Clin Pharmacol Drug Dev
October 2024
Composite materials built in part from living organisms have the potential to exhibit useful autonomous, adaptive, and self-healing behavior. The physicochemical, biological, and mechanical properties of such materials can be engineered through the genetic manipulation of their living components. Successful development of living materials will require not only new methods for design and preparation but also new analytical tools that are capable of real-time noninvasive mapping of chemical compositions.
View Article and Find Full Text PDFSince its initial identification, the Forkhead Box P2 gene (FOXP2) has maintained its singular status as the archetypal monogenic determinant implicated in Mendelian forms of human speech and language impairments. Despite the passage of two decades subsequent to its discovery, extant literature remains disproportionately sparse with regard to case-specific instances and loci of mutational perturbations. The objective of the current investigation centers on furnishing an enriched delineation of both its clinical manifestations and its mutational heterogeneity.
View Article and Find Full Text PDFBackground: Ovarian stimulation (OS) during assisted reproductive technology (ART) appears to be an independent factor influencing the risk of low birth weight (LBW). Previous studies identified the association between LBW and placenta deterioration, potentially resulting from disturbed genomic DNA methylation in oocytes caused by OS. However, the mechanisms by which OS leads to aberrant DNA methylation patterns in oocytes remains unclear.
View Article and Find Full Text PDFBackground: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia.
Methods: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE.
Introduction: To investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Chinese patients with type 2 diabetes (T2D).
Methods: In this phase 1, double-blind, placebo-controlled, multiple dose study, patients were randomized into one of two cohorts to receive once-weekly subcutaneous tirzepatide or placebo. The initial tirzepatide dose in both cohorts was 2.
Ovarian stimulation is associated with an increased incidence of abnormal placentation. Uterine natural killer (uNK) cells are the major subpopulation of decidual immune cells, which are crucial for placentation. In a previous study, we found that ovarian stimulation impairs uNK cell density on gestation day (GD) 8.
View Article and Find Full Text PDFThe sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring of the transcriptional and signaling drivers that regulate cellular states. Many of the drivers, referred to as "hidden drivers", are difficult to identify via conventional expression analysis due to low expression and inconsistency between RNA and protein activity caused by post-translational and other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised clustering analysis and cell-type specific inference of intracellular networks, hidden drivers and network rewiring from single-cell RNA-seq data.
View Article and Find Full Text PDFThe sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring of the transcriptional and signaling drivers that regulate cellular states. Many of the drivers, referred to as "hidden drivers", are difficult to identify via conventional expression analysis due to low expression and inconsistency between RNA and protein activity caused by post-translational and other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised clustering analysis and cell-type specific inference of intracellular networks, hidden drivers and network rewiring from single-cell RNA-seq data.
View Article and Find Full Text PDFOffspring conceived by assisted reproductive technologies (ART) have increased risk of suffering from gestational complications, and placental dysfunction is related with the adverse outcomes. Studies have revealed that abnormal or adaptive changes can occur in ART placentas, but the potential reasons are not fully understood. Hereby, we tried to use proteomics and phospho-proteomics to find the underlying mechanisms responsible for the changes of ART placentas.
View Article and Find Full Text PDFThe universal utilization of fluorescence microscopy, especially super-resolution microscopy, has greatly advanced knowledge about modern biology. Conversely, the requirement of fluorophore labeling in fluorescent techniques poses significant challenges, such as photobleaching and non-uniform labeling of fluorescent probes and prolonged sample processing. In this protocol, the detailed working procedures of vibrational imaging of swelled tissue and analysis (VISTA) are presented.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most prevalent form of dementia in the old adult and characterized by progressive cognitive decline and neuronal damage. The mammalian Ste20-like kinase1/2 (MST1/2) is a core component in Hippo signaling, which regulates neural stem cell proliferation, neuronal death and neuroinflammation. However, whether MST1/2 is involved in the occurrence and development of AD remains unknown.
View Article and Find Full Text PDFCellular metabolism plays an important role in regulating both human and murine NK cell functions. However, it remains unclear whether cellular metabolic process impacts on the function of decidual NK cells (dNK), essential tissue-resident immune cells maintaining the homeostasis of maternal-fetal interface. Remarkably, we found that glycolysis blockage enhances dNK VEGF-A production but restrains its proliferation.
View Article and Find Full Text PDFHippo signalling plays key role in tissue growth and homeostasis, and its dysregulation is implicated in various human diseases. Expanded (Ex) is an important upstream activator of Hippo signalling; however, how Ex activates Hippo signalling is still poorly understood. Here, we demonstrate that Ex forms a homodimer via C-terminal interaction, and that the ExC2 region (912-1164 aa) is sufficient and essential for Ex dimerization.
View Article and Find Full Text PDFObjective: Although there has been increased utilization of assisted reproductive technologies (ART) in the world, there is no conclusive definition about the relationship between the success rate of ART and national wealth.
Methods: In this study, using the data from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART), we sought to determine whether there is a correlation between the success rate of ART (represented by pregnancy and delivery rates) and national wealth represented by the gross domestic product (GDP) per capita. Moreover, to further understand the effect of GDP per capita on ART effectiveness, we analyzed the association between ART success rate and GDP per capita in 50 US states.
Urea, an agricultural fertilizer, nourishes humanity. The century-old Bosch-Meiser process provides the world's urea. It is multi-step, consumes enormous amounts of non-renewable energy, and has a large CO footprint.
View Article and Find Full Text PDFIntroduction: Children conceived by assisted reproductive technologies have a high risk of suffering from obstetrical complications and long-term health problems, but the related mechanisms are not fully understood. Normal placental function is closely linked with foetal growth and future health. Given the significance of glycogen metabolism in placentas, we investigated the effect of in vitro fertilization (IVF) on glycogen storage in placentas using a mouse model.
View Article and Find Full Text PDFInnovations in high-resolution optical imaging have allowed visualization of nanoscale biological structures and connections. However, super-resolution fluorescence techniques, including both optics-oriented and sample-expansion based, are limited in quantification and throughput especially in tissues from photobleaching or quenching of the fluorophores, and low-efficiency or non-uniform delivery of the probes. Here, we report a general sample-expansion vibrational imaging strategy, termed VISTA, for scalable label-free high-resolution interrogations of protein-rich biological structures with resolution down to 78 nm.
View Article and Find Full Text PDFAmyloid aggregation, formed by aberrant proteins, is a pathological hallmark for neurodegenerative diseases, including Alzheimer's disease and Huntington's disease. High-resolution holistic mapping of the fine structures from these aggregates should facilitate our understanding of their pathological roles. Here, we achieved label-free high-resolution imaging of the polyQ and the amyloid-beta (Aβ) aggregates in cells and tissues utilizing a sample-expansion stimulated Raman strategy.
View Article and Find Full Text PDFReversibly photoswitchable probes allow for a wide variety of optical imaging applications. In particular, photoswitchable fluorescent probes have significantly facilitated the development of super-resolution microscopy. Recently, stimulated Raman scattering (SRS) imaging, a sensitive and chemical-specific optical microscopy, has proven to be a powerful live-cell imaging strategy.
View Article and Find Full Text PDFSilicon (Si)-based material is a promising anode material for next-generation lithium-ion batteries (LIBs). Herein, we report the fabrication of a silicon oxide-carbon (SiO/C) nanocomposite through the reaction between silicon particles with fresh surface and HO in a mild hydrothermal condition, as well as conducting carbon coating synchronously. We found that controllable oxidation could be realized for Si particles to produce uniform SiO after the removal of the native passivation layer.
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