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Food Chemistry Oct 2024Understanding the evolution of aroma profiles in stored sesame paste (SP) is essential for maintaining its quality. This study investigated the storage quality of SP and...
Understanding the evolution of aroma profiles in stored sesame paste (SP) is essential for maintaining its quality. This study investigated the storage quality of SP and potential aroma markers indicative of sensory degradation. The descriptive sensory analysis demonstrated changes in aroma attributes during storage, transitioning from roasted sesame and nutty aromas to fermented and green aromas. Physicochemical analysis showed deepening color, intensified lipid oxidation, decreased levels of bioactive components, increased particle aggregation, and deteriorated flowability over 63 days at 40 °C. Gas chromatography-olfactometry-mass spectrometry identified 37 aroma-active compounds, with pyrazines, aldehydes, and phenols identified as the major constituents. Partial least squares regression analysis revealed 2-ethyl-3-methyl-pyrazine, 2-methoxy-4-vinylphenol, and benzaldehyde as key aroma-active compounds contributing significantly to the distinctive aromas "roasted nut and roasted sesame" found in SP. Conversely, hexanal and dimethyl disulfide emerged as potential markers of undesirable aromas in SP, including "rancid, green, and fermented". These findings provide insights into SP changes during storage, which is vital for preservation and quality enhancement strategies.
Topics: Sesamum; Odorants; Gas Chromatography-Mass Spectrometry; Food Storage; Taste; Humans; Volatile Organic Compounds; Olfactometry
PubMed: 38815324
DOI: 10.1016/j.foodchem.2024.139809 -
Journal of Agricultural and Food... Jun 2024Structure-activity relationships of diazinoyl nicotinic insecticides (diazinoyl isomers and 5- or 6-substituted pyrazin-2-oyl analogues) are considered in terms of...
Structure-activity relationships of diazinoyl nicotinic insecticides (diazinoyl isomers and 5- or 6-substituted pyrazin-2-oyl analogues) are considered in terms of affinity to the insect nicotinic acetylcholine receptor (nAChR) and insecticidal activity against the imidacloprid-resistant brown planthopper. Among the test compounds, 3-(6-chloropyridin-3-ylmethyl)-2-(pyrazinoyl)iminothiazoline shows the highest potency in nAChR affinity and insecticidal activity. acetylcholine binding protein (AChBP) mutants (Y55W + Q57R and Y55W + Q57T) are utilized to compare molecular recognition of nicotinic insecticides with diverse pharmacophores. -nitro- or -cyanoimine imidacloprid or acetamiprid, respectively, exhibits a high affinity to these AChBP mutants at a similar potency level. Intriguingly, the pyrazin-2-oyl analogue has a higher affinity to AChBP Y55W + Q57R than that to Y55W + Q57T, thereby indicating that pyrazine nitrogen atoms contact Arg57 guanidinium and Trp55 indole NH. Furthermore, nicotine prefers AChBP Y55W + Q57T over Y55W + Q57R, conceivably suggesting that the protonated nicotine is repulsed by Arg57 guanidinium, consistent with its inferior potency to insect nAChR.
Topics: Animals; Insecticides; Receptors, Nicotinic; Hemiptera; Structure-Activity Relationship; Insect Proteins; Neonicotinoids; Nitro Compounds; Aplysia; Nicotine
PubMed: 38814790
DOI: 10.1021/acs.jafc.4c01499 -
Journal of Molecular Modeling May 2024The compounds of the "565" parent ring structure have received much attention from researchers because of their excellent detonation performance. In the present study,...
CONTEXT
The compounds of the "565" parent ring structure have received much attention from researchers because of their excellent detonation performance. In the present study, 81 derivatives were designed by introducing different substituents based on 6-dinitrophenyl-5,6,7,8-tetrahydro-4-imidazo[4,5-e]furazano[3,4-b] pyrazine (DIOP), which is a compound of the parent ring structure of 565, and the performance of these derivatives, such as the electronic structure, energy gap, heat of formation, and detonation performance, were investigated. Among these energy-containing derivatives, the density ranges from 1.70 to 2.17 g/cm, the detonation velocity ranges from 8.01 to 10.26 km/s, and the detonation pressure ranges from 27.99 to 49.88 GPa. Through comprehensive analysis of several properties of DIOP derivatives, it was found that the oxygen balance of derivatives with the -ONO group was greater than zero and close to zero, while the oxygen balance of derivatives with other groups was almost all less than zero. Among them, G8 (D = 10.1 km/s, P = 47.72 GPa), H8 (D = 10.11 km/s, P = 47.92 GPa), and I8 (D = 10.26 km/s, P = 49.88 GPa) had higher detonation velocity and pressure among all derivatives, and their impact sensitivity was better than RDX. Therefore, three potential high-energy and less sensitive energy-containing derivatives, G8, H8, and I8, were screened out. The intramolecular interactions of the three derivatives were further analyzed, and it was found that there were intensive van der Waals interactions and significant spatial steric effects within the molecules, which had a positive effect on reducing the shock sensitivity of the compounds. Moreover, the three derivatives have a large degree of stacking, which leads to a high density.
