Molecular turn in pathogenesis: implications of the frameshift for bacterial survival in human macrophage.

, the etiological agent of the devastating plague, has caused three pandemics in human history. While known for its fatality, it has long been intriguing that biovar microtus strains are highly attenuated to humans. The survival and replication within macrophages are critical in the early stages of the lifestyle within warm-blooded hosts.

Hotspots of genetic change in Yersinia pestis.

The relative contributions of mutation rate variation, selection, and recombination in shaping genomic variation in bacterial populations remain poorly understood. Here we analyze 3318 Yersinia pestis genomes, spanning nearly a century and including 2336 newly sequenced strains, to shed light on the patterns of genetic diversity and variation distribution at the population level. We identify 45 genomic regions ("hot regions", HRs) that, although comprising a minor fraction of the genome, are hotbeds of genetic variation.

Autophagy: the misty lands of infection.

are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate intracellular replication, these bacteria must engage in host-pathogen interactions to obtain nutrients and membranes required for the growth of the inclusion, thereby sustaining prolonged bacterial colonization. Autophagy is a highly conserved process that delivers cytoplasmic substrates to the lysosome for degradation.

TCF-1 and TOX regulate the memory formation of intestinal group 2 innate lymphoid cells in asthma.

Immune memory has been expanded to group 2 innate lymphoid cells (ILC2s), but the cellular and molecular bases remain incompletely understood. Based on house dust mite (HDM)-induced mice asthma models and human samples, we applied flow cytometry, parabiosis, in vivo imaging and adoptive transplantation to confirm the persistence, migration and function of CD45lineageCD90.2NK1.

TagP, a PAAR-domain containing protein, plays roles in the fitness and virulence of .

Background: Type VI secretion system (T6SS) is widely present in Gram-negative bacteria and directly mediates antagonistic prokaryote interactions. PAAR (proline-alanine-alanine-arginine repeats) proteins have been proven essential for T6SS-mediated secretion and target cell killing. Although PAAR proteins are commonly found in , their biological functions are not fully disclosed yet.

Delivery of antigens via outer membrane vesicles offered improved protection against plague.

Outer membrane vesicles (OMVs) from Gram-negative bacteria can be used as a vaccine platform to deliver heterologous antigens. Here, the major protective antigens of F1 and LcrV, were fused either with the leader sequence or the transmembrane domain of the outer membrane protein A (OmpA), resulting in chimeric proteins OmpA-ls-F1V and OmpA-F1V, respectively. We show that OmpA-ls-F1V and OmpA-F1V can be successfully delivered into the lumen and membrane of the OMVs of respectively.

A protein O-GlcNAc glycosyltransferase regulates the antioxidative response in Yersinia pestis.

Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis, a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments.

Unveiling the dance of evolution: Pla-mediated cleavage of Ymt modulates the virulence dynamics of .

Unlabelled: has recently evolved into a highly lethal flea-borne pathogen through the pseudogenization of extensive genes and the acquisition of exogenous plasmids. Particularly noteworthy are the newly acquired pPCP1 and pMT1 plasmids, which encode the virulence determinants Pla and murine toxin (Ymt), crucial for subcutaneous infection and survival within flea vector of , respectively. This study reveals that Pla can cleave Ymt at K299 both and expressing Ymt displays enhanced biofilm formation and increased blood survival, indicating significant roles of Pla-mediated Ymt cleavage in these phenotypes.

A Model to Predict Prognosis of Renal Cell Clear Cell Carcinoma Based on 3 Angiogenesis-related Long Non-coding RNAs.

Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be potential biomarkers for predicting ccRCC prognosis. With this study, we aimed to construct a prognostic model based on lncRNAs and explore its underlying mechanisms.

Development and evaluation of a multi-target droplet digital PCR assay for highly sensitive and specific detection of Yersinia pestis.

Background: Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis.

A novel sORF gene mutant strain of Yersinia pestis vaccine EV76 offers enhanced safety and improved protection against plague.

We recently identified two virulence-associated small open reading frames (sORF) of Yersinia pestis, named yp1 and yp2, and null mutants of each individual genes were highly attenuated in virulence. Plague vaccine strain EV76 is known for strong reactogenicity, making it not suitable for use in humans. To improve the immune safety of EV76, three mutant strains of EV76, Δyp1, Δyp2, and Δyp1&yp2 were constructed and their virulence attenuation, immunogenicity, and protective efficacy in mice were evaluated.

Luminol-conjugated cyclodextrin biological nanoparticles for the treatment of severe burn-induced intestinal barrier disruption.

