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Proton exchange membrane fuel cells (PEMFCs) have garnered considerable interest owing to their high conversion efficiency and eco-friendliness. However, the components of PEMFCs are prone to degradation caused by generated radicals, hindering their widespread application. To counteract the chemical attack of radicals on PEMFC components, the key solution is to incorporate radical scavengers, as they can effectively eliminate harmful radicals. Ce-based scavengers exhibit the highest radical scavenging capacity, whereas they are susceptible to dissolution and may exert poisoning effects on ionomers, thereby impacting proton conductivity and gas mass transfer. Additionally, Ce-based radical scavengers may degraded and migrated due to varying chemical and electrochemical conditions. This study delves into the scavenging mechanisms and influences of Ce-based radical scavengers. Furthermore, it addresses the issues of poisoning and migration and outlines appropriate measures to mitigate these challenges. This review aims to offer an innovative solution to enhance the durability of PEMFCs. [Display omitted] • Reviewed the scavenging mechanisms of Ce-based radical scavengers and their effects. • Discussed the poisoning effects of Ce-based radical scavengers and provided some mitigation strategies. • Highlighted the migration of Ce species and the corresponding stabilization strategies. • Presented the technical challenges and future development prospects of Ce-based radical scavengers. [ABSTRACT FROM AUTHOR]

SLC25A26 is the only known human mitochondrial S-adenosylmethionine carrier encoding gene. Recent studies have shown that SLC25A26 is abnormally expressed in some cancers, such as cervical cancer, low-grade glioma, non-small cell lung cancer, and liver cancer, which suggests SLC25A26 can affect the occurrence and development of some cancers. This article in brief briefly reviewed mitochondrial S-adenosylmethionine carrier in different species and its encoding gene, focused on the association of SLC25A26 aberrant expression and some cancers as well as potential mechanisms, summarized its potential for cancer prognosis, and characteristics of mitochondrial diseases caused by SLC25A26 mutation. Finally, we provide a brief expectation that needs to be further investigated. We speculate that SLC25A26 will be a potential new therapeutic target for some cancers. [ABSTRACT FROM AUTHOR]

Convective Self‐Aggregation (CSA) is a common feature of idealized numerical simulations of the tropical atmosphere in Radiative‐Convective Equilibrium (RCE). However, at coarse grid resolution where deep convection is not fully resolved, the occurrence of this phenomenon is extremely sensitive to subgrid‐scale processes. This study examines the role of mixing and entrainment, provided by the turbulence model and the implicit numerical diffusion. The study compares the results of two models, WRF and SAM, by varying turbulence models, initial conditions, and horizontal spatial resolution. At a coarse grid resolution of 3 km, the removal of turbulent mixing prevents CSA in models with low numerical diffusivity but is preserved in models with high numerical diffusivity. When the horizontal grid resolution is refined to 1 km, CSA can only be achieved by increasing explicit turbulent mixing, even with a small amount of shallow clouds. Therefore, the sensitivity of CSA to horizontal grid resolution is not primarily caused by the decrease in shallow clouds. The analysis of the total water path spectrum suggests that the amplitude of initial humidity perturbations introduced by convection in the free troposphere is the key factor. This amplitude is regulated by turbulent mixing and diffusion at small scales. Prior to the onset of CSA, increased mixing makes updrafts more sensitive to the dryness of the free troposphere, which strengthens the moisture‐convection feedback. This leads to an increased distance between convective cores and a stronger humidity perturbation in the free troposphere, which can destabilize the RCE state. Plain Language Summary: Convection transports moisture from the surface to the troposphere and forms clouds. Clouds developing in dry environments can be diluted by turbulent mixing, while mixing in moist environments favors their deepening. Turbulent mixing thus favors convection over moist regions, making them moister, while the opposite is true for dry regions. This phenomenon is known as the moisture‐convection feedback. In atmospheric models with a horizontal grid resolution of about 1 km, the feedback is represented by the turbulence model and the numerical discretization errors. This study found that when simulating deep tropical convection, the use of coarse grid resolution strengthens the moisture‐convection feedback, initially creating larger clusters of clouds separated by larger areas free of convection. In these areas where convection is suppressed, the upper troposphere will dry out. The amplitude of this area and its associated dry perturbation of the upper troposphere are key factors in determining whether convection will continue to be suppressed or if it will be able to penetrate the free troposphere. The final clustering of clouds into a single moist patch, known as convective self‐aggregation, depends on these conditions. Therefore, it is necessary to accurately represent sub‐grid scale mixing processes to capture the convective self‐aggregation phenomenon in high‐resolution atmospheric models. Key Points: The initial amplitude of humidity perturbations introduced by convection in the free troposphere is the key factor for the onset of convective self‐aggregation.Prior to the onset of self‐aggregation, this amplitude is regulated by turbulent mixing and numerical diffusion, rather than the amount of shallow clouds.Coarse resolutions impose larger mixing which increases the distance between convective cores and the associated humidity perturbation in the free troposphere. [ABSTRACT FROM AUTHOR]

BACKGROUND: The study aimed to determine the effects of instant controlled decompression of steam pressure, termed as ICPD (instant controlled pressure drop) on fresh tea leaves, when combined with refractance window drying (RWD) of rolled green teas during green tea manufacturing. The ICPD steam treatment pressure (TP; 0.1–0.3 MPa), treatment time (TT; 10–20 s) and refractance window drying temperature (RWDT; 70–90 °C) were used as the processing parameters for manufacturing of green tea. RESULT: Response surface methodology was employed to enumerate the effects of ICPD process conditions and temperature of RWD on total phenolic content (TPC), total flavonoid content (TFC) and DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) radical scavenging activity of the green tea infusion. An optimum condition for green tea processing was found at TP 0.2 MPa, TT 20 s with RWDT at 70 °C. In comparison to made green tea manufactured without ICPD treatment, the ICPD treated green tea showed enhanced TPC, TFC and DPPH radical scavenging activity along with better colour and sensory attributes. The microstructural study of ICPD treated green tea samples showed more deformed cell surface integrity, larger stomatal pore size and cracks at the leaf surface in comparison with non‐treated green tea sample. CONCLUSION: Present study reveals that an ICPD treatment at 0.2 MPa for 20 s can be used as an alternative to the traditional enzyme inactivation step of hot water treatment, for green tea leaves to improve the infusion quality in terms of increased levels of TPC and TFC and DPPH radical scavenging activity. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The unsustainable and widespread utilization of fossil fuels continues to drive the rapid depletion of global supplies. Biodiesel has emerged as one of the most promising alternatives to conventional diesel, leading to growing research interest in its production. Microbes can facilitate the de novo synthesis of a type of biodiesel in the form of fatty acid methyl esters (FAMEs). In this study, Saccharomyces cerevisiae metabolic activity was engineered to facilitate enhanced FAME production. Initially, free fatty acid concentrations were increased by deleting two acetyl-CoA synthetase genes (FAA1, FAA4) and an acyl-CoA oxidase gene (POX1). Intracellular S-adenosylmethionine (SAM) levels were then enhanced via the deletion of an adenosine kinase gene (ADO1) and the overexpression of a SAM synthetase gene (SAM2). Lastly, the S. cerevisiae strain overproducing free fatty acids and SAM were manipulated to express a plasmid encoding the Drosophila melanogaster Juvenile Hormone Acid O-Methyltransferase (DmJHAMT). Using this combination of engineering approaches, a FAME concentration of 5.79 ± 0.56 mg/L was achieved using these cells in the context of shaking flask fermentation. To the best of our knowledge, this is the first detailed study of FAME production in S. cerevisiae. These results will provide a valuable basis for future efforts to engineer S. cerevisiae strains for highly efficient production of biodiesel. Key points: De novo synthesis of FAMEs was demonstrated in Saccharomyces cerevisiae. FAME production was improved by increasing concentrations of fatty acids and SAM. FAMEs produced in S. cerevisiae mainly included C16 and C18 fatty acid methyl esters. [ABSTRACT FROM AUTHOR]

