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Complete understanding of the route of HIV-1 transmission is an important prerequisite for curbing the HIV/AIDS pandemic. So far, the known routes of HIV-1 transmission include sexual contact, needle sharing, puncture, transfusion and mother-to-child transmission. Whether HIV can be vertically transmitted from human sperm to embryo by fertilization is largely undetermined. Direct research on embryo derived from infected human sperm and healthy human ova have been difficult because of ethical issues and problems in the collection of ova. However, the use of inter-specific in vitro fertilization (IVF) between human sperm and hamster ova can avoid both of these problems. Combined with molecular, cytogenetical and immunological techniques such as the preparation of human sperm chromosomes, fluorescent in situ hybridization (FISH), and immunofluorescence assay (IFA), this study mainly explored whether any integrated HIV provirus were present in the chromosomes of infected patients' sperm, and whether that provirus could be transferred into early embryos by fertilization and maintain its function of replication and expression. Evidence showed that HIV-1 nucleic acid was present in the spermatozoa of HIV/AIDS patients, that HIV-1 provirus is present on the patient sperm chromosome, that the integrated provirus could be transferred into early embryo chromosomally integrated by fertilization, and that it could replicate alongside the embryonic genome and subsequently express its protein in the embryo. These findings indicate the possibility of vertical transmission of HIV-1 from the sperm genome to the embryonic genome by fertilization. This study also offers a platform for the research into this new mode of transmission for other viruses, especially sexually transmitted viruses.

The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. UC-MSCs were isolated from Wharton’s jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 30 Gy of radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after-irradiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of radiation myelopathy could significantly improve the antioxidative microenvironment in vivo.

Trisomy 21 is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. There has been limited research into the DNA methylation status of CpG islands (CGIs) in trisomy 21, therefore, exploring the DNA methylation status of CGIs in 21q is essential for the development of a series of potential epigenetic biomarkers for prenatal screening of trisomy 21. First, DNA sequences of CGIs in 21q from the USCS database were obtained and 149 sequences and 148 pairs of primers in the BGI YH database were aligned. All 300 cases were analyzed by a heavy methyl-polymerase chain reaction (HM-PCR) assay and a comparison of the DNA methylation status of CGIs was made between trisomy 21 and the control. The HM-PCR assay results did not show a difference in the DNA methylation status between individuals with trisomy 21 and the control. In total, there were 11 CGIs that showed various DNA methylation statuses between Japanese and Chinese patients. Subsequently, bisulfite genomic sequencing found variations in the methylation status of CpG dinucleotides in CGIs (nos. 14, 75, 109, 134 and 146) between trisomy 21 and the control. The different DNA methylation status of CpG dinucleotides in CGIs may be a potential epigenetic marker for diagnosing trisomy 21. No difference was identified in the DNA methylation status of 21q CGIs among Chinese individuals with trisomy 21 and the control. The homogeneity of the DNA methylation status of 21q CGIs in Chinese patients indicates that DNA methylation is likely to be an epigenetic marker distinguishing ethnicities.

Studying the methylation status of long terminal repeats (LTR) and its relationship to gag expression of HIV-1 in order to explore regulation mechanism of HIV-1 gene expression in vertical transmission from sperm to embryo. Sperm samples were collected from a healthy donor and seven patients with HIV/AIDS. Zona-free hamster ova were fertilized by donor's spermatozoa transfected with pIRES2-EGFP-LTR-gag and patient's spermatozoa to obtain zygotes and 2-cell embryos, respectively. Interspecific in vitro fertilization, bisulfite sequencing PCR (BSP), RT-PCR, nested RT-PCR, nested real-time qRT-PCR and 2(-△△Ct) method, indirect immunofluoresence (IF) assay were performed. For donor's samples, the methylation rates of HIV-1 LTR were 0.56%, 1.67%, 0.56%, 0.56% in plasmid, spermatozoa, zygotes and 2-cell embryos, respectively while spermatozoa were transfected with unmethylated plasmid, and were 95.0%, 84.44%, 3.3%, 1.67% while transfected with methylated plasmid. The positive bands for HIV-1 gag cDNA were detected in spermatozoa and 2-cell embryos. The positive signals for HIV-1 p24 Gag protein were detected in 2-cell embryos but not in spermatozoa. For patient's samples, methylation rates of HIV-1 LTR were different in spermatozoa among patients. After fertilization, CpG sites in HIV-1 LTR were highly demethylated in zygotes and 2-cell embryos. The gag transcription levels increased with decreasing of methylation rates of HIV-1 LTR, which showed a strong negative correlations between gag transcription levels and methylation rates of HIV-LTR ether in the spermatozoa (r = -0.9877, P<0.0001) or in the sperm-derived 2-cell embryos (r = -0.9092, P = 0.0045). LTR methylation regulates expression of HIV-1 gag in vertical transmission from sperm to embryo.

We formulate an HIV/AIDS transmission model that considers the dependence of HIV/AIDS progress on infection age (the time since infection), disease age (the time elapsed since the onset), and impulsive antiretroviral treatment. Since no effective vaccine is available for HIV/AIDS, our impulsive disease-control strategy is targeted at infected individuals (I control). Thus the model only includes infective class and AIDS class: infected population is the state at birth, and AIDS population is not the state at birth. Assuming the theoretical strategy can provide HIV testing for risk population groups every T years and immediate antiretroviral treatment for HIV-positive people. The action is approximated by impulsive differential equations. We demonstrate the effect of the impulsive drug treatment and show that there exists a globally stable infection-free state when the impulsive period Tand drug-treatment proportion p satisfy R(p,T)<1. This result shows that the prevention effects can drive HIV/AIDS epidemic towards to elimination.

