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Transforming growth factor (TGF)-β1 is an important multifunctional cytokine in the TGF-β signaling pathway, which is involved in the molecular regulation of multiple activities, including follicle development and ovulation in female reproductive physiology. However, the biological function of TGF-β1 in follicular development and in regulating the proliferation or apoptosis of granulosa cells in small tail Han sheep remain unclear. In this study, we analyzed the expression levels of TGF-β1 in the ovary at the follicular stage in small tail Han sheep. We further examined the effects of TGF-β1 on the viability, proliferation, and apoptosis of granulosa cells. Differential expression of TGF-β1 at the mRNA and protein levels was detected in the ovaries between the beginning of estrus and at preovulation. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine (EdU) labeling, and flow cytometry assays showed that adding 5 and 10 ng/mL TGF-β1 could improve the viability and growth rate, reduce the apoptosis rate, and reduce the expression level of the pro-apoptotic factor Bcl-2-modifying factor (BMF) in granulosa cells. Treatment of 10 ng/mL TGF-β1 at all time points (except 72 h) significantly increased the positive rate of EdU labeling compared to that of the control group. RNA interference of SMAD4 reversed the decreased apoptosis rate caused by stimulation with 10 ng/mL TGF-β1, accompanied by a corresponding increase in the BMF expression level. Collectively, these results indicate that TGF-β1 plays a role in the ovarian follicular-phase activity of small tail Han sheep by inhibiting the apoptosis of sheep granulosa cells through the SMAD4/BMF pathway to promote proliferation and vitality. This study provides new insight into the molecular mechanism underlying TGF-β1 function regulation in granulosa cells, suggests a new target for the regulation of follicle development, and expands the new field of animal reproduction regulation technology. • TGF-β1 was differentially expressed in the ovary at the follicular stage in small tail Han sheep. • Adding 5 and 10 ng/mL TGF-β1 to cultured granulosa cells could improve the viability and growth rate, reduce the apoptosis rate. • The study initially reveals the role of the TGF-β1-SMAD4-BMF signaling axis in the regulation of ovarian granulosa cells of small tail Han sheep. [ABSTRACT FROM AUTHOR]

Salt stress is a major abiotic stress threatening plant growth and development throughout the world. In this study, we investigated the salt stress adaptation mechanism of Carex rigescens (Franch.) V. Krecz, a stress-tolerant turfgrass species with a wide distribution in northern China. Specifically, we analyzed the growth, physiology, and transcript expression patterns of two C. rigescens genotypes (Huanghua and Lvping No.1) exposed to salt stress. Results show that Huanghua demonstrated better growth performance, and higher turf quality (TQ), photochemical efficiency (Fv/Fm), relative water content (RWC), proline content, and lower relative electrolyte leakage (REL) during seven days of salt treatment compared to Lvping No.1, suggesting that Huanghua is more salt tolerant. Significant differences in reactive oxygen species (ROS), Malondialdehyde (MDA), melatonin, non-enzymatic antioxidants, lignin, and flavonoid content, as well as in antioxidant activity between Huanghua and Lvping No.1 after salt stress indicate the diverse regulation involved in salt stress adaptation in C. rigescens . These results, combined with those of the transcript expression pattern of involved genes, suggest that Huanghua is more active and efficient in ROS scavenging, Ca 2+ binding, and its phytohormone response than Lvping No.1. Meanwhile, Lvping No.1 showed relatively higher phenylpropanoid synthesis, using flavonoid and lignin as supplements for the inadequate ROS-scavenging capacity and the development of vascular tissues, respectively. These performances illustrate the differences between the two genotypes in multifaceted and sophisticated actions contributing to the tolerance mechanism of salt stress in C. rigescens . In addition, the significantly higher content of melatonin and the rapid induction of Caffeic acid O -methyltransferase ( COMT ) highlight the role of melatonin in the salt stress response in Huanghua. The results of our study expand existing knowledge of the complexity of the salt stress response involving the antioxidant system, Ca 2+ signaling, phytohormone response signaling, and phenylpropanoid pathways. It also provides a basis for further study of the underlying mechanism of salt tolerance in C. rigescens and other plant species. [ABSTRACT FROM AUTHOR]

Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma ( P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification. [ABSTRACT FROM AUTHOR]

