) as an Essential Mediator in Promoting Myogenic Differentiation in Cattle.

Meat quality and meat composition are not separated from the influences of animal genetic improvement systems; the growth and development of skeletal muscle are the primary factors in agricultural meat production and meat quality. Though the muscle-type cofilin (CFL2) gene has a crucial influence on skeletal muscle fibers and other related functions, the epigenetic modification mechanism of the CFL2 gene regulating meat quality remains elusive. After exploring the spatiotemporal expression data of CFL2 gene in a group of samples from fetal bovine, calf, and adult cattle, we found that the level of CFL2 gene in muscle tissues increased obviously with cattle age, whereas DNA methylation levels of CFL2 gene in muscle tissues decreased significantly along with cattle age by BSP and COBRA, although DNA methylation levels and mRNA expression levels basically showed an opposite trend. In cell experiments, we found that bta-miR-183 could suppress primary bovine myoblast differentiation by negatively regulated CFL2. In addition, we packaged recombinant adenovirus vectors for CFL2 gene knockout and overexpression and found that the CFL2 gene could promote the differentiation of primary bovine myoblasts by regulating marker genes MYOD, MYOG and MYH3. Therefore, CFL2 is an essential mediator for promoting myogenic differentiation by regulating myogenic marker genes in cattle myoblasts.