The effects of choline chloride/oxalic acid deep eutectic solvents (ChCl/OA DES) as a green and effective promoter assisting the synthesis of vanadium phosphorus oxide (VPO) catalysts for the selective oxidation of n-butane to maleic anhydride were investigated in detail. A combination of characterizations with the performance was considered to understand the essential effects of DES. DES play the role of a crystal induced agent and structural modifier, facilitating the formation of a single-crystal structure on the surface of precursor; correspondingly, topological transformation to the single-crystal active phase under the activation conditions accompany the decomposition of DES. It is suggested that ChCl/OA DES can interact with V2O5 and form a new vanadium complex, which affects the reaction between V2O5 and H3PO4. Meanwhile, the ChCl/OA DES could regulate the surface chemical state and redox characteristic, resulting in the enhancement on the catalytic performance of VPO.

Human herpesvirus 6B (HHV-6B) belongs to the β-herpesvirus subfamily of the Herpesviridae. To understand capsid assembly and capsid-tegument interactions, here we report atomic structures of HHV-6B capsid and capsid-associated tegument complex (CATC) obtained by cryoEM and sub-particle reconstruction. Compared to other β-herpesviruses, HHV-6B exhibits high similarity in capsid structure but organizational differences in its CATC (pU11 tetramer). 180 “VΛ”-shaped CATCs are observed in HHV-6B, distinguishing from the 255 “Λ”-shaped dimeric CATCs observed in murine cytomegalovirus and the 310 “Δ”-shaped CATCs in human cytomegalovirus. This trend in CATC quantity correlates with the increasing genomes sizes of these β-herpesviruses. Incompatible distances revealed by the atomic structures rationalize the lack of CATC’s binding to triplexes Ta, Tc, and Tf in HHV-6B. Our results offer insights into HHV-6B capsid assembly and the roles of its tegument proteins, including not only the β-herpesvirus-specific pU11 and pU14, but also those conserved across all subfamilies of Herpesviridae.

Catalytic performance of undoped and Fe-doped VPO catalysts.

Efficacy of immunotherapy in hepatocellular carcinoma (HCC) is blocked by its high degree of inter‐ and intra‐tumor heterogeneity and immunosuppressive tumor microenvironment. However, the correlation between tumor heterogeneity and immunosuppressive microenvironment in HCC has not been well addressed. Here, we endeavored to dissect inter‐ and intra‐tumor heterogeneity in HCC and uncover how they contribute to the immunosuppressive microenvironment. We performed consensus molecular subtyping with non‐negative matrix factorization (NMF) clustering to stratify the inter‐heterogeneity profile of HCC tumors. We grouped HCC tumors from the Cancer Genome Atlas (TCGA) patients into three subtypes (S1, S2 and S3), where S1 was characterized as a ‘hot tumor’ profile with high expression level of T cell genes and rate of immune scores. S2 was characterized as a ‘cold tumor’ profile with the highest tumor purity score, and S3 as an ‘immunosuppressed tumor’ profile with the poorest prognosis and a high expression level of immunosuppressive genes such as cytotoxic T‐lymphocyte‐associated protein‐4, TIGIT, and PDCD1 . Moreover, we combined weighted gene co‐expression network analysis and single‐cell regulatory network inference and clustering (SCENIC) in the single‐cell dataset of the S3‐like subtype (CS3) and identified a transcription factor, BATF , which could upregulate immunosuppressive genes. Finally, we identified a cell interaction network in which a myeloid‐derived suppressor cell‐like macrophage subtype could promote the formation of immunosuppressive T‐cells.

