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Background In 2019, the National Health Commission launched the construction of compact county medical alliance to strengthen chronic diseases management in primary care, and the construction of chronic disease management models varies among county medical alliance sites. Xindu District, as one of the first national compact county medical alliance sites in Sichuan Province, has explored both dimensions of theoretical and practical innovation in the construction of the innovative model of chronic disease management in compact county medical alliance with treatment-prevention integration, providing a new approach for the innovative development of primary compact county medical alliance in China. Objective To analyze the innovation model and its effectiveness of chronic disease management in compact county medical alliance with treatment-prevention integration of Xindu District with the experience of international integrated medical models. Methods The chronic disease management in compact county medical alliance with treatment-prevention integration of Xindu District was constructed with "one center, two integration, three reforms and four safeguard mechanisms" under the leadership of Xindu District Health Bureau, to strengthen the management of chronic diseases mainly including hypertension and diabetes. Results As of June 2022, the number of hypertension or diabetes patients under standardized management in the district increased by 50.87% compared with the initial stage of construction, the number of hypertension or diabetes patients increased by 55.28% and 49.04%, respectively; while the proportion of patients with HbA1c

Virus-like vesicles (VLVs) are membrane-enclosed vesicles that resemble native enveloped viruses in organization but lack the viral capsid and genome. During the productive infection of tumor-associated gammaherpesviruses, both virions and VLVs are produced and are released into the extracellular space. However, studies of gammaherpesvirus-associated VLVs have been largely restricted by the technical difficulty of separating VLVs from mature virions. Here we report a strategy of selectively isolating VLVs by using a Kaposi's sarcoma-associated herpesvirus (KSHV) mutant that is defective in small capsid protein and is unable to produce mature virions. Using mass spectrometry analysis, we found that VLVs contained viral glycoproteins required for cellular entry, as well as tegument proteins involved in regulating lytic replication, but lacked capsid proteins. Functional analysis showed that VLVs induced the expression of the viral lytic activator RTA, initiating KSHV lytic gene expression. Furthermore, employing RNA sequencing, we performed a genomewide analysis of cellular responses triggered by VLVs and found that PRDM1, a master regulator in cell differentiation, was significantly upregulated. In the context of KSHV replication, we demonstrated that VLV-induced upregulation of PRDM1 was necessary and sufficient to reactivate KSHV by activating its RTA promoter. In sum, our study systematically examined the composition of VLVs and demonstrated their biological roles in manipulating host cell responses and facilitating KSHV lytic replication.IMPORTANCE Cells lytically infected with tumor-associated herpesviruses produce a high proportion of virus-like vesicles (VLVs). The composition and function of VLVs have not been well defined, largely due to the inability to efficiently isolate VLVs that are free of virions. Using a cell system capable of establishing latent KSHV infection and robust reactivation, we successfully isolated VLVs from a KSHV mutant defective in the small capsid protein. We quantitatively analyzed proteins and microRNAs in VLVs and characterized the roles of VLVs in manipulating host cells and facilitating viral infection. More importantly, we demonstrated that by upregulating PRDM1 expression, VLVs triggered differentiation signaling in targeted cells and facilitated viral lytic infection via activation of the RTA promoter. Our study not only demonstrates a new strategy for isolating VLVs but also shows the important roles of KSHV-associated VLVs in intercellular communication and the viral life cycle.

Inspired by the fabrication of zigzag MoSe2 nanoribbons and MoS2 nanoribbons with well‐defined atomically precise edges, we study the stability, electronic structures, and magnetic properties of zigzag VS2 nanoribbons (ZNRs) with different edge structures and widths. The calculated edge energies for all studied VS2 nanoribbons are less than 0.9 eV/Å, lower than that of fabricated armchair and zigzag graphene nanoribbons, indicating the easy formation of ZNRs. The results show N‐ZNRs terminated with S and V atoms (N‐SV‐ZNRs) is a ferrimagnetic metal. The magnetic moments are mainly contributed by d orbitals of V atoms, and the V2 atom exhibits a spin that is antiparallel to the other V atoms due to the increase of through–space interaction. With hydrogen passivation, the magnetic moment of V2 atom in N‐SV‐ZNRs couples ferromagnetically with other V atoms and N‐SV‐ZNRs becomes half metallic. The N‐ZNRs terminated with V atom (N‐VV‐ZNRs) is found to be a magnetic metal, and the magnetic moments of V atoms around edges are very sensitive to ribbon width. Furthermore, N‐ZNRs with S atom terminations (N‐SS‐ZNRs) is a ferromagnetic quasi‐semiconductor. Only select bands intersect with the Fermi level near the Γ point, and the magnetic moments of all V atoms couple ferromagnetically. These findings are essential for applications of VS2 nanoribbons–based low‐dimensional spintronic devices. [ABSTRACT FROM AUTHOR]

Tumor microenvironment (TME) is essential for the development and progression of hepatocellular carcinoma (HCC). Exosomes participate in constructing TME by passing biological information, but the regulatory effect of PDL1 in exosomes on anticancer activity of CD8+ T cells in HCC still needs to be further explored. In this study, high level of PDL1 was found in plasma exosomes of HCC patients, which turned out to be significantly associated with the increased number of tumor nodules, the upregulated level of serum AFP, the raised tendency of TNM stage, and the poor prognosis of HCC. The expression of CD8 may be inhibited in HCC that is characterized with high level of PDL1, and the protein level of exosomal PDL1 was determined by intracellular PDL1 abundance. High level of exosomal PDL1 inhibited the proliferation and activation of CD8+ T cells, but exhibited limited effect on the proliferation of hepatic cancer cells. Moreover, the growth of tumors formed by hepatic cancer cells Hepa1–6 in C57L mice was significantly promoted by the exosomal PDL1, which might be caused by the inhibitory effect of exosomal PDL1 on CD8+ T cells. Thus, exosomal PDL1 promotes the development and progression of HCC through inhibiting the anticancer activity of CD8+ T cells. This study provides sights for understanding the oncogenic role of PDL1 and a reasonable explanation for the low efficacy of anti‐PD1/PDL1 immunotherapies in HCC. [ABSTRACT FROM AUTHOR]