Nano-enabled repurposing of Benproperine phosphate enhances pancreatic Cancer chemotherapy through lethal autophagy arrest and immune activation.

Gemcitabine-based chemotherapy remains a cornerstone in pancreatic cancer treatment, yet its efficacy is hindered by poor bioavailability and adaptive resistance mechanisms, such as autophagy. In this study, we developed a hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) drug-repurposing nanoplatform (HA/ZIF-8@BPP/Gem) against pancreatic cancer through the co-delivery of the antitussive benproperine phosphate (BPP) and gemcitabine (Gem). Using cell lines, patient-derived xenograft models, and orthotopic tumor models, we demonstrated that BPP and Gem, rapidly released from the nanoplatform in the acidic tumor microenvironment, exhibited synergistic cytotoxicity without causing significant biochemical abnormalities or organ toxicity.

In situ ischemic postconditioning for acute ischemic stroke: preliminary exploratory study.

Background: Endovascular therapy within 24 hours of stroke onset is effective and safe, but successful recanalization does not always give favorable outcomes. Ischemic postconditioning (IPostC), a reperfusion strategy with potential neuroprotective effects, has been extensively studied in preclinical models, but its impact in humans remains unclear. Building on a previous dose escalation study, we aimed to investigate the effect of in situ IPostC on infarct volume in patients with acute ischemic stroke following mechanical thrombectomy.

Prediction of Occlusion Duration in Nonacute Intracranial Large Artery Through High-Resolution Vessel Wall Imaging.

Background: Accurately assessing the duration of nonacute intracranial large vessel occlusion (ILVO) is critical, because occlusion exceeding 3 months significantly reduces endovascular treatment efficacy. This study explores high-resolution vessel wall imaging to differentiate subacute (3 days-1 month), short-duration chronic (1-3 months), and long-duration chronic (>3 months) ILVOs.

Methods: A retrospective analysis was conducted on consecutive patients with nonacute ILVOs with well-documented clinical courses (June 2018-March 2022).

A hypoxia-responsive nanomedicine for cancer immunotherapy through ligand competition-induced dual-prodrug activation.

Diethyldithiocarbamate (DTC), a strong Cu chelator that can bind with Cu to form toxic bis(N, N-diethyldithiocarbamate) copper (II) (Cu(DTC)) complex, has been shown to have excellent Cu-dependent anti-tumor activity. Unfortunately, the treatment outcome of DTC administration is limited by low level of endogenous Cu in tumor cells and insufficient Cu(DTC)in situ generation; while direct delivery of Cu(DTC) complexes often leads to toxic side effects in normal cells. To simultaneously deliver DTC and Cu with high efficacy, a hypoxia/nitroreductase-responsive DTC prodrug is designed, which is co-assembled with curcumin-Cu complex (Cur-Cu) and decorated with bovine serum albumin to form a nanodrug.

Evaluation of the Safety and Efficacy of Remimazolam Combined With Remifentanil for Sedation in Adult Dental Anxiety Patients Undergoing Mandibular Impacted Third Molar Extraction: A Single-Center, Retrospective Cohort Analysis.

Dental anxiety (DA) often leads to significant fear and anxiety in the patients undergoing dental procedures, and increases the complexity and difficulty of treatment. Currently, remimazolam, a benzodiazepine-like sedative drug, has been found effective and safe during endoscopic and surgical procedures. Therefore, this study aimed to evaluate the safety levels and efficacy profile of remimazolam combined with remifentanil for sedation in adult patients with DA who underwent the mandibular impacted third molar extraction.

Improved preoperative planning for endovascular therapy: High-resolution vessel wall magnetic resonance imaging shows promise in identifying proximal occlusion site and distal boundary of the occlusion of acute ischemic stroke.

Background And Purpose: Detecting the proximal occlusion site (POS) and distal boundary of the occlusion (DBO) of arterial occlusion is very important for the prognosis of endovascular treatment. Recent studies have shown that magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) are also beneficial for preoperative patient selection for endovascular therapy. High-resolution vessel wall MRI (HRVW-MRI) for intraluminal detection of arterial largevessel occlusions (LVOs) is receiving increasing attention.

Experimental study on surface protection support that uses polymer thin spray-on layer.

The thin spray-on liner (TSL) is widely used in the seal engineering of mines. TSL with high bearing capability is a new method that can be used to replace metal mesh in the roadway support of underground coal mines. This method exhibits the advantages of fast development, automation, and applicability of geo-conditions.

DTI-RME: a robust and multi-kernel ensemble approach for drug-target interaction prediction.

