An agricultural drought index to incorporate the irrigation process and reservoir operations:A case study in the Tarim River Basin

To help the decision making process and reduce climate change impacts, hydrologically-based drought indices have been used to determine drought severity in the Tarim River Basin (TRB) over the past decades. As the major components of the surface water balance, however, the irrigation process and reservoir operations have not been incorporated into drought indices in previous studies. Therefore, efforts are needed to develop a new agricultural drought index, which is based on the Variable Infiltration Capacity (VIC) model coupled with an irrigation scheme and a reservoir module. The new drought index was derived from the simulated soil moisture data from a retrospective VIC simulation from 1961 to 2007 over the irrigated area in the TRB. The physical processes in the coupled VIC model allow the new agricultural drought index to take into account a wide range of hydrologic processes including the irrigation process and reservoir operations. Notably, the irrigation process was found to dominate the surface water balance and drought evolution in the TRB. Furthermore, the drought conditions identified by the new agricultural drought index presented a good agreement with the historical drought events that occurred in 1993–94, 2004, and 2006–07, respectively. Moreover, the spatial distribution of coupled VIC model outputs using the new drought index provided detailed information about where and to what extent droughts occurred

Impacts of different culture times on pregnancy outcomes after thawing of cleavage stage embryos

Abstract Objective This study assessed the impacts of in vitro culture times of cleavage embryos on clinical pregnancy outcomes. Methods This retrospective cohort study was performed at the Reproductive Medicine Department of Hainan Modern Women and Children’s Hospital in China between January 2018 and December 2022. Patients who first underwent frozen embryo transfer with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles on day 3 were included. According to the time of embryo culture after thawing, the embryos were divided into long-term culture group(18-20 h) and short-term culture group (2-4 h). The clinical pregnancy rate was regarded as he primary outcome. To minimize confounding factors and reduce selection bias, the propensity score matching was used to balance the effects of known confounding factors and to reduce selection bias. Stratified analyses and multiple logistic regression analyses were used to evaluate the risk factors affecting the clinical pregnancy outcomes after matching. Results General characteristics between two groups were comparable after matching. In the long-term culture group, 266/381 (69.81%) embryos had more than 10 blastomeres, and 75/381 (19.68%) reached the morula stage. After overnight culture, the implantation rate (27.97% vs. 14.28%, P = 0.018) and clinical pregnancy rate (38.46% vs. 22.5%, P = 0.05) were increased in the group with proliferating blastomeres. The long-term culture group trended to have a higher clinical pregnancy rate compared with the short-term culture group (35.74% vs. 29.79%). No statistical differences in clinical pregnancy outcomes between the two groups were observed after matching, including the rates of implantation (25.46% vs23.98%), miscarriages (25% vs. 22.85%), ongoing pregnancy rate (76.2% vs. 77.15%) and live birth rate (26.8% vs. 22.98%). Stratified analyses were performed according to the age of the patients. After matching, there were no significant differences in the clinical pregnancy, implantation and miscarriage rates between the two groups for patients > 35 or ≤ 35 years of age. Subgroup analyses were performed according to the quality of the transferred embryos. There were no significant differences in the clinical outcomes, between two groups after embryos transferred with the same quality. Multivariate Logistic regression analysis was used to evaluate the influencing factors of clinical pregnancy outcomes after matching. Culture time was not found to be an independent predictor for clinical pregnancy [OR 0.742, 95%CI 0.487 ~ 1.13; P = 0.165]. The age of oocyte retrieval [OR 0.906, 95%CI 0.865 ~ 0.949; P <0.001] and the number of high-quality embryos transferred [OR 1.787, 95%CI 1.256 ~ 2.543; P = 0.001] were independent factors affecting clinical pregnancy outcomes. Conclusions In vitro 18–20 h culture of embryos with either good-or non-good-quality will not adversely affect the clinical pregnancy

HSP90 C-terminal domain inhibition promotes VDAC1 oligomerization via decreasing K274 mono-ubiquitination in Hepatocellular Carcinoma

Voltage-dependent anion-selective channel protein 1 (VDAC1) is the most abundant protein in the mitochondrial outer membrane and plays a crucial role in the control of hepatocellular carcinoma (HCC) progress. Our previous research found that cytosolic molecular chaperone heat shock protein 90 (Hsp90) interacted with VDAC1, but the effect of the C-terminal and N-terminal domains of Hsp90 on the formation of VDAC1 oligomers is unclear. In this study, we focused on the effect of the C-terminal domain of Hsp90 on VDAC1 oligomerization, ubiquitination, and VDAC1 channel activity. We found that Hsp90 C-terminal domain inhibitor Novobiocin promoted VDAC1 oligomerization, release of cytochrome c, and activated mitochondrial apoptosis pathway. Atomic coarse particle modeling simulation revealed C-terminal domain of Hsp90α stabilized VDAC1 monomers. The purified VDAC1 was reconstituted into a planar lipid bilayer, and electrophysiology experiments of patch clamp showed that the Hsp90 C-terminal inhibitor Novobiocin increased VDAC1 channel conductance via promoting VDAC1 oligomerization. The mitochondrial ubiquitination proteomics results showed that VDAC1 K274 mono-ubiquitination was significantly decreased upon Novobiocin treatment. Site-directed mutation of VDAC1 (K274R) weakened Hsp90α-VDAC1 interaction and increased VDAC1 oligomerization. Taken together, our results reveal that Hsp90 C-terminal domain inhibition promotes VDAC1 oligomerization and VDAC1 channel conductance by decreasing VDAC1 K274 mono- ubiquitination, which provides a new perspective for mitochondria-targeted therapy of HCC