Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis.

Richter syndrome (RS), characterized by aggressive lymphoma arising from chronic lymphocytic leukaemia (CLL), presents a poor response to treatment and grim prognosis. To elucidate RS mechanisms, paired samples from a patient with DLBCL-RS were subjected to single-cell RNA sequencing (scRNA-seq) and high-throughput chromosome conformation capture (Hi-C) sequencing. Over 10,000 cells were profiled via scRNA-seq, revealing the comprehensive B cell transformation in RS.

Whole-genome evaluation and prophages characterization associated with genome of carbapenem-resistant Acinetobacter baumannii UOL-KIMZ-24-2.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an emerging threat to healthcare settings in many countries, principally in South Asia. The current study was aimed to identify, evaluate whole-genome and characterize the prophages in genome of CRAB strain, recovered from patients of Lahore General Hospital, Lahore. More than 200 samples were collected and identified by morphological and biochemical tests.

Mitochondria and its epigenetic dynamics: Insight into synaptic regulation and synaptopathies.

Mitochondria, the cellular powerhouses, are pivotal to neuronal function and health, particularly through their role in regulating synaptic structure and function. Spine reprogramming, which underlies synapse development, depends heavily on mitochondrial dynamics-such as biogenesis, fission, fusion, and mitophagy as well as functions including ATP production, calcium (Ca) regulation, and retrograde signaling. Mitochondria supply the energy necessary for assisting synapse development and plasticity, while also regulating intracellular Ca homeostasis to prevent excitotoxicity and support synaptic neurotransmission.

Pretreatment attrition after rifampicin-resistant tuberculosis diagnosis with Xpert MTB/RIF or ultra in high TB burden countries: a systematic review and meta-analysis.

Introduction: The WHO endorsed the Xpert MTB/RIF (Xpert) technique since 2011 as initial test to diagnose rifampicin-resistant tuberculosis (RR-TB). No systematic review has quantified the proportion of pretreatment attrition in RR-TB patients diagnosed with Xpert in high TB burden countries.Pretreatment attrition for RR-TB represents the gap between patients diagnosed and those who effectively started anti-TB treatment regardless of the reasons (which include pretreatment mortality (death of a diagnosed RR-TB patient before starting adequate treatment) and/or pretreatment loss to follow-up (PTLFU) (drop-out of a diagnosed RR-TB patient before initiation of anti-TB treatment).

Biotransformation of Ganoderma lucidum and Hericium erinaceus for ex vivo gut-brain axis modulation and mood-related outcomes in humans: CREB/BDNF signaling and microbiota-driven synergies.

Background: The human gut microbiota plays a crucial role in various aspects of health, extending beyond digestion and nutrient absorption. Ganoderma lucidum (Reishi) and Hericium erinaceus (Lion's Mane), traditional medicinal mushrooms, have garnered interest due to their potential to exert positive health effects. The aim of our study was to investigate the molecular impact of Reishi and Lion's Mane on mood regulation through the gut-brain axis.

Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors.

Background And Objective: Myeloid-derived suppressor cells (MDSCs) are a crucial and diverse group of cells found in the tumor microenvironment (TME) that facilitate progression, invasion, and metastasis within solid tumors. CD84, a homophilic adhesion molecule expressed on MDSCs, plays a critical role in their accumulation and function within the TME. This study aims to investigate the protein-protein interactions of CD84 using molecular dynamics simulations and to explore potential therapeutic strategies targeting these interactions.

Conventional MRI-Based Structural Disconnection and Morphometric Similarity Networks and Their Clinical Correlates in Multiple Sclerosis.

Background And Objectives: Although multiple sclerosis (MS) can be conceptualized as a network disorder, brain network analyses typically require advanced MRI sequences not commonly acquired in clinical practice. Using conventional MRI, we assessed cross-sectional and longitudinal structural disconnection and morphometric similarity networks in people with MS (pwMS), along with their relationship with clinical disability.

Methods: In this longitudinal monocentric study, 3T structural MRI of pwMS and healthy controls (HC) was retrospectively analyzed.

Calothrixin B by docking JAK2 is a potential therapeutic inhibitor for pancreatic ductal adenocarcinoma.

