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The damage to the back of the target plate is a phenomenon that occurs when concrete is subjected to high-speed impact. In order to study the motion parameters of prefabricated spherical fragments penetrating finite thickness concrete targets at high speeds and the occurrence rules of concrete damage, as well as the impact of target back damage on the motion of fragments, experiments were conducted on 100 mm finite thickness concrete targets with prefabricated spherical fragments. The concrete model parameters in LS-DYNA were modified based on the residual velocity of fragments, and numerical simulations were conducted on the penetration of prefabricated fragments with different impact velocities and concrete target plates with different thicknesses. By analyzing the location of concrete target plate damage, the relationship between concrete thickness and concrete damage was obtained; Combining the motion parameters of fragment penetration process, the phenomenon of concrete collapse was linked to fragment motion, and the influence of concrete thickness on fragment motion parameters was analyzed. The results indicate that the thickness of the finite thickness concrete target plate and the penetration speed of fragments have a significant impact on the damage state of the target back, and further affect the motion change response stage during the penetration process of prefabricated fragments. [ABSTRACT FROM AUTHOR]

The high purine diet could result in the increase of the level of blood uric acid, causing serious health problems such as hyperuricemia, gout, nephropathy and cardiovascular diseases. To find out a safe, cheap and super adsorption material for removing purines in stomach or pretreating high-purine beverages, we used different tissues of pomelo peel to prepare biomass carbon by drying, chemical modification and carbonization and then applied it to remove purine compounds in strong acidic solution, beer and soybean milk. The characteristic analysis of pomelo-peel-derived carbons (PPCs) indicated that the preparation methods significantly affected the structures and adsorption capacities of PPCs. Compared with the biomass carbon derived from bamboo, PPCs exhibited higher adsorption capabilities for purine compounds in strong acidic solution (adsorption rates > 99% in 15 min) and soybean milk (adsorption rates > 56% in 30 min) but slightly lower adsorption capabilities in beer (adsorption rates > 52% in 30 min). In addition, the adsorption capabilities of PPCs for purine compounds in beer and soybean milk were not obviously affected by temperatures. Therefore, PPCs are promising absorbents for applications in removing purine compounds from beverages to produce low-purine, healthier products for treating hyperuricemia. The strong adsorption capabilities of PPCs on purine compounds in strong acidic environment also provides a possibility of using the PPCs as food additives for removing purines in stomach for healthcare applications such as gout prevention after confirming their biosafety. [Display omitted] • The structures of PPCs were significantly affected by the preparation methods. • PPCs showed superior ability for removing purines in strong acidic solution than EBBC. • PPCs showed higher adsorption ability for purines in high-purine beverages than EBBC. [ABSTRACT FROM AUTHOR]

RNA‐binding proteins (RBPs) play vital roles in organisms through binding with RNAs to regulate their functions. Small molecules affecting the function of RBPs have been developed, providing new avenues for drug discovery. Herein, we describe the perspectives on developing small molecule regulators of RBPs. The following types of small molecule modulators are of great interest in drug discovery: small molecules binding to RBPs to affect interactions with RNA molecules, bifunctional molecules binding to RNA or RBP to influence their interactions, and other types of molecules that affect the stability of RNA or RBPs. Moreover, we emphasize that the bifunctional molecules may play important roles in small molecule development to overcome the challenges encountered in the process of drug discovery. [ABSTRACT FROM AUTHOR]

Bucket foundations are widely used in offshore fixed platforms, wind turbines, and floating structures. They are subjected to complex loads from the superstructure, among which the torsional load has a significant impact on foundation performance. Therefore, this study focuses on the bucket foundation under torsional load to address inaccurate calculations owing to the partial bearing phenomenon. First, the torsional bearing mechanisms of bucket foundations in normally consolidated and homogeneous soils are revealed through numerical simulations, and the limitations of the general equations for calculating the ultimate torsional capacity of bucket foundations are elaborated. Next, the torsional bearing characteristics under diversified conditions are determined considering the soil–bucket friction coefficient, bucket aspect ratio, and soil strength–heterogeneity ratio. A theoretical bucket foundation model under torsional loads is subsequently developed by summarising the observed torsional failure modes, and novel equations are derived to compute the ultimate torsional capacity of the bucket foundation accordingly. Finally, the effectiveness and accuracy of the proposed theoretical model are verified against the results of numerical simulations and its improved efficacy is demonstrated through comparison with the general equations. • The torsional failure mechanisms of bucket foundations are revealed through numerical simulations. • Key factors are investigated to reflect the torsional bearing characteristics of bucket foundations. • A novel theoretical method is proposed to calculate the ultimate torsional capacity of bucket foundations. [ABSTRACT FROM AUTHOR]

