Remodeling of the endothelial cell transcriptional program via paracrine and DNA-binding activities of MPO.

Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO is released into the vascular lumen by neutrophils during inflammation and may adhere and subsequently penetrate endothelial cells (ECs) coating vascular walls. We show that MPO enters the nucleus of ECs and binds chromatin independently of its enzymatic activity.

Evaluation of tumor microvasculature with 3D ultrasound localization microscopy based on 2D matrix array.

Objective: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive.

3D-bioprinted anisotropic bicellular living hydrogels boost osteochondral regeneration via reconstruction of cartilage-bone interface.

Reconstruction of osteochondral (OC) defects represents an immense challenge due to the need for synchronous regeneration of special stratified tissues. The revolutionary innovation of bioprinting provides a robust method for precise fabrication of tissue-engineered OCs with hierarchical structure; however, their spatial living cues for simultaneous fulfilment of osteogenesis and chondrogenesis to reconstruct the cartilage-bone interface of OC are underappreciated. Here, inspired by natural OC bilayer features, anisotropic bicellular living hydrogels (ABLHs) simultaneously embedding articular cartilage progenitor cells (ACPCs) and bone mesenchymal stem cells (BMSCs) in stratified layers were precisely fabricated via two-channel extrusion bioprinting.

Levofloxacin alleviates blood-brain barrier disruption following cerebral ischemia and reperfusion via directly inhibiting A-FABP.

Reperfusion therapy is currently the most effective treatment for acute ischemic stroke, but often results in secondary brain injury. Adipocyte fatty acid-binding protein (A-FABP, FABP4, or aP2) was shown to critically mediate cerebral ischemia/reperfusion (I/R) injury by exacerbating blood-brain barrier (BBB) disruption. However, no A-FABP inhibitors have been approved for clinical use due to safety issues.

A NIR-driven green affording-oxygen microrobot for targeted photodynamic therapy of tumors.

Photodynamic therapy (PDT) is a light-activated local treatment modality that has promising potential in cancer therapy. However, ineffective delivery of photosensitizers and hypoxia in the tumor microenvironment severely restrict the therapeutic efficacy of PDT. Herein, phototactic Chlorella (C) is utilized to carry photosensitizer-encapsulated nanoparticles to develop a near-infrared (NIR) driven green affording-oxygen microrobot system (CurNPs-C) for enhanced PDT.

Polysaccharide from Polygala tenuifolia alleviates cognitive decline in Alzheimer's disease mice by alleviating Aβ damage and targeting the ERK pathway.

Ethnopharmacological Relevance: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb.

Aim Of The Study: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs.

Materials And Methods: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus.

Isolation and characterization of phage ISTP3 for bio-control application against drug-resistant .

including drug-resistant strains are major foodborne pathogens causing serious illness and pose a great threat to the prevention and control for food safety. Phages can naturally defect the bacterium, is considered as a new and promising biological antimicrobial agent in the post-antibiotic era. A poultry facility in Wuhan, China provided wastewater samples from which a collection of 29 phages were isolated and purified.

The power of phages: revolutionizing cancer treatment.

Cancer is a devastating disease with a high global mortality rate and is projected to increase further in the coming years. Current treatment options, such as chemotherapy and radiation therapy, have limitations including side effects, variable effectiveness, high costs, and limited availability. There is a growing need for alternative treatments that can target cancer cells specifically with fewer side effects.

A Weakly Supervised Learning Method for Cell Detection and Tracking Using Incomplete Initial Annotations.

The automatic detection of cells in microscopy image sequences is a significant task in biomedical research. However, routine microscopy images with cells, which are taken during the process whereby constant division and differentiation occur, are notoriously difficult to detect due to changes in their appearance and number. Recently, convolutional neural network (CNN)-based methods have made significant progress in cell detection and tracking.

miR-455-5p promotes pathological cardiac remodeling via suppression of PRMT1-mediated Notch signaling pathway.

Pathological cardiac remodeling plays an essential role in the progression of cardiovascular diseases, and numerous microRNAs have been reported to participate in pathological cardiac remodeling. However, the potential role of microRNA-455-5p (miR-455-5p) in this process remains to be elucidated. In the present study, we focused on clarifying the function and searching the direct target of miR-455-5p, as well as exploring its underlying mechanisms in pathological cardiac remodeling.

Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke.

Background And Purpose: Adipocyte fatty acid-binding protein (A-FABP) exacerbates cerebral ischaemia injury by disrupting the blood-brain barrier (BBB) through inducing expression of MMP-9. Circulating A-FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A-FABP by a neutralizing antibody would alleviate ischaemic stroke outcome.

Is epigenome editing non-inheritable? Implications for ethics and the regulation of human applications.

Epigenome editing offers ethical advantages with non-inheritable gene expression control. However, concerns arise regarding potential transgenerational effects in humans. Ethical and regulatory evaluation is crucial, considering recent advancements and enhanced understanding of transgenerational epigenetics in both mammals and humans.

Sesquiterpenoids from with GLP-1 Stimulative Effects through Ca/CaMKII and PKA Pathways and Multiple-Enzyme Inhibition.

Six new sesquiterpenoids (-), a pair of enantiomers ( and ), and six known ones (-) were isolated from the fruits of . The structures of the new compounds were elucidated by extensive spectroscopic data and ECD calculations. The stereochemistry of and was reported for the first time.

Cartilage-inspired self-assembly glycopeptide hydrogels for cartilage regeneration via ROS scavenging.

Cartilage injury represents a frequent dilemma in clinical practice owing to its inherently limited self-renewal capacity. Biomimetic strategy-based engineered biomaterial, capable of coordinated regulation for cellular and microenvironmental crosstalk, provides an adequate avenue to boost cartilage regeneration. The level of oxidative stress in microenvironments is verified to be vital for tissue regeneration, yet it is often overlooked in engineered biomaterials for cartilage regeneration.

Lymphocyte recovery from radiation-induced lymphopenia in locally advanced esophageal squamous cell carcinoma: correlations with prognosis and lymphocyte-related organs.

Background: Limited studies explored the relationship between lymphocyte recovery after definitive concurrent chemoradiotherapy (dCCRT) and prognosis in esophageal squamous cell carcinoma (ESCC).

Methods: ESCC patients with obtainable absolute lymphocyte counts (ALCs) at 6 months after dCCRT were screened from prospective trials. Patients were divided into groups according to the grade of ALC nadir during radiotherapy (G4 or G1-3) and lymphocyte recovery status, which was assessed by lymphocyte recovery index (LRI), calculated as the ratio of post- to pre-treatment lymphocyte counts.

Engineered Selenium/Human Serum Albumin Nanoparticles for Efficient Targeted Treatment of Parkinson's Disease via Oral Gavage.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopamine (DA) neurons in the midbrain substantia nigra pars compacta (SNpc). While existing therapeutic strategies can alleviate PD symptoms, they cannot inhibit DA neuron loss. Herein, a tailor-made human serum albumin (HSA)-based selenium nanosystem (HSA/Se nanoparticles, HSA/Se NPs) to treat PD that can overcome the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) is described.

USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer.

A review of recent advances in biomedical applications of smart cellulose-based hydrogels.

In biomedical engineering, smart materials act as media to communicate physiological signals inspired by environmentally responsive stimuli with outer indicators for timely scrutiny and precise therapy. Various physical and chemical processes are applied in the design of specific smart functions. Hydrogels are polymeric networks consisting of hydrophilic chains and chemical groups and they have contributed their unique features in biomedical application as one of the most used smart materials.

Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell-mediated immune surveillance.

Tumorigenesis entails circumventing cell-intrinsic regulatory mechanisms while avoiding extrinsic immune surveillance and other host defence systems. Nevertheless, how tumour cells' ability to eliminate misfolded proteins affects immune surveillance remains poorly understood. In this study, we find that overexpression of murine tripartite motif-containing protein 30a (TRIM30a) sensitises tumour cells to natural killer (NK) cells-mediated cytolysis.

Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics.

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity.

ER translocon inhibitor ipomoeassin F inhibits triple-negative breast cancer growth via blocking ER molecular chaperones.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer where no effective therapy has been developed. Here, we report that the natural product ER translocon inhibitor ipomoeassin F is a selective inhibitor of TNBC cell growth. A proteomic analysis of TNBC cells revealed that ipomoeassin F significantly reduced the levels of ER molecular chaperones, including PDIA6 and PDIA4, and induced ER stress, unfolded protein response (UPR) and autophagy in TNBC cells.