Mass Spectrometry Research Articles

Chemical Composition, In vitro and In silico Evaluation of Essential Oil from Ocimum tenuiflorum and Coriandrum sativum Linn for Lung Cancer.

Medicinal plants play an essential role in everyday life; plants highly contain therapeutic phytoconstituents commonly used to treat various diseases. This paper discusses the Chemical composition, In vitro antiproliferative activity and In silico study of essential oil extracted from Ocimum tenuiflorum (family Lamiaceae) and Coriandrum sativum (family Apiaceae). In present study GC-MS was used to identify the chemical constituents from O. tenuiflorum and C. sativum. In vitro antiproliferative activity was performed on A549 cancer cell lines. In silico study was performed by Schrodinger's maestro software to identify chemical constituents in both plants as potential EGFR inhibitors for the treatment of lung cancer. The essential oil was extracted by hydro distillation from aerial parts of O. tenuiflorum and C. sativum. The volatile oil sample was analyzed by (GC-MS) Gas Chromatography- Mass Spectrometry. Different chemical constituents were identified based on the retention index and compared with the NIST library. The oil samples from O. tenuiflorum and C. sativum was also evaluated for antiproliferative activity against human lung cancer A549 cell lines. In silico study was performed by Schrodinger maestro software against EGFR (PDB ID 5HG8). O. tenuiflorum essential oil contains Eugenol (42.90%), 2-β-Elemene (25.98%), β- Caryophyllene (19.12%) are the major constituents. On the other side, C. sativum contains nnonadecanol- 1 (16.37%), decanal (12.37%), dodecanal (12.27%), 2-Dodecanal (9.67%), Phytol (8.81%) as the major constituents. Both the oils have shown in vitro antiproliferative activity against human lung cancer cell lines A549 having IC50 values of 38.281 μg/ml (O. tenuiflorum) and 74.536 μg/ml (C. sativum). Molecular interactions of constituents hydro distilled from two oils was analysed by schrodinger maestro software against EGFR (PDB ID 5HG8). The oil sample extracted from O. tenuiflorum showed more antiproliferative activity than C. sativum. In silico study showed that two chemical constituents, namely di-isobutyl phthalate (-7.542 kcal/mol) and dibutyl phthalate (-7.181 kcal/mol) from O. tenuiflorum and one diethyl phthalate (-7.224 kcal/mol) from C. sativum having more docking score than standard Osimertinib which indicates the effectiveness of oils for lung cancer.

To Explore the Mechanism of Maiwei Dihuang Decoction in the Treatment of Non-small Cell Lung Cancer based on Network Pharmacology Combined with LC-MS.

To explore the mechanism of Maiwei Dihuang decoction in the treatment of non-small cell lung cancer (NSCLC) by using network pharmacology and LC-MS technology. The effective components in Maiwei Dihuang decoction were detected by liquid chromatography- mass spectrometry (LC-MS). Use the SuperPred database to collect the relevant targets of the active ingredients of Mai Wei Di Tang, and then collect the relevant targets of nonsmall cell lung cancer from GeneCards, DisgenNET and OMIM databases. On this basis, PPI network construction, GO enrichment analysis and KEGG pathway annotation analysis were carried out for target sites. Finally, AutoDock Vina is used for molecular docking. We further screened 16 effective Chinese herbal compounds through LC-MS combined with ADME level. On this basis, we obtained 77 core targets through protein interaction network analysis. Through GO, KEGG analysis and molecular docking results, we finally screened out the potential targets of Maiwei Dihuang Decoction for NSCLC: TP53, STAT3, MAPK3. Maiwei Dihuang decoction may play a role in the treatment of NSCLC by coregulating TP53/STAT3/MAPK3 signal pathway.

Non-radical oxidation driven by iron-based materials without energy assistance in wastewater treatment.

