HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation.

Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used the single particle cryo-electron microscopy method to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 Å resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag lattice structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 Å resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10-12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation.

Optimal method for detecting cervical lymph node metastasis from papillary thyroid cancer.

PURPOSE: Papillary thyroid cancer (PTC) is often accompanied by cervical lymph node metastases (LNM). This study compared the diagnostic performance of fine needle aspiration (FNA), the combination of FNA and thyroglobulin measurement in the washout (FNA-Tg), and core needle biopsy(CNB) in order to determine the optimal method in detecting cervical LNM from PTC. METHODS: PTC patients with suspicious cervical lymph nodes, who underwent ultrasonography-guided FNA, or CNB before surgery were retrospectively reviewed between January 2021 and April 2022. Patients' demographics, lymph node size, and results of FNA, FNA-Tg, CNB and surgical pathology were collected. Sensitivitity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and the area under the curves (AUC) of receiver operating characteristic were obtained. RESULTS: FNA-Tg had a higher AUC with a threshold of 55 ng/mL than that with a threshold of 1 ng/mL (0.782 vs. 0.636, P = 0.005). The sensitivity of the combination of FNA and FNA-Tg was higher than that of FNA alone (91.3% vs. 81.0%, P = 0.01), but it was not different from that of CNB (91.3% vs. 88.0%, P > 0.05). No significant difference was found in specificity, PPV, NPV, accuracy and AUC among FNA alone, CNB alone, and the combination of FNA and FNA-Tg. CONCLUSIONS: FNA-Tg is useful to improve the sensitivity of FNA. The diagnostic performance of the combination of FNA and FNA-Tg is better than that of FNA or FNA-Tg alone, but is not different from that of CNB in detecting LNM from PTC.

Exploration of molecular features of PCOS with different androgen levels and immune-related prognostic biomarkers associated with implantation failure.

Background: Polycystic ovary syndrome (PCOS), the most common heterogeneous reproductive disease afflicting women of childbearing age, has been recognized as a chronic inflammatory disease recently. Most PCOS patients have hyperandrogenism, indicating a poor prognosis and poor pregnancy outcomes. The molecular mechanism underlying PCOS development is still unknown. In the present study, we investigated the gene expression profiling characteristics of PCOS with hyperandrogenism (HA) or without hyperandrogenism (NHA) and identified immune-related factors that correlated with embryo implantation failure. Methods: PCOS and recurrent implantation failure (RIF) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. ClueGO software was used to perform enrichment analysis of differentially expressed genes (DEGs) in PCOS with varying androgen levels. The Weighted Co-Expression Network Analysis (WGCNA) was used to identify co-expressed modules and shared gene signatures between HA PCOS and RIF. Moreover, the upregulated DEGs of HA PCOS and RIF were intersected with shared gene signatures screening by WGCNA to excavate further key prognostic biomarkers related to implantation failure of HA PCOS. The selected biomarker was verified by qRT-PCR. Results: A total of 271 DEGs were found in HA PCOS granulosa cell samples, and 720 DEGs were found in NHA PCOS. According to CuleGO enrichment analysis, DEGs in HA PCOS are enriched in immune activation and inflammatory response. In contrast, DEGs in NHA PCOS are enriched in mesenchymal cell development and extracellular space. Using WGCNA analysis, we discovered 26 shared gene signatures between HA PCOS and RIF, which were involved in corticosteroid metabolism, bone maturation and immune regulation. DAPK2 was furtherly screened out and verified to be closely related with the development of HA PCOS, acting as an independent predictor biomarker of the embryo implantation failure. DAPK2 expression was negatively correlated to the embryo implantation rate (r=-0.474, P=0.003). The immune infiltration results suggested that upregulated DAPK2 expression was closely related with NK cell infiltration and macrophage M2, playing an essential role in the pathogenesis of implantation failure in HA PCOS. Conclusion: Our research revealed the expression profiling of PCOS with different androgen levels and identified DAPK2 as a critical prognostic biomarker for implantation failure in PCOS.

Role of politically motivated internet addiction and ideological passion in linking college student's mental health education and wellbeing.