Background: Drug-target interaction (DTI) refers to the specific mechanisms by which drug molecules interact with biological targets within a biological system. Computational methods are widely employed for DTI prediction, as they are time-efficient and resource-saving compared to experimental approaches. Although numerous DTI prediction methods have achieved promising results, accurately modeling DTIs remains challenging due to three key issues: noisy interaction labels, ineffective multi-view fusion, and incomplete structural modeling.

PGSFusion streamlines polygenic score construction and epidemiological applications in biobank-scale cohorts.

Background: The polygenic score (PGS) is an estimate of an individual's genetic susceptibility to a specific complex trait and has been instrumental to the development of precision medicine. As an increasing number of genome-wide association studies (GWAS) have emerged, numerous sophisticated statistical and computational methods have been developed to facilitate the PGS construction. However, both the complex statistical estimation procedure and the various data formats of summary statistics and reference panel make the PGS calculation challenging and not easily accessible to researchers with limited statistical and computational backgrounds.

LEO or LEO baby within enterprise overlapping stents combined with coil embolization treatment for ruptured vertebrobasilar artery dissecting aneurysms.

This study sought to evaluate the feasibility and effectiveness of the LEO or LEO baby within enterprise (EP) overlapping stents for treating ruptured vertebrobasilar artery dissecting aneurysms (VBDAs). A retrospective analysis was conducted on 20 patients with a total of 20 ruptured VBDAs, who received reconstructive treatment utilizing the LEO/LEO baby within enterprise overlapping stents combined with coil embolization, between December 2018 and June 2023. Patient characteristics, clinical outcomes, and radiological results were thoroughly reviewed.

LRRC8A Regulates Outer Hair Cell Volume and Electromotility and is Required for Hearing.

Damage to the cochlear outer hair cell (OHC) is a major cause of deafness in mammals. OHCs amplify the auditory signals to enhance the sensitivity and sound frequency selectivity of the auditory system. However, detailed mechanisms underlying functional OHC regulation remain unclear.

Engineered Outer Membrane Vesicles for Antigen Delivery: Exploratory Study on Adjuvant Activity and Systemic Reactogenicity.

Background: Outer Membrane Vesicles (OMVs), nanosized particles derived from Gram-negative bacteria, are promising vaccine carriers due to innate immunogenicity and self-adjuvant properties. Yet the systematic evaluations of OMV-associated toxicity remain limited.

Methods: We developed a CRISPR/Cas9-engineered serovar Typhimurium mutant (Mut4_STM) to produce detoxified OMVs (Mut4_OMVs) with enhanced yield.

Aromatic dicarboxylates induced structural diversity of Cd metal-organic frameworks from a 2D layer to a 3D pillar-layer network for fluorescence sensing of cations, anions and L-serine.

Two distinct Cd metal-organic frameworks (MOFs) with the formulas {[Cd(BBZB)(oba)]·HO} (JXUST-45) and {[Cd(BBZB)(bpdc)]·2HO} (JXUST-46) featuring 2D layer and 3D pillar-layer structures, respectively, have been prepared, which were regulated by aromatic dicarboxylate ligands (4,4'-diphenyl ether dicarboxylic acid, Hoba; 4,4'-biphenyldicarboxylic acid, Hbpdc; and 4,7-bis(1-benzimidazol-1-yl)-2,1,3-benzothiazole, BBZB). JXUST-45 and JXUST-46 can be considered good fluorescence sensors toward Al, Fe, AcO, CrO, and L-serine. Meanwhile, JXUST-45 and JXUST-46 have good thermal stability and recovery ability.

Use of Technology to Support Health Care Providers Delivering Care in Low- and Lower-Middle-Income Countries: Systematic Umbrella Review.

Background: Health care providers are at the forefront of the digital health transformation underway in low- and lower-middle-income countries (LLMICs). Digital health innovations (DHIs) promise more efficient and equitable health care delivery. However, their implementation often outpaces the generation of evidence supporting their effectiveness, resulting in fragmented projects that are poorly aligned with local system needs.

3D bioprinted scaffolds for osteochondral regeneration: advancements and applications.

Osteochondral defects, involving concurrent damage to articular cartilage and subchondral bone, pose significant clinical challenges due to their complex hierarchical structure and limited self-healing capacity. Traditional repair strategies often fail to replicate the biomechanical and biological gradients inherent to native osteochondral tissue, leading to suboptimal outcomes. Three-dimensional (3D) bioprinting has emerged as a transformative approach, enabling precise spatial deposition of biomaterials, cells, and signaling factors to construct biomimetic scaffolds with tailored gradients.

De Novo Design of Efficient NIR-II-Activated Heavy-Atom-Free Type-I Photosensitizer for Anti-Tumor Photoimmunotherapy.