Chemical oxidation is extensively utilized to mitigate the impact of organic pollutants in wastewater. The non-radical oxidation driven by iron-based materials is noted for its environmental friendliness and resistance to wastewater matrix, and it is a promising approach for practical wastewater treatment. However, the complexity of heterogeneous systems and the diversity of evolutionary pathways make the mechanisms of non-radical oxidation driven by iron-based materials elusive. This work provides a systematic review of various non-radical oxidation systems driven by iron-based materials, including singlet oxygen (1O2), reactive iron species (RFeS), and interfacial electron transfer. The unique mechanisms by which iron-based materials activate different oxidants (ozone, hydrogen peroxide, persulfate, periodate, and peracetic acid) to produce non-radical oxidation are described. The roles of active sites and the unique structures of iron-based materials in facilitating non-radical oxidation are discussed. Commonly employed identification methods in wastewater treatment are compared, such as quenching, chemical probes, spectroscopy, mass spectrometry, and electrochemical testing. According to the process of iron-based materials driving non-radical oxidation to remove organic pollutants, the driving factors at different stages are summarized. Finally, challenges and countermeasures are proposed in terms of mechanism exploration, detection methods and practical applications of non-radical oxidation driven by iron-based materials. This work provides valuable insights for understanding and developing non-radical oxidation systems.

Deleterious Biological Effects of Endocrine Disruptors: An Insight into Human Health Risks.

Endocrine-disrupting chemicals (EDCs) are environmental pollutants. Since EDCs are present in various consumer products, contamination of human beings is very common. EDCs have deleterious effects on various systems of the body, especially the endocrine and reproductive systems. EDCs interfere with the synthesis, metabolism, binding, or cellular responses of natural estrogens and alter various pathways. Biological samples such as blood, saliva, milk, placental tissue, and hair are frequently used for biomonitoring and the detection of EDCs. Early detection and intervention may help in preventing congenital anomalies and birth defects. The common methods for determining the presence of EDCs in body fluids include gas chromatography, high-performance liquid chromatography, and mass spectrometry. Understanding the health effects and dangers of EDC is important, given their widespread use. This mini-review aims to summarize the adverse biological effects of several important classes of EDCs and highlights future perspectives for appropriate control.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing–antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

An Investigation of Pharmacokinetic Interaction of Vericiguat with Apigenin based on a Newly Developed Ultra-performance Liquid Chromatography-tandem Mass Spectrometry Assay.

Vericiguat, as a new stimulator of soluble guanylate cyclase (s- GC), was recently approved as a first-in-class treatment for reducing risks in patients with ejection fraction less than 45 percent and heart failure (HF) in the USA. The main aim of the present experiment was to establish an acceptable, sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentration levels of vericiguat in rats, and to further evaluate the effect of apigenin on the metabolism of vericiguat in vivo. In sample processes, acetonitrile was finally chosen for quickly precipitating protein. The levels of vericiguat in plasma were analyzed by a Xevo TQ-S triple quadrupole tandem mass spectrometry (Milford, MA, USA) in a positive ion mode. The scope of the calibration standard for vericiguat ranged from 0.5 to 1000 ng/mL, where a great linearity was acceptable. The lower limit of quantification (also called LLOQ) of vericiguat presented the sensitivity of this assay was evaluated as low as 0.5 ng/mL. Additionally, selectivity, accuracy and precision, extraction recovery, matrix effect, and stability were all verified. Subsequently, this approach also supported to assess the plasmatic concentrations of vericiguat from an interaction survey on herb-- drug, in which oral administration of apigenin (20 mg/kg) obviously increased the plasmatic levels of vericiguat and altered the pharmacokinetics of vericiguat in rats. These results would help us to further understand the pharmacokinetic properties of vericiguat when co-administration with apigenin, and to avoid unexpected clinical risks in the future.

Synthesis, Docking Study of Some Novel Chromeno[4',3'-b]Pyrano [6,5-d]Pyrimidine Derivatives Against COVID-19 Main Protease (Mpro) (6LU7, 6M03).

In this work, some new chromeno[4',3'-b]pyrano[6,5-d]pyrimidines,3-amino and 3-methyl-5-aryl-4-imino-5(H)-chromeno[4',3'-b]pyrano[6,5-d]pyrimidine-6-ones derivatives were synthesized. Chromenopyrimidines have attracted significant attention recently because of their activities, such as antiviral and cytotoxic activity. All synthesized compounds were characterized using IR, 1H-NMR, Mass Spectroscopy, and elemental analysis data. Molecular docking studies were carried out to determine the inhibitory action of studied ligands against the Main Protease (6LU7, 6m03) of coronavirus (COVID-19). Moreover, the Lipinski Rule parameters were calculated for the synthesized compounds. The result of the docking studies showed a significant inhibitory action against the Main protease (Mpro) of SARS-CoV-2, and the binding energy (ΔG) values of the ligands against the protein (6LU7, 6M03) are -7.8 to -9.9 Kcal/mole. It may conclude that some ligands were likely to be considered lead-like against the main protease of SARS-CoV-2.

