The vast majority of new HIV infections result from relatively inefficient transmission1,2 of the virus across mucosal surfaces during sexual intercourse3. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections4. This natural bottleneck to transmission has stimulated efforts to develop interventions aimed at blocking this step of the infection process5. Despite the promise of this strategy, clinical trials of pre-exposure prophylaxis have had limited degrees of success in humans, due in part to lack of adherence to the recommended pre-exposure treatment regimens6,7. In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza8 and HPV9. We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV using broadly neutralizing antibodies10. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse viral strains, despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain11, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans.

Objectives To assess the value of transvaginal sonography (TVS) in the diagnosis of heterotopic pregnancy (HP) in the first trimester after in-vitro fertilization with embryo transfer (IVF-ET). Methods

Novel nanoporous magnetic cellulose−chitosan composite microspheres (NMCMs) were prepared by sol−gel transition method using ionic liquids as solvent for the sorption of Cu(II). The composite microspheres were studied by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). Subsequelty, the adsorption of Cu(II) to NMCMs was investigated systematically with varried parameters such as pH, contact time, and initial concentration. Results revealed that the composite microspheres exhibited efficient adsorption capacity of Cu(II) from aqueous solution, due to their favorable chelating groups in structure. The adsorption process was best described by a pseudo-second-order kinetic model, while isotherm modeling revealed that the Langmuir equation better describe the adsorption of Cu(II) on NMCMs as compared to Freundlich model. Moreover, the loaded NMCMs can be easily regenerated with HCl and reused repeatedly for Cu(II) adsorption up to five cycles. The environmental friendly microspheres were expected to be a promising candidate for future practical use in heavy metal ions removal.

Breast cancer is the most common female cancer worldwide and represents 12% of all cancer cases. Improvements in survival rates are largely attributed to improved screening and diagnosis. Conventional chemotherapy remains an important treatment option but it is beset with poor cell selectivity, serious side effects and resistance. Nanoparticle drug delivery systems bring promising opportunities to breast cancer treatment. They may improve chemotherapy by targeting drugs to tumors, generating high drug concentrations at tumors providing slow release of the drug, increased drug stability and concomitant reductions in side effects. The nanotechnology-based drug delivery approaches and the current research and application status of nano-targeted agents for breast cancer are discussed in this review to provide a basis for further study on targeted drug delivery systems.

Key Points miR-125b is epigenetically silenced in B cells. Physiological silencing of miR-125b is required for normal B-cell development.

BackgroundAlthough Caesarean scar pregnancy (CSP) is rare, it can cause life-threatening complications. The increasing rate of Cesarean delivery plus rapid development of in vitro fertilization-embryo transfer (IVF-ET) may increase the occurrence of CSP as well as the ratio of heterotopic CSP (HCSP)/CSP. Therefore, early diagnosis and management of CSP are necessary to avoid serious complications. And the purpose of this article is to evaluate the importance and feasibility of the first-trimester diagnosis and management of CSP after IVF-ET.MethodsAll the 12 cases were secondary infertility patients who had a history of Cesarean section and underwent IVF-ET in our reproductive center. All cases with CSP were diagnosed using transvaginal color Doppler sonography (TVS). Medical, surgical and expectant managements were implemented, and the management results were traced.ResultsPatients with CSP (n = 12) were diagnosed from January 2011 to April 2015, 6 (50 %) of which were HCSP. The prevalence of CSP was 1:1688 pregnancies. The gestational age ranged from 5 + 3 to 7 + 4 weeks in all CSP, and from 5 + 6 to 7 + 4 weeks in HCSP at diagnosis. Five patients received successful surgical treatment. The success rate of medical and expectant management was 50 % (1/2) and 100 % (5/5), respectively. One patient with failed medical management needed an emergency laparotomy to evacuate CSP. The uterus was preserved in all 12 patients.ConclusionsThe Caesarean section and IVF-ET may increase the ratio of HCSP/CSP. TVS is a noninvasive and effective tool for use in diagnosing CSP. CSP should be carefully excluded in patients who have had a history of Caesarean section. Early diagnosis of CSP in the first trimester may contribute towards the preservation of uterus as well as intrauterine pregnancy (IUP) in HCSP.

HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties. Transduced T cells comparably, albeit modestly, also suppressed HIV infection in vitro and in humanized mice. We also performed extensive molecular dynamics simulations that provided a structural basis for similarities in cytotoxicity and epitope cross-reactivity. These results demonstrate that the differential abilities of HIV-specific CD8+ T cells from HCs and CPs are not genetically encoded in the TCRs alone and must depend on additional factors.

Glioma is one of the most lethal malignancies, and increasing reports revealed that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role in the development and pathology of human gliomas. MiR-424 has been found to be dysregulated in many different types of human cancers. However, the clinical significance and function of miR-424 in glioma remains unclear. Here, based on RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was significantly decreased in glioma tumor tissues than in adjacent non-neoplastic brain tissues, and decreased miR-424 expression was associated with glioma KPS (P = 0.009) and high grades (P = 0.029). In vitro cellular function assays further revealed that miR-424 inhibited cell invasion and migration, and promoted cell apoptosis. In addition, based on DNA methylation analysis on clinical specimens and cell lines, we found miR-424 promoter CpG island was frequently methylated and correlated with glioma high grades (P = 0.035) and IDH mutation status (P = 0.042). Moreover, the promoter CpG island was demethylated by 5-aza-2'-deoxycytidine treatment in a time-dependent manner and the expression levels of miR-424 were gradually induced and increased. Taken together, our data suggest that the promoter region CpG island methylation is associated with tumor suppressive miR-424 silencing and the pathology of human gliomas.