METHODS
All calculations in this paper are performed using Gaussian16 based on density functional theory. Firstly, the structures of the derivatives were optimized at the level of B3LYP-D3/6-311G**, and then single-site energy calculations were carried out at the level of M06-2X-D3/def2-TZVPP, to reveal the effects of single substituents versus multiple substituents and isomerism on the properties of the DIOP-based energetic derivatives. Multiwfn was used to plot the density of states (DOS) of the derivatives and to calculate the molecular surface electrostatic potential at 0.001 e/Bohr electron density, 0.25 Bohr lattice spacing surface.
PubMed: 38814476
DOI: 10.1007/s00894-024-05993-2 -
Oncoimmunology 2024Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and...
Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and surface exposure of calreticulin (CALR) in multiple myeloma (MM) cells responding to bortezomib. Hence, GABARAP-defective MM cells fail to undergo immunogenic cell death.
Topics: Multiple Myeloma; Humans; Bortezomib; Adaptor Proteins, Signal Transducing; Antineoplastic Agents; Microtubule-Associated Proteins; Apoptosis Regulatory Proteins; Immunogenic Cell Death; Cell Line, Tumor; Autophagy; Calreticulin
PubMed: 38812570
DOI: 10.1080/2162402X.2024.2360275 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery...
This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.
Topics: Animals; Pyrazines; Neural Stem Cells; Rats; Male; Rats, Sprague-Dawley; Receptors, CXCR4; Brain Ischemia; NF-E2-Related Factor 2; Doublecortin Protein; Chemokine CXCL12; Kelch-Like ECH-Associated Protein 1; Stem Cell Transplantation; Cell Proliferation; Cell Movement; Humans; Reperfusion Injury; Infarction, Middle Cerebral Artery; NAD(P)H Dehydrogenase (Quinone)
PubMed: 38812132
DOI: 10.19540/j.cnki.cjcmm.20230821.401 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024This study aims to decipher the mechanism of tetramethylpyrazine(TMP) in regulating the migration of neural stem cells(NSCs) in the rat model of middle cerebral artery...
This study aims to decipher the mechanism of tetramethylpyrazine(TMP) in regulating the migration of neural stem cells(NSCs) in the rat model of middle cerebral artery occlusion(MCAO) via the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/C-X-C motif chemokine receptor 4(CXCR4) pathway. SD rats were randomized into sham, MCAO(model), and tetramethylpyrazine(TMP, 20 mg·kg~(-1) and 40 mg·kg~(-1)) groups. The neurological impairment was assessed by the modified neurological severity score(mNSS). The immunofluorescence assay was employed to detect the cells stained with both 5-bromodeoxyuridine(BrdU) and doublecortin(DCX) in the brain tissue. The effect of TMP on the migration of C17.2 cells was observed. Western blot was employed to determine the protein levels of Nrf2, HO-1, p62, NAD(P)H quinone oxidoreductase 1(NQO1), stromal cell-derived factor 1(SDF-1), and CXCR4 in the brain tissue and C17.2 cells. The results showed that after 7 days and 21 days of mode-ling, the mNSS and BrdU~+/DCX~+ cells were increased, and the expression of Nrf2 and CXCR4 in the brain tissue was up-regulated. Compared with the model group, TMP(40 mg·kg~(-1)) reduced the mNSS, increased the number of BrdU~+/DCX~+ cells, and up-regulated the expression of Nrf2, CXCR4, and SDF-1. In addition, TMP promoted the migration of C17.2 cells and up-regulated the expression of p62, Nrf2, HO-1, and NQO1 in a time-and dose-dependent manner. The expression was the highest at the time point of 12 h in the TMP(50 μg·mL~(-1)) group(P<0.01). In conclusion, TMP activates the Nrf2/HO-1/CXCR4 pathway to promote the migration of NSCs to the ischemic area, thus exerting the therapeutic effect on the ischemia-reperfusion injury. This study provides experimental support for the application of TMP in ischemic stroke.
Topics: Animals; Receptors, CXCR4; NF-E2-Related Factor 2; Pyrazines; Rats; Neural Stem Cells; Cell Movement; Rats, Sprague-Dawley; Male; Heme Oxygenase-1; Doublecortin Protein; Signal Transduction; Reperfusion Injury; Humans
PubMed: 38812131
DOI: 10.19540/j.cnki.cjcmm.20240124.401 -
PloS One 2024To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency...
To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs.