The marriage between stable isotope ecology and plant metabolomics - new perspectives for metabolic flux analysis and the interpretation of ecological archives.

Even though they share many thematical overlaps, plant metabolomics and stable isotope ecology have been rather separate fields mainly due to different mass spectrometry demands. New high-resolution bioanalytical mass spectrometers are now not only offering high-throughput metabolite identification but are also suitable for compound- and intramolecular position-specific isotope analysis in the natural isotope abundance range. In plant metabolomics, label-free metabolic pathway and metabolic flux analysis might become possible when applying this new technology. This is because changes in the commitment of substrates to particular metabolic pathways and the activation or deactivation of others alter enzyme-specific isotope effects. This leads to differences in intramolecular and compound-specific isotope compositions. In plant isotope ecology, position-specific isotope analysis in plant archives informed by metabolic pathway analysis could be used to reconstruct and separate environmental impacts on complex metabolic processes. A technology-driven linkage between the two disciplines could allow us to extract information on environment-metabolism interaction from plant archives such as tree rings but also within ecosystems. This would contribute to a holistic understanding of how plants react to environmental drivers, thus also providing helpful information on the trajectories of the vegetation under the conditions to come.

Phenolic Bisabolane Sesquiterpene Derivatives from an Arctic Marine-derived Fungus Aspergillus sydowii MNP-2

Background:: Filamentous fungi in the genus Aspergillus are well known for their important roles in production of bioactive secondary metabolites with diversely chemical structures and potential application in pharmaceutical industry. Objective:: The present study aimed to investigate the phenolic bisabolane sesquiterpene (PBS) derivatives from an Arctic marine-derived fungus Aspergillus sydowii MNP-2. Methods:: In this study, antimicrobial activities were carried out according to the broth microdilution assay, nitric oxide (NO) production in mouse macrophages (RAW264.7) and BV2 microglial cells was used to detect the inhibitory effect of compounds in inflammatory reactions, and in vitro inhibitory cell proliferation activity was determined by the cell counting kit-8 (CCK-8) assay. Results:: In this work, chemical investigation of an Arctic marine-derived strain A. sydowii MNP-2 led to the isolation of 11 PBSs (1-11) using various chromatographic methods. Their chemical structures were unambiguously determined by 1H NMR spectroscopy and mass spectrometry analyses as well as comparison with literature data. It is noteworthy that compounds 1, 7 and 11 were firstly obtained from A. sydowii. Antimicrobial assay showed that these chemicals had no potent inhibitory effect on Staphylococcus aureus, Escherichia coli, and Candida albicans with MIC values > 16 μg/mL. Additionally, the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)- induced inflammation in mouse macrophages (RAW264.7) and BV2 microglial cells were all below 10% for compounds 4-6 and 8, indicating almost negligible anti-inflammatory efficacy. Among the tested compounds 4-6 and 8 for tumor-cell proliferation inhibition activities, compound 5 demonstrated the strongest inhibitory effect against human acute promyelocytic leukemia cells (HL-6) with a 44.76% inhibition rate. Conclusion:: In the present study, 11 PBS derivatives were purified and characterized from the solidand liquid-state fermentations of the Arctic marine-derived fungus A. sydowii MNP-2. Unfortunately, none of these metabolites had significant antimicrobial, anti-inflammatory, or tumor-cell proliferation inhibition activities.

Improved Discrimination of Mass Spectral Isomers Using the High-Dimensional Consensus Mass Spectral Similarity Algorithm.

This study employs a high-dimensional consensus mass spectral (HDCMS) similarity scoring technique to discriminate isomers collected using an electron ionization mass spectrometer. The HDCMS method was previously introduced and applied to the discrimination of mass spectra of constitutional isomers, methamphetamine and phentermine, collected with direct analysis real-time mass spectrometry (DART-MS). The method formulates the problem of discriminating mass spectra in a mathematical Hilbert space and is hence called "high dimensional." It requires replicate mass spectra to build a Gaussian model and evaluate the inner products between these functions. The resulting measurement variability is used as a signature by which to discriminate spectra. In this work, HDCMS is tested on electron impact ionization (EI) mass spectra of 7 terpene and terpene-related (C10H16 and C10H14) isomers with experimental retention indices that differ by less than 30 and with traditional cosine similarity scores greater than 0.9, on a scale of 0 to 1, when compared with at least one other compound in the test set. Using identical instrument parameters, 15 replicate gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) spectra of each isomer were collected and separated into distinct library and query sets. The HDCMS algorithm discriminated each isomer, indicating the method's potential. Because the method requires replicate measurements, observations from a simple heuristic study of the number of replicates required to discriminate these isomers is presented. The paper concludes with a discussion of compound discrimination using HDCMS and the benefits and drawbacks of applying the method to EI-MS data.

