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Cellulose-based impact polypropylene copolymers (IPC) has been developed by utilizing Arenga pinnata “ijuk” fiber. The cellulose from pristine ijuk fiber (IF) was extracted via alkalization and bleaching treatment using NaClO, with KMnO4 as the activator. The purpose of using KMNO4 is to replace the use of acid buffers in every process that uses NaClO. The fibers’ properties, namely their compound content, morphology, crystallinity index, and crystallite size, were characterized and investigated to examine the treatment effect. The Fourier-transform infrared (FTIR) spectroscopy shows that the majority of lignin and hemicellulose were removed throughout the treatment process. FTIR semi-quantitative analysis, based on absorbance ratio, reveals that IFB5, the fiber treated with 5% NaClO for 5 h, exhibits the highest cellulose content. The scanning electron microscopy (SEM) was performed to observe the fibers’ morphology. The X-ray diffraction (XRD) characterization reveals that IFB5 contains cellulose Iβ type and exhibits the highest crystallinity index, 62.27%. The fiber was then utilized to develop a cellulose-based IPC composite. The IPC Ijuk Treatment (IPC Ijuk T) shows a good bonding characteristic between fiber and the matrix, the highest crystallinity percentage, 67,18%, the lowest melting point, 162.8 °C, and the highest thermal stability, started to degrade at 265 °C and decomposed at 447 °C. Thus, IPC Ijuk T can be considered applicable as IPC composite filler.

Lung cancer has one of the highest mortality rates worldwide, with non-small-cell lung cancer (NSCLC) constituting approximately 85% of all cases. Demethylzeylasteral (DEM), extracted from Tripterygium wilfordii Hook F, exhibits notable anti-tumor properties. In this study, we revealed that DEM could effectively induce NSCLC cell apoptosis. Specifically, DEM can dose-dependently suppress the viability and migration of human NSCLC cells. RNA-seq analysis revealed that DEM regulates the P53-signaling pathway, which was further validated by assessing crucial proteins involved in this pathway. Biacore analysis indicated that DEM has high affinity with the P53 protein. The CDX model demonstrated DEM's anti-tumor actions. This work provided evidence that DEM-P53 interaction stabilizes P53 protein and triggers downstream anti-tumor activities. These findings indicate that DEM treatment holds promise as a potential therapeutic approach for NSCLC, which warrants further clinical assessment in patients with NSCLC.

Cement production consumes large amounts of depleted resources and energy, and causes environmental pollution. In order to reduce cement consumption and realize the closed-loop recycling of solid waste, cold bonded solid waste wrap-shell lightweight aggregates (SWSLAs) with a sextuplet blended system composed of dredged sediments, mineral powder, steel slag, phosphogypsum, fly ash, and a minimal amount of cement were prepared. Through the single-factor experiment, the influences of the types and dosages of solid wastes in the nuclear phase of SWSLAs (SWSLAs-NP) and shell phase of SWSLAs (SWSLAs-SP) on the strength and water resistance were explored, and the optimum ratio was obtained. On this basis, the influence of the types and amounts of activators incorporated in SWSLAs on the physical properties of aggregates was studied, and the primary microstructure of the aggregate was characterized. Our results showed that the optimal ratio of solid waste in the SWSLAs-NP was: 40 wt% of dredged sediments, 24 wt% of mineral powder, 18 wt% of steel slag, and 18 wt% of phosphogypsum. The optimal weight ratio of cement and solid waste in the SWSLAs-SP was 5:95. The resulting aggregate had a bearing capacity of single grain of 73.83 N and a water-resistance coefficient of 0.67. After the above aggregates were treated with Na2SO4 (activator) at 2%, the bearing capacity and water-resistance coefficient of the aggregates increased by 47.00% and 11.94%, respectively. The performances were even better than that of the aggregate composed of100w cement in the shell phase. Microstructural observations demonstrated that the structure of the raw material was reconstructed under the action of Na2SO4, and the raw materials reacted with each other, and thus the densification of the aggregate and its core-shell interface structure was enhanced, which improved the comprehensive performance of the aggregate. This study represents a step toward efficient utilization of industrial solid wastes.

Sakuranetin, a flavonoid phytoalexin in rice, plays a crucial role in defense against pathogen infection. While MYB-type transcription factors are well-known to regulate plant growth, development, secondary metabolism, and adaptation to environmental stresses, the function of rice MYB-related transcription factors in sakuranetin biosynthesis and sakuranetin-mediated defense remains unclear. In this study, we identified and characterized OsMYB1R, a novel single repeat MYB transcription factor that acts as a transcriptional activator in sakuranetin biosynthesis. Protein-DNA binding and activation assays revealed that OsMYB1R directly regulates the gene promoter of OsNOMT, a key enzyme in sakuranetin synthesis. Molecular analyses and infection studies using OsMYB1R-overexpressing (OsMYB1R-OE) and OsMYB1R-knockout (Osmyb1r, generated using CRISPR/Cas9) plants demonstrated that OsMYB1R increases sakuranetin production and decreases Magnaporthe oryzae infection by transcriptionally regulating OsNOMT expression. This finding indicates a positive regulation of sakuranetin biosynthesis and antifungal resistance by the OsMYB1R-OsNOMT crosstalk. Interestingly, the alteration of OsMYB1R expression did not affect yield-related agronomic traits. Our results reveal a novel and positive role of 1R-MYB in secondary metabolite biosynthesis and pathogen defense, suggesting that OsMYB1R is a potential gene for effectively enhancing rice resistance without compromising yield.

