The bacterial CBASS(cyclic-oligonucleotide-based anti-phage signaling system) represents a novel innate immune defense mechanism mediated by cyclic nucleotides.The system employs cGAS/DncV-like nucleotidyltransferases (CD-NTases) to recognize exogenous nucleic acids, catalyzing the production of second messenger molecules such as cyclic GMP-AMP (cGAMP) to activate effector proteins (e.g., nucleases), thereby triggering "cell suicide" to combat phage infection. The molecular mechanisms and evolutionary features of CBASS not only uncover the diversity of bacterial immune defenses but also provide critical insights into the conservation of prokaryotic-eukaryotic immune pathways. Notably, the bacterial CBASS system exhibits profound homology with the eukaryotic cGAS-STING (Cyclic GMP-AMP Synthase—Stimulator of Interferon Genes) pathway across multiple dimensions, including the catalytic domains of CD-NTase/cGAS and cyclic nucleotide signaling mechanisms. This finding supports the hypothesis that eukaryotic innate immunity may have originated from prokaryotic horizontal gene transfer and highlights an evolutionary shift in defense strategies from bacterial "population lysis" to "individual inflammatory activation" in higher organisms.This review systematically synthesizes the functional architecture and mechanisms of the CBASS system, with a deep exploration of its evolutionary connections to the eukaryotic cGAS-STING pathway. The insights gained herein offer fresh perspectives for understanding the origin and evolution of the innate immune system, and for driving advancements in biotechnological research and development.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a member of the B7 family that maintains homeostasis in T cells and myeloid cells.Blocking VISTA inhibits tumor development in in vitro and in vivo trials, and is an important target for tumor immunotherapy.This review focuses on its structural features, expression and biological functions in tumor microenvironment, summarizes the current stage of small molecule inhibitors and antibodies targeting VISTA, and discusses the research approaches.It aims to provide a rationale for subsequent study on VISTA and the development of related immune checkpoint antitumor drugs.

The CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated) system is an "adaptive immune system" found in the genomes of bacteria and archaea which is mediated by RNA and resists foreign nucleic acid invasion.Take advantage of specific recognition of target nucleic acid, CRISPR-Cas system can efficiently edit their target site or accurately regulate gene expression, and now have been developed into a powerful tool for gene editing.According to the different compositions of the effector complex, the system has been divided into two categories: class 1 (type I, type IV, and type III) and class 2 (type II, type V, and type VI).Class 2 system, like the CRISPR-Cas9, is widely used in basic research due to the earliest discovery and best research.However, class 1 has not been maturely developed and utilized though it makes up 90% of the entire CRISPR-Cas system.In this essay, the classification of subtype, the assembly of Cascade complex, the cleavage and degradation mechanism of Cas3, and the application in gene editing of class 1 type I CRISPR-Cas system will be discussed and summarized to provide new ideas and methods for further mechanism studying and application of this category.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.