Stable Amino Research Articles

Hydroxyl and amino co-modified imidazole based ionic liquid functionalized TS-1 molecular sieve for efficient CO2 capture

Herein, an integrative solid adsorbent of [AHOPMIm]Cl with hydroxyl and amino groups functional sites modified TS-1 molecular sieve is designed and fabricated for efficient CO2 adsorption. The optimal [AHOPMIm]Cl/TS-1 exhibits 73% enhancement in CO2 adsorption capacity compared with the TS-1 molecular sieve, even outperforming other state of the art adsorbent systems. The greatly improved CO2 adsorption capacity is mainly attributed to the strong adsorption of amino groups on the ionic liquids surface, which can form low-temperature stable amino ester species. Moreover, it is preserved that the hydroxyl groups on the surface of ionic liquids can form stable hydrogen bonds with oxygen atoms in CO2, and coordinate with amino groups to capture CO2 from different directions based on in situ DRIFTS and DFT. The porous TS-1 molecular sieve provides a structural basis for the uniform dispersion, effective support, and enhanced CO2 adsorption capacity of ionic liquids. A new design concept for constructing ionic liquid-based composite adsorbent with dual functional sites using TS-1 molecular sieve as a carrier is provided, and the avenues for efficient CO2 adsorption are paved.

Exopeptidase combination enhances the degradation of isotopically labelled gluten immunogenic peptides in humans.

Celiac disease is a common autoimmune-like enteropathy caused by an aberrant response to incompletely digested dietary gluten. Gluten immunogenic peptides including the immunodominant 33-mer are thought to be resistant to proteolytic digestion by human gastrointestinal peptidases. We developed a novel enzyme therapy approach to support gluten peptide digestion using a combination of two tandem-acting exopeptidases, AMYNOPEP, that complement the intrinsic enzymatic activity of intestinal brush border enterocytes. We evaluated the effects of AMYNOPEP supplementation on 33-mer degradation in vitro and in vivo. In a cross-over clinical study, healthy volunteers with no gastrointestinal disorders were given stable isotope (SI) labelled 33-mer peptides in the presence of varying peptide substrates and caloric loads, with and without AMYNOPEP. 33-mer degradation products (SI-labelled single amino acids) were measured in the blood plasma using LC-MS/MS. AMYNOPEP achieved rapid, complete amino-to-carboxyl terminal degradation of the 33-mer in vitro, generating single amino acids and dipeptides. In healthy volunteers, AMYNOPEP supplementation significantly increased 33-mer degradation and absorption of SI-labelled amino acids even in the presence of competing substrates. Specifically, we observed a 2.8-fold increase in the Cmax of stable isotope-labelled amino acids in the presence of wheat gluten. The absorption kinetics of labelled amino acids derived from 33-mer digestion with AMYNOPEP closely resembled that of SI-labelled X-Proline dipeptides administered without enzyme supplementation, highlighting the rapid hydrolytic activity of AMYNOPEP on polypeptides. AMYNOPEP achieved complete degradation of the 33-mer into single amino acids and dipeptides in vitro and significantly improved 33-mer degradation kinetics in healthy volunteers, as measured by labelled amino acid detection, warranting further investigation into the potential therapeutic benefits of exopeptidase combinations for patients with gluten-related health disorders including celiac disease.

Metabolic kinetics and muscle and brain health markers in older adults, and the role of age and presence of chronic morbidities: A large cross-sectional cohort study