In this study, coffee grounds biochar was successfully applied to remove amoxicillin (AMX) in water, addressing the potential of coffee grounds recycling as an adsorbent for contaminants. The coffee grounds biochar was produced using different activators (ZnCl2 and H3PO4) and varied carbonized temperatures (300, 450, and 600°C). Overall, the AMX adsorption was noteworthy, with ZnCl2-activated biochar at 600°C, achieving a 99.83 % removal efficiency and a maximum adsorption density of 178.57 mg/g. This was attributed to its highly porous structure with a substantial meso/micropore surface area. The pseudo models aligned well with the experimental results, indicating surface reaction predominantly governed adsorption. This study underscores the significance of activator choice and carbonization temperature in the production of coffee grounds biochar as a water contaminant adsorbent, given its impressive removal efficacy and availability.

This study investigates the potential use of calcined lime mud as an activator in the development of a sustainable, ground granulated blast furnace slag (GGBFS)-based cementless UHPC. The effects of the calcination temperature (550 °C to 850 °C) of lime mud and its weight percentage in the UHPC mixture were evaluated with various tests, such as compressive strength, isothermal calorimeter, and thermogravimetric analysis. Microstructural changes and pore size distribution were also analyzed using XRD, FTIR, and MIP. The results showed that calcined lime mud can be an effective activator in the UHPC mix, and its mechanical properties are influenced by the calcination temperature and weight percentage. The addition of 10% calcined lime mud enhanced the compressive strength of the UHPC up to 150 MPa without negatively affecting its microstructural and hydration characteristics, suggesting that calcined lime mud has the potential to be used as a sustainable alternative to CaO in GGBFS-based cementless UHPC.

Enzyme activation remains a largely under-represented and poorly exploited area of drug discovery despite some key literature examples of the successful application of enzyme activators by various mechanisms and their importance in a wide range of therapeutic interventions. Here we describe the background nomenclature, present the current position of this field of drug discovery and discuss the challenges of hit identification for enzyme activation, as well as our perspectives on the approaches needed to overcome these challenges in early drug discovery.

Aldehyde dehydrogenase 2 (ALDH2) plays an important role in the detoxification of reactive aldehydes under oxidative stress. Because an estimated 50% of East Asians carry a common ALDH2 deficient variant with decreased enzyme activity and are more susceptible to toxic aldehydes, more recent findings have highlighted the therapeutic potential of ALDH2 activators in aldehyde-related diseases such as cardiovascular injury. Drug repurposing has unique advantages in providing new lead compounds with good drug-like properties. Herein, we identified Tadalafil from DrugBank as a novel ALDH2 activator using a combination strategy of docking-based and pharmacophore-based virtual screening based on exploring the activation mechanism. Then a hit-based substructure search was completed and has led to the discovery of 5 hits, among which A1 showed better ALDH2 activation activity than Tadalafil. This study provides a good basis for the further research of ALDH2 activators.

Human amylin, called also islet amyloid polypeptide (hIAPP), is the principal constituent of amyloid deposits in the pancreatic islets. Together with hyperglycemia, hIAPP-derived oligomers and aggregates are important culprits in type 2 diabetes mellitus (T2DM). Preventing aggregation, and in particular inhibiting the formation and/or stimulating degradation of toxic amylin oligomers formed early in the process, may reduce the negative effects of T2DM. Such therapeutic intervention may be enabled by activation of the 20S proteasome, a proteolytic system responsible for digesting proteins that are damaged or natively exhibit aggregation tendencies. In this work, we showed that in the lag phase of the aggregation process, soluble oligomers of small size (dimer to heptamer) were present alongside the amylin monomer. These oligomers inhibited the activity of the human 20S proteasome (h20S). To counteract this inhibition, we designed two activators that proved to be effective in restoring the peptidase efficiency of h20S to basal levels and even stimulating the enzyme to degrade the fluorogenic substrate more efficiently. They showed this effect both against isolated h20S and in cell lysate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Preparation of Li 4 ZrF 8 :Ce 3+ and Li 4 ZrF 8 :Ce 3+ ,Gd 3+ phosphors is described. Data on luminescence characteristics are presented. Hydrothermal route was employed for the synthesis. Li 4 ZrF 8 crystallizes in orthorhombic system with Pnma space group. Li atoms are distributed over two sites, both having same coordination of six. Zr is also similarly distributed over two 8 coordinated sites. Li 4 ZrF 8 :Ce 3+ emits a broad band UVB light, while the emission of Li 4 ZrF 8 :Ce 3+ ,Gd 3+ is in form of a narrow line around 311 nm attributed to 6 P 7/2  →  8 S 7/2 . Both phosphors exhibited a broad excitation spectrum with a peak at 253 nm. The excitation and emission properties are thus adequate enough to obtain UVB light sources using a conventional high pressure mercury vapour lamp or an ultraviolet LED., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

