Harnessing the Streptomyces-originating type I-E CRISPR/Cas system for efficient genome editing in Streptomyces.

Since their discovery, CRISPR/Cas systems have significantly expanded the genetic toolbox, aiding in the exploration and enhanced production of natural products across various microbes. Among these, class 2 CRISPR/Cas systems are simpler and more broadly used, but they frequently fail to function effectively in many Streptomyces strains. In this study, we present an engineered class 1 type I CRISPR/Cas system derived from Streptomyces avermitilis, which enables efficient gene editing in phylogenetically distant Streptomyces strains.

Emerging role of adaptive immunity in diabetes-induced cognitive impairment: from the periphery to the brain.

Diabetic cognitive impairment (DCI) is a central nervous system complication induced by peripheral metabolic dysfunction of diabetes mellitus. Cumulative studies have shown that neuro-immune crosstalk is involved in the pathological progression of DCI. However, current studies mostly focus on the interaction between innate immunity cells and neurons, while ignoring the role of adaptive immunity cells in DCI.

Single-atom nanozymes with intelligent response to pathological microenvironments for bacterially infected wound healing.

Wound healing is a complex and dynamic process often accompanied by bacterial infection, inflammation, and excessive oxidative stress. Single-atom nanozymes with multi-enzymatic activities show significant potential for promoting the healing of infected wounds by modulating their antibacterial and anti-inflammatory properties in response to the wound's physiological environment. In this study, we synthesized MN single-atom nanozymes with multi-enzymatic activities that intelligently respond to pH value changes in the wound healing process.

FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis.

Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation, which is crucial for maintaining homeostasis. Acute infections can prompt a hematopoietic response known as emergency myelopoiesis. In this study, using a Candida albicans (C.

U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production.

Establishment of a novel large-scale targeted metabolomics method based on NFSWI-DDA mode utilizing HRMS and TQ-MS.

Metabolites identification is the major bottleneck in untargeted LC-MS metabolomics, primarily due to the limited availability of MS information for most detected metabolites in data dependent acquisition (DDA) mode. To solve this problem, we have integrated the iterative, interval, and segmented window acquisition concepts to develop an innovative non-fixed segmented window interval data dependency acquisition (NFSWI-DDA) mode, which achieves comparable MS coverage to data independent acquisition (DIA) mode. This acquisition strategy harnesses the strengths of both DDA and DIA, which could provide extensive coverage and excellent reproducibility of MS spectra.

Single-atom nanozyme-based catalytic ROS clearance for efficiently alleviating eczema.

Single-atom nanozymes (SAzymes) with excellent biological catalytic activity have emerged as promising candidates for advancing biomedical applications. Herein, we synthesized a RuN-SAzyme by thermal decomposition. In experiments, the RuN-SAzyme demonstrated exceptional catalytic efficiency in mimicking the activity of peroxidase, with a Michaelis-Menten constant () for 3,3',5,5'-tetramethylbenzidine reaching 0.

Individuals with high autistic traits exhibit altered interhemispheric brain functional connectivity patterns.

Individuals with high autistic traits (AT) encounter challenges in social interaction, similar to autistic persons. Precise screening and focused interventions positively contribute to improving this situation. Functional connectivity analyses can measure information transmission and integration between brain regions, providing neurophysiological insights into these challenges.

New insights into constitutive neutrophil death.

Neutrophils undergo rapid aging and death known as constitutive or spontaneous death. Constitutive neutrophil death (CND) contributes to neutrophil homeostasis and inflammation resolution. CND has long been considered to be apoptotic until our findings reveal that it was a heterogeneous combination of diverse death.

Protocol for differentiating hematopoietic progenitor cells from human pluripotent stem cells in chemically defined monolayer culture.

Human pluripotent stem cells (hPSCs) provide a powerful platform for generating hematopoietic progenitor cells (HPCs) and investigating hematopoietic development. Here, we present a protocol for maintaining hPSCs and inducing their differentiation into HPCs through the endothelial-to-hematopoietic transition (EHT) on vitronectin-coated plates. We outline steps for evaluating the efficiency of HPC generation and assessing their potential to differentiate into various hematopoietic lineages.

How age affects human hematopoietic stem and progenitor cells and the strategies to mitigate aging.

Hematopoietic stem cells (HSCs) are central to blood formation and play a pivotal role in hematopoietic and systemic aging. With aging, HSCs undergo significant functional changes, such as an increased stem cell pool, declined homing and reconstitution capacity, and skewed differentiation toward myeloid and megakaryocyte/platelet progenitors. These phenotypic alterations are likely due to the expansion of certain clones, known as clonal hematopoiesis (CH), which leads to disrupted hematopoietic homeostasis, including anemia, impaired immunity, higher risks of hematological malignancies, and even associations with cardiovascular disease, highlighting the broader impact of HSC aging on overall health.

[The impact of mitochondrial transfer on leukemia progression].

The objective of the present study was to investigate the role and mechanism of bone marrow microenvironmental cells in regulating the mitochondrial mass of leukemia cells, and to uncover the mechanism of leukemia progression at the metabolic level. A mouse model of acute myeloid leukemia (AML) induced by the overexpression of the MLL-AF9 (MA9) fusion protein was established, and the bone marrow cells of AML mice were transplanted into mitochondrial fluorescence reporter mice expressing the Dendra2 protein (mito-Dendra2 mice). The proportion of Dendra2 cells in bone marrow leukemia cells at different stages of AML was quantified by flow cytometry.