Background & aimsOlder adults are at risk for muscle and cognitive function decline during advanced aging, but the underlying metabolic mechanisms and the role of aging-associated chronic morbidities remain unclear. In the present study, we examined whether protein and amino acid kinetics in older adults with and without chronic morbidities are different when 50-70 and 70-90 of age and related to markers of muscle and brain health declines. MethodsIn a large cross-sectional observational study, 575 older adults from 12 trials (2014-2022) were stratified based on their age (50-70y vs. 70-95y) and the presence of chronic morbidities. The main outcomes were whole-body production (WBP) and interconversions of amino acids by stable amino acid tracers, body composition, and muscle and cognitive performance. Additionally, the association between metabolic markers and muscle and brain health was assessed. ResultsOverall lower muscle strength, muscle and fat mass, and cognitive function (p<0.03), but no mood disturbances, were found in 70-95y compared to 50-70y older adults. Presence of morbidities was associated with lower muscle strength and mass, and cognitive function, but higher visceral adipose tissue, and mood disturbances (p<0.05). Aging was associated with suppressed WBP of most amino acids, de novo arginine production, and net protein breakdown, but higher myofibrillar protein breakdown (p<0.007). Presence of morbidities was associated with lower WBP of glutamine, glutamate, histidine, isoleucine, phenylalanine, tyrosine, and net protein breakdown, and higher WBP of valine and taurine (p<0.04). Age showed significant negative correlations with WBP of nearly all amino acids, de novo arginine production and net protein breakdown (r: [-0.407, -0.136], p<0.01) but a positive correlation with WBP of myofibrillar protein breakdown (r=0.133, p=0.009). Lean mass showed positive correlations with de novo arginine production and net protein breakdown and WBP of all amino acids except for isoleucine (r: [0.16, 0.799], p<0.005). Worse cognitive performance was positively associated with WBP of tau-methylhistidine and taurine (r: [0.13, 0.141], p<0.04), but negatively associated with WBP of glycine, valine, and net protein breakdown (r: [-0.222, -0.135], p<0.05). ConclusionComprehensive phenotyping of a large group of older adults revealed differences in metabolic health in response to advanced aging and chronic morbidities. Poor muscle health accompanied by advanced aging was associated with overall metabolic downregulation, except for enhanced myofibrillar (muscle) protein breakdown. Presence of chronic morbidities was further associated with disturbed muscle health, mood, arginine, and taurine pathways, and higher visceral adipose tissue. Therefore, different phenotypes among older adults need to be considered when evaluating therapeutic approaches to improve muscle and brain health.

Phenylalanine-embedded carbazole-based fluorescent ‘turn-off’ chemosensor for the detection of metal ions

Fluorescent chemosensors are highly important for various applications including medical diagnostics, environmental monitoring, and industrial processing. Significant advancements have been made to produce sensors capable of detecting biologically and environmentally relevant ions. Specifically, carbazole-derived fluorophores are chemically stable agents with the ability to detect anions, cations, and small bioorganic molecules. However, most carbazole-based fluorescent probes for the detection of metal ions are Schiff bases and require stringent pH control to prevent hydrolysis. On the other hand, amide-based sensors that utilize stable amino acid scaffolds provide a robust sensing platform as well as a soft-chemical environment for detecting both soft and heavy metal ions. Herein, we explored an aromatic amino acid Phe-containing carbazole-based “turn-off” fluorescent chemosensor to improve the sensor specificity using π-conjugation and additional binding sites. The structure of the novel chemosensor was characterized by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. In addition, the sensing properties towards metal ions were studied using UV–vis and fluorescence spectroscopy. Among the various metal ions tested, the chemosensor showed high selectivity and sensitivity towards Co2+, Ni2+, and Cu2+ ions. The detection limits for Co2+, Ni2+, and Cu2+ ions were found to be 4.78 µM, 3.50 µM, and 5.17 µM respectively. Furthermore, the interaction of Phe-amino-carbazole with the various tested metal ions resulted in a flakes-like supramolecular structure, similar to the native Phe-amino-carbazole, whereas the interaction of the designed chemosensor with the Pb2+ metal ion resulted in a uniform 3D-circular disc-like supramolecular structure, as confirmed by electron microscopy experiment. This highlights the potential of the Phe-containing carbazole-derived chemosensor for the detection of multiple cations with a decrease in the fluorescence response with a lower detection limit.