Topics: Mycobacterium tuberculosis; Microbial Sensitivity Tests; China; Antitubercular Agents; Humans; Laboratory Proficiency Testing; Reproducibility of Results; Phenotype; Amikacin; Pyrazinamide
PubMed: 38809914
DOI: 10.1371/journal.pone.0304265 -
Current Microbiology May 2024The endolichenic fungi are an unexplored group of organisms for the production of bioactive secondary metabolites. The aim of the present study is to determine the...
The endolichenic fungi are an unexplored group of organisms for the production of bioactive secondary metabolites. The aim of the present study is to determine the antibacterial potential of endolichenic fungi isolated from genus Parmotrema. The study is continuation of our previous work, wherein a total of 73 endolichenic fungi were isolated from the lichenized fungi, which resulted in 47 species under 23 genera. All the isolated endolichenic fungi were screened for preliminary antibacterial activity. Five endolichenic fungi-Daldinia eschscholtzii, Nemania diffusa, Preussia sp., Trichoderma sp. and Xylaria feejeensis, were selected for further antibacterial activity by disc diffusion method. The zone of inhibition ranged from 14.3 ± 0.1 to 23.2 ± 0.1. The chemical composition of the selected endolichenic fungi was analysed through GC-MS, which yielded a total of 108 compounds from all the selected five endolichenic fungi. Diethyl phthalate, 1-hexadecanol, dibutyl phthalate, n-tetracosanol-1, 1-nonadecene, pyrrol[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl) and tetratetracontane were found to be common compounds among one or the other endolichenic fungi, which possibly were responsible for antibacterial activity. GC-MS data were further analysed through Principal Component Analysis which showed D. eschscholtzii to be with unique pattern of expression of metabolites. Compound confirmation test revealed coumaric acid to be responsible for antibacterial activity in D. eschscholtzii. So, the study proves that endolichenic fungi that inhabit lichenized fungal thalli could be a source of potential antibacterial compounds.
Topics: Secondary Metabolism; Anti-Bacterial Agents; Microbial Sensitivity Tests; Lichens; Bacteria; Ascomycota; Gas Chromatography-Mass Spectrometry
PubMed: 38809483
DOI: 10.1007/s00284-024-03719-4 -
Georgian Medical News Mar 2024Changing the vision, understanding, interpretation and analysis of certain data or scientific dilemmas is what is able to change the status quo and revitalize a mission,...
(NDMA) METFORMIN AND (NTTP) SITAGLIPTIN INDUCED CUTANEOUS MELANOMAS: LINKS TO NITROSOGENESIS, NITROSO-PHOTOCARCINOGENESIS, ONCOPHARMACOGENESIS AND THE METABOLIC REPROGRAMMING.
Changing the vision, understanding, interpretation and analysis of certain data or scientific dilemmas is what is able to change the status quo and revitalize a mission, an impulse or important thoughts, thus creating the conditions for it to increase immensely the chances of bringing it to success. Or, following Albert Einstein's postulate: ˝We cannot solve our problems with the same thinking we used when we created them˝, we should think: ˝Where does the road to success start? How do we solve or neutralize a problem? ˝ And the answer is: ˝ By taking a consistent and systematic approach, analyzing each component! And we eliminate every possibility of negative influence.˝ These thoughts apply with full force to cancer rates in general, but also to melanoma rates in particular: the murderous tempo of globalization and modernization in medicine has not yet led to the desired decrease in these rates; on the contrary, they are rising headlong and remain largely unpredictable and difficult to regulate. The conclusion is that a solution should be sought by refracting light through another prism: that of Nitrosogenesis and Pharmaco-Oncogenesis. A step-by-step and systematic approach to solving a problem requires patience, determination, and perseverance. As this perseverance is needed mainly to overcome the general ignorance, neglect, disinterest, uneducation and uncertainty of others, rather than doubt in one's own thesis, analysis, and the need for an active approach. Careful analysis of concepts such as ˝Drug Mediated Nitrosogenesis˝ and ˝Onco-pharmacogenesis/Pharmaco-oncogenesis˝ of skin cancer would certainly contribute to the elucidation of skin carcinogenesis in the context of polymedication of the contamination and polymorbidity worldwide. The FDA has already in 2019 taken this much needed first step of universal awareness and its ˝arm˝ has been taken seriously and responsibly solely by dermatologists and dermatosurgeons. It was this guild and only this guild that launched its independent, never-ending observations, logically grounded (hypo)theses, remaining to date confirmatory, unshakable, and enigmatic regarding the unit: intake of potentially contaminated medication and subsequent development of melanomas. It is this and only this branch of the medical guild that has also become the guarantor of safety and objectivity in science, and thus of safety in the fight for survival of a huge number of skin cancer patients. Contaminated oral antidiabetic drugs in the face of Metformin and Sitagliptin do not make an exception in this respect. Similarly