As(III) S‐adenosylmethionine methyltransferases, pivotal enzymes in arsenic metabolism, facilitate the methylation of arsenic up to three times. This process predominantly yields trivalent mono‐ and dimethylarsenite, with trimethylarsine forming in smaller amounts. While this enzyme acts as a detoxifier in microbial systems by altering As(III), in humans, it paradoxically generates more toxic and potentially carcinogenic methylated arsenic species. The strong affinity of As(III) for cysteine residues, forming As(III)‐thiolate bonds, is exploited in medical treatments, notably in arsenic trioxide (Trisenox®), an FDA‐approved drug for leukemia. The effectiveness of this drug is partly due to its interaction with cysteine residues, leading to the breakdown of key oncogenic fusion proteins. In this study, we extend the understanding of As(III)′s binding mechanisms, showing that, in addition to As(III)−S covalent bonds, noncovalent O⋅⋅⋅As pnictogen bonding plays a vital role. This interaction significantly contributes to the structural stability of the As(III) complexes. Our crystallographic analysis using the PDB database of As(III) S‐adenosylmethionine methyltransferases, augmented by comprehensive theoretical studies including molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM), and natural bond orbital (NBO) analysis, emphasizes the critical role of pnictogen bonding in these systems. We also undertake a detailed evaluation of the energy characteristics of these pnictogen bonds using various theoretical models. To our knowledge, this is the first time pnictogen bonds in As(III) derivatives have been reported in biological systems, marking a significant advancement in our understanding of arsenic's molecular interactions. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), the most frequent and lethal brain cancer in adults, is characterized by short survival times and high mortality rates. Due to the resistance of GBM cells to conventional therapeutic treatments, scientific interest is focusing on the search for alternative and efficient adjuvant treatments. S-Adenosylmethionine (AdoMet), the well-studied physiological methyl donor, has emerged as a promising anticancer compound and a modulator of multiple cancer-related signaling pathways. We report here for the first time that AdoMet selectively inhibited the viability and proliferation of U87MG, U343MG, and U251MG GBM cells. In these cell lines, AdoMet induced S and G2/M cell cycle arrest and apoptosis and downregulated the expression and activation of proteins involved in homologous recombination DNA repair, including RAD51, BRCA1, and Chk1. Furthermore, AdoMet was able to maintain DNA in a damaged state, as indicated by the increased γH2AX/H2AX ratio. AdoMet promoted mitotic catastrophe through inhibiting Aurora B kinase expression, phosphorylation, and localization causing GBM cells to undergo mitotic catastrophe-induced death. Finally, AdoMet inhibited DNA repair and induced cell cycle arrest, apoptosis, and mitotic catastrophe in patient-derived GBM cells. In light of these results, AdoMet could be considered a potential adjuvant in GBM therapy. [ABSTRACT FROM AUTHOR]

Emerging consumer demand for safer, more sustainable flavors and fragrances has created new challenges for the industry. Enzymatic syntheses represent a promising green production route, but the broad application requires engineering advancements for expanded diversity, improved selectivity, and enhanced stability to be cost-competitive with current methods. This review discusses recent advances and future outlooks for enzyme engineering in this field. We focus on carboxylic acid reductases (CARs) and unspecific peroxygenases (UPOs) that enable selective productions of complex flavor and fragrance molecules. Both enzyme types consist of natural variants with attractive characteristics for biocatalytic applications. Applying protein engineering methods, including rational design and directed evolution in concert with computational modeling, present excellent examples for property improvements to unleash the full potential of enzymes in the biosynthesis of value-added chemicals. • Carboxylic acid reductases (CARs) directly reduce carboxylic acids into aldehydes without a second enzyme for substrate activation. • Unspecific peroxygenases (UPOs) are self-sufficient mono peroxygenases that catalyze similar reactions as P450 enzymes. • Both groups of enzymes have broad substrate scopes and perform chemistries that are challenging to chemical methods. • We present enzyme engineering examples that improved and/or altered the catalytic property or stability of these enzymes. • The engineering achievements are steppingstones towards the ultimate industrial syntheses using CARs and UPOs. [ABSTRACT FROM AUTHOR]

The SAM1 and SAM2 genes encode for S-Adenosylmethionine (AdoMet) synthetase enzymes, with AdoMet serving as the main cellular methyl donor. We have previously shown that independent deletion of these genes alters chromosome stability and AdoMet concentrations in opposite ways in Saccharomyces cerevisiae. To characterize other changes occurring in these mutants, we grew wildtype, sam1Δ /sam1 Δ , and sam2Δ /sam2 Δ strains in 15 different Phenotypic Microarray plates with different components and measured growth variations. RNA-Sequencing was also carried out on these strains and differential gene expression determined for each mutant. We explored how the phenotypic growth differences are linked to the altered gene expression, and hypothesize mechanisms by which loss of the SAM genes and subsequent AdoMet level changes, impact pathways and processes. We present 6 stories, discussing changes in sensitivity or resistance to azoles, cisplatin, oxidative stress, arginine biosynthesis perturbations, DNA synthesis inhibitors, and tamoxifen, to demonstrate the power of this novel methodology to broadly profile changes due to gene mutations. The large number of conditions that result in altered growth, as well as the large number of differentially expressed genes with wide-ranging functionality, speaks to the broad array of impacts that altering methyl donor abundance can impart. Our findings demonstrate that some cellular changes are directly related to AdoMet-dependent methyltransferases and AdoMet availability, some are directly linked to the methyl cycle and its role in production of several important cellular components, and others reveal impacts of SAM gene mutations on previously unconnected pathways. [ABSTRACT FROM AUTHOR]

S‐adenosylmethionine (SAM), generated from methionine and ATP by S‐adenosyl methionine synthetase (SAMS), is the universal methyl group donor required for numerous cellular methylation reactions. In Caenorhabditis elegans, silencing sams‐1, the major isoform of SAMS, genetically or via dietary restriction induces a robust mitochondrial unfolded protein response (UPRmt) and lifespan extension. In this study, we found that depleting SAMS‐1 markedly decreases mitochondrial SAM levels. Moreover, RNAi knockdown of SLC‐25A26, a carrier protein responsible for transporting SAM from the cytoplasm into the mitochondria, significantly lowers the mitochondrial SAM levels and activates UPRmt, suggesting that the UPRmt induced by sams‐1 mutations might result from disrupted mitochondrial SAM homeostasis. Through a genetic screen, we then identified a putative mitochondrial tRNA methyltransferase TRMT‐10C.2 as a major downstream effector of SAMS‐1 to regulate UPRmt and longevity. As disruption of mitochondrial tRNA methylation likely leads to impaired mitochondrial tRNA maturation and consequently reduced mitochondrial translation, our findings suggest that depleting mitochondrial SAM level might trigger UPRmt via attenuating protein translation in the mitochondria. Together, this study has revealed a potential mechanism by which SAMS‐1 regulates UPRmt and longevity. [ABSTRACT FROM AUTHOR]

