The difficulties of early detection for infectious disease outbreak in China:A qualitative investigation

Objective： To make intensified analysis upon the existing difficulties in early detection for the infectious diseases outbreak in China and put forward some effective measures to improve it. Methods： Field investigation and in-depth interview were applied in 23 interviewees from different-level CDC. Results：The study findings suggest that although the timeliness of outbreak detection has been improved since SARS epidemic in China, some problems still exist, such as： ① lacking syndrome surveillance; ② report quality of infectious disease should be improved; ③ difficulties of identifying the cases at lower social economic status; ④a definite financial compensation mechanism for the operation of web-based report system is absent; ⑤insufficient information exchange among different branches. Conclusion：Some effective measures must be taken including developing syndrome surveillance system; affording more education and txaining for related staff; increasing payout on surveillance and establishing an information exchange platform for early detection of disease outbreak.

Deep tumor-penetrating nano-delivery strategy to improve diagnosis and therapy in patient-derived xenograft(PDX)oral cancer model and patient tissue

Nanoprodrugs that are directly assembled by prodrugs attract considerable attention with high anticancer potentials.However,their stability and efficiency of tumor-targeted delivery remain a major challenge in practical biomedical applications.Here,we report a new deep tumor-penetrating nano-delivery strategy to achieve enhanced anti-cancer performance by systematic optimization of a porphyrin-doxorubicin-based nanoprodrug using various PEGylations/crosslinks and co-administration of targeting peptide iRGD.Polyethylene glycols(PEGs)with different molecular weights and grafts are employed to crosslink the nanoprodrug and optimize size,charge,tumor accumulation and penetration,and anti-cancer efficiency,etc.The tumor penetration was validated in syngeneic oral cancer mouse models,patient-derived xenograft(PDX)models,and oral cancer tissue from patients.The optimized nanoprodrug co-administrated with iRGD remarkably enhances the accumulation and penetration both in tumor vascular and PDX tumor tissue.It is effective and safe to improve in vivo therapeutic efficacy via the passive tumor targeting dependent and independent mode.Our tumor-penetrating nano-delivery strategy is promising to strengthen the nanoprodrugs in clinical implementation.

HIV-1 viral cores enter the nucleus collectively through the nuclear endocytosis-like pathway

It is recognized that HIV-1 capsid cores are disassembled in the cytoplasm, releasing their genomes into the nucleus through nuclear pores, but there is also evidence showing the capsid(CA) exists in the nucleus. Whether HIV-1 enters the nucleus and how it enters the nucleus through the undersized nuclear pore remains mysterious. Based on multicolor labeling and real-time imaging of the viral and cellular components, our observations via light and electron microscopy suggest that HIV-1 selectively gathered at the microtubule organization center(MTOC), leading the nearby nuclear envelope(NE) to undergo deformation,invagination and restoration to form a nuclear vesicle in which the viral particles were wrapped;then, the inner membrane of the nuclear vesicle ruptured to release HIV-1 into the nucleus. This unexpected discovery expands our understanding of the complexity of HIV-1 nuclear entry, which may provide new insights to HIV-1 virology.