Advancements in Antiviral Drug Development: Comprehensive Insights into Design Strategies and Mechanisms Targeting Key Viral Proteins.

Viral infectious diseases have always been a threat to human survival and quality of life, impeding the stability and progress of human society. As such, researchers have persistently focused on developing highly efficient, low-toxicity antiviral drugs, whether for acute or chronic infectious diseases. This article presents a comprehensive review of the design concepts behind virus-targeted drugs, examined through the lens of antiviral drug mechanisms.

Dynamics of carbon storage driven by land use/land cover transformation in coal mining areas with a high groundwater table: A case study of Yanzhou Coal Mine, China.

Intensive anthropogenic activities have led to drastic changes in land use/land cover (LULC) and impacted the carbon storage in high-groundwater coal basins. In this paper, we conduct a case study on the Yanzhou Coalfield in Shandong Province of China. We further classify waterbodies by using the Google Earth Engine (GEE) to better investigate the process of LULC transformation and the forces driving it in four periods from 1985 to 2020 (i.

Differential responses of 23 maize cultivar seedlings to an arbuscular mycorrhizal fungus when grown in a metal-polluted soil.

Modern breeding efforts have been accelerating crop improvement and yielding numerous cultivars with distinct genetic traits; however, interactions between different cultivars and their root-associated arbuscular mycorrhizal fungi (AMF) are not clear. Herein, we selected the 22 most common commercial maize (Zea mays) varieties in China and an inbred line (B73) to study the differential responses of these 23 cultivars to mycorrhizal inoculation when grown in an arable soil polluted by multiple metals (Pb, Zn, and Cd). We found that the different cultivars exhibited significant variations in plant metal accumulation, ranging from strong metal exclusion (ZYY9) to strong metal accumulation (B73).

H3K36 methyltransferase SDG708 enhances drought tolerance by promoting abscisic acid biosynthesis in rice.

Chromatin modifications play important roles in plant adaptation to abiotic stresses, but the precise function of histone H3 lysine 36 (H3K36) methylation in drought tolerance remains poorly evaluated. Here, we report that SDG708, a specific H3K36 methyltransferase, functions as a positive regulator of drought tolerance in rice. SDG708 promoted abscisic acid (ABA) biosynthesis by directly targeting and activating the crucial ABA biosynthesis genes NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (OsNCED3) and NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 5 (OsNCED5).

Development of Human iPSC-Derived Functional Neuronal Networks on Laser-Fabricated 3D Scaffolds.

Neural progenitor cells generated from human induced pluripotent stem cells (hiPSCs) are the forefront of ″brain-on-chip″ investigations. Viable and functional hiPSC-derived neuronal networks are shaping powerful models for evaluating the normal and abnormal formation of cortical circuits, understanding the underlying disease mechanisms, and investigating the response to drugs. They therefore represent a desirable instrument for both the scientific community and the pharmacological industry.

Polarization whorls from M87* at the event horizon telescope.

The event horizon telescope (EHT) is expected to soon produce polarimetric images of the supermassive black hole at the centre of the neighbouring galaxy M87. There are indications that this black hole is rapidly spinning. General relativity predicts that such a high-spin black hole has an emergent conformal symmetry near its event horizon.

Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer's Disease Patients Carrying the APOE Epsilon 4 Allele.

Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (A) peptides, which form lethal deposits in the brain.

Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks.

Efficient derivation of human cerebral neocortical neural stem cells (NSCs) and functional neurons from pluripotent stem cells (PSCs) facilitates functional studies of human cerebral cortex development, disease modeling and drug discovery. Here we provide a detailed protocol for directing the differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to all classes of cortical projection neurons. We demonstrate an 80-d, three-stage process that recapitulates cortical development, in which human PSCs (hPSCs) first differentiate to cortical stem and progenitor cells that then generate cortical projection neurons in a stereotypical temporal order before maturing to actively fire action potentials, undergo synaptogenesis and form neural circuits in vitro.

A human stem cell model of early Alzheimer's disease pathology in Down syndrome.

Human cellular models of Alzheimer's disease (AD) pathogenesis would enable the investigation of candidate pathogenic mechanisms in AD and the testing and developing of new therapeutic strategies. We report the development of AD pathologies in cortical neurons generated from human induced pluripotent stem (iPS) cells derived from patients with Down syndrome. Adults with Down syndrome (caused by trisomy of chromosome 21) develop early-onset AD, probably due to increased expression of a gene on chromosome 21 that encodes the amyloid precursor protein (APP).

Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses.

Efforts to study the development and function of the human cerebral cortex in health and disease have been limited by the availability of model systems. Extrapolating from our understanding of rodent cortical development, we have developed a robust, multistep process for human cortical development from pluripotent stem cells: directed differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells to cortical stem and progenitor cells, followed by an extended period of cortical neurogenesis, neuronal terminal differentiation to acquire mature electrophysiological properties, and functional excitatory synaptic network formation. We found that induction of cortical neuroepithelial stem cells from human ES cells and human iPS cells was dependent on retinoid signaling.