The value of plasma presepsin as a diagnostic and prognostic biomarker for sepsis in Southern China.

Background: Presepsin is a soluble CD14 subtype that has been considered as a novel marker for patients with sepsis. This study explored the clinical value of presepsin for sepsis in Southern China, and further established models for diagnosis and prognosis of sepsis through using machine learning (ML), by combining presepsin and other laboratory parameters.

Methods: 269 subjects (105 infected patients, 164 sepsis and septic shock) and 198 healthy controls were enrolled.

Serum aspartate aminotransferase is an adverse prognostic indicator for patients with resectable pancreatic ductal adenocarcinoma.

Objective: In this study, the association between preoperative levels of serum liver enzymes and overall survival (OS) was evaluated in patients with resectable pancreatic cancer.

Methods: Preoperative serum levels of alanine aminotransferase (ALT), aspartate aminotransferases (AST), γ-glutamyltransferase, alkaline phosphatase, and lactate dehydrogenase of 101 patients with pancreatic ductal adenocarcinoma (PDAC) were collected. Univariate and multivariate Cox hazard models were used to identify independent variables associated with OS in this cohort.

Novel biomarker panel for the diagnosis and prognosis assessment of sepsis based on machine learning.

The authors investigated a panel of novel biomarkers for diagnosis and prognosis assessment of sepsis using machine learning (ML) methods. Hematological parameters, liver function indices and inflammatory marker levels of 332 subjects were retrospectively analyzed. The authors constructed sepsis diagnosis models and identified the random forest (RF) model to be the most optimal.

Diagnostic and Prognostic Value of Monocyte Distribution Width in Sepsis.

Monocyte distribution width (MDW) is a blood monocyte morphological parameter that can be easily detected by an automated hemocyte analyzer and can provide clinicians with important information about cell volume variability in peripheral blood monocyte populations. The United States' Food and Drug Administration and Conformite Europeenne have both been cleared for their clinical application in the detection of sepsis and developing sepsis in adult patients in the emergency department (ED). Recently, MDW has been found to have an early diagnosis and predictive value for sepsis in neonates and COVID-19 patients.

CGAS is a micronucleophagy receptor for the clearance of micronuclei.

Micronuclei are constantly considered as a marker of genome instability and very recently found to be a trigger of innate immune responses. An increased frequency of micronuclei is associated with many diseases, but the mechanism underlying the regulation of micronuclei homeostasis remains largely unknown. Here, we report that CGAS (cyclic GMP-AMP synthase), a known regulator of DNA sensing and DNA repair, reduces the abundance of micronuclei under genotoxic stress in an autophagy-dependent manner.

Host-mediated ubiquitination of a mycobacterial protein suppresses immunity.

Mycobacterium tuberculosis is an intracellular pathogen that uses several strategies to interfere with the signalling functions of host immune molecules. Many other bacterial pathogens exploit the host ubiquitination system to promote pathogenesis, but whether this same system modulates the ubiquitination of M. tuberculosis proteins is unknown.

Oxidization of TGFβ-activated kinase by MPT53 is required for immunity to Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-β-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner.

PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1.

Excessive or uncontrolled release of proinflammatory cytokines caused by severe viral infections often results in host tissue injury or even death. Phospholipase C (PLC)s degrade phosphatidylinositol-4, 5-bisphosphate (PI(4,5)P2) lipids and regulate multiple cellular events. Here, we report that PLCβ2 inhibits the virus-induced expression of pro-inflammatory cytokines by interacting with and inhibiting transforming growth factor-β-activated kinase 1 (TAK1) activation.

Nuclear cGAS suppresses DNA repair and promotes tumorigenesis.

Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING-IRF3-type I IFN signalling cascade. Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response, but the potential involvement of cGAS in DNA repair remains unknown.

Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist.