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Reprogramming of cellular energy metabolism is considered an emerging feature of cancer. Mitochondrial metabolism plays a crucial role in cancer cell proliferation, survival, and metastasis. As a major mitochondrial NAD+-dependent deacetylase, sirtuin3 (SIRT3) deacetylates and regulates the enzymes involved in regulating mitochondrial energy metabolism, including fatty acid oxidation, the Krebs cycle, and the respiratory chain to maintain metabolic homeostasis. In this article, we review the multiple roles of SIRT3 in various cancers, and systematically summarize the recent advances in the discovery of its activators and inhibitors. The roles of SIRT3 vary in different cancers and have cell- and tumor-type specificity. SIRT3 plays a unique function by mediating interactions between mitochondria and intracellular signaling. The critical functions of SIRT3 have renewed interest in the development of small molecule modulators that regulate its activity. Delineation of the underlying mechanism of SIRT3 as a critical regulator of cell metabolism and further characterization of the mitochondrial substrates of SIRT3 will deepen our understanding of the role of SIRT3 in tumorigenesis and progression and may provide novel therapeutic strategies for cancer targeting SIRT3. [ABSTRACT FROM AUTHOR]

Copyright of Electroplating & Finishing is the property of Electroplating & Finishing Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Purpose: Non‐alcoholic steatohepatitis (NASH) is the more severe form of metabolic associated fatty liver disease (MAFLD) and no pharmacological treatment as yet been approved. Identification of novel therapeutic targets and their agents is critical to overcome the current inadequacy of drug treatment for NASH. Experimental Approach The correlation between heat shock factor 1 (HSF1) levels and the development of NASH and the target genes of HSF1 in hepatocyte were investigated by chromatin‐immunoprecipitation sequencing. The effects and mechanisms of SYSU‐3d in alleviating NASH were examined in relevant cell models and mouse models (the Ob/Ob mice, high‐fat and high‐cholesterol diet and the methionine‐choline deficient diet‐fed mice). The actions of SYSU‐3d in vivo were evaluated. Key Results: HSF1 is progressively reduced with mitochondrial dysfunction in NASH pathogenesis and activation of this transcription factor by its newly identified activator SYSU‐3d effectively inhibited all manifestations of NASH in mice. When activated, the phosphorylated HSF1 (Ser326) translocated to nucleus and bound to the promoter of PPARγ coactivator‐1α (PGC‐1α) to induce mitochondrial biogenesis. Thus, increasing mitochondrial adaptive oxidation and inhibiting oxidative stress. The deletion of HSF1 and PGC‐1α or recovery of HSF1 in HSF1‐deficiency cells showed the HSF1/PGC‐1α pathway was mainly responsible for the anti‐NASH effects of SYSU‐3d independent of AMP‐activated protein kinase (AMPK). Conclusion and Implications: Activation of HSF1 is a practical therapeutic approach for NASH treatment via the HSF1/PGC‐1α/mitochondrial pathway and SYSU‐3d can be considered as a potential candidate for the treatment of NASH. [ABSTRACT FROM AUTHOR]

Introduction: Class II malocclusions are the most commonly seen, and therefore, the most commonly treated type of anomalies. Dental and skeletal factors are involved in the development of Class II malocclusions. The purpose of this study was to investigate whether or not there were any changes in the increased cranial base angle and cranial base dimensions, which have been reported to be among the morphological characteristics of Class II malocclusions, with functional orthopedic treatment and to evaluate effects of these changes on facial structures. Materials and Methods: The study was conducted on hand-wrist radiographs and lateral cephalometric radiographs of 50 patients taken at the beginning and at the end of treatment. The control group comprised 17 patients and the treatment group comprised 17 patients who were treated with a Class II division 1 activator and 16 patients who were treated with a combination of Class II division 1 activator and an Occipital Headgear (Hg). Results: Among the measurements for cranial base dimensions, only the increase in S-N in the treatment group was smaller than that in the control group. No significant differences were found among groups regarding the values of NSBa and NSAr angles, which are known to be cranial base angles. Conclusion: The increase in the S-N dimension being smaller in the treatment group brings about the idea that the activator treatment may influence maxillary development and consequently the nasomaxillary complex. [ABSTRACT FROM AUTHOR]

Copyright of Bulletin of the Chinese Ceramic Society is the property of Bulletin of the Chinese Ceramic Society Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bulletin of the Chinese Ceramic Society is the property of Bulletin of the Chinese Ceramic Society Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The electrical conductivity of pure and Cr3+ -doped β-Ga2O3 thin films is studied. As found, the thin films of β-Ga2O3 and β-Ga2O3 :Cr3+ annealed in an oxygen atmosphere have a low conductivity of the order of 10-10 Ohm-1 cm-1 . The conductivity of such films is associated with the release of electrons from deep donor levels due to oxygen vacancies. At annealing within the reducing atmosphere, the specific conductivity of β-Ga2O3 thin films increases to 10-3 Ohm-1 cm-1 and is associated with shallow donor levels due to interstitial gallium atoms. At annealing within the reducing atmosphere, the specific conductivity of β-Ga2O3 :Cr3+ thin films increases to 10-8 Ohm-1 cm-1 and related with deep donor levels due to chromium impurity ions in the Cr2+ state. The relationship between the luminescence and the conductivity in β-Ga2O3 :Cr3+ thin films is analyzed. As shown, by changing the thermal-treatment conditions for the β-Ga2O3 :Cr thin films, it is possible to change the concentration of chromium-impurity ions in the Cr2+ and Cr3+ states and, thus, to control the electrical conductivity and luminescence. [ABSTRACT FROM AUTHOR]