Type-I photosensitizers (PSs) are considered to be efficient agents for overcoming the oxygen-dependent deficiency of traditional photodynamic therapy (PDT). However, it is still challenging to design type-I PSs that can be activated by the second near-infrared (NIR-II) irradiation. Herein, a series of organic heavy-atom-free molecules are designed (named as CTU1, CTU2, and CTU3) and exhibit strong absorption bands over the first near-infrared and NIR-II regions.

Medical Graph Diffusion: Hybrid Graph Diffusion with Heterogeneous Graph Convolutional Networks for Medical Text Classification.

Text classification is a critical task for understanding the knowledge behind text, especially in medical text. In this paper, we propose a medical graph diffusion model, named the MGD model, for the medical text classification task. To model more structural relationships within a document, our MGD model constructs a text heterogeneous graph to represent word-level, sentence-level, and word-sentence-level structural relationships.

Time-variant and tissue-level collaterals predict postoperative neurological recovery and clinical outcomes of patients with endovascular thrombectomy.

Background: A comprehensive assessment of collateral status can yield profound insights into the ischemic mechanism in patients experiencing acute ischemic stroke. This study aims to investigate whether time-variant and tissue-level collateral characteristics may serve as predictors for functional outcomes in patients undergoing endovascular thrombectomy (EVT) through the application of machine learning (ML) algorithms, and to stratify postoperative neurological recovery of these patients.

Methods: In this retrospective study, 128 acute ischemic stroke patients characterized by anterior large-vessel occlusion and received EVT between May 2020 and December 2022 were enrolled.

Heterogeneous Graph Contrastive Learning with Graph Diffusion for Drug Repositioning.

Drug repositioning, which identifies novel therapeutic applications for existing drugs, offers a cost-effective alternative to traditional drug development. However, effectively capturing the complex relationships between drugs and diseases remains challenging. We present HGCL-DR, a novel heterogeneous graph contrastive learning framework for drug repositioning that effectively integrates global and local feature representations through three key components.

Highly Stable Zn(II) Metal-Organic Framework as an "On-Off-On" Fluorescence Sensor toward HPO Anion in the pH-Dynamic System.

In a dynamic system, fluorescent probes with dual signals not only efficiently identify target analytes but also resist interference from the system, aiding in further system differentiation. A new three-dimensional (4,6)-connected Zn(II)-based metal-organic framework with the formula {[Zn(BTDI)(3,5-BBIP)]·2.5HO·2DMF} () was solvothermally used with 5,5'-(benzothiadiazole-4,7-diyl)diisophthalic acid (HBTDI), which incorporates benzothiadiazole luminescent groups.

Advances in 3D-printed scaffold technologies for bone defect repair: materials, biomechanics, and clinical prospects.

The treatment of large bone defects remains a significant clinical challenge due to the limitations of current grafting techniques, including donor site morbidity, restricted availability, and suboptimal integration. Recent advances in 3D bioprinting technology have enabled the fabrication of structurally and functionally optimized scaffolds that closely mimic native bone tissue architecture. This review comprehensively examines the latest developments in 3D-printed scaffolds for bone regeneration, focusing on three critical aspects: (1) material selection and composite design encompassing metallic; (2) structural optimization with hierarchical porosity (macro/micro/nano-scale) and biomechanical properties tailored; (3) biological functionalization through growth factor delivery, cell seeding strategies and surface modifications.

Numerical study of decoupling charge drilling and blasting under high stress conditions.

The inherent characteristics of plateau stress impose constraints on the expansion of rock cracks induced by blasting operations. Utilizing decoupling blasting in deep rock excavation projects can significantly alter the outcomes of rock blasting. This study conducted comprehensive analyses for investigating the impacts of both concentric and eccentric decoupling on rock damage with the aim of identifying the optimal concentric/eccentric decoupling coefficient (DC).

Surface Display of Type 1 Fimbriae on Induces Antigen-Specific Immune Response via Oral Route.

Background: Live attenuated bacteria are promising candidates for mucosal vaccine delivery due to their ability to elicit robust immune responses. FimH is the adhesion protein of type 1 fimbriae, which is used as mucosal adjuvants. This study aims to develop a novel attenuated live bacterial vector via fimbriae recovery on Methods: We generated pBAD-Fim/FWL01 by deleting IS elements in the fimbrial cluster of 2a strain T32.

AgrC biotinylation inhibits Staphylococcus aureus infection.

Staphylococcus aureus (S. aureus) is a leading cause of nosocomial infections, particularly among antibiotic-resistant strains. S.