Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors.

The COVID-19 pandemic, exacerbated by persistent viral mutations, underscored the urgent need for diverse inhibitors targeting multiple viral proteins. In this study, we utilized covalent DNA-encoded libraries to discover innovative triazine-based covalent inhibitors for the 3-chymotrypsin-like protease (3CL, Nsp5) and the papain-like protease (PL) domains of Nsp3, as well as novel non-nucleoside covalent inhibitors for the nonstructural protein 12 (Nsp12, RdRp). Optimization through molecular docking and medicinal chemistry led to the development of , a nonpeptide 3CL inhibitor with an IC of 0.

Enhancing the Predictive Power of Machine Learning Models through a Chemical Space Complementary DEL Screening Strategy.

DNA-encoded library (DEL) technology is an effective method for small molecule drug discovery, enabling high-throughput screening against target proteins. While DEL screening produces extensive data, it can reveal complex patterns not easily recognized by human analysis. Lead compounds from DEL screens often have higher molecular weights, posing challenges for drug development.

Composition and storage of soil inorganic carbon as well as the controlling factors in coastal area of the northern Jiangsu, China.

The sequestration of soil inorganic carbon (SIC) especially pedogenic carbonate (PC) is one of the important pathways reducing the concentration of atmospheric carbon dioxide and thus mitigating climate change in coastal areas. Using the technology of C stable isotope, we analyzed the differences in the composition and storage of SIC, and explored the key physicochemical properties influencing soil PC storage in different horizons (0-10, 11-20, 21-40, 41-60, 61-80 and 81-100 cm) from wetland (SS), wetland (SA), young poplar plantation (YP), and mature poplar plantation (MP) in coastal area of the northern Jiangsu Province. The results showed that except for the surface (0-10 cm) soil in MP, the SIC content was higher than SOC in all soil horizons.

The Encounter of Two Worlds: Divided Narratives of Decision-Making on Cancer Treatment Between Physicians and Patients.

Introduction: Divided narratives pose long-standing difficulties in physician and patient communication. In decision-making on cancer treatment, divided narratives between physicians and patients hinder mutual understanding and agreement over the illness and its treatment. For effective decision-making on treatments, it is necessary to investigate the similarities and differences in these divided narratives.

Stable Cu/CuO/CuN@NC Catalysts for Aqueous Phase Reforming of Methanol.

Aqueous-phase reforming of methanol represents a promising avenue for hydrogen (H) production. However, developing highly efficient and low-cost nonprecious catalysts remains challenging. Here, we report the synthesis of Cu-based catalysts with Cu, CuO, and CuN nanoparticles anchored on the nitrogen-doped carbon, forming Cu/Cu/Cu-N active sites.

[Research on Electromagnetic Compatibility Immunity Testing Methods for Proton Therapy System].

The proton therapy system has significant clinical advantages over traditional tumor radiation treatment equipment and is also far more complex in terms of system architecture. However, due to the large size and complexity of these devices, electromagnetic compatibility testing faces considerable challenges. To address these challenges, this paper studies the electromagnetic characteristics and working principles of various components in the proton therapy system, combines them with corresponding standard requirements, and delves into the difficulties and testing methods of electromagnetic compatibility immunity detection through actual repeated tests.

The Research Effects of Variable Temperature and Early Strength Agent on the Mechanical Properties of Cement-Stabilized Macadam.

In cold regions with high daily temperature gradients (>20 °C), the durability of cement-stabilized macadam (CSM) base materials is poor and prone to cracking. To effectively reduce the cracking of semi-rigid base layers in cold regions with high daily temperature gradients and extend fatigue life, this study focused on cracking and fatigue characteristics of CSM with a 10% commercial early strength agent (ESA) added by the external mixing method under different curing conditions. The ESA was manufactured by Jiangsu Subote New Materials Co.

Discovery Small-Molecule p300 Inhibitors Derived from a Newly Developed Indazolone-Focused DNA-Encoded Library.

The DNA-encoded library (DEL) is a robust tool for chemical biology and drug discovery. In this study, we developed a DNA-compatible light-promoted reaction that is highly efficient and plate-compatible for DEL construction based on the formation of the indazolone scaffold. Employing this high-efficiency approach, we constructed a DEL featuring an indazolone core, which enabled the identification of a novel series of ligands specifically targeting E1A-binding protein (p300) after DEL selection.

Effects of photodegradation on the composition characteristics and metal binding behavior of sediment-derived dissolved organic matter (SDOM) in nansi lake, China.

Sediment-derived dissolved organic matter (SDOM) is instrumental in the cycling of nutrients and heavy metals within lakes, influencing ecological balance and contaminant distribution. Given the influence of photodegradation on the alteration and breakdown of SDOM, further understanding of this process is essential. In this research, the properties of the SDOM photodegradation process and its metal-binding reactions in Nansi Lake were analyzed using the EEM-PARAFAC and 2D-SF/FTIR-COS techniques.