The combustion of gaseous fuel in burners in the presence of electromagnetic fields is considered. Activation of the gas fluxes by the field improves the combustion efficiency and decreases atmospheric emissions of toxic oxides. On activation, methane is converted to hydrogen, ethane, and ethylene. The experimental apparatus is described. The fundamentals of the refined physical model describing the activation of air and gas fluxes are outlined. The quality of fuel combustion may be assessed by an indirect index of air ionization (the electrical conductivity) and the activation time. Active control of combustion by subjecting the fuel and oxidant to an electromagnetic field improves the energy and resource efficiency of the fuel and the environmental impact of the equipment. [ABSTRACT FROM AUTHOR]

Oil palm shell is one of biomass-wastes which is abundantly found in palm oil industries. Its economical value can be enhanced by converting it into hydrochar using a hydrothermal carbonization process (HTC). In this study, preparation of oil palm shell hydrochar was performed and the material was used as adsorbent to remove methylene blue from waste water. Effects of HTC temperature, KOH activator concentration, and adsorption time were studied. Functional groups of hydrochar were evaluated by Fourier transform infrared (FTIR) spectroscopy. Meanwhile, the uptake capacity of hydrochar to adsorp methylene blue was measured by using UV-Vis spectrophotometer. The results showed that dehydration and decarboxylation reactions took place more progressively at the higher temperature of HTC. It was also found that activation process resulted higher removal efficiency of methylene blue. The highest adsorption capacity (16.58 mg/g, with removal efficiency 99.51%) was obtained by hydrochar prepared by HTC 270°C, KOH 1.5 N, and carried out for 80 minutes. Keywords: activator; adsorption; hydrothermal carbonization; methylene blue; oil palm shell A B S T R A K Tempurung kelapa sawit merupakan salah satu limbah biomassa yang jumlahnya cukup melimpah di industri minyak kelapa sawit. Nilai ekonomi tempurung kelapa sawit dapat ditingkatkan, salah satunya melalui hydrothermal carbonization process (HTC). Dalam penelitian ini, hydrochar dari tempurung kelapa sawit dibuat dan digunakan sebagai adsorben untuk menjerap metilen biru dari limbah cair. Dalam hal ini, akan dipelajari pengaruh suhu HTC, konsentrasi aktivator KOH, dan durasi adsorpsi. Gugus fungsional hydrochar dianalisis dengan FT-IR spectroscopy, sementara itu kapasitas adsorpsi terhadap metilen biru diukur dengan spektrofotometer UV-Vis. Hasil percobaan menunjukkan bahwa reaksi dehidrasi dan dekarboksilasi pada kondisi hidrotermal terjadi lebih cepat pada suhu HTC yang lebih tinggi. Selain itu, proses aktivasi dengan KOH terbukti dapat meningkatkan efisiensi penyisihan metilen biru. Kapasitas adsorpsi maksimum sebesar 16,58 mg/g (dengan efisiensi penyisihan 99,51%) dihasilkan dari adsorpsi dengan menggunakan hydrochar yang diperoleh dari HTC suhu 270 °C, diaktivasi dengan KOH 1,5 N dan durasi adsorpsi selama 80 menit. Kata kunci: adsorpsi; aktivator; karbonisasi hidrotermal; metilen biru; tempurung kelapa sawit

The article presents the results of research on the selection of the saturating mixture optimal composition during chromium plating of gray cast iron. It’s carried out the microstructural studies of the surface layer of gray cast iron SCh 12, obtained using saturating mixtures with different activators and their different percentages. Phase X-ray analysis showed that the obtained coatings on cast iron consist of chromium carbides Cr23C6 and Cr7C3. The carbide zone under the same conditions of diffusion saturation is formed at the amounts of activators exceeding 7%. It is shown that the coefficient of relative wear resistance of gray cast iron after diffusion chromium plating is directly dependent on the depth of the diffusion layer. The corrosion resistance of the coating with increasing thickness of the carbide zone also increases. At the same time, heat resistance decreases sharply with increasing percentage of activator. That is, the phase composition and morphology of the layer structure have a significant influence on the oxidation processes According to the method of experiment simplex-lattice planning, mathematical models of the dependences of the depth of the diffusion layer, corrosion resistance, oxidation, and the coefficient of relative wear resistance on the saturating mixture composition were obtained. Based on the obtained dependences, triple "property-composition" diagrams are constructed. The diagrams analysis confirmed the important role of activators in the process of diffusion chromium plating. It is shown that they promote the formation of active chromium atoms, which provides the formation of a continuous carbide coating. It has been established that during diffusion chromium plating of gray cast iron SCh 12 in order to increase the corrosion resistance of the diffusion layer in the saturating mixture, it is necessary to introduce NH4Cl and NH4F activators in an amount of 10…13%. It also provides with an increase in the coefficient of relative wear resistance of gray cast iron. The introduction into the saturating mixture of NH4Cl and NH4F activators, within 4…6% provides an increase in the scale resistance of the diffusion chromium layer by 10…15 times. The use of NaCl and NaF activators during diffusion chromium plating is impractical because when introduced into the mixture it saturates, in an amount of ≤ 13% they do not give a continuous carbide layer, significantly worsens its performance.