Hineka is a type of off-flavor of sake and is attributed to the presence of several compounds, including a major one called dimethyl trisulfide (DMTS). The production of the main precursor of DMTS involves yeast methionine salvage pathway. The DMTS-producing potential (DMTS-pp) of sake brewed using the Km67 strain, a non-Kyokai sake yeast, is lower than that of sake brewed using Kyokai yeast; however, the detailed mechanism is unclear. We focused on S -adenosyl-methionine (SAM) and aimed to elucidate the mechanism that prevents DMTS production in sake brewed using the Km67 strain. We revealed that SAM is involved in DMTS production in sake, and that the conversion of SAM to the DMTS precursor occurs through an enzymatic reaction rather than a chemical reaction. Based on previous reports on ADO1 and MDE1 genes, sake brewing tests were performed using the Km67 Δ mde1 , Δ ado1 , and Δ mde1 Δ ado1 strains. A comparison of the SAM content of pressed sake cakes and DMTS-pp of sake produced using the Km67 Δ ado1 strain showed an increase in both SAM content and DMTS-pp compared to those produced using the parent strain. However, the Km67 Δ mde1 Δ ado1 strain showed little increase in DMTS-pp compared to the Km67 Δ mde1 strain, despite an increase in SAM content. These results suggest that SAM accumulation in yeast plays a role in the production of DMTS in sake through the methionine salvage pathway. Moreover, the low SAM-accumulation characteristic of the Km67 strain contributes to low DMTS production in sake. [ABSTRACT FROM AUTHOR]

LIBS is an analytical technique for direct analysis, capable of performing elemental, molecular and isotopic characterization. This technique involves the physical processes of ablation and plasma formation by the incidence of high-energy laser pulses. The direct analysis of liquid samples is challenging due to the occurrence of splashes that impairs the measurement in many aspects. In this work, an inorganic solid substrate consisting of a bentonite/sepiolite composite (70/30 wt%) is described as a support for organic liquids in molecular LIBS analysis. The substrate allowed molecular LIBS measurements of solvents, fuels and even aqueous solution with minimal spectral interference and made it possible to identify molecular radical emissions (CN and C2). Therefore, the proposed substrate is believed to be an alternative material for sampling organic liquids for molecular LIBS analyses. [ABSTRACT FROM AUTHOR]

Immunotherapy has become one of the most effective therapeutic modalities for achieving long‐term cancer remission, but the available immunotherapeutic strategies suffer from modest response rates owing to the insufficient immunogenicity of tumor cells. In this work, a nanomedicine strategy for maintaining highly immunogenic tumor cells by inducing cascade‐mediated immunogenic tumor‐cell ferroptosis is proposed and developed. A PdMoP nanoplatform is engineered that not only induces initial immunogenic tumor cell ferroptosis through its multienzyme‐mimicking activities but also accelerates Mo(IV)‐to‐Mo(VI) transition, which aggravates glutathione (GSH) depletion for deactivating glutathione peroxidase 4 (GPX4) enzyme and lead to excessive radical production for promoting p53 expression and reducing SLC7A11, thereby resulting in efficient ferroptosis and apoptosis. Additionally, PdMoP nanoparticles induce the breakdown of hydrogen peroxide into oxygen to alleviate tumor hypoxia, working synergistically with GSH depletion to reverse the immunosuppressive tumor microenvironment. Significant ferroptosis (through the classical p53‐SLC7A11‐GPX4 pathway) is monitored in both in vitro cellular level and in vivo tumor models, achieving effective tumor suppression and elimination. The distinct ultrasound‐enhanced enzyodynamic therapy strategy represents a simple and effective paradigm for treating cancer by nanocatalytic medicine and catalytic biomaterials. [ABSTRACT FROM AUTHOR]

Objective: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. Subjects and Methods: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis‐mass spectrometry. Gene expression was evaluated using real‐time reverse transcription‐polymerase chain reaction. Results: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2‐hydroxyglutarate, and S‐adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. Conclusions: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated. [ABSTRACT FROM AUTHOR]

Confronted with the substantial environmental threat posed by organophosphorus pesticides, the urgency to develop reliable and efficient mitigation strategies is paramount. Photocatalytic technology, which catalyzes the generation of potent oxidizing radicals, emerges as a promising solution. In this study, we have successfully synthesized In 2 O 3 /WO 3 (IO/WO) nanocomposites, endowed with oxygen defects and S-scheme heterojunctions, exhibiting exceptional photocatalytic degradation activity and mineralization efficiency. Notably, the WO material synthesized in this study is blue in color, unlike the traditional yellow color of WO, indicating a rich presence of oxygen defects. The 60-IO/WO nanocomposite, containing 60 % IO, achieved superior photocatalytic degradation, reducing triazophos pesticide from 100 % to 21.29 % within 60 min, outperforming the individual materials IO (56.97 %) and WO (48.02 %). This nanocomposite also exhibited remarkable corrosion resistance across multiple cycles, showcasing significantly enhanced stability compared to the individual IO and WO materials. Electron paramagnetic resonance (EPR) spectroscopy confirmed the presence of oxygen defects in the blue WO, while both EPR and theoretical calculations substantiated the formation of the S-scheme heterojunction in the 60-IO/WO nanocomposite. The new nanocomposite's excellent photocatalytic degradation activity is influenced by various factors such as differing surface areas, composite amounts, photocurrent responses, and resistances, all of which impact the degradation performance of triazophos. Compared to traditional photocatalytic materials, the IO/WO nanocomposite demonstrates a significant edge in photocatalytic efficiency and chemical stability, offering considerable potential for environmental remediation, especially in the degradation of organophosphorus pesticides. [Display omitted] • The 60-In 2 O 3 /WO 3 nanocomposite with oxygen vacancies shows enhanced photocatalytic degradation of triazophos. • Tests confirm oxygen vacancies and an S-scheme heterojunction in the In 2 O 3 /WO 3 nanocomposite. • Oxygen defects and S-scheme heterojunctions increase photocatalytic efficiency by enhancing charge dynamics. [ABSTRACT FROM AUTHOR]

The use of cell growth‐based assays to identify inhibitory compounds is straightforward and inexpensive, but is also inherently insensitive and somewhat nonspecific. To overcome these limitations and develop a sensitive, specific cell‐based assay, two different approaches were combined. To address the sensitivity limitation, different fluorescent proteins have been introduced into a bacterial expression system to serve as growth reporters. To overcome the lack of specificity, these protein reporters have been incorporated into a plasmid in which they are paired with different orthologs of an essential target enzyme, in this case l‐methionine S‐adenosyltransferase (MAT, AdoMet synthetase). Screening compounds that serve as specific inhibitors will reduce the growth of only a subset of strains, because these strains are identical, except for which target ortholog they carry. Screening several such strains in parallel not only reveals potential inhibitors but the strains also serve as specificity controls for one another. The present study makes use of an existing Escherichia coli strain that carries a deletion of metK, the gene for MAT. Transformation with these plasmids leads to a complemented strain that no longer requires externally supplied S‐adenosylmethionine for growth, but its growth is now dependent on the activity of the introduced MAT ortholog. The resulting fluorescent strains provide a platform to screen chemical compound libraries and identify species‐selective inhibitors of AdoMet synthetases. A pilot study of several chemical libraries using this platform identified new lead compounds that are ortholog‐selective inhibitors of this enzyme family, some of which target the protozoal human pathogen Cryptosporidium parvum. [ABSTRACT FROM AUTHOR]

