This study reconstructed molecular networks of human immunodeficiency virus (HIV) transmission history in an area affected by an epidemic of multiple HIV-1 subtypes and assessed the efficacy of strengthened early antiretroviral therapy (ART) and regular interventions in preventing HIV spread. We collected demographic and clinical data of 2221 treatment-naïve HIV-1-infected patients in a long-term cohort in Shenyang, Northeast China, between 2008 and 2016. HIV pol gene sequencing was performed and molecular networks of CRF01_AE, CRF07_BC, and subtype B were inferred using HIV-TRACE with separate optimized genetic distance threshold. We identified 168 clusters containing ≥ 2 cases among CRF01_AE-, CRF07_BC-, and subtype B-infected cases, including 13 large clusters (≥ 10 cases). Individuals in large clusters were characterized by younger age, homosexual behavior, more recent infection, higher CD4 counts, and delayed/no ART (P less then 0.001). The dynamics of large clusters were estimated by proportional detection rate (PDR), cluster growth predictor, and effective reproductive number (R e ). Most large clusters showed decreased or stable during the study period, indicating that expansion was slowing. The proportion of newly diagnosed cases in large clusters declined from 30 to 8% between 2008 and 2016, coinciding with an increase in early ART within 6 months after diagnosis from 24 to 79%, supporting the effectiveness of strengthened early ART and continuous regular interventions. In conclusion, molecular network analyses can thus be useful for evaluating the efficacy of interventions in epidemics with a complex HIV profile.Bacteria evolved multiple strategies to survive and develop optimal fitness in their ecological niche. They deployed protein secretion systems for robust and efficient delivery of antibacterial toxins into their target cells, therefore inhibiting their growth or killing them. To maximize antagonism, recipient factors on target cells can be recognized or hijacked to enhance the entry or toxicity of these toxins. To date, knowledge regarding recipient susceptibility (RS) factors and their mode of action is mostly originating from studies on the type Vb secretion system that is also known as the contact-dependent inhibition (CDI) system. Yet, recent studies on the type VI secretion system (T6SS), and the CDI by glycine-zipper protein (Cdz) system, also reported the emerging roles of RS factors in interbacterial competition. Here, we review these RS factors and their mechanistic impact in increasing susceptibility of recipient cells in response to CDI, T6SS, and Cdz. Past and future strategies for identifying novel RS factors are also discussed, which will help in understanding the interplay between attacker and prey upon secretion system-dependent competition. Understanding these mechanisms would also provide insights for developing novel antibacterial strategies to antagonize aggressive bacteria-killing pathogens.Viral infections are a global disease burden with only a limited number of antiviral agents available. Due to newly emerging viral pathogens and increasing occurrence of drug resistance, there is a continuous need for additional therapeutic options, preferably with extended target range. In the present study, we describe a novel antiviral peptide with broad activity against several double-stranded DNA viruses. The 22-mer peptide TAT-I24 potently neutralized viruses such as herpes simplex viruses, adenovirus type 5, cytomegalovirus, vaccinia virus, and simian virus 40 in cell culture models, while being less active against RNA viruses. The peptide TAT-I24 therefore represents a novel and promising drug candidate for use against double-stranded DNA viruses.Fusarium graminearum virus 1 (FgV1) is a positive-sense ssRNA virus that confers hypovirulence in its fungal host, Fusarium graminearum. Like most mycoviruses, FgV1 exists in fungal cells, lacks an extracellular life cycle, and is therefore transmitted during sporulation or hyphal anastomosis. To understand FgV1 evolution and/or adaptation, we conducted mutation accumulation (MA) experiments by serial passage of FgV1 alone or with FgV2, 3, or 4 in F. graminearum. We expected that the effects of positive selection would be highly limited because of repeated bottleneck events. To determine whether selection on the virus was positive, negative, or neutral, we assessed both the phenotypic traits of the host fungus and the RNA sequences of FgV1. We inferred that there was positive selection on beneficial mutations in FgV1 based on the ratio of non-synonymous to synonymous substitutions (d N /d S ), on the ratio of radical to conservation amino acid replacements (p NR /p NC ), and by changes in the predicted proteiAdditional research is needed to clarify the effects of virus co-infection on the adaptation or evolution of FgV1 to its environments.To date, a variety of Brucella effector proteins have been found to mediate host cell secretion, autophagy, inflammation, and other signal pathways, but nuclear effector proteins have not yet been reported. We identified the first Brucella nucleomodulin, BspJ, and we screened out the BspJ interaction host proteins NME/NM23 nucleoside diphosphate kinase 2 (NME2) and creatine kinase B (CKB) through yeast two-hybrid and co-immunoprecipitation assays. These proteins are related to the host cell energy synthesis, metabolism, and apoptosis pathways. Brucella nucleomodulin BspJ will decrease the expression level of NME2 and CKB. In addition, BspJ gene deletion strains promoted the apoptosis of macrophages and reduced the intracellular survival of Brucella in host cells. https://www.selleckchem.com/products/GDC-0449.html In short, we found nucleomodulin BspJ may directly or indirectly regulate host cell apoptosis through the interaction with NME2 and CKB by mediating energy metabolism pathways in response to the intracellular circulation of Brucella infection, but the mechanism needs further study.Nicotine is a major N-heterocyclic aromatic alkaloid produced in tobacco plants and the main toxic chemical in tobacco waste. Due to its complex physiological effects and toxicity, it has become a concern both in terms of public health and the environment. A number of bacteria belonging to the genera Arthrobacter and Pseudomonas can degrade nicotine via the pyridine and pyrrollidine pathways. Recently, a novel hybrid of the pyridine and pyrrolidine pathways (also known as the VPP pathway) was found in the Rhizobiale group bacteria Agrobacterium tumefaciens S33, Shinella sp. HZN7 and Ochrobactrum sp. SJY1 as well as in other group bacteria. The special mosaic pathway has attracted much attention from microbiologists in terms of the study of their molecular and biochemical mechanisms. This will benefit the development of new biotechnologies in terms of the use of nicotine, the enzymes involved in its catabolism, and the microorganisms capable of degrading the alkaloid. In this pathway, some metabolites are hydroxylated in the pyridine ring or modified in the side chain with active groups, which can be used as precursors for the synthesis of some important compounds in the pharmaceutical and agricultural industries.