• This study identified the important role of Bmf in the apoptosis of sheep GCs. • Bmf is essential for Smad4 knockdown to induce apoptosis of sheep GCs. • This study speculated that the TGF-β – Smad4 – Bmf axis may be critically involved in the proliferation of livestock GCs. Bcl-2-modifying factor (Bmf) functions to mediate follicular atresia and oocyte growth in mice. It has been proven that TGF-β can induce Bmf expression via the Smad4 pathway in a variety of cells, and then induce cell apoptosis. Based on this, we hypothesized that Smad4 and Bmf may play important roles in the apoptosis of granulosa cells (GCs) in domestic animals. This study used small-tailed Han sheep follicular GCs cultured in vitro as a model system, and overexpression or interference experiments, to explore the biological roles of Bmf and reveal the preliminary regulatory mechanisms between Smad4 and Bmf in the process of GCs' apoptosis. We found that the proliferation rate of sheep GCs was significantly increased after the knockdown of Bmf , whereas overexpressing Bmf increased the apoptosis rate of GCs, results also verified by the expression patterns of PCNA , Bcl-2 , and Bax genes. After the Smad4 knockdown, the apoptosis rate of GCs was increased, while the mRNA and protein expression of Bmf was significantly up-regulated. A rescue experiment verified that the Bmf knockdown could alleviate GCs' apoptosis induced by Smad4 knockdown. In conclusion, our study not only elucidated an important role for Bmf in the apoptosis of sheep GCs but also revealed a new regulatory pathway between Smad4 and Bmf in this process. [ABSTRACT FROM AUTHOR]

Soil salinity constrains growth, development and yield of alfalfa (Medicago sativa L.). To illustrate the molecular mechanisms responsible for salt tolerance, a comparative proteome analysis was explored to characterize protein profiles of alfalfa seedling roots exposed to 100 and 200 mM NaCl for three weeks. There were 52 differentially expressed proteins identified, among which the mRNA expressions of 12 were verified by Real-Time-PCR analysis. The results showed increase in abundance of ascorbate peroxidase, POD, CBS protein and PR-10 in salt-stressed alfalfa, suggesting an effectively antioxidant and defense systems. Alfalfa enhanced protein quality control system to refold or degrade abnormal proteins induced by salt stress through upregulation of unfolded protein response (UPR) marker PDIs and molecular chaperones (eg. HSP70, TCP-1, and GroES) as well as the ubiquitin‐proteasome system (UPS) including ubiquitin ligase enzyme (E3) and proteasome subunits. Upregulation of proteins responsible for calcium signal transduction including calmodulin and annexin helped alfalfa adapt to salt stress. Specifically, annexin (MsANN2), a key Ca2+-binding protein, was selected for further characterization. The heterologous of the MsANN2 in Arabidopsis conferred salt tolerance. These results provide detailed information for salt-responsive root proteins and highlight the importance of MsANN2 in adapting to salt stress in alfalfa. • Comparative proteomics study revealed 52 salt-responsive proteins of alfalfa root. • Upregulation of the proteins involved in antioxidation and defense suggested amelioration of oxidative stress. • Alfalfa enhanced protein quality control system (UPR and UPS) to refold or degrade abnormal proteins induced by salt stress. • The heterologous of the MsANN2 in Arabidopsis conferred salt tolerance. [ABSTRACT FROM AUTHOR]

Salt stress is a serious abiotic stressor impeding plant growth and crop production around the world. Plant glycosyltransferases are thought to serve important roles in dealing with stress conditions, however, the functional role of how UGTs cope with salt stress is not well understood. Carex rigescens (Franch.) V. Krecz, is a widely distributed species of turfgrass with strong salinity tolerance found in northern China. To investigate how the glycosyltransferase gene, CrUGT87A1 , functions in C. rigescens , we performed analyses of cloning, transcriptional expression, subcellular localization, and overexpression. The full-length sequence of CrUGT87A1 is 1455 bp with a 1338 bp length ORF, which encodes 445 amino acids, while CrUGT87A1 was found to be a nuclear and plasmalemma-localized protein. We found that the transcriptional expression of CrUGT87A1 was up-regulated under ABA, heat, salt, and drought treatments in leaf tissues. CrUGT87A1 overexpression in Arabidopsis plants had a significantly higher germination rate, better growth and physiology, and a higher expression levels of transcripts related to salt stress-related genes under high-salinity conditions, suggesting that CrUGT87A1 is involved in salt tolerance. The transcriptional expression of genes related to flavonoid-synthesis related and the flavonoid content reflected higher accumulations of flavonoids in transgenic plants. Our study demonstrated that CrUGT87A1 could play an important role in resisting salt stress due to increased flavonoid accumulation, which can promote antioxidation when dealing with high-salinity conditions. This study advances our collective understanding of the functional role of UGTs and can be used to improve the salt tolerance and breeding of crops and plants. • The expression of CrUGT87A1 was induced by ABA, heat, salt, and drought treatments in leaf tissues. • CrUGT87A1 was demonstrated as a nuclear and plasmalemma-localized protein. • Transgenic Arabidopsis conferred CrUGT87A1 could enhance salt tolerance. • CrUGT87A1 might affect plant salt tolerance by regulating the expression of stress marker genes and flavonoid content. [ABSTRACT FROM AUTHOR]

