Molecular transmission network analysis of newly diagnosed HIV-1 infections in Nanjing from 2019 to 2021.

OBJECTIVE: The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing. METHODS: Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters. RESULTS: A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P < 0.05). Furthermore, the analysis of larger clusters revealed that individuals aged ≥ 60, peasants, those without TDR, and individuals infected with the CRF119_0107 were more likely to be part of these clusters. CONCLUSIONS: This study revealed the high risk of local HIV transmission and high TDR prevalence in Nanjing, especially the rapid spread of CRF119_0107. It is crucial to implement targeted interventions for the molecular transmission clusters identified in this study to effectively control the HIV epidemic.

Genes and Pathways Underpinning Klinefelter Syndrome at Bulk and Single-Cell Levels.

Klinefelter syndrome (KS) is the most frequent genetic anomaly in infertile men. Given its unclear mechanism, we aim to investigate critical genes and pathways in the pathogenesis of KS based on three bulk and one single-cell transcriptome data sets from Gene Expression Omnibus. We merged two data sets (GSE42331 and GSE47584) with human KS whole blood samples. When comparing the control and KS samples, five hub genes, including defensin alpha 4 (DEFA4), bactericidal permeability increasing protein (BPI), myeloperoxidase (MPO), intelectin 1 (ITLN1), and Xg Glycoprotein (XG), were identified. Besides, infiltrated degree of certain immune cells such as CD56bright NK cell were positively associated with the expression of ITLN1 and XG. Kyoto Encyclopedia of Genes and Genomes analysis identified upregulated phosphatidylinositol 3-kinase (PI3K)/AKT pathway in KS. Gene set enrichment analysis followed by gene set variation analysis confirmed the upregulation of G2M checkpoint and heme metabolism in KS. Thereafter, the GSE200680 data set was used for external validation of the expression variation of hub genes from healthy to KS testicular samples, and each hub gene yielded excellent discriminatory capability for KS without exception. At the single-cell level, the GSE136353 data set was utilized to evaluate intercellular communication between different cell types in KS patient, and strong correlations were detected between macrophages/ dendritic cells/ NK cells and the other cell types. Collectively, we provided hub genes, pathways, immune cell infiltration degree, and cell-cell communication in KS, warranting novel insights into the pathogenesis of this disease.