Discovery of novel dihydropteridone derivatives as orally bioavailable PLK1 inhibitors with reduced hERG inhibitory activity for acute myeloid leukemia treatment.

Polo like kinase 1 (PLK1) is a serine/threonine kinase that plays an important role in multiple phases of the cell cycle, inhibiting its activity has been considered an effective treatment for acute myeloid leukemia (AML). Here, we reported a series of highly potent PLK1 inhibitors. Among them, compound WD6 was identified as the most promising PLK1 inhibitor, with an IC value of 0.

Lycium barbarum extract improves brain and visual functions in mice models of Alzheimer's disease through activating WNT pathway.

Background: Alzheimer's disease (AD) is the leading cause of dementia in the elderly, characterized by visual deficits and cognitive impairment. However, current therapies have limited efficacy.

Purpose: This study aims to investigate whether Lycium barbarum extract (LBE) can mitigate the decline in brain and visual function in mouse models of AD during the middle and late stages.

Melatonin ameliorates Pb-induced mitochondrial homeostasis and ovarian damage through regulating the p38 signaling pathway.

Lead (Pb), a widespread metallic pollutant in the environment, has been found to have detrimental effects on the female reproduction system. Recently, our group discovered a significant correlation between toxic metals and reproductive endocrine diseases. However, there is limited research on the relationship between blood concentration of Pb and the risk of diminished ovarian reserve function (DOR).

Overexpression of the R2R3-MYB transcription factor GmMYB3a enhances isoflavone accumulation in soybean.

Soybean isoflavones, natural phytoestrogens within the flavonoid family, exhibit diverse physiological benefits such as anticancer, antioxidant, and cardioprotective properties. Yet, the underlying biosynthetic pathways remain unclear. Research is required to get better knowledge of soybean isoflavone production and its potential uses.

Sleep-wake modulation and pathogenesis of Alzheimer disease: Suggestions for postponement and treatment.

Sleep-wake disorders are recognized as one of the earliest symptoms of Alzheimer disease (AD). Accumulating evidence has highlighted a significant association between sleep-wake disorders and AD pathogenesis, suggesting that sleep-wake modulation could be a promising approach for postponing AD onset. The suprachiasmatic nucleus (SCN) and the pineal hormone melatonin are major central modulating components of the circadian rhythm system.

The complete mitochondrial genome of Gyrodactylus pseudorasborae (Platyhelminthes: Monogenea) with a phylogeny of Gyrodactylidae parasites.

Background: Gyrodactylus von Nordmann, 1832, a genus of viviparous parasites within the family Gyrodactylidae, contains one of the largest nominal species in the world. Gyrodactylus pseudorasborae Ondračková, Seifertová & Tkachenko, 2023 widely distributed in Europe and China, although its mitochondrial genome remains unclear. This study aims to sequence the mitogenome of G.

FAP-targeting biomimetic nanosystem to restore the activated cancer-associated fibroblasts to quiescent state for breast cancer radiotherapy.

Cancer associated fibroblasts (CAFs) are one of the most important stromal cells in the tumor microenvironment, playing a pivotal role in the development, recurrence, metastasis, and immunosuppression of cancer and treatment resistance. Here, we developed a core-shell biomimetic nanosystem termed as FAP-C NPs. This system was comprised of 4T1 extracellular vesicles fused with a FAP single-chain antibody fragment to form the biomimetic shell, and PLGA nanoparticles loaded with calcipotriol as the core.

Effect of different restorative design and materials on stress distribution in cracked teeth: a finite element analysis study.

Objectives: To compare the stress distribution and crack propagation in cracked mandibular first molar restored with onlay, overlay, and two types of occlusal veneers using two different CAD/CAM materials by Finite Element Analysis (FEA).

Materials And Methods: A mandibular first molar was digitized using a micro CT scanning system in 2023. Three-dimensional dynamic scan data were transformed, and a 3D model of a cracked tooth was generated.

Amino acid transporter GmAAP6-like contributes to seed quality and responds to jasmonic acid pathway under MSX toxicity stress.

Amino acid transporters participate in the transport and distribution of amino acids in plants and are vital for plant growth and development. Despite their importance, few works have investigated the functions of amino acid permeases (AAP) amino acid transporters in soybean. In this study, we re-identified the AAP family genes in soybean using a new public genome database and cloned a soybean AAP gene renamed GmAAP6-like.

Neutrophil Gelatinase-Associated Lipocalin and Interleukin-18 in the Prediction of Acute Kidney Injury in Sepsis Patients.