Background: Obesity in common marmosets (Callithrix jacchus) can lead to various liver pathologies. In other species, reduced caloric intake and weight loss improve prognosis, and, often, hepatoprotectants are used to halt or reverse hepatocellular damage from fat deposition in the liver. There are no published therapies for reducing hepatocellular damage in obese marmosets. Methods: Fifteen obese marmosets were used to evaluate the ability of caloric restriction and pharmacologic therapy (S-adenosylmethionine + milk thistle extract, or SMT), alone and combined, to reduce elevated liver enzymes. Body weight and serum chemistries were measured every 4 weeks for 6 months. Results: Across treatment groups, there was a significant reduction in liver enzymes ALT and AST over time. SMT alone significantly reduced liver enzymes ALT and AST at 6 months from baseline. Conclusions: Caloric restriction and SMT, alone and combined, are effective at reducing liver enzyme levels in obese marmosets. [ABSTRACT FROM AUTHOR]

The demand for the ubiquitous detection of gases in complex environments is driving the design of highly specific gas sensors for the development of the Internet of Things, such as indoor air quality testing, human exhaled disease detection, monitoring gas emissions, etc. The interaction between analytes and bioreceptors can described as a "lock-and-key", in which the specific catalysis between enzymes and gas molecules provides a new paradigm for the construction of high-sensitivity and -specificity gas sensors. The electrochemical method has been widely used in gas detection and in the design and construction of enzyme-based electrochemical gas sensors, in which the specificity of an enzyme to a substrate is determined by a specific functional domain or recognition interface, which is the active site of the enzyme that can specifically catalyze the gas reaction, and the electrode–solution interface, where the chemical reaction occurs, respectively. As a result, the engineering design of the enzyme electrode interface is crucial in the process of designing and constructing enzyme-based electrochemical gas sensors. In this review, we summarize the design of enzyme-based electrochemical gas sensors. We particularly focus on the main concepts of enzyme electrodes and the selection and design of materials, as well as the immobilization of enzymes and construction methods. Furthermore, we discuss the fundamental factors that affect electron transfer at the enzyme electrode interface for electrochemical gas sensors and the challenges and opportunities related to the design and construction of these sensors. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is an intractable disease requiring long-term treatment. S-adenosyl-L-methionine (SAMe), a natural substance, has antidepressant effects, but the exact effect remains unclear. This study examines the evidence concerning the efficacy of SAMe as a monotherapy or in combination with antidepressants. The PubMed, EMBASE, and Cochrane electronic databases were searched for meta-analyses of randomized controlled clinical trials (RCTs) until June 30, 2023. We performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria, with the aim to compare the effects of SAMe to those of a placebo or active agents, or SAMe combined with other antidepressants in the treatment of MDD. Fourteen trials, with a total of 1522 subjects, were included in this review. The daily dose of SAMe varied from 200 to 3200 mg and the study duration ranged between 2 and 12 weeks. The results of SAMe versus placebo as a monotherapy, SAMe versus imipramine or escitalopram as a monotherapy, and SAMe versus placebo as an adjunctive therapy, showed no significant difference in depression with SAMe compared to the comparison treatment. SAMe may provide relief of depression symptoms similar to imipramine or escitalopram. However, the results of the comparisons should be interpreted with caution due to the small number of studies and the large range of SAMe doses that were used in the included trials. Therefore, we recommend that patients discuss treatment options with their doctor before taking SAMe. [ABSTRACT FROM AUTHOR]

Upon SARS-CoV-2 infection, patients with severe forms of COVID-19 often suffer from a dysregulated immune response and hyperinflammation. Aberrant expression of cytokines and chemokines is associated with strong activation of the immunoregulatory transcription factor NF-κB, which can be directly induced by the SARS-CoV-2 protein NSP14. Here, we use NSP14 mutants and generated cells with host factor knockouts (KOs) in the NF-κB signaling pathways to characterize the molecular mechanism of NSP14-induced NF-κB activation. We demonstrate that full-length NSP14 requires methyltransferase (MTase) activity to drive NF-κB induction. NSP14 WT, but not an MTase-defective mutant, is poorly expressed and inherent post-translational instability is mediated by proteasomal degradation. Binding of SARS-CoV-2 NSP10 or addition of the co-factor S-adenosylmethionine (SAM) stabilizes NSP14 and augments its potential to activate NF-κB. Using CRISPR/Cas9-engineered KO cells, we demonstrate that NSP14 stimulation of canonical NF-κB activation relies on NF-κB factor p65/RELA downstream of the NEMO/IKK complex, while c-Rel or non-canonical RelB are not required to induce NF-κB transcriptional activity. However, NSP14 overexpression is unable to induce canonical IκB kinase β (IKKβ)/NF-κB signaling and in co-immunoprecipitation assays we do not detect stable associations between NSP14 and NEMO or p65, suggesting that NSP14 activates NF-κB indirectly through its methyltransferase activity. Taken together, our data provide a framework how NSP14 can augment basal NF-κB activation, which may enhance cytokine expression in SARS-CoV-2 infected cells. [ABSTRACT FROM AUTHOR]

S‐adenosylmethionine‐dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme‐catalyzed F‐methylation of carboxylate substrates produces F‐methyl esters that readily react with N‐ or S‐nucleophiles under physiological conditions. We demonstrate the applicability of this approach to the synthesis of small amides, hydroxamates, and thioesters, as well as to site‐specific protein modification and native chemical ligation. [ABSTRACT FROM AUTHOR]

S‐adenosylmethionine‐dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme‐catalyzed F‐methylation of carboxylate substrates produces F‐methyl esters that readily react with N‐ or S‐nucleophiles under physiological conditions. We demonstrate the applicability of this approach to the synthesis of small amides, hydroxamates, and thioesters, as well as to site‐specific protein modification and native chemical ligation. [ABSTRACT FROM AUTHOR]

Herein, we present a new Ag(I)-catalyzed three-component radical cascade reaction for the construction of 3-organoselenyl chromones from 2-methoxyaryl alkynones, Se powder and organic boronic acids. With 20 mol% of AgNO3 as a catalyst, 10 mol% of SDS as an additive and under an O2 atmosphere in 1,4-dioxane, a wide range of multi-functionalized 3-organoselenyl chromones have been achieved in good to excellent yields. This protocol features easy availability of starting materials, simple operation, high step-economy and high structural diversity of products. [ABSTRACT FROM AUTHOR]

Introduction: Angiogenic behaviour has been shown as highly versatile among Endothelial cells (ECs) causing problems of in vitro assays of angiogenesis considering their reproducibility. It is indispensable to investigate influencing factors of the angiogenic potency of ECs. Objective: The present study aimed to analyse the impact of knocking down triosephosphate isomerase (TPI) on in vitro angiogenesis and simultaneously on vimentin (VIM) and adenosylmethionine synthetase isoform type 2 (MAT2A) expression. Furthermore, native expression profiles of TPI, VIM and MAT2A in the course of angiogenesis in vitro were examined. Methods: Two batches of human dermal microvascular ECs were cultivated over 50 days and stimulated to undergo angiogenesis. A shRNA-mediated knockdown of TPI was performed. During cultivation, time-dependant morphological changes were detected and applied for EC-staging as prerequisite for quantifying in vitro angiogenesis. Additionally, mRNA and protein levels of all proteins were monitored. Results: Opposed to native cells, knockdown cells were not able to enter late stages of angiogenesis and primarily displayed a downregulation of VIM and an uprise in MAT2A expression. Native cells increased their TPI expression and decreased their VIM expression during the course of angiogenesis in vitro. For MAT2A, highest expression was observed to be in the beginning and at the end of angiogenesis. Conclusion: Knocking down TPI provoked expressional changes in VIM and MAT2A and a deceleration of in vitro angiogenesis, indicating that TPI represents an angiogenic protein. Native expression profiles lead to the assumption of VIM being predominantly relevant in beginning stages, MAT2A in beginning and late stages and TPI during the whole course of angiogenesis in vitro. [ABSTRACT FROM AUTHOR]