Characteristics of organic amendments induce diverse microbial metabolisms for exogenous C turnover in Mollisols

The response of microbial community to organic amendments is closely related to the amendment-derived carbon (C) turnover, which in turn influences the enhancement of soil organic C, including the quantity and quality. The objective of this study was to quantify the decomposition and retention of exogenous C derived from amendments, and to identify the microbial regulatory mechanisms of exogenous C turnover in response to the characteristics of organic amendments. The 13C-labelled glucose, straw and biochar, characterizing organic amendments with high, medium and low labilities, respectively, were used to conduct a 90-day incubation experiment, in conjunction with stable isotope probing technology and amino sugar molecular biomarkers. It was found that the cumulative mineralization of amendment-derived C increased with increasing the corresponding lability of organic amendment, and the decompositions of the added glucose, straw and biochar, expressed as a percentage of the initially added C, were 53.6 %, 37.0 %, and 0.6 %, respectively. Among all treatments, the addition of straw significantly enhanced the total dissolved organic C (DOC) concentration and its ratio to total organic C by increasing the input of exogenous DOC and reducing the decomposition of native soil DOC. The exogenous C use efficiency by microorganisms was significantly enhanced with decreasing the amendment lability, and showed a positive correlation with the total amendment-derived C. However, the microbial growth efficiency was the highest when straw was added, and was closely related to the concentration of amendment-derived DOC. Different functional groups of soil microbes exhibited distinct capacities to metabolize various organic amendments. Generally, the incorporation of amendment-derived C into microbial biomass was significantly affected by fungi and gram-positive (G+) bacteria, while the relative contributions of microbial communities incorporating amendment-derived C into necromass were decreased in the order of gram-negative (G−) bacteria > fungi > actinomycetes > G+ bacteria. From the perspective of microbial metabolism, the larger incorporations of exogenous C into microbial biomass and necromass were observed in the soil with mediumly labile amendment, which contributed to enhance the quantity and quality of organic C in soil. These results would be informative to optimize the organic amendment strategy for integrated soil fertility management.

Removal of Pb(II) pollution by algae-Fe-Ni magnetic nanocomposite

A magnetic nanocomposite material was synthesized by combining Chaetomorpha Algae with a Fe–Ni alloy. The dry algae, Fe, and Ni were mechanically alloyed using a ball milling technique in an argon atmosphere. The resulting Algae-Fe-Ni Magnetic Nanocomposite (AFNMN) was characterized using various analytical techniques, including particle size distribution (PSD) analysis, Brunauer-Emmett-Teller (BET) surface area analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), vibrating sample magnetometry (VSM), atomic absorption spectroscopy (AAS), and Fourier transform infrared (FTIR) spectroscopy. Multiple isotherm models were employed to study the adsorption of Pb(II) ions onto the AFNMN material. Density functional theory (DFT) was applied to predict the most stable amino acids for the removal of Pb(II) pollutants from a set of 14 amino acids. To optimize the Pb(II) uptake performance, three key experimental parameters were fine-tuned: pH, temperature, and reactor vessel geometry. Four different optimization methods were utilized, including response surface methodology (RSM), fuzzy logic, adaptive network-based fuzzy inference system (ANFIS), and artificial neural network genetic algorithms (ANN-GA). Additionally, a heat transfer simulation was conducted to determine the optimal vessel positions for achieving the desired temperature variations within the reactor during the adsorption process.

Similarity recognition approach to identify zero-added MSG soy sauce using stable isotopes and amino acid profiles

Seasonings such as naturally fermented soy sauce without added monosodium glutamate (MSG), are currently a growth market in China. However, fraudulent and mislabeled zero-added MSG soy sauce may cause a risk of excessive MSG intake, increasing food safety issues for consumers. This study investigates stable carbon and nitrogen isotopes and 16 amino acids in typical Chinese in-market soy sauces and uses a similarity method to establish criteria to authenticate MSG addition claims. Results reveal most zero-added MSG soy sauces had lower δ13C values (−25.2 ‰ to −17.7 ‰) and glutamic acid concentrations (8.97 mg mL−1 to 34.76 mg mL−1), and higher δ15N values (−0.27 ‰ +0.95 ‰) and other amino acid concentrations than added-MSG labeled samples. A combined approach, using isotopes, amino acids, similarity coefficients and uncertainty values, was evaluated to rapidly and accurately identify zero-added MSG soy sauces from MSG containing counterparts.