Range-extended electric vehicles combine the benefits of electric propulsion with the convenience and range flexibility of conventional internal combustion engine vehicles. In the energy management system, an equivalent consumption minimization strategy (ECMS) ensures balanced utilization of various energy sources to meet driving demand in real time, thereby enhancing energy efficiency. This paper proposes a driving pattern personalized reconstruction (DPPR) method to maximizes the accuracy of velocity prediction and to serve a predictive ECMS (P-ECMS) with high adaptability to uncertain scenarios. In this context, open-source driving cycles are segmented, and features of each driving pattern are extracted for cluster analysis. Utilizing the results from clustering, new driving cycles are reconstructed for the purpose of training adaptive neuro-fuzzy inference system (ANFIS) models. Personalized velocity prediction is achieved through bias fusion in the multi-ANFIS model, adapting to various driving conditions. The performance of the proposed P-ECMS is validated across various driving conditions and compared with conventional ECMS (C-ECMS), adaptive ECMS (A-ECMS), dynamic programming (DP), and fuzzy logic (FL) strategy. The results indicate that using the proposed P-ECMS is strongly robust in terms of battery pack SoC stabilization under various driving conditions, whose SoC difference achieves 97.02% of using the DP strategy. Compared to using other strategies, using P-ECMS achieves better SoC's stability and lower fuel consumption than using the FL strategy (11.1%), using A-ECMS (1.7%), and using C-ECMS (26.6%). • A method of driving pattern personalized reconstruction is proposed. • Adaptability of the equivalent factor for uncertain scenarios is improved. • A multi-ANFIS model is designed to capture the diversity of driving conditions. • A co-simulation platform is established for algorithm validation. • Better charge-sustaining performance and fuel economy are achieved. [ABSTRACT FROM AUTHOR]

Microbial fabrication is eco-friendly for nobel-metal catalysts typically used in proton exchange membrane fuel cell (PEMFC). In our study, nano-Pd electrocatalysts were successfully prepared by using three Shewanella s as precursors through hydrogen reduction (200 °C) and carbonization (800 °C). The analysis revealed that the catalysts showed outstanding ORR electrocatalytic performance via a predominant four-electron oxygen reduction pathway in alkaline medium. The best performance was obtained for Pd/HNC-32, which showed a mass activity at 0.526 A mg−1, 3.78 times higher than that of commercial Pd/C. Shewanella putrefaciens CN-32 was a more effective Pd-adsorbent. The enhanced performance can be ascribed to the small Pd-particle size and uniform dispersion on microbial support, which results from stronger hydrophilicity of Shewanella putrefaciens CN-32. The content of nitrogen is another key to the performance of Pd/HNC-32. This study developed a promising strategy for screening microbial strains for electrocatalyst fabrication. • Carboxyl is a key surface functional group, which determines the positive ability of Shewanella s to adsobing Pd2+. • Good wetting performances of cells would effectively avoid the agglomeration of Pd particles supported on Shewanella s. • Pd/HNC-32 has best catalytic performances due to smaller size of monodispersed Pd and high content of Pd and nitrogen. • CN-32 is optimal precursor of three Shewanella s for Pd electrocatalyst prepared via our convenient and environmental method. [ABSTRACT FROM AUTHOR]

In this paper, Pd catalysts supported on novel composite carbon supports were synthesized by the carbonization and hydrogen reduction of Pd2+-doped bacteria containing Ketjen EC600JD, CNT and rGO, respectively. The analysis results show that the prepared catalysts exhibit excellent ORR electrocatalytic performance in acid medium. The best ORR electrocatalytic performance was obtained for Pd/carbonized-bacteria-rGO, which exbibits a mass activity at 0.345 A mg−1 that is 9.58 times higher than commercial Pd/C, and meanwhile displays a better stability than that of Pd/C. The enhanced performance can be attributed to nitrogen doping and flexible carbon-coating microstructure. Herein, we elaborate an efficient and ecofriendly method for the synthesis of electrocatalysts used for oxygen reduction reaction. • Preparation of Pd/bacteria-rGO(CNT, Ketjen) catalysts is facile and eco-friendly. • rGO(CNT, Ketjen) can enhance conductivity of carbonized-bacteria composite. • The flexible carbon-coating microstructure can improve Pd catalyst performance. • Pd/bacteria-rGO catalysts show outstanding performance than standard Pd/C. • Nitrogen and phosphorus doping can enhance the catalyst performance. [ABSTRACT FROM AUTHOR]

Flexible piezoelectric ceramic composites (FPCCs) hold promising applications in fields such as flexible sensing and energy harvesting. However, the previous methods are difficult to achieve high-precision preparation of the FPCCs with complex structures, as well as the synergistic enhancement of piezoelectric performance and flexibility. In this study, by configuring a flexible resin matrix and employing a surface functionalization treatment on the piezoelectric ceramic particles, the flexibility and piezoelectric performance of the FPCCs are synergistically improved. Moreover, the addition of a light absorber, TiO 2 , significantly improves the 3D printing precision. The mechanical properties, piezoelectric performance, and printing precision of the FPCCs are analyzed. It is found that the printing error is less than 2 μm, the tensile fracture strength is 4.07 MPa, the elongation at break is 350 %, and the piezoelectric constant d 33 can reach 7.7 pC/N. In addition, the cyclic loading tests show that FPCCs with high-precision 3D complex microstructure have good recovery performance. This study not only enriches the formulation of FPCCs slurry for 3D printing, but also provides a research foundation for the multifunctional applications. [ABSTRACT FROM AUTHOR]

Syndecans are single‐span membrane proteins playing important roles in cell–cell and cell–matrix interactions. The transmembrane domain of syndecans is critical for signal transduction across the cell membrane. Here, the structure of the transmembrane domain of syndecan‐2 in detergent micelles was investigated using solution NMR spectroscopy. Backbone resonance assignment was obtained, and NMR studies show that the transmembrane domain forms a helix in detergent micelles, which is also supported by the hydrogen and deuterium exchange experiment. A study of the dynamics revealed the rigid structure of the transmembrane domain formed in solution, and paramagnetic relaxation enhancement defined the topology of the transmembrane domain in detergent micelles. This structural analysis may facilitate a better understanding of the role of the syndecan‐2 transmembrane domain in signal transduction. [ABSTRACT FROM AUTHOR]