MYB proteins are ubiquitous in nature, regulating key aspects of plant growth and development. Although MYB proteins are known for regulating genes involved in secondary metabolite biosynthesis, particularly phenylpropanoids, their roles in terpenoid, glucosinolate, and alkaloid biosynthesis remain less understood. This review explores the structural and functional differences between activator and repressor MYB proteins along with their roles in plant growth, development, stress responses, and secondary metabolite production. MYB proteins serve as central hubs in protein-protein interaction networks that regulate expression of numerous genes involved in the adaptation of plants to varying environmental conditions. Thus, we also highlight key interacting partners of MYB proteins and their roles in these adaptation mechanisms. We further discuss the mechanisms regulating MYB proteins, including autoregulation, epigenetics, and post-transcriptional and post-translational modifications. Overall, we propose MYB proteins as versatile regulators for improving plant traits, stress responses, and secondary metabolite production., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of this paper is to discuss the effect of different molarity, Alkaline to Binder ratio (A/B), and Sodium silicate to sodium hydroxide (SS/SH) ratios on the enhancement of fresh and mechanical properties of geopolymer concrete. In addition, it also reveals the investigation of recent trends and technology of developments of geopolymer concrete in recent years. The fresh and hardened properties like, slump, compressive, split tensile and flexural strength, water absorption, and bulk density of geopolymer concrete data for molarity variations ranging from 5, 8–18 M, with A/B ratios ranging from 0.30 to 0.5, and SS/SH ratios. These data further assessed using kernel density plot. Molarity and A/B ratio maximum the strength development of geopolymer concrete is computed from the graph. The various binding materials used and tests performed on geopolymer concrete by the researchers are also highlighted in this paper. Increasing the molarity and A/B ratios results in the strength development of geopolymer concrete up to a specific limit.Further increment of these parameters will not significantly affect the performance. The optimal value of molarity and A/B ratios at which give better performance is discussed in this paper. Structural performances of geopolymer concrete are higher than traditional concrete.

Degradation of trypan blue (TB) by persulfate/CuNPs system was investigated as a function of TB concentration, persulfate concentration, CuNPs concentration, pH, and reaction temperature in aqueous solution. The rate of the decolorization and destruction of aromatic ring were studied spectrophotometrically. The dye mineralization was performed with potassium dichromate for the determination of chemical oxygen demand (COD) in solution. The blue color reaction mixture became red-chocolate, purple, light blue to dark blue as a function of time. The CuNPs acted as an activator of K2S2O8 and generates various reactive oxygen and/or sulphur species. Decolorization of dye starts due to the cleavage of azo bond by the generated radical species. The role of sulfate radicals (SO4•-), and hydroxyl radicals (HO•) were established by using different radical scavengers. Degradation and mineralization of dye follows first-order kinetics. These results can support the design of remediation processes and also assist in predict their fate in environment.

The main aim of this study is to analyze effective thrombolytic drugs of natural origin for the treatment of stroke. Thrombolytic activity of natural sources has been reported and active molecules have been isolated and characterized. In this study, a total of ten compounds from nature were selected for docking studies. Caesalpinine c, caesalpinine a, vanillylamine, terpinen-4-Ol, dihydrocapsaicin and 3-carene showed fibrinolytic properties on analysis with PASS server. The present work is based on computer aided molecular modeling and the strength of the ligand was validated using binding energy. Caesalpinine c exhibited good docking score and this compound showed potent thrombolytic activity than other compounds. The drug likeliness varied based on the chemical and physical properties of the ligand. Lipinski’s rule of five was accepted by all of the selected compounds. Pfizer’s rule, and GSK rule were accepted in caesalpinine C. The drug likeliness properties of the all ten selected ligands were accepted in most of the cases and few rejections were observed mostly in Golden Triangle rule. However further in vitro or in vivo trials are required to validate thrombolytic potential of caesalpinine c and vanillylamine.

Eukaryotic gene expression requires the coordination of multiple factors to overcome the repressive nature of chromatin. However, the mechanistic details of this coordination are not well understood. The SAGA family of transcriptional coactivators interacts with DNA-binding activators to establish regions of hyperacetylation. We have previously shown that, contrary to the prevailing model in which activator protein increases SAGA affinity for nucleosome substrate, the Gal4-VP16 activator model system augments the rate of acetylation turnover for the SAGA complex from budding yeast. To better understand how this stimulation occurs, we have identified necessary components using both kinetics assays and binding interactions studies. We find that Gal4-VP16-mediated stimulation requires activator binding to DNA flanking the nucleosome, as it cannot be reproduced in trans by activator protein alone or by exogenous DNA containing the activator binding site in combination with the activator protein. Further, activator-mediated stimulation requires subunits outside of the histone acetylation (HAT) module, with the Tra1 subunit being responsible for the majority of the stimulation. Interestingly, for the HAT module alone, nucleosome acetylation is inhibited by activator proteins due to non-specific binding of the activator to the nucleosomes. This inhibition is not observed for the yeast ADA complex, a small complex comprised mostly of the HAT module, suggesting that subunits outside of the HAT module in both it and SAGA can overcome non-specific activator binding to nucleosomes. However, this activity appears distinct from activator-mediated stimulation, as ADA complex acetylation is not stimulated by Gal4-VP16.

