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Toll/interleukin-1 receptor (TIR) domain-containing proteins play a critical role in immune responses in diverse organisms, but their function in bacterial systems remains to be fully elucidated. This study, focusing on Escherichia coli, addresses how TIR domain-containing proteins contribute to bacterial immunity against phage attack. Through an exhaustive survey of all E. coli genomes available in the NCBI database and testing of 32 representatives of the 90% of the identified TIR domain-containing proteins, we found that a significant proportion (37.5%) exhibit antiphage activities. These defense systems recognize a variety of phage components, thus providing a sophisticated mechanism for pathogen detection and defense. This study not only highlights the robustness of TIR systems in bacterial immunity, but also draws an intriguing parallel to the diversity seen in mammalian Toll-like receptors (TLRs), enriching our understanding of innate immune mechanisms across life forms and underscoring the evolutionary significance of these defense strategies in prokaryotes.Here, Wang et al survey Escherichia coli genomes to show that TIR domain-containing proteins in E. coli serve as robust anti-phage systems. [ABSTRACT FROM AUTHOR]

Designing artificial viral vectors (AVVs) programmed with biomolecules that can enter human cells and carry out molecular repairs will have broad applications. Here, we describe an assembly-line approach to build AVVs by engineering the well-characterized structural components of bacteriophage T4. Starting with a 120 × 86 nm capsid shell that can accommodate 171-Kbp DNA and thousands of protein copies, various combinations of biomolecules, including DNAs, proteins, RNAs, and ribonucleoproteins, are externally and internally incorporated. The nanoparticles are then coated with cationic lipid to enable efficient entry into human cells. As proof of concept, we assemble a series of AVVs designed to deliver full-length dystrophin gene or perform various molecular operations to remodel human genome, including genome editing, gene recombination, gene replacement, gene expression, and gene silencing. These large capacity, customizable, multiplex, and all-in-one phage-based AVVs represent an additional category of nanomaterial that could potentially transform gene therapies and personalized medicine. Safe delivery of genes is needed for gene therapy. Here the authors build "artificial viral vectors" (AVVs) by engineering the well-characterised structural components of bacteriophage T4: the large capacity, all-in-one, multiplex, programmable, and phage-based AVV nanomaterials have potential for gene therapy. [ABSTRACT FROM AUTHOR]

Lithium-ion micro-batteries (LIMBs) with higher energy density have drawn extensive attention. 3D printing technique based on direct ink writing (DIW) is a low-cost and simple approach to fabricate LIMBs especially with higher areal capacity. Herein, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) nanofibrils are first combined with carbon methyl cellulose (CMC) to achieve the 3D printing of thick LFP (LiFePO4)-PEDOT-CMC electrodes at room temperature by DIW. 3D-printed PEDOT-CMC-based composite thick electrodes demonstrate high conductivity because of the interconnected 3D network including hierarchical macro-micro porous criss-crossing filaments which can provide effective transport paths for Li ions and electrons. Further, LFP-PEDOT-CMC electrodes of different thicknesses are 3D-printed to study the effect of thicknesses on the electrochemical performances. The 3D-printed ultra-thick LFP-CMC-PEDOT electrode of 1.43 mm thickness at lower rate exhibits a highly improved areal capacity (5.63 mAh cm−2, 0.2 C) and high capacity retention (after 100 cycles, 0.2 C, 92%). The rate capability decreases steadily with the increasing thickness. However, for the extra-thick electrodes greater than 1.43 mm thickness, the discharge capacity, rate, and cycle capability decline dramatically. Electrochemical impedance spectroscopy measurements are used to explain the kinetic mechanism. For 3D-printed LFP-CMC-PEDOT electrodes blow 1.43 mm thickness, the 3D network plays the dominant role to maintain the effective transmission dynamics regardless of electrode thickness. But for the extra-thick electrodes, the greater transport distance becomes the major limiting factor resulting in the degradation of electrochemical performances. This work will offer guidance on how to apply 3D-printed ultra-thick electrodes with high energy density to LIMBs. [ABSTRACT FROM AUTHOR]

Large biological structures are assembled from smaller, often symmetric, sub-structures. However, asymmetry among sub-structures is fundamentally important for biological function. An extreme form of asymmetry, a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, is found in numerous icosahedral viruses, including tailed bacteriophages, herpesviruses, and archaeal viruses. This vertex is critical for driving capsid assembly, DNA packaging, tail attachment, and genome ejection. Here, we report the near-atomic in situ structure of the symmetry-mismatched portal vertex from bacteriophage T4. Remarkably, the local structure of portal morphs to compensate for symmetry-mismatch, forming similar interactions in different capsid environments while maintaining strict symmetry in the rest of the structure. This creates a unique and unusually dynamic symmetry-mismatched vertex that is central to building an infectious virion. In icosahedral viruses, a symmetry-mismatched portal vertex is assembled by inserting a 12-fold-symmetric portal complex into a 5-fold-symmetric capsid environment. Here, the authors report a near-atomic-resolution in situ cryo-electron microscopy structure of this symmetrically mismatched viral vertex from bacteriophage T4. [ABSTRACT FROM AUTHOR]

