In situ architecture and membrane fusion of SARS-CoV-2 Delta variant.

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.

The quantum confinement effects on the electronic properties of monolayer GeS nanoribbon with tube-edged reconstruction.

Monolayer α-phase GeS is promising for many novel applications due to its high carrier mobility and suitable bandgap. Recently, the metal and nonmetal zigzag edges of monolayer α-phase GeS have been predicted to undergo universal ZZ(Ge-Tube)/ZZ(S-R) edge reconstruction. Therefore, studies on GeSNR should be reconsidered. In this paper, we study the quantum confinement effects on the electronic properties of edge reconstructed monolayer GeS nanoribbon by using first-principles calculations. As width of the nanoribbon increases from 10 Å to 41 Å, the band gap keeps indirect and linearly decreases from 1.57 eV to 0.87 eV. Robust spatial separation of valence band maximum and conduction band minimum exist in reconstructed GeS nanoribbon with width larger than 19 Å. Moreover, high carrier mobility is expected in the reconstructed GeS nanoribbon. Our results suggest that reconstructed GeS nanoribbon is an important candidate for optoelectronics and photocatalytic.

Emotion-Semantic-Aware Dual Contrastive Learning for Epistemic Emotion Identification of Learner-Generated Reviews in MOOCs.

Identifying the epistemic emotions of learner-generated reviews in massive open online courses (MOOCs) can help instructors provide adaptive guidance and interventions for learners. The epistemic emotion identification task is a fine-grained identification task that contains multiple categories of emotions arising during the learning process. Previous studies only consider emotional or semantic information within the review texts alone, which leads to insufficient feature representation. In addition, some categories of epistemic emotions are ambiguously distributed in feature space, making them hard to be distinguished. In this article, we present an emotion-semantic-aware dual contrastive learning (ES-DCL) approach to tackle these issues. In order to learn sufficient feature representation, implicit semantic features and human-interpretable emotional features are, respectively, extracted from two different views to form complementary emotional-semantic features. On this basis, by leveraging the experience of domain experts and the input emotional-semantic features, two types of contrastive losses (label contrastive loss and feature contrastive loss) are formulated. They are designed to train the discriminative distribution of emotional-semantic features in the sample space and to solve the anisotropy problem between different categories of epistemic emotions. The proposed ES-DCL is compared with 11 other baseline models on four different disciplinary MOOCs review datasets. Extensive experimental results show that our approach improves the performance of epistemic emotion identification, and significantly outperforms state-of-the-art deep learning-based methods in learning more discriminative sentence representations.

Lipid Profile in Patients With Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

Backgrounds: A large number of studies have investigated the effect of early menopause on cardiovascular disease (CVD) outcomes and the relationship between the levels of lipid profile and primary ovarian insufficiency (POI). However, the results are inconsistent. The aim of this meta-analysis was to assess whether the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) changed in women with POI relative to healthy controls. Methods: To identify eligible studies, references published prior to December 2021 were searched in the PubMed, Embase, Cochrane Library and Web of Science databases. DerSimonian-Laird random-effects model was used to estimate the overall standard mean difference (SMD) between POI and healthy control subjects. Subgroup analysis and sensitivity analysis were preformed, and publication bias was assessed. Results: A total of 12 studies featuring 846 women with primary ovarian insufficiency and 959 healthy women were selected for analysis. The meta-analysis showed that the levels of TC (SMD: 0.60; 95% CI: 0.32 to 0.89; P<0.0001), TG (SMD: 0.36; 95% CI: 0.12 to 0.60; P=0.003), LDL (SMD: 0.46; 95% CI: 0.16 to 0.76; P=0.003) were significantly increased in women with POI. There was no significant change in the level of HDL (SMD: 0.25; 95% CI: -0.12 to 0.61; P=0.19). Subgroup analysis showed that the heterogeneity in this meta-analysis of the correlation between lipid profile and POI might come from by region, sample size, number of cases, mean body mass index (BMI) value of cases and mean age of cases. Conclusions: Scientific evidence suggests that the lipid profile levels were altered in patients with primary ovarian insufficiency compared to healthy controls. Therefore, we recommend that early medical intervention (e.g., hormone replacement therapy) to minimize the risk of CVD morbidity and mortality associated with dyslipidemia in patients with POI. Systematic Review Registration: PROSPERO, identifier CRD42021297088.

Reactive Fibroblasts in Response to Optic Nerve Crush Injury.

Traumatic optic neuropathy leads to bidirectional degeneration of retinal ganglion cells and axons and results in optic nerve scaring, which inhibits the regeneration of damaged axons. Compared with its glial counterpart, the fibrotic response causing nerve scar tissue is poorly permissive to axonal regeneration. Using collagen1α1-GFP reporter mice, we characterize the development of fibrotic scar formation following optic nerve crush injury. We observe that perivascular collagen1α1 cells constitute a major cellular component of the fibrotic scar. We demonstrate that extracellular molecules and monocytes are key factors contributing to the pathogenesis of optic nerve fibrotic scar formation, with a previously unrecognized encapsulation of this scar. We also characterize the distribution of collagen1α1 cells in the retina after optic nerve crush injury based on in vivo and whole-mount retinal imaging. Our results identify collagen1α1 cells as a major component of fibrotic scarring following ONC and are a potential molecular target for promoting axonal regeneration after optic nerve injury.

Association between retinol binding protein 4 and diabetic retinopathy among type 2 diabetic patients: a meta-analysis.

AIMS: The aim of this study was to investigate the association between retinol-binding protein 4 (RBP4) and diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM). METHODS: Databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, and Wangfang were searched to July 30, 2019. The Newcastle-Ottawa Scale was applied to assess the quality of all identified studies, and those qualified were included in the meta-analysis. The Chi squared Q test and I2 statistics were conducted to evaluate heterogeneity. Standardized mean differences (SMD) and 95% confidence intervals (CI) among RBP4 within the DR and T2DM without retinopathy (DWR) groups were pooled using the random effects model depending on the heterogeneity. Subgroup analyses were conducted among the groups having different diabetes duration, detection methods, body mass index, and total cholesterol and triglyceride levels. The funnel plot was used to assess publication bias. RESULTS: Nineteen observational studies were included in our meta-analysis. RBP4 was significantly higher in both nonproliferative DR (SMD: 0.72, 95% CI 0.48-0.95, P < 0.00001) and proliferative DR (SMD: 2.68, 95% CI 1.69-3.67, P < 0.00001) groups despite high heterogeneity (I2 = 87 and 97% in DR and PDR groups, respectively). Significant differences were noted among most subgroups (P < 0.05). Among those accompanied by hypercholesterolemia, the association between RBP4 and DR were unclear (P = 0.09). CONCLUSIONS: Elevated RBP4 is strongly associated with DR and may play an essential role in its progression. Additional large-scale controlled studies are needed to confirm these findings.