Saline-alkali stress is one of the main abiotic stresses that limits plant growth. Salt stress has been widely studied, but alkaline salt degradation caused by NaHCO 3 has rarely been investigated. In the present study, the alfalfa cultivar 'Zhongmu No. 1′ was treated with 50 mM NaHCO 3 (0, 4, 8, 12 and 24 h) to study the resulting enzyme activity and changes in mRNA, miRNA and metabolites in the roots. The results showed that the enzyme activity changed significantly after alkali stress treatment. The genomic analysis revealed 14,970 differentially expressed mRNAs (DEMs), 53 differentially expressed miRNAs (DEMis), and 463 differentially accumulated metabolites (DAMs). Combined analysis of DEMs and DEMis revealed that 21 DEMis negatively regulated 42 DEMs. In addition, when combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEMs and DAMs, we found that phenylpropanoid biosynthesis, flavonoid biosynthesis, starch and sucrose metabolism and plant hormone signal transduction played important roles in the alkali stress response. The results of this study further elucidated the regulatory mechanism underlying the plant response to alkali stress and provided valuable information for the breeding of new saline-alkaline tolerance plant varieties. [Display omitted] • Integrate transcriptome and metabolomics to analyse the alkaline stress of alfalfa. • Candidate genes, miRNAs and metabolites in response to alkaline stress in alfalfa were identified. • Alfalfa response to alkali is related to abscisic acid, ethylene, jasmonic acid and auxin signal transduction pathways. • Flavonoid synthesis was found to be associated with alkaline stress in alfalfa. • Five new miRNAs were identified, which could respond to alkaline stress. [ABSTRACT FROM AUTHOR]

Abstract: Background: Atrial remodeling is considered as the structural basis for the development and sustaining of atrial fibrillation (AF). Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) axis, a key regulatory system in bone metabolism, was recently identified in some cardiovascular disorders for its regulation to myocardial remodeling. We hypothesized that the OPG/RANK/RANKL axis is involved in development and perpetuation of AF by regulating atrial remodeling. Methods: Biopsies of right atrial appendage and clinical data were collected from sex- and age-matched 24 persistent AF, 24 paroxysmal AF, 24 sinus rhythm (SR) patients undergoing isolated mitral valve surgery and 24 healthy heart donors (normal controls). Results: A significantly increasing gradient of atrial expression of OPG, RANKL, RANK and RANKL/OPG ratio was identified in normal controls, SR and AF groups. RANKL/OPG ratio was also found significantly higher in paroxysmal AF than persistent AF. Furthermore, atrial expression and activity of the axis was statistically correlated with collagen III/I levels and ratio and the degree of interstitial fibrosis reflected by collagen volume fraction in right atrial appendages. Conclusions: The present findings suggest a potential role for known mediators of bone homeostasis in the pathogenesis of AF and possibly represent new targets for therapeutic intervention in AF. [Copyright &y& Elsevier]

