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Objective New rationally designed i,i+7 -hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i+7 -hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication (IC 50 ) in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the IC 50 s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate distinctive features in drug-resistant mutations (DRMs) and interpretations for reverse transcriptase inhibitors (RTIs) between proviral DNA and paired viral RNA in HIV-1-infected patients. Methods Forty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared between viral RNA and paired proviral DNA. Results Compared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher's exact test, P <0.05). Considering ‘majority resistant variants’, 15 samples (19.48%) showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs. Considering ‘minority resistant variants’, 22 samples (28.57%) were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA. Conclusion Compared with viral RNA, the distinctive information of DRMs and drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effect of factors relevant to blastocyst transfer on the pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET)., Methods: The clinical data of 790 pregnant women who underwent IVF-ET in our hospital from July 2015 to July 2020 were retrospectively analyzed. The pregnancy outcome of blastocysts transferred on day 5 (D5, n =705) and those transferred on day 6 (D6, n =85) were compared. According to the pregnancy outcome, the cases were divided into a live birth group ( n =322) and a non-live birth group ( n =468), and multivariate logistic regression was conducted to study the effect of factors relevant to blastocyst transfer on the live birth outcome of IVF-ET., Results: In the D5 group, the biochemical pregnancy rate, clinical pregnancy rate and live birth rate of blastocyst transfer were 69.93%, 64.96%, and 41.84%, respectively, which were significantly higher than those of the D6 group at 50.59%, 45.88%, and 30.59%, respectively. The difference was statistically significant ( P <0.05). There was no statistically significant difference in the miscarriage rate between the D5 group and the D6 group ( P >0.05). Multivariate logistic analysis revealed that age>35 years, years of infertility>5 years, endometrium thickness<9 mm on the day of blastocyst transfer, trophoblast cell rating of C, blastocyst transfer performed on D6, and multiparity were all risk factors for non-live birth outcome of IVF-ET ( P <0.05)., Conclusion: The adverse pregnancy outcomes of IVF-ET were found to be associated with age, duration of infertility, endometrial thickness on the day of to blastocyst transfer, trophoblast cell rating, and blastocyst transfer performed after how many days of embryo development, and multiparity, which should be closely monitored, and effective measures should be adopted accordingly to prevent adverse outcomes of pregnancy., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Three new alkaloids, iizukines C-E (1-3), including two aspochalasins (1 and 2), and one brasiliamide derivative (3), along with two known aspochalasins, rosellichalasin (4) and cytochalasin Z17 (5), were isolated from the culture of Aspergillus iizukae. Compound 1 was the first aspochalasin uniquely featuring a 1,2,4-triazole functionality, and 3 showed a pair of NMR signals in CDCl 3 with a ratio of about 2:1 due to the existence of conformational isomers. Their structures were determined by extensive spectroscopic analyses and single-crystal X-ray diffractions. In particular, the 1,2,4-triazole moiety in 1 was assigned on the basis of extremely valuable 1 H- 15 N HMBC spectrum. Compound 1 exhibited cytotoxic effect towards HL-60 and A549 cell lines with IC 50 values of 3.8 and 7.2 μM, respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Three new diastereomers of polyketides (PKs), raistrickiones A&minus;C ( 1 ⁻ 3 ), together with two new analogues, raistrickiones D and E ( 4 and 5 ), were isolated from a highly productive strain of Penicillium raistrickii , which was subjected to an experimental thermo-change strategy to tap its potential of producing new secondary metabolites. Metabolites 1 and 2 existed in a diastereomeric mixture in the crystal packing according to the X-ray data, and were laboriously separated by semi-preparative HPLC on a chiral column. The structures of 1 ⁻ 5 were determined on the basis of the detailed analyses of the spectroscopic data (UV, IR, HRESIMS, 1D, and 2D NMR), single-crystal X-ray diffractions, and comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1 ⁻ 5 represented the first case of 3,5-dihydroxy-4-methylbenzoyl derivatives of natural products. Compounds 1 ⁻ 5 exhibited moderate radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH).

In the title compound, C(18)H(19)NO, the dihedral angle between 4-methyl-phenyl and 4-(dimethyl-amino)phenyl rings is 45.5 (3)°. The C-C=C-C torsion angle of 173.8 (3)° indicates that the mol-ecule adopts an E configuration. The dimethyl-amino group is nearly coplanar with the attached benzene ring, making a dihedral angle of 2.7 (3)°. Weak inter-molecular C-H⋯π inter-actions are observed in the crystal structure.

Objective: To investigate the single nucleotide polymorphism (SNP) of HIV-1 coreceptor CCR5 gene in Chinese Yi ethnic group and the association between these SNPs and HIV/AIDS., Methods: Peripheral blood samples of 102 HIV negative persons of Chinese Yi nationality, 87 males amd 15 females, aged 23 (12-37), and 68 HIV carriers, 61 males and 7 females, aged 27 (17-51). The regulatory and structural regions of the HIV coreceptor CCR5 gene were amplified from the genomic DNA by nested PCR, each of the two regions was divided into three gene fragments which were overlapped. High throughput DHPLC was used for screening of unknown mutations in each gene fragment. The PCR products showing different peak traces from wild types in DHPLC were sequenced by forward and reverse primers respectively. The sequences were analyzed with the help of Sequence Navigator software to search for SNP loci. Statistical analysis by SPSS and PPAP softwares were made to study the association between these SNPs and HIV infection., Results: Five SNPs (A77G, G316A, T532C, C921T, and G668A) and a AGA deletion of the 686-688 nucleotides were discovered in the coding region of this gene in Chinese Yi ethnic group. C921T mutation was a nonsense mutation, and the other SNPs (A77G, G316A, T532C, and G668A) are sense mutation, with the amino acid changes of K26R, G106R, C178R, and R223Q. Only the frequency of R223Q allelic gene was high (0.08) but those of the others were low (less than 0.01). There was no significant difference in the allele frequency between the HIV negative and HIV positive groups (all P > 0.05). Five SNP loci (T58934G, G59029A, T59353C, G59402A, and C59653T) were found in the regulatory region of CCR5 gene with high allelic frequencies of 0.1912-0.2941. Between the HIV negative and HIV positive groups, there were no differences in the SNP loc (all P > 0.05). Statistical analysis of the association between the linkage of mutation loci with HIV infection suggested a significant difference in the haplotype frequency of T59353C-G59402A between the HIV negative and HIV positive groups of the Yi population., Conclusion: A high throughput screening method of detecting unknown genetic mutation DHPLC can effectively analyze the SNP of CCR5 regulatory and structural regions in Chinese Yi ethnic group.