Analysis Of Mass Spectra Research Articles

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

P62 promotes FSH-induced antral follicle formation by directing degradation of ubiquitinated WT1

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR.

Optimization, Production, and characterization of cottonseed methyl ester based on Box-Behnken in response surface design and gas Chromatography-Mass spectrum analysis

Renewable energy sources have a significant approach to eco-friendly systems with economically cost-effective and efficient use of biodiesel. The creation of innovative catalysts is attracting the attention and concern of the chemical and manufacturing sectors to be used in the production of biodiesel. The main objective of this work is to produce the optimum biodiesel yield using BBD design and the base-catalyzed method. The production of biodiesel was achieved through experimental investigation (alkali-catalyzed transesterification) and optimized using the BBD design method.The most important parameters such as methanol to oil ratios, KOH as catalysts, and reaction times were provided with variable conditions. The variation of methanol to oil ratios has significant relationships and is highly correlated in findings. The physicochemical properties of cottonseed biodiesel were carried out according to ASTM and EN standards. The maximum yield was achieved at 96.708 at a molar ratio of 6:1, reaction time of 60 min, and catalyst concentration of 1 wt%. The strong correlation between actual and predicted values of COSME was analyzed using ANOVA variances. The F-value and P-value validated the outcomes of produced biodiesel having a model value of 43.68 and 0.00, respectively. The coefficient of determinations and adjusted R2 of CSOME were achieved at 98.7% and 98.6%, respectively. The gas chromatogram mass spectrum analysis was also obtained to identify the acid profile present in COSME. The major percentage of ester available in COSME has been determined using GC–MS analysis and presented by its weight percentages. The main esters have been including myristic acid methyl ester (1.7%), palmitic acid methyl ester (26.65%), methyl 9-cis,11-trans-octadecadienoate(44.05%), ethyl 9. Cis.11.trans octadecadienoate(9.67%), methyl 20-methyl-heneicosanoate(6.83%), 9,12-Octadecadienoic acid (Z,Z)-, 2-hydroxy-1-(hydroxymethyl)ethyl ester(1.93%), and Pentacosanoic acid, methyl ester(7.14%).

Nitrospirillum viridazoti sp. nov., an Efficient Nitrogen-Fixing Species Isolated from Grasses.

A group of Gram-negative plant-associated diazotrophic bacteria belonging to the genus Nitrospirillum was investigated, including both previously characterized and newly isolated strains from diverse regions and biomes, predominantly in Brazil. Phylogenetic analysis of 16S rRNAand recA genes revealed the formation of a distinct clade consisting of thirteen strains, separate from the formally recognized species N. amazonense (the closest species) and N. iridis. Comprehensive taxonomic analyses using the whole genomes of four strains (BR 11140T = AM 18T = Y-2T = DSM 2788T = ATCC 35120T, BR 11142T = AM 14T = Y-1T = DSM 2787T = ATCC 35119T, BR 11145 = CBAmC, and BR 12005) supported the division of these strains into two species: N. amazonense (BR 11142T and BR 12005) and a newly proposed species (BR 11140T and BR 11145), distinct from N. iridis. The phylogenomic analysis further confirmed the presence of the new Nitrospirillum species. Additionally, MALDI-TOF MS analysis of whole-cell mass spectra provided further evidence for the differentiation of the proposed Nitrospirillum species, separate from N.amazonense. Analysis of chemotaxonomy markers (i.e., genes involved in fatty acid synthesis, metabolism and elongation, phospholipid synthesis, and quinone synthesis) revealed that the new species highlights high similarity and evolutionary convergence with other Nitrospirillum species. This new species exhibited nitrogen fixation ability in vitro, it has similar NifHDK protein phylogeny position with the closest species, lacked denitrification capability, but possessed the nosZ gene, enabling N2O reduction, distinguishing it from the closest species. Despite being isolated from diverse geographic regions, soil types, and ecological niches, no significant phenotypic or physiological differences were observed between the proposed new species and N. amazonense. Based on these findings, a new species, Nitrospirillum viridazoti sp. nov., was classified, with the strain BR 11140T (DSM 2788T, ATCC 35120T) designated as the type strain.

