Piwi/piRNAs control food intake by promoting neuropeptide F expression in locusts

Animal feeding, which directly affects growth and metabolism, is an important physiological process. However, the contribution of PIWI proteins and PIWI‐interacting RNAs (piRNAs) to the regulatory mechanism of animal feeding is unknown. Here, we report a novel function of Piwi and piRNAs in regulating food intake in locusts. Our study shows that the locust can serve as a representative species for determining PIWI function in insects. Knockdown of Piwi1 expression suppresses anabolic processes and reduces food consumption and body weight. The reduction in food intake by knockdown of Piwi1 expression results from decreased expression of neuropeptide NPF1 in a piRNA‐dependent manner. Mechanistically, intronic piRNAs might enhance RNA splicing of NPF1 by preventing hairpin formation at the branch point sites. These results suggest a novel nuclear PIWI/piRNA‐mediated mechanism that controls food intake in the locust nervous system.     

Exostosin glycosyltransferase 1 reduces porcine reproductive and respiratory syndrome virus infection through proteasomal degradation of nsp3 and nsp5

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a serious threat to the swine industry worldwide. Exostosin glycosyltransferase 1 (EXT1), an enzyme involved in the biosynthesis of heparin sulfate, has also been reported to be a host factor essential for a wide variety of pathogens. However, the role of EXT1 in PRRSV infection remains uncharted. Here, we identified that PRRSV infection caused an increase of EXT1 expression. EXT1 knockdown promoted virus infection, whereas its overexpression inhibited virus infection, suggesting an inhibitory function of EXT1 to PRRSV infection. We found that EXT1 had no effects on the attachment, internalization, or release of PRRSV but did restrict viral RNA replication. EXT1 was determined to interact with viral nonstructural protein 3 (nsp3) and nsp5 via its N-terminal cytoplasmic tail and to enhance K48-linked polyubiquitination of these two nsps to promote their degradation. Furthermore, the C-terminal glycosyltransferase activity domain of EXT1 was necessary for nsp3 and nsp5 degradation. We also found that EXT2, a EXT1 homolog, interacted with EXT1 and inhibited PRRSV infection. Similarly, EXT1 effectively restricted porcine epidemic diarrhea virus and porcine enteric alphacoronavirus infection in Vero cells. Taken together, this study reveals that EXT1 may serve as a broad-spectrum host restriction factor and suggests a molecular basis for the potential development of therapeutics against PRRSV infection.     

Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2

Host cellular receptors play key roles in the determination of virus tropism and pathogenesis.However,little is known about SARS-CoV-2 host receptors with the e...     

A mini-review on ion fluxes that regulate NLRP3 inflammasome activation

The activation of NLR family pyrin domain containing 3(NLRP3)inflammasome can be induced by a wide spectrum of activators.This is unlikely achieved by the binding of different activators directly to the NLRP3 protein itself,as the activators found so far show different forms of chemical structures.Previous studies have shown that these activators can induce potassium ion(K+)and chloride ion(Cl?)efflux,calcium(Ca2+)and other ion mobilization,mitochondrial dysfunction,and lysosomal disruption,all of which are believed to cause NLRP3 inflammasome activation;how these events are induced by the activators and how they coordinate with each other in inducing the NLRP3 inflammasome activation are not fully understood.Increasing evidence suggests that the coordinated change of intracellular ion concentrations may be a common mechanism for the NLRP3 activation by different activators.In this mini-review,we present a brief summary of the current knowledge about how different ionic flows(including K+,sodium ion,Ca2+,magnesium ion,manganese ion,zinc ion,iron ion,and Cl?)are involved in regulating the NLRP3 inflammasome activation in macrophages.     

Cancer-associated adipocytes promote the invasion and metastasis in breast cancer through LIF/CXCLs positive feedback loop

Cancer-associated adipocytes (CAAs), which are adipocytes transformed by cancer cells, are of great importance in promoting the progression of breast cancer. However, the underlying mechanisms involved in the crosstalk between cancer cells and adipocytes are still unknown. Here we report that CAAs and breast cancer cells communicate with each other by secreting the cytokines leukemia inhibitory factor (LIF) and C-X-C subfamily chemokines (CXCLs), respectively. LIF is a pro-inflammatory cytokine secreted by CAAs, which promotes migration and invasion of breast cancer cells via the Stat3 signaling pathway. The activation of Stat3 induced the secretion of glutamic acid-leucine-arginine (ELR) motif CXCLs (CXCL1, CXCL2, CXCL3 and CXCL8) in tumor cells. Interestingly, CXCLs in turn activated the ERK1/2/NF-κB/Stat3 signaling cascade to promote the expression of LIF in CAAs. In clinical breast cancer pathology samples, the up-regulation of LIF in paracancerous adipose tissue was positively correlated with the activation of Stat3 in breast cancer. Furthermore, we verified that adipocytes enhanced lung metastasis of breast cancer cells, and the combination of EC330 (targeting LIF) and SB225002 (targeting C-X-C motility chemokine receptor 2 (CXCR2)) significantly reduced lung metastasis of breast cancer cells in vivo. Our findings reveal that the interaction of adipocytes with breast cancer cells depends on a positive feedback loop between the cytokines LIF and CXCLs, which promotes breast cancer invasion and metastasis.     

Exosomes from adipose-derived mesenchymal stem cells promote survival of fat grafts by regulating macrophage polarization via let-7c

The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years.Owing to their anti-inflammatory ef...     

树突状表皮T细胞在胸腺内发育的研究进展

树突状表皮T淋巴细胞(DETC),特异性分布在表皮组织内,在皮肤免疫监视,皮肤伤面愈合中发挥重要作用.小鼠DETC发育仅涉及胚胎14.5 ～ 18 d这一短暂时间窗,而后则不再产生这类细胞.本综述拟从DETC T细胞受体(TCR)基因重排特点及调控机制,DETC在胸腺中的阳性选择及调控机制等方面进行论述,以期对DETC...