Mechanical properties of geopolymer mortar made with class F fly ash and class C fly ash are evaluated and compared in this paper. Fly ashes were activated with a combined NaOH and Na2SiO3 alkali solution, and their strength development was observed during one year. It was observed that compressive strength values were between 10.22 and 15.83 MPa for geopolymer mortar mixtures made with class C fly ash. The values of up to 56.44 MPa were obtained for geopolymer made with class F fly ash.

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.

Reprogramming of cellular energy metabolism is considered an emerging feature of cancer. Mitochondrial metabolism plays a crucial role in cancer cell proliferation, survival, and metastasis. As a major mitochondrial NAD+-dependent deacetylase, sirtuin3 (SIRT3) deacetylates and regulates the enzymes involved in regulating mitochondrial energy metabolism, including fatty acid oxidation, the Krebs cycle, and the respiratory chain to maintain metabolic homeostasis. In this article, we review the multiple roles of SIRT3 in various cancers, and systematically summarize the recent advances in the discovery of its activators and inhibitors. The roles of SIRT3 vary in different cancers and have cell- and tumor-type specificity. SIRT3 plays a unique function by mediating interactions between mitochondria and intracellular signaling. The critical functions of SIRT3 have renewed interest in the development of small molecule modulators that regulate its activity. Delineation of the underlying mechanism of SIRT3 as a critical regulator of cell metabolism and further characterization of the mitochondrial substrates of SIRT3 will deepen our understanding of the role of SIRT3 in tumorigenesis and progression and may provide novel therapeutic strategies for cancer targeting SIRT3.

The technology for obtaining hydrofluoric acid and the peculiarities of its production were studied, and the physical and chemical properties of the waste were examined. Activators that accelerated the hardening of the anhydrite binder were selected. The process of recycling fluorine hydrite waste from the production of hydrofluoric acid at Ulba Metallurgical Plant JSC was studied, and anhydrite unburnt binder with a setting time of 30 min was obtained. On the basis of the obtained data, a technological scheme of anhydrite binder production was developed. The effectiveness of the technological scheme was confirmed experimentally. This work aimed to study the possibility of the integrated use of secondary and anthropogenic raw materials from Ulba Metallurgical Plant, which represents an important means of not only increasing production efficiency and economic benefits and reducing the irrational alienation of land resources, but also protecting against the pollution of water and air basins, as the environmental policy of UMP JSC is nowadays of great importance.

Based on a clinical staged small molecular hClpP activator ONC201, a class of novel hClpP agonists with a [1,8]naphthyridinone scaffold was designed, synthesized and evaluated in a series of biochemical and biological assays. Mechanism studies for the representative compound F20 indicated that it can potently bind to and activate hClpP, efficiently promote the degradation of hClpP substrates, robustly induce ATF4/CHOP regulated integrated stress responses, strongly inhibit cell growth and effectively induce apoptosis in a subset of cancer cell lines. F20 showed good PK profiles when dosed by intravenous injection and exhibited moderate oral bioavailability in mice., (© 2024 Wiley-VCH GmbH.)

Introduction: Cancer cells adopt a glycolytic phenotype to fulfill their energy needs in unfavorable conditions. In metabolic rewiring, cancer cells upregulate the expression of glycolytic pathway regulators including glucose transporter 1, hexokinase 2, and PKM2 (pyruvate kinase) into its M2 splice form. Among these regulators, PKM2 plays a major role in metabolic reprogramming and is overexpressed in various diseases, including cancer. Dimerization of PKM2 causes the generation of synthetic precursors from glycolytic intermediates, which are essential for cellular growth and cancer cell proliferation., Covered Areas: This article is focused on examining recent patents (2018-2023) on PKM2 activators, inhibitors and their biological and synthesis properties by using the advanced search service of the European Patent Office (EPO). Moreover, other databases including PubMed, Google Scholar and Elsevier were also examined for scientific data. On basis of their chemical structures, PKM2 activators and inhibitors are classified into pyrazole, pyrolidine-pyrazole, phenol, benzoxazine, isoselenazolo-pyridinium, phthalazine, and propiolylamide derivatives., Expert Opinion: Activating PKM2 reduces proliferation and development of cells by reducing the quantity of biomolecules needed for cell formation. PKM2 activators and inhibitors are highly effective in treating many cancer pathogens. It is important to find new, more potent and selective molecules for PKM2 activation and inhibition.

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.