The Michael addition of thiols to 13-oxo-octadecadienoate (13-oxo-ODE) with implications for LC-MS analysis of glutathione conjugation

Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise structures of the conjugates. Herein we reacted 13-keto-octadecadienoic acid (13-oxo-ODE or 13-KODE) with glutathione (GSH), N-acetyl-cysteine, and β-mercaptoethanol and identified the adducts. HPLC-UV analyses indicated none of the products exhibit a conjugated enone UV chromophore, a result that conflicts with the literature and relevant to mass spectral interpretation of 1,4 versus 1,6 thiol adduction. Aided by development of an HPLC solvent system that separates the GSH diastereomers and thus avoids overlap of signals in proton NMR experiments, we established the two major conjugates are formed by 1,6 addition of GSH at the 9-carbon of 13-oxo-ODE with the remaining double bond α to the thiol in the 10,11 position. N-acetyl cysteine reacts similarly, while β-mercaptoethanol gives equal amounts of 1,4 and 1,6 addition products. Equine glutathione transferase catalyzed 1,6 addition of GSH to the two major diastereomers in 44:56 proportions. LC-MS in positive ion mode gives a product ion interpreted before as evidence of 1,4-thiol adduction, whereas here we find this ion using the authentic 1,6 adduct. LC-MS with negative ion APCI gave a fragment selective for 1,4 adduction. These results clarify the structures of thiol conjugates of a prototypical unsaturated keto fatty acid and have relevance to the application of LC-MS for the structural analysis of keto-fatty acid glutathione conjugation.

Characterization of the fragmentation mechanisms in electrospray ionization tandem mass spectrometry of chloroquinoline derivatives with larvicidal activity against Aedes aegypti.

4,7-Dichloroquinoline (DCQ) represents a group of synthetic molecules inspired by natural products with important roles in biological and biomedical areas. This work aimed to characterize DCQ and its derivatives by high-resolution electrospray ionization (ESI) mass spectrometry and tandem mass spectrometry (ESI-MS/MS), supported by theoretical calculations. Biological assays were carried out with DCQ and its derivatives to determine LC50 values against Aedes aegypti larvae. Five DCQ derivatives were synthesized by using previously described protocols. ESI-MS/MS analyses were carried out with a quadrupole/time-of-flight and ion-trap instrument. The proposed gas-phase protonation sites and fragmentation were supported by density functional theory calculations. The larvicidal tests were performed with the Ae. aegypti Rockefeller strain, and the LC50 values were determined by employing five test concentrations. Larval mortality was determined after treatment for 48 h. DCQ bromides or aldehydes (C-3 or C-8 positions), as well as the trimethylsilyl derivative (C-3 position), were prepared. Detailed ESI-MS/MS data revealed heteroatom elimination through an exception to the even-electron rule, to originate open-shell species. Computational studies were used to define the protonation sites and fragmentation pathways. High activity of DCQ and its derivatives against Ae. aegypti larvae was demonstrated. Our results provided a well-founded characterization of the fragmentation reactions of DCQ and its derivatives, which can be useful for complementary studies of the development of a larvicidal product against Ae. aegypti.

Chemical properties and single-particle mixing state of soot aerosol in Houston during the TRACER campaign