Six novel keratin-based fluorescent hierarchical porous hydrogels, pure keratin (FK), keratin-seaweed (FK-SP), keratin-chitosan (FK-CS), and keratin-rhodamine B (FK-Rh B) with three-dimensional (3D) interconnected network structures have been prepared via a one-pot crosslinking method. The green-red dual emissions of the FK-SP and FK-Rh B hydrogels were observed under a single-wavelength excitation. [ABSTRACT FROM AUTHOR]

Non-structural (NS) proteins of dengue virus (DENV) are important for viral replication. There are four membrane proteins that are coded by viral genome. NS2B was shown to be one of the membrane proteins and its main function was confirmed to regulate viral protease activity. Its membrane topology is still not known because only few studies have been conducted to understand its structure. Here we report the determination of membrane topology of NS2B from DENV serotype 4 using NMR spectroscopy. NS2B of DENV4 was expressed and purified in detergent micelles. The secondary structure of NS2B was first defined based on backbone chemical resonance assignment. Four helices were identified in NS2B. The membrane topology of NS2B was defined based on relaxation analysis and paramagnetic relaxation enhancement experiments. The last three helices were shown to be more stable than the first helix. The NS3 protease cofactor region between α2 and α3 is highly dynamic. Our results will be useful for further structural and functional analysis of NS2B. [ABSTRACT FROM AUTHOR]

KCNQ1 plays important roles in the cardiac action potential and consists of an N-terminal domain, a voltage-sensor domain, a pore domain and a C-terminal domain. KCNQ1 is a voltage-gated potassium channel and its channel activity is regulated by membrane potentials. The linker between transmembrane helices 4 and 5 (S4–S5 linker) is important for transferring the conformational changes from the voltage-sensor domain to the pore domain. In this study, the structure of the S4–S5 linker of KCNQ1 was investigated by solution NMR, circular dichroism and fluorescence spectroscopic studies. The S4–S5 linker adopted a helical structure in detergent micelles. The W248 may interact with the cell membrane. [ABSTRACT FROM AUTHOR]

The gating of the hERG channel is regulated by its eag domain through molecular interaction with either the cyclic nucleotide‐binding homology domain (CNBHD) or the linker between transmembrane segments 4 and 5. Our NMR study on the purified CNBHD demonstrated that it contains nine β‐strands and does not bind cAMP. We show that the eag domain binds to the CBND through an interface containing several disease‐associated mutations. The N‐terminal cap domain and R56 in the eag domain are important for the interaction with the CNBHD. Residues from the CNBHD that were affected by the interaction with the eag domain were also identified. A R56Q mutation does not cause major structural changes in the eag domain and showed reduced interaction with the CNBHD.Purified CNBHD of the hERG channel does not bind cAMP. CNBHD contains 9 β‐strands and four helices. The binding interface between the CNBHD and eag domain was defined. R56Q mutant reduced the domain–domain interactions. [ABSTRACT FROM AUTHOR]

Spike protein of SARS-CoV-2 contains a single-span transmembrane (TM) domain and plays roles in receptor binding, viral attachment and viral entry to the host cells. The TM domain of spike protein is critical for viral infectivity. Herein, the TM domain of spike protein of SARS-CoV-2 was reconstituted in detergent micelles and subjected to structural analysis using solution NMR spectroscopy. The results demonstrate that the TM domain of the protein forms a helical structure in detergent micelles. An unstructured linker is identified between the TM helix and heptapeptide repeat 2 region. The linker is due to the proline residue at position 1213. Side chains of the three tryptophan residues preceding to and within the TM helix important for the function of S-protein might adopt multiple conformations which may be critical for their function. The side chain of W1212 was shown to be exposed to solvent and the side chains of residues W1214 and W1217 are buried in micelles. Relaxation study shows that the TM helix is rigid in solution while several residues have exchanges. The secondary structure and dynamics of the TM domain in this study provide insights into the function of the TM domain of spike protein. [ABSTRACT FROM AUTHOR]

Empty fruit bunch (EFB) of oil palm trees was converted to fermentable sugars by the combined use of dilute acids and whole fungal cell culture-catalyzed hydrolyses. EFB (5%, w/v) was hydrolyzed in the presence of 0.5% H2SO4 and 0.2% H3PO4 at 160 °C for 10 Min. The solid fraction was separated from the acid hydrolysate by filtration and subjected to enzymatic hydrolysis at 50 °C using the whole cell culture of Trichoderma reesei RUT-C30 (2%, w/v), which was prepared by cultivation at 30 °C for 7 days to reach its maximal cellulase activity. The combined hydrolyses of EFB gave a total sugar yield of 82.0%. When used as carbon sources for cultivating Escherichia coli in M9 medium at 37 °C, the combined EFB hydrolysates were shown to be more favorable or at least as good as pure glucose for cell growth in terms of the higher (1.1 times) optical density of E. coli cells. The by-products generated during the acid-catalyzed hydrolysis did not seem to obviously affect cell growth. The combined use of acid and whole cell culture hydrolyses might be a commercially promising method for pretreatment of lignocellulose to get fermentable sugars. [ABSTRACT FROM AUTHOR]

