Efficacy and safety of tirofiban in acute ischemic stroke patients with ideal reperfusion: A cohort study of LAA and CE subgroups.

Background And Objectives: Despite achieving ideal reperfusion (eTICI = 3) through endovascular treatment (EVT), some acute ischemic stroke (AIS) patients still experience poor outcomes. This study aims to evaluate the efficacy and safety of tirofiban in AIS patients with ideal reperfusion, focusing on its effects in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke.

Methods: A total of 474 AIS patients from the RESCUE-BT database were included.

Discovery of INCB159020, an Orally Bioavailable KRAS G12D Inhibitor.

The inhibition of mutant KRAS proteins has emerged as a promising approach for treating KRAS-driven cancers, as evidenced by the clinical success of KRAS G12C inhibitors. KRAS G12D, the most common mutant, promises significant expansion of the addressable patient population; however, the reduced nucleophilicity of aspartate compared to cysteine poses significant challenges in balancing sufficient potency with ADME properties to support oral exposure. Herein, we describe the discovery of KRAS G12D inhibitor (), which achieves oral exposure in nonhuman primate (NHP).

Prediction of SPT-07A Pharmacokinetics in Rats, Dogs, and Humans Using a Physiologically-Based Pharmacokinetic Model and In Vitro Data.

SPT-07A, a D-borneol, is currently being developed in China for the treatment of ischemic stroke. We aimed to create a whole-body physiologically-based pharmacokinetic (PBPK) model to predict the pharmacokinetics of SPT-07A in rats, dogs, and humans. The in vitro metabolism of SPT-07A was studied using hepatic, renal, and intestinal microsomes.

Portable SpectroChip-Based Immunoassay Platform for Rapid and Accurate Melamine Quantification in Urine Samples.

Growing concerns about the health risks of melamine adulteration in food products highlight the urgent need for reliable detection methods. However, the long-term effects of chronic low-level melamine exposure remain inadequately explored. This study introduces THE ONE InstantCare platform, a portable immunoassay analyzer integrating a SpectroChip-based spectral processing unit (SPU) with lateral flow immunoassay (LFIA) for sensitive and accurate quantification of melamine in human urine.

CRISPR-Cas12a-driven aptasensor for sensitive detection of alternariol by using a personal glucose meter.

Alternariol (AOH) has attracted much attention as an emerging toxin in edible herbs that can pose potential carcinogenic risks to human. However, the rapid detection of AOH to ensure food safety remains a challenge. Here, a CRISPR-Cas12a-mediated aptamer-based sensor (aptasensor) was proposed for the sensitive quantification of AOH by using a personal glucose meter.

Causality of genetically determined glucosamine supplementation on cognition and sarcopenia: a Mendelian randomization study.

Background: Evidence indicates a negative link between glucosamine and age-related cognitive decline and sarcopenia. However, the causal relationship remains uncertain. This study aims to verify whether glucosamine is causally associated with cognitive function and sarcopenia.

Runx2-NLRP3 Axis Orchestrates Matrix Stiffness-evoked Vascular Smooth Muscle Cell Inflammation.

Arterial stiffening is a hallmark of chronic kidney disease (CKD) related cardiovascular events and is primarily attributed to the elevated matrix stiffness. Stiffened arteries are accompanied by low-grade inflammation, but the causal effects of matrix stiffness on inflammation remain unknown. For analysis of the relationship between arterial stiffness and vascular inflammation, pulse wave velocity (PWV) and aortic inflammatory markers were analyzed in an adenine-induced mouse model of CKD in chronological order.

Evaluation of parent reminder-recall letters to promote human papillomavirus vaccination.

Objective: Human papillomavirus (HPV) vaccine uptake remains suboptimal. Our stepped-wedge cluster randomized trial found that reminder-recall letters sent to parents of age-eligible children significantly increased vaccine uptake compared to usual care. Subsequently, we conducted a process evaluation to assess the mechanisms of the letter's effectiveness.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

A modular approach to catalytic stereoselective synthesis of chiral 1,2-diols and 1,3-diols.