Abstract. A high-resolution soot particle aerosol mass spectrometer (SP-AMS) was used to selectively measure refractory black carbon (rBC) and its associated coating material using both the ensemble size-resolved mass spectral mode and the event trigger single particle (ETSP) mode in Houston, Texas, in summer 2022. This study was conducted as part of the Department of Energy Atmospheric Radiation Measurement (ARM) program's TRacking Aerosol Convection interactions ExpeRiment (TRACER) field campaign. The study revealed an average (±1σ) rBC concentration of 103 ± 176 ng m−3. Additionally, the coatings on the BC particles were primarily composed of organics (59 %; 219 ± 260 ng m−3) and sulfate (26 %; 94 ± 55 ng m−3). Positive matrix factorization (PMF) analysis of the ensemble mass spectra of BC-containing particles resolved four distinct types of soot aerosol, including an oxidized organic aerosol (OOABC,PMF) factor associated with processed primary organic aerosol, an inorganic sulfate factor (SO4,BC,PMF), an oxidized rBC factor (O-BCPMF), and a mixed mineral dust–biomass burning aerosol factor with significant contribution from potassium (K-BBBC,PMF). Additionally, K-means clustering analysis of the single-particle mass spectra identified eight different clusters, including soot particles enriched in hydrocarbon-like organic aerosol (HOABC,ETSP), sulfate (SO4,BC,ETSP), two types of rBC, OOA (OOABC,ETSP), chloride (ClBC,ETSP), and nitrate (NO3,BC,ETSP). The single-particle measurements demonstrate substantial variation in BC coating thickness with coating-to-rBC mass ratios ranging from 0.1 to 100. The mixing state index (χ), which denotes the degree of homogeneity of the soot aerosol, varied from 4 % to 94 % with a median of 40 %, indicating that the aerosol population lies in between internal and external mixing but has large temporal and source type variability. In addition, a significant fraction of BC-containing particles, a majority enriched with oxidized organics and sulfate, exhibit sufficiently high κ values and diameters conducive to activation as cloud nuclei under atmospherically relevant supersaturation conditions. This finding bears significance in comprehending the aging processes of rBC-containing particles and their activation into cloud droplets. Our analysis highlights the complex nature of soot aerosol and underscores the need to comprehend its variability across different environments for accurate assessment of climate change.

Effortless Fabrication of Bi2O3‐Co3O4 Nanocomposite Catalyst: Harnessing Photocatalytic Power for Efficient Cationic Dye Degradation

AbstractA cost‐effective and simple co‐precipitation approach was used to create an efficient photocatalyst Co3O4‐Bi2O3 with identical stoichiometry (1 : 1 of both Co3O4 and Bi2O3). XRD, FTIR, TEM, SEM‐EDS, XPS, UV‐DRS, PL, BET, and TGA were used to characterize the produced material‘s structural and optical properties. The presence of a single phase spinel structure with a distinctive plane (311) was verified by the XRD peak of 2 at 36.9° for Co3O4‐Bi2O3. The SEM pictures revealed clustered consolidated spheres, suggesting particle homogeneity and high interconnectedness. The HR‐TEM and SAED pictures revealed an average crystallite size of 28 nm for the Co3O4‐Bi2O3 heterojunction. The UV‐DRS spectral data demonstrated a 2.1 eV reduction in band gap energy for Co3O4‐Bi2O3 (whereas Co3O4 is 2.4 eV and Bi2O3 is 2.7 eV). Under solar light irradiation, pristine Co3O4, Bi2O3, and Co3O4‐Bi2O3 composites were investigated for photocatalytic degradation of Methylene Blue (MB) and Malachite green (MG) dyes. By adjusting factors such as pH, starting dye concentration, catalyst dosage, and agitation duration, the optimal efficiency was determined. The acquired results showed Co3O4‐Bi2O3 ′s superior activity over both precursors. The composite obtained maximal degradation of 98 % (at pH=11) and 97 % (at pH=9) for MB and MG, respectively. The enhanced photo degradation activity of Co3O4‐Bi2O3 can be due to larger visible light absorption, increased surface area, and decreased h+/e− recombination. The reactive species trapping study was performed to determine the importance of superoxide and hydroxyl radicals during photo degradation. Dye degradation was governed by a pseudo‐first‐order kinetic model. The reusability and stability of Co3O4‐Bi2O3 were confirmed by utilizing the same material for five consecutive runs with both MB and MG dyes. Mass spectra analysis provided insights into the successful degradation of dyes, elucidating intermediate products. The synthesized Co3O4‐Bi2O3 nanocomposite offers unrivalled advantages in terms of structural and optical properties, superior photocatalytic activity, and remarkable stability, making it a promising candidate for efficient dye degradation applications without the formation of toxic by‐products.

