Cryo-EM structures of orphan GPR21 signaling complexes.

GPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling to multiple G proteins in the absence of any known endogenous agonist or synthetic ligand. Here, we present the structures of ligand-free human GPR21 bound to heterotrimeric miniGs and miniG15 proteins, respectively. We identified an agonist-like motif in extracellular loop 2 (ECL2) that occupies the orthosteric pocket and promotes receptor activation. A side pocket that may be employed as a new ligand binding site was also uncovered. Remarkably, G protein binding is accommodated by a flexible cytoplasmic portion of transmembrane helix 6 (TM6) which adopts little or undetectable outward movement. These findings will enable the design of modulators for GPR21 for understanding its signal transduction and exploring opportunity for deorphanization.

Adsorption of Pb (II) and Cu (II) by magnetic beads loaded with xanthan gum.

Green and environmentally friendly and efficient separation adsorbents have attracted much attention in the treatment of heavy metal ions wastewater. In this study, xanthan gum (XG) was supported by fly ash magnetic beads (FAMB) to prepare adsorbent XG@FAMB. The effects of XG@FAMB dosage, pH value of the solution, adsorption time, and initial Pb (II) and Cu (II) concentration on its adsorption performance for Pb (II) and Cu (II) were investigated. The results show that under the conditions of pH 6, dosage of XG@FAMB 4.0 g/L, adsorption time 120 min, and initial concentration 60 mg/L, the maximum adsorption capacity of XG@FAMB for Pb (II) and Cu (II) was 14.93 mg/g and 14.88 mg/g, respectively. The adsorption process of Pb (II) and Cu (II) by XG@FAMB could be better described by the quasi-second-order kinetic model and Langmuir isothermal adsorption model, that is, the adsorption process is monolayer adsorption controlled by chemical action. The adsorption mechanism is that Pb (II) and Cu (II) coordinate with oxygen-containing functional groups hydroxyl and carboxyl on XG@FAMB surface, accompanied by electrostatic adsorption. XG@FAMB has the advantages of environmental protection of XG and easy solid-liquid separation of FAMB, and has a good removal effect on Pb (II) and Cu (II).

Impact of intracytoplasmic sperm injection in women with non-male factor infertility: A systematic review and meta-analysis.

Objective: The purpose of this study is to determine whether intracytoplasmic sperm injection (ICSI) is beneficial in patients with non-male factor infertility. Methods: This systematic review and meta-analysis included articles from inception to May 2022. Published studies of non-male factor infertile women undergoing ICSI or in vitro fertilization (IVF) included in PubMed, Embase, web of science, Wanfang Database, and CNKI were searched by computer, without language restrictions. A random-effect model was applied to calculate the risk ratios (RRs) and their 95% confidence intervals (CIs). Letters, case reports, and review articles including meta-analyses and expert opinions were excluded. The primary endpoints were laboratory outcomes and pregnancy outcomes. The Secondary endpoints were neonatal outcomes. Results: Six randomized controlled studies and 20 retrospective cohort studies met the inclusion criteria. In meta-analytic forest plots, compared with IVF, those who received ICSI treatment were not different in fertilization rate (RR = 0.99, 95% CI [0.90-1.09], P = 0.88), total fertilization failure rate (RR = 1.30, 95% CI [1.17-1.45], P < 0.00001), and good quality embryo rate (RR = 0.94, 95% CI [ 0.86-1.02], P = 0.15), clinical pregnancy rate (RR = 0.84, 95% CI [0.70-1.01], P = 0.06), live birth rate (RR = 0.89, 95% CI [0.77-1.03], P = 0.13), miscarriage rate (RR = 1.06, 95% CI [0.78-1.43], P = 0.71), preterm neonatal delivery rate (RR = 0.92, 95% CI [0.67-1.26], P = 0.61), and low neonatal weight rate (RR = 1.13, 95% CI [0.80-1.61], P = 0.48). However, the implantation rate of IVF was better than ICSI (RR = 0.77, 95% CI [0.64-0.93], P = 0.005). In the subgroup analysis of the live birth rate of fresh embryo transfer, IVF performed in those ≥35 years had a higher live birth rate (RR = 0.82, 95% CI [0.78-0.83], P < 0.001). Conclusion: The findings of this study indicate that ICSI is not superior to IVF in the treatment of infertility related to non-male factors. In order to confirm this result, more high-quality clinical studies are needed.