Shaping immune landscape of colorectal cancer by cholesterol metabolites.

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC.

Mechanochemically Reprogrammed Interface Orchestrates Neutrophil Bactericidal Activity and Apoptosis for Preventing Implant-Associated Infection.

The onset of implant-associated infection (IAI) triggers a cascade of immune responses, which are initially dominated by neutrophils. Bacterial aggregate formation and hypoxic microenvironment, which occur shortly after implantation, may be two major risk factors that impair neutrophil function and lead to IAI. Here, the implant surface with phytic acid-Zn coordinated TiO nanopillar arrays (PA-Zn@TiNPs) and oxygen self-supporting CaO nanoparticles, named as CPZTs, is mechanochemically reprogrammed.

Pain alleviation improves balance control and muscular coordination of lower limbs in patients with chronic ankle instability during sinusoidal perturbations.

Background: It is well established that individuals with chronic ankle instability manifest deficits in balance control and muscle activation. Given the prevalence of pain as a prominent symptom in this population, there is a need for in-depth investigation of its role in contributing to these impairments.

Methods: A Stewart platform was used to generate translational sinusoidal perturbations in the antero-posterior direction.

Identification of eight genomic protective alleles for mitochondrial diabetes by Kinship-graph convolutional network.

Aims: Nearly 85% of maternally inherited diabetes and deafness (MIDD) are caused by the m.3243A>G mutation in the mitochondrial DNA. However, the clinical phenotypes of MIDD may also be influenced by the nuclear genome, this study aimed to investigate nuclear genome variants that influence clinical phenotypes associated with m.

Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer: a clinical and translational study.

p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis.

Development and validation of a rabbit model of non-ventilated pneumonia for preclinical drug development.

Background: New drugs targeting antimicrobial resistant pathogens, including , have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated pneumonia indications. Development of new antibacterial drugs is facilitated by preclinical animal models that could predict clinical efficacy in patients with these infections.

Methods: We report here an FDA-funded study to develop a rabbit model of non-ventilated pneumonia with by determining the extent to which the natural history of animal disease reproduced human pathophysiology and conducting validation studies to evaluate whether humanized dosing regimens of two antibiotics, meropenem and tobramycin, can halt or reverse disease progression.

A novel hypoglycemia alarm framework for type 2 diabetes with high glycemic variability.

In patients with type 2 diabetes (T2D), accurate prediction of hypoglycemic events is crucial for maintaining glycemic control and reducing their frequency. However, individuals with high blood glucose variability experience significant fluctuations over time, posing a challenge for early warning models that rely on static features. This article proposes a novel hypoglycemia early alarm framework based on dynamic feature selection.

GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes.

Objective: To investigate the relationship between gene polymorphisms and susceptibility to early onset type 2 diabetes.

Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes ( = 137) and late-onset type 2 diabetes ( = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group.

A machine learning-based model for clinical prediction of distal metastasis in chondrosarcoma: a multicenter, retrospective study.

Background: The occurrence of distant metastases (DM) limits the overall survival (OS) of patients with chondrosarcoma (CS). Early diagnosis and treatment of CS remains a great challenge in clinical practice. The aim of this study was to investigate metastatic factors and develop a risk stratification model for clinicians' decision-making.

Development and validation of the Nurse Team Resilience Scale (NTRS) in the context of public health emergencies.

Background: Team resilience can help nurse to respond positively to adversity at work and maintain normal team function in complex and unstable environments. However, much less research attention has been paid to team resilience than to individual resilience, and nurses lack reliable and valid tools to measure team resilience. This study aimed to develop and evaluate the psychometric properties of a scale that measures the nursing team resilience in the context of a public health emergency.

Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells.

Stem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models.

Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma.

Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC.

Anti-Acidification and Immune Regulation by Nano-Ceria-Loaded Mg-Al Layered Double Hydroxide for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease featuring an abnormal immune microenvironment and resultant accumulation of hydrogen ions (H ) produced by activated osteoclasts (OCs). Currently, clinic RA therapy can hardly achieve sustained or efficient therapeutic outcomes due to the failures in generating sufficient immune modulation and manipulating the accumulation of H that deteriorates bone damage. Herein, a highly effective immune modulatory nanocatalytic platform, nanoceria-loaded magnesium aluminum layered double hydroxide (LDH-CeO ), is proposed for enhanced immune modulation based on acid neutralization and metal ion inherent bioactivity.