This study aimed to determine whether plasma testosterone is associated with the severity of coronary atherosclerosis in a group of 803 men who underwent elective coronary angiography. Testosterone levels were measured in 803 male patients who were categorized into three groups according to testosterone level tertiles. All patients underwent elective coronary angiography, and the severity of coronary artery disease （CAD） was determined by the Gensini score. Moreover, patients were classified into two groups according to Gensini scores （score ≤ 26 and score 〉26） using the median values as cutoff points. The plasma testosterone levels were measured by an ELISA kit. The level of testosterone was negatively associated with the Gensini score （r=-0. 188; P=0.000）. A multiple linear regression analysis revealed that testosterone was an independent risk factor for the Gensini score （β=-0,110; P=0.002） after adjusting for confounding covariates. In a multivariate logistic regression model, the severity of CAD was shown to be significantly lower in the third tertile （highest） of testosterone compared to the first tertile （lowest） of testosterone （odds ratio （0R）=0.465; 95% confidence interval （C1）. 0.327-0.662; P=0.000）. In this study, patients with lower testosterone levels had higher Gensini scores in a group of 803 men who underwent elective coronary angiography. Additional studies are needed to clarify the direction of causality and possible underlying mechanisms.

Gastrodia elata Blume, a fully mycoheterotrophic perennial plant of the family Orchidaceae, is a traditional Chinese herb with medicinal and edible value. Interestingly, G. elata requires symbiotic relationships with Mycena and Armillaria strains for seed germination and plant growth, respectively. However, there is no comprehensive summary of the symbiotic mechanism between fungi and G. elata . Here, the colonization and digestion of hyphae, the bidirectional exchange of nutrients, the adaptation of fungi and G. elata to symbiosis, and the role of microorganisms and secondary metabolites in the symbiotic relationship between fungi and G. elata are summarized. We comprehensively and deeply analyzed the mechanism of symbiosis between G. elata and fungi from three perspectives: morphology, nutrition, and molecules. The aim of this review was to enrich the understanding of the mutualistic symbiosis mechanisms between plants and fungi and lay a theoretical foundation for the ecological cultivation of G. elata .

The artificial breeding of fireflies is vital for supplementing natural populations. Unfortunately, mycosis is being observed with increasing frequency in the artificial breeding of fireflies, resulting in increased mortality. This study reports the identification of a microfungus that infects larval Pygoluciola sp., a species of semi-aquatic fireflies, during artificial breeding. Morphological and molecular analysis identified the fungi as Trichoderma koningiopsis (named as ZL01 strain). In addition, nystatin was selected out of five candidates as the optimal antifungal agent against T. koningiopsis ZL01, with a minimum inhibitory concentration of 25.00 μg/mL. Acute oral and contact in vivo toxicity tests on larval Pygoluciola sp. confirmed the safety of nystatin. Furthermore, compared to a Pygoluciola sp. larval population infected with T. koningiopsis ZL01, nystatin treatment increased the survival rate of larvae by twofold (spray administration) and threefold (drip administration) at the end of a nine-day artificial breeding experiment. These findings indicate that nystatin could be used as a potential antifungal agent to control mycosis in artificially bred fireflies. This study was the first to document the infection of semi-aquatic fireflies by pathogens and provide a corresponding treatment strategy.

Aimed at the nonlinearity and uncertainty of the manipulator system, a RBF (radial basis function) neural network-based fuzzy sliding-mode control method was proposed in this paper, in order to make the manipulator track the given trajectory at an ideal dynamic quality. In this method, the equivalent part of the sliding-mode control is approximated by the RBF neural network, in which no model information is required. Meanwhile, a fuzzy controller is developed to make adaptive adjustment of the sliding-mode control’s switching gains according to the distance between the current motor point and the sliding-mode surface, thus effectively the problem of chattering is solved. This method has, to some extent, improved the performance of response and tracking, and reduced the time of adjustment and chattering of input control. The system stability is verified by Lyapunov’s theorem. The simulation result suggests that the algorithm designed for the three-degree-of-freedom (3DOF) manipulator system is effective.

Objective： To investigate the effects of CAL-101, particularly when combined with bortezomib（BTZ） on mantle cell lymphoma（MCL） cells, and to explore its relative mechanisms.Methods： MTT assay was applied to detect the inhibitory effects of different concentrations of CAL-101. MCL cells were divided into four groups： control group, CAL-101 group, BTZ group, and CAL-101/BTZ group. The expression of PI3K-p110σ, AKT, ERK, p-AKT and p-ERK were detected by Western blot. The apoptosis rates of CAL-101 group, BTZ group, and combination group were detected by flow cytometry. The location changes of nuclear factor kappa-B（NF-κB） of 4 groups was investigated by NF-κB Kit exploring. Western blot was applied to detect the levels of caspase-3 and the phosphorylation of AKT in different groups. Results： CAL-101 dose- and time-dependently induced reduction in MCL cell viability. CAL-101 combined with BTZ enhanced the reduction in cell viability and apoptosis. Western blot analysis showed that CAL-101 significantly blocked the PI3K/AKT and ERK signaling pathway in MCL cells. The combination therapy contributed to the inactivation of NF-κB and AKT in MCL cell lines. However, cleaved caspase-3 was up-regulated after combined treatment. Conclusion： Our study showed that PI3K/p110σ is a novel therapeutic target in MCL, and the underlying mechanism could be the blocking of the PI3K/AKT and ERK signaling pathways. These findings provided a basis for clinical evaluation of CAL-101 and a rationale for its application in combination therapy, particularly with BTZ.