Phytoremediation has emerged as a common technique for remediating Cd pollution in farmland soil. Moreover, phosphorus, an essential element for plants, can alter the pectin content of plant cell walls and facilitate the accumulation of Cd in plant tissues, thereby enhancing phytoremediation efficiency. Therefore, pot experiments were conducted in order to investigate the effect of phosphorus levels on Cd extraction, phosphorus transformation and phosphorus-related genes during phytoremediation. The results revealed that an optimal application of suitable phosphate fertilizers elevated the soil's pH and electrical conductivity (EC), facilitated the conversion of soil from insoluble phosphorus into available forms, augmented the release of pertinent enzyme activity, and induced the expression of phosphorus cycling-related genes. These enhancements in soil conditions significantly promoted the growth of ryegrass. When applying phosphorus at a rate of 600 mg/kg, ryegrass exhibited plant height, dry weight, and chlorophyll relative content that were 1.27, 1.26, and 1.18 times higher than those in the control group (P 0 ), while the Cd content was 1.12 times greater than that of P 0 . The potentially toxic elements decline ratio and bioconcentration factor were 42.86% and 1.17 times higher than those of P 0 , respectively. Consequently, ryegrass demonstrated the highest Cd removal efficiency under these conditions. Results from redundancy analysis (RDA) revealed a significant correlation among pH, total phosphorus, heavy metal content, phosphorus forms, soil enzyme activity, and phosphorus-related genes. In conclusion, this study suggests applying an optimal amount of suitable phosphate fertilizers can enhance restoration efficiency, leading to a reduction in soil Cd content and ultimately improving the safety of crop production in farmlands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Here, we report that human lactoferrin (hLF), known for its anticancer properties, induced intracellular activation of the Na + /H + exchanger (NHE) 7 in human lung cancer PC-9 cells. Compared to non-fused hLF, the fusion of human serum albumin (HSA) with hLF (hLF-HSA) facilitated its internalization into PC-9 cells in a caveolae-mediated manner, thereby exhibiting enhanced anti-proliferative effects. Although hLF alone did not exhibit any discernible effects, hLF-HSA resulted in organelle alkalization as detected using an acidotropic pH indicator. hLF-HSA-induced elevation of organelle pH and inhibition of cancer growth were abolished by NHE7 siRNA. hLF-HSA upregulated NHE7. Thus, upon cellular uptake, hLF-HSA triggers proton leakage through the upregulation of NHE7. This process led to organelle alkalization, probably in the trans-Golgi network (TGN) as suggested by the localization of NHE7 in PC-9 cells, thereby suppressing lung cancer cell growth. Forcing the cellular uptake of hLF alone using a caveolae-mediated endocytosis activator led to an increase in organelle pH. Furthermore, cell entry of hLF also activated proton-loading NHE7, leading to organelle acidification in the pancreatic cancer cell line MIA PaCa-2. Therefore, the intracellularly delivered hLF functions as an activator of NHE7., Competing Interests: Declaration of competing interest A. Sato is the founder of S&K Biopharma Inc. (Kawasaki, Kanagawa, Japan)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