Abstract: The insulin receptor (IR) binds insulin and plays important roles in glucose homeostasis by regulating the tyrosine kinase activity at its C-terminus. Its transmembrane domain (TMD) is shown to be important for transferring conformational changes induced by insulin across the cell membrane to regulate kinase activity. In this study, a construct IR940–988 containing the TMD was expressed and purified for structural studies. Its solution structure in dodecylphosphocholine (DPC) micelles was determined. The sequence containing residues L962 to Y976 of the TMD of the IR in micelles adopts a well-defined helical structure with a kink formed by glycine and proline residues present at its N-terminus, which might be important for its function. Paramagnetic relaxation enhancement (PRE) and relaxation experimental results suggest that residues following the TMD are flexible and expose to aqueous solution. Although purified IR940–988 in micelles existed mainly as a monomeric form verified by gel filtration and relaxation analysis, cross-linking study suggests that it may form a dimer or oligomers under micelle conditions. [Copyright &y& Elsevier]

Abstract: The carboxy-terminal region of the KCNH family of potassium channels contains a cyclic-nucleotide binding homology domain (CNBHD) that is important for channel gating and trafficking. The solution structure of the CNBHD of the KCNH potassium of zebrafish was determined using solution NMR spectroscopy. This domain exists as a monomer under solution conditions and adopts a similar fold to that determined by X-ray crystallography. The CNBHD does not bind cAMP because residue Y740 blocks the entry of cyclic-nucleotide to the binding pocket. Relaxation results show that the CNBHD is rigid except that some residues in the loop between β6 and β7 are flexible. Our results will be useful to understand the gating mechanism of KCNH family members through the CNBHD. [Copyright &y& Elsevier]

Highlights: [•] A protease construct containing full length NS2B and NS3pro of Dengue virus was expressed. [•] Detergent screening was conducted for protein extraction from membrane. [•] Protease was active in the LMPC micelles. [Copyright &y& Elsevier]

Signals between a cell and its environment are often transmitted through membrane proteins; therefore, many membrane proteins, including G protein-coupled receptors (GPCRs) and ion channels, are important drug targets. Structural information about membrane proteins remains limited owing to challenges in protein expression, purification and the selection of membrane-mimicking systems that will retain protein structure and function. This review describes recent advances in solution NMR applied to the structural study of integral membrane proteins. The examples herein demonstrate that solution NMR spectroscopy will play a unique role not only in structural analysis, but also drug discovery of membrane proteins. [ABSTRACT FROM AUTHOR]

Abstract: The human Ether-à-go-go Related Gene (hERG) potassium channel mediates the rapid delayed rectifier current (IKr) in the cardiac action potential. Mutations in the 135 amino acid residue N-terminal domain (NTD) cause channel dysfunction or mis-translocation. To study the structure of NTD, it was overexpressed and purified from Escherichia coli cells using affinity purification and gel filtration chromatography. The purified protein behaved as a monomer under purification conditions. Far- and near-UV, circular dichroism (CD) and solution nuclear magnetic resonance (NMR) studies showed that the purified protein was well-folded. The solution structure of NTD was obtained and the N-terminal residues 13–23 forming an amphipathic helix which may be important for the protein–protein or protein-membrane interactions. NMR titration experiment also demonstrated that residues from 88 to 94 in NTD are important for the molecular interaction with the peptide derived from the S4–S5 linker. [ABSTRACT FROM AUTHOR]

Bacillus sp. (M-12) was able to decrease the chemical oxygen demand (COD) of the waste water significantly. Polyvinyl Alcohol (PVA) was chosen to immobilize the bacterial cells and the immobilized cells could be used for waste water treatment for many cycles with high COD removal efficiency. The efficiency of decreasing COD could be improved when a nitrogen source such as (NH4)2SO4 was added into the waste water. A continuous waste water treatment system with immobilized cells and a cinder column was developed and this continuous system had a significant effect on decreasing the COD of the waste water, which could be reduced from 2600 to 240 mg/L. [Copyright &y& Elsevier]

Animal feed is vulnerable to fungal infections, and the use of bio-preserving probiotics has received increasing attention. In contrast to Lactobacillus and Bifidobacteria spp., fewer Bacillus spp. have been recognized as antifungal probiotics. Therefore, our objective was to screen antifungal strains and provide more Bacillus candidates to bridge this gap. Here, we screened 56 bacterial strains for cyclic lipopeptide genes and conducted an antifungal assay with Aspergillus niger as a representative fungus. We found that a Bacillus strain Bacillus amyloliquefaciens PM415, isolated from pigeon manure, exhibited the highest fungal inhibition activity as demonstrated by the confrontation assay and morphological observation under scanning electron microscope (SEM). Preliminary safety assessment and probiotic characterization revealed its non-pathogenic feature and stress tolerance capability. Whole genome sequencing of Bacillus amyloliquefaciens PM415 revealed a genome size of 4.16 Mbp and 84 housekeeping genes thereof were used for phylogenetic analysis showing that it is most closely related to Bacillus amyloliquefaciens LFB112. The in silico analysis further supported its non-pathogenic feature at the genomic level and revealed potential biosynthetic gene clusters responsible for its antifungal property. RNA-seq analysis revealed genome-wide changes in transportation, amino acid metabolism, non-ribosomal peptides (NRPs) biosynthesis and glycan degradation during fungal antagonism. Our results suggest that Bacillus amyloliquefaciens PM415 is a safe and effective probiotic strain that can prevent fungal growth in animal feeds. [ABSTRACT FROM AUTHOR]

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design. [ABSTRACT FROM AUTHOR]

Abstract: Affinity tags are typically used to facilitate membrane protein purification. A protease needs to remain active in the presence of detergent to remove a fusion tag from a recombinant membrane protein. Our results show that the West Nile virus (WNV) protease activity was not affected while in the presence of a wide range of detergents. In a detergent solution, the WNV protease can remove the fusion tag from a recombinant protein containing KCNE3 and a WNV protease site. Therefore, the WNV protease may be useful as an alternative enzyme to remove affinity tags in protein purifications. [Copyright &y& Elsevier]

