QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite.

The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydroxyapatite nanoparticles to mimic and compensate for synthetic estrogens and biomineralization. Hypothesizing this bimodal approach, hydroxyapatite nanoparticles (HAPNPs) were synthesized using the chemical-precipitation method followed by drug loading (DZHAPNPs) via sorption.

Global expansion of microphysiological systems (MPS) and Japan's initiatives: Innovation in pharmaceutical development and path to regulatory acceptance.

Microphysiological systems (MPS) are gaining global attention as potential game-changers in pharmaceutical development. Since 2013, MPS suppliers from university laboratories in the United States and Europe have competed to develop these devices. After the development phase, the focus shifted to the accumulation of applications using MPS for pharmaceutical companies and end users.

Ageing and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19.

CD8+ T cells are critical for immune protection against severe COVID-19 during acute infection with SARS-CoV-2. However, the induction of antiviral CD8+ T cell responses varies substantially among infected people, and a better understanding of the mechanisms that underlie such immune heterogeneity is required for pandemic preparedness and risk stratification. In this study, we analyzed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in relation to age, clinical status, and inflammation among patients infected primarily during the initial wave of the pandemic in France or Japan.

Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends.

Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, are stable and grow very slowly, but the underlying mechanisms are poorly understood. Here, we reconstituted in vitro the interplay between the proteins that cap distal centriole ends and control their elongation: CP110, CEP97, and CPAP/SAS-4.

Chemical structure-biological activity of 1,4-naphthoquinone analogs as potential Aedes aegypti larvicides.

Background: 1,4-Naphthoquinone compounds have shown pesticidal activity against Aedes aegypti larvae, a key vector of diseases such as dengue and Zika. However, limited knowledge of their structure-activity relationships has hindered their optimization for pesticide development. This study investigates the structure-activity relationships of 1,4-naphthoquinone, particularly 2-hydroxy-1,4-naphthoquinone and its derivatives.

Study on Interaction Between 5-(4 Methoxyphenyl)-1-Phenyl-1H-1,2,3-Triazole with High-Abundant Blood Proteins and Identification of Low-Abundant Proteins by Serum Proteomics.

A comprehensive strategy, including spectroscopic, molecular simulation, proteomics, and bioinformatics techniques, was employed to investigate a novel triazole, 5-(4-methoxyphenyl)-1-phenyl-1H-1,2,3-triazole, its interactions with high-abundance blood proteins, and identification of low-abundance proteins. The binding constants and thermodynamic parameters of the triazole to two high-abundance blood globular proteins, human serum albumin, and human immunoglobulin G (HIgG), were obtained by spectroscopic techniques and computational chemistry. The two-dimensional gel electrophoresis in combination with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was employed to isolate and identify differentially expressed low-abundance proteins in human blood serum samples following exposure to the triazole.

The metabolic pathway of Deg-AZM and investigations into the contribution of drug metabolizing enzymes and drug transporters in the drug interactions of Deg-AZM, a clinical-stage new transgelin agonist.

Introduction: Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM.

Methods: A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile.

(Omphalotaceae, Agaricales), A New Species from Danang, Vietnam.

During the collection of macrofungi resources in Son Tra Nature Reserve, Danang, Vietnam, two fungal specimens of the genus , designated as M34295 and M3457, living on dead still-attached branches of L. at an elevation around 360 m above the sea level were recorded. The morphological characteristics of the specimens shared some common characteristics with spp.

Synthesis, HS releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5'-dithioacetates.

Hydrogen sulfide (HS) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-HS-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Nonapoptotic caspase-3 guides C1q-dependent synaptic phagocytosis by microglia.

Caspases are known to mediate neuronal apoptosis during brain development. However, here we show that nonapoptotic activation of caspase-3 at presynapses drives microglial synaptic phagocytosis. Real-time observation and spatiotemporal manipulation of synaptic caspase-3 in the newly established, mouse-derived culture system demonstrate that increased neuronal activity triggers localized presynaptic caspase-3 activation, facilitating synaptic tagging by complements.

Compact Disc-Derived Nanocarbon-Supported Catalysts with Extreme Catalytic Activity.

Advanced carbon-metal hybrid materials with controllable electronic and optical properties, as well as chemical reactivities, have attracted significant attention for emerging applications, including energy conversion and storage, catalysis and environmental protection. However, the commercialization of these materials is hampered by several vital problems, including energy-intensive synthesis and expensive chemicals, and inefficient control of their structures and properties. Herein, we report the simple and controllable engineering of nanocarbon-metal self-assembled silver nanocatalysts (SSNs) derived from polycarbonate (PC)-based optical discs using microplasmas under ambient conditions.

Cold plasma: A nonthermal pretreatment, extraction, and solvent activation technique for obtaining bioactive compounds from agro-food industrial biomass.