KCNQ (Kv7) channels are voltage-gated, phosphatidylinositol 4,5-bisphosphate- (PIP 2 -) modulated potassium channels that play essential roles in regulating the activity of neurons and cardiac myocytes. Hundreds of mutations in KCNQ channels are closely related to various cardiac and neurological disorders, such as long QT syndrome, epilepsy, and deafness, which makes KCNQ channels important drug targets. During the past several years, the application of single-particle cryo-electron microscopy (cryo-EM) technique in the structure determination of KCNQ channels has greatly advanced our understanding of their molecular mechanisms. In this review, we summarize the currently available structures of KCNQ channels, analyze their special voltage gating mechanism, and discuss their activation mechanisms by both the endogenous membrane lipid and the exogenous synthetic ligands. These structural studies of KCNQ channels will guide the development of drugs targeting KCNQ channels., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuan Huang reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Given the indispensability and immense value of rare earth elements for scientific and technological advancements in the 21st century, extracting high-quality rare earth resources from nature has become a global priority. Bastnäsite-(Ce) is one of the known rare earth minerals with high rare earth content and wide distribution, which occupies a pivotal position in human life and high-end production activities, making its efficient development and utilization crucial. In recent years, research on separating bastnäsite-(Ce) from gangue minerals has focused on the flotation process, with flotation reagents playing a critical role in achieving effective separation. This paper provides a detailed summary of current research on the behavior of bastnäsite-(Ce) flotation agents on minerals, their interaction with mineral surfaces during flotation separation, and outlines future prospects for further research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Activators affect the physical and chemical properties of carbon products. However, the effects of different activation mechanisms and pyrolysis conditions on the properties of carbon products still need to be explored. In this study, we obtained a new biochar by impregnation of reed powder with an alkali metal salt (CaCl 2 ) under a specific pyrolysis procedure and pyrolysis conditions. Impregnation by CaCl 2 can reduce the activation energy of the biomass while capturing and immobilizing oxygenated organic matter during pyrolysis. The new biochar has a high adsorption capacity of organic matters, for example Bisphenol A (BPA). The adsorption results showed that the modified biochar demonstrated a 364.5 % improvement in the adsorption capacity compared to the original biochar. The final performance enhancement was correlated with the confinement conditions of the environment and the procedure of pyrolysis. These procedures ultimately changed the pore distribution, functional group type, aromaticity, and degree of defects of the modified biochar. This study is important to screen synthetic pathways for identifying compounds with excellent adsorption effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Geopolymer is always regarded as a promising material for the immobilization of radioactive waste. In the present study, the stabilization of Cs in geopolymers activated by NaOH and Na 2 SiO 3 solutions and calcined at various temperatures was studied via toxicity characteristic leaching procedure (TCLP), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope and energy dispersive spectroscopy (SEM-EDS), solid-state nuclear magnetic resonance (SSNMR), and N 2 adsorption-desorption isotherm. For both NaOH-activated and Na 2 SiO 3 -activated geopolymers, the leaching concentrations of Cs decreased with the increase of calcination temperature. Specifically, most of the amorphous substance was crystallized to nepheline at 1000 °C for NaOH-activated geopolymer, and Cs + can be incorporated into the structure of nepheline, contributing to the reduction of Cs leaching concentration. However, the amorphous structure was still maintained for Na 2 SiO 3 -activated geopolymer even after calcination at 1000 °C. It has been deduced that the main structure of Na 2 SiO 3 -activated geopolymer after calcination at 1000 °C should be in short-range order and Cs + can be locked in a micro "crystal" structure. In addition, the change of specific surface area was not fully consistent with the decreasing trend of Cs leaching concentration. Therefore, the inner structure and the specific surface area of geopolymer should have a combined effect on the leaching behavior of Cs. This study can provide new insights into the application of geopolymer to immobilize radionuclides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To realize low-cost green backfill mining, this paper proposes a novel model of aeolian sand-cement-modified gasification slag-paste backfill (ACGPB). This model realizes the safe disposal and resource utilization of hazardous solid wastes. A comprehensive experiment (including slump test, uniaxial compressive strength tests, microscopic test, and leaching toxicity tests) was conducted to explore how the mechanism of ACGPB depends on activator type and dosage. The results showed that fresh ACGPB slurry can be expressed by the Herschel-Bulkley model (R 2 ≥ 0.965 in all recipes). With Na 2 SO 4 as activator type, the yield stress, apparent viscosity, thixotropy, and slump of ACGPB slurry increased with increasing activator dosage. With CaO as activator type, the yield stress, apparent viscosity, thixotropy, and slump of ACGPB slurry fluctuated with increasing activator dosage. The mechanical properties of all recipes (not including Control group and C-C1) met the mechanical requirement (3 d ≥ 0.5 MPa and 28 d ≥ 1.0 MPa). In addition, the concentrations of all heavy metals remained within the range specified by the national standard. Specifically, the activator exerted a positive effect on the stabilization/solidification of heavy metal ions (Cu, Cd, Ba, Ni, Cr, Se, and As). Finally, FTIR, TG-DTG, SEM, and hydration heat were used to analyze the microstructure of ACGPB. The research results provide a creative way for the resource utilization of solid waste., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest concerning the publication of this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

