Guanidyl-rich highly branched poly(β-amino ester)s for the delivery of dual CRISPR ribonucleoprotein for efficient large DNA fragment deletion.

Gene editing technologies, particularly clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, have revolutionized the ability to modify gene sequences in living cells for therapeutic purposes. Delivery of CRISPR/Cas ribonucleoprotein (RNP) is preferred over its DNA and RNA formats in terms of gene editing effectiveness and low risk of off-target events. However, the intracellular delivery of RNP poses significant challenges and necessitates the development of non-viral vectors.

Implantable Microneedles Loaded with Nanoparticles Surface Engineered for Efficient Eradication of Triple-Negative Breast Cancer Stem Cells.

Eliminating cancer stem cells (CSCs) is essential for the effective treatment of triple-negative breast cancer (TNBC). This study synthesized Au@cerium-zinc composite core@shell nanoparticles (Au@Zn/CeO) that were subsequently conjugated with () to create the engineered bacterium AZCE, which was then combined with microneedle carriers and freeze-dried to obtain AZCE-MN. Upon implantation into TNBC tumors, the inherent properties of facilitate AZCE to penetrate the extracellular matrix and break through the basement membrane, enabling effective delivery of AZC to CSCs-enriched regions deep within the tumor.

Treatment of Denervated Muscle Atrophy by Injectable Dual-Responsive Hydrogels Loaded with Extracellular Vesicles.

Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness of current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating muscle atrophy, their therapeutic potential is hindered by challenges in delivery and bioactivity within the complex microenvironment of the injury site. To address this issue, an injectable hydrogel is developed that is responsive to both ultrasound and pH, with inherent anti-inflammatory and antioxidant properties, designed to improve the targeted delivery of stem cell-derived EVs.

The efficacy and safety of suvemcitug, envafolimab, and FOLFIRI in microsatellite-stable or mismatch repair-proficient colorectal cancer: preliminary results of a phase 2 study.

Purpose: This phase II study is designed to evaluate the combination therapy involving suvemcitug and envafolimab with FOLFIRI in microsatellite-stable or mismatch repair-proficient (MSS/pMMR) colorectal cancer (CRC) in the second-line treatment setting.

Methods: This study is a non-randomized, open-label prospective study comprising multiple cohorts (NCT05148195). Here, we only report the data from the CRC cohort.

Prussian Blue Nanozyme Featuring Enhanced Superoxide Dismutase-like Activity for Myocardial Ischemia Reperfusion Injury Treatment.

The blood flow, when restored clinically following a myocardial infarction (MI), disrupts the physiological and metabolic equilibrium of the ischemic myocardial area, resulting in secondary damage termed myocardial ischemia-reperfusion injury (MIRI). Reactive oxygen species (ROS) generation and inflammatory reactions stand as primary culprits behind MIRI. Current strategies focusing on ROS-scavenging and anti-inflammatory actions have limited remission of MIRI.

Validation of the efficacy of the porous medium model in hemodynamic analysis of iliac vein compression syndrome.

Iliac Vein Compression Syndrome (IVCS) is a common risk factor for deep vein thrombosis in the lower extremities. The objective of this study was to investigate whether employing a porous medium model to simulate the compressed region of an iliac vein could improve the reliability and accuracy of Computational Fluid Dynamics (CFD) analysis outcomes of IVCS. Pre-operative Computed Tomography (CT) scan images of patients with IVCS were utilized to reconstruct models illustrating both the compression and collateral circulation of the iliac vein.

TransferBAN-Syn: a transfer learning-based algorithm for predicting synergistic drug combinations against echinococcosis.

Echinococcosis is a zoonotic parasitic disease caused by the larvae of echinococcus tapeworms infesting the human body. Drug combination therapy is highly valued for the treatment of echinococcosis because of its potential to overcome resistance and enhance the response to existing drugs. Traditional methods of identifying drug combinations via biological experimentation is costly and time-consuming.

Dietary supplementation with proanthocyanidins and rutin alleviates the symptoms of type 2 diabetes mice and regulates gut microbiota.

Background: Obesity and high fasting blood glucose (FBG) resulting from high-fat diets (HFDs) have emerged as significant public health concerns, garnering increasing attention. Recently, gut microbiota has been linked with metabolic diseases such as type 2 diabetes (T2DM), and its mediating role in dietary supplements has been confirmed. Seeking various dietary supplements to lose body weight (BW) and decrease FBG and explaining the underlying mechanism have become the research hotspots in T2DM studies.

Extracellular Matrix-Inspired Dendrimer Nanogels Encapsulating Cyclophosphamide for Systemic Sclerosis Treatment.

Cyclophosphamide has a certain therapeutic effect on treating systemic sclerosis (SSc), while difficulties exist in controlling severe systematic side effects and enhancing targeting capacity. Here, inspired from the natural extracellular matrix composition, we propose a cyclophosphamide-encapsulated nanogel based on dendritic polymers polyamidoamine (PAMAM) for SSc treatment. We combine bovine serum albumin and generation 5 (G5) PAMAM dendrimers with polyphenol modification to obtain nanogels featured with antioxidant and anti-inflammatory effects.

Cardiac metabolic index as a predictor of new-onset diabetes in non-alcoholic fatty liver disease patients: a longitudinal cohort analysis.