College students are increasingly reporting common mental health issues like depression and anxiety, raising severe concerns for students' psychological wellbeing. Specifically, after the emergence of Post-COVID-19, digitization caused a potential role in mitigating students' psychological concerns. Therefore, the role of mental health education has been regarded as a topic of interest in managing the issue of Chinese college students' mental wellbeing. This study intends to look into the relationship between mental health education and psychological wellbeing, along with the moderating role of politically motivated internet addiction and the ideological passion of college students. For the given reason, the random sampling method was employed for collecting data from target respondents. The study uses 750 questionnaires prepared on a five-point Likert scale that were distributed to the respondents with an expected response rate of 50%. The partial least square (PLS) software was used to analyze the data for this study. The study concludes that there is a significant moderating role of politically motivated internet addiction and ideological passion in the relationship between college students' mental health and wellbeing. The study meaningfully contributes to the body of knowledge by establishing the unique, positive moderating role of Politically motivated internet addition in strengthening the relationship which undoubtedly will assist in improving the psychological wellbeing of college students through mental health education policies and implications.

Tandem Cross-Coupling of Alkynyl Sulfides and Alkynyl Sulfoxides/[3,3]-Sulfonium Rearrangement to Construct Tetrasubstituted Furans.

In the presence of boron trifluoride, a variety of alkynyl sulfides and alkynyl sulfoxides undergo tandem cross-coupling/[3,3]-sulfonium rearrangement followed by 5-exo-dig heterocyclization. The strategy provides concise access to novel tetrasubstituted furans in good to high yields with 100% atom-economy efficiency. Further derivatization of the resultant furans was feasible by utilizing the incorporated alkylthio groups.

Synthesis of Antimicrobial Benzo[1,2,4]triazoloazepinium Salts and Tetrahydronaphtho[1,2-e][1,2,4]triazines by Polar [3+ + 2] and [4 + 2]-Cycloaddition Reactions.

Novel annulated azaheterocycles of benzo[1,2,4]triazoloazepine and tetrahydronaphtho[1,2-e][1,2,4]triazine derivatives have been synthesized. Treatment of 2-diazenyl-1,2,3,4-tetrahydronaphthalen-2-yl acetates with BF3·Et2O generates 1-aza-2-azoniaallenium cation intermediates (or azocarbenium ions), which are intercepted by nitriles via cascade polar [3+ + 2]-cycloaddition/rearrangement reactions to afford benzo[1,2,4]triazoloazepinium salts. These literature unprecedented fused tricycle compounds have been shown to exhibit antimicrobial activity against Gram-positive Staphylococcus aureus with in silico docking studies, suggesting that they may exhibit their antibiotic activity through inhibition of DNA gyrase. Additionally, when ethyl 2-(1-acetoxy-1,2,3,4-tetrahydronaphthalen-2-yl)diazene-1-carboxylate is employed, the reaction with BF3·Et2O produces 1,2-diaza-1,3-diene, which reacts with nitriles via a diaza-Diels-Alder reaction with inverse electron demand, leading to ethyl tetrahydronaphtho[1,2-e][1,2,4]triazine carboxylates. The DFT calculation has been performed to further prove the D-A reaction speculation.

Cascade intramolecular Prins/Friedel-Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols.

The treatment of 2-(2-vinylphenyl)acetaldehydes or 3-(2-vinylphenyl)propanals with BF3·Et2O results in an intramolecular Prins reaction affording intermediary benzyl carbenium ions, which are then trapped by a variety of electron-rich aromatics via Friedel-Crafts alkylation. This cascade Prins/Friedel-Crafts cyclization protocol paves an expedient path to medicinally useful 4-aryltetralin-2-ol and 5-aryltetrahydro-5H-benzo[7]annulen-7-ol derivatives.

Total Synthesis of Marine Alkaloids Motuporamines A and B via Ring Expansion of Cyclic ß-Keto Esters.

An expedient total synthesis of the title marine sponge alkaloids has been developed. The salient features of the synthesis are as follows: (i) preparation of the required 13- and 14-membered cyclic lactams with n + 4 ring-expansion strategy of cyclic ß-keto esters and (ii) functional group manipulation of the resulted keto ester lactams. This approach used easily accessible and inexpensive materials/reagents, thus providing a promising alternative to the existing preparations.

Organocatalytic Mukaiyama Mannich Reactions of 2,5-Bis(trimethylsilyloxy)furan.

The organocatalytic synthesis of densely substituted mono- and bis-γ-lactams involving the Mukaiyama Mannich addition of 2,5-bis(trimethylsilyloxy)furan to imines is described. Use of a ditoluenesulfonylimide catalyst produces γ-lactams from monoaddition, whereas a more acidic catalyst (triflic acid) produces fused bis-lactams from double addition. Optimized organocatalytic conditions allow for the selective synthesis of either desired core as well as the one-pot, multicomponent assembly of the trisubstituted monolactams from aldehydes, amines, and bis-trimethylsilyloxyfuran. An examination of chiral acids found these organocatalysts to be highly active and diastereoselective in the monoaddition reaction, albeit with no enantioselectivity.