Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression.

Mitochondria play important roles in angiogenesis. However, the mechanisms remain elusive. In this study, we found that mitochondrial ubiquinol-cytochrome c reductase complex assembly factor 3 (UQCC3) is a key regulator of angiogenesis. TALEN-mediated knockout of Uqcc3 in mice caused embryonic lethality at 9.5-10.5 days postcoitum, and vessel density was dramatically reduced. Similarly, knockout of uqcc3 in zebrafish induced lethality post-fertilization and impaired vascular development. Knockout of UQCC3 resulted in slower tumor growth and angiogenesis. Mechanistically, UQCC3 was upregulated under hypoxia, promoted reactive oxygen species (ROS) generation, enhanced HIF-1α stability and increased VEGF expression. Finally, higher expression of UQCC3 was associated with poor prognosis in multiple types tumors, implying a role for UQCC3 in tumor progression. In conclusion, our findings highlight the important contribution of UQCC3 to angiogenesis under both physiological and pathological conditions, indicating the potential of UQCC3 as a therapeutic target for cancer.

A More Comprehensive Clinical and Laboratory Characterization of 61 Acute HIV Infection Patients in Southwest China.

Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk and reduction of missed diagnosis, we characterized 61 AHI patients in a Southwest China hospital with 4300 beds; specifically, we characterized their general clinical characteristics, evolution in results of a novel HIV screening assay called Elecsys® HIV Duo, and by programming, we analyzed the ability of all routine laboratory tests (e.g., routine blood analysis) to identify AHI patients. Among 61 AHI patients, 85.2% were male and the median age was 42 (interquartile range, 25-62) years. A total of 61.9% of patients visit the emergency department first during AHI. Clinical presentation of AHI patients included fever, fatigue, chills, rash, and various respiratory, digestive, and nervous system symptoms. Two of three results from Elecsys® HIV Duo show clear evolution trends: HIV P24 antigen decreased while HIV antibody increased in consecutive samples of nearly all patients. High fluorescence lymphocytes have a very high positive likelihood ratio (LR+) of 10.33 and a relatively high "rate of out-of-range tests" of 56.8% (21 in 37 patients who received this test had a result outside the reference range). In addition, we identified more than ten tests with LR+ greater than two. In summary, the emergency department is important for AHI screening. The evolution of HIV P24 Ag and HIV Ab and those laboratory tests with a high "rate of out-of-range tests" or high LR+ may aid the AHI identification and missed diagnosis reduction.

Recent advances in metal-organic framework-based materials for anti-staphylococcus aureus infection.

The rapid spread of staphylococcus aureus (S. aureus) causes an increased morbidity and mortality, as well as great economic losses in the world. Anti-S. aureus infection becomes a major challenge for clinicians and nursing professionals to address drug resistance. Hence, it is urgent to explore high efficiency, low toxicity, and environmental-friendly methods against S. aureus. Metal-organic frameworks (MOFs) represent great potential in treating S. aureus infection due to the unique features of MOFs including tunable chemical constitute, open crystalline structure, and high specific surface area. Especially, these properties endow MOF-based materials outstanding antibacterial effect, which can be mainly attributed to the continuously released active components and the exerted catalytic activity to fight bacterial infection. Herein, the structural characteristics of MOFs and evaluation method of antimicrobial activity are briefly summarized. Then we systematically give an overview on their recent progress on antibacterial mechanisms, metal ion sustained-release system, controlled delivery system, catalytic system, and energy conversion system based on MOF materials. Finally, suggestions and direction for future research to develop and mechanism understand MOF-based materials are discussed in antibacterial application.

Fluorescence and visual immunoassay of HIV-1 p24 antigen in clinical samples via multiple selective recognitions of CdTe QDs.

Human immunodeficiency virus (HIV) infection inflicts significant economic and social burdens on many countries worldwide. Given the substantial morbidity and mortality from HIV infection, there is an urgent need for accurate and early detection of the virus. In this study, immunofluorescence and visual techniques are described that detect the HIV-1 p24 antigen, which relied on selective recognition of Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+ using cadmium telluride quantum dots (CdTe QDs). After the sandwich immunoreactions were accomplished, the alkaline phosphatase (ALP) hydrolyzed L-ascorbic acid 2-phosphate (AAP) to form ascorbic acid (AA) that further reduces Ag+ and Cu2+ to Ag NPs and Cu+, respectively. This method was highly sensitive and selective and could detect as low as 1 pg/mL of p24 antigen by naked eyes and had a good linearity in the concentration range 1-100 pg/mL. When using Ag+ and Cu2+ as media, the limit of detection (LOD) of the new method was 0.3 pg/mL and 0.2 pg/mL, respectively. Compared with clinical electrochemiluminescence immunoassay (ECLIA) results and clinical data, this method demonstrated good consistency for the quantification of HIV-1 p24 antigen in 34 clinical serum samples. In addition, this method could accurately distinguish HIV from other viruses and infections such as hepatitis B virus, systemic lupus erythematosus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, lipemia, and hemolysis. Therefore, our dual-mode analysis method may provide additional solutions to identify clinical HIV infection. An immunofluorescence and visualization dual-mode strategy for the detection of p24 antigen was constructed based on immune recognition reaction and a phenomenon that cadmium telluride quantum dots (CdTe QDs) can selectively recognize Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+.