Streptomyces antibiotic regulatory proteins ( SARPs ) are well characterized as transcriptional activators for secondary metabolites in Streptomyces species. Streptomyces rochei 7434AN4 harbors 15 SARP genes, among which 3 were located on a giant linear plasmid pSLA2-L and others were on the chromosome. Some SARP genes were cloned into an integrative thiostrepton-inducible vector pIJ8600, and their recombinants were cultivated. The recombinant of SARP gene, SRO_3163, accumulated a UV-active compound YM3163-A, which was not detected in the parent strain and other SARP recombinants. Its molecular formula was established to be C 8 H 11 NO. Extensive NMR analysis revealed that YM3163-A is a novel enamide, 2- ( cyclohex-2-en-1-ylidene ) acetamide, and its structure was confirmed by chemical synthesis including Horner-Wadsworth-Emmons reaction and ammonolysis. [ABSTRACT FROM AUTHOR]

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Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nanosistemi, Nanomateriali, Nanotehnologii is the property of G.V. Kurdyumov Institute for Metal Physics, N.A.S.U and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We here report a study on the activation of the ι-class bacterial CA from Burkholderia territorii (BteCAι). This protein was recently characterised as a zinc-dependent enzyme that shows a significant catalytic activity (kcat 3.0 × 105 s−1) for the physiological reaction of CO2 hydration to bicarbonate and protons. Some amino acids and amines, among which some proteinogenic derivatives as well as histamine, dopamine and serotonin, showed efficient activating properties towards BteCAι, with activation constants in the range 3.9–13.3 µM. L-Phe, L-Asn, L-Glu, and some pyridyl-alkylamines, showed a weaker activating effect towards BteCAι, with KA values ranging between 18.4 µM and 45.6 µM. Nowadays, no information is available on active site architecture, metal ion coordination and catalytic mechanism of members of the ι-group of CAs, and this study represents another contribution towards a better understanding of this still uncharacterised class of enzymes. [ABSTRACT FROM AUTHOR]

We report the first activation study of the β-class carbonic anhydrase (CA, EC 4.2.1.1) encoded in the genome of the protozoan pathogen Trichomonas vaginalis, TvaCA1. Among 24 amino acid and amine activators investigated, derivatives incorporating a second carboxylic moiety, such as L-Asp, L- and D-Glu, were devoid of activating effects up to concentrations of 50 µM within the assay system, whereas the corresponding compounds with a CONH2 moiety, i.e. L-Gln and L-Asn showed modest activating effects, with activation constants in the range of 26.9 − 32.5 µM. Moderate activation was observed with L- and D-DOPA, histamine, dopamine, serotonin, (2-Aminoethyl)pyridine/piperazine and morpholine (KA's ranging between 8.3 and 14.5 µM), while the best activators were L-and D-Trp, L-and D-Tyr and 4-amino-Phe, which showed KA's ranging between 3.0 and 5.1 µM. Understanding in detail the activation mechanism of β-CAs may be relevant for the design of enzyme activity modulators with potential clinical significance. [ABSTRACT FROM AUTHOR]

Flower color is the decisive factor that affects the commercial value of ornamental flowers. Therefore, it is important to study the regulation of flower color formation in lily to discover the positive and negative factors that regulate this important trait. In this study, MYB transcription factors (TFs) were characterized to understand the regulatory mechanism of anthocyanin biosynthesis in lily. Two R2R3-MYB TFs, LvMYB5, and LvMYB1, were found to regulate anthocyanin biosynthesis in lily flowers. LvMYB5, which has an activation motif, belongs to the SG6 MYB protein subgroup of Arabidopsis thaliana. Transient expression of LvMYB5 indicated that LvMYB5 can promote coloration in Nicotiana benthamiana leaves, and that expression of LvMYB5 increases the expression levels of NbCHS , NbDFR , and NbANS. VIGS experiments in lily petals showed that the accumulation of anthocyanins was reduced when LvMYB5 was silenced. Luciferase assays showed that LvMYB5 can promote anthocyanin synthesis by activating the ANS gene promoter. Therefore, LvMYB5 plays an important role in flower coloration in lily. In addition, the transient expression experiment provided preliminary evidence that LvMYB1 (an R2R3-MYB TF) inhibits anthocyanin synthesis in lily flowers. The discovery of activating and inhibitory factors related to anthocyanin biosynthesis in lily provides a theoretical basis for improving flower color through genetic engineering. The results of our study provide a new direction for the further study of the mechanisms of flower color formation in lilies. [ABSTRACT FROM AUTHOR]

