Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

Downregulation of lncRNA EPB41L4A-AS1 promotes gastric cancer cell proliferation, migration and invasion.

BACKGROUND: The incidence of gastric cancer ranks the first among digestive tract tumors in China. However, there are no specific symptoms in the early stage of the tumor and the diagnosis process is complex, so more effective detection methods are very needed. In this study, a novel long noncoding RNA (lncRNA) was introduced as a diagnostic biomarker for gastric cancer, which brought new thinking to the exploration of its pathological mechanism and clinical prediction. METHODS: The level of lncRNA EPB41L4A-AS1 (EPB41L4A-AS1) in gastric cancer serum and cells was verified via real-time quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve was performed based on the EPB41L4A-AS1 level, and the diagnostic possibility of EPB41L4A-AS was analyzed. The chi-square test evaluated the correlation between EPB41L4A-AS expression and clinical information. The cells were cultured and transfected in vitro, and the mediations of abnormal EPB41L4A-AS level on the viability and motility of gastric cancer cells were verified through cell counting kit-8 (CCK-8) and Transwell assay. Furthermore, luciferase activity assay was performed to confirm the sponge molecule microRNA-17-5p (miR-17-5p) of EPB41L4A-AS1. RESULTS: EPB41L4A-AS1 was decreased in gastric cancer, and low EPB41L4A-AS1 level indicated resultful diagnostic value. Overexpression of EPB41L4A-AS1 inhibited the activity of gastric cancer cells, while knockdown of EPB41L4A-AS1 promoted tumor deterioration. EPB41L4A-AS1 directly targeted and regulated the expression ofmiR-17-5p. CONCLUSION: This study elaborated that EPB41L4A-AS1 is lowly expressed in gastric cancer. Silencing EPB41L4A-AS1 was beneficial to cell proliferation, migration, and invasion. EPB41L4A-AS1 provides a new possibility for the diagnosis of gastric cancer patients by targeting miR-17-5p.

MiR-21-mediated Metabolic Alteration of Cancer-associated Fibroblasts and Its Effect on Pancreatic Cancer Cell Behavior: Retraction.

[This retracts the article DOI: 10.7150/ijbs.22555.].

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvß3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM: To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS: SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 µg/kg cerulein plus lipopolysaccharide. mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvß3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS: The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8's beneficial effects in SAP-induced liver injury. CONCLUSION: MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVß3/5.