Abstract 5579: MGAloss-of-function regulates mitochondrial oxidative metabolism-induced cancer stem cell phenotype during lymphomagenesis with therapeutic potential

Abstract As an antagonist of MYC oncogene, Max gene associated (MGA) gene are implicated in multiple cancers, proposing the potential role of tumor suppressor. Using multi-omics data of The Cancer Genome Atlas (TCGA, n=10,295) and lymphoma datasets from our group (n=702), we defined genetic features associated with MGA and its related MYC/MAX/MXD network members across 36 cancers. Pan-cancer, MGA mutation, predominant as nonsense or frameshift, was observed in 4.39% of all samples. MGA expression was significantly downregulated in mutated samples than that of wild type samples. Moreover, MGA mutation was positively associated with inferior clinical outcomes in diffuse large B-cell lymphoma (P=0.001 and P<0.001 in 2 independent datasets), peripheral T-cell lymphoma (P=0.044) and natural killer/T-cell lymphoma (P=0.012), encouraging in-depth study on the important role of MGA in lymphomagenesis. Conditional knockout of MGA in hematopoietic system using Vav-iCre (Mgafl/fl, Vav-iCre mice) led to reduction in the numbers of peripheral blood lymphocyte due to blockade differentiation and enhanced stemness as evidenced by flowcytometry and RNA-sequencing (RNA-seq). To investigate the molecular mechanism, we performed pulldown assay in NK-92 cells molecular silencing of MGA or scramble control, and subsequently subjected for mass spectrum analysis. A total of 97 proteins were identified to interaction with MGA and mainly enriched to nucleosome (26), cytosolic ribosome (16), immune response (13), and glycolysis (6). Molecular silencing of MGA, localizing in the nucleolus, interfered with ribosomal RNA processing, enhanced “onco-ribosome” biogenesis, and contributed to aberrant translational program characterized by mitochondrial oxidative metabolism. Changes in mitochondrial respiration and membrane potential are key to maintaining stemness in cancer cells. Considering that stemness is important for tumorigenesis, recurrence, metastasis, and drug resistance, we exploited high-throughput drug screening platform and found that targeted inhibition of Exportin 1 (XPO1) significantly suppressed the viability of tumor cells molecular silencing MGA, which were resistant to chemotherapeutic agents such as gemcitabine, etoposide, etc. Mechanically, molecular silencing MGA induced abnormalities of nucleocytoplasmic localization in 739 proteins involving in mitochondrial respiratory chain complex I assembly, oxidative phosphorylation, and mitochondrial translation, 50% (332/739) of which were rescued by treatment with XPO1 inhibitor Selinexor. In summary, MGA initiated lymphoma cell stemness via onco-ribosome mediated activation of mitochondrial oxidative metabolism. Selinexor targeted the aberrant nucleocytoplasmic localization and served as a promising therapeutic agent. Citation Format: Jie Xiong, Wen-Fang Wang, Wei-Li Zhao. MGAloss-of-function regulates mitochondrial oxidative metabolism-induced cancer stem cell phenotype during lymphomagenesis with therapeutic potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5579.

Sarcomeric tropomyosin expression during human iPSC differentiation into cardiomyocytes.

Tropomyosin (TPM) is an essential sarcomeric component, stabilizing the thin filament and facilitating actin's interaction with myosin. In mammals, including humans, there are four TPM genes (TPM1, TPM2, TPM3, and TPM4) each of which generates a multitude of TPM isoforms via alternative splicing and using different promoters. In this study, we have examined the expression of transcripts as well as proteins of various sarcomeric TPM isoforms during human inducible pluripotent stem cell differentiation into cardiomyocytes. During the differentiation time course, we harvested cells on Days 0, 5, 10, 15, and 20 to analyze for various sarcomeric TPM transcripts by qRT-PCR and for sarcomeric TPM proteins using two-dimensional Western blot with sarcomeric TPM-specific CH1 monoclonal antibody followed by mass spectra analyses. Our results show increasing levels of total TPM transcripts and proteins during the period of differentiation, but varying levels of specific TPM isoforms during the same period. By Day 20, the rank order of TPM transcripts was TPM1α > TPM1κ > TPM2α > TPM1μ > TPM3α > TPM4α. TPM1α was the dominant protein produced with some TPM2 and much less TPM1κ and μ. Interestingly, small amounts of two lower molecular weight TPM3 isoforms were detected on Day 15. To the best of our knowledge this is the first demonstration of TPM1μ non-muscle isoform protein expression before and during cardiac differentiation.