Expedient Synthesis of Thermally Stable Acyclic Amino(haloaryl)carbenes: Experimental and Theoretical Evidence of “Push–Pull” Stabilized Carbenes

Expedient Synthesis of Thermally Stable Acyclic Amino(haloaryl)carbenes: Experimental and Theoretical Evidence of “Push–Pull” Stabilized Carbenes

Synthesis of Benzimidazole Based 1,2,4‐Triazole Derivatives as Potential Anticancer Agents: In Silico Techniques

AbstractCompounds with a 1,2,4–triazole scaffold serve an essential role in organic synthesis, particularly in the synthesis of bioactive organic compounds; thus, the development of new approaches for modifying this scaffold is a very interesting framework of this study. To contribute to the development of an efficient method for the conversion of anticancer triazoles, a novel series of benzimidazole based 1,2,4‐triazoles was designed and synthesized. All the newly synthesized derivatives were characterized by NMR (1H &amp;13C), FT–IR and mass spectrometry. Among the tested compounds, hybrids 5 b, 5 g exhibited exceptional anticancer susceptibilities with IC50=8.8±0.9, 9.2±1.5 μM against the tested HCA‐7cancer cell line. Anticancer profiles showed that compounds 5 d, 5 i had better anticancer inhibitory potency against a breast cancer cell line MCF‐7with IC50values 8.3±2.1, 10.6±1.2 μM, whereas 5 d, and 5 g showed potent anticancer activity against colorectal cancer cell line HT29 with IC50 values 7.1±±0.9, 7.7±1.2 μM respectively. From docking results, 5 d demonstrated highly stable binding amino acids LeuA : 2247, GlyA : 2449, SerA : 2409, HisA : 2379, AspA : 2373, LysA : 2318, IleA : 2317, IleA : 2246, IleA : 2412, AlaA : 2410, GlnA : 2452, AsnA : 2245, TyrA : 2243, and HisA : 2448, which play a crucial role enabling optimal ligand binding in a crystal structure tyrosine phosphatase mutated in colorectal cancer (PDB: 1WCH). Furthermore, the physicochemical and absorption, distribution, metabolism, and excretion (ADME) filtration molecular properties, estimation of bioactivity, and toxicity scores of these scaffolds were evaluated.

Vacuum Ultraviolet Single Photon Ionization and Decomposition of 2-Aminopropionitrile in Astrophysical Objects

The molecule 2-aminopropionitrile (2-APN; H3CCH(NH2)CN) is a chiral precursor of the amino acid alanine and could play an important role in the emergence of the homochirality of life. To date, 2-APN has not yet been detected in the interstellar medium. To address the question of its absence, possibly through destruction by vacuum ultraviolet radiation in astrophysical media, we studied its photoionization and dissociative photoionization in the 9–14 eV (89–137 nm) energy range using photoelectron–photoion coincidence spectroscopy with velocity map imaging. Density functional theory calculations were performed at the PBE0/aug-cc-pVTZ level to determine structures for the various cationic fragments identified experimentally. Their appearance energies were calculated. The adiabatic ionization energy (AIE) of 2-APN is AIE = (9.85±0.01) eV and the appearance energy (AE) of the major fragment ion N≡CC(H)NH2 + is AE = (10.57±0.01) eV. Both ions, 2-APN+ and N≡CC(H)NH2 +, make up more than 90% of the formed ions. N≡CC(H)NH2 +, an isomer of the protonated HCN dimer, is also formed with high yield in the dissociative photoionization of aminoacetonitrile (NH2CH2CN), another α-aminonitrile observed in Sgr B2(N). Photoion yield spectra have been calibrated to absolute ionization cross sections. From these, we derive photoionization rates in several typical radiation fields relevant to different astrophysical objects. The rates show that, under almost all explored radiation fields, dissociative ionization is the dominant pathway for photoionization, leading to the loss of a methyl group (CH3) to form the planar thermodynamically stable amino cyano methylidynium ion N≡CC(H)NH2 +. The observed absence of 2-APN in Sgr B2 could thus be due to dominant dissociative photoionization.

