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overed the novel roles of the PX domain involved in septation and apex targeting, which could provide new fungicidal targets for controlling the devastating FHB disease.Shigellosis causes most diarrheal deaths worldwide, particularly affecting children. Shigella invades and replicates in the epithelium of the large intestine, eliciting inflammation and tissue destruction. To understand how Shigella rewires macrophages prior to epithelium invasion, we performed genome-wide and focused secondary CRISPR knockout and CRISPR interference (CRISPRi) screens in Shigella flexneri-infected human monocytic THP-1 cells. Knockdown of the Toll-like receptor 1/2 signaling pathway significantly reduced proinflammatory cytokine and chemokine production, enhanced host cell survival, and controlled intracellular pathogen growth. Knockdown of the enzymatic component of the mitochondrial pyruvate dehydrogenase complex enhanced THP-1 cell survival. Small-molecule inhibitors blocking key components of these pathways had similar effects; these were validated with human monocyte-derived macrophages, which closely mimic the in vivo physiological state of macrophages postinfection. High-throughput CRIar pathogens manipulate innate immune cells.The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance. We urge cocktail development for all viruses with pandemic potential both in the short term ( less then 1 to 2 years) and longer term with pairs of drugs in advanced clinical testing or repurposed agents approved for other indications. While significant efforts were launched against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in vitro and in the clinic, many studies employed solo drugs and had disappointing results. Here, we review drug combination studies against SARS-CoV-2 and other viruses and introduce a model-driven approach to assess drug pairs with the highest likelihood of clinical efficacy. Where component agents lack sufficient potency, we advocate for synergistic combinations to achieve therapeutic levels. We also discuss issues that stymied therapeutic progress against COVID-19, including testing of agents with low likelihood of efficacy late in clinical disease and lack of focus on developing virologic surrogate endpoints. There is a need to expedite efficient clinical trials testing drug combinations that could be taken at home by recently infected individuals and exposed contacts as early as possible during the next pandemic, whether caused by a coronavirus or another viral pathogen. The approach herein represents a proactive plan for global viral pandemic preparedness.Infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is causally associated with numerous cancers. The mechanism of KSHV-induced oncogenesis remains unclear. By performing a CRISPR-Cas9 screening in a model of KSHV-induced cellular transformation of primary cells, we identified epigenetic regulators that were essential for KSHV-induced cellular transformation. Examination of TCGA data sets of the top 9 genes, including glutamate-rich WD repeat containing 1 (GRWD1), a WD40 family protein upregulated by KSHV, that had positive effects on cell proliferation and survival of KSHV-transformed cells (KMM) but not the matched primary cells (MM), uncovered the predictive values of their expressions for patient survival in numerous types of cancer. We revealed global epigenetic remodeling including H3K4me3 epigenetic active mark in KMM cells compared to MM cells. Knockdown of GRWD1 inhibited cell proliferation, cellular transformation, and tumor formation and caused downregulation of global H3K4me3 mark in KMM c, GRWD1 regulates epigenetic active mark H3K4me3 by interacting with WDR5 and MLL2 and recruiting them to chromatin loci of specific genes in KSHV-transformed cells. Hence, KSHV hijacks the GRWD1-WDR5-MLL2 complex to remodel cellular epigenome and induce cellular transformation. Since the dysregulation of GRWD1 is associated with poor prognosis in several types of cancer, GRWD1 might also be a critical driver in other viral or nonviral cancers.Microbiomes provide a range of benefits to their hosts which can lead to the coevolution of a joint ecological niche. However, holometabolous insects, some of the most successful organisms on Earth, occupy different niches throughout development, with larvae and adults being physiologically and morphologically highly distinct. Furthermore, transition between the stages usually involves the loss of the gut microbiome since the gut is remodeled during pupation. Most eusocial organisms appear to have evolved a workaround to this problem by sharing their communal microbiome across generations. However, whether this vertical microbiome transmission can overcome perturbations of the larval microbiome remains untested. Honey bees have a relatively simple, conserved, coevolved adult microbiome which is socially transmitted and affects many aspects of their biology. In contrast, larval microbiomes are more variable, with less clear roles. Here, we manipulated the gut microbiome of in vitro-reared larvae, and after pupter emergence overrides any variation in the larvae, indicating that larval and adult microbiome stages are effectively decoupled. Together with the reliable vertical transfer in the eusocial system, this decoupling ensures that the adults are colonized with a consistent and derived microbiome after eclosion. Taken all together, our data provide additional support that the evolution of sociality, at least in the honey bee system tested here, is linked with host-microbiome relationships.High-throughput 16S rRNA sequencing has allowed the characterization of helminth-uninfected (HU) and helminth-infected (HI) gut microbiomes, revealing distinct profiles. However, there have been no qualitative or quantitative syntheses of these studies, which show marked variation in participant age, diet, pathogen of interest, and study location. A predefined minimally biased search strategy identified 23 studies in humans. For each of these studies, we qualitatively addressed the effects of helminth infection on within-individual (alpha) and between-individual (beta) fecal microbiome diversity, infection-associated microbial taxa, the effect of helminth clearance on microbiome composition, microbiome composition as a predictor of infection status or treatment outcome, and treatment-specific effects on the fecal microbiome. Concomitantly, we performed a meta-analysis on a subset of 7 of these studies containing raw, paired-end 16S reads and individual-level metadata, comprising 424 pretreatment or untreated the microbiome, less is known about the effects of intestinal helminth parasites (worms), which together affect one-sixth of the world's population. Through a comprehensive qualitative systematic review and quantitative meta-analysis of existing literature, we provide strong evidence that helminth infection dynamically shifts the intestinal microbiome structure. Moreover, we demonstrated that such influence seems to be specific to helminth species and host anatomical niche. Our findings suggest that the gut microbiome may underlie some of the pathology associated with intestinal worm infection and support future work to understand the precise nature of the helminth-microbiome relationship.