Price-makers in the generation sector can utilize offer data published by independent system operators (ISOs) for strategic bidding. Many research uses system-wide offer information for strategic bidding because individual offers are usually published with masked identifications. However, these methods are not applicable in markets with transmission congestion because the nodal information is not used. A research gap remains in using system-wide offer information and accessible nodal information for strategic bidding in markets with congestion. System-wide aggregated supply curves can be formed just with anonymous offers, and locational marginal price (LMP) is accessible nodal data containing the congestion information. This paper proposes a framework for price-makers to bid strategically by predicting LMPs with aggregated supply curves. A feature extraction method is proposed to make aggregated supply curves applicable for LMP prediction, and the maximal information coefficient is developed for feature selection. A convolutional neural network is combined with a long short-term memory network to model the impact of aggregated supply curves on LMPs. In this framework, price-makers can investigate the impact of their strategies on aggregated supply curves, predict LMPs with aggregated supply curves, and make the optimal bidding strategies. Numerical results based on the PJM-5 bus system and real data from the Midcontinent Independent System Operator validate the effectiveness of the proposed framework. • We propose a method to use aggregated supply curves for LMP prediction. • We design a CNN-LSTM for price-makers to bid strategically by LMP prediction. • Experiments based on the PJM 5-bus system and MISO validate the proposed framework. [ABSTRACT FROM AUTHOR]

Bolaamphiphile-class surfactants composed of two hydrophilic (maltoside) headgroups connected by long saturated alkyl chains were tested for their ability to stabilize a solubilized membrane protein, Escherichia co/i diacylglycerol kinase (DAGK), and to sustain its native function. Members of this "Bis-MALT-C18-28" series were poor solubilizers of DAGK in the absence of conventional detergent. However, mixed micelles of the bolaamphiphiles with either dodecylphosphocholine or -n-decyl maltoside were more effective and enhanced DAGK's thermal stability relative to corresponding detergent-only conditions. Moreover, certain bolaamphiphiles were seen to be lipid-like by providing partial activation of DAGK's catalytic activity. Finally, addition of bolaamphiphiles to miceilar NMR samples of DAGK did not result in a degradation of spectral quality, indicating their compatibility with high-resolution structural studies. To the best of our knowledge, this work represents the first documentation of the potential of bolaamphiphile-class surfactants for use in biochemical and biophysical studies of MPs. [ABSTRACT FROM AUTHOR]

Solution nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to study structures and dynamics of biomolecules under physiological conditions. As there are numerous NMR-derived methods applicable to probe protein–ligand interactions, NMR has been widely utilized in drug discovery, especially in such steps as hit identification and lead optimization. NMR is frequently used to locate ligand-binding sites on a target protein and to determine ligand binding modes. NMR spectroscopy is also a unique tool in fragment-based drug design (FBDD), as it is able to investigate target-ligand interactions with diverse binding affinities. NMR spectroscopy is able to identify fragments that bind weakly to a target, making it valuable for identifying hits targeting undruggable sites. In this review, we summarize the roles of solution NMR spectroscopy in drug discovery. We describe some methods that are used in identifying fragments, understanding the mechanism of action for a ligand, and monitoring the conformational changes of a target induced by ligand binding. A number of studies have proven that 19F-NMR is very powerful in screening fragments and detecting protein conformational changes. In-cell NMR will also play important roles in drug discovery by elucidating protein-ligand interactions in living cells. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) spectroscopy plays important roles in structural biology and drug discovery, as it is a powerful tool to understand protein structures, dynamics, and ligand binding under physiological conditions. The protease of flaviviruses is an attractive target for developing antivirals because it is essential for the maturation of viral proteins. High-resolution structures of the proteases in the absence and presence of ligands/inhibitors were determined using X-ray crystallography, providing structural information for rational drug design. Structural studies suggest that proteases from Dengue virus (DENV), West Nile virus (WNV), and Zika virus (ZIKV) exist in open and closed conformations. Solution NMR studies showed that the closed conformation is predominant in solution and should be utilized in structure-based drug design. Here, we reviewed solution NMR studies of the proteases from these viruses. The accumulated studies demonstrated that NMR spectroscopy provides additional information to understand conformational changes of these proteases in the absence and presence of substrates/inhibitors. In addition, NMR spectroscopy can be used for identifying fragment hits that can be further developed into potent protease inhibitors. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa (P-1) and its metabolic products (PIMP) of 10% could enhance the oil recovery in the model reservoir by 11.2% and also decrease injection pressure by 40.1%. Further, PIMP (10%) could reduce the crude oil viscosity by 38.5%. In the pilot tests, about 80% of wells used showed a significant increase in crude oil production after PIMP injection and shut-in for about 1 month. The pilot tests also revealed that PIMP could prolong cycle of oil well washing so that the total oil production increased. [Copyright &y& Elsevier]

