Transmission of new CRF07_BC Strains with 7 amino acid deletion in Gag p6

A 7 amino acid deletion in Gag p6 (P6delta7) emerged in Chinese prevalent HIV-1 strain CRF07_BC from different epidemic regions. It is important to determine whether this mutation could be transmitted and spread. In this study, HIV-1 Gag sequences from 5 different epidemic regions in China were collected to trace the transmission linkage and to analyze genetic evolution of P6delta7 strains. The sequence analysis demonstrated that P6delta7 is a CRF07_BC specific deletion, different P6delta7 strains could be originated from different parental CRF07_BC recombinants in different epidemic regions, and the transmission of P6delta7 strain has occurred in IDU populations. This is for the first time to identify the transmission linkage for P6delta7 strains and serves as a wake-up call for further monitoring in the future; In addition, P6delta7 deletion may represent an evolutionary feature which might exert influence on the fitness of CRF07_BC strain

Antiretroviral Therapy Normalizes Autoantibody Profile of HIV Patients by Decreasing CD33⁺CD11b⁺HLA-DR⁺ Cells: A Cross-Sectional Study

Autoimmune manifestations are common in human immunodeficiency virus (HIV) patients. However, the autoantibody spectrum associated with HIV infection and the impact of antiretroviral therapy (ART) remains to be determined. The plasma autoantibody spectrum for HIV patients was characterized by protein microarrays containing 83 autoantigens and confirmed by enzyme-linked immunosorbent assay (ELISA). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were analyzed by flow cytometry and their effects on autoantibodies production were determined by B cell ELISpot. Higher levels of autoantibody and higher prevalence of elevated autoantibodies were observed in ART-naive HIV patients compared to healthy subjects and HIV patients on ART. The highest frequency of CD33(+)CD11b(+)HLA-DR(+) cells was observed in ART-naive HIV patients and was associated with the quantity of elevated autoantibodies. In addition, CD33(+)CD11b(+)HLA-DR(+) cells other than Tregs or MDSCs boost the B cell response in a dose-dependent manner by in vitro assay. In summary, HIV infection leads to elevation of autoantibodies while ART suppresses the autoimmune manifestation by decreasing CD33(+)CD11b(+)HLA-DR(+) cells in vivo.The roles of CD33(+)CD11b(+)HLA-DR(+) cells on disease progression in HIV patients needs further assessment

Phenotypic and genotypic characterization of Human Immunodeficiency Virus type 1 CRF07_BC strains circulating in the Xinjiang Province of China

BACKGROUND: HIV-1 CRF07_BC recombinant previously circulated mainly among the intravenous drug users (IDUs) in Xinjiang province of China and is currently spreading in the entire country. The aim of this study is to characterize the genotypic and phenotypic properties of HIV-1 CRF07_BC isolates in comparison with those of the subtype B' (Thailand B) which is prevalent in the former plasma donors (FPDs) in China. RESULTS: Twelve HIV-1 CRF07_BC variants were isolated from the blood of the HIV-1-infected IDUs in Xinjiang province, and 20 subtype B' isolates were obtained from the FPDs in Anhui and Shanxi provinces of China. All the CRF07_BC viruses utilized CCR5 co-receptor, whereas 12 subtype B' viruses were R5-tropic, and the remaining B' isolates were dual (R5X4) tropic. CRF07_BC viruses had lower net charge value in the V3 loop and exhibited slower replication kinetics than subtype B' viruses. The number and location of the potential N-linked glycosylation sites in V1/V2 and the C2 region of the CRF07_BC viruses were significantly different from those of the subtype B' viruses. CONCLUSION: The HIV-1 CRF07_BC recombinant strains with relatively lower net charges in the V3 loop exclusively utilize CCR5 co-receptor for infection and exhibit slow replication kinetics in the primary target cells, suggesting that CRF07_BC may be superior over B' and other HIV-1 subtypes in initiating infection in high-risk population. These findings have molecular implications for the adaptive evolution of HIV-1 circulating in China and the design of tailored therapeutic strategy for treatment of HIV-1 CRF07_BC infection

Activation of aldehyde dehydrogenase-2 improves ischemic random skin flap survival in rats

ObjectiveRandom skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action.MethodsModified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed via laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence.ResultsAlda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion.ConclusionALDH2 activation can effectively enhance random skin flap viability via inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties

Identification of a large, fast-expanding HIV-1 subtype B transmission cluster among MSM in Valencia, Spain

We describe and characterize an exceptionally large HIV-1 subtype B transmission cluster occurring in the Comunidad Valenciana (CV, Spain). A total of 1806 HIV-1 protease-reverse transcriptase (PR/RT) sequences from different patients were obtained in the CV between 2004 and 2014. After subtyping and generating a phylogenetic tree with additional HIV-1 subtype B sequences, a very large transmission cluster which included almost exclusively sequences from the CV was detected (n = 143 patients). This cluster was then validated and characterized with further maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. With these analyses, the CV cluster was delimited to 113 patients, predominately men who have sex with men (MSM). Although it was significantly located in the city of Valencia (n = 105), phylogenetic analyses suggested this cluster derives from a larger HIV lineage affecting other Spanish localities (n = 194). Coalescent analyses estimated its expansion in Valencia to have started between 1998 and 2004. From 2004 to 2009, members of this cluster represented only 1.46% of the HIV-1 subtype B samples studied in Valencia (n = 5/143), whereas from 2010 onwards its prevalence raised to 12.64% (n = 100/791). In conclusion, we have detected a very large transmission cluster in the CV where it has experienced a very fast growth in the recent years in the city of Valencia, thus contributing significantly to the HIV epidemic in this locality. Its transmission efficiency evidences shortcomings in HIV control measures in Spain and particularly in Valencia