Spirolactam ring locking and unlocking tuned solvent regulated unique Hg(II) sensing by a novel AIE active Rhodamine −1, 2 diamino propane-based Schiff chemosensor and its pH sensor performance

The present study highlights the development, identification, and solvent-regulated chemosensing property of a Schiff base chemosensor (E)-2-(2-((5-chloro-2-hydroxybenzylidene)amino)propyl)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one (RBAS). The Schiff base RBAS is developed by the simple condensation of 5-chloro salicylaldehyde and rhodamine-1,2 diamino propane derivative (RBAP). Interestingly this probe can optically as well as fluorometrically exhibit pH sensor activity and the spirolactam ring opening and the conversion from enol to keto form in lower and higher pH regions respectively are the main key factors to show pH sensor activity. Several spectroscopic, Dynamic Light Scattering (DLS), and scanning electron microscopy (SEM) studies confirm the AIE active property of the probe in 2:8 DMSO-water and ethanol-water mediums where the probe exhibits strong luminescence properties. Interestingly in ethanol-water and DMSO-water medium, it can detect Hg(II) via turn-on and off fluorescence respectively. Actually, in different solvent mediums, the presence of Hg(II) plays a crucial role in the spirolactam ring opening and closing of the developed probe. Simultaneously in an ethanol-water medium, it can detect picric acid by turning off fluorescence. By using mass and NMR spectrum analysis, the 1:1 stoichiometric addition of the probe and target analytes has been verified and the density functional theory (DFT) study is implemented in optimizing the probe-analyte structure. The live cell imaging study gives the approval of the biosensing ability of the probe. Impressively the probe can be successfully used to detect Hg(II) in real soil samples.

MALDI-TOF as a powerful tool for identifying and differentiating closely related microorganisms: the strange case of three reference strains of Paenibacillus polymyxa

Accurate identification and typing of microbes are crucial steps in gaining an awareness of the biological heterogeneity and reliability of microbial material within any proprietary or public collection. Paenibacillus polymyxa is a bacterial species of great agricultural and industrial importance due to its plant growth-promoting activities and production of several relevant secondary metabolites. In recent years, matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) has been widely used as an alternative rapid tool for identifying, typing, and differentiating closely related strains. In this study, we investigated the diversity of three P. polymyxa strains. The mass spectra of ATCC 842T, DSM 292, and DSM 365 were obtained, analysed, and compared to select discriminant peaks using ClinProTools software and generate classification models. MALDI-TOF MS analysis showed inconsistent results in identifying DSM 292 and DSM 365 as belonging to P. polimixa species, and comparative analysis of mass spectra revealed the presence of highly discriminatory biomarkers among the three strains. 16S rRNA sequencing and Average Nucleotide Identity (ANI) confirmed the discrepancies found in the proteomic analysis. The case study presented here suggests the enormous potential of the proteomic-based approach, combined with statistical tools, to predict and explore differences between closely related strains in large microbial datasets.

Airmass history, night-time particulate organonitrates, and meteorology impact urban SOA formation rate