Targeting the E2F1/Rb/HDAC1 axis with the small molecule HR488B effectively inhibits colorectal cancer growth.

Colorectal cancer (CRC), the third most common cancer worldwide, remains highly lethal as the disease only becomes symptomatic at an advanced stage. Growing evidence suggests that histone deacetylases (HDACs), a group of epigenetic enzymes overexpressed in precancerous lesions of CRC, may represent promising molecular targets for CRC treatment. Histone deacetylase inhibitors (HDACis) have gradually become powerful anti-cancer agents targeting epigenetic modulation and have been widely used in the clinical treatment of hematologic malignancies, while only few studies on the benefit of HDACis in the treatment of CRC.

Hypoxia and Matrix Metalloproteinase 13-Responsive Hydrogel Microspheres Alleviate Osteoarthritis Progression In Vivo.

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction.

Correlation between membrane proteins and sizes of extracellular vesicles and particles: A potential signature for cancer diagnosis.

Extracellular vesicles and particles (EVPs) are recognized as ideal liquid biopsy tools for cancer detection, and membrane proteins are commonly used EVP biomarkers. However, bulk analysis of EVP membrane protein biomarkers typically fails to meet the clinical requirement for diagnostic accuracy. We investigated the correlation between the membrane protein expression level, the binding kinetics to aptamers and the sizes of EVPs with interferometric plasmonic microscopy (iPM), and demonstrated the implementation of the correlative signature to determine cancer types.

Green One-Step Strategy of Conductive Ink for Active Health Monitoring in Rehabilitation and Early Care.

Conductive ink deposited on flexible substrates through simple methods such as dyeing or printing is one of the most promising approaches for scalable fabrication of wearable electronics. However, excessive chemical additives or a complex preparation process has limited the practical applications of conductive inks. Herein, a highly stable and antibacterial AgNPs/CNT/rGO (SACR) conductive ink with the only assistance of sustainable silk sericin (SS) is developed through a green one-step strategy.

The landscape of patellofemoral arthroplasty research: a bibliometric analysis.

Purpose: Patellofemoral arthroplasty (PFA) was shown to be a potentially effective surgical technique for isolated patellofemoral osteoarthritis but varying reports on PFA-related implant failure and complications have rendered the procedure controversial. This study aimed to identify impactful publications, research interests/efforts, and collaborative networks in the field of PFA research.

Methods: The study used the Web of Science Core Collection (WOSCC) database, Medline, Springer, BIOSIS Citation Index, and PubMed to retrieve relevant publications on PFA research published between 1950-2022.

Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury.

Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain.

A common spectrum underlying brain disorders across lifespan revealed by deep learning on brain networks.

Brain disorders in the early and late life of humans potentially share pathological alterations in brain functions. However, the key neuroimaging evidence remains unrevealed for elucidating such commonness and the relationships among these disorders. To explore this puzzle, we build a restricted single-branch deep learning model, using multi-site functional magnetic resonance imaging data ( = 4,410, 6 sites), for classifying 5 different early- and late-life brain disorders from healthy controls (cognitively unimpaired).

Intestinal Ultrasound Combined with Blood Inflammatory Markers Is a More Efficient Tool in Evaluating Severity of Crohn's Disease: A Pilot Study.

Background And Aims: Intestinal ultrasound (IUS) is considered a nonirradiating, noninvasive, well-tolerated, and valuable tool for objectively assessing Crohn's disease (CD) activity. However, there is no widely accepted intestinal ultrasound scoring system. This study is aimed at evaluating the efficacy of IUS key parameters, the International Bowel Ultrasound Activity Score (IBUS-SAS), and IBUS-SAS combined with blood inflammatory markers in assessing CD activity.

deficiency impairs HSPC homeostasis and erythropoiesis via and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 () mutations in patients with MDS, while the exact role of in hematopoiesis remains poorly delineated. Here, we report that deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS.