Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives.

Primary liver cancer is a solid malignancy with a high mortality rate. The success of immunotherapy has shown great promise in improving patient care and highlights a crucial need to understand the complexity of the liver tumor immune microenvironment (TIME). Recent advances in single-cell and spatial omics technologies, coupled with the development of systems biology approaches, are rapidly transforming the landscape of tumor immunology.

MiR181-5p promotes pathogenic angiogenesis of hepatopulmonary syndrome by negatively regulating Wnt inhibitor Wif1.

Objectives: Hepatopulmonary syndrome is a serious respiratory injury caused by chronic liver disease. Excessive pulmonary capillary angiogenesis is the key pathological event. However, the mechanism of microRNA regulatory pulmonary capillary angiogenesis is still unclear.

Zfp281 and Zfp148 control CD4 T cell thymic development and T2 functions.

How CD4 lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (T2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4 T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4 lineage-committing factor Thpok.

Molecular basis for protein histidine N1-specific methylation of the "His-x-His" motifs by METTL9.

Histidine methylation serves as an intriguing strategy to introduce altered traits of target proteins, including metal ion chelation, histidine-based catalysis, molecular assembly, and translation regulation. As a newly identified histidine methyltransferase, METTL9 catalyzes N1-methylation of protein substrates containing the "His-x-His" motif (HxH, x denotes small side chain residue). Here our structural and biochemical studies revealed that METTL9 specifically methylates the second histidine of the "HxH" motif, while exploiting the first one as a recognition signature.

Generation and Use of Glycosyl Radicals under Acidic Conditions: Glycosyl Sulfinates as Precursors.

We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which are bench-stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction.

Heat Stress Weakens the Skin Barrier Function in Sturgeon by Decreasing Mucus Secretion and Disrupting the Mucosal Microbiota.

Heat stress induced by global warming has damaged the well-being of aquatic animals. The skin tissue plays a crucial role as a defense barrier to protect organism, however, little is known about the effect of heat stress on fish skin, particularly in cold-water fish species. Here, we investigated the effects of mild heat stress (24°C, MS) and high heat stress (28°C, HS) on Siberian sturgeon skin using RNA-seq, histological observation, and microbial diversity analysis.

Glycosyl-Radical-Based Synthesis of -Alkyl Glycosides via Photomediated Defluorinative -Difluoroallylation.

We have developed a stereoselective, glycosyl radical-based method for the synthesis of -alkyl glycosides via a photomediated defluorinative -difluoroallylation reaction. We demonstrate for the first time that glycosyl radicals, generated from glycosyl bromides, can readily participate in a photomediated radical polar crossover process, affording a diverse array of -difluoroalkene containing -glycosides. Notable features of this method include scalability, mild conditions, broad substrate scope, and suitability for the late-stage modification of complex molecules.

An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development.

αβ lineage T cells, most of which are CD4 or CD8 and recognize MHC I- or MHC II-presented antigens, are essential for immune responses and develop from CD4CD8 thymocytes. The absence of in vitro models and the heterogeneity of αβ thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human αβ thymocyte developmental trajectories.

Cyanide-Free Synthesis of Glycosyl Carboxylic Acids and Application for the Synthesis of Scleropentaside A.

We have developed a cyanide-free strategy for the synthesis of glycosyl carboxylic acids, which can provide 1,2- or 1,2- glycosyl carboxylic acids and is compatible with common protecting groups. The synthetic utility was demonstrated by the synthesis of 12 unreported glycosyl acids and the total synthesis of scleropentaside A.

Binding of HMGN proteins to cell specific enhancers stabilizes cell identity.

The dynamic nature of the chromatin epigenetic landscape plays a key role in the establishment and maintenance of cell identity, yet the factors that affect the dynamics of the epigenome are not fully known. Here we find that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 preferentially colocalize with epigenetic marks of active chromatin, and with cell-type specific enhancers. Loss of HMGNs enhances the rate of OSKM induced reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs), and the ASCL1 induced conversion of fibroblast into neurons.

