Bone Marrow Endothelial Progenitor Cells remodelling facilitates normal hematopoiesis during Acute Myeloid Leukemia Complete Remission.

Although acute myeloid leukemia (AML) affects hematopoietic stem cell (HSC)-supportive microenvironment, it is largely unknown whether leukemia-modified bone marrow (BM) microenvironment can be remodeled to support normal hematopoiesis after complete remission (CR). As a key element of BM microenvironment, endothelial progenitor cells (EPCs) provide a feasible way to investigate BM microenvironment remodeling. Here, we find reduced and dysfunctional BM EPCs in AML patients, characterized by impaired angiogenesis and high ROS levels, could be partially remodeled after CR and improved by N-acetyl-L-cysteine (NAC).

NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.

Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.

METTL14 Mediates m6A methylation to improve osteogenesis under oxidative stress condition.

Objectives: Bone remodeling imbalance contributes to osteoporosis. Though current medications enhance osteoblast involvement in bone formation, the underlying pathways remain unclear. This study was aimed to explore the pathways involved in bone formation by osteoblasts, we investigate the protective role of glycolysis and N6-methyladenosine methylation (m6A) against oxidative stress-induced impairment of osteogenesis in MC3T3-E1 cells.

Mitophagy in ischemic heart disease: molecular mechanisms and clinical management.

The influence of the mitochondrial control system on ischemic heart disease has become a major focus of current research. Mitophagy, as a very crucial part of the mitochondrial control system, plays a special role in ischemic heart disease, unlike mitochondrial dynamics. The published reviews have not explored in detail the unique function of mitophagy in ischemic heart disease, therefore, the aim of this paper is to summarize how mitophagy regulates the progression of ischemic heart disease.

Brainstem BDNF neurons are downstream of GFRAL/GLP1R signalling.

Growth differentiation factor 15, GDF15, and glucagon-like peptide-1 (GLP-1) analogues act through brainstem neurons that co-localise their receptors, GDNF-family receptor α-like (GFRAL) and GLP1R, to reduce food intake and body weight. However, their use as clinical treatments is partially hampered since both can also induce sickness-like behaviours, including aversion, that are mediated through a well-characterised pathway via the exterolateral parabrachial nucleus. Here, in mice, we describe a separate pathway downstream of GFRAL/GLP1R neurons that involves a distinct population of brain-derived neurotrophic factor (BDNF) cells in the medial nucleus of the tractus solitarius.

Aldehyde Dehydrogenase 2 Lactylation Aggravates Mitochondrial Dysfunction by Disrupting PHB2 Mediated Mitophagy in Acute Kidney Injury.

Mitochondrial dysfunction is a crucial event in acute kidney injury (AKI), leading to a metabolic shift toward glycolysis and increased lactate production. Lactylation, a posttranslational modification derived from lactate, plays a significant role in various cellular processes, yet its implications in AKI remain underexplored. Here, a marked increase in lactate levels and pan-Kla levels are observed in kidney tissue from AKI patients and mice, with pronounced lactylation activity in injured proximal tubular cells identified by single-cell RNA sequencing.

Critical assessment of commercially available microtitre panels for antimicrobial susceptibility testing of veterinary pathogens.

Antimicrobial susceptibility testing (AST) in the veterinary sector by broth microdilution is mainly based on commercially available microtitre plates with specific panels. A critical review of commercially available microtitre panels identified AST panels that fulfil the requirements for obtaining reliable AST results by covering the necessary antimicrobial concentrations for both clinical breakpoints as well as quality control (QC) ranges for approved QC strains. However, there are AST panels in which these prerequisites are only in part fulfilled, and some AST panels that do not fulfil the aforementioned criteria at all.

Multifaceted Immunomodulatory Nanocomplexes Target Neutrophilic-ROS Inflammation in Acute Lung Injury.

The sepsis-induced acute lung injury (ALI) still represents one of the leading causes of death in critically ill patients, underscoring the need for novel therapies. Excessive activation of immune cells and damage of reactive oxygen species (ROS) are the main factors that exacerbate lung injury. Here, the multifaceted immunomodulatory nanocomplexes targeting the proinflammatory neutrophilic activation and ROS damage are established.

Molecular Mechanisms Underlying the Loop-Closing Dynamics of β-1,4 Galactosyltransferase 1.

The β-1,4 galactosylation catalyzed by β-1,4 galactosyltransferases (β4Gal-Ts) is not only closely associated with diverse physiological and pathological processes in humans but also widely applied in the -glycan modification of protein glycoengineering. The loop-closing process of β4Gal-Ts is an essential intermediate step intervening in the binding events of donor substrate (UDP-Gal/Mn) and acceptor substrate during its catalytic cycle, with a significant impact on the galactosylation activities. However, the molecular mechanisms in regulating loop-closing dynamics are not entirely clear.

Mechanical Force-Induced cGAS Activation in Carcinoma Cells Facilitates Splenocytes into Liver to Drive Metastasis.

Liver metastasis is the main cause of cancer-related mortality. During the metastasis process, circulating carcinoma cells hardly pass through narrow capillaries, leading to nuclear deformation. However, the effects of nuclear deformation and its underlying mechanisms on metastasis need further study.

Specific Monitoring the DNA Helicase Function via Anchor-Embedded DNA Probe.

DNA helicases play a pivotal role in maintaining genome integrity by unwinding the DNA double helix and are often considered promising targets for drug development. However, assessing specific DNA helicase activity in living cells remains challenging. Herein, the first anchor-embedded duplex (ATED) probe, 17GC, is constructed to uniquely monitor the unwinding activity of Werner syndrome helicase (WRN), a clinical anticancer target.

