Evaluating mAbs binding abilities to Omicron subvariant RBDs: implications for selecting effective mAb therapies.

The ongoing evolution of the Omicron lineage of SARS-CoV-2 has led to the emergence of subvariants that pose challenges to antibody neutralization. Understanding the binding dynamics between the receptor-binding domains (RBD) of these subvariants spike and monoclonal antibodies (mAbs) is pivotal for elucidating the mechanisms of immune escape and for advancing the development of therapeutic antibodies. This study focused on the RBD regions of Omicron subvariants BA.2, BA.5, BF.7, and XBB.1.5, employing molecular dynamics simulations to unravel their binding mechanisms with a panel of six mAbs, and subsequently analyzing the origins of immune escape from energetic and structural perspectives. Our results indicated that the antibody LY-COV1404 maintained binding affinities across all studied systems, suggesting the resilience of certain antibodies against variant-induced immune escape, as seen with the mAb 1D1-Fab. The newly identified mAb 002-S21F2 showed a similar efficacy profile to LY-COV1404, though with a slightly reduced binding to BF.7. In parallel, mAb REGN-10933 emerged as a potential therapeutic candidate against BF.7 and XBB.1.5, reflecting the importance of identifying variant-specific antibody interactions, akin to the binding optimization observed in BA.4/5 and XBB.1.5. And key residues that facilitate RBD-mAb binding were identified (T345, L441, K444, V445, and T500), alongside residues that hinder protein-protein interactions (D420, L455, K440, and S446). Particularly noteworthy was the inhibited binding of V445 and R509 with mAbs in the presence of mAb 002-S21F2, suggesting a mechanism for immune escape, especially through the reduction of V445 hydrophobicity. These findings enhance our comprehension of the binding interactions between mAbs and RBDs, contributing to the understanding of immune escape mechanisms. They also lay the groundwork for the design and optimization of antiviral drugs and have significant implications for the development of treatments against current and future coronaviruses.

Characterization and nutritional value of hydrothermal liquid products from distillers grains.

Hydrothermal liquid products (HLPs) produced by hydrothermal treatment (HTT) contain a large amount of nitrogen, phosphorus and other substances, while the environmental problems caused by arbitrary discharge. This work explored the effects of temperature, reaction time and solid-liquid ratio on the chemistry of HLPs of two different distillers grains, with a focus on nutrient composition. Increased HTT temperature was related to increased HLPs pH, dissolved organic carbon content, and aromaticity, and decreased electrical conductivity. Maximum nutrient extraction efficiencies observed for NH4+-N, NO3--N and PO43- were 92.0, 89.9, and 94.3%, respectively. Response surface methodology showed that the release of nutrient extraction efficiency was the greatest at the hydrothermal treatment of 200 °C for 1 h, and using a solid/liquid ratio of 10%. Comparative studies, the nutritional value of HLPs are appropriate for use as an agricultural fertilizer, and its use as a substitute for synthetic fertilizers could increase the sustainability and profitability of farming.

Palladium-catalyzed C-S activation/aryne insertion/coupling sequence: synthesis of functionalized 2-quinolinones.

The insertion of an aryne into a C-S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)2, a wide range of α-carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2-quinolinones in high yields under neutral reaction conditions by a C-S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio-substituted quinolinone products.

Prediction of land use for the next 30 years using the PLUS model's multi-scenario simulation in Guizhou Province, China.

Land use changes significantly impact the structure and functioning of ecosystems. The current research focus lies in how to utilize economic and policy instruments to regulate conflicts among stakeholders effectively. The objective is to facilitate rational planning and sustainable development of land utilization resources. The PLUS model integrates a rule-based mining method for land expansion analysis and a CA model based on multi-type stochastic seeding mechanism, which can be used to mine the driving factors of land expansion and predict the patch-level evolution of land use landscapes. Using the PLUS model, a simulation was conducted to study the future land use distribution in the research area over the next 30 years. Based on land use data from Guizhou Province in 2000, 2010, and 2020, a total of 16 driving factors were selected from three aspects: geographical environment, transportation network, and socio-economic conditions. Four scenarios, namely natural development, urban development, ecological conservation, and farmland rotection, were established. Comparative analysis of the simulated differences among the various scenarios was performed. (1) The overall accuracy of the land use simulation using the PLUS model in the study area was 0.983, with a Kappa coefficient of 0.972 and a FoM coefficient of 0.509. The research accuracy meets the simulation requirements. (2) Through the simulation of four different scenarios, the study investigated the land use changes in Guizhou Province over the next 30 years. Each scenario exhibited distinct impacts on land utilization. Comprehensive comparison of the different simulation results revealed that the farmland protection scenario aligns with the sustainable development goals of the research area. Currently, there is a relative scarcity of research on land use simulation, particularly in model application, for Guizhou Province. This study aims to provide a reference for the rational planning of land resources and high-quality urban construction in Guizhou, promoting the high-quality economic development in tandem with advanced ecological and environmental protection.

Designing of trimetallic-phase ternary metal sulfides coupled with N/S doped carbon protector for superior and safe Li/Na storage.