Copyright of Kieferorthopädie: die Zeitschrift für die Praxis is the property of Quintessenz Verlags GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Flower color is the decisive factor that affects the commercial value of ornamental flowers. Therefore, it is important to study the regulation of flower color formation in lily to discover the positive and negative factors that regulate this important trait. In this study, MYB transcription factors (TFs) were characterized to understand the regulatory mechanism of anthocyanin biosynthesis in lily. Two R2R3-MYB TFs, LvMYB5, and LvMYB1, were found to regulate anthocyanin biosynthesis in lily flowers. LvMYB5, which has an activation motif, belongs to the SG6 MYB protein subgroup of Arabidopsis thaliana. Transient expression of LvMYB5 indicated that LvMYB5 can promote coloration in Nicotiana benthamiana leaves, and that expression of LvMYB5 increases the expression levels of NbCHS, NbDFR, and NbANS. VIGS experiments in lily petals showed that the accumulation of anthocyanins was reduced when LvMYB5 was silenced. Luciferase assays showed that LvMYB5 can promote anthocyanin synthesis by activating the ANS gene promoter. Therefore, LvMYB5 plays an important role in flower coloration in lily. In addition, the transient expression experiment provided preliminary evidence that LvMYB1 (an R2R3-MYB TF) inhibits anthocyanin synthesis in lily flowers. The discovery of activating and inhibitory factors related to anthocyanin biosynthesis in lily provides a theoretical basis for improving flower color through genetic engineering. The results of our study provide a new direction for the further study of the mechanisms of flower color formation in lilies.

The human sirtuins are a group of NAD+-dependent protein deacylases. They “erase” acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of diseases such as cancer, neurodegenerative diseases, and metabolic disorders. The last two decades have witnessed a flood of small molecule sirtuin regulators. However, there remain relatively few compounds targeting human sirtuins in clinical development. This reflects the inherent issues concerning the development of isoform-selective and potent molecules with good drug-like properties. In this article, small molecule sirtuin regulators that have advanced into clinical trials will be discussed in details as “successful” examples for future drug development. Special attention is given to the discovery of these compounds, the mechanism of action, pharmacokinetics analysis, formulation, as well as the clinical outcomes observed in the trials.

Sirtuins use NAD+ to remove various acyl groups from protein lysine residues. Through working on different substrate proteins, they display many biological functions, including regulation of cell proliferation, genome stability, metabolism, and cell migration. There are seven sirtuins in humans, SIRT1-7, each with unique enzymatic activities, regulatory mechanisms, subcellular localizations, and substrate scopes. They have been indicated in many human diseases, including cancer, neurodegeneration, microbial infection, metabolic and autoimmune diseases. Consequently, interests in development of sirtuin modulators have increased in the past decade. In this brief review, we specifically summarize genetic and pharmacological modulations of sirtuins in cancer, neurological, and cardiovascular diseases. We further anticipate this review will be helpful for scrutinizing the significance of sirtuins in the studied diseases.

Copyright of Wool Textile Journal is the property of National Wool Textile Science & Technology Information Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Inorganic salt pretreatment of lignocellulosic biomass has proven to be an efficient way to increase the efficiency of enzymatic saccharification. However, it is not clear that this improvement is the result of modification of the lignocellulosic substrate after pretreatment, or removal of inhibitor, or enhancement of cellulase or a combination of these events. Therefore, this study aimed to analyze the effects of inorganic salts on kinetics of cellulase enzymes (celluclast 1.5L and accellerase 1500). Two substrates rich in cellulose content [carboxymethylcellulose (CMC), avicel (AV)] and lignocellulose substrate [sugarcane bagasse (SB)] were considered. The enzymatic saccharification was carried with and without the addition of inorganic salts (NaCl and KCl) at 0.5 M and 1.0 M concentration. The kinetic parameters, Km and Vm, were determined to mechanically understand the pattern of inhibition and enhancement of inorganic salts on enzymatic saccharification. The kinetics parameters of celluclast 1.5L and accellerase 1500 for hydrolysis of CMC and AV with NaCl showed uncompetitive inhibition. Whereas, influences of KCl on both cellulase were differentiated to function in inhibition or enhancement modes when challenged with different substrates. On the other hand, enzymatic hydrolysis efficiencies of SB using both cellulases were enhanced under addition of NaCl and KCl, by increasing Vm of celluclast 1.5L from 0.303 to 0.635 mg/mL min (0.5 M KCl) and accellerase 1500 from 0.383 to 0.719 mg/mL min (1.0 M NaCl). The details of kinetic analysis in this work revealed the mechanism of inorganic salts on cellulase kinetics to be involved in substrate modification and removal of inhibitor. [ABSTRACT FROM AUTHOR]

The human sirtuins are a group of NAD+-dependent protein deacylases. They "erase" acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of diseases such as cancer, neurodegenerative diseases, and metabolic disorders. The last two decades have witnessed a flood of small molecule sirtuin regulators. However, there remain relatively few compounds targeting human sirtuins in clinical development. This reflects the inherent issues concerning the development of isoform-selective and potent molecules with good drug-like properties. In this article, small molecule sirtuin regulators that have advanced into clinical trials will be discussed in details as "successful" examples for future drug development. Special attention is given to the discovery of these compounds, the mechanism of action, pharmacokinetics analysis, formulation, as well as the clinical outcomes observed in the trials. [ABSTRACT FROM AUTHOR]