Owing to the increasing need for green synthesis and environmental protection, the utilization of biological organism‐derived carbons as supports for noble‐metal electrocatalysts has garnered public interest. Nevertheless, the mechanism by which microorganisms generate nanometals has not been fully understood yet. In the present study, we used genetically engineered bacteria of Shewanella oneidensis MR‐1 (∆SO4317, ∆SO4320, ∆SO0618 and ∆SO3745) to explore the effect of surface substances including biofilm‐associated protein (bpfA), protein secreted by type I secretion systems (TISS) and type II secretion systems (T2SS), and lipopolysaccharide in microbial synthesis of metal nanoparticles. Results showed Pd/∆SO4317 (the catalyst prepared with the mutant ∆SO4317) shows better performance than other biocatalysts and commercial Pd/C, where the mass activity (MA) and specific activity (SA) of Pd/∆SO4317 are 3.1 and 2.1 times higher than those of commercial Pd/C, reaching 257.49 A g−1 and 6.85 A m−2 respectively. It has been found that the exceptional performance is attributed to the smallest particle size and the presence of abundant functional groups. Additionally, the absence of biofilms has been identified as a crucial factor in the formation of high‐quality bio‐Pd. Because the absence of biofilm can minimize metal agglomeration, resulting in uniform particle size dispersion. These findings provide valuable mechanical insights into the generation of biogenic metal nanoparticles and show potential industrial and environmental applications, especially in accelerating oxygen reduction reactions. [ABSTRACT FROM AUTHOR]

Karstification plays a crucial role in forming magnificent scenery, and storing oil, natural gas, mineral resources, and water. Through the inspiration of karstification, a hierarchical layered double hydroxide (LDH) with funnel-like and cave-like structures (called Karst-LDH) is formed by the dissolution of acrylic acid/water solution. Meanwhile, the results of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) show that Karst-LDH has complicated and interconnected internal pipe networks. The actual maximum phosphate adsorption capacity of Karst-LDH reaches 126.38 mg g−1 due to the unique structures, protonation, ligand exchange, ion exchange, and hydrogen bonding, which is over ten times that of general LDH with a regular hexagonal structure. The results of isotherms and thermodynamics also indicate that Karst-LDH conforms to more heterogeneous and multilayer adsorption with a higher entropy-driven process. Karst-LDH exhibits good selectivity for chloride and nitrate ions. The change in the frontier orbital interaction between phosphate and different LDHs is a significant reason for quick macropore transmission, mesopore interception, and finally, phosphate storage in Karst-LDH. This work provides an efficient way for the design and fabrication of high adsorption performance materials with unique karst-type structures, which can be used for multiple fields potentially. [ABSTRACT FROM AUTHOR]

Many studies have been conducted on the microbial reduction of Pd (II) to palladium nanoparticles (Pd-NPs) due to the environmental friendliness, low cost, and the decreased toxicity of Pd (II) ions. In this study, we investigate the reduction mechanism of Pd (II) by Bacillus megaterium Y-4 through proteomics. The data are available via ProteomeXchange with identifier PXD049711. Our results revealed that B. megaterium Y-4 may use the endogenous electron donor (NAD(P)H) generated by nirB, tdh, and fabG and reductase to reduce Pd (II) to Pd-NPs. The expression levels of fabG, tdh, gudB, and rocG that generate NAD(P)H were further increased, and the number of reduced Pd-NPs was further increased with the exogenous electron donor sodium formate. Endogenous electron mediators such as quinones and flavins in B. megaterium Y-4 can further enhance Pd (II) reduction. The findings provided invaluable information regarding the reduction mechanism of Pd (II) by B. megaterium Y-4 at the proteome level. [ABSTRACT FROM AUTHOR]

Rhamnolipids are a class of biosurfactants with effective surface-active properties. The high cost of microbial production of rhamnolipids largely affects their commercial applications. To reduce the production post, research has been carried out in screening more powerful strains, engineering microbes with higher biosurfactant yields and exploring cheaper substrates to reduce the production cost. Extensive refining is required for biosurfactant production using oils and oil-containing wastes, necessitating the use of complex and expensive biosurfactant recovery methods such as extraction with solvents or acid precipitation. As raw materials normally can account for 10–30% of the overall production cost, sugars have been proven to be an alternative carbon source for microbial production of rhamnolipids due to its lower costs and straightforward processing techniques. Studies have thus been focused on using tropical agroindustrial crop residues as renewable substrates. Herein, we reviewed studies that are using sugar-containing substrates as carbon sources for producing rhamnolipids. We speculate that sugars derived from agricultural wastes rich in cellulose and sugar-containing wastes are potential carbon sources in fermentation while challenges still remain in large scales. [ABSTRACT FROM AUTHOR]

Erythropoiesis is regulated by the erythropoietin receptor (EpoR) binding to its ligand. The transmembrane domain (TMD) and the juxtamembrane (JM) regions of the EpoR are important for signal transduction across the cell membrane. We report a solution NMR study of the mouse erythropoietin receptor (mEpoR) comprising the TMD and the JM regions reconstituted in dodecylphosphocholine (DPC) micelles. The TMD and the C-terminal JM region of the mEpoR are mainly α-helical, adopting a similar structure to those of the human EpoR. Residues from S216 to T219 in mEpoR form a short helix. Relaxation study demonstrates that the TMD of the mEpoR is rigid whilst the N-terminal region preceding the TMD is flexible. Fluorescence spectroscopy and sequence analysis indicate that the C-terminal JM region is exposed to the solvent. Helix wheel result shows that there is hydrophilic patch in the TMD of the mEpoR formed by residues S231, S238 and T242, and these residues might be important for the receptor dimerization. [ABSTRACT FROM AUTHOR]

