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.

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen.

Tenascin-C (TN-C) is an extracellular matrix glycoprotein markedly upregulated during liver fibrosis. The study is performed to explore the role of TN-C during the growth and activation of hepatic stellate cells (HSCs). We found that TN-C was accumulated accompanying with the HSC activation. Our data on cell migration assay revealed that the rTN-C treatment enhanced HSC migration in a dose- and time-dependent manner, but did not influence their proliferation. HSCs transfected with pTARGET-TN-C overexpression vector displayed increased the type I collagen (Col I) production. TN-C overexpression enhanced the process of HSC activation through TGF-ß1 signaling. Moreover, the anti-α9ß1 integrin antibody treatment blocked the TN-C-driven Col I increase in rat HSCs. Collectively, TN-C had a positive role in activation of HSCs mediated by TGF-ß1 and α9ß1 integrin, manifesting elevation of Col I production and promotion of cell migration. Our results provide a potential insight for the therapy of hepatic fibrosis.

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.

[Effects of alprostadil in prevention of portal vein thrombogenesis after splenectomy and devascularization: a clinical observation of 76 patients with portal hypertension].

OBJECTIVE: To investigate the effects of alprostadil (Lipo PGE1) in prevention of portal vein thrombogenesis (PVT) after splenectomy for portal hypertension. METHODS: Seventy-six patients with portal hypertension undergoing splenectomy and pericardial devascularization were randomly divided into 2 groups :treatment group (n = 40), receiving intravenous drip of injection of radix Salviae miliorrhazae (RSM) 40 ml and alprostadil 20 microg, both once a day since the third day after operation for 2 weeks and then oral administration of dropping pill of SM, and control group (n = 36), receiving intravenous drip of injection of RSM and taking enteric coated aspirin 3 times a day for 2 weeks and then taking dropping pill of SM. Platelets (PLT), prothrombin time (PT), and liver function were detected periodically. Color Doppler ultrasonography was conducted every week to observe the blood flow velocity and diameter of the portal and splenic veins, and if PVT event and ascites occurred. All patients were followed up for 8 - 20 months. RESULTS: No prolongation of coagulation time and bleeding tendency was found in both groups. The PLT number increased remarkably in the 7th to 14th days after operation without significant difference between the 2 groups (P >0.05). The PVT rate of the treatment group was 5.0%, significantly lower than that of the control group (25.0%, chi2 = 6.12, P < 0.05). The ascites rate of the treatment group was 10.0%, significantly lower than that of the control group (33.3%, chi2 = 7.44, P <0.01). The levels of ALT and total bilirubin 7 and 16 days after operation of the treatment group were all significantly lower than those of the control group (all P <0.05). CONCLUSION: Use of alprostadil early after devascularization is an effective and safe measure to prevent PVT, improve liver function, and decrease ascites rate.

Mycobiota of maize seeds revealed by rDNA-ITS sequence analysis of samples with varying storage times.

Fungi are an integral component of the plant microbiome. However, the composition and variation in the fungal communities (mycobiota) associated with seeds are poorly understood. In this study, we investigated the mycobiota of 11 maize seed samples with storage times ranging from 6 months to 12 years. Mycobiota were characterized by a culture-based approach, and fungal species were identified through rDNA-ITS sequence analyses. From a total of 169 pure fungal isolates obtained from both the seed surface and internal tissues, we identified 16 distinct species (belonging to 10 genera) associated with maize seeds, all but one of which were ascomycetes. Among these species, seven were exclusively isolated from internal tissues, two species were isolated only from the seed surface, and another six species were isolated from both the surface and internal tissues. Aspergillus niger was consistently found under all storage conditions and dominated fungal communities with a relative abundance of 36%-100%. Species of Fusarium (9%-40%) and Penicillium (9%-20%) were also frequently isolated, but other species appeared sporadically and were isolated from fewer than three seed stocks. According to our results, while the overall incidence of fungal infection generally declined with storage time, there was no consistent association between seed storage time and fungal species richness or relative abundance; furthermore, the composition of the mycobiota associated with maize seeds was highly variable among the samples. The detection of the four major mycotoxigenic fungal genera, specifically Aspergillus, Fusarium, Penicillium, and Alternaria, was alarming, and the isolation of a potential controlling agent as well as information about their temporal occurrence will contribute to the management of mycotoxins in the future.

Clinical epidemiological survey of gallbladder carcinoma in northwestern China, 2009-2013: 2379 cases in 17 centers.

OBJECTIVE: To analyze the clinical epidemiological characteristics of patients with gallbladder carcinoma recruited from 17 hospitals in five northwestern provinces of China (Shaanxi Province, Gansu Province, Qinghai Province, Ningxia Hui Autonomous Region, and Xinjiang Uygur Autonomous Region) from 2009 to 2013, and to summarize the clinical diagnosis and treatment data of gallbladder carcinoma. METHODS: Clinical information of 2379 patients with gallbladder carcinoma from 17 hospitals in five northwestern provinces of China was retrospectively collected and analyzed using the "Questionnaire for Gallbladder Carcinoma Patients in Northwestern Area of China." All information was verified with EpiData software and analyzed with SPSS 13.0 software. RESULTS: (1) Gallbladder carcinoma accounted for 2.7% (2379/86,609) of all biliary tract diseases during the study period, which was significantly higher than that from 1986 to 1998 (P < 0.001). (2) Gallbladder carcinoma was more prone to occur in elderly women. The male:female incidence ratio was 1.0:2.1, the average age of onset of disease was 63.7 ± 11.3 years, and the incidence was higher in farmers than in other occupational groups. (3) A total of 57.2% (1360/2379) of patients with gallbladder carcinoma also had gallstones. (4) Abdominal pain (1796/2379, 75.5%) and jaundice (727/2379, 30.6%) were the most common clinical manifestations, 81.2% (1527/1881) were positive in those receiving B ultrasound examinations and 90.7% (1567/1727) were positive in those undergoing computed tomography, and 64.5% (1124/1742) of patients with gallbladder carcinoma were positive for carbohydrate antigen (CA) 19-9. (5) The pathological type of gallbladder carcinoma was mainly moderately and poorly differentiated adenocarcinoma with a high degree of malignancy. At admission, 55.1% (1091/1981) of patients had stage IV cancer among patients with TNM staging information; 55.9% (1331/2379) had lymphatic metastasis, 29.7% (706/2379) had bile duct metastasis, and 53.1% (1263/2379) had liver metastasis. (6) A total of 283 patients (283/2379, 11.9%) had incidentally detected gallbladder carcinoma. (7) The rate of radical surgical resection was 30.4% (723/2379). CONCLUSION: The proportion of gallbladder carcinoma in biliary tract diseases in the northwestern area of China was significantly higher from 2009 to 2013 than from 1986 to 1998. Gallbladder carcinoma was common in older women and mainly diagnosed at an advanced stage. Compared with other surveys in different regions, the rate of metastasis in this survey was high, leading to a low resection rate. Populations at high risk should undergo B-ultrasound examinations at regular follow-up intervals to increase the rate of early diagnosis of gallbladder carcinoma.