Relationships between IL-1ß, TNF-α genetic polymorphisms and HBV infection: A meta-analytical study.

BACKGROUND: IL-1ß and TNF-α have been demonstrated as pro-inflammatory cytokines to participate in the innate immune response and suppression of HBV infection. However, the exact relationship between IL-1ß, TNF-α gene polymorphisms and HBV infection remains unknown. Our study aims to assess the associations between IL-1ß, TNF-α gene polymorphisms and HBV infection. METHODS: A systematic literature search of PubMed and Embase databases was conducted through February 2020, and studies that were included in the present meta-analysis should fulfil the following conditions: (1) case-control studies focusing on the associations between IL-1ß, TNF-α polymorphisms and HBV infection; (2) patients in the case group should be tested positive for the HBsAg and/or HBV-DNA without liver cirrhosis or hepatocellular carcinoma; (3) the control group including healthy population or HBV spontaneous clearance population; (4) odds ratios (ORs) and their 95% confidence intervals (CIs) could be calculated based on the allele and genotype frequencies provided in articles. The quality of included studies was assessed according to the Newcastle-Ottawa scale (NOS) assessment system. Pooled ORs and 95% CIs were used to analyze the strength of associations. Subgroup analysis was performed according to ethnicity and control type. RESULTS: In the present meta-analysis, 49 articles including 10,218 cases and 9,557 controls were enrolled and seven polymorphisms (IL-1ß rs16944, rs1143634, TNF-α rs1799724, rs1799964, rs1800629, rs1800630, rs361525) were studied. In overall meta-analysis, significant associations were found in IL-1ß rs1143634, TNF-α rs1799724 and TNF-α rs1799964. For subgroup analysis under ethnicity, TNF-α rs1799724 and rs1800630 were markedly related to HBV infection in both Asian and Caucasian populations. In terms of control type subgroup, TNF-α rs1799724, rs1799964, rs1800630 were significantly associated with HBV persistence in HBV spontaneous clearance group. CONCLUSION: In the present study, we identified that three polymorphisms (IL-1ß rs1143634, TNF-α rs1799724, rs1799964) might serve as potential genetic biomarkers in HBV infection.

An enlightening role for cytokine storm in coronavirus infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).

The evaluation of low cut-off index values of Elecsys® HIV combi PT assay in predicting false-positive results.

OBJECTIVE: To analyze the results of different cut-off index (COI) values of Elecsys® HIV combi PT assay and to assess the role of COI in reducing the frequency of false-positive results. METHODS: We conducted a retrospective study of samples analyzed by Elecsys® HIV combi PT assay, a 4th-generation ECLIA, between 2016 and 2017. A total amount of 379 122 samples were collected for HIV (Human Immunodeficiency Virus) screening. RESULTS: A total of 379 122 samples were analyzed. 2528 (0.67%) were positive by Elecsys® HIV combi PT. Of these, 468 were false-positive results, and most of them (94.87%) were in samples with 1 < COI < 15. The false-positive rate was 0.12%. Patients with false-positive samples were more distributed in elder (P < .001) and female (P < .001) than true-positive specimens. The median COI in true-positive specimens was (385.20), which is significantly higher than false-positive specimens (2.08). The consistency between Elecsys® HIV combi PT assay and 3rd-generation and positive predictive value (PPV) increased with higher COI values. Cancer, infection, and neurological diseases were considered the potential confounding factors of HIV false-positive results (19.44%, 11.11%, and 6.62%, respectively). CONCLUSION: Samples with low COI values, especially those contain confounding factors, need to be further scrutinized to determine whether the confounding factors may cause false-positive problem. In addition, the hypothesis that low COI values may predict false-positive results is valid.

Acute HIV infection in a large teaching hospital in western China: Clinical, virological, and molecular epidemiological characteristics.

OBJECTIVE: To provide information on clinical, virological, and molecular epidemiological characteristics for early identification, diagnosis, and treatment of acute HIV infection (AHI). METHODS: A retrospective study was conducted with patients with AHI from 2012 to 2017 in West China Hospital. RESULTS: A total of 47 patients with AHI were found using a fourth-generation kit. Thirteen (27.66%) of these patients were negative if tested by third-generation tests. Median age of patients with AHI was 26 and 91.49% of them were males. Homosexual contact was responsible for 46.81% of AHI transmission. Among the individuals with AHI, 80.85% were outpatients. Common symptoms/signs were fever, headache, rash, cough and sputum, and sore throat. The syphilis coinfection rate was 17.24%. Most of the AHI was distributed in Fiebig stages IV (61.70%) and II (27.66%) with different clinical and virological characteristics. The increasing trend of cut-off index values was obvious in the course of AHI, helpful for auxiliary diagnosis. The main genetic forms of AHI were CRF07_BC and CRF01_AE, and a rare subtype CRF55_01B in Sichuan province was found. The drug resistance mutation rate was relatively high (17.65%) and five different mutations were identified. CONCLUSIONS: Fourth-generation assays are strongly recommended for screening AHI compared to third-generation ones. Different clinical and virological characteristics in different Fiebig stages were found. Young individuals and outpatients were the majority of patients with AHI and this deserves special attention. Attention should also be paid to the rare CRF55_01B in Sichuan province and surveillance of HIV resistance ought to be strengthened.