This paper describes the preparation of several sludge-based activated carbons (SACs) from sewage sludge with different carburants and activators. A comparative study of COD removal efficiency from the mature leachate by different SACs, and the effects of different carburants and activators on the COD removal performance of SACs are discussed. The results show that COD removal efficiency from the mature leachate by the prepared SACs reaches 72.06% to 85.61%, and the adsorption process was composed of monolayer adsorption and multilayer adsorption, with predominantly multilayer adsorption. The best performance in adsorption efficiency was given by the SAC prepared by using corn stalks as the carburant and ZnCl2 as the activator: a dosage of 2%, adsorption time of 40 min, and pH = 4, led to a COD removal efficiency of 82.25%. Corn straw as the carburant was more positively significant in improving the adsorption performance of SACs: the surface of that SAC was dominated by basic functional groups, and a larger qL of 227.27 mg/g was obtained, which is 3.68 times that of the SAC prepared with Brassica oleracea as the carburant. From the perspective of the activator, ZnCl2 had the best activation effect. Though SAC prepared with K2 CO3 as its activator obtained the largest qL of 231.05 mg/g, the apparent adsorption rate was slow, and the adsorption time was much longer than those of the SACs prepared with ZnCl2 and KOH. [ABSTRACT FROM AUTHOR]

For the reverse flotation of phosphate ore, a high amount of sulfuric acid is required. In this study, we used NaF as a flotation activator to separate dolomite and fluorapatite to reduce acid consumption in the flotation process. Both single and actual mineral flotations were conducted. The NaF addition significantly improved the floatability of dolomite and reduced the flotation system's acid consumption. We employed X‐ray photoelectron spectroscopy and Material Studio simulation to examine the effect of dolomite activator (NaF) on the surface of dolomite and fluoroapatite. The addition of NaF showed much less effect on fluoroapatite than dolomite, thereby increasing the difference in floatability between dolomite and fluoroapatite, which is beneficial to flotation. [ABSTRACT FROM AUTHOR]

Sirtuins use NAD+ to remove various acyl groups from protein lysine residues. Through working on different substrate proteins, they display many biological functions, including regulation of cell proliferation, genome stability, metabolism, and cell migration. There are seven sirtuins in humans, SIRT1-7, each with unique enzymatic activities, regulatory mechanisms, subcellular localizations, and substrate scopes. They have been indicated in many human diseases, including cancer, neurodegeneration, microbial infection, metabolic and autoimmune diseases. Consequently, interests in development of sirtuin modulators have increased in the past decade. In this brief review, we specifically summarize genetic and pharmacological modulations of sirtuins in cancer, neurological, and cardiovascular diseases. We further anticipate this review will be helpful for scrutinizing the significance of sirtuins in the studied diseases. [ABSTRACT FROM AUTHOR]

Sludge-based adsorbent (S-AB) converted by oily sludge can make full use of the precious resource. In this paper, oily sludge and discarded sawdust are used to prepare adsorbent through chemical activation. The adsorbent prepared is used to adsorb raw petroleum. Firstly, the most reasonable chemical activator ZnCl2 is ascertained through parallel comparative experiments. The characterization results of N2-adsorption are consistent with adsorption experiment results, which shows that higher mesopore surface area and volume are benefitted by the adsorption process. Secondly, the optimization of preparation technology is investigated through orthogonal experiments after parallel comparative experiments. The adsorption capacity of S-AB-ZnCl2 is stronger when the preparation conditions are as follows: an activation temperature of 550°C, an activation time of 3.5 h, a solid–liquid ratio of 1:1.5, a sludge-sawdust ratio of 1:0.5 and the heating rate of 15°C/min. The maximum quantity adsorbed Q0 = 434.78 mg/g, calculated through the Langmuir adsorption isothermal models, of S-AB-ZnCl2 prepared under optimized condition is higher than that before optimization. In addition, the most reasonable kinetics fits were of the second-order model. [ABSTRACT FROM AUTHOR]

• The activator of NHase (not NHase itself) is firstly focused. • The mode for activator mediating NHase maturation may be flexible. • The activator may be structurally dependent. Nitrile hydratase (NHase) is a crucial enzyme in the industry for converting nitriles into amides through hydration. Most NHases require activators to incorporate metal cofactors and achieve maturity. These activators utilize diverse mechanisms for NHase activation, which is essential for their widespread industrial applications. However, the limited understanding of activator structures and functions hampers the broader application of NHases. This review firstly offers a thorough analysis of the latest developments in the mechanism, energy utilization, flexibility and expression of NHase activators. A better understanding of NHase activators will enhance the industrial application of NHase and deepen insights into the structure and function of activator proteins. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [Display omitted] • The combination of P and EC-OG improved the growth of ryegrass. • P and EC-OG association drives changes in P morphology and enzymes. • 600 mg/kg P had the best effect on the phytoremediation efficiency. • P conversion and gene expression were optimal when P level at 600 mg/kg. • RDA showed that pH and TP had the greatest influence on the whole process. [ABSTRACT FROM AUTHOR]

The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms.

The β-carbonic anhydrase (CA, EC 4.2.1.1) from the genome of the opportunistic pathogen Malassezia restricta (MreCA), which was recently cloned and characterised, herein has been investigated for enzymatic activation by a panel of amines and amino acids. Of the 24 compounds tested in this study, the most effective MreCA activators were L-adrenaline (KA of 15 nM), 2-aminoethyl-piperazine/morpholine (KAs of 0.25–0.33 µM), histamine, L-4-amino-phenylalanine, D-Phe, L-/D-DOPA, and L-/D-Trp (KAs of 0.32 − 0.90 µM). The least effective activators were L-/D-Tyr, L-Asp, L-/D-Glu, and L-His, with activation constants ranging between 4.04 and 12.8 µM. As MreCA is involved in dandruff and seborrhoeic dermatitis, these results are of interest to identify modulators of the activity of enzymes involved in the metabolic processes of such fungi.