With respect to air quality, the San Antonio metropolitan area, with a population of 1.45 million and the second largest city in Texas, has been designated as non-attainment by the United States Environmental Protection Agency in recent years. Despite the operation of multiple stationary air quality monitoring sites by the Texas Commission on Environmental Quality, the in-situ measurements of submicron aerosol and its precursors in the region is limited. To better understand the formation of secondary organic aerosol (SOA) in the San Antonio urban core, we conducted observations of a range of trace gases, volatile organic compounds, submicron aerosol, and meteorological parameters in May 2017. Data from a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) show that organic aerosol (OA) was the dominant component of non-refractory submicron particulate matter (average±1σ, 55 ± 32 %, 5.86 ± 3.40 μg m−3), followed by sulfate (33 ± 23 %, 3.52 ± 2.47 μg m−3). Aerosol liquid water contents predicted by ISORROPIA-II greatly increase from Continental to Oceanic airmass history scenarios, while inorganic aerosol pH remains very acidic. Positive matrix factorization (PMF) analysis of the OA mass spectra indicates that two classes of oxygenated OA (less and more-oxidized OOA, LO and MO) together constituted the bulk of OA mass during the study period (MO-OOA: 44 ± 39 %, 2.35 ± 2.07 μg m−3; LO-OOA: 42 ± 34 %, 2.22 ± 1.77 μg m−3), while the fraction of hydrocarbon-like OA was limited (13 ± 21 %, 0.71 ± 1.11 μg m−3). Using in-situ meteorological data and location-specific empirical coefficients, a zero-dimensional model that utilized PMF factors as proxies to calculate the net rate of formation of types of SOA has been developed; similar calculations were used to estimate the formation rate of particulate organonitrates (pON). The results from the model reveal the importance of pON formation in LO-OOA formation overnight and the influence of temperature and photochemistry during the day. The relationships between local atmospheric factors and the net rate of formation of MO-OOA are not statistically significant. These results emphasize how HR-ToF-AMS-PMF factors could be incorporated into chemistry modeling to evaluate quantitatively the rates of formation of SOA and reveal diurnal differences in SOA formation pathways in a major urban area in southern United States.

An Efficient Synthesis and Characterization of Amine and Amide Derivatives of Ethyl 6‐(trifluoromethyl)nicotinate

AbstractA new bioactive amine and amide derivatives of trifluoromethyl pyridine was produced with good yields from commercially accessible and inexpensive starting materials and characterized using 1HNMR, 13CNMR, and mass spectrum analysis. We prepared all the intermediates in gram scale, it will be viable for industrial production, because the compounds contain a bioactive core component, trifluoromethylpyridine, they will be useful in developing new insecticides with improved therapeutic action.

Neolignan Glycoside and Other Constituents From the Leaves of Ligustrum sinense and Their Anti-Inflammatory Activity

Objectives: The aim of the project was the isolation, structure elucidation, and anti-inflammatory evaluation of compounds from the leaves of Ligustrum sinense Lour. Methods: Chromatographic techniques were used to isolate anti-inflammatory compounds from the methanol extract of L sinense leaves. The structures of compounds were elucidated by analyses of mass spectra, nuclear magnetic resonance data, and Circular dichroism spectra. Compounds were evaluated using anti-inflammatory assays. Results: One new neolignane glucoside, neoligustrume A (1), along with eleven known compounds, ligujaponoside A (2), ligujaponoside B (3), ligustroside (4), oleuropein (5), ligustaloside A dimethyl acetal (6), ligustaloside B dimethyl acetal (7), olivil (8), (+)-cycloolivil (9), kaempferol 3- O-β-D-glucopyranoside-7- O-α-L-rhamnopyranoside (10), oleanoic acid (11), and hydroxytyrosol (12) were isolated from the methanol extract of L sinense leaves. Compounds 2, 3, and 12 showed significant inhibitory NO production with IC50 values of 16.3 ± 0.5, 18.2 ± 1.1, and 15.7 ± 1.9 μM, respectively. Compounds 4-7 and 11 showed moderate inhibitory NO production with IC50 values ranging from 21.4 to 45.0 µM. Moreover, compound 12 showed the most TNF-α inhibition with 58.1 ± 5.7% at a concentration of 50 μM. Conclusions: One new and 11 known compounds were isolated from L sinense. This is the first report of compounds 2-9 from L sinense. Compounds 2, 3, and 12 showed significant inhibitory NO production with IC50 values of 16.3 ± 0.5, 18.2 ± 1.1, and 15.7 ± 1.9 μM, respectively. Compound 12 could be the anti-inflammatory source.