Optically pure 1,2-diols and 1,3-diols are the most privileged structural motifs, widely present in natural products, pharmaceuticals and chiral auxiliaries or ligands. However, their synthesis relies on the use of toxic or expensive metal catalysts or suffer from low regioselectivity. Catalytic asymmetric synthesis of optically pure 1,n-diols from bulk chemicals in a highly stereoselective and atom-economical manner remains a formidable challenge.

Tracheal mucosal keratosis: Case discussion and literature review.

A 57-year-old female presented with a chief complaint of cough, with productive yellow sputum particularly severe in the morning. Bronchoscopy revealed inflammatory changes in both main bronchi, with abundant white purulent secretions and necrotic material adhering to the luminal surface. Histopathological examination showed chronic inflammatory changes in the mucosal tissue, with mild hyperplasia of the local squamous epithelium and evidence of keratinization in the surrounding area, consistent with a diagnosis of tracheal mucosal keratosis.

A novel quantitative angiogenesis assay based on visualized vascular organoid.

Angiogenesis describes the sprouting of blood vessels from existing vasculatures and it plays a pivotal role in disease progress such as diabetes, age-related macular degeneration and cancer. However, the most widely used anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) pathway still lacked of specificity and therapeutic efficacy. To establish a method suitable for high-throughput drug screening and faithfully recapitulate the feature of in vivo angiogenesis, we generated a PECAM1-mRuby3-secNluc; ACTA2-EGFP dual reporter human pluripotent stem cell (hPSC) line and utilizing the cell line to establish a visualized and quantifiable in vitro angiogenesis model with stem cell-derived vascular organoid.

CircRNA-loaded DC vaccine in combination with low-dose gemcitabine induced potent anti-tumor immunity in pancreatic cancer model.

Although promising, dendritic cell (DC) vaccines may not suffice to fully inhibit tumor progression alone, mainly due to the short expression time of the antigen in DC vaccines, immunosuppressive tumor microenvironment, and tumor antigenic modulation. Overcoming the limitations of DC vaccines is expected to further enhance their anti-tumor effects. In this study, we constructed a circRNA-loaded DC vaccine utilizing the inherent stability of circular RNA to enhance the expression level and duration of the antigen within the DC vaccine.

Ultrasonography, contrast-enhanced ultrasonography and contrast-enhanced computer tomography features of hepatic sarcomatoid carcinoma and hepatic sarcoma: a retrospective study of 23 cases.

Background: Hepatic sarcomatoid carcinoma (HSC) and hepatic sarcoma (HS) are rare malignancies. Without pathology, the differential diagnosis between these two tumors is difficult due to their frequent overlaps in clinical presentations and imaging features. Currently, there are limited analyses about the ultrasound (US), contrast-enhanced ultrasound (CEUS) and contrast-enhanced computer tomography (CECT) characteristics of HSC and HS.

Extracellular matrix in vascular homeostasis and disease.

The extracellular matrix is an essential component and constitutes a dynamic microenvironment of the vessel wall with an indispensable role in vascular homeostasis and disease. From early development through to ageing, the vascular extracellular matrix undergoes various biochemical and biomechanical alterations in response to diverse environmental cues and exerts precise regulatory control over vessel remodelling. Advances in novel technologies that enable the comprehensive evaluation of extracellular matrix components and cell-matrix interactions have led to the emergence of therapeutic strategies that specifically target this fine-tuned network.

In Pursuit of Lead Innovation: Pharmaceutically Important and Distinct Amide-Free Succinate Dehydrogenase Inhibitors.

Though succinate dehydrogenase inhibitors (SDHIs) are quite successful in the modern agrochemical industry, the Fungicide Resistance Action Committee has classified the resistance risk as "medium to high". Structural analysis reveals that these antifungal chemotypes are highly conserved with amides as a consistent feature. This chemical factor may be a potential factor for the ever-increasing resistance risk.

Covalent Modification of Selenium in Polysaccharide Enhances Immunoregulation Activity via the TLR4-Mediated MAPK/NF-κB Signaling Pathway.

Selenium (Se) is a crucial trace element that demonstrates significant immunomodulatory effects, which are attributed to the variability in its valence states and metabolic pathways. To investigate the Se-related immunoregulatory effects, locust bean gum (LBG), a typical galactomannan, was selenized by employing deep eutectic solvents (DESs) as high-efficiency solvents to obtain Se-covalent modified LBG (SeLBGs) with similar molecular mass and different Se contents (SeLBG, 1049.57 and SeLBG, 4926.

Genetically Encoded Fluorogenic DNA Aptamers for Imaging Metabolite in Living Cells.

Genetically encoded fluorescent protein and fluorogenic RNA sensors are indispensable tools for imaging biomolecules in cells. To expand the toolboxes and improve the generalizability and stability of this type of sensor, we report herein a genetically encoded fluorogenic DNA aptamer (GEFDA) sensor by linking a fluorogenic DNA aptamer for dimethylindole red with an ATP aptamer. The design enhances red fluorescence by 4-fold at 650 nm in the presence of ATP.

Product oriented upcycling of waste polyethylene terephthalate plastic and carbon dioxide via decoupled electrolysis.

End-of-life plastics and carbon dioxide (CO2) are anthropogenic waste carbon resources; it is imperative to develop efficient technologies to convert them to value-added products. Here we report the upcycling of polyethylene terephthalate (PET) plastic and CO2 toward valuable potassium diformate, terephthalic acid, and H2 fuel via decoupled electrolysis. This product-oriented process is realized by two electrolyzers: (1) a solid-state-electrolyte based CO2 electrolyzer and (2) a solid-polymer-electrolyte-based PET electrolyzer.

Viral-Mediated Connexin 26 Expression Combined with Dexamethasone Rescues Hearing in a Conditional Gjb2 Null Mice Model.

GJB2 encodes connexin 26 (Cx26), the most commonly mutated gene causing hereditary non-syndromic hearing loss. Cx26 is mainly expressed in supporting cells (SCs) and fibrocytes in the mammalian cochlea. Gene therapy is currently considered the most promising strategy for eradicating genetic diseases.

Predicting epidermal growth factor receptor mutation status of lung adenocarcinoma based on PET/CT images using deep learning.

Background: The aim of this study is to develop deep learning models based on F-fluorodeoxyglucose positron emission tomography/computed tomographic (F-FDG PET/CT) images for predicting individual epidermal growth factor receptor () mutation status in lung adenocarcinoma (LUAD).

Methods: We enrolled 430 patients with non-small-cell lung cancer from two institutions in this study. The advanced Inception V3 model to predict EGFR mutations based on PET/CT images and developed CT, PET, and PET + CT models was used.

The effects of 'small private online course + flipped classroom' teaching on job competency of nuclear medicine training trainees.

Background: Nuclear medicine is an interdisciplinary field that integrates basic science with clinical medicine. The traditional classroom teaching model lacks interactive and efficient teaching methods and does not adequately address the learning needs and educational goals associated with standardized training for residents. The teaching model that combines Small Private Online Courses (SPOCs) with a flipped classroom approach is more aligned with the demands of real-life scenarios and workplace requirements, thereby assisting students in developing comprehensive literacy and practical problem-solving skills.

Anti-diabetic effects of GLP-1 receptor agonists on obese and overweight patients across diabetes status, administration routes, treatment duration and baseline characteristics: A systematic review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for anti-obesity indications. However, little is known of the comparative effect of GLP-1 RAs and their glycemic impact across the different routes of administration, diabetic statuses and durations of prescription. PubMed, EMBASE and CENTRAL were searched from inception to 13 February 2024.