Characterizing the diabetes-induced pathological changes of the mouse lung by single-cell RNA sequencing.

Pulmonary disorders are exacerbated by high blood sugar, leading to a disordered immune defense and increased susceptibility to infection. Type 2 diabetes mellitus (T2D) is characterized by insulin resistance and inadequate insulin production. Mechanisms leading to pulmonary alternation due to T2D are not clear.

Control Performance Of Amphibian Metamorphosis Assays With Xenopus Laevis.

The amphibian metamorphosis assay (AMA) is an in vivo screen to assess potential interactions of chemicals with the amphibian thyroid system. Tadpoles are exposed for 21-days, then assessed for development and growth after 7 days and at test termination. This paper presents data from studies performed to satisfy test orders from the US EPA's Endocrine Disruptor Screening Program.

Enhancing biobutanol production by optimizing acetone-butanol-ethanol fermentation from sorghum grains through strategic immobilization of amylolytic enzymes.

Tannin-containing sorghum grains, suitable for acetone-butanol-ethanol (ABE) production by Clostridium acetobutylicum, have required pretreatment to eliminate tannins inhibiting the strain's amylolytic activity. This study investigates biobutanol production enhancement by immobilizing enzymes on polydopamine-functionalized polyethersulfone (PES) membranes with magnetic nanoparticles for Separated Hydrolysis and Fermentation (SHF) and Simultaneous Saccharification and Fermentation (SSF) processes. After multi-stage hot water treatment, TG3 sorghum (from the third stage) was used, where the enzyme-immobilized PES membrane produced 4.

Physicochemical properties, structural analysis, and activity of Shancigu polysaccharides.

Objective: To investigate the physicochemical properties, structural characteristics and in vitro activities of Shancigu polysaccharides to identify the authenticity of Shancigu, safeguard its medicinal value, and ensure the safety of its market distribution.

Methods: Eleven polysaccharides from different sources of Shancigu were obtained using water extraction and alcohol precipitation. Physicochemical properties were determined using colorimetry.

Discovery of sugar-based natural framework as phytopathogenic virus capsid protein inhibitors using a state-of-the-art multiple screening strategy.

The prompt and efficient identification of targeted inhibitors against unscrupulous pathogenic viruses holds promise for preventing epidemic disease outbreaks. Herein, a comprehensive multichannel screening method (multiple docking cross-validation, molecular dynamics simulation, and density functional theory calculation) integrated with bioactivity identification is rationally established using sugar-based natural ligand libraries to target tobacco mosaic virus (TMV) capsid proteins. Encouragingly, compounds A0 (K = 0.

Dynamic Neural Mechanisms Underlying Sustained Motor Training Post-Stroke: An fNIRS Investigation Employing Time-Varying ALFF and Functional Connectivity Analysis.

Motor dysfunction of the upper limbs following a stroke predominantly arises from abnormal motor patterning caused by the disrupted balance of inter-cortical communication within motor-associated cortical regions. Temporal analysis offers a more precise reflection of the cortical functional state in affected patients. This study employed fNIRS to capture hemodynamic responses among 20 stroke patients and 19 healthy controls in both resting and Baduanjin task state.

N-Branched Tricyclic Guanidines as Novel Melanocortin-3 Receptor Agonists and Melanocortin-4 Receptor Antagonists.

The melanocortin receptors are a class of centrally and peripherally expressed G protein-coupled receptors, of which the MC3R and MC4R subtypes are implicated in the regulation of appetite and energy homeostasis and can serve as potential therapeutic targets for disorders such as obesity and cachexia. An unbiased high-throughput mixture-based library screen was implemented to identify novel ligands with an emphasis on the identification of nanomolar-potent agonists of the mouse melanocortin-3 receptor. This screen yielded the discovery of an N-branched tricyclic guanidine scaffold (TPI2408) that contained three nanomolar potent mMC3R agonists and additional compounds that possessed antagonism for the mMC4R.

Efficacy and Safety of Sulforaphane Added to Antipsychotics for the Treatment of Negative Symptoms of Schizophrenia: A Randomized Controlled Trial.

There are few established treatments for negative symptoms in schizophrenia, which persist in many patients after positive symptoms are reduced. Oxidative stress, inflammation, and epigenetic modifications involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor.

Efficacy and Safety of BI 1358894 in Patients With Borderline Personality Disorder: Results of a Phase 2 Randomized, Placebo-Controlled, Parallel Group Dose-Ranging Trial.

To provide proof-of-concept (PoC), dose-range finding, and safety data for BI 1358894, a TRPC4/5 ion channel inhibitor, in patients with borderline personality disorder (BPD). This was a phase 2, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to oral placebo or BI 1358894 (5 mg, 25 mg, 75 mg, or 125 mg) once daily in a 2.

A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer.

Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC.

Patients And Methods: Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor-targeted therapy or chemotherapy were eligible.

An Educational Intervention to Promote Central Nervous System-Active Deprescribing in Dementia: A Pilot Study.

Background: Central nervous system (CNS)-active polypharmacy (defined as concurrent exposure to three or more antidepressant, antipsychotic, antiseizure, benzodiazepine, opioid, or nonbenzodiazepine benzodiazepine receptor agonists) is associated with significant potential harms in persons living with dementia (PLWD).We conducted a pilot trial to assess a patient nudge intervention's implementation feasibility and preliminary effectiveness to prompt deprescribing conversations between PLWD experiencing CNS-active polypharmacy and their primary care clinicians ("clinicians").

Methods: We used the electronic health record to identify PLWD prescribed CNS-active polypharmacy in primary care clinics from two health systems.

Coumarin derivatives containing the 1,3,4 oxadiazole/thiadiazole moiety discovered as potential anti-tobacco mosaic virus agents.

In this paper, a series of oxadiazole/thidiazole containing coumarin derivative derivatives were designed, synthesized and characterized using NMR and HRMS. The evaluation of antiviral activity revealed that some of the synthesized compounds exhibited good in vivo antiviral efficacy against tobacco mosaic virus (TMV). Notably, compounds H6 and Y5 demonstrated exceptional therapeutic and protective effects against TMV, with EC values of 180.

Perfusion estimation from dynamic non-contrast computed tomography using self-supervised learning and a physics-inspired U-net transformer architecture.

Purpose: Pulmonary perfusion imaging is a key lung health indicator with clinical utility as a diagnostic and treatment planning tool. However, current nuclear medicine modalities face challenges like low spatial resolution and long acquisition times which limit clinical utility to non-emergency settings and often placing extra financial burden on the patient. This study introduces a novel deep learning approach to predict perfusion imaging from non-contrast inhale and exhale computed tomography scans (IE-CT).

The effects of estrogen depletion in female rats: differential influences on somato-motor and sensory cortices.

Aging women experience a significant decline of ovarian hormones, particularly estrogen, following menopause, and become susceptible to cognitive and psychomotor deficits. Although the effects of estrogen depletion had been documented in the prefrontal and somatosensory cortices, its impact on somatomotor cortex, a region crucial for motor and cognitive functions, remains unclear. To explore this, we ovariectomized young adult female rats and fed subsequently with phytoestrogen-free diet and studied the effects of estrogen depletion on the somato-sensory and motor cortices.

Aptamer-based fluorescence biosensor for rapid detection of chloramphenicol based on pyrene excimer switch.

Chloramphenicol (CAP) is widely used in treating bacteria infection in animals and humans. However, the accumulation of CAP in food and environment caused serious health risk to human. Consequently, sensitive and selective detection of CAP is of great importance in environmental monitoring and food safety.

Health Risk of Heavy Metal and Implication for Ecological Threat in Soils Weathered from the Black Shale.

Heavy metals were analyzed in rhizosphere soils and rice grains collected from typical black shale areas. The concentrations of As, Cd, Cu, and Zn in the rhizosphere soil exceeded the current soil environmental quality standards. Cd exhibited the highest bioaccumulation capacity, with 45% of rice grains exceeding food safety limit.

AntiBinder: utilizing bidirectional attention and hybrid encoding for precise antibody-antigen interaction prediction.

Antibodies play a key role in medical diagnostics and therapeutics. Accurately predicting antibody-antigen binding is essential for developing effective treatments. Traditional protein-protein interaction prediction methods often fall short because they do not account for the unique structural and dynamic properties of antibodies and antigens.

Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity.

Background And Aims: Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims to demonstrate the pre-clinical efficacy and safety of extracellular vesicles (EVs) loaded with VEGF-A mRNA for the treatment of ischaemic vascular disease.

Methods: After encapsulation of full-length VEGF-A mRNA into fibroblast-derived EVs via cellular nanoporation (CNP), collected VEGF-A EVs were delivered into mouse models of ischaemic injury.

Acid-Triggered Cascaded Responsive Supramolecular Peptide Alleviates Myocardial Ischemia‒Reperfusion Injury by Restoring Redox Homeostasis and Protecting Mitochondrial Function.

Redox imbalance, including excessive production of reactive oxygen species (ROS) caused by mitochondrial dysfunction and insufficient endogenous antioxidant capacity, is the primary cause of myocardial ischemia‒reperfusion (I/R) injury. In the exploration of reducing myocardial I/R injury, it is found that protecting myocardial mitochondrial function after reperfusion not only reduces ROS bursts but also inhibits cell apoptosis triggered by the release of cytochrome c. Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2) is considered a potential therapeutic target for treating myocardial I/R injury by enhancing the cellular antioxidant capacity through the induction of endogenous antioxidant enzymes.

A Regio- and Stereoselective Ring-Opening Polymerization Approach to Isotactic Alternating Poly(lactic-co-glycolic acid) with Stereocomplexation.

Poly(lactic-co-glycolic acid) (PLGA) has been widely employed for various biomedical applications owing to its biodegradability and biocompatibility. The discovery of the stereocomplex formation between enantiomeric alternating PLGA pairs underscored its potential as high-performance biodegradable materials with diverse material properties and biodegradability. Herein, we have established a regio- and stereoselective ring-opening polymerization approach for the synthesis of stereocomplexed isoenriched alternating PLGA from racemic methyl-glycolide (rac-MG).

A Practical Synthetic Route to Cinnolines: Application to the Design and Synthesis of RSV NNI Inhibitor JNJ-8003 Analogues.

The manuscript describes the development of an efficient synthetic route to cinnolines, facilitating faster access to JNJ-8003 related Respiratory Syncytial Virus (RSV) non-nucleoside (NNI) inhibitors. Starting from correctly functionalized aryl halides, a Sonogashira reaction followed by SNAr reaction with hydrazine 1,2-dicabroxylate reagents provided dihydrocinnolines directly via in situ 6-endo-dig cyclization. The dihydrocinnolines were conveniently transformed to corresponding cinnolines in one step.

Continuous Abrupt Vegetation Shifts in the Global Terrestrial Ecosystem.

Previous studies have primarily focused on single abrupt shifts; however, the actual ecosystem will experience continuous abrupt shifts (CAS), including different directions shifts (DDS) and same direction shifts (SDS). The patterns and drivers of these CAS remain unclear. We examined the patterns of the DDS and SDS by two vegetation datasets and then tested climate drivers comprising atmospheric temperature (MAT), atmospheric precipitation (MAP), soil temperature (ST) and soil water content (SW); finally, hysteresis effects were examined with reference to principal drivers.

A Population-Based Study of the Association Among Dry Mouth, Vitamin B2, and Mortality.

Background: Previous studies have indicated that older adults with the symptom of dry mouth have an increased risk of death. B vitamins are strongly linked to oral and systemic health. However, the relationship among dry mouth, vitamin B2 and mortality remains unclear.

Clinical patterns of vitiligo in Japan: A descriptive study using the JMDC claims database.

Vitiligo is a chronic autoimmune disorder that profoundly impacts patients' quality of life. Real-world data on vitiligo in Japan are limited. This descriptive, cross-sectional study used a claims database to evaluate vitiligo prevalence, patient demographics, treatments, and comorbidities in Japanese patients with vitiligo.