Advances in high-throughput sequencing have facilitated remarkable insights into the diversity and functioning of naturally occurring microbes; however, current sequencing strategies are insufficient to reveal physiological states of microbial communities associated with protein translation dynamics. Transfer RNAs (tRNAs) are core components of protein synthesis machinery, present in all living cells, and are phylogenetically tractable, which make them ideal targets to gain physiological insights into environmental microbes. Here we report a direct sequencing approach, tRNA-seq, and a software suite, tRNA-seq-tools, to recover sequences, abundance profiles, and post-transcriptional modifications of microbial tRNA transcripts. Our analysis of cecal samples using tRNA-seq distinguishes high-fat- and low-fatfed mice in a comparable fashion to 16S ribosomal RNA gene amplicons, and reveals taxonand diet-dependent variations in tRNA modifications. Our results provide taxon-specific in situ insights into the dynamics of tRNA gene expression and post-transcriptional modifications within complex environmental microbiomes. [ABSTRACT FROM AUTHOR]

Patients with hepatocellular carcinoma (HCC) always require routine surveillance and repeated treatment, which leads to accumulation of huge amount of clinical data. A predictive model utilizes the time-series data to facilitate dynamic prognosis prediction and treatment planning is warranted. Here we introduced an analytical approach, which converts the timeseries data into a cascading survival map, in which each survival path bifurcates at fixed time interval depending on selected prognostic features by the Cox-based feature selection. We apply this approach in an intermediate-scale database of patients with BCLC stage B HCC and get a survival map consisting of 13 different survival paths, which is demonstrated to have superior or equal value than conventional staging systems in dynamic prognosis prediction from 3 to 12 months after initial diagnosis in derivation, internal testing, and multicentric testing cohorts. This methodology/model could facilitate dynamic prognosis prediction and treatment planning for patients with HCC in the future. [ABSTRACT FROM AUTHOR]

H7N9 influenza A virus (IAV)-infected human cases are increasing and reported over 200 mortalities since its first emergence in 2013. Host inflammatory response contributes to the clearance of influenza virus; meanwhile, the induced 'cytokine storm' also leads to pathological lesions. However, what inflammation-related response of the host for H7N9 influenza A virus infection to survival from injures of exuberant cytokine release is still obscure. In this research, expression pattern and histological distribution of inflammation-related genes, RIP3, NLRP3, IL-1β, TNF-α, Slit2 and Robo4 in the lung of BALB/c mice infected with two H7N9 IAV strains with only a PB2 residue 627 difference were investigated, as well as the histopathological injury of the lung. Results showed that significantly higher expression level of NLRP3, RIP3, IL-1β and TNF-α in H7N9-infected groups compared with the control would play a key role in driving lung pathological lesion. While the expression level of Slit2 and Robo4 in H7N9 rV group had significantly increased trend than V which might be the main factor to inhibit the interstitial pneumonia and infiltration. Also, H7N9 induced the histopathological changes in the lung of infected mice, and RIP3, NLRP3, IL-1β, TNF-α, Slit2 and Robo4 showed cell-specific distribution in the lung. The results will provide basic data for further research on the mechanism of inflammatory response and understanding of the role of site 627 in PB2 in H7N9 IAVs infection. In addition, enhancing the resilience of the host vascular system to the inflammatory response by regulation of Slit2-Robo4 signaling pathway might provide a novel strategy for H7N9 IAVs infection. [ABSTRACT FROM AUTHOR]

RIP3, a member of receptor-interacting protein family, is serine/threonine kinase that contributes to necrosis and promotes systematic inflammation. However, detailed information of the expression pattern and tissue distribution in BALB/c mice, a commonly used laboratory animal model, is still unavailable. Here, we provided the basic data of expression profile and histologic distribution of RIP3 in tissues of BALB/c mice. Rip3 mRNA expression levels and tissue distribution were detected by real-time quantitative PCR and immunohistochemical detection, respectively. Rip3 mRNA expression showed the highest level in the spleen and duodenum, while with the lowest level in brain. Immunohistochemical detection revealed this protein located in different type cells in different tissues. What's more, the obvious positive staining in nuclear was detected in liver cells and neurons in cerebral cortex of the brain, while cells in other organs, including heart, spleen, lung, kidney, stomach, duodenum and trachea, showed strong positive mainly in cytoplasm. The results will help us to further understand the site-specific functions of RIP3 in necrosis and inflammatory responses. [ABSTRACT FROM AUTHOR]