A β-carbonic anhydrase (CA, EC 4.2.1.1) from the widespread bacterium Escherichia coli (EcoCAβ), encoded by the CynT2 gene, has been investigated for its catalytic properties and enzymatic activation by a panel of amino acids and amines. EcoCAβ showed a significant catalytic activity for the hydration of CO2 to bicarbonate and a proton, with a kinetic constant kcat of 5.3 × 105 s− and a Michaelis–Menten constant KM of 12.9 mM. The most effective EcoCAβ activators were L- and D-DOPA, L-Tyr, 4-amino-Phe, serotonin and L-adrenaline, with KAs from 2.76 to 10.7 µM. L-His, 2-pyridyl-methylamine, L-Asn and L-Gln were relatively weak activators (KAs from 36.0 to 49.5 µM). D-His, L- and D-Phe, L- and D-Trp, D-Tyr, histamine, dopamine, 2-(aminoethyl)pyridine/piperazine/morpholine, L-Asp, L- and D-Glu have KAs from 11.3 to 23.7 µM. Endogenous CA activators may play a role in bacterial virulence and colonisation of the host.

The relevance of the researchis caused by the need to develop technological solutions and hardware design for production of by-products at small distributed energy facilities. The majority of small energy objects described in the literature and presented on the market are focused on generation of heat and electrical energy, i.e. on operation of the cogeneration principle. Obtaining by-products by thermal processing of solid fuels allows optimizing the system for production of heat and electricity at mini thermal power plants, improving fuel efficiency, solving environmental problems, and providing valuable chemical products to nearby areas and consumers. The main aim of the researchis to develop the design and carry out the calculation of the apparatus of low power to obtain activated carbon at mini thermal power plants. Object: the apparatus of low power for obtaining activated carbon by thermal processing of solid carbon-containing raw materials in the fluidized bed. Methods:hydrodynamic calculation of non-isothermal jets in a fluidized bed, heat calculation, calculation of parameters of the gas distribution grid. Results.The authors have developed the design of a low-power apparatus for producing activated carbon at mini thermal power plant and chose the design of a fluidized bed reactor as a prototype of the installation.The activator is a sealed apparatus with a perforated gas distribution grid. For the considered activator, the simplest perforated grating with a vertical orientation of round holes concave toward the center was chosen. Coal enters from the top through the loading nozzle and is distributed by a layer on the gas distribution grid, steam is supplied to the activation of coal in a jet fluidization mode through the nozzles. Hot gases – the products of fuel combustion – are fed under the grate and bring the layer into a fluidized state.The authors carried out the hydrodynamic and thermal calculations of the apparatus, namely, they determined the critical velocity of the onset of fluidization, the degree of expansion of the bed, the flow rate of combustion products, the calculation of the isothermal jet in the fluidized bed, the parameters of the gas distribution grid: the length of the gas jet, the area of ​​the cross section of the lattice.

Abstract Biodesulfurization helps in removal of sulfur from organosulfur present in petroleum fractions. All microorganisms isolated to date harbor a desulfurization operon consisting of three genes dszA, -B and -C which encode for monooxygenases (DszA & C) and desulfinase (DszB). Most of the studies have been carried out using dibenzothiophene as the model organosulfur compound, which is converted into 2 hydroxybiphenyl by a 4S pathway which maintains the calorific value of fuel. There are few studies reported on the regulation of this operon. However, there are no reports on the proteins which can enhance the activity of the operon. In the present study, we used in vitro and in vivo methods to identify a novel TetR family transcriptional regulator from Gordonia sp. IITR100 which functions as an activator of the dsz operon. Activation by TetR family regulator resulted in enhanced levels of desulfurization enzymes in Gordonia sp. IITR100. Activation was observed only when the 385 bp full length promoter was used. Upstream sequences between − 385 and − 315 were found to be responsible for activation. We provide evidence that the TetR family transcription regulator serves as an activator in other biodesulfurizing microorganisms such as Rhodococcus erythropolis IGTS8 and heterologous host Escherichia coli. This is the first report on the isolation of a possible transcriptional regulator that activates the desulfurization operon resulting in improved biodesulfurization.

To intensify the working process of diesel engines of automotive engineering, to improve power, fuel, economic and environmental performance, a distributed method of enriching the air charge in the intake stroke with a 10 ... 20% dose of liquid activator (gasoline, alcohol, kerosene, etc.) is proposed. To implement this method, an electronic system of distributed enrichment of the diesel air charge was developed. It contains a filter, an electric pump, electromagnetic nozzles, a ramp, a pressure regulator, a fuel consumption sensor (a meter of motor fuel mass flow), a phase sensor and an electronic control unit (ECU). The general arrangement of the main system units and the principle of their operation are described. The formulas for programming the ECU that controls the operation of electromagnet nozzles are given. The results of experimental studies found that with distributed enrichment of the air charge of a tractor diesel D-243-648, depending on the activator dose and load-speed mode of operation, the activator cycle supply can be from 1 mg / cycle to 13 mg / cycle, while the duration of control pulses generated by the ECU varies from 0.27 ms to 3.5 ms. The developed system provides high-quality distribution of the activator-air mixture across the cylinders of a diesel engine in the intake stroke and automatic metering of the activator depending on the load and speed modes of the engine.

