Diosgenin, a natural steroidal saponin, can exert antitumor effect by regulating immune function and improving intestinal microbiota. The response to anti-PD-1 immunotherapy is associated with intestinal microbiota and effector T cells in tumor microenvironment. We hypothesize that the modulation of diosgenin on intestinal microbiota can facilitate antitumor immunity and the therapeutic efficacy of PD-1 antibody. In melanoma-bearing C57BL/6 mice, we observed that the anti-melanoma effect of diosgenin relied more on antitumor immunity than direct tumor inhibition activity evidenced by obvious CD4⁺/CD8⁺ T-cell infiltration and IFN-γ expression in tumor tissues, and it could improve the compositions of intestinal microbiota. Antibiotics impaired the therapeutic efficacy and immunity responses of diosgenin through disturbing intestinal microbiota, indicating the importance of intestinal microbiota in diosgenin’s in vivo antitumor activity. More importantly, the combined administration of PD-1 antibody with diosgenin aggravated the tumor necrosis and apoptosis by eliciting augmented T-cell responses. Taken together, diosgenin can be used as a microecological regulator to induce antitumor immunity and improve the efficacy of immune checkpoint antibody, making it more suitable for the treatment of malignant tumors.

In recent years, the population of men who have sex with men (MSM) have become the most significant increasing group of HIV-1 transmission in China. To identify new recombinant strains and transmission patterns of HIV-1 in Chinese MSM population, a cross-sectional investigation of MSM in Anhui Province (in south-eastern China) was performed in 2011. The diagnosed AIDS case rate, CD4 T-cell counts, HIV subtypes, and origin of the recombinant strains were investigated in 138 collected samples. The phylogenetic and bootscan analyses demonstrated that, apart from three previously reported circulating strains (CRF07_BC, CRF01_AE, subtype B), various recombinant strains among subtype B, subtype C, CRF01_AE, and CRF07_BC were simultaneously identified in Chinese MSM for the first time. The introducing time of B subtype in Chinese MSM populations was estimated in 1985, CRF01_AE in 2000, and CRF07_BC in 2003; the latter two account for more than 85% of MSM infections. Notably, in comparison with B subtype infections in Anhui MSM, CRF01_AE, with the highest prevalence rate, may accelerate AIDS progression. Over half of patients (56%) infected with new recombinant strains infection are diagnosed as progression into AIDS. Both Bayes and phylogenetic analyses indicated that there was active HIV transmission among MSM nationwide, which may facilitate the transmission of the new 01B recombinant strains in MSM. In conclusion, new recombinant strains and active transmission were identified in the Chinese MSM population, which may lead to a new alarming HIV pandemic in this population due to the increased pathogenesis of the newly emerging strains.

As one of prevalence HIV-1 strains in IDUs in Asia, the origination and full transmission map of CRF07_BC is of great interested and remains unclear. In the study, we collected 769 CRF07_BC derived sequences (including 45 sequences generated in our laboratory) from 12 provinces in China for reconstructing transmission map. Meanwhile, ample historic epidemic evidences were also reviewed to assist sequences analysis. In the study, we collected 769 CRF07_BC derived sequences and identified 138 independent sequences from 12 provinces in China for subsequent phylogeographic tree analysis, Bayes Factor test and the estimation of state tMRCA. The analyses demonstrated that CRF07_BC was originated in 1993 in IDU in Yunnan province and then initially spread to Guangxi (eastern neighbor to Yunnan) in 1994, to Xinjiang (northwest) in 1995 and to Sichuan (northern neighbor to Yunnan) in 1996. The subsequent transmissions occurred from Yunnan to Liaoning (northeast) in 1997 and to Jiangsu in 1998. Interestingly, after the early introduction of CRF07_BC into Guangxi, Xinjiang and Sichuan, these three regions served as secondary epicenters for further spreading into Gansu, Ningxia, Qinghai, Beijing and Hunan during 1999–2001. These analyzed results are in accordance with early epidemic investigations. Our data not just reconstructed the migration map of CRF07_BC, but also firstly revealed the active roles of these secondary epicenters in the dynamic migration of CRF07_BC in China.

Syphilis is a systemic sexually transmitted disease caused by Treponema pallidum ssp. pallidum (TPA). The origin and genetic background of Chinese TPA strains remain unclear. We identified a total of 329 single-nucleotide variants (SNVs) in eight Chinese TPA strains using next-generation sequencing. All of the TPA strains were clustered into three lineages, and Chinese TPA strains were grouped in Lineage 2 based on phylogenetic analysis. The phylogeographical data showed that TPA strains originated earlier than did T. pallidum ssp. pertenue (TPE) and T. pallidum ssp. endemicum (TPN) strains and that Chinese TPA strains might be derived from recombination between Lineage 1 and Lineage 3. Moreover, we found through a homology modeling analysis that a nonsynonymous substitution (I415F) in the PBP3 protein might affect the structural flexibility of PBP3 and the binding constant for substrates based on its possible association with penicillin resistance in T. pallidum. Our findings provide new insight into the molecular foundation of the evolutionary origin of TPA and support the development of novel diagnostic/therapeutic technology for syphilis.