Oligodendrocytes generate myelin sheaths vital for the formation, health, and function of the central nervous system. Mounting evidence suggests that receptor tyrosine kinases (RTKs) are crucial for oligodendrocyte differentiation and myelination in the CNS. It was recently reported that discoidin domain receptor 1 (Ddr1), a collagen-activated RTK, is expressed in oligodendrocyte lineage. However, its specific expression stage and functional role in oligodendrocyte development in the CNS remain to be determined. In this study, we report that Ddr1 is selectively upregulated in newly differentiated oligodendrocytes in the early postnatal CNS and regulates oligodendrocyte differentiation and myelination. Ddr1 knock-out mice of both sexes displayed compromised axonal myelination and apparent motor dysfunction. Ddr1 deficiency alerted the ERK pathway, but not the AKT pathway in the CNS. In addition, Ddr1 function is important for myelin repair after lysolecithin-induced demyelination. Taken together, the current study described, for the first time, the role of Ddr1 in myelin development and repair in the CNS, providing a novel molecule target for the treatment of demyelinating diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-β1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-β1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-β1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-β1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases. [ABSTRACT FROM AUTHOR]

Noble-metal electrocatalysts supported by biological-organism-derived carbons have attracted attention from the public due to the growing demands for green synthesis and environmental protection. Carbonization at high temperatures and hydrogen reduction are critical steps in this technical route. Herein, Shewanella oneidensis MR-1 were used as precursors, and the effects of the hydrogen-reduction procedure on catalysts were explored. The results showed that the performances of FHTG (carbonization followed by hydrogen reduction) displayed the best performance. Its ECSA (electrochemical surface area), MA (mass activity), and SA (specific activity) reached 35.01 m2 g−1, 58.39 A·g−1, and 1.66 A cm−2, respectively, which were 1.17, 1.75, and 1.50 times that of PHTG (prepared through hydrogen reduction followed by carbonization) and 1.56, 2.26, and 1.44 times that of DHTG (double hydrogen reduction). The high performance could be attributed to its fine particle size and rich N content, and the specific regulation mechanism was also proposed in this paper. This study opens a practical guide for effectively avoiding particle agglomeration during the fabrication process for catalysts. [ABSTRACT FROM AUTHOR]

Duckweed (Lemna minor L.) is a common plant in paddy fields, absorbing nutrients, heavy metals, and agrochemical residues from irrigation water, thus playing a pivotal role in ecosystem sustainability. To reveal the combined effects of irrigation modes, rice cultivars, and fertilizer types on duckweed, tank experiments were conducted in two rice-growing seasons (2019 and 2020) in Jiangsu Province, China. The experiment included three factors, each consisting of two levels: rice cultivars (R) (japonica rice (J) and indica rice (X)), fertilizer types (F) (organic fertilizer (O) and chemical fertilizer (C)), and irrigation modes (I) (controlled irrigation (1) and shallow-frequent irrigation (2)). Results indicated that organic fertilizer significantly increased the total phosphorus concentration by 396% and promoted DCR by 703% in floodwater as compared with chemical fertilizer. The significantly higher tiller numbers of indica rice increased the shade level, repressing maximum electron transfer rate (ETR max) of duckweed, and consequently reduced DCR by 32.8% as compared with japonica rice. A cyclic pattern of Production-Death-Reproduction of duckweed under controlled irrigation was observed, which depended on the periodic cycle of Appear-Disappear-Reappear of the floodwater. Setting the irrigation lower limit to 87.9% saturation water content(θs) can benefit the regeneration of duckweed after re-watering. Similar to a capacitor that could store and release electric charge in circuit system by regulating voltage, under the application of organic fertilizer (battery), duckweed (capacitors) efficiently absorbs, decomposes, and subsequently reabsorbs nutrients by the regulation of controlled irrigation (switch), releasing fertility gradually for the rice plant (electrical appliance). • Duckweed is influenced by combined effects of fertilizer, rice and irrigation types. • Setting irrigation lower limit at 87.9% θ s aids duckweed regrowth. • Duckweed absorbs, decomposes, reabsorbs nutrients—acts as "fertilizer capacitors". [ABSTRACT FROM AUTHOR]

Abstract: Dengue virus causes serious diseases affecting people in tropical and sub-tropical regions. The nonstructural (NS) protein 2B is an integral membrane protein and important for the regulation of viral protease NS3, which is significant for virus replication. The NS2B-NS3 complex is an important drug target for treating dengue fever. However, little is known about the structure of NS2B in its entirety. Herein, we describe the expression and purification of this integral membrane protein from cell membrane and inclusion bodies of Escherichia coli cells. The initial nuclear magnetic resonance (NMR) and circular dichroism (CD) results indicate that the purified protein adopts alpha-helical structures in LMPG and TDPC micelles. [Copyright &y& Elsevier]

Nickel chloride is a promising material as cathode candidate for thermal battery, attributed to its superior electrochemical performance including high operating voltage and high specific energy. However, high polarization and structural collapse have emerged as major challenge hindering the practical application of NiCl 2 cathode. Herein we propose an engineering strategy to construct a high-specific-energy NiCl 2 -based cathode with rhombohedral structure and amorphous carbon-layer skin structure. Benefited from delicate structural characteristic and improved electrochemical activity, the cathode designed remarkably elevates the plateau voltage of a single cell to 2.5 V and achieves, for the first time, a specific energy of 266.5 Wh/kg at current density of 600 mA/cm2 in the thermal battery tests. Notably, in contrast to the lab-level methods, this engineering strategy is an industrially feasible approach to manufacture NiCl 2 -based cathode for expanded application in thermal battery. This strategy also provides new insight into the design of high-performance cathode. [ABSTRACT FROM AUTHOR]

