Galectin-3 critically mediates the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling

We previously documented that M2-like macrophages exert a hepatoprotective effect in acute-on-chronic liver failure (ACLF) by inhibiting necroptosis signalling. Nevertheless, the molecular mechanism behind this hepatoprotection still needs to be further dissected. Galectin-3 (GAL3) has been reported to be critically involved in the pathogenesis of multiple liver diseases, whereas the potential role of GAL3 in ACLF remains to be explored. Herein, we hypothesised that GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting necroptosis. To test this hypothesis, we first assessed the expression of GAL3 in control and fibrotic mice with or without acute insult. Second, loss- and gain-of-function experiments of GAL3 were performed. Third, the correlation between GAL3 and M2-like macrophage activation was analysed, and the potential role of GAL3 in M2-like macrophage-conferred hepatoprotection was confirmed. Finally, the molecular mechanism underlying GAL3-mediated hepatoprotection was dissected. GAL3 was found to be obviously upregulated in fibrotic mice with or without acute insult but not in acutely injured mice. Depletion of GAL3 aggravated hepatic damage in fibrotic mice upon insult. Conversely, adoptive transfer of GAL3 provided normal mice enhanced resistance against acute insult. The expression of GAL3 is closely correlated with M2-like macrophage activation. Through adoptive transfer and depletion experiments, M2-like macrophages were verified to act as a major source of GAL3. Importantly, GAL3 was confirmed to hold a pivotal place in the hepatoprotection conferred by M2-like macrophages through loss- and gain-of-function experiments. Unexpectedly, the depletion and adoptive transfer of GAL3 resulted in significant differences in the expression levels of pyroptosis but not necroptosis signalling molecules. Taken together, GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling. Our findings provide novel insights into the pathogenesis and therapy of ACLF.Subject terms: Inflammasome, Necroptosis     

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR) to neoadjuvant chemotherapy(NAC). Here, we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS) in 755 HRpositive breast cancer patients(273, 265, and 217 in the training, internal, and external validation sets, respectively). This model,pres...     

Modification of alternative splicing in bovine somatic cell nuclear transfer embryos using engineered CRISPR-Cas13d

Animal cloning can be achieved by somatic cell nuclear transfer(SCNT), but the resulting live birth rate is relatively low. We previously improved the efficiency of bovine SCNT by exogenous melatonin treatment or by overexpression of lysine-specific demethylase 4D(KDM4D) and 4E(KDM4E). In this study, we revealed abundant alternative splicing(AS) transitions during fertilization and embryonic genome activation, and demonstrated abnormal AS in bovine SCNT embryos compared with in vitro fertilized ...     

强度石漠化区不同植被修复模式下土壤螨类群落差异

石漠化治理区不同植被修复模式下的土壤螨类群落差异反映了生态系统的恢复状况,可籍以反映石漠化治理的生态效果。2014年1月、4月、8月和10月,对贵州花江喀斯特峡谷区顶坛小流域强度石漠化区域的"花椒"、"金银花"、"花椒+金银花"3种植被修复生境的土壤螨类进行了调查,共捕获土壤螨类1372头,隶属3目55科89属。采用类群(属)数、个体数量、个体密度、多样性指数(H')、丰富度指数(SR)、均匀性指数(J)、相似性指数(CN)、捕食性螨类成熟度指数(MI)和甲螨MGP类群等参数对土壤螨类群落差异进行了表征。结果显示,花椒林拥有较丰富的螨类属,金银花林拥有较高的的个体数量和个体密度。不同模式下的科、属类群组成呈现差异;属数、个体数量存在一定的季节差异,花椒林的螨类属数、金银花林的螨类个体数量和个体密度呈现一定的表聚性;群落多样性大多存在季节差异;捕食性革螨以r选择型为主,甲螨主要为O型和M型。研究表明,强度石漠化在不同植被修复模式下,土壤螨类生物生态类群存在差异,土壤生态系统仍处于修复之中,其中螨类优势属、具有典型生物学与生态学特性差异的螨类类群对石漠化治理的生态效果具有重要的指示作用。     

溶藻弧菌群体基因组学研究

溶藻弧菌(Vibrio alginolyticus)是一种能够对人类以及鱼、虾、贝类等水产品致病的弧菌,给人类健康带来威胁,也给水产养殖业造成巨大的经济损失.目前该物种基于全基因组的遗传多样性和重要遗传元件研究报道较少.本研究对采集自全国4个省份的68株溶藻弧菌进行高通量测序,获得全基因组序列,并结合113株公开发表的...     

Development of a biosensor assessing SARS-CoV-2 main protease proteolytic activity in living cells for antiviral drugs screening

Highlights:
The biosensor reported in our study can monitor SARS-CoV-2 M^pro activity in living cells instead of in vitro solutions.
The biosensor reported in our study is sensitive and easy to operate.
It is suitable for high-throughput screening.
It has the potential to be used in small animal models.     

Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration

Poor healing of cutaneous wounds is a common medical problem in the field of traumatology. Due to the intricate pathophysiological processes of wound healing, the use of conventional treatment methods, such as chemical molecule drugs and traditional dressings, have been unable to achieve satisfactory outcomes. Within recent years, explicit evidence suggests that mesenchymal stem cells (MSCs) have great therapeutic potentials on skin wound healing and regeneration. However, the direct application of MSCs still faces many challenges and difficulties. Intriguingly, exosomes as cell-secreted granular vesicles with a lipid bilayer membrane structure and containing specific components from the source cells may emerge to be excellent substitutes for MSCs. Exosomes derived from MSCs (MSC-exosomes) have been demonstrated to be beneficial for cutaneous wound healing and accelerate the process through a variety of mechanisms. These mechanisms include alleviating inflammation, promoting vascularization, and promoting proliferation and migration of epithelial cells and fibroblasts. Therefore, the application of MSC-exosomes may be a promising alternative to cell therapy in the treatment of cutaneous wounds and could promote wound healing through multiple mechanisms simultaneously. This review will provide an overview of the role and the mechanisms of MSC-derived exosomes in cutaneous wound healing, and elaborate the potentials and future perspectives of MSC-exosomes application in clinical practice.