Objective: The purpose of this investigation is to assess the clinical risk linked to the onset of diabetes in individuals with non-alcoholic fatty liver disease (NAFLD) through the utilization of the cardiac metabolic index (CMI), which is derived from triglycerides, high-density lipoprotein, height, and waist circumference. Research focusing on the application of CMI for evaluating diabetes risk among NAFLD patients remains scarce, and an exploration of the association between CMI and the emergence of diabetes within this demographic has not been conducted. This investigation aims to illuminate this connection, thereby providing novel insights into the prevention of diabetes progression in individuals with NAFLD.

Tip-of-the-pen states in Mandarin handwriting: The effect of brief non-target language exposure.

The tip-of-the-pen (TOP) is a phenomenon in which individuals fail to completely retrieve the orthographic information of a known character, and mainly occurs in Mandarin (a non-alphabetic language in which the orthography is largely independent of the phonology). The present study examined whether and how long-term language experience and brief exposure to non-target language affected TOP rates in Mandarin handwriting. In Experiment 1, high and low proficiency Mandarin-English bilinguals completed a Mandarin character dictation task before and after watching a short English movie.

HDAC9-mediated deacetylation of CALML6 promotes excessive proliferation of glomerular mesangial cells in IgA nephropathy.

Purpose: This study seeks to investigate the fundamental molecular processes through which histone deacetylase 9 (HDAC9) governs the proliferation of glomerular mesangial cells in the context of immunoglobulin A nephropathy (IgAN) and to identify novel targets for clinical research on IgAN.

Methods: Data from high-throughput RNA sequencing for IgAN were procured from the Gene Expression Omnibus database to assess the expression profiles and clinical diagnostic significance of histone deacetylase family proteins (HDACs). Blood samples from 20 IgAN patients were employed in RT-qPCR analysis, and the spearman linear regression method was utilized to analyze the clinical correlation.

Diffusion transformer model with compact prior for low-dose PET reconstruction.

Positron emission tomography (PET) is an advanced medical imaging technique that plays a crucial role in non-invasive clinical diagnosis. However, while reducing radiation exposure through low-dose PET scans is beneficial for patient safety, it often results in insufficient statistical data. This scarcity of data poses significant challenges for accurately reconstructing high-quality images, which are essential for reliable diagnostic outcomes.

Pan-cancer analysis and single-cell analysis identifies the CENPN as a biomarker for survival prognosis and immunotherapy.

Background: Centromere protein N (CENPN), located on chromosome 16q23.2, encodes vital nucleosome-associated complexes that are essential for dynamic assembly processes. CENPN plays a pivotal role in regulating cell proliferation and cell cycle progression by influencing mitotic events.

Sex differences in the association between metabolic disorder and inflammatory cytokines in Han Chinese patients with chronic schizophrenia.

Background: Previous evidence suggests that immune-inflammatory dysfunction plays an important role in metabolic disorder (MD) of patients with schizophrenia, yet studies on sex differences in the association between both are limited. The current study aimed to investigate sex differences in the association between MD and inflammatory cytokines in Han Chinese patients with chronic schizophrenia (CS).

Methods: This multicentre cross-sectional study was conducted in one general hospital and two psychiatric hospitals in Anhui Province, China.

Global research status and trends of somatic symptom disorder: A bibliometric study.

Background: With the growing scholarly and clinical fascination with somatic symptom disorder (SSD), a bibliometric analysis is lacking.

Aim: To conduct a bibliometric analysis to investigate the current status and frontiers of SSD.

Methods: The documents related to SSD are obtained from the web of science core collection database (WoSCC), and VOSviewer 1.

A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against .

The efficacy of many compounds against is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lungs. However, previous models, typically employing wild-type strains, were intricate, time-consuming, labor-intensive, and with poor reproducibility.

Trajectories of Maternal Urinary Iodine Concentration Are Associated With Gestational Diabetes Mellitus.

Objectives: The relationship between iodine status and gestational diabetes mellitus (GDM) is inconclusive. This study aimed to explore the trajectories of urinary iodine concentrations (UIC) in pregnant women before GDM diagnosis and to assess the associations between maternal UIC trajectories and the risk of developing GDM.

Methods: A prospective cohort study was conducted in China.

Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO nanoparticles via mTOR-TFEB pathway autophagic flux inhibition.

Chemotherapeutic drugs often fail to provide long-term efficacy due to their lack of specificity and high toxicity. To enhance the biosafety and reduce the side effects of these drugs, various nanocarrier delivery systems have been developed. In this study, we loaded the anticancer drug doxorubicin (DOX) and an MRI contrast agent into silica nanoparticles, coating them with pH-responsive and tumor cell-targeting polymers.

Purification, crystal structural characterization of porcine kidney dipeptidyl peptidase IV (PkDPP-IV) and its interaction with oyster derived inhibitory peptide ILAPPER.

Dipeptidyl peptidase IV (DPP-IV) is an important target enzyme for the treatment of type 2 diabetes mellitus (T2DM). Increasing researchers try to screen DPP-IV inhibitory peptides while the cost of DPP-IV is high. In this study, PkDPP-IV was efficiently purified by acid precipitation, ammonium sulfate salting out and gel filtration chromatography with a purification of 283.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.

CDK14 regulates the development and repair of lung.

Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury.

Within-host evolution of a transcriptional regulator contributes to the establishment of chronic Pseudomonas aeruginosa infection.

As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear.

Alterations of amino acids in older adults with Alzheimer's Disease and Vascular Dementia.

Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls.