Species-specific serine metabolism differentially controls natural killer cell functions.

Immune cells undergo rapid metabolic reprogramming to fuel effector responses. However, whether the metabolic pathways that supply these functions differ between human and mouse immune cells is poorly understood. Using a comparative metabolomics approach, here we show both conserved and species-distinct metabolite alterations in cytokine-activated primary human and mouse natural killer (NK) cells.

Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution.

Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis.

Effect of urea and squaramide IMPDH inhibitors on C. parvum: in vitro trial design impacts the assessment of drug efficacy.

The protozoan parasite Cryptosporidium is the etiological agent of cryptosporidiosis, a ubiquitous diarrheic disease affecting humans and animals. Treatment options are limited, highlighting an urgent need for novel therapeutics. Despite decades of research and a wide diversity of strategies to tackle parasite metabolic pathways, no completely effective drug has been identified to date.

Impact of margin thermal ablation after cold-forceps avulsion with snare-tip soft coagulation for nonlifting large nonpedunculated colorectal polyps.

Nonlifting large nonpedunculated colorectal polyps (NL-LNPCPs) account for 15% of LNPCPs and are effectively managed by endoscopic mucosal resection (EMR) with adjunctive cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST). Recurrence rates >10% at surveillance colonoscopy are however a significant limitation. We aimed to compare the outcomes of CAST plus margin thermal ablation (MTA) versus CAST alone for NL-LNPCPs.

BDSF Analogues Inhibit Quorum Sensing-Regulated Biofilm Production in .

is an aerobic, Gram-negative bacterium that is responsible for many plant diseases. The bacterium is the causal agent of Pierce's disease in grapes and is also responsible for citrus variegated chlorosis, peach phony disease, olive quick decline syndrome and leaf scorches of various species. The production of biofilm is intrinsically linked with persistence and transmission in .

PPARγ-dependent remodeling of translational machinery in adipose progenitors is impaired in obesity.

Adipose tissue regulates energy homeostasis and metabolic function, but its adaptability is impaired in obesity. In this study, we investigate the impact of acute PPARγ agonist treatment in obese mice and find significant transcriptional remodeling of cells in the stromal vascular fraction (SVF). Using single-cell RNA sequencing, we profile the SVF of inguinal and epididymal adipose tissue of obese mice following rosiglitazone treatment and find an induction of ribosomal factors in both progenitor and preadipocyte populations, while expression of ribosomal factors is reduced with obesity.

Synthesis, evaluation and mechanistic insights of novel IMPDH inhibitors targeting ESKAPEE bacteria.

Antimicrobial resistance poses a significant threat to global health, necessitating the development of novel therapeutic agents with unique mechanisms of action. Inosine 5'-monophosphate dehydrogenase (IMPDH), an essential enzyme in guanine nucleotide biosynthesis, is a promising target for the discovery of new antimicrobial agents. High-throughput screening studies have previously identified several urea-based leads as potential inhibitors, although many of these are characterised by reduced chemical stability.

Impact of margin thermal ablation after endoscopic mucosal resection of large (≥20 mm) non-pedunculated colonic polyps on long-term recurrence.

Background And Aims: The efficacy of colorectal endoscopic mucosal resection (EMR) is limited by recurrence and the necessity for conservative surveillance. Margin thermal ablation (MTA) after EMR has reduced the incidence of recurrence at the first surveillance colonoscopy at 6 months (SC1). Whether this effect is durable to second surveillance colonoscopy (SC2) is unknown.

Cold versus hot snare endoscopic mucosal resection for large (≥15 mm) flat non-pedunculated colorectal polyps: a randomised controlled trial.

Background And Aims: Conventional hot snare endoscopic mucosal resection (H-EMR) is effective for the management of large (≥20 mm) non-pedunculated colon polyps (LNPCPs) however, electrocautery-related complications may incur significant morbidity. With a superior safety profile, cold snare EMR (C-EMR) of LNPCPs is an attractive alternative however evidence is lacking. We conducted a randomised trial to compare the efficacy and safety of C-EMR to H-EMR.

Send it, receive it, quick erase it: A mouse model to decipher chemokine communication.

A method to precisely determine which cells respond to chemokines in vivo is currently lacking. A novel class of dual fluorescence reporter mice could help identify cells that produce and/or sense a given chemokine in vitro and in vivo (Rodrigo et al. 2024.

MEF2C regulates NK cell effector functions through control of lipid metabolism.

Natural killer (NK) cells are a critical first line of defense against viral infection. Rare mutations in a small subset of transcription factors can result in decreased NK cell numbers and function in humans, with an associated increased susceptibility to viral infection. However, our understanding of the specific transcription factors governing mature human NK cell function is limited.

Long-term outcomes after endoscopic submucosal dissection for relative indication early gastric cancer in nonsurgical candidates.

Background And Aims: Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). Its role in patients with comorbidities along with more advanced disease is unknown. We sought to evaluate this in a large Western cohort.

A simplified algorithm to evaluate the risk of submucosal invasive cancer in large (≥20 mm) nonpedunculated colonic polyps.

Background: Recognition of submucosal invasive cancer (SMIC) in large (≥20 mm) nonpedunculated colonic polyps (LNPCPs) informs selection of the optimal resection strategy. LNPCP location, morphology, and size influence the risk of SMIC; however, currently no meaningful application of this information has simplified the process to make it accessible and broadly applicable. We developed a decision-making algorithm to simplify the identification of LNPCP subtypes with increased risk of potential SMIC.

No time to die: Epigenetic regulation of natural killer cell survival.

NK cells are short-lived innate lymphocytes that can mediate antigen-independent responses to infection and cancer. However, studies from the past two decades have shown that NK cells can acquire transcriptional and epigenetic modifications during inflammation that result in increased survival and lifespan. These findings blur the lines between the innate and adaptive arms of the immune system, and suggest that the homeostatic mechanisms that govern the persistence of innate immune cells are malleable.

When less is more: lower esophageal sphincter-preserving peroral endoscopic myotomy is effective for non-achalasia esophageal motility disorders.

Background: Non-achalasia esophageal motility disorders (NAEMDs), encompassing distal esophageal spasm (DES) and hypercontractile esophagus (HCE), are rare conditions. Peroral endoscopic myotomy (POEM) is a promising treatment option. In NAEMDs, unlike with achalasia, the lower esophageal sphincter (LES) functions normally, suggesting the potential of LES preservation during POEM.

Adipose cDC1s contribute to obesity-associated inflammation through STING-dependent IL-12 production.

Obesity is associated with chronic low-grade white adipose tissue (WAT) inflammation that can contribute to the development of insulin resistance in mammals. Previous studies have identified interleukin (IL)-12 as a critical upstream regulator of WAT inflammation and metabolic dysfunction during obesity. However, the cell types and mechanisms that initiate WAT IL-12 production remain unclear.

Hybrid resection versus conventional resection for laterally spreading lesions of the papilla.

Background And Aims: Although conventional hot snare resection (CR) of laterally spreading lesions of the major papilla (LSL-Ps) is effective, it can be associated with delayed bleeding in upward of 25% of cases. Given the excellent safety profile of cold snare polypectomy in the colorectum, we investigated the efficacy and safety of a novel hybrid resection (HR) technique for LSL-P management, consisting of hot snare papillectomy plus cold snare resection of the laterally spreading component.

Methods: A prospective cohort of patients underwent HR in a tertiary referral center over 60 months until December 2022.