Objectives: Pancreatic cancer, a highly invasive and prognostically unfavorable malignant tumor, consistently exhibits resistance to conventional chemotherapy, leading to substantial side effects and diminished patient quality of life. This highlights the critical need for the discovery of novel, effective, and safe chemotherapy drugs. This study aimed to explore bioactive compounds, particularly natural products, as an alternative for JAK2 protein inhibitor in cancer treatment.

Physico-chemical properties and substrate specificity of α-(1→3)-d-glucan degrading recombinant mutanase from expressed in .

Unlabelled: The gene encoding fungus mutanase (MutA, GH71 family, α-1,3-glucanase, EC 3.2.1.

Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues.

Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues.

Computational structure-based design of antiviral peptides as potential protein-protein interaction inhibitors of rabies virus phosphoprotein and human LC8.

Rabies is a serious zoonotic disease caused by the rabies virus (RABV). Despite the successful development of vaccines and efforts made in drug discovery, rabies is incurable. Therefore, development of novel drugs is of interest to the scientific community.

Benzimidazole-phenoxy-1,2,3-triazole-benzyl Derivatives as the New Potent α-glucosidase Inhibitors: Design, Synthesis, In Vitro, and In Silico Biological Evaluations.

Background: α-Glucosidase inhibitors play an important role in the treatment of type 2 diabetes mellitus. Inhibitors of the latter enzyme that are available on the market created gastrointestinal side effects and achieve to a high potent and low side effect potent α-glucosidase inhibitors is a valuable target for medicinal chemists.

Objective: In this study, derivatives of benzimidazole-phenoxy-1,2,3-triazole-benzyl skeleton were introduced as new α-glucosidase inhibitors.

The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes.

Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes.

Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus.

Bisphenol A (BPA), an endocrine-disrupting chemical, is increasingly linked to the pathogenesis of autism spectrum disorder (ASD). This study investigates the effects of prenatal BPA exposure on neural stem cells (NSCs) from the hippocampi of rat offspring, a brain region critical for neurodevelopment and implicated in ASD. Pregnant rats were administered with BPA or vehicle control once daily via oral gavage from gestational day 1 until parturition.

Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice.

Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted.

Blood pressure variability as predictor of cancer therapy-related cardiovascular toxicity in patients with Multiple Myeloma.

Blood pressure (BP) variability (BPV) is an independent predictor of cardiovascular (CV) events. The role of BPV in defining risk of cancer therapy-related cardiovascular toxicity (CTR-CVT) is currently unknown. The aims of this study were: (i) to evaluate BPV in a population of patients with Multiple Myeloma, undergoing proteasome inhibitors therapy; (ii) to assess the predictive value of BPV for CTR-CVT; (iii) to analyze clusters of subjects based on BPV.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Leveraging a phased pangenome for haplotype design of hybrid potato.

The tetraploid genome and clonal propagation of the cultivated potato (Solanum tuberosum L.) dictate a slow, non-accumulative breeding mode of the most important tuber crop. Transitioning potato breeding to a seed-propagated hybrid system based on diploid inbred lines has the potential to greatly accelerate its improvement.

BioClocks UK: driving robust cycles of discovery to impact.

Chronobiology is a multidisciplinary field that extends across the tree of life, transcends all scales of biological organization, and has huge translational potential. For the UK to harness the opportunities presented within applied chronobiology, we need to build our network outwards to reach stakeholders that can directly benefit from our discoveries. In this article, we discuss the importance of biological rhythms to our health, society, economy and environment, with a particular focus on circadian rhythms.

Informatics strategies for early detection and risk mitigation in pancreatic cancer patients.

This review provides a comprehensive overview of the current landscape in pancreatic cancer (PC) screening, diagnosis, and early detection. This emphasizes the need for targeted screening in high-risk groups, particularly those with familial predispositions and genetic mutations, such as BRCA1, BRCA2, and PALB2. This review highlights the sporadic nature of most PC cases and significant risk factors, including smoking, alcohol consumption, obesity, and diabetes.

Autophagy in Plant Health and Disease.

Autophagy has emerged as an essential quality control pathway in plants that selectively and rapidly removes damaged or unwanted cellular components to maintain cellular homeostasis. It can recycle a broad range of cargoes, including entire organelles, protein aggregates, and even invading microbes. It involves the de novo biogenesis of a new cellular compartment, making it intimately linked to endomembrane trafficking pathways.

Perinatal dysfunction of innate immunity in cystic fibrosis.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.