A nanotrap infused ultrathin hybrid composite material for rapid and highly selective entrapment of 99TcO4.

99Tc is one of the potentially toxic radioactive substances owing to its long half-life and a high degree of environmental mobility. Hence, the sequestration of 99Tc from radioactive waste has become enormously important and a contemporary research priority. However, selective extraction of this species in its stable oxoanionic form (99TcO4 -) is very challenging on account of bottlenecks such as low charge density, less hydrophilic nature, etc. Herein, an ultrathin hybrid composite material has been strategically designed and fabricated by covalent anchoring of a chemically stable amino functionalized nanosized cationic metal-organic polyhedron with a positively charged robust ionic covalent organic framework. The resulting thin-layer-based hybrid composite presented multiple exfoliated exposed interactive sites, including a Zr(iv)-secondary building unit, amine and triaminoguanidine functional groups, which can selectively interact with TcO4 - oxoanions through a synergistic combination of electrostatic, H-bonding and various other supramolecular interactions. Thus synthesized function-tailored composite, by virtue of its multiple unique characteristics, manifested an ultrafast and very selective, high distribution coefficient (∼106 mL g-1), as well as recyclable entrapment of TcO4 - oxoanions from the complex mixture of superfluous (∼5000-fold) other interfering anions in both high and ultra-trace concentrations along with simulated nuclear waste and from different water systems. Dynamic flow-through experiments were conducted with the membrane of the hybrid material in simulated wastewater, which reduced the concentration of ReO4 - (surrogate of radioactive TcO4 -) to below the WHO permissible level with rapid sequestration kinetics and excellent selectivity over excessive competing anions.

Design, synthesis and in silico docking techniques of new 1,2,3-triazolylpyrrolidines bearing chalcone derivatives: Discovery of potent antitubercular agents

Compounds with a pyrrolidine scaffold play an important role in organic synthesis and especially in the synthesis of bioactive organic compounds, therefore, the development of new methods for modifying this scaffold is a very interesting framework of this study. We developed a rational approach for the synthesis of 1,2,3-trazolylchalcone substituted pyrrolidines derivatives, which were then examined using a variety of spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, mass spectroscopy and elemental analysis. Biological profiles showed that compounds 5e, 5h had better antibacterial inhibitory potency against S. aureus, E. coli with zone of inhibition 34 ± 0.1, 33 ± 0.3 mm, whereas 5a, 5e showed potent antifungal activity against C. parapsilosis, A. flavus with dimeter zone of inhibition 26 ± 0.2, and 30 ± 0.2 mm respectively. Among the tested compounds 5b, and 5h were the most potent antitubercular activity against Mycobacterium tuberculosis H37Rv and showing MIC values 5.23 µg/mL, 6.85 µg/mL respectively, which are similar activity that of the standard Streptomycin (MIC = 5.02 µg/mL). The binding mode for compound 5 inside the catalytic pocket of M. tuberculosis cytochrome P450 CYP121A1 and produced a network of hydrophobic and hydrophilic interactions (6GEO). From docking results, 5b demonstrated highly stable binding amino acids SerA:237, ArgA:386, ArgA:286, CysA:345, MetA:62, GlnA:385, AspA:282, PheA:280, LeuA:284, ValA:83, ProA:285, AlaA:337, HisA:343, AsnA:74, and ThrA:65, which are plays a crucial role in ensuring efficient binding of the ligand in a crystal structure of tubercular receptor. Furthermore, the physicochemical and ADME (absorption, distribution, metabolism, and excretion) filtration molecular properties, estimation of toxicity, and bioactivity scores of these scaffolds were evaluated.

Physicochemical studies of some bioactive molecules in aqueous solution of tetrabutylammonium methanesulphonate (TBAMS) to investigate assorted molecular interaction at different temperatures simultaneously optimized by computational approach

Aqueous tetrabutylammonium methanesulphonate (TBAMS) solvent was used to solubilize the simplest stable amino acid (AA) Glycine and protein maker amino acid (AA) L-Alanine, and their solution behaviour has been meticulously examined to explore how they interact under various temperature conditions, using parameters like density (ρ), viscosity (η), surface tension (σ), and electrolytic conductivity. 1H NMR was also performed to verify further the mode of interactions prevailing in the solution, which is further supported by the DFT study. This research primarily aims to understand the interactions between biologically significant TBAMS and important amino acids in aqueous solutions, with potential implications for the pharmaceutical field. These results are anticipated to contribute crucial foundational knowledge for grasping the influence of sugar alcohols on the stability of protein structures.

