We found that MANF expression and secretion are dramatically up-regulated during hepatic I/R. Hepatocyte-specific MANF knockout aggravates the I/R injury through the over-activated ER stress. The systemic administration of rhMANF before ischaemia has the potential to ameliorate I/R-triggered UPR and liver injury. click here Further study showed that MANF deficiency activated ATF4/CHOP and JNK/c-JUN/CHOP pathways, and rhMANF inhibited the activation of the two proapoptotic pathways caused by MANF deletion. Collectively, our study unravels a previously unknown relationship among MANF, UPR and hepatic I/R injury.Collectively, our study unravels a previously unknown relationship among MANF, UPR and hepatic I/R injury.The present study aimed to investigate the palyno-morphological features of species of family Vitaceae from Pakistan. A total of nine species, belonging to four genera were collected, pressed, identified, and then analyzed microscopically. Both quantitative and qualitative characters of the pollen grains were recorded including polar and equatorial diameter, P/E ratio, number of colpi and pores, exine thickness and shapes of the pollen in both polar and equatorial view, and exine sculpturing using Leica microscope fitted with camera Meiji Infinity 1 and then analyzed statistically using software IBM SPSS Statistics 20. The results of the present study demonstrated the variations in polar and equatorial diameter, exine thickness, P/E ratio, pollen shape, and exine sculpturing of the studied species and highlighted the significance of pollen morphology as an identification tool. The present study may contribute to better understand the classification at genus level, which will support the future phylogenetic characterization of the family. The association between depression and poor medication adherence is based on cross-sectional studies and cohort studies that measure adherence rates after depression status is determined. However, depressive symptoms occur well before diagnosis. This study examined adherence patterns in the year before a depressive episode. This retrospective cohort study followed new metformin users identified in Alberta Health's administrative data between 2008 and 2018. Depressive episodes starting ≥1year after metformin initiation were identified using a validated case definition. Controls were randomly assigned a pseudo depression date. Adherence to oral antihyperglycemic medications was estimated using proportion of days covered (PDC) and group-based trajectory models to explore the association between depression and poor adherence (PDC<0.8). A depressive episode occurred in 17,418 (10.6%) of 165,056 new metformin users. Individuals with depression were more likely to have poor adherence compared to controls (adjusted odds ratio 1.21; 95% CI 1.17, 1.26). Five trajectories were identified nearly perfect adherence (PDC >0.95 [34.8% of cohort]), discontinued (PDC=0 [18.3% of cohort], poor initial adherence (PDC 0.75) that declined either rapidly (9.2% of cohort) or gradually (30.1% of cohort), and poor initial adherence (PDC 0.26) that increased gradually (7.6% of cohort). Individuals with depression were more likely to be in one of the four trajectories of poor adherence compared to controls (adjusted odds ratio 1.24; 95% CI 1.19-1.29). Poor medication adherence occurs in the year before a depressive episode; therefore, poor medication use patterns could be used as an early warning sign for depression.Poor medication adherence occurs in the year before a depressive episode; therefore, poor medication use patterns could be used as an early warning sign for depression.Tumor angiogenesis is required for tumor growth and metastasis. Interleukin-35 (IL35), a member of the IL12 family, is a dimer composed of IL12A and EBV-induced gene 3（EBI3）. Elevated plasma IL35 levels have been reported to be associated with the occurrence and development of tumors. However, the role of IL35 in the angiogenesis of gastric cancer (GC) is still unclear. Here, we report that expression of IL35 is correlated with higher microvessel density, distant metastasis and poor prognosis in GC. Moreover, in vitro tube formation assays were performed to show that IL35 may contribute to the tube formation abilities of human umbilical vein endothelial cells. IL12A was observed to be the dominant subunit in promotion of tube formation. IL12A also inhibited expression of tissue inhibitor of metalloproteinase 1 and enhanced expression of plasminogen activator inhibitor 1 and insulin-like growth factor-binding protein 1 in a GC cell line. In conclusion, our data suggest that IL35 is involved in angiogenesis and is associated with poor prognosis for GC.To conduct a systematic review and meta-analysis investigating the effect of tofacitinib and baricitinib on venous thromboembolism (VTE) risk. Search of PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, LILACS, and Google Scholar databases to identify controlled observational and clinical trials reporting on adverse effects in patients treated with oral tofacitinib or baricitinib up to July 2020. The outcome measure was occurrence of VTE events. We analyzed 59 studies involving 14,335 patients treated with tofacitinib or baricitinib and 11,612 patients who received another active drug or placebo. The meta-analysis showed an odds ratio (OR) for VTE events of 0.29 (95% confidence interval [CI] = 0.10-0.84) overall for tofacitinib based on data from 10 clinical trials with 15 treatment arms; similar ORs were observed for the 10 mg/d dose (OR = 0.18; 95% CI = 0.02-1.60) and the 20 mg/d dose (OR = 0.19; 95% CI = 0.04-0.91). The ORs for VTE events for baricitinib were 3.39 (95% CI = 0.82-14.04) overall, 3.05 (95% CI = 0.12-75.43) for 2 mg, 3.64 (95% CI = 0.59-22.46) for 4 mg, and 3.0 (95% CI = 0.12-76.49) for 7 mg. The indirect meta-analysis comparing tofacitinib with baricitinib (10 clinical trials with 15 treatment arms) showed an OR for VTE events of 0.086 (95% CI = 0.02-0.51) for tofacitinib and a superior safety profile for VTE events. In the meta-regression analysis (19 clinical trials with 21 treatment arms), the effect was 0.02 (95% CI = -0.04 to 0.08) for tofacitinib and -0.01 (95% CI = -1.29 to 1.26 for baricitinib. Plotting of the data for tofacitinib showed that VTE risk increased with high doses. The effect, however, was less than 1 for the 10-mg and 20-mg doses, indicating a protective effect. This effect was not observed for baricitinib. Tofacitinib is not associated with an increased risk of VTE and has a superior safety profile to baricitinib in this respect. Tofacitinib may exert a protective effect against VTE.