Targeted Degradation of HCV Polymerase by GalNAc-Conjugated ApTACs for Pan-Genotypic Antiviral Therapy with High Resistance Barriers.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Although interferon-free direct-acting antivirals have led to significant advancements in the treatment of HCV infection, the high genetic variability of the virus and the emergence of acquired drug resistance pose potential threats to their effectiveness. In this study, we develop a broad-spectrum aptamer-based proteolysis targeting chimera, designated dNS5B, which effectively degrades both pan-genotypic NS5B polymerase and drug-resistant mutants through ubiquitin proteasome system.

[Progress in risk stratification and treatment of high-risk smoldering multiple myeloma].

Smoldering multiple myeloma (SMM) patients are a heterogeneous group with variable prognosis. A subset of SMM patients have a higher risk of progressing to multiple myeloma (MM) within 2 years. The definition of high-risk patients is not consistent among different risk models, and the combination of various biomarkers and new technologies improves the predictive performance of risk models.

[Next-generation sequencing-based minimal residual disease detection reveals clonal evolution in pediatric acute B-lymphoblastic leukemia: a case report and literature review].

Minimal residual disease (MRD), a crucial biomarker for assessing efficacy and predicting recurrence, refers to residual tumor cells remaining in the body of patients with hematological malignancies who achieved complete remission after treatment. This study aimed to conduct a retrospective analysis of the clinical diagnosis, treatment, and MRD monitoring of a pediatric patient with multiple acute B-lymphocytic leukemia relapses, alongside a review of relevant literature. In this case, Ig rearrangement based on next-generation sequencing (NGS) was more accurate in assessing the MRD level, compared with the traditional method of MRD detection, indicating the risk of earlier relapse and guided interventions in time.

[Mitoxantrone hydrochloride liposome combined with cytarabine for treating pediatric acute myeloid leukemia with RUNX1∷MTG16 fusion gene: a case report and literature review].

This case report presents a patient with pediatric acute myeloid leukemia (AML) with RUNX1∷MTG16, admitted to the Blood Disease Hospital of the Chinese Academy of Medical Sciences in October 2023. He was 13 years old, with a chief complaint of fatigue for 20 days. Bone marrow smear revealed 17.

[Clinical observation of allogeneic hematopoietic stem cell transplantation for treating five cases of classic paroxysmal nocturnal hemoglobinuria].

This study enrolled five patients with classic paroxysmal nocturnal hemoglobinuria (cPNH) who underwent allogeneic hematopoietic stem cell transplantation in our hospital from 2019 to 2023. All five patients were male, with a median age of 26 (range: 26-46) years. The median time from diagnosis to allo-HSCT was 5.

[Clinical characteristics and treatment efficacy of newly diagnosed acute leukemia in the plateau].

This study aimed to retrospectively analyze the clinical characteristics and prognosis of patients with acute leukemia in the plateau. The clinical information of patients diagnosed with acute leukemia from February 2010 to April 2023 at the People's Hospital of Tibet Autonomous Region was reviewed and collected, including blood cell count, morphology, immunophenotype, cytogenetics, and molecular data. Survival analysis was conducted to analyze the outcome of patients with acute leukemia.

[Clinical characteristics and prognosis analysis in patients with bone marrow invasive follicular lymphoma].

This study aimed to summarize the clinical characteristics and prognosis of patients with bone marrow invasive follicular lymphoma (FL) and discuss the treatment modalities. This study included 183 consecutive patients with FL accompanied by bone marrow invasion and receiving regular treatment at the Hospital of Hematology, Chinese Academy of Medical Sciences, from January 2013 to December 2022. Clinical data were retrospectively collected and analyzed, and single and multifactorial analyses of survival prognosis were conducted with the Kaplan-Meier method and Cox regression model.

Understanding structural-functional connectivity coupling in patients with major depressive disorder: A white matter perspective.

Purpose: To elucidate the structural-functional connectivity (SC-FC) coupling in white matter (WM) tracts in patients with major depressive disorder (MDD).

Methods: A total of 178 individuals diagnosed with MDD and 173 healthy controls (HCs) were recruited for this study. The Euclidean distance was calculated to assess SC-FC coupling.

[Refractory or resistant cytomegalovirus infections after hematopoietic stem cell transplantation: diagnosis and management].

Cytomegalovirus (CMV) infection is one of the most prevalent opportunistic infections after hematopoietic stem cell transplantation (HSCT). Prophylaxis and preemptive therapy have demonstrated promise in reducing the incidence of CMV infection and CMV disease, but the management of refractory/resistant (R/R) CMV infections after HSCT remains a challenge that significantly affects the prognosis of patients undergoing HSCT. Intolerance and resistance to antivirals are the primary reasons for developing refractory CMV infections.

[Clinical characteristics and prognostic analysis of carbapenem-resistant Enterobacteriaceae bloodstream infections in patients with hematologic diseases].

This study aimed to analyze the clinical and molecular characteristics of carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) in patients with hematological diseases and to explore prognostic risk factors. This retrospective study included patients with hematologic diseases with CRE BSI at the Institute of Hematology and Blood Diseases Hospital from January 2015 to December 2022. The clinical features, carbapenemase test results, antimicrobial treatments, and outcomes were analyzed.

[Improving the application of metagenomic next-generation sequencing for pathogen diagnosis in infections related to hematological diseases].

Patients with hematologic diseases are prone to infections, and infection-related mortality is high in this population. Accurate diagnosis of infectious pathogens is crucial; however, conventional microbiological testing often fails to meet clinical needs, presenting a significant challenge in clinical practice. Metagenomic next-generation sequencing (mNGS), with its high sensitivity, broad coverage, and short turnaround time, has been widely adopted in diagnosing infectious diseases.