Rhodium-Promoted C-H Activation/Annulation between DNA-Linked Terminal Alkyne and Aromatic Acid: A Finding from the Selection Outcomes.

Inspired by previous selection outcomes, we investigated and developed a rhodium-promoted C-H activation/annulation reaction of DNA-linked terminal alkynes and aromatic acids. This reaction exhibits excellent efficiency with high conversions and a broad substrate scope. Most importantly, the unique DEL-compatible conditions provide a better scenario for yielding an isocoumarin scaffold compared to conventional organic reaction conditions, and this newly developed on-DNA method has confirmed its feasibility in preparing DNA-encoded libraries.

Rheological Properties of Silica-Fume-Modified Bioasphalt and Road Performance of Mixtures.

The objective of this research is to enhance the high-temperature antirutting and antiaging characteristics of bioasphalt. In this study, silica fume (SF) was selected to modify bioasphalt. The dosage of bio-oil in bioasphalt was 5%, and the dosage of SF was 2%, 4%, 6%, 8%, and 10% of bioasphalt.

Therapeutic roles of platelet-rich plasma to restore female reproductive and endocrine dysfunction.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine.

A Vancomycin-Templated DNA-Encoded Library for Combating Drug-Resistant Bacteria.

It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds.

New Perspectives on the Role and Therapeutic Potential of Melatonin in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. It is essential to develop novel interventions to prevent/delay CVDs by targeting their fundamental cellular and molecular processes. Melatonin is a small indole molecule acting both as a hormone of the pineal gland and as a local regulator molecule in various tissues.

Mechanisms of anaerobic treatment of sulfate-containing organic wastewater mediated by Fe under different initial pH values.

The anaerobic treatment of sulfide-containing organic wastewater (SCOW) is significantly affected by pH, causing dramatic decrease of treatment efficiency when pH deviates from its appropriate range. Fe has proved as an effective strategy on mitigating the impact of pH. However, systematic analysis of the influence mechanism is still lacking.

Discovery and Optimization of WDR5 Inhibitors via Cascade Deoxyribonucleic Acid-Encoded Library Selection Approach.

The DNA-encoded library (DEL) is a powerful hit generation tool for chemical biology and drug discovery; however, the optimization of DEL hits remained a daunting challenge for the medicinal chemistry community. In this study, hit compounds targeting the WIN binding domain of WDR5 were discovered by the initial three-cycle linear DEL selection, and their potency was further enhanced by a cascade DEL selection from the focused DEL designed based on the original first run DEL hits. As expected, these new compounds from the second run of focused DEL were more potent WDR5 inhibitors in the protein binding assay confirmed by the off-DNA synthesis.

Sulfhydryl-Functionalized Amino Group Polymer Microcomposites toward Efficient Adsorption of Aqueous Cr(VI), As(III), Cd(II), and Pb(II).

The development of efficient adsorbents for heavy metal pollution, especially five toxic heavy metals, has attracted great research interest. Polymer-based adsorbents have aroused research value for their abundant functional groups and high porosity to the ability to capture metal ions. We designed a sulfhydryl-functionalized polymer microcomposite to take up Cr(VI), As(III), Cd(II), and Pb(II).

Prefrontal cortex activity of active motion, cyclic electrical muscle stimulation, assisted motion, and imagery of wrist extension in stroke using fNIRS.

Objectives: This study aimed to determine whether the prefrontal cortex (PFC) was activated during four training approaches for wrist extension in patients with stroke, including active motion, cyclic electrical muscle stimulation (EMS), assisted motion, and motor imagery (MI).

Materials And Methods: We conducted a cross-sectional study involving 16 patients with stroke, and adopted functional near-infrared spectroscopy (fNIRS) to observe PFC activity during four treatment paradigms. The beta value of 53 channels in fNIRS under each paradigm, compared to the baseline, was evaluated using single sample t-test.

ABPP-CoDEL: Activity-Based Proteome Profiling-Guided Discovery of Tyrosine-Targeting Covalent Inhibitors from DNA-Encoded Libraries.

DNA-encoded chemical library (DEL) has been extensively used for lead compound discovery for decades in academia and industry. Incorporating an electrophile warhead into DNA-encoded compounds recently permitted the discovery of covalent ligands that selectively react with a particular cysteine residue. However, noncysteine residues remain underexplored as modification sites of covalent DELs.

Recognizing the variation of DNA-P during and after the algal bloom in lake Hulun.

Eutrophication has spread from shallow lakes in temperature zones to lakes in cold regions as a result of a continuous warm climate and human activities. Little proof for the importance of dissolved organic phosphorus (DOP) in contributing to phosphorus cycling and algae growth has been generated for aquatic ecosystems, particularly in cold eutrophic lakes. In this study, a comprehensive in situ study was conducted in overlying water, suspended particulate matter, and sediment during and after algal bloom (in July and September, respectively) in Lake Hulun.