RAS proteins play major roles in many human cancers, but programs to develop direct RAS inhibitors so far have only been successful for the oncogenic KRAS mutant G12C. As an alternative approach, inhibitors for the RAS guanine nucleotide exchange factor SOS1 have been investigated by several academic groups and companies, and major progress has been achieved in recent years in the optimization of small molecule activators and inhibitors of SOS1. Here, we review the discovery and development of small molecule modulators of SOS1 and their molecular binding modes and modes of action. As targeting the RAS pathway is expected to result in the development of resistance mechanisms, SOS1 inhibitors will most likely be best applied in vertical combination approaches where two nodes of the RAS signaling pathway are hit simultaneously. We summarize the current understanding of which combination partners may be most beneficial for patients with RAS driven tumors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this study, a novel Cu 0 -Cu 2 O@CNTs composite was synthesized, characterized and applied to activate peroxydisulfate (PDS) for the degradation of 2, 4-dichlorophenol (2,4-DCP) in contaminated lake water. The results indicated that Cu 0 -Cu 2 O@CNTs can effectively activate PDS to produce O 2 • - radical, which has high selectivity to degrade organic pollutants in actual contaminated water. The efficiency of 2,4-DCP degradation and mineralization was 99.27% and 66.90%, respectively under the optimal condition. In the presence of Cl - , HCO 3 - and natural organic matters (NOMs) or in real wastewater containing 2,4-DCP, Cu 0 -Cu 2 O@CNTs/PDS system had a good selectivity for 2,4-DCP degradation. O 2 • - was the dominant reactive species in Cu 0 -Cu 2 O@CNTs/PDS system for 2,4-DCP degradation. The possible degradation pathway of 2,4-DCP was proposed. It was concluded that Cu 0 -Cu 2 O@CNTs composite could overcome the shortcomings of PDS activation by Cu 0 and Cu 2 O alone, such as low activating capability of Cu 0 and instability of Cu 2 O, which was high efficient for activating PDS. Cu 0 -Cu 2 O@CNTs composite can be used as an efficient catalyst to activate PDS for the degradation of toxic organic pollutants in water and wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Extracellular environment conditions, ionic concentration, pH, osmolality, and temperature influence sperm activation and sperm quality. The aim of this study was to evaluate the effects of different activating solutions on sperm quality and fertilization rate of fresh and post-thaw sperm in Brycon orbignyanus and Prochilodus vimboides. Activation solutions with ions: NaCl, KCl, CaCl 2 (150 mOsm kg -1 ), without ions: glucose (150 mOsm kg -1 ) and water: reverse osmosis (RO) (∼0 mOsm kg -1 ) and tank water (TW) were tested. In experiment 1, fresh sperm motility was activated in each activating solution and motility rate (%), motility quality score (0-5), and motility duration (seconds) were subjectively evaluated using a microscope. In experiment 2, sperm was cryopreserved and post-thaw sperm quality was assessed in each activating solution. Methyl glycol was used as cryoprotectant and for B. orbignyanus a solution of BTS® 5% in water reverse osmosis - 325 mOsm kg -1 was used as extender, while for P. vimboides it was used a solution of glucose 5% in water reverse osmosis - 325 mOsm kg -1 . In straw, cryoprotectant, extender, sperm were respectively 10%, 80% 10% (V/V). B. orbignyanus fresh sperm activated in NaCl, KCl, glucose solutions, TW and RO yielded higher averages for all the subjective parameters analysed. In fresh sperm of P. vimboides the highest values were observed when glucose solution was used for sperm motility activation, and the highest fertilization rates were observed in samples activated in glucose or RO solutions. B. orbignyanus post-thaw sperm activated in TW (45.1%) or RO (39.7%) presented the highest values for motility. The highest values of curvilinear velocity (VCL) were observed using glucose (69.5 μm s -1 ), NaCl (67 μm s -1 ) and KCl (68.4 μm s -1 ), but the highest fertilization rates were observed when glucose (3.6%), RO (3.5%) and TW (2.5%) were used. P. vimboides post-thaw sperm activated in glucose solution presented the highest motility rate (41%), VCL (43.7 μm s -1 ), fertilization rate (18.2%) and hatching rate (13.7%). In order to achieve the best seminal quality, fertilization and hatching rates in both fresh and post-thaw sperm, the glucose solution, TW and RO are indicated for use as sperm motility activators in B. orbignyanus, whereas for P. vimboides the glucose solution and RO are indicated., Competing Interests: Declaration of competing interest We declare no actual or potential conflict of interest regarding the submitting manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Geopolymers have been widely adopted to stabilize the cationic pollutants. However, few studies have focused on the immobilization of anionic species. In this study, the immobilization of SeO 3 2- and SeO 4 2- was explored for the first time using geopolymer activated by different alkaline solutions (NaOH and Na 2 SiO 3 ) with and without calcined hydrotalcite (CHT), characterized by TCLP, XRD, FTIR, TG, NMR, XAFS, and N 2 adsorption-desorption isotherm. Na 2 SiO 3 -activated geopolymers without CHT additive showed lower leaching percentages of SeO 3 2- and SeO 4 2- (approximately 10 % and 18 %) than NaOH-activated geopolymers (approximately 58 % and 74 %). It has been proven that electrostatic interaction is the main association mode of SeO 3 2- and SeO 4 2- in both NaOH- and Na 2 SiO 3 -activated geopolymers. Hence, compactness plays a vital role in the Se leaching from geopolymer. The addition of CHT reduced the compactnesses of both NaOH- and Na 2 SiO 3 -geopolymers. Due to the formation of hydrotalcite, the CHT additive contributed to immobilize SeO 3 2- and SeO 4 2- in NaOH-activated geopolymers. However, this phenomenon was not observed in Na 2 SiO 3 -activated geopolymers. Thus, the leaching amount of Se greatly increased from Na 2 SiO 3 -activated geopolymers with CHT additive. This study provides new insights on the application of geopolymer to immobilize anionic pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

TREK2 (KCNK10, K 2P 10.1) is a two-pore domain potassium (K2P) channel and a potential target for the treatment of pain. Like the majority of the K2P superfamily, there is currently a lack of useful pharmacological tools to study TREK2. Here we present a strategy for identifying novel TREK2 activators. A cell-based thallium flux assay was developed and used to screen a library of drug-like molecules, from which we identified the CysLT1 antagonist Pranlukast as a novel activator of TREK2. This compound was selective for TREK2 versus TREK1 and showed no activity at TRAAK. Pranlukast was also screened against other members of the K2P superfamily. Several close analogues of Pranlukast and other CysLT1 antagonists were also tested for their ability to activate K2P channels. Consistent with previous work, structure activity relationships showed that subtle structural changes to these analogues completely attenuated the activation of TREK2, whereas for TREK1, analogues moved from activators to inhibitors. Pranlukast's activity was also confirmed using whole-cell patch clamp electrophysiology. Studies using mutant forms of TREK2 suggest Pranlukast does not bind in the K2P modulator pocket or the BL-1249 binding site. Pranlukast therefore represents a novel tool by which to study the mechanism of TREK2 activation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Calcium-activated chloride channels (CaCCs)/TMEM16A control diverse fundamental physiological functions, and abnormal function of TMEM16A will lead to various diseases including asthma, hypertension, gastrointestinal hypomotility and cancers. Therefore, TMEM16A as drug targets for related diseases has been increasingly concerned by researchers. In this work, COS were reported as novel natural activators of TMEM16A. It was demonstrated that COS can activate TMEM16A in a concentration dependent manner, with an EC 50 of 74.5 μg/mL. Then, fluorescence experiments and inside-out patch clamp experiments were combined to confirm that COS can directly activate TMEM16A. Further, we compared the activation effects of COS monomers DP2 to DP6, with DP3 the best activator. Molecular simulation was performed to find that the binding sites between DP3 and TMEM16A are E143 and E146 in TMEM16A, and it was speculated that COS and TMEM16A may be combined by electrostatic interaction. Finally, we verified that guinea pig ileum contraction was promoted by COS and the monomers through activating TMEM16A. Collectively, COS are novel efficient natural activators of TMEM16A, with potential to be developed to treatment diseases caused by down-regulation of TMEM16A including gastrointestinal hypomotility., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

