Enhancing Alcohol Dehydrogenase Activity for the Efficient Synthesis of ()-2-Chloro-1-(2,4-dichlorophenyl)ethanol Using Computer-Aided Combinational Mutagenesis.

()-2-chloro-1-(2,4-dichlorophenyl)ethanol (()-CPEO) is an important chiral precursor of the antifungal drug luriconazole. In this study, a mutant alcohol dehydrogenase, ADH from , was redesigned for the efficient synthesis of ()-CPEO by using virtual saturation mutagenesis to assess beneficial site combinations. Five poorly conserved sites in the active pocket of the enzyme were identified via multiple sequence alignment with enzymes exhibiting high activity toward acetophenone derivatives.

Discovery of multi-target anti-gout agents from Eurycoma longifolia Jack through phenotypic screening and structural optimization.

Developing anti-gout medications that simultaneously reduce uric acid and exert anti-inflammatory effects represents a critical breakthrough for managing gout progression. Natural products with polypharmacological properties offer promising leads for drug discovery. In this study, β-carboline-1-propionic acid, a bioactive constituent of Eurycoma longifolia Jack, served as the starting point for drug design.

Mechanochemical force driven activation of endogenous iron species in coal gasification fine slag for oxidative removal of phenolic pollutants.

Coal gasification fine slag (CGFS) is a kind of solid waste with large output in the coal chemical industry, which contains rich aluminosilicate minerals and residual carbon. A magnetic composite (Fe-MCGFS-800) was prepared from CGFS via the mechanochemical method, enabling the migration and transformation of endogenous iron species within the system. The composite, with an effective active iron species content as high as 34 %, demonstrated excellent performance in the removal of bisphenol A (BPA) in the peroxymonosulfate (PMS) system.

Cleavage of CAD by caspase-3 determines the cancer cell fate during chemotherapy.

Metabolic heterogeneity resulting from the intra-tumoral heterogeneity mediates massive adverse outcomes of tumor therapy, including chemotherapeutic resistance, but the mechanisms inside remain largely unknown. Here, we find that the de novo pyrimidine synthesis pathway determines the chemosensitivity. Chemotherapeutic drugs promote the degradation of cytosolic Carbamoyl-phosphate synthetase II, Aspartate transcarbamylase, and Dihydroorotase (CAD), an enzyme that is rate-limiting for pyrimidine synthesis, leading to apoptosis.

Viral Infections in Elderly Individuals: A Comprehensive Overview of SARS-CoV-2 and Influenza Susceptibility, Pathogenesis, and Clinical Treatment Strategies.

As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific progress. This review delves into the genetic structure, infection mechanisms, and impact of coinfections with these two viruses and provides a detailed analysis of the reasons for the increased susceptibility of elderly individuals to dual viral infections.

[Potential and Mechanism of High-temperature Pretreatment Composting of Food Waste for Amendment of Cadmium and Lead-contaminated Soil].

To investigate the potential of high-temperature pretreatment composting of food waste for the amendment of cadmium （Cd） and lead （Pb）-contaminated soil, food waste subjected to high-temperature pretreatment composting （HC）, traditional composting （TC）, and only high-temperature pretreatment were combined with inorganic passivators （lime/zeolite） for an indoor passivation cultivation experiment. The results indicated that HC combined with the inorganic passivators group （HLZ） exhibited the most effective passivation potential for Cd and Pb in soil, achieving passivation rates of 76.92% and 86.

Discovery of cyanidin-3-O-galactoside as a novel CNT2 inhibitor for the treatment of hyperuricemia.

Inhibition of human concentrative nucleoside transporter 2 (CNT2) could suppress increases in serum urate levels derived from dietary purines. However, the structural basis for substrate recognition of CNT2 is still unknown and only a few inhibitors have been reported. In this study, a homology model of CNT2 was constructed and residues T315, E316, N426, N491, E492, F536 and N538 were identified as binding sites for adenosine through site-directed mutagenesis and a H-adenosine uptake assay.