Computational design, synthesis, and assessment of 3-(4-(4-(1,3,4-oxadiazol-2-yl)-1H-imidazol-2-yl)phenyl)-1,2,4-oxadiazole derivatives as effective epidermal growth factor receptor inhibitors: a prospective strategy for anticancer therapy.

The epidermal growth factor receptor (EGFR) enzyme plays a critical role in governing the cell cycle, positioning it as a promising target for the development of anticancer drugs. In this study, we endeavored to design and synthesize innovative EGFR inhibitors with potential applications in anticancer therapy. A novel series of compounds, namely 3-(4-(4-(1,3,4-oxadiazol-2-yl)-1H-imidazol-2-yl)phenyl)-1,2,4-oxadiazoles (30a-j), were meticulously designed using FBDD efforts and synthesized. The synthesized compounds underwent thorough characterization using 1HNMR, 13CNMR, HRMS, and mass spectrum analyses. The in vitro anticancer activities of the newly developed compounds (30a-j) were evaluated against four human cancer cell lines such as prostate cancer (PC3 & DU-145), lung cancer (A549), and liver cancer (HEPG2) using the MTT method. The results, expressed as IC50 values, demonstrated significant anticancer activity for several compounds, with five compounds (30a, 30b, 30c, 30i, and 30j) exhibiting superior potency compared to the established anticancer drug etoposide. Notably, compound 30a emerged as the most promising compound, displaying potent cytotoxicity. We also conducted a screening of the compounds on the normal Vero cell line, revealing a pronounced selectivity of the compounds against cancer cell lines, with no observable impact on the normal cell lines. Moreover, the synthesized compounds were investigated for their impact on enzyme EGFR activity. The findings revealed a robust inhibitory effect against the EGFR wild-type enzyme and a 10-fold inferior potency against the mutant form of EGFR. This observation underscores the potential of the new derivatives as effective EGFRWT inhibitors with substantial anticancer efficacy. Further studies, including cell cycle analysis and apoptosis assays in HEPG2 cell lines, revealed cell cycle arrest at G1/G0 and G2 phases. We also evaluated the potential influence of compound 30a on the EGFR pathway using western blot analysis, revealing a significant inhibition of EGFR autophosphorylation in HEPG2 cells. In conclusion, our findings highlight the promise of these novel compounds as potent EGFR inhibitors, encouraging further investigation and development for the creation of novel and effective anticancer therapeutics.

Cardiomyocyte-derived USP28 negatively regulates antioxidant response and promotes cardiac hypertrophy via deubiquitinating TRIM21.

Rationale: Cardiac hypertrophy is an important pathological basis for heart failure. Most physiological activities of cardiomyocytes are regulated by proteins and their post-translational modification. Deubiquitinating enzymes (DUBs) are involved in protein stability maintenance and closely related to myocardial hypertrophy. In this study, we aimed to clarify the regulatory role of a DUB, ubiquitin-specific peptidase 28 (USP28), in cardiac hypertrophy and explore the molecular mechanism behind. Methods: Transcriptome and single-cell mRNA sequencing was used to demonstrate the association of USP28 and cardiac hypertrophy. Cardiomyocyte-specific USP28 knockout mice (USP28CKO) were subjected to angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) models. Coimmunoprecipitation combined mass spectrum analysis (Co-IP/MS) was applied to screen out the substrate of USP28. Results: We first showed the up-regulation of USP28 in cardiac hypertrophy, and its cellular localization of cardiomyocytes. USP28CKO protects mouse heart against Ang II- or TAC-induced cardiac dysfunction and hypertrophy. Mechanistically, we identified tripartite motif-containing protein 21 (TRIM21) as the potential substrate of USP28 by Co-IP/MS analysis. Cardiomyocyte USP28 deubiquitinates and stabilizes TRIM21 to negatively regulate nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response, increasing oxidative stress in cardiomyocytes and promoting cardiac hypertrophy and injury. Finally, using a selective USP28 inhibitor Otilonium Bromide, we confirmed the therapeutic effect of pharmacological inhibition of USP28 against TAC-induced established hypertrophic heart failure. Conclusion: Our study illustrates a cardiomyocyte-specific USP28-TRIM21 axis in regulating hypertrophic cardiomyopathy and presents USP28 as a potential target for the treatment of cardiac hypertrophy.