Synthesis and in Silico Studies of Some New 1,2,3-Triazolyltetrazole Bearing Indazole Derivatives as Potent Antimicrobial Agents.

1,2,3-Triazole and tetrazole derivatives bearing pyrrolidines are found to exhibit notable biological activity and have become useful scaffolds in medicinal chemistry for application in lead discovery and optimization. Novel indazole bearing 1,2,3-triazolyltetrazoles were designed as potential antimicrobial candidates. The structure of duel heterocyclics was validated by a spectroscopic technique of infrared (IR), nuclear magnetic resonance (1 H and 13 C NMR), and mass spectral data. Compounds 4b, 4c, 4d, and 4h were found to have a stronger antibacterial effect against Gram-positive (S. aureus, B. subtilis, M. Luteus) and Gram-negative (E. coli, P. aeruginosa) microorganisms with MICs ranging from 5±0.03-18±0.02 μM, respectively. Moreover, scaffolds 4a, 4h showed potent antifungal activity against A. flavus, M. gypsuem strains with MIC values of 10±0.02, 11±0.01 μM, which are similar activity that of the standard Itraconazole (MIC=8±0.02, 10±0.01 μM). The binding mode for compound 4 inside the catalytic pocket of S. aureus complexed with nicotinamide adenine dinucleotide phosphate and trimethoprim and produced a network of hydrophobic and hydrophilic interactions (3FRE). From in silico results, 4b demonstrated highly stable hydrogen binding amino acids Leu62(X) [N18…O, 2.47 Å], Arg44(X) [N17…N, 3.11 Å], Thr96(X) [N10…OG1, 3.05 Å], Gly94(X) [F7…N, 2.82 Å], and Gly43(X) [F7…N, 2.90 Å], which are plays a crucial role in ensuring efficient binding of the ligand in a crystal structure of antibacterial receptor. Furthermore, the physicochemical and ADME filtration molecular properties, estimation of toxicity, and bioactivity scores of these novel scaffolds were evaluated by using SwissADME and ADMETlab2.0 online protocols. Thus, the significant antimicrobial activity of indazole linked to duel heterocyclic compounds can be used for development of new antimicrobial agents with further modifications.

Unraveling Antioxidative Metabolic Pathways in Multiple Myeloma: Augmenting IMiD Sensitivity through Intracellular Cysteine Biosynthesis Inhibition