Salinomycin, a potent inhibitor of XOD and URAT1, ameliorates hyperuricemic nephropathy by activating NRF2, modulating the gut microbiota, and promoting SCFA production.

Long-term hyperuricemia can induce kidney damage, clinically referred to as hyperuricemic nephropathy (HN), which is characterized by renal fibrosis, inflammation, and oxidative stress. However, currently used uric acid-lowering drugs are not capable of protecting the kidneys from damage. Therefore, uric acid-lowering drugs that can also protect the kidneys are urgently needed.

Simultaneous nitrification and denitrification in a hybrid activated sludge-membrane aerated biofilm reactor (H-MABR) for nitrogen removal from low COD/N interflow: A pilot-scale study.

There are a large number of simple landfills in hilly areas, and the results of previous studies have shown that pollutants in landfills can spread via interflow and cause surface source pollution. The hybrid activated sludge-membrane aerated bioreactor (H-MABR) developed in a previous study can be used for the treatment of interflow with a low chemical oxygen demand (COD)/total nitrogen (TN) ratio, and it has been shown to be effective in laboratory simulations. To investigate the effectiveness of the H-MABR in treating interflow around landfills in real-world applications, an in-situ pilot-scale evaluation of the effectiveness of H-MABR operation was conducted at a landfill.

Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia.

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC of 5.

Superelastic carbon aerogels with anisotropic and hierarchically-enhanced cellular structure for wearable piezoresistive sensors.

Elastic carbon aerogels have promising applications in the field of wearable sensors. Herein, a new strategy for preparing carbon aerogels with excellent compressive strength and strain, shape recovery, and fatigue resistance was proposed based on the structure design and carbonization optimization of nanocellulose-based precursor aerogels. By the combination of directional freezing and zinc ion cross-linking, bacterial cellulose (BC)/alginate (SA) composite aerogels with high elasticity and compressive strength were first achieved.

Short-term high-temperature pretreated compost increases its application value by altering key bacteria phenotypes.

Short-term high-temperature pretreatment can effectively shorten the maturity period of organic waste composting and improve the fertilizer efficiency and humification degree of products. To investigate the effect and mechanism of the end products on the saline-alkali soil improvement and plant growth, the short-term high-temperature pretreatment composting (SHC) and traditional composting (STC) were separately blended with saline-alkali soil in a ratio of 0-40 % to establish a soil-fertilizer blended matrix for cultivating Lolium perenne L. The pot experiments combined with principal component analysis showed Lolium perenne L.

Effect of Mowing on Wheat Growth at Seeding Stage.

Winter wheat is used as forage at the tillering stage in many countries; however, the regrowth pattern of wheat after mowing remains unclear. In this study, the growth patterns of wheat were revealed through cytological and physiological assessments as well as transcriptome sequencing. The results of agronomic traits and paraffin sections showed that the shoot growth rate increased, but root growth was inhibited after mowing.

Superelastic chitin nanofibril/chitosan aerogel for effective circulating and continuous oil-water separation.

Elastic and hydrophobic aerogels have received a lot of attention in dealing with the increasing oil pollution due to their recyclable properties. Herein, we present an ultralight and superelastic aerogel with highly oriented polygon structure based on chitin nanofibril (ChNF) and chitosan (CS) by directional freezing. The chemical cross-linking enables good mechanical strength at low aerogel density.

Genome-wide identification, classification, and expression analysis of heat shock transcription factor family in switchgrass (Panicum virgatum L.).

Switchgrass is one of the most promising bioenergy crops and is generally cultivated in arid climates and poor soils. Heat shock transcription factors (Hsfs) are key regulators of plant responses to abiotic and biotic stressors. However, their role and mechanism of action in switchgrass have not been elucidated.

Integrated genome-centric metagenomic and metaproteomic analyses unravel the responses of the microbial community to ammonia stress.