De-polymerisation and hydrolysis of seed storage protein is involved in the freezing tolerance of hydrated Brassica oleracea seeds

Hydrolysis of globulins might be involved in the freezing tolerance of hydrated lettuce seeds. The mechanism was further explored in hydrated brassica (Brassica oleracea) seeds, by application of 5,5'-dithiobis(2-nitro- benzoicacid) (DTNB), the Ellman's reagent, which can bind to the free sulphydryl side chain of cysteine. DTNB increased the viability of hydrated brassica seeds after slow cooling (-3°C hour-1 ) to -17°C. Two-dimensional electrophoresis and mass spectra analysis indicated the accumulation of small peptides derived from 12S globulins (cruciferin) in DTNB-treated seeds after slow cooling. The seed storage peptides with different molecular weight were cooled and the ice formation during cooling observed by cryomicroscopy, which proved that peptides of smaller molecular size produced smaller and rounder crystals. The smallest peptide in DTNB- treated seeds produced the smallest and roundest crystals during cooling. The levels of ASA, DHA and GSH were specifically up-regulated after DTNB treatment and following slow cooling, which indicates that DTNB enhanced the circulation of ASA and GSH to resist the oxidative stress. Consistent with this finding, RNA-seq and real time PCR indicated that glutathione reductase (GR) was up-regulated after DTNB treatment.

Deubiquitinase USP39 promotes SARS-CoV-2 replication by deubiquitinating and stabilizing the envelope protein

The SARS-CoV-2 envelope (E) protein is highly conserved among different viral variants and important for viral assembly and production. Our recent study found that the E protein is ubiquitinated and degraded by the E3 ligase RNF5 through the proteasome pathway. However, whether E ubiquitination can be reversed by host deubiquitinase has not yet been determined. Here, we identify by mass spectrum analysis that the deubiquitinases USP14 and USP39 specifically interact with E, while USP39 potently reverses E polyubiquitination. USP39 interacts with E via the arginine-rich motif (AR) and deubiquitinates E polyubiquitination via the inactive ubiquitin-specific protease domain. Therefore, USP39 protects E from RNF5-mediated degradation, resulting in the enhancement of E stability and E-induced cytokine storms. Moreover, loss-and-gain assays demonstrated that USP39 promotes the replication of various SARS-CoV-2 strains by stabilizing protein level of E that can be ubiquitinated but not other viral proteins. Our findings provide useful targets for the development of novel anti-SARS-CoV-2 strategies.

CuFeS2/activated carbon heterostructure as a microwave-responsive catalyst for reductive and oxidative degradation of ibuprofen, ketoprofen, and diclofenac

We prepared a novel microwave (MW) responsive catalyst by assembling CuFeS2 (CFS) nanoparticles to activated carbon (AC), creating a stable heterostructure named ACFS. The efficiency, structural aspects, and surface mechanisms of the ACFS catalyst were investigated through the degradation of ibuprofen (IBP), ketoprofen (KTP), and diclofenac (DCF) under optimized mild reaction conditions. Total mineralization was reached between 20 and 30 min for all compounds, following pseudo-first-order kinetics, with high catalyst recycling stability in up to 10 consecutive cyclic runs. The plausible degradation pathways proposed according to the mass spectra analysis revealed that while IBP and KTP were oxidized, DCF degradation routes split into direct oxidation or reduction followed by oxidation after 15 min of MW irradiation. We demonstrated by employing quantum chemical calculations that the preferential degradation routes for each compound were related to the generation of reactive oxygen species and its relation to the surface phenomena. The combined mechanisms revealed the occurrence of an effective electronic-charge transfer during catalytic reductions as well as •OH production enhanced by hot spots formed during oxidations. Consequently, this work proves that metal/carbon heterostructures can be robust and versatile for reductive and oxidative reactions assisted by MW.