Fructus Choerospondiatis is the dried and mature fruit of Choerospondias axillaris (Roxb.) Burtt et Hill. It has been used for a long time in Tibetan and Mongolian medicine, first recorded in the ancient Tibetan medicine book "Medicine Diagnosis of the King of the Moon" in the early 8th century. Fructus Choerospondiatis shows multiple pharmacological activities, especially in treating cardiovascular diseases. This paper reviews the progress in research on the botanical characteristics, traditional uses, chemical constituents, pharmacological activity, clinical studies, and quality control of Fructus Choerospondiatis. This review aims to summarize current research and provide a reference for further development and utilization of Fructus Choerospondiatis resources. The sources for this review include the Pharmacopeia of the People's Republic of China (2020), theses, and peer-reviewed papers (in both English and Chinese). Theses and papers were downloaded from electronic databases including Web of Science, PubMed, SciFinder, Scholar, Springer, and China National Knowledge Infrastructure.The search terms used were " Choerospondias axillaris ", " C. axillaris ", " Choerospondias axillaris (Roxb.) Burtt et Hill", "Fructus choerospondiatis", "Guangzao", "Lapsi", and "Lupsi". Fructus Choerospondiatis contains polyphenols, organic acids, amino acids, fatty acids, polysaccharides, and other chemical components. These ingredients contribute to its diverse pharmacological activities such as antioxidant activity, protection against myocardial ischemia-reperfusion injury, anti-myocardial fibrosis, heart rhythm regulation, anti-tumor, liver protection, and immunity enhancement. It also affects the central nervous system, with the ability to repair damaged nerve cells. Fructus Choerospondiatis , with its various chemical compositions and pharmacological activities, is a promising medicinal resource. However, it remains under-researched, particularly in pharmacodynamic material basis and quality control. These areas require further exploration by researchers in the future. [Display omitted] • This is the first review systemically summarized Choerospondiatis Fructus (CF). • The cardiovascular effect of CF was reviewed, which accords to its traditional use. • The structure-activity relationship of chemical constituents in CF was summarized. • The clinical uses of major prescriptions containing CF were summarized. • The possible quality control components of CF were summarized for the first time. [ABSTRACT FROM AUTHOR]

High salinity is one of the detrimental environmental factors restricting plant growth and crop production throughout the world. This study demonstrated that the GARP family transcription factor MtHHO3 is involved in response to salt stress and abscisic acid (ABA) signaling in Medicago truncatula. The transcription of MtHHO3 was repressed by salt, osmotic stress, and ABA treatment. The seed germination assay showed that, overexpression of MtHHO3 in Arabidopsis thaliana caused hypersensitivity to salt and osmotic stress, but increased resistance to ABA inhibition. Overexpression of MtHHO3 in M. truncatula resulted in decreased tolerance of salinity, while loss-of-function mutants mthho3-1 and mthho3-2 were more resistant to salt stress compared with wild-type plants. qRT-PCR analyses showed that MtHHO3 downregulated the expression of genes in stress and ABA responsive pathways. We further demonstrated that MtHHO3 repressed the transcription of the pathogenesis-related gene MtPR2 by binding to its promoter. Overall, these results indicate that MtHHO3 negatively regulates salt stress response in plants and deepen our understanding of the role of the GARP subfamily transcription factors in modulating salt stress and ABA signaling. • MtHHO3 is involved in salt stress response and ABA signaling pathway. • Overexpression of MtHHO3 decreases salt stress tolerance in plants. • Disruption of MtHHO3 confers enhanced salt stress tolerance in Medicago trncatula. • HHO3 regulates the expression of PR2 , a pathogenesis-related gene. [ABSTRACT FROM AUTHOR]

Abstract: New norcantharidin-conjugated hydroxypropyltrimethyl ammonium chloride chitosan derivatives (NCTD-HACCs) were synthesized and characterized by 1H NMR, Fourier-transform infrared spectroscopy (FT-IR), and wide-angle X-ray diffraction (WAXD). Two NCTD-HACCs with different degrees of substitution (DS) (12.2% and 24.8%) were obtained, which had good water solubility. NCTD was released from the NCTD-HACCs via hydrolysis, faster in pH 5.0 than pH 7.4 and presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. Fluorescence microscope and flow cytometry analysis demonstrated that the NCTD-HACC was endocytosized into MGC80-3 cells and the uptaken amount increased as incubation time. Compared with free NCTD, the NCTD-HACCs showed lower in vitro anti-tumor activity against human gastric cancer MGC80-3 cells, but higher in vivo tumor growth inhibition in S180 tumor-bearing mice. The in vivo near-infrared (NIR) fluorescence real-time imaging result showed the fluorescence intensity in tumor was much higher than that in heart, liver, spleen and lung (except kidney) after i.v. injection of the FITC-labeled NCTD-HACC2, indicating specific accumulation of the NCTD-HACC in tumor. [Copyright &y& Elsevier]