Essential oil of (L.) ssp. (Apiaceae) flower: chemical composition, antimicrobial potential, and insecticidal activity on (L.).

In order to search for new chemotypes and to carry out a comparative study with the literature, the current study investigated the chemical composition of the essential oil of the flowers of (L.) ssp. using gas chromatography coupled with mass spectrometry (GC-MS).

Haplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.

Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.

Non-Invasive Diagnosis of Moyamoya Disease Using Serum Metabolic Fingerprints and Machine Learning.

Moyamoya disease (MMD) is a progressive cerebrovascular disorder that increases the risk of intracranial ischemia and hemorrhage. Timely diagnosis and intervention can significantly reduce the risk of new-onset stroke in patients with MMD. However, the current diagnostic methods are invasive and expensive, and non-invasive diagnosis using biomarkers of MMD is rarely reported.

Changes in Disc Status and Condylar Regeneration After Intracapsular Condylar Fractures in Rabbits.

Background: The treatment procedure for intracapsular condylar fractures (ICF) is still being debated. The temporomandibular joint (TMJ) disc is a key factor for treating ICF. The study aims to investigate the changes in TMJ disc status and condylar cartilage regeneration following ICF in a rabbit model, to assist in planning treatment.

CENP-E haploinsufficiency causes chromosome misalignment and spindle assembly checkpoint activation in the spermatogonia.

Background: The establishment of kinetochore-microtubule attachment is essential for error-free chromosome alignment and segregation during cell division. Defects in chromosome alignment result in chromosome instability, birth defects, and infertility. Kinesin-7 CENP-E mediates kinetochore-microtubule capture, chromosome alignment, and spindle assembly checkpoint in somatic cells, however, mechanisms of CENP-E in germ cells remain poorly understood.

Adiposity and risks of gastrointestinal cancers: A 10-year prospective study of 0.5 million Chinese adults.

Associations of adiposity with risks of oesophageal squamous cell carcinoma (ESCC) and non-cardia stomach cancer, both prevalent in China, are still inconclusive. While adiposity is an established risk factor for colorectal cancer, the relevance of fat-free mass and early-adulthood adiposity remains to be explored. The prospective China Kadoorie Biobank study included 0.

The Critical Role of Polyphenols in Immunomodulation and Periodontal Regeneration.

Objectives: Periodontitis, the main cause of tooth loss in adults, is a widespread oral disease characterized by chronic inflammation primarily triggered by periodontopathic bacterial infection. Polyphenols are a class of compounds extracted from herbs and diets, characterized by the presence of more than one phenol unit per molecule. Emerging evidence has revealed that polyphenols show significant effectiveness in ameliorating tissue destruction in periodontitis.

WALINET: A water and lipid identification convolutional neural network for nuisance signal removal in MR spectroscopic imaging.

Purpose: Proton magnetic resonance spectroscopic imaging ( -MRSI) provides noninvasive spectral-spatial mapping of metabolism. However, long-standing problems in whole-brain -MRSI are spectral overlap of metabolite peaks with large lipid signal from scalp, and overwhelming water signal that distorts spectra. Fast and effective methods are needed for high-resolution -MRSI to accurately remove lipid and water signals while preserving the metabolite signal.

Guidelines for the standardization of pre-analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group.

There is a pressing need for accessible biomarkers with high diagnostic accuracy for Alzheimer's disease (AD) diagnosis to facilitate widespread screening, particularly in underserved groups. Saliva is an emerging specimen for measuring AD biomarkers, with distinct contexts of use that could complement blood and cerebrospinal fluid and detect various analytes. An interdisciplinary, international group of AD and related dementias (ADRD) researchers convened and performed a narrative review of published studies on salivary AD biomarkers.

Efficacy of Conservative Therapy in Juvenile Recurrent Parotitis: A Retrospective Study.

Objective: The objective of this study is to evaluate the therapeutic effect of conservative treatment in children with juvenile recurrent parotitis (JRP).

Methods: Clinical data from 55 children who were diagnosed with JRP from June 2019 to January 2022 were collected. On admission, patients underwent comprehensive examinations, and a questionnaire was completed by the patients and their parents.

HOPX as a tumour-suppressive protein in T-cell acute lymphoblastic leukaemia.

The homeodomain protein homeobox (HOPX), a multifaceted regulator of cellular functions and developmental processes, is predominantly expressed in stem cells across diverse tissues; it has also emerged as a tumour suppressor in various solid cancers. However, its role in haematological malignancies still remains undefined. This study aimed to elucidate its significance in T-cell acute lymphoblastic leukaemia (T-ALL).

Multi-Functional Bio-HJzyme Engineered Polyetheretherketone Implant with Cascade-Amplification Therapeutic Capabilities Toward Intractable Implant-Associated Infections.

Intractable implant-associated infections (IAIs) are the primary cause of prosthetic implant failure, particularly in the context of diabetes mellitus. There is an urgent need to design and construct versatile engineered implants integrated with cascade amplification therapeutic modality to significantly improve the treatment of diabetic IAIs. To address this issue, a multi-functional MXene/AgPO@glucose oxidase bio-heterojunction enzyme (M/A@GOx bio-HJzyme) coating is developed, which is decorated with an inert sulfonated polyetheretherketone implant (SP-M/A@G) via hydrothermal treatment and layered deposition.