Inflammation plays a central role in the pathophysiology of rheumatic diseases as well as in osteoarthritis. Temperature, which can be quantified using infrared thermography, provides information about the inflammatory component of joint diseases. This systematic review aims at assessing infrared thermography potential and limitations in these pathologies.

A systematic review was performed on 3 major databases PubMed, Cochrane library, and Web of Science, on clinical reports of any level of evidence in English language, published from 1990 to May 2021, with infrared thermography used for diagnosis of osteoarthritis and rheumatic diseases, monitoring disease progression, or response to treatment. Relevant data were extracted, collected in a database, and analyzed for the purpose of this systematic review.

Of 718 screened articles 32 were found to be eligible for inclusion, for a total of 2094 patients. Nine studies reported the application to osteoarthritis, 21 to rheumatic diseases, 2 on both. The publi, and response to medical treatment.

The systematic literature review showed an increasing interest in this technology, with several applications in different joints affected by inflammatory and degenerative pathologies. Infrared thermography proved to be a simple, accurate, noninvasive, and radiation-free method, which could be used in addition to the currently available tools for screening, diagnosis, monitoring of disease progression, and response to medical treatment.

The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC).

This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study.

Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR.

The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.

The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.Hepatic fibrogenesis (HF) is the common consequence of various chronic liver diseases (CLD) induced by a variety of pathogenic factors. The mechanism of HF involves the interactions within different types of liver cells, cytokines, chemokines, cell mediators and multiple signaling pathways in a way of networks. As a result, excessive production and deposition of extracellular matrix (ECM) mainly composed of type I and type III fibril forming collagen destroys the original morphology, structure and function of the liver. The activation of hepatic stellate cells (HSCs), the major scar forming cells in liver, plays a crucial role in hepatic fibrogenesis. MicroRNAs are a group of short, single stranded, non-coding RNAs that can inhibit mRNA expression at the transcriptional and post transcriptional levels. They can be loaded and transferred as cargos by exosomes, to regulate the function of nearby and distant receptive cells. The expressions of many microRNAs such as miR-21, miR-29, miR-708, miR-101, miR-455, miR-146, miR-193 change significantly in activated HSCs, which regulate the activation, fibrogenic function, proliferation, apoptosis and autophagy of HSCs via affecting target genes expression and signaling pathway molecules.