to cutaneous melanomas occurring (and published in the scientific literature) after combined intake (or monomedication) of/ between ranitidine, valsartan, olmesartan, candesartan, telmisartan, irbesartan, losartan, enalapril, lisinopril, perindopril, hydrochlorothiazide, nifedipine, amlodipine, propafenone, bisoprolol, nebivolol, melitracen and a number of others, we inform about another rare but not unexpected clinical observation: occurrence of cutaneous melanomas after taking another class of drugs- oral antidiabetic ones. Or after the intake of nitrosamine-contaminated antidiabetic drugs. And whether this contamination is "real or potential" is left to regulators and manufacturers to decide. We accept it as `real-potential' or `potentially-real' because of the fact that neither the regulators nor the manufacturers know what it is or whether it is there or how it arose. The data shared in patients one and two in the presented scientific work are confirmatory in relation to the potential pathogenetic action of nitrosamine contaminated drugs such as 1) bisoprolol/ nebivolol/ candesartan/ hydrochlorothiazide and amlodipine, as well as 2) furosemide in the direction of cutaneous melanoma. Patient 3 in fact also represents the first formally described patient with subsequent melanoma development worldwide, having developed it following intake of potentially/actually nitrosamine-contaminated metformin and metformin/sitagliptin (both drugs are themed in the FDA's Potentially Contaminated Drug Bulletin: 1) metformin, multiple times between 2020-21, due to its contamination with NDMA and 2) sitagliptin, as of September 2022, due to its contamination with NTTP). It should not be seen as surprising to anyone that the intake of relatively similar carcinogens/nitrosamines or NDSRIs, but as an unofficial component of heterogeneous drugs, produces a relatively monomorphic clinical picture- that of cutaneous melanoma. Or to put it metaphorically: ˝The wolf changes its hair, but not its mood˝. A carcinogen remains a carcinogen, regardless of whether it is ingested in a lemonade, a tablet, a sandwich, or a bonbon. Similarly to the intake of nitrosamines in food. Future studies should address the important tasks/dilemmas to elucidate 1) the phototoxic/photocarcinogenic effect of unmetabolized nitrosamines identified in drug formulations; 2) the phototoxic/photocarcinogenic effect of DNA adducts generated after their metabolization, and 3) the availability of specific DNA adducts in lesional/tumor tissue and blood of patients after ingestion of nitroso-containing drug formulations. This level of evidence is likely to lead to a reconsideration of the arguments for the introduction of permanent elimination regimes for nitrosamines in medicines. Metabolic reprogramming (and its relationship to UVB radiation) due to the availability of nitrosamines in cigarette smoke is also currently a proven reality. Based on the available clinicopathological correlations, we believe that nitrosamines in drugs have a similar effect and are part of the key pathway activating skin carcinogenesis under the influence of solar radiation. Intake of contaminated medication is associated with skin cancer generation and progression. It is up to regulators and manufacturers to justify the merits and benefits of the self-imposed presence of carcinogens in drugs or the benefits of such drugs. Apart from the "cancer-generating benefit", of course, which is already widely known. And let us not forget that: "A lie stops being a lie and becomes a truth the moment it is officially refuted".
Topics: Humans; Melanoma; Skin Neoplasms; Metformin; Sitagliptin Phosphate; Carcinogenesis; Melanoma, Cutaneous Malignant; Hypoglycemic Agents; Metabolic Reprogramming
PubMed: 38807407
DOI: No ID Found -
Inorganic Chemistry Jun 2024Five- and six-membered heterocycles containing nitrogen or oxygen have been considered as privileged scaffolds in organic chemistry and the chemical industry because of...
Five- and six-membered heterocycles containing nitrogen or oxygen have been considered as privileged scaffolds in organic chemistry and the chemical industry because of their usage in high-value commodities. Herein, we report a two-dimensional (2D) Cu(II)-based MOF catalyst, via the strategic employment of ample Lewis acid-base bifunctional sites (open metal nodes and free pyrazine moieties) along the pore wall. could convert toxic CO to cyclic carbonates in an atom-economical manner under solvent-free conditions and aromatic aldehyde to bioactive 1,4-DHPs via Hantzsch condensation. Exceptional catalytic performance (99%) and turnover number under mild reaction conditions for CO fixation using sterically hindered styrene oxide, and good-to-excellent yields for a wide range of aromatic aldehydes toward 1,4-dihydropyridines (1,4-DHPs) make promising as a multipurpose heterogeneous catalyst. Moreover, to demonstrate the practical utility of the catalyst, two biologically important drug molecules, diludine and nitrendipine analogue, have also been synthesized. is recyclable for at least three consecutive runs without significant loss of activity, making it promising for real-time applications.
PubMed: 38807309
DOI: 10.1021/acs.inorgchem.4c01565