Background: The breakdown of intestinal barrier integrity occurs after severe burn injury and is responsible for the subsequent reactions of inflammation and oxidative stress. A new protective strategy for the intestinal barrier is urgently needed due to the limitations of the traditional methods. Recently, the application of nanoparticles has become one of the promising therapies for many inflammation-related diseases or oxidative damage.

Amyloid and Tau as cerebrospinal fluid biomarkers in anti-N-Methyl-D-aspartate receptor encephalitis.

Introduction: Neuroinfection is associated with the deposition of amyloid-beta (Aβ) peptides, and subsequent decrease in cerebrospinal fluid (CSF) amyloid levels. However, whether autoimmune encephalitis involves extracellular deposition of Aβ peptides in the brain is unreported.

Methods: We examined CSF amyloid and tau values in adults with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E).

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in .

, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from approximately 7,400 years ago. We observed unusually frequent mutations in YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of , and there was no apparent pattern in the spatial distribution of the mutant strains.

Regulatory Functions of PurR in : Orchestrating Diverse Biological Activities.

The bacterium has developed various strategies to sense and respond to the complex stresses encountered during its transmission and pathogenic processes. PurR is a common transcriptional regulator of purine biosynthesis among microorganisms, and it modulates the transcription level of the operon to suppress the production of hypoxanthine nucleotide (IMP). This study aims to understand the functions and regulatory mechanisms of in .

Case Report: MR-LINAC-guided adaptive radiotherapy for gastric cancer.

Background: The stomach is one of the most deformable organs. Its shape can be easily affected by breathing movements, and daily diet, and it also varies when the body position is different. The susceptibility of stomach has made it challenging to treat gastric cancer using the conventional image-guided radiotherapy, i.

and Plague: some knowns and unknowns.

Since its first identification in 1894 during the third pandemic in Hong Kong, there has been significant progress of understanding the lifestyle of , the pathogen that is responsible for plague. Although we now have some understanding of the pathogen's physiology, genetics, genomics, evolution, gene regulation, pathogenesis and immunity, there are many unknown aspects of the pathogen and its disease development. Here, we focus on some of the knowns and unknowns relating to and plague.

Genomic epidemiological analysis of county-scale Yersinia pestis spread pattern over 50 years in a Southwest Chinese prefecture.

Plague, one of the most devastating infectious diseases in human history, is caused by the bacterium Yersinia pestis. Since the 1950s, the Dehong Dai-Jingpo Autonomous Prefecture (DH) in Yunnan Province, China, has recorded plague outbreaks that have resulted in 1,153 human cases and 379 deaths. The genetic diversity and transmission characteristics of Y.

Comparative Lysine Acetylome Analysis of Y. pestis YfiQ/CobB Mutants Reveals that Acetylation of SlyA Lys73 Significantly Promotes Biofilm Formation of Y. pestis.

Increasing evidence shows that protein lysine acetylation is involved in almost every aspect of cellular physiology in bacteria. Yersinia pestis is a flea-borne pathogen responsible for millions of human deaths in three global pandemics. However, the functional role of lysine acetylation in this pathogen remains unclear.

Feasibility study of adaptive radiotherapy for esophageal cancer using artificial intelligence autosegmentation based on MR-Linac.

Objective: We proposed a scheme for automatic patient-specific segmentation in Magnetic Resonance (MR)-guided online adaptive radiotherapy based on daily updated, small-sample deep learning models to address the time-consuming delineation of the region of interest (ROI) in the adapt-to-shape (ATS) workflow. Additionally, we verified its feasibility in adaptive radiation therapy for esophageal cancer (EC).

Methods: Nine patients with EC who were treated with an MR-Linac were prospectively enrolled.

Interplays of mutations in , , and contribute to phage resistance in .

Plague caused by remains a public health threat worldwide. Because multidrug-resistant strains have been found in both humans and animals, phage therapy has attracted increasing attention as an alternative strategy against plague. However, phage resistance is a potential drawback of phage therapies, and the mechanism of phage resistance in is yet to be investigated.

Case Report: A case of infection in an HIV patient.

is the pathogen of psittacosis and infects a wide range of birds and even humans. Human infection occurs most commonly in those with a history of contact with birds or poultry. We describe a case of psittacosis in a human immunodeficiency virus infected patient in Zhejiang Province for the first time.

Vibrio parahaemolyticus from Migratory Birds in China Carries an Extra Copy of tRNA-Gly and Plasmid-Mediated Quinolone Resistance Gene .

Vibrio parahaemolyticus is a marine bacterium coming from estuarine environments, where the migratory birds can easily be colonized by V. parahaemolyticus. Migratory birds may be important reservoirs of V.