The present review provides a comprehensive overview of cold plasma treatment and its applications in solvent activation and bioactive component extraction. The study has summarized the principles, types, uses, and mechanisms of cold plasma treatment in activating various solvents, extracting biomolecules, and affecting the characteristics of the extracted compound. This review also explores the environmental benefits of implementing this sustainable technology, highlighting the influence of key parameters such as gas type, treatment time, voltage, and plasma flow rate on the extraction process, providing insights into optimizing these conditions for maximum efficiency.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Evaluation of methoxyflavones as dengue NS2B-NS3 protease inhibitors: an in silico and in vitro studies.

Dengue is one of the most prevalent viruses transmitted by the Aedes aegypti mosquitoes. Currently, no specific medication is available to treat dengue diseases. The NS2B-NS3 protease is vital during post-translational processing, which is a key target in this study.

Molecular Symphony of Mitophagy: Ubiquitin-Specific Protease-30 as a Maestro for Precision Management of Neurodegenerative Diseases.

Introduction: Mitochondrial dysfunction stands as a pivotal feature in neurodegenerative disorders, spurring the quest for targeted therapeutic interventions. This review examines Ubiquitin-Specific Protease 30 (USP30) as a master regulator of mitophagy with therapeutic promise in Alzheimer's disease (AD) and Parkinson's disease (PD). USP30's orchestration of mitophagy pathways, encompassing PINK1-dependent and PINK1-independent mechanisms, forms the crux of this exploration.

A Clinical Drug as the Three-Photon Fluorescence Probe for In Vivo Microscopic Imaging of Mouse Kidney.

Three-photon fluorescence (3PF) microscopy encounters significant challenges in biological research and clinical applications, primarily due to the limited availability of high-performance probes. We took a shortcut by exploring the excellent 3PF property of berberine hydrochloride (BH), a clinically utilized drug derived from the traditional Chinese medicine, Coptis. Capitalizing on its renal metabolism characteristics, we employed BH for in vivo 3PF microscopic imaging of the mouse kidney.

Comprehensive comparative metabolome study of a large collection of Corsican bryophytes.

Introduction: Bryophytes are non-vascular plants that appeared on Earth before vascular plants. More than 24,000 species are reported worldwide, and only a small proportion have been studied. However, part of their biosynthetic potential has been unveiled and more than 1,600 terpenoids have been detected and identified.

Microenvironment Mechanical Torque from ZnFeO (ZFO) Micromotors Inhibiting Tumor Migration.

Mechanical force attracts booming attention with the potential to tune the tumor cell behavior, especially in cell migration. However, the current approach for introducing mechanical input is difficult to apply in vivo. How the mechanical force affects cell behavior in situ also remains unclear.

Review and meta-analysis of gene expression biomarkers predictive of chemical-induced genotoxicity in vivo.

There is growing recognition across broad sectors of the toxicology community that gene expression biomarkers have the potential to identify genotoxic and nongenotoxic carcinogens through a weight-of-evidence approach, providing opportunities to reduce reliance on the 2-year bioassay to identify carcinogens. In August 2022, a workshop within the International Workshops on Genotoxicity Testing (IWGT) was held to critically review current methods to identify genotoxicants using various 'omics profiling methods. Here, we describe the findings of a workshop subgroup focused on the state of the science regarding the use of biomarkers to identify chemicals that act as genotoxicants in vivo.

Fine-tuned calcium homeostasis is crucial for murine erythropoiesis.

Intracellular calcium (Ca) is a crucial signaling molecule involved in multiple cellular processes. However, the functional role of Ca in terminal erythropoiesis remains unclear. Here, we uncovered the dynamics of intracellular Ca levels during mouse erythroid development.

Robust circulating microRNA signature for the diagnosis and early detection of pancreatobiliary cancer.

Background: A new circulating biomarker superior to carbohydrate antigen 19-9 (CA19-9) is needed for diagnosing pancreatobiliary cancer (PBca). The aim of this study was to identify serum microRNA (miRNA) signatures comprising reproducible and disease-related miRNAs.

Methods: This multicenter study involved patients with treatment-naïve PBca and healthy participants.

Barcoded screening identifies nanocarriers for protein delivery to kidney.

Targeted protein delivery with nanocarriers holds significant potential to enhance therapeutic outcomes by precisely directing proteins to specific organs or tissues. However, the complex interactions between nanocarriers and the biological environment pose considerable challenges in designing effective targeted delivery vehicles. In this study, we address this challenge by leveraging DNA-barcoded high-throughput screening.

Simultaneous Detection of 4-Nitroquinoline-1-oxide and Nitroimidazole Drug Using a Perovskite-BaZrO@NbN-Nanocomposite-Modified Disposable Carbon Electrode.

Pharmaceutical ingredients in water have become a serious threat to living bodies and lead to assorted ecological predicaments. In this study, we have established an electrochemical probe for the simultaneous detection of synthetic pharmaceutical ingredients, including 4-nitroquinoline-N-Oxide (NQN) and ornidazole (ODZ), in both human and environmental samples. This study establishes the detection of NQN and ODZ using a screen-printed carbon electrode (SPCE) modified by highly conducting NbN incorporated with BaZrO perovskite.