Ammonia is a major inhibitor in anaerobic digestion of nitrogen-rich organic wastes. In this study, integrated genome-centric metagenomic and metaproteomic analyses were used to identify the key microorganisms and metabolic links causing instability by characterizing the process performance, microbial community, and metabolic responses of key microorganisms during endogenous ammonia accumulation. The identification of 89 metagenome-assembled genomes and analysis of their abundance profile in different operational phases permitted the identification of key taxa (Firmicutes and Proteobacteria) causing poor performance.

Analysis of morphological traits and regulatory mechanism of a semi-dwarf, albino, and blue grain wheat line.

Unlabelled: The plant height and leaf color are important traits in crops since they contribute to the production of grains and biomass. Progress has been made in mapping the genes that regulate plant height and leaf color in wheat ( L.) and other crops.

Efficient and Controllable Synthesis of 1-Aminoanthraquinone via High-Temperature Ammonolysis Using Continuous-Flow Method.

Anthraquinone dyes are the second most important type of dyes after azo dyes. In particular, 1-aminoanthraquinone has been extensively utilized in the preparation of diverse anthraquinone dyes. This study employed a continuous-flow method to synthesize 1-aminoanthraquinone safely and efficiently through the ammonolysis of 1-nitroanthraquinone at high temperatures.

Convergent Biocatalytic Mediated Synthesis of siRNA.

New technologies are required to combat the challenges faced with manufacturing commercial quantities of oligonucleotide drug substances which are required for treating large patient populations. Herein we report a convergent biocatalytic synthesis strategy for an Alnylam model siRNA. The siRNA chemical structure includes several of the unnatural modifications and conjugations typical of siRNA drug substances.

Enhancing the Activity of an Alcohol Dehydrogenase by Using "Aromatic Residue Scanning" at Potential Plasticity Sites.

An alcohol dehydrogenase LkADH was successfully engineered to exhibit improved activity and substrate tolerance for the production of (S)-2-chloro-1-(3,4-difluorophenyl)ethanol, an important precursor of ticagrelor. Five potential hotspots were identified for enzyme mutagenesis by using natural residue abundance as an indicator to evaluate their potential plasticity. A semi-rational strategy named "aromatic residue scanning" was applied to randomly mutate these five sites simultaneously by using tyrosine, tryptophan, and phenylalanine as "exploratory residues" to introduce steric hindrance or potential π-π interactions.

Genome-Wide Identification of Wheat KNOX Gene Family and Functional Characterization of in Plants.

The KNOX genes play important roles in maintaining SAM and regulating the development of plant leaves. However, the genes in wheat are still not well understood, especially their role in abiotic stress. In this study, a total of 36 KNOX genes were identified, and we demonstrated the function of the gene under mechanical injury and cold stress.

Evaluation of digestate-derived biochar to alleviate ammonia inhibition during long-term anaerobic digestion of food waste.

The feasibility of using food waste anaerobic digestate-derived biochar (FWDB) to mitigate ammonia toxicity in an anaerobic digester was evaluated. The optimal conditions for preparing and adding the activated FWDB were explored using response surface experiments, and the long-term effects of adding activated FWDB on digester performance under optimum conditions were verified in semi-continuous experiments. The results showed that the optimal preparation and addition conditions for activated FWDB were pyrolysis temperature of 565 °C, particle size of 0-0.

Nitrogen removal from low COD/N interflow using a hybrid activated sludge membrane-aerated biofilm reactor (H-MABR).

A hybrid activated sludge membrane-aerated biofilm reactor based on a two-stage simultaneous nitrification-denitrification (SND) process was built, and its utility for treating interflow with low chemical oxygen demand (COD)/total nitrogen (TN) (COD/N) was explored. The operating performance, functional microbial communities, and functional genes for nitrogen metabolism were evaluated at low COD/N (4-1.3).