Introduction Multiple myeloma (MM) patients often become unresponsive to immunomodulatory drugs (IMiDs) over time. Research has indicated that the cellular ability to counteract oxidative stress plays a crucial role in determining the sensitivity to IMiDs in MM. This study aims to comprehend the metabolic pathways responsible for MM's antioxidative capability and develop new treatments to augment the effectiveness of IMiDs. Methods We experimented using MM cells to investigate how different nutrient conditions affect cell proliferation and drug response. We utilized stable isotope-labeled amino acids and mass spectrometry to analyze the metabolites in these cells. We evaluated cell viability through the MTT assay, the CellTiter-Glo® Luminescent Assay, and direct cell counting. Furthermore, we conducted Western blots to measure the levels of various proteins expressed in MM cells grown under different nutrient conditions. To create CRBN knockout cells, we employed the CRBN CRISPR/Cas9 KO plasmid, and for the overexpression of CRBN in MM cells, we used a lentivirus system. Results Our research findings reveal that the production of cellular cysteine enhances the cell's ability to counteract oxidative damage, leading to resistance to IMiDs even with the presence of the wild-type CRBN protein. However, MM cells not producing enough cysteine rely on consuming extracellular cystine, which increases sensitivity to lenalidomide and reduces antioxidative capacity. Lenalidomide-sensitive cells acquire more cystine from the extracellular environment than resistant cells. The analysis of cysteine uptake in various MM cell lines using C13-labeled cysteine revealed that the lenalidomide-sensitive cell line, OCIMY5-CRBN, consumed more cysteine from the media, and the presence of L-glutamine further increased this uptake. Lenalidomide treatment increased the catabolism of cysteine into taurine in sensitive cell lines, confirming the link between lenalidomide's molecular action and cysteine catabolism. Our study also identified that lenalidomide treatment led to an accumulation of CDO protein, which adds molecular oxygen to cysteine, transforming it into cysteine sulfinic acid. Our study suggests that CRBN may play a role in maintaining intracellular CDO protein levels, and the accumulation of CDO protein induced by lenalidomide is the molecular factor responsible for cystine catabolism and sensitivity to IMiDs in multiple myeloma. We found that by inhibiting intracellular cysteine biosynthesis, we could improve the effectiveness of IMiD against MM. One drug that can achieve this is 5-aza-2-deoxycytidine (DAC), which acts as a DNA methylation inhibitor. Additionally, combining DAC with IMiDs improves their effectiveness, even in cell lines that are resistant to treatment. Furthermore, we attempted to inhibit cysteine biosynthesis by promoting the synthesis of methionine from homocysteine with the supplementation of 5-methyltetrahydrofolate. We discovered that treatment with 5-methyltetrahydrofolate further enhanced the sensitivity of IMiDs in resistant MM cell lines. Our results confirm that interfering with intracellular cysteine biosynthesis is a promising therapeutic approach for MM and can improve the effectiveness of IMiDs. Conclusions The biosynthesis of L-Cysteine is vital for the cellular ability to resist oxidation. Cancer cells that create high levels of cysteine within the cell from methionine generate a more significant amount of reduced cysteine, which can act as antioxidants and make MM cells resistant to IMiDs. On the other hand, cells that cannot produce enough cysteine increase their consumption of extracellular cystine and are more susceptible to IMiDs. Cells that consume an oxidized form of cystine from outside the cell require a reduction process inside the cell, which further reduces their ability to resist oxidation. Additionally, the accumulation of CDO protein induced by lenalidomide can enhance the breakdown of intracellular cysteine and cystine uptake in vulnerable cells. Overall, MM cells that rely on extracellular cysteine are sensitive to IMiDs. Therefore, interfering with intracellular cysteine biosynthesis is a better option for myeloma treatment and enhancing the sensitivity of IMiDs.

Deconvolving feeding niches and strategies of abyssal holothurians from their stable isotope, amino acid, and fatty acid composition

Deconvolving feeding niches and strategies of abyssal holothurians from their stable isotope, amino acid, and fatty acid composition

Non-avian dinosaur eggshell calcite can contain ancient, endogenous amino acids

Proteins are the most stable of the macromolecules that carry genetic information over long periods of time. Closed systems are more likely to retain endogenous proteins or their degradation products. Amino acid racemisation data in experimental and subfossil material suggests that mollusc shell and avian eggshell calcite crystals can demonstrate closed system behaviour, retaining endogenous amino acids. Here, Late Cretaceous (Campanian–Maastrichtian) Argentine titanosaurian sauropod eggshells show dark, organic stains under light microscopy/photography and fluorescence imaging. Raman spectroscopy can yield bands consistent with various organic molecules, possibly including N-bearing molecules or geopolymers. Pyrolysis-gas chromatography-mass spectrometry reveals pyrolysates consistent with amino acids as well as aliphatic hydrocarbon homologues that are not present in modern eggshell, consistent with kerogen formation deriving from eggshell lipids. High-performance liquid chromatography reveals that their intra-crystalline fraction can be enriched in some of the most stable amino acids (Glx, Gly, Ala, and possibly Val) and are fully racemic (despite being some of the slowest racemising amino acids), indicating ancient origin. This preservation varies across localities, but similar ancient amino acid profiles were also observed in Late Cretaceous Spanish titanosaurians from several localities and Chinese putative hadrosaurid eggshell. These amino acid results are consistent with previous studies on degradation trends deduced from modern, thermally matured, sub-fossil, and ∼3.8–6.5 Ma avian eggshell, as well as ∼30 Ma calcitic mollusc opercula. Selective preservation of certain fully racemic amino acids, which do not racemise in-chain, and the concentration of free amino acids suggests likely complete hydrolysis of original peptides. Liquid chromatography-tandem mass spectrometry supports this hypothesis by failing to detect any non-contamination peptide sequences from the Mesozoic eggshell. These closed-system amino acids are possibly the most thoroughly supported non-avian dinosaur endogenous protein-derived constituents, at least those that have not undergone oxidative condensation with other classes of biomolecules. Biocrystal matrices can help preserve mobile organic molecules by trapping them (perhaps with the assistance of resistant organic polymers), but trapped organics are nevertheless prone to diagenetic degradation, even if such reactions might be slowed in exceptional circumstances. Future work should survey fossil biocalcite to determine variability in amino acid preservation.