Abstract The Zika virus (ZIKV) genome encodes a polyprotein that can be post-translationally processed into functional viral proteins. The viral protease is indispensable in the maturation of viral proteins. The Zika protease comprises of two components crucial for catalysis. The N-terminal region of NS3 contains the catalytic triad and approximately 40 amino acids of NS2B are essential for folding and protease activity. NS2B is a membrane protein with transmembrane domains that are critical for the localization of NS3 to the membrane. In this study, we expressed and purified full-length NS2B from ZIKV in E. coli. Purified NS2B was then reconstituted into lyso-myristoyl phosphatidylglycerol (LMPG) micelles. It was found that compared to wild type NS2B, NS2B C11S mutation in LMPG exhibited dispersed cross peaks in the 1H 15N-HSQC spectrum, thereby suggesting the feasibility for structural characterization using solution NMR spectroscopy. Highlights • Full length NS2B of Zika virus was purified. • NS2B in LMPG micelles exhibited dispersed NMR signals. • Structure and dynamics of NS2B were explored. • Free NS2B contains a long unstructured region. [ABSTRACT FROM AUTHOR]

• Platelet camouflaged IL-10 is a promising approach for kidney injury treatment. • IL-10@PLT could selectively accumulate in injured kidneys. • IL-10@PLT could be activated, aggregated, and released IL-10 in the injury kidney. • High accumulation and strong anti-inflammatory of IL-10@PLT enhanced therapeutic efficiency. Inflammatory factors have emerged as key pathophysiological molecules involved in the progression of acute and chronic kidney disease. However, the anti-inflammatory effect of interleukin-10 (IL-10) is largely attenuated because of its insufficient concentration in an injured kidney. To overcome this challenge, we demonstrate in this study that platelet (PLT) camouflaged IL-10 (IL-10@PLT) can selectively accumulate in injured kidneys for treating kidney inflammation and resulting complications. In this system, the PLT drug carrier maintained its original attributes over the study duration, with a good inflammation target effect, confirmed by in vivo imaging. IL-10@PLT could be activated and aggregated, and also released IL-10 at the injury site in the kidney because of high levels of Tumor Necrosis Factor-α (TNF-α). Compared with free IL-10, IL-10@PLT displayed a higher anti-inflammatory effect with fewer mitochondrial disorders (P < 0.01) and lower expression of NOD-like receptor (NLR)-P3 (NLRP3) (P < 0.05), resulting in reduced inflammation and pyroptosis in ischemia/reperfusion injury (I/R) mice. Treatment with IL-10@PLT also exhibited significantly reduced nuclear factor kappa-B (NF-kB) expression, reduced inflammatory response, as well as improved renal fibrosis (P < 0.05) in the recovery phase in unilateral ureteral obstruction (UUO) mice. At the same time, IL-10@PLT therapy continued to exhibit a favorable safety profile. This study established a promising approach for I/R- and UUO-induced kidney injury and fibrosis by taking advantage of the high accumulation and strong anti-inflammatory of IL-10@PLT. Our study also reveals the importance PLT as an effective drug carrier for targeted therapies. [ABSTRACT FROM AUTHOR]

Dengue virus nonstructural protein 4B (NS4B) is a membrane protein consisting of 248 residues with a crucial role in virus replication and interference with the host innate immunity. The dengue virus serotype 3 NS4B was reconstituted into lyso-myristoyl phosphatidylglycerol (LMPG) micelles. Backbone resonance assignment of NS4B was obtained using conventional solution NMR experiments. Further studies suggested that NS4B contained eleven helices and six of them form five potential transmembrane regions. This study provides atomic level information for an important drug target to control flavivirus infections. [ABSTRACT FROM AUTHOR]

Dengue virus nonstructural protein 4B (NS4B) is a membrane protein consisting of 248 residues with a crucial role in virus replication and interference with the host innate immunity. The dengue virus serotype 3 NS4B was reconstituted into lyso-myristoyl phosphatidylglycerol (LMPG) micelles. Backbone resonance assignment of NS4B was obtained using conventional solution NMR experiments. Further studies suggested that NS4B contained eleven helices and six of them form five potential transmembrane regions. This study provides atomic level information for an important drug target to control flavivirus infections. [ABSTRACT FROM AUTHOR]

Dengue protease is a two-component enzyme and is an important drug target against dengue virus. The protease activity and protein stability of dengue nonstructural protein 3 (NS3) require a co-factor region from a four-span membrane protein NS2B. A natural form of dengue protease containing full-length NS2B and NS3 protease domain NS2BFL-NS3pro will be useful for dengue drug discovery. In current study, detergents that can be used for protease purification were tested. Using a water soluble protease construct, 39 detergents were selected for both NS2B and NS2BFL-NS3pro purification. The results showed that 18 detergents were able to sustain the activity of the natural dengue protease and 11 detergents could be used for NS2B purification. The results obtained in this study will be useful for biochemical and biophysical studies on dengue protease. [ABSTRACT FROM AUTHOR]

A joint analytical–numerical integration method is proposed to solve the time domain boundary integral equations for 2-D elastodynamics. The analytical integration method is adopted to solve the discrete boundary integral equations for elastodynamics with singular integrals, while the numerical integration method is conventionally adopted to solve the discrete boundary integral equations for elastodynamics without singular integrals. Accurate quantitative relationships for G and H matrices between elastostatics and elastodynamics are established, under certain assumptions. All the singularities in G and H matrices for 2-D elastodynamics are analytically solved in the process of the discretization in space and time. The analytical method to solve singular integrals in space and time is verified by the examples of 1-D rod and 2-D cantilever beam under sudden loads. [ABSTRACT FROM AUTHOR]