A novel approach to inhibit HIV-1 infection and enhance lysis of HIV by a targeted activator of complement

<p>Abstract</p> <p>Background</p> <p>The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.</p> <p>Presentation of the hypothesis</p> <p>Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.</p> <p>Testing the hypothesis</p> <p>Our hypothesis was tested using cell-free HIV-1 virions cultivated <it>in vitro </it>and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.</p> <p>Implications of the hypothesis</p> <p>The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.</p

Effectiveness of Post-Traumatic Growth Intervention to Promote Positive Post-Traumatic Traits in Chinese Breast Cancer Patients:A Randomized Controlled Trial

Objective: The purpose of this study was to evaluate the effectiveness of post-traumatic growth (PTG) model-based intervention to improve positive psychological traits in Chinese breast cancer patients. Design: A randomized control trial of a psychological group intervention based on PTG model. Methods: The Clinical Trial was registered on 17 August 2019 at Chinese Clinical Trials.gov with Registration number ChiCTR1900025264. A total of 92 patients with breast cancer were recruited. The participants were randomly assigned to the experimental group (n = 46) and the control group (n = 46). A six-session psychological group intervention based on PTG model was implemented in the experimental group, and a six-session health education was implemented in the control group. The outcomes were measured at baseline (pre-intervention), 3 weeks, 6 weeks after the intervention. The primary outcome was post-traumatic growth assessed by the Chinese version of the Post-Traumatic Growth Inventory (PTGI); Secondary outcomes included psychological resilience, family resilience, rumination, and self-disclosure. Results: A total of 87 patients with breast cancer completed this study, including 44 patients in the experimental group and 43 patients in the control group. There was no significant difference in baseline data of breast cancer patients between the two groups except for the treatment regimen (p &gt; 0.05). The two groups were compared after the intervention; the interaction effects between the total scores of post-traumatic growth, family resilience, and self-disclosure and the time term were statistically significant (p &lt; 0.05), indicating that the trend of change in total scores of post-traumatic growth, family resilience, and self-disclosure differed between the experimental and control groups over time, and the scores improved in the experimental group were significantly higher than those in the control group. The comparison of psychological resilience and total score of rumination at each time point was statistically significant (p &lt; 0.05), indicating that group intervention based on the PTG model could improve the psychological recovery ability and rumination level of the experimental group. Conclusion: The psychological group intervention based on the PTG model significantly improved post-traumatic growth, family resilience, and self-disclosure in patients with breast cancer. However, the impact on psychological resilience and rumination was relatively small. Long-term intervention is needed to further test the effect of the PTG model on psychological resilience and rumination.</p

Red Wine Polyphenols for Cancer Prevention

Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient's lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin

Objective Bayesian analysis of spatial models with separable correlation functions

This paper considers general linear models for Gaussian geostatistical data with multi-dimensional separablecorrelation functions involving multiple parameters. We derive various objective priors, such as the Jeffreys-rule, independence Jeffreys, and usual and exact reference priors for the model parameters. In addition, we relax and simplifythe assumptions in Paulo [2005] for the propriety of the posteriors in the general setup. We show that the frequentist coverage of posterior credible intervals for a function of range parameters do not depend on the regression coefficient or error variance. These objective priors and a proper flat prior based on ML estimates are compared by examining the frequentist coverage of equal-tailed Bayesian credible intervals. An illustrative example is given from the field of complex computer model validations

Diastereoselective Synthesis of Cyclopentanediols by InCl3/Al Mediated Intramolecular Pinacol Coupling Reaction in Aqueous Media

molecule

Identification of quantitative trait loci for growth traits in red swamp crayfish (Procambarus clarkii)

Genetic breeding is an important approach to improve the economic traits of aquaculture animals. Unfortunately, the genetic basis for important economic traits of red swamp crayfish, including growth-related traits, has not yet been reported. In the present study, two full-sib families and two natural populations were employed to identify quantitative trait loci (QTLs) for growth-related traits of red swamp crayfish. In total, 28 QTLs for five growth-related traits, including body weight, body length, carapace length, carapace width, and abdomen length, were repeatedly identified in more than two families/populations, by means of association analysis; nine of these displayed a heterosis effect. The phenotypic variations of the five investigated traits explained by the 28 QTLs ranged from 4.2% to 19.0%. Eight additive and three heterosis QTLs were further successfully validated using comparative analysis of favoured alleles between the small and big size crayfish groups in the natural population. In conclusion, this study investigated the genetic basis of growth-related traits in red swamp crayfish, which is of great significance for their application in the future molecular breeding of the species