Efficient and Selective Removal of Hg(II) from Aqueous Solution by a Highly Stable Amino Isonicotinic-Based Coordination Polymer

Efficient and Selective Removal of Hg(II) from Aqueous Solution by a Highly Stable Amino Isonicotinic-Based Coordination Polymer

Identification of Solanum pimpinellifolium genome regions for increased resilience to nitrogen deficiency in cultivated tomato

High-quality crop production with minimal fertilizer inputs is a key goal for the agriculture of the future. Globally, tomato is one of the most important vegetable crops and its intensive production and breeding has been based on the application of large quantities of nitrogen (N) fertilizers. Therefore, the development of N use efficient (NUE) cultivars with low N inputs needs to be addressed. Some variability in plant growth, fruit quality and NUE traits among tomato (Solanum lycopersicum L.) varieties under low N supply has been reported, however, the relevance of wild relatives of tomato has not yet been assessed. In this study, we found that S. pimpinellifolium accession To-937 (SP) may be a suitable resource to increase NUE in tomato. We studied a set of 29 introgression lines (IL) from SP into the Moneymaker cultivar (MM) in different seasons to investigate the potential of SP introgressions to maintain the tomato plant performance during the growth cycle under low N input in greenhouse conditions. We identified specific regions in the SP genome, on chromosomes 1, 3 and 10, involved in the responses to N inputs of fruit production and fruit quality. Notably, the line SP_10-4 maintained vegetative biomass and fruit yield production under limiting N supply. The introgressed region contained putative candidate genes as sucrose phosphate phosphatase (SPP), invertases (INV) and glutamine synthase 1 (GS1) genes, implicated in C and N metabolism. Genomic and expression analyses revealed differences in coding and non-coding sequences as well as in mRNA levels in SP_10-4, suggesting that these genes might well contribute to the reported biomass responses to N. Additionally, line SP_1-4 showed stable fruit amino acid contents under both sufficient and limiting N supplies, indicating that assimilated N partitioning to the fruit is maintained in response to N. Altogether, our results confirmed the suitability of SP as a source of NUE related traits and the interest in the studied ILs for developing new tomato cultivars with improved NUE under sustainable fertilization conditions.

Evaluation of the rapid phase change absorbents based on potassium glycinate for CO2 capture

Phase-change process is deemed as an energy-saving approach for CO2 capture, however, the low phase change rate of the current absorbents leads to low separation efficiency, difficult operation and solvent loss. Herein, a novel rapid phase change absorbent composed of ether solvent (SA) and potassium glycinate (GlyK) aqueous solution was developed, and the phase-change behavior, phase separation mechanism, and the energy consumption were investigated. Results showed that the GlyK-30SA absorbent exhibited the highest CO2 capacity of 0.64 molCO2/molGlyK, the liquid-liquid phase separation within 2 min and more than 91% CO2 enrichment in the lower phase. The mechanism of the split phase and regeneration was explored by 13C NMR. More significantly, the absorbent also showed excellent cycling stability and a 30% reduction in energy consumption compared to the 3 M MEA system. It provided a new possibility for the development of stable and energy-saving amino acid salts phase change absorbents.