Cordycepin and pentostatin biosynthesis gene identified through transcriptome and proteomics analysis of Cordyceps kyushuensis Kob.

Cordyceps kyushuensis is the only species of cordyceps growing on the larvae of Clanis bilineata Walker, and has been demonstrated that there are lots of pharmacological components including cordycepin. Cordycepin shows lots of pharmacological action but it could be converted to 3'-deoxyinosine by adenosine deaminase in vivo, which weakens the efficiency of cordycepin. That pentostatin, which has been reported to inhibit adenosine deaminase, combining cordycepin could enhance the efficiency of cordycepin in vivo.

Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma.

Unlabelled: Intratumor molecular heterogeneity of hepatocellular carcinoma is partly attributed to the presence of hepatic cancer stem cells (CSCs). Different CSC populations defined by various cell surface markers may contain different oncogenic drivers, posing a challenge in defining molecularly targeted therapeutics. We combined transcriptomic and functional analyses of hepatocellular carcinoma cells at the single-cell level to assess the degree of CSC heterogeneity.

Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is Protective in LPS-Induced Sepsis.

Sepsis, an exaggerated systemic inflammatory response, remains a major medical challenge. Both hyperinflammation and immunosuppression are implicated as causes of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic patients and in experimental sepsis models, but the role of DCs in sepsis, and the mechanisms and significance of DC loss, are poorly understood.

Optineurin insufficiency impairs IRF3 but not NF-κB activation in immune cells.

Optineurin is a widely expressed polyubiquitin-binding protein that has been implicated in regulating cell signaling via its NF-κB essential modulator-homologous C-terminal ubiquitin (Ub)-binding region. Its functions are controversial, with in vitro studies finding that optineurin suppressed TNF-mediated NF-κB activation and virus-induced activation of IFN regulatory factor 3 (IRF3), whereas bone marrow-derived macrophages (BMDMs) from mice carrying an optineurin Ub-binding point mutation had normal TLR-mediated NF-κB activation and diminished IRF3 activation. We have generated a mouse model in which the entire Ub-binding C-terminal region is deleted (Optn(470T)).

Pursuing gene regulation 'logic' via RNA interference and chromatin immunoprecipitation.

RNA interference and chromatin immunoprecipitation are now firmly established as useful methods for studying mechanisms of gene regulation in vivo. Their combined use can help elucidate gene regulation 'logic' by aiding in target gene identification for transcription factors and chromatin-modifying complexes.

Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response.

Studies of mammalian genes activated in response to an acute stimulus have suggested diverse mechanisms through which chromatin structure and nucleosome remodeling events contribute to inducible gene transcription. However, because of this diversity, the logical organization of the genome with respect to nucleosome remodeling and gene induction has remained obscure. Numerous proinflammatory genes are rapidly induced in macrophages in response to microbial infection.

Quorum-sensing Escherichia coli regulator A: a regulator of the LysR family involved in the regulation of the locus of enterocyte effacement pathogenicity island in enterohemorrhagic E. coli.

The locus of enterocyte effacement (LEE) is a chromosomal pathogenicity island that encodes the proteins involved in the formation of the attaching and effacing lesions by enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). The LEE comprises 41 open reading frames organized in five major operons, LEE1, LEE2, LEE3, tir (LEE5), and LEE4, which encode a type III secretion system, the intimin adhesin, the translocated intimin receptor (Tir), and other effector proteins.

ToxR interferes with CRP-dependent transcriptional activation of ompT in Vibrio cholerae.

In pathogenic Vibrio cholerae, the transmembrane DNA-binding protein ToxR co-ordinates the expression of over 20 genes, including those encoding important virulence factors such as cholera toxin and the toxin-co-regulated pilus. The outer membrane protein OmpT is the only member of the ToxR regulon known to be repressed by ToxR. In this study, we examined the environmental conditions that regulate OmpT expression and demonstrated that ompT transcription is upregulated 14-fold when the bacteria enter late log phase from early log phase.