Diet outperforms microbial transplant to drive microbiome recovery post-antibiotics.

High-fat, low-fiber Western-style diets (WD) induce microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth, which in turn increases risk for a wide array of metabolic, immune and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations like antibiotic treatment, although we know little about the mechanism of impairment and the specific host consequences of prolonged post-antibiotic dysbiosis. Here, we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) and WD, and find that only mice on RC undergo a rapid successional process of recovery.

Necroptosis in immunity, tissue homeostasis, and cancer.

Immune and tissue homeostasis is achieved through balancing signals that regulate cell survival, proliferation, and cell death. Recent studies indicate that certain cell death programs can stimulate inflammation and are often referred as 'immunogenic cell death' (ICD). ICD is a double-edged sword that can confer protection against pathogen infection but also cause tissue damage.

Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort.

A second-generation M1-polarized CAR macrophage with antitumor efficacy.

Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Epidemiology, Symptomatology, and Risk Factors for Long COVID Symptoms: Population-Based, Multicenter Study.

Background: Long COVID induces a substantial global burden of disease. The pathogenesis, complications, and epidemiological and clinical characteristics of patients with COVID-19 in the acute phase have been evaluated, while few studies have characterized the epidemiology, symptomatology, and risk factors of long COVID symptoms. Its characteristics among patients with COVID-19 in the general population remain unaddressed.

Gut microbiome signatures reflect different subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a heterogeneous condition with multifactorial pathogenesis. We studied deeply phenotyped individuals with microbiota sequencing enrolled in the American Gut Project. The IBS subjects were matched by age, gender, body mass index, geography, and dietary patterns with non-IBS controls.

Necroptosis at a glance.

Necroptosis, or programmed necrosis, is an inflammatory form of cell death with important functions in host defense against pathogens and tissue homeostasis. The four cytosolic receptor-interacting protein kinase homotypic interaction motif (RHIM)-containing adaptor proteins RIPK1, RIPK3, TRIF (also known as TICAM1) and ZBP1 mediate necroptosis induction in response to infection and cytokine or innate immune receptor activation. Activation of the RHIM adaptors leads to phosphorylation, oligomerization and membrane targeting of the necroptosis effector protein mixed lineage kinase domain-like (MLKL).

Erratum: Epigenomic characterization of a p53-regulated 3p22.2 tumor suppressor that inhibits STAT3 phosphorylation via protein docking and is frequently methylated in esophageal and other carcinomas: Erratum.

[This corrects the article DOI: 10.7150/thno.20893.

Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events.

Objective: The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty).

Design: We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination.

Tumor-intrinsic and immune modulatory roles of receptor-interacting protein kinases.

Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are signaling adaptors that critically regulate cell death and inflammation. Tumors have adapted to subvert RIPK-dependent cell death, suggesting that these processes have key roles in tumor regulation. Moreover, RIPK-driven cancer cell death might bolster durable antitumor immunity.

Risks of post-colonoscopic polypectomy bleeding and thromboembolism with warfarin and direct oral anticoagulants: a population-based analysis.

Background: There were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.

Methods: We performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020.

A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation.

The vaccine strain against smallpox, vaccinia virus (VACV), is highly immunogenic yet causes relatively benign disease. These attributes are believed to be caused by gene loss in VACV. Using a targeted small interfering RNA (siRNA) screen, we identified a viral inhibitor found in cowpox virus (CPXV) and other orthopoxviruses that bound to the host SKP1-Cullin1-F-box (SCF) machinery and the essential necroptosis kinase receptor interacting protein kinase 3 (RIPK3).

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.

Objective: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.

Methods: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection.

Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19.

Objective: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19.

Design: We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19.

Regulatory mechanisms of RIPK1 in cell death and inflammation.

Receptor Interacting Protein Kinase 1 (RIPK1) and RIPK3 are key adaptors that play critical roles in inflammatory and cell death signaling. Work in recent years have shown that their activities are tightly regulated by ubiquitination, phosphorylation and proteolysis. In addition to these post-translational modifications, the expression and activities of these kinases can further be tuned by environmental changes in pH and oxygen content.

A Hybrid Residual Network and Long Short-Term Memory Method for Peptic Ulcer Bleeding Mortality Prediction.

The prediction of patient mortality, which can detect high-risk patients, is a significant yet challenging problem in medical informatics. Thanks to the wide adoption of electronic health records (EHRs), many data-driven methods have been proposed to forecast mortality. However, most existing methods do not consider correlations between static and dynamic data, which contain significant information about mutual influences between these data.

Machine learning model to predict recurrent ulcer bleeding in patients with history of idiopathic gastroduodenal ulcer bleeding.

Background: Patients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have an increased risk of recurring ulcer complications.

Aim: To build a machine learning model to identify patients at high risk for recurrent ulcer bleeding.

Methods: Data from a retrospective cohort of 22 854 patients (training cohort) diagnosed with peptic ulcer disease in 2007-2016 were analysed to build a model (IPU-ML) to predict recurrent ulcer bleeding.

Subverts Necroptosis by Modulating RIPK3 Expression.

infection causes skin ulcers, typically found in localized cutaneous leishmaniasis (LCL). This tissue pathology associates with different modalities of cell necrosis, which are subverted by the parasite as a survival strategy. Herein we examined the participation of necroptosis, a specific form of programmed necrosis, in LCL lesions and found reduced RIPK3 and PGAM5 gene expression compared to normal skin.

RIPK1-RIPK3-MLKL-Associated Necroptosis Drives Killing in Neutrophils.

Necroptosis is a pro-inflammatory cell death, which happens in the context of caspase-8 inhibition, allowing activation of the receptor interacting protein kinase 1-receptor interacting protein kinase 3-mixed lineage kinase domain-like (RIPK1-RIPK3-MLKL) axis. Recently, necroptosis has emerged as a key component of resistance against pathogens including infected macrophage by , the ethiologic agent of Visceral leishmaniasis (VL). VL is the most severe form of Leishmaniasis, characterized by systemic inflammation and neutropenia.

Loss-of-Function RNAi Screen to Identify Necrosis-Signaling Molecules.

Over the recent years, genome-wide RNA interference (RNAi) library screens have been instrumental in the identification of key regulators of various biological pathways. The prolific use of this technique is attributed to its amenability to a high-throughput format. Here, we present the step-by-step method to conduct a siRNA screen to identify genes involved in necroptosis, a nonapoptotic form of proinflammatory cell death.

Effectiveness of reminder strategies on cancer screening adherence: a randomised controlled trial.

Background: Few randomised controlled trials (RCTs) have evaluated the different recalling approaches for enhancing adherence to faecal immunochemical test (FIT)-based screening.

Aim: The authors evaluated the effectiveness of two telecommunication strategies on improving adherence to yearly FIT screening.

Design And Setting: A randomised, parallel group trial was performed in a primary care screening practice.