AMP-activated protein kinase (AMPK) plays a major role in maintaining cellular energy homeostasis by sensing and responding to AMP/ADP concentrations relative to ATP. AMPK has attracted widespread attention as a potential therapeutic target for metabolic diseases such as cancer and cardiovascular diseases. The structure-based 3D pharmacophore model was developed based on the training set. The best pharmacophore model Hypo5 was proposed and validated using a decoy set, an external test set. Hypo5, with the correlation coefficient value of 0.936, cost difference value of 112.08 and low RMS value of 1.63, includes a ionizable positive, a hydrogen bond donor, a hydrogen bond acceptor and two hydrophobic features, which showed a high goodness of fit and enrichment factor. Thus it was used as a 3D query to find potential activator from the SPECS Database. Then the ADMET descriptors were used to filter all of 158 screening molecules. The 41 filtering compounds were subsequently subjected to molecular docking and Quantitative structure-activity relationship (QSAR) analysis. Finally, the compound H2 was picked out from those filtering compounds based on the receptor-ligand interaction analysis and the prediction of the QSAR models. And then it was submitted for molecular dynamics (MD) simulations to explore the stability of complex. The result indicates that the candidate could be considered a potential AMPK activator., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Nitrile hydratase which catalyzes the hydration of nitriles to the corresponding amides is operon-encoded. However, when heterologously expressed, genes in the same operon are usually not equally expressed, and the ratio needs to be fine-tuned. A gene cluster of three genes (corresponding to α-subunit, β-subunit and activator) encoding the nitrile hydratase was cloned from Aurantimonas manganoxydans ATCC BAA-1229 and expressed in Escherichia coli. However, difficulty was encountered in heterologous expression of the activator and the expression level of β-subunit was lower than that of α-subunit, which together resulted in low catalytic efficiency. To improve the expression of activator, a set of SKIK tags were fused to the N-terminus of the activator. To elevate the expression level of β-subunit, a silent mutation strategy was applied in the overlapping sequence with α-subunit around its translation initial region. Finally, the expression of β-subunit and activator were improved and the maximum activity of NHase1229 was doubled, reaching 160 U/mL towards 3-cyanopyridine. These results indicate that N-terminal engineering is an efficient strategy for optimizing the expression of multiple genes in operons., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Phosphorus (P) is one of the most limiting macronutrients for crop productivity and P deficiency is a common phenomenon in agricultural soils worldwide. Despite long-term application of phosphate fertilizers to increase crop yields, P availability is often low, due to the high affinity of phosphate for the soil solid phase. It has been suggested that the accumulated (surplus) P in agricultural soils is sufficient to sustain crop yields worldwide for about 100years. In this paper, we try to clear up the potential for making use of legacy P in soils for crop growth potentially alleviating the global P resource shortage. Specifically, we try to clear up the potential of soil "P activators" for releasing fixed P. P activators accelerate and strengthen process which transform P into bio-available forms via a range of chemical reactions and biological interactions. They include phosphate solubilizing microorganisms, phosphatase enzymes and enzyme activators, low molecular weight organic acids, humic acids, lignin, crop residues, biochar and zeolites. Although reported performance is variable, there is growing evidence that P activators can promote the release of phosphate from soil and, hence, have potential for mitigating the impending global P crisis. Further basic and applied research is required to better understand the mechanisms of interaction of P activators with natural soils and to maximize activator efficacy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Multidrug resistance (MDR) is the main cause of diminished success in cancer chemotherapy. ABC transport proteins are considered to be one important factor of MDR. Besides P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) is associated with non-response to chemotherapy in different cancers. While considerable effort was spent in overcoming MDR during the last two decades, almost nothing is known with respect to activators of transport proteins. In this work we present certain pyrrolo[3,2-d]pyrimidine derivatives with variations at positions 4 and 5 and purine analogs with variations at position 6 as novel activators of MRP1-mediated transport of the MRP1 substrate calcein AM and the anticancer drug daunorubicin in low nanomolar concentration range. Two different MRP1 overexpressing cell lines were used, the doxorubicin-selected human lung cancer cell line H69 AR and the transfected Madin-Darby Canine Kidney cell line MDCK II MRP1. No effect was observed in the sensitive counterparts H69 and MDCK II wild type (wt). Derivatives with higher molecular weight possessed also inhibitory properties at low micromolar concentrations, although most compounds were rather poor MRP1 inhibitors. Purine analogs derived from potent MRP1 inhibitors of the pyrrolopyrimidine class showed equal activating, but no inhibiting effects at all. All tested compounds were non-toxic and had only minor impact on P-gp or BCRP, showing no inhibition or activation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Congestive heart failure (CHF) is a significant health care burden in developed countries. However, the molecular events leading from cardiac