Despite the existing knowledge regarding the metabolic dysregulation of sulfur-containing amino acids in athletes during intense physical exercise, the precise role of S-adenosylmethionine and S-adenosylhomocysteine as biomarkers for adaptive changes remains unresolved. The challenge in addressing this issue lies in the substantial impact of matrix effects on quantitative outcomes under electrospray ionization conditions. To overcome this issue, we propose the adoption of a surrogate matrix for constructing calibration curves. In our study, a surrogate matrix was prepared by incubating pooled plasma from volunteers for 120 h at 37°C. By utilizing external calibration with a surrogate matrix and the standard addition method, we achieved a maximum concentration variation of 4 ng mL–1 for the determination of both S-adenosylmethionine and S-adenosylhomocysteine. [ABSTRACT FROM AUTHOR]

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the efficacy of glucosamine-sulfate (GS), nonanimal chondroitin-sulfate (naCS), and S-adenosylmethionine (SAMe) combination on ultrasound findings, inflammation, pain, and functionality in knee osteoarthritis. Patients and methods: In the prospective, randomized, double-blind, placebo-controlled pilot study conducted between August 2019 and November 2019, 120 participants (28 males, 92 females; mean age: 66.4±7.9 years; range, 42.4 to 74.5 years) were randomized at a 1:1:1 ratio to the placebo group, the first experimental group (a combination of GS, naCS, and SAMe was administered to the experimental groups. The first experimental group received 375 mg of GS, 300 mg of naCS, and 100 mg of SAMe, whereas the second experimental group received 750 mg of GS, 600 mg of naCS, and 200 mg of SAMe). Laboratory (erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, interleukin [IL]-1β, IL-6, IL-17), clinical (Visual Analog Scale [VAS], short form health survey [SF-36], the Western Ontario and McMaster Universities Arthritis Index [WOMAC], and the Tegner Lysholm Knee Scoring Scale [TLKS]), and musculoskeletal ultrasound (MSUS) assessments were performed at baseline and after three and six months. Results: A minor increase was observed in the second experimental group after six months using ultrasonography to evaluate articular cartilage thickness (p<0.05). The investigational product's superiority in reducing osteoarthritis ultrasonographic findings was not proven. A moderately negative association was found between cartilage thickness and VAS scores at baseline (ρ=-0.36, p<0.01), while the presence of massive osteophytes on MSUS showed a low to moderate association with all clinical outcomes. There was no difference in the delta changes between groups for the VAS, TLKS, WOMAC, and SF-36. The only serum inflammatory marker outside the reference range was IL-1β, but no significant changes were observed after six months. Conclusion: According to the results of our investigation, treatment for knee osteoarthritis should be evaluated using more objective outcomes. The most important conclusion of our study is that IP may result in a slight increase in articular cartilage thickness, which was associated with a decrease in pain intensity at baseline. Clarification of the potential influence of this combination on radiographic progression and laboratory markers of inflammation requires further exploration. [ABSTRACT FROM AUTHOR]

In this article, the enrichment of graphene and graphene oxide with free radicals through their functionalization with tyrosine is studied. In contrast with what is commonly observed in the functionalization of graphene with organic species the addition of tyrosine radicals on to the graphene substrate led to a remarkable increase of the aromatic character as indicated by the spectroscopic data. Similar behaviour was observed for the functionalization of graphene oxide. In addition, a brief analysis of the tyrosine functionalized graphene with EPR spectroscopy showed a remarkable enhancement of the spin density that could be useful in spintronics. [ABSTRACT FROM AUTHOR]

Background: Seleno-methylselenocysteine (SeMCys) is an effective component of selenium supplementation with anti-carcinogenic potential that can ameliorate neuropathology and cognitive deficits. In a previous study, a SeMCys producing strain of Bacillus subtilis GBACB was generated by releasing feedback inhibition by overexpression of cysteine-insensitive serine O-acetyltransferase, enhancing the synthesis of S-adenosylmethionine as methyl donor by overexpression of S-adenosylmethionine synthetase, and expressing heterologous selenocysteine methyltransferase. In this study, we aimed to improve GBACB SeMCys production by synthesizing methylmethionine as a donor to methylate selenocysteine and by inhibiting the precursor degradation pathway. Results: First, the performance of three methionine S-methyltransferases that provide methylmethionine as a methyl donor for SeMCys production was determined. Integration of the NmMmt gene into GBACB improved SeMCys production from 20.7 to 687.4 μg/L. Next, the major routes for the degradation of selenocysteine, which is the precursor of SeMCys, were revealed by comparing selenocysteine hyper-accumulating and non-producing strains at the transcriptional level. The iscSB knockout strain doubled SeMCys production. Moreover, deleting sdaA, which is responsible for the degradation of serine as a precursor of selenocysteine, enhanced SeMCys production to 4120.3 μg/L. Finally, the culture conditions in the flasks were optimized. The strain was tolerant to higher selenite content in the liquid medium and the titer of SeMCys reached 7.5 mg/L. Conclusions: The significance of methylmethionine as a methyl donor for SeMCys production in B. subtilis is reported, and enhanced precursor supply facilitates SeMCys synthesis. The results represent the highest SeMCys production to date and provide insight into Se metabolism. [ABSTRACT FROM AUTHOR]

The reaction mechanism of ClO 2 -mediated TEMPO oxidation was investigated by EPR spectroscopy and UV–Vis spectroscopy in the context of an alternative TEMPO sequence for cellulose fiber oxidation. Without the presence of a cellulosic substrate, a reversibility between TEMPO and its oxidation product, TEMPO + , was displayed, with an effect of the pH and reagent molar ratios. The involvement of HOCl and Cl − , formed as byproducts in the oxidation mechanism, was also evidenced. Trapping HOCl partly inhibits the reaction, whereas adding methylglucoside, a cellulose model compound, inhibits the reversibility of the reaction to TEMPO. [ABSTRACT FROM AUTHOR]

Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH. Maleimide stabilizes the NO radicals in the cell lysates by consumption of the NADPH/NADH that are essential for the enzymes involved in destabilizing NO radicals, instead of serving as the solo thiol scavenger. The maleimide treatment retains the crowding properties of the intracellular components and allows to perform long‐time EPR measurements of NO labeled biomolecules close to the intracellular conditions. The strategy of maleimide treatment on cell lysates for the EPR applications has been demonstrated on double electron‐electron resonance (DEER) measurements on a number of NO labeled protein samples. The method opens a broad application range for the NO labeled biomolecules by EPR in conditions that resemble the intracellular milieu. [ABSTRACT FROM AUTHOR]