No abstract

The α-keto acid dehydrogenase complex family catalyzes the essential oxidative decarboxylation of α-keto acids to yield acyl-CoA and NADH. Despite performing the same overarching reaction, members of the family have different component structures and structural organization between each other and across phylogenetic species. While native structures of α-keto acid dehydrogenase complexes from bacteria and fungi became available recently, the atomic structure and organization of their mammalian counterparts in native states remain unknown. Here, we report the cryo-electron microscopy structures of the endogenous cubic 2-oxoglutarate dehydrogenase complex (OGDC) and icosahedral pyruvate dehydrogenase complex (PDC) cores from bovine kidney determined at resolutions of 3.5 Å and 3.8 Å, respectively. The structures of multiple proteins were reconstructed from a single lysate sample, allowing direct structural comparison without the concerns of differences arising from sample preparation and structure determination. Although native and recombinant E2 core scaffold structures are similar, the native structures are decorated with their peripheral E1 and E3 subunits. Asymmetric sub-particle reconstructions support heterogeneity in the arrangements of these peripheral subunits. In addition, despite sharing a similar monomeric fold, OGDC and PDC E2 cores have distinct interdomain and intertrimer interactions, which suggests a means of modulating self-assembly to mitigate heterologous binding between mismatched E2 species. The lipoyl moiety lies near a mobile gatekeeper within the interdomain active site of OGDC E2 and PDC E2. Analysis of the twofold related intertrimer interface identified secondary structural differences and chemical interactions between icosahedral and cubic geometries of the core. Taken together, our study provides a direct structural comparison of OGDC and PDC from the same source and offers new insights into determinants of interdomain interactions and of architecture diversity among α-keto acid dehydrogenase complexes.

Background and Aims Intrahepatic cholangiocarcinoma (ICC) is not fully investigated, and how stromal cells contribute to ICC formation is poorly understood. We aimed to uncover ICC origin, cellular heterogeneity, and critical modulators during ICC initiation/progression, and to decipher how fibroblast and endothelial cells in the stromal compartment favor ICC progression. Approach and Results We performed single‐cell RNA sequencing (scRNA‐seq) using AKT/Notch intracellular domain–induced mouse ICC tissues at early, middle, and late stages. We analyzed the transcriptomic landscape, cellular classification and evolution, and intercellular communication during ICC initiation/progression. We confirmed the findings using quantitative real‐time PCR, western blotting, immunohistochemistry or immunofluorescence, and gene knockout/knockdown analysis. We identified stress‐responding and proliferating subpopulations in late‐stage mouse ICC tissues and validated them using human scRNA‐seq data sets. By integrating weighted correlation network analysis and protein–protein interaction through least absolute shrinkage and selection operator regression, we identified zinc finger, MIZ‐type containing 1 (Zmiz1) and Y box protein 1 (Ybx1) as core transcription factors required by stress‐responding and proliferating ICC cells, respectively. Knockout of either one led to the blockade of ICC initiation/progression. Using two other ICC mouse models (YAP/AKT, KRAS/p19) and human ICC scRNA‐seq data sets, we confirmed the orchestrating roles of Zmiz1 and Ybx1 in ICC occurrence and development. In addition, hes family bHLH transcription factor 1, cofilin 1, and inhibitor of DNA binding 1 were identified as driver genes for ICC. Moreover, periportal liver sinusoidal endothelial cells could differentiate into tip endothelial cells to promote ICC development, and this was Dll4‐Notch4‐Efnb2 signaling–dependent. Conclusions Stress‐responding and ICC proliferating subtypes were identified, and Zmiz1 and Ybx1 were revealed as core transcription factors in these subtypes. Fibroblast–endothelial cell interaction promotes ICC development.

Vanadyl pyrophosphate contained catalysts (VPP) are of great importance for the selective oxidation of light alkane to chemicals. Achieving high conversion of alkane with a high selectivity of target products is critical for the practical applications of VPP. Here we selected three Mo species H5Mo12O41P (PMA), MoO3, and (NH4)6Mo7O4⋅4H2O (HAM) as promoters for VPP catalysts. Performance evaluation shows that all Mo‐promoted VPP catalysts have much better catalytic performance than those without Mo promoter, which are mainly attributed to the different Mo species could induce the formation of active crystal and affect the redox characteristic to varying degrees. Moreover, SEM revealed that the PMA possess a “shape memory” function, which result in crystallinity of (200) in PMA‐VPO is higher than others. H2‐TPR suggested that PMA could increase the amount of oxygen and reduce the reduction activation energy, which is beneficial to enhance the activity of VPP. The presented results may be helpful for selecting superior metal promoter and facilitated the process of VPP catalyst development for n‐butane selective oxidation.