hypertrophy to CHF are unclear and preventive therapeutic approaches are limited. We have previously described that microphthalmia-associated transcription factor (MITF) is a key regulator of cardiac hypertrophy, but its cardiac targets are still uncharacterized., Methods and Results: Gene array analysis of hearts from MITF-mutated mice indicated that ErbB2 interacting protein (Erbin) is a candidate target gene for MITF. We have recently demonstrated that Erbin is decreased in human heart failure and plays a role as a negative modulator of pathological cardiac hypertrophy. Here we show that Erbin expression is regulated by MITF. Under basal conditions MITF activates Erbin expression by direct binding to its promoter. However, under β-adrenergic stimulation Erbin expression is decreased only in wild type mice, but not in MITF-mutated mice. Yeast two-hybrid screening, using MITF as bait, identified an interaction with the cardiac-predominant four-and-a-half LIM domain protein 2 (FHL2), which was confirmed by co-immunoprecipitation in both mouse and human hearts. Upon β-adrenergic stimulation, FHL2 and MITF bind Erbin promoter as a complex and repress MITF-directed Erbin expression. Overexpression of FHL2 alone had no effect on Erbin expression, but in the presence of MITF, Erbin expression was decreased. FHL2-MITF association was also increased in biopsies of heart failure patients., Conclusion: MITF unexpectedly regulates both the activation and the repression of Erbin expression. This ligand mediated fine tuning of its gene expression could be an important mechanism in the process of cardiac hypertrophy and heart failure., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed in the apical membrane of serous epithelial cells. Both deficiency and overactivation of CFTR may cause fluid and salt secretion related diseases. In the present study, we identified tangeretin from Pericarpium Citri Reticulatae Viride as a CFTR activator using high-throughput screening based on FRT cell-based fluorescence assay. The activation effect of tangeretin on CFTR chloride channel and the possible underlying mechanisms were investigated. Fluorescence quenching tests showed that tangeretin dose- and time-dependently activated CFTR chloride channel, the activity had rapid and reversible characteristics and the activation effect could be completely reversed by the CFTR specific blocker CFTRinh-172. Primary mechanism studies indicated that the activation effect of tangeretin on CFTR chloride channel was FSK dependent as well as had additional effect with FSK and IBMX suggesting that tangeretin activates CFTR by direct interacting with the protein. Ex-vivo tests revealed that tangeretin could accelerate the speed of the submucosal gland fluid secretion. Short-circuit current measurement demonstrated that tangeretin activated rat colonic mucosa chloride current. Thus, CFTR Cl(-) channel is a molecular target of natural compound tangeretin. Tangeretin may have potential use for the treatment of CFTR-related diseases like cystic fibrosis, bronchiectasis and habitual constipation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The AMP-activated protein kinase (AMPK) regulates cellular and whole-body energy balance in response to changes in adenylate charge and hormonal signals. Activation of AMPK in tissues such as skeletal muscle and liver reverses many of the metabolic defects associated with obesity and Type 2 diabetes. Here we report a bi-quinoline (JJO-1) that allosterically activates all AMPK αβγ isoforms in vitro except complexes containing the γ3 subunit. JJO-1 does not directly activate the autoinhibited α subunit kinase domain and differs among other known direct activators of AMPK in that allosteric activation occurs only at low ATP concentrations, and is not influenced by either mutation of the γ subunit adenylate-nucleotide binding sites or deletion of the β subunit carbohydrate-binding module. Our findings indicate that AMPK has multiple modes of allosteric activation that may be exploited to design isoform-specific activators as potential therapeutics for metabolic diseases., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Lupus anticoagulant (LA) is an antibody that interferes with phospholipid-dependent coagulation reactions. Activated partial thromboplastin time (APTT) is widely used as a test for LA screening. APTT reagents are composed of activators, such as silica or ellagic acid, and phospholipids, and APTT reagents with silica are recommended for LA screening because of greater sensitivity. However, the effects of activators on LA activity have not been adequately investigated., Objectives: In this study, we examined whether an ellagic acid-based reagent was highly sensitive to LA in a low phospholipid condition and useful for LA screening., Methods: Silica-based (SL) and ellagic acid-based (EA) reagents were prepared in-house with the same composition and concentration of phospholipids, while the commercial APTT reagents APTT-SLA (SLA), Actin FSL (FSL), APTT-SP (SP) and PTT-LA (PTT) were also included in the study., Results: The normal reference ranges for SL and EA were 30.1-47.0 and 28.0-40.2 s, respectively, while the cut-off index values for circulating anticoagulant activity (ICA) calculated from the results obtained with SL, EA, SLA, FSL, SP and PTT were 12.9, 11.5, 13.2, 15.6, 14.3 and 14.0, respectively. The sensitivity of those reagents based on those cut-off values was 91%, 96%, 68%, 46%, 91% and 86%, respectively., Conclusions: Our results showed that the ellagic acid-based reagent was more sensitive to LA than silica-based reagents in a low phospholipid condition and had adequate sensitivity to detect LA. We concluded that the sensitivity of APTT reagents for LA is dependent on phospholipid concentration and not the activator., (© 2012 International Society on Thrombosis and Haemostasis.)