We examined standard clinical and laboratory biochemical parameters, as well as the levels of aminothiols in the blood and urine (homocysteine (Hcy), cysteine (Cys), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)) via capillary electrophoresis in patients with CKD at stages II–V. Patient outcomes were assessed after five years. To complete forecasting, correlation and ROC analysis were performed. It was found that the levels of Cys and Hcy in blood plasma were earlier markers of CKD starting from stage II, while the levels of SAM and SAM/SAH in urine made it possible to differentiate between CKD at stages II and III. Blood plasma Hcy and urinary SAM and SAM/SAH correlated with mortality, but plasma Hcy concentrations were more significant. Thus, plasma Hcy, urine SAM, and SAM/SAH can be considered to be potential diagnostic and prognostic markers in patients with CKD. [ABSTRACT FROM AUTHOR]

Protein methylation is mainly observed in lysine, arginine and histidine residues. Histidine methylation occurs at one of two different nitrogen atoms of the imidazole ring, producing N τ-methylhistidine and N π-methylhistidine, and it has recently attracted attention with the identification of SETD3, METTL18 and METTL9 as catalytic enzymes in mammals. Although accumulating evidence had suggested the presence of more than 100 proteins containing methylated histidine residues in cells, much less information has been known regarding histidine-methylated proteins than lysine- and arginine-methylated ones, because no method has been developed to identify substrates for histidine methylation. Here, we established a method to screen novel target proteins for histidine methylation, using biochemical protein fractionation combined with the quantification of methylhistidine by LC-MS/MS. Interestingly, the differential distribution pattern of N τ-methylated proteins was found between the brain and skeletal muscle, and identified γ-enolase where the His-190 at the N τ position is methylated in mouse brain. Finally, in silico structural prediction and biochemical analysis showed that the His-190 in γ-enolase is involved in the intermolecular homodimeric formation and enzymatic activity. In the present study, we provide a new methodology to find histidine-methylated proteins in vivo and suggest an insight into the importance of histidine methylation. [ABSTRACT FROM AUTHOR]

Covering: from 2000 up to the very early part of 2023 S-Adenosyl- L -methionine (SAM) is a naturally occurring trialkyl sulfonium molecule that is typically associated with biological methyltransfer reactions. However, SAM is also known to donate methylene, aminocarboxypropyl, adenosyl and amino moieties during natural product biosynthetic reactions. The reaction scope is further expanded as SAM itself can be modified prior to the group transfer such that a SAM-derived carboxymethyl or aminopropyl moiety can also be transferred. Moreover, the sulfonium cation in SAM has itself been found to be critical for several other enzymatic transformations. Thus, while many SAM-dependent enzymes are characterized by a methyltransferase fold, not all of them are necessarily methyltransferases. Furthermore, other SAM-dependent enzymes do not possess such a structural feature suggesting diversification along different evolutionary lineages. Despite the biological versatility of SAM, it nevertheless parallels the chemistry of sulfonium compounds used in organic synthesis. The question thus becomes how enzymes catalyze distinct transformations via subtle differences in their active sites. This review summarizes recent advances in the discovery of novel SAM utilizing enzymes that rely on Lewis acid/base chemistry as opposed to radical mechanisms of catalysis. The examples are categorized based on the presence of a methyltransferase fold and the role played by SAM within the context of known sulfonium chemistry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. OBJECTIVES: This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. METHODS: Dams were exposed to 0.15, 1.5, and 15 mg/L NaAsO2 throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to NaAsO2 (2 μM) to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. 푁6-Methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation–quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography– tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro As+3 methyltransferase (As3MT) knockdown or SAM supplementation and in vivo folic acid (FA) supplementation were used to evaluate the protective effect. A case–control study verified the findings. RESULTS: Sizes of fetuses (exposed to 1.5 and 15 mg/L NaAsO2) and placentas (exposed to 15 mg/L NaAsO2) were lower in As-exposed mice. More glycogen+ trophoblasts accumulated and the expression of markers of interstitial invasion was lower in the 15 mg/L NaAsO2-exposed mouse group in comparison with control. Placental RNA sequencing identified cysteine-rich angiogenic inducer 61 (Cyr61) as a candidate gene of interest. Mechanistically, mice and cells exposed to As had lower protein expression of CYR61, and this was attributed to a lower incidence of Cyr61 m6A. Furthermore, cells exposed to As had lower methyltransferase activity, suggesting that this could be the mechanism by which Cyr61 m6A was affected. Depletion of intracellular SAM, a cofactor for m6A methyltransferase catalytic domain, partially contributed to As-induced methyltransferase activity reduction. Either As3MT knockdown or SAM supplementation attenuated As-induced Cyr61 m6A down-regulation. In mice, FA supplementation rescued As-induced defective trophoblastic invasion and FGR. In humans, a negative correlation between maternal urinary As and plasma CYR61 was observed in infants who were small for gestational age. DISCUSSION: Using in vitro and in vivo models, we found that intracellular SAM depletion–mediated Cyr61 m6A down-regulation partially contributed to As-induced defective trophoblastic invasion and FGR. [ABSTRACT FROM AUTHOR]

S-adenosylmethionine decarboxylase (AdoMetDC/SpeD) is a key polyamine biosynthetic enzyme required for conversion of putrescine to spermidine. Autocatalytic self-processing of the AdoMetDC/SpeD proenzyme generates a pyruvoyl cofactor from an internal serine. Recently, we discovered that diverse bacteriophages encode AdoMetDC/SpeD homologs that lack AdoMetDC activity and instead decarboxylate L-ornithine or L-arginine. We reasoned that neofunctionalized AdoMetDC/ SpeD homologs were unlikely to have emerged in bacteriophages and were probably acquired from ancestral bacterial hosts. To test this hypothesis, we sought to identify candidate AdoMetDC/SpeD homologs encoding L-ornithine and L-arginine decarboxylases in bacteria and archaea. We searched for the anomalous presence of AdoMetDC/SpeD homologs in the absence of its obligatory partner enzyme spermidine synthase, or the presence of two AdoMetDC/SpeD homologs encoded in the same genome. Biochemical characterization of candidate neofunctionalized genes confirmed lack of AdoMetDC activity, and functional presence of L-ornithine or L-arginine decarboxylase activity in proteins from phyla Actinomycetota, Armatimonadota, Planctomycetota, Melainabacteria, Perigrinibacteria, Atribacteria, Chloroflexota, Sumerlaeota, Omnitrophota, Lentisphaerota, and Euryarchaeota, the bacterial candidate phyla radiation and DPANN archaea, and the δ-Proteobacteria class. Phylogenetic analysis indicated that L-arginine decarboxylases emerged at least three times from AdoMetDC/SpeD, whereas L-ornithine decarboxylases arose only once, potentially from the AdoMetDC/SpeD-derived L-arginine decarboxylases, revealing unsuspected polyamine metabolic plasticity. Horizontal transfer of the neofunctionalized genes appears to be the more prevalent mode of dissemination. We identified fusion proteins of bona fide AdoMetDC/SpeD with homologous L-ornithine decarboxylases that possess two, unprecedented internal protein-derived pyruvoyl cofactors. These fusion proteins suggest a plausible model for the evolution of the eukaryotic AdoMetDC. [ABSTRACT FROM AUTHOR]