Manufacturing and Performance of Carbon Short Fiber Reinforced Composite Using Various Aluminum Matrix

A new fabrication process without preform manufacturing has been developed for carbon short fiber (CSF) reinforced various aluminum matrix composites. And their mechanical and thermal properties were evaluated. Electroless Ni plating was conducted on the CSF for improving wettability between the carbon fiber (CF) and aluminum. It was confirmed that pores in Ni plated CSF/Al and Al alloy matrix composites prepared by applied pressure, 0.8 MPa, had some imperfect infiltration regions between the CF/CF and CF/matrix in all composites. However, pores size in the region between the CF/CF and CF/matrix to use the A336 matrix was about 1 µm. This size is smaller than that of other aluminum-based composites. Vickers hardness of Ni plated CSF/A1070, A356 alloy, and A336 alloy composites were higher as compared to matrix. However, the A1070 pure aluminum matrix composite had the highest hardness improvement. The Ultimate tensile strength of the A1070 and A356 aluminum matrix composite was increased due to carbon fiber compared to only aluminum, but the Ultimate tensile strength of the A336 aluminum matrix composite was rather lowered due to the highest content of Si precipitate and large size of Al3Ni compounds. The Thermal Conductivity of Ni plated CSF/A1070 composite has the highest value (167.1 W·m−1·K−1) as compared to composites

Multiple independent introductions of HIV-1 CRF01_AE identified in China: what are the implications for prevention?

BackgroundHIV-1 CRF01_AE accounts for an important fraction of HIV infections in Asia including China, but little is known about the phylogenetic and evolutionary history of this CRF (circulating recombinant form). In the current study, we collected a large number of 1,957 CRF01_AE gag p17 sequences with known sampling year (1990-2010) from 5 global regions representing 15 countries to better understand the phylogenetic relationships and epidemic history of CRF01_AE strains in China.Methodology/principal findingsCRF01_AE gag p17 sequences were retrieved from public databases to explore phylogenetic relationships and phylogeographic dynamics of CRF01_AE in Asia by using maximum-likelihood phylogenetics and Bayesian coalescent-based analyses. We found close phylogenetic relationships between sequences from Thailand, Vietnam and China. Moreover, at least 5 independent introductions and 5 independent autochthonous clades of CRF01_AE, which descended from Thailand or Vietnam were identified in China from 1991 through 2003.Conclusion/significanceThe current study not only defines the migration of CRF01_AE clades to/in Asia, but also demonstrates the criticalness of identifying the circulating strains in the population for the development of vaccine and microbicides

Effect of excitation coil voltage on TiAlSiN coating on 42CrMo steel surface

TiAlSiN coating was painted on the surface of 42CrMo steel by arc ion plating technology, and the influence of excitation coil voltage on the structure and friction property of the coating were analyzed. Results showed that there were a lot of holes on TiAlSiN coatings under different voltages. With the increase of voltage, the structure and friction property changed a lot: the roughness and thickness of the coating increased obviously and all layers were in a state of tight bond and formed a columnar structure; many voids appeared led to the decrease of coating density; the coating with higher microhardness was obtained, which was higher than that of alloy steel substrate; the friction coefficient and wear rate of the coating first decreased then increased, and the minimum wear rate occurred when the voltage reached 30 V, under condition of which the coating mainly suffered from abrasive wear, so more flat surface and denser structure of the coating formed, which significantly improved the wear resistance

Optimization of Thermo-Mechanical Fatigue Life for Eutectic Al–Si Alloy by the Ultrasonic Melt Treatment

The eutectic cast Al–Si alloys with excellent high-temperature and casting performance are widely used in engine pistons. During frequent starts and stops, the thermo-mechanical fatigue (TMF) is the most important failure cause. Ultrasonic melt treatment (UT) was chosen to compare and investigate the influence of micro-structures on fatigue life and damage mechanisms of as-cast (AC) eutectic Al–Si alloys under TMF loading. After UT, the grain size, primary Si, and intermetallic particles are reduced significantly in the alloy; fatigue life increases obviously. As a result of pilling-up of dislocations, the competitive effects of the critical strain/stress for fatigue crack nucleation can be found. There are two different crack initiation mechanisms under TMF: one is primary Si fracture for AC alloys with limited critical strain/stress for fatigue crack nucleation at fractured Si particles, and the other is primary Si debonding for UT alloys with increasing critical fracture strain/stress. After the crack initiation, the fractured or debonded primary phases provide the advantages for the further development of main cracks for both alloys. The UT alloy (805 ± 253 cycles) has about twice the TMF life of the AC alloy (403 ± 98 cycles). The refinement of micro-structures is instrumental in improving the fatigue resistance and life of TMF for the UT alloy

ML tree of HIV-1 CRF01_AE gag p17 sequences from 5 global regions (15 countries).

<p>The boxes highlight the position of the Chinese CRF01_AE lineages. The color of the branches represents the geographic region from where the CRF01_AE sequences originated, according to the map given at the top left of the figure. For visual clarity, some clades comprised of sequences sampled from SSE region were collapsed in orange triangles. The tree was rooted using outgroup (black branches). Horizontal branch lengths are drawn to scale with the bar at the bottom indicating nucleotide substitutions per site.</p