Chronic pain is a debilitating condition affecting millions of people worldwide, and an improved understanding of the pathophysiology of chronic pain is urgently needed. Nociceptors are the sensory neurons that alert the nervous system to potentially harmful stimuli such as mechanical pressure or noxious thermal temperature. When an injury occurs, the nociceptive threshold for pain is reduced and an increased pain signal is produced. This process is called nociceptive sensitization. This sensitization normally subsides after the injury is healed. However, dysregulation can occur which results in sensitization that persists after the injury has healed. This process is thought to perpetuate chronic pain. The Hedgehog (Hh) signaling pathway has been previously implicated in nociceptive sensitization in response to injury in Drosophila melanogaster. Downstream of Hh signaling, the Bone Morphogenetic Protein (BMP) pathway has also been shown to be necessary for this process. Here, we describe a role for nuclear components of BMP's signaling pathway in the formation of injury-induced nociceptive sensitization. Brinker (Brk), and Schnurri (Shn) were suppressed in nociceptors using an RNA-interference (RNAi) "knockdown" approach. Knockdown of Brk resulted in hypersensitivity in the absence of injury, indicating that it normally acts to suppress nociceptive sensitivity. Animals in which transcriptional activator Shn was knocked down in nociceptors failed to develop normal allodynia after ultraviolet irradiation injury, indicating that Shn normally acts to promote hypersensitivity after injury. These results indicate that Brk-related transcription regulators play a crucial role in the formation of nociceptive sensitization and may therefore represent valuable new targets for pain-relieving medications. [ABSTRACT FROM AUTHOR]

Sedum plumbizincicola (S. plumbizincicola) is known as a sufficient plant for phytoremediation of cadmium (Cd) polluted soils. This study aimed to investigate the effects of ethylene diamine tetraacetic acid (EDTA), tea saponin (TS), and citric acid (CA) on Cd uptake and translocation by S. plumbizincicola. To do so, using a pot experiment, we set four concentration levels of activators (1, 3, 5, and 10 mmol L−1) and a control (CK). Results showed that none of the applied activators had significant impact on soil pH. Except for CA-10, the concentration of available Cd in Cd polluted soils increased by 65.8–72.9% compared with CK. The EDTA-1, CA-1, and TS-5 treatments caused significant increases of 52.3, 67.2, and 38.4%, respectively, in the biomass of aerial parts of S. plumbizincicola (p < 0.05) compared with CK. Except for CA-3, activators increased Cd accumulation in the aerial parts of plants by 47–124% compared with CK. Of all activators, EDTA-3 caused the highest Cd accumulation of 6.64 g pot−1 in the aerial plant tissues followed by CA-10 (6.25 g pot−1) and TS-1 (5.48 g pot−1). Finally, our results suggested that the application of S. plumbizincicola together with different activators sufficiently reduced soil total Cd by 4.64–48.4% compared with CK. These findings suggest that appropriate application of EDTA, TS, and CA can promote phytoremediation of Cd contaminated soils by hyper-accumulators. In particular, the combined use of EDTA and S. plumbizincicola is an affordable and promising strategy for remediation of Cd contaminated soil. Novelty statement:Sedum plumbizincicola (S. plumbizincicola) is a well-known hyper-accumulator plant for remediation of cadmium (Cd) and zinc (Zn) contaminated soils. In addition, low molecular rganic acids and macromolecular chelating agents can improve the solubility and leaching of soil heavy metals. In the present work, we examined the combined effects of three activators (EDTA, tea saponin, and citric acid) with S. plumbizincicola to remediate a Cd contaminated soil in Anhui Province, East China. Our results indicated the effectiveness of these activators to increase soil available Cd, as well as improving the biomass of S. plumbizincicola and its Cd uptake. We believe that this study provides an efficient approach to increase the uptake of Cd by S. plumbizincicola, restoring Cd contaminated soils. Nevertheless, excessive activators may have adverse effects on soil aggregates and soil microorganisms. Therefore, it is necessary to control the amount of chelating agents and subsequently the deterioration of soil quality. [ABSTRACT FROM AUTHOR]

How to achieve ideal bone regeneration is an important clinical problem, which has not been effectively solved at present. AMP-activated protein kinase (AMPK) is the central regulator of cell energy metabolism and plays an important role in regulating cell and systemic energy homeostasis. It can regulate osteocyte differentiation and bone formation, plays a vital role in the regulation of bone metabolism. This article intends to review the research progress on the role of AMPK in regulating bone metabolism in order to provide a reference for better clinical repair of bone defects. [ABSTRACT FROM AUTHOR]