Intracellular calcium signaling is essential for many cellular processes, including store-operated Ca2+ entry (SOCE), which is initiated by stromal interaction molecule 1 (STIM1) detecting endoplasmic reticulum (ER) Ca2+ depletion. STIM1 is also activated by temperature independent of ER Ca2+ depletion. Here we provide evidence, from advanced molecular dynamics simulations, that EF-SAM may act as a true temperature sensor for STIM1, with the prompt and extended unfolding of the hidden EF-hand subdomain (hEF) even at slightly elevated temperatures, exposing a highly conserved hydrophobic Phe108. Our study also suggests an interplay between Ca2+ and temperature sensing, as both, the canonical EF-hand subdomain (cEF) and the hidden EF-hand subdomain (hEF), exhibit much higher thermal stability in the Ca2+-loaded form compared to the Ca2+-free form. The SAM domain, surprisingly, displays high thermal stability compared to the EF-hands and may act as a stabilizer for the latter. We propose a modular architecture for the EF-hand-SAM domain of STIM1 composed of a thermal sensor (hEF), a Ca2+ sensor (cEF), and a stabilizing domain (SAM). Our findings provide important insights into the mechanism of temperature-dependent regulation of STIM1, which has broad implications for understanding the role of temperature in cellular physiology. [ABSTRACT FROM AUTHOR]

Herein, the effect of intermediate layers for high‐speed InGaN growth using trihalide vapor‐phase epitaxy (THVPE) on ScAlMgO4 (SAM) is investigated. The coverage and thickness of the intermediate layer have a significant impact on both composition and crystalline quality. Herein, InGaN is successfully fabricated with 17% of indium on SAM in a lattice‐matched state employing THVPE, showing the X‐ray rocking curve full width at half maximum values less than 1000 arcsec, in a two‐step growth. THVPE is used to indicate the possibility of fabricating high‐quality InGaN quasi‐substrate with high indium composition. [ABSTRACT FROM AUTHOR]

Enzymatic methyltransferase reactions are of crucial importance for cell metabolism. S-Adenosyl-L-methionine (AdoMet) is a main donor of the methyl group. DNA, RNA, proteins, and low-molecular-weight compounds are substrates of methyltransferases. In mammals, DNA methyltransferase Dnmt3a de novo methylates the C5 position of cytosine residues in CpG sequences in DNA. The methylation pattern is one of the factors that determine the epigenetic regulation of gene expression. Here, interactions with the catalytic domain of Dnmt3a was for the first time studied for phosphonous and phosphonic analogs of AdoMet and S-adenosyl-L-homocysteine (AdoHcy), in which the carboxyl group was substituted for respective phosphorus-containing group. These AdoMet analogs were shown to be substrates of Dnmt3a, and the methylation efficiency was only halved as compared with that of natural AdoMet. Both phosphorus-containing analogs of AdoHcy, which is a natural methyltransferase inhibitor, showed similar inhibitory activities toward Dnmt3a and were approximately four times less active than AdoHcy. The finding that the phosphonous and phosphonic analogs are similar in activity was quite unexpected because the geometry and charge of their phosphorus-containing groups differ substantially. The phosphorus-containing analogs of AdoMet and AdoHcy are discussed as promising tools for investigation of methyltransferases. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that supplementation of S-adenosylmethionine (SAM) can improve cognitive function in animals and humans, although the outcomes are not always inconsistent. Objective: We conducted a systematic review and meta-analysis to evaluate the correlation between SAM supplementation and improved cognitive function. Methods: We searched studies in the PubMed, Cochrane Library, Embase, Web of Science, and Clinical Trials databases from January 1, 2002 to January 1, 2022. Risk of bias was assessed using the Cochrane risk of bias 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation risk of bias (animal studies) tools; and evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. STATA software was employed to perform meta-analysis, and the random-effects models was used to evaluate the standardized mean difference with 95% confidence intervals. Results: Out of the 2,375 studies screened, 30 studies met the inclusion criteria. Meta-analyses of animal (p = 0.213) and human (p = 0.047) studies showed that there were no significant differences between the SAM supplementation and control groups. The results of the subgroup analyses showed that the animals aged ≤8 weeks (p = 0.027) and the intervention duration >8 weeks (p = 0.009) were significantly different compared to the controls. Additionally, the Morris water maze test (p = 0.005) used to assess the cognitive level of the animals revealed that SAM could enhance spatial learning and memory in animals. Conclusion: SAM supplementation showed no significant improvement in cognition. Therefore, further studies are needed to assess the effectiveness of SAM supplementation. [ABSTRACT FROM AUTHOR]

DNA methylation, the main epigenetic modification regulating gene expression, plays a role in the pathophysiology of neurodegeneration. Previous evidence indicates that 5′-flanking hypomethylation of PSEN1, a gene involved in the amyloidogenic pathway in Alzheimer's disease (AD), boosts the AD-like phenotype in transgenic TgCRND8 mice. Supplementation with S-adenosylmethionine (SAM), the methyl donor in the DNA methylation reactions, reverts the pathological phenotype. Several studies indicate that epigenetic signatures, driving the shift between normal and diseased aging, can be acquired during the first stages of life, even in utero, and manifest phenotypically later on in life. Therefore, we decided to test whether SAM supplementation during the perinatal period (i.e., supplementing the mothers from mating to weaning) could exert a protective role towards AD-like symptom manifestation. We therefore compared the effect of post-weaning vs. perinatal SAM treatment in TgCRND8 mice by assessing PSEN1 methylation and expression and the development of amyloid plaques. We found that short-term perinatal supplementation was as effective as the longer post-weaning supplementation in repressing PSEN1 expression and amyloid deposition in adult mice. These results highlight the importance of epigenetic memory and methyl donor availability during early life to promote healthy aging and stress the functional role of non-CpG methylation. [ABSTRACT FROM AUTHOR]

Deciphering the crosstalk between metabolic reprogramming and epigenetic regulation is a promising strategy for cancer therapy. In this study, we discovered that the gluconeogenic enzyme PCK1 fueled the generation of S-adenosylmethionine (SAM) through the serine synthesis pathway. The methyltransferase SUV39H1 catalyzed SAM, which served as a methyl donor to support H3K9me3 modification, leading to the suppression of the oncogene S100A11. Mechanistically, PCK1 deficiency-induced oncogenic activation of S100A11 was due to its interaction with AKT1, which upregulated PI3K/AKT signaling. Intriguingly, the progression of hepatocellular carcinoma (HCC) driven by PCK1 deficiency was suppressed by SAM supplement or S100A11 KO in vivo and in vitro. These findings reveal the availability of the key metabolite SAM as a bridge connecting the gluconeogenic enzyme PCK1 and H3K9 trimethylation in attenuating HCC progression, thus suggesting a potential therapeutic strategy against HCC. [ABSTRACT FROM AUTHOR]

S-adenosylmethionine (SAM) is the methyl donor for sitespecific methylation reactions on histone proteins, imparting key epigenetic information. During SAM-depleted conditions that can arise from dietary methionine restriction, lysine diand tri-methylation are reduced while sites such as Histone-3 lysine-9 (H3K9) are actively maintained, allowing cells to restore higher-state methylation upon metabolic recovery. Here, we investigated if the intrinsic catalytic properties of H3K9 histone methyltransferases (HMTs) contribute to this epigenetic persistence. We employed systematic kinetic analyses and substrate binding assays using four recombinant H3K9 HMTs (i.e., EHMT1, EHMT2, SUV39H1, and SUV39H2). At both high and low (i.e., sub-saturating) SAM, all HMTs displayed the highest catalytic efficiency (kcat/KM) for monomethylation compared to di- and trimethylation on H3 peptide substrates. The favored monomethylation reaction was also reflected in kcat values, apart from SUV39H2 which displayed a similar kcat regardless of substrate methylation state. Using differentially methylated nucleosomes as substrates, kinetic analyses of EHMT1 and EHMT2 revealed similar catalytic preferences. Orthogonal binding assays revealed only small differences in substrate affinity across methylation states, suggesting that catalytic steps dictate the monomethylation preferences of EHMT1, EHMT2, and SUV39H1. To link in vitro catalytic rates with nuclear methylation dynamics, we built a mathematical model incorporating measured kinetic parameters and a time course of mass spectrometry-based H3K9 methylation measurements following cellular SAM depletion. The model revealed that the intrinsic kinetic constants of the catalytic domains could recapitulate in vivo observations. Together, these results suggest catalytic discrimination by H3K9 HMTs maintains nuclear H3K9me1, ensuring epigenetic persistence after metabolic stress. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clone S‐adenosylmethionine synthase (BtSAMS) from Balsas teosinte (Zea mays ssp. parviglumis) and investigate its function via heterologous expression in Arabidopsis plants. The BtSAMS coding sequence was cloned and its length is 1185 bp. The expression of BtSAMS in Z. mays ssp. parviglumis was a 12.2‐fold increase after aphid infestation. Transgenic Arabidopsis plants heterologously expressing BtSAMS were generated and their morphological characters were observed. A prolonged vegetative growth period was displayed by BtSAMS‐OX plants. The more and longer trichomes were observed on the upper surface of BtSAMS seedlings. The ethylene content in BtSAMS‐OX plants was not significantly different compared with the untransformed controls. These BtSAMS‐OX transgenic plants showed greater resistance to peach aphids compared with the untransformed control plants. Peach aphids appeared to prefer the untransformed controls in that aphids number reduced by more than 50% on BtSAMS plants compared to controls. When sprayed with the insecticide avi‐imidacloprid, the number of peach aphids decreased on BtSAMS‐OX plants and untransformed controls by 91.6% and 80.5%, respectively. Peach aphids also showed lower reproduction ability when forced to feed on the transgenic plants. The number of newly born nymphs on BtSAMS plants was less than 50% of that on the untransformed control. We therefore propose that BtSAMS may be a suitable candidate gene to confer resistance to peach aphids in plants. [ABSTRACT FROM AUTHOR]

N-terminal methionine excision from newly synthesized proteins, catalyzed cotranslationally by methionine aminopeptidases (METAPs), is an essential and universally conserved process that plays a key role in cell homeostasis and protein biogenesis. However, how METAPs interact with ribosomes and how their cleavage specificity is ensured is unknown. We discovered that in eukaryotes the nascent polypeptide-associated complex (NAC) controls ribosome binding of METAP1. NAC recruits METAP1 using a long, flexible tail and provides a platform for the formation of an active methionine excision complex at the ribosomal tunnel exit. This mode of interaction ensures the efficient excision of methionine from cytosolic proteins, whereas proteins targeted to the endoplasmic reticulum are spared. Our results suggest a broader mechanism for how access of protein biogenesis factors to translating ribosomes is controlled. [ABSTRACT FROM AUTHOR]

Radical S-adenosylmethionine (SAM) enzymes use a site-differentiated [4Fe-4S] cluster and SAM to initiate radical reactions through liberation of the 5′-deoxyadenosyl (5′-dAdo•) radical. They form the largest enzyme superfamily, with more than 700,000 unique sequences currently, and their numbers continue to grow as a result of ongoing bioinformatics efforts. The range of extremely diverse, highly regio- and stereo-specific reactions known to be catalyzed by radical SAM superfamily members is remarkable. The common mechanism of radical initiation in the radical SAM superfamily is the focus of this review. Most surprising is the presence of an organometallic intermediate, Ω, exhibiting an Fe–C5′-adenosyl bond. Regioselective reductive cleavage of the SAM S–C5′ bond produces 5′-dAdo• to form Ω, with the regioselectivity originating in the Jahn–Teller effect. Ω liberates the free 5′-dAdo• as the catalytically active intermediate through homolysis of the Fe–C5′ bond, in analogy to Co–C5′ bond homolysis in B12, which was once viewed as biology's choice of radical generator. [ABSTRACT FROM AUTHOR]

Visible‐light‐driven C−C bond formation utilizing ketyl radical (Cketyl) species has attracted increasing attention recently, as it provides a direct route for the synthesis of complex molecules. However, the most‐developed homogeneous photocatalytic systems for the generation and utilization of ketyl radicals usually entail noble metal‐based (e. g. Ru and Ir) photosensitizers, which suffer from not only high cost but also potential degradation and hence pose challenges in product separation and purification. In contrast, readily accessible, inexpensive, and recyclable semiconductors represent a class of attractive and alternative photocatalysts but remain much less explored for photocatalytic ketyl radical initiated C−C bond formation. This work demonstrates that a wide range of industrially important chemicals, including substituted chromanes and tertiary alcohols, can be produced on ZnIn2S4 under visible light irradiation through intramolecular cyclization (Cketyl−Csp2) and intermolecular cross‐coupling (Cketyl−Csp3) reactions, respectively, using ketyl radicals. A suite of experimental studies aided by computational investigation were carried out to shed light on the mechanistic insights of these two types of ketyl radical initiated C−C coupling reactions on ZnIn2S4. [ABSTRACT FROM AUTHOR]

Harnessing a bis(selenomethyl)tetrathiafulvalene (TTF) derivative as a donor, conducting charge transfer (CT) salts are realized thanks to original packing structures supported by chalcogen bonding (ChB) interactions. Specifically, reaction of EDT-TTF(SeMe)2 (EDT = ethylenedithio) with an acceptor, 2,5-difluoro-7,7,8,8-tetracyanoquinodimethane (F2TCNQ), afforded two polymorphs of 1 : 1 CT salts, α- and β-[EDT-TTF(SeMe)2](F2TCNQ). The donor and the acceptor molecules in both polymorphs organize into segregated and uniform stacks. Based on the structure, the α-salt shows a quasi-complete CT while the β-salt shows a partial CT with ρ ∼±0.8. The oxidation of TTF activates the σ-hole on Se atoms to be engaged in highly linear ChB interactions with the N atoms on F2TCNQ. The formation of directional ChB interactions resulted in original packing structures of the donor and the acceptor stacks that are distinct between α- and β-salts. In particular, the ChB motif observed in the β-salt allows F2TCNQ molecules within the stack to be closer than those in the α-salt. Consequently, the α-salt is a semi-conductor, while the β-salt shows metallic behaviour with a two-step metal-to-insulator (MI) transition. Moreover, the observed MI transition temperature in the β-salt (180 K) is substantially higher than that in other known CT salts, likely owing to the 3D coupling of the modulation in different chains brought about by the –SeMe substituents. [ABSTRACT FROM AUTHOR]

Both organic radicals and organoboron reagents have been broadly investigated, but the combination of them via direct C−H borylation as organic radical building blocks has never been achieved. Herein, a series of organoradical boron reagents, such as TTM‐Bpin and TTM‐BOH, were synthesized through the key step of C−H borylation of substrate TTM‐H ((2,6‐dichlorophenyl) bis(2,4,6‐trichlorophenyl)methyl) radical for the first time. They are air stable enough to be stored in the solid state for several months under dark conditions, and fully investigated through single crystal analysis, EPR and DFT calculations. Furthermore, they can smoothly work in the standard Suzuki–Miyaura coupling (SMC) reaction with retention of the carbon radical center. Meanwhile, these radical species bearing different boron units display fluorescent character and are potentially applied for the collective synthesis of luminescent organic radicals, as well as other functionalized open‐shell materials. [ABSTRACT FROM AUTHOR]