Traditional transition metal sulfides (TMSs) have shown favorable potentials in energy storage. Nevertheless, its further usage is plagued by the issues of particle breakage and large volume change. In this work, the nanostructured ternary TMSs coupled with N/S doped carbon protector (NiCoFe-S@NSC) is delicately designed via compositional regulation and spatial structure protection strategies. As lithium ion batteries anode, this electrode gives an impressive capacity of 995.7 mAh/g after running 1000 cycles at 1 A/g. More importantly, NiCoFe-S@NSC electrode still shows a discharge capacity of 221.94 mAh/g after running 20,000 cycles at 10 A/g, reflecting an extremely-low capacity decay rate of 0.0377 ‰ per cycle. As sodium ion batteries anode, a high initial discharge capacity of 896.4 mA h g-1 can be found. Even after running 400 cycles at 5 A/g, the electrode still displays a reversible capacity of 334.5 mAh/g with outstanding coulombic efficiency above 98.0 %. Impressively, LiNixCoyMn1-x-yO2//NiCoFe-S@NSC full cell gives incipient discharge/charge capacities of 186.89/240.18 mAh/g. Moreover, the discharge capacities for the following 100 cycles remain above 150 mAh/g. Thermal runaway tests also demonstrate the higher thermal safety of cells with NiCoFe-S@NSC electrode, accompanying with the promoted activation energy.

Hydrothermal carbonization of distillers grains with clay minerals for enhanced adsorption of phosphate and methylene blue.

A novel one-pot synthesis method was developed to prepare modified hydrochar by co-hydrothermal carbonization of waste distillers grains using low-cost clay minerals (attapulgite or vermiculite). The loading of the clay minerals onto hydrochar surfaces altered the structure and surface composition of the hydrochar such that the clay-modified hydrochars showed better ability to adsorb methylene blue and phosphate in aqueous solution than the pristine hydrochar. The maximum methylene blue and phosphate adsorption capacities of the modified hydrochar reached 340.3 and 96.9 mg g-1, respectively, comparable or higher than that of many commercial sorbents. Multiple mechanisms, including electrostatic attraction, ion exchange, complexation, and physical adsorption, controlled the adsorption process. These results highlight excellent potential for distillers grains-derived hydrochar-clay composites as an environmental sorbent, capable of removing a variety of contaminants from aqueous solutions.

Host CDK-1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.

Biochemical characterization of the small ubiquitin-like modifiers of Chlamydomonas reinhardtii.

Dynamic modification of target proteins by small ubiquitin-like modifier (SUMO) is known to modulate many important cellular processes and is required for cell viability and development in all eukaryotes. However, understanding of SUMO systems in plants, especially in unicellular green algae, remains elusive. In this study, Chlamydomonas reinhardtii CrSUMO96, CrSUMO97 and CrSUMO148 were characterized. We show that the formation of polymeric CrSUMO96 and CrSUMO97 chains can be catalyzed either by the human SAE1/SAE2 and Ubc9 SUMOylation system in vitro or by an Escherichia coli chimeric SUMOylation system in vivo. An exposed C-terminal di-glycine motif of CrSUMO96 or CrSUMO97 is essential for functional SUMOylation. The human SUMO-specific protease, SENP1, demonstrates more processing activity for CrSUMO97 than for CrSUMO96. The CrSUMO148 precursor notably has four repeated di-glycine motifs at the C-terminus. This unique feature is not found in other known SUMO proteins. Interestingly, only 83-residual CrSUMO148(1-83) with the first di-glycine motif can form SAE1/SAE2-SUMO complex and further form polymeric chains with the help of Ubc9. More surprisingly, CrSUMO148 precursor is digested by SENP1, solely at the peptide bond after the first di-glycine motif although there are four theoretically identical processing sites in the primary sequence. This process directly generates 83-residual CrSUMO148(1-83) mature protein, which is exactly the form suitable for activation and conjugation. We also show that SENP1 displays similar isopeptidase activity in the deconjugation of polymeric CrSUMO96, CrSUMO97 or CrSUMO148 chains, revealing that the catalytic mechanisms of processing and deconjugation of CrSUMOs by SENP1 may differ.

HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.

Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.

Pd-Catalyzed C-S Activation/Isocyanide Insertion/Hydrogenation Enables a Selective Aerobic Oxidation/Cyclization.

Unique imidoylation of thioorganics with isocyanides endows an unprecedented aerobic oxidation process. Catalyzed by Pd(Ph3P)2Cl2 in the presence of Ph3SiH under N2 then upon exposure to air, a wide range of α-acyl ketene dithioacetals react with isocyanides to afford 5-hydroxy-α,ß-unsaturated γ-lactams via a C-S bond activation, isocyanide migratory insertion, hydrogenation, selective aerobic oxidation, and intramolecular nucleophilic addition sequence.

Regio- and stereoselective synthesis of 2-cyclopentenones via a hydrogenolysis-terminated Heck cyclization of ß-alkylthio dienones.

Palladium-catalyzed cyclization of ß-alkylthio dienone derivatives affords 2-cyclopentenones in a regio- and stereoselective manner in the presence of silane. C-S activation, intramolecular carbopalladation and hydrogenolysis construct the cascade process.