Objective: We assessed the predictive value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in predicting the onset of acute kidney injury (AKI) in sepsis patients in the intensive care unit (ICU).

Methods: In this retrospective analysis, we examined the medical records of sepsis patients admitted to the ICU. After ICU admission, blood samples were taken at 0 h, 6 h, 12 h, 24 h, and 48 h.

Hepatotoxicity, developmental toxicity, and neurotoxicity risks associated with co-exposure of zebrafish to fluoroquinolone antibiotics and tire microplastics: An in silico study.

This study aimed to investigate the differences in the mechanisms of microscopic hepatotoxicity, developmental toxicity, and neurotoxicity in aquatic organisms co-exposed to styrene-butadiene rubber tire microplastics (SBR TMPs) and fluoroquinolone antibiotics (FQs). We found that hepatotoxicity in zebrafish induced by SBR TMPs and FQs was significantly higher than developmental toxicity and neurotoxicity. Furthermore, the main effects of the FQs primarily manifested as synergistic toxicity, whereas the low- and high-order interactions of the FQs mainly exhibited synergistic and antagonistic effects, respectively.

Cardiomyocyte-derived exosomes promote cardiomyocyte proliferation and neonatal heart regeneration.

Heart regeneration was mainly achieved by intrinsic capacity. Exosomes are crucial in cardiovascular disease, yet their involvement in myocardial regeneration remains underexplored. To understand the role of cardiomyocyte-derived exosomes (CM-Exos) in heart regeneration.

pH-activated metal-organic layer nanozyme for ferroptosis tumor therapy.

Nanozymes have made great achievements in the research of tumor therapy. However, due to the complex tumor microenvironment, the catalytic activity and biosafety of nanozymes are limited. High catalytic efficiency is a relentless pursuit for the preparation of high-performance nanozymes.

Near-Infrared Dual-Range Methane Sensor Using the OAIC-HC Mode Based on VMD-SG-Assisted Optical Noise Suppression.

Based on tunable diode laser absorption spectroscopy and off-axis integrated cavity output spectroscopy, a dual-range methane hybrid sensor was constructed utilizing the overtone absorption band of CH gas molecules at 1653.7 nm. By simultaneously utilizing an off-axis integrated cavity and Herriott cell with an effective absorption path of 11 and 405 m, respectively, the two received photoelectric signals are decomposed into different frequency components by VMD and then reconstructed after SG filtering.

Clonality Determination by Detecting Unmodified Monoclonal Serum Free Light Chains Using On-Probe Extraction Coupled with Liquid Chromatography-High-Resolution Mass Spectrometry.

Background: Serum free light chains (FLCs) are an essential clinical biomarker for the diagnosis and monitoring of patients with plasma cell neoplasms. The current widely used immunoassay methods quantify total serum FLCs, which include monoclonal FLCs as well as FLCs in the polyclonal background. Patients with chronic diseases, inflammatory disorders, or renal dysfunction can have elevated total FLCs that lead to ambiguous results.

The crucial role of NR2A mediating the activation of satellite glial cells in the trigeminal ganglion contributes to orofacial inflammatory pain during TMJ inflammation.

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear.

Melatonin attenuates hepatic oxidative stress by regulating the P62/LC3 autophagy pathway in PCOS.

The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant.

Erratum: Adipocytes fuel gastric cancer omental metastasis PITPNC1-mediated fatty acid metabolic reprogramming: Erratum.

[This corrects the article DOI: 10.7150/thno.28219.

Chromosome doubling increases PECTIN METHYLESTERASE 2 expression, biomass, and osmotic stress tolerance in kiwifruit.

Chromosome doubling-induced polyploidization is a popular tool for crop breeding. Polyploidy crops commonly have multiple advantages, including increased biomass and stress tolerance. However, little is known about the genes responsible for these advantages.

Toxicological mechanisms and molecular impacts of tire particles and antibiotics on zebrafish.

Tire microplastics (TMPs) and antibiotics are emerging pollutants that widely exist in water environments. The coexistence of these pollutants poses severe threats to aquatic organisms. However, the toxicity characteristics and key molecular factors of the combined exposure to TMPs in aquatic organisms remain unknown.

Canadian Inpatient Orthogeriatric Models of Care: A Mixed Methods Survey of Facilitators and Barriers.

Background: Fragility fractures are a serious and common consequence of falls in older adults. Orthogeriatric models of care reduce mortality and morbidity, but, despite this evidence, orthogeriatric programs (OGPs) are not standardized across Canada. The aim of this study was to better understand the facilitators and barriers of OGPs across Canada.