Arsenic exposure and measures of glucose tolerance in Bangladeshi adults: A cross-sectional study.

Arsenic has been associated with diabetes and impaired glucose tolerance in many studies, although some reports have shown null findings. We conducted a cross-sectional study among 300 adults in Bangladesh. Participants were randomly selected from a roster of 1800 people who previously participated in studies of arsenic and skin lesions. We measured fasting glucose and insulin levels. We assessed drinking water arsenic concentration using graphite furnace atomic absorption spectrophotometry (GF-AAS) and toenail arsenic concentration using inductively coupled mass spectrometry (ICP-MS). We ran covariant-adjusted, linear regression and spline models to examine associations of arsenic concentrations with the homeostatic model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, and HOMA of beta-cell function (HOMA-β), a marker of beta-cell function. Among 285 participants with complete data, the median (IQR) arsenic concentration was 4.0 (6.9) μg/g in toenails and 39.0 (188.5) μg/L in drinking water. Arsenic concentrations were not associated with insulin resistance or beta-cell function. HOMA-IR was 0.67% lower and HOMA-β was 0.28% lower per µg/g increment in toenail arsenic, but these effect estimates were small, and confidence intervals crossed the null value. Although arsenic exposure has been associated with diabetes, we found no evidence of an adverse effect on insulin resistance or beta-cell function.

A Differential Protein Study on Bronchoalveolar Lavage Fluid at Different Stages of Silicosis.

In this study, by comparing the difference in protein expression in bronchoalveolar lavage fluid between silicosis patients in different stages and healthy controls, the pathogenesis of pneumoconiosis was discussed, and a new idea for the prevention and treatment of pneumoconiosis was provided. The lung lavage fluid was pretreated by 10 K ultrafiltration tube, Agilent 1100 conventional liquid phase separation, strong cation exchange column (SCX) HPLC pre-separation, and C18 reverse phase chromatography desalting purification, and protein was labeled with isotope. GO, KEGG pathway, and PPI analysis of differential proteins were conducted by bioinformatics, and protein types and corresponding signal pathways were obtained. Thermo Q-Exactive mass spectrometry identified 943 proteins. T-test analysis was used to evaluate the different significance of the results, and the different protein of each group was obtained by screening with the Ratio≥1.2 or Ratio≤0.83 and P<0.05. We found that there are 16 kinds of protein throughout the process of silicosis. There are different expressions of protein in stages Ⅲ/control, stages Ⅱ/control, stage Ⅰ/control, stages Ⅲ/ stages Ⅱ, stages Ⅲ/ stage Ⅰ and stages Ⅱ/ stage Ⅰ groups. The results of ontology enrichment analysis of total differential protein genes show that KEGG pathway enrichment analysis of differential protein suggested that there were nine pathways related to silicosis. The main biological changes in the early stage of silicosis are glycolysis or gluconeogenesis, autoimmunity, carbon metabolism, phagocytosis, etc., and microfibril-associated glycoprotein 4 may be involved in the early stage of silicosis. The main biological changes in the late stage of silicosis are autoimmunity, intercellular adhesion, etc. Calcium hippocampus binding protein may participate in the biological changes in the late stage of silicosis. It provides a new idea to understand the pathogenesis of silicosis and also raises new questions for follow-up research.

Phosphoproteomics predict response to midostaurin plus chemotherapy in independent cohorts of FLT3-mutated acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a bone marrow malignancy with poor prognosis. One of several treatments for AML is midostaurin combined with intensive chemotherapy (MIC), currently approved for FLT3 mutation-positive (FLT3-MP) AML. However, many patients carrying FLT3 mutations are refractory or experience an early relapse following MIC treatment, and might benefit more from receiving a different treatment. Development of a stratification method that outperforms FLT3 mutational status in predicting MIC response would thus benefit a large number of patients. We employed mass spectrometry phosphoproteomics to analyse 71 diagnosis samples of 47 patients with FLT3-MP AML who subsequently received MIC. We then used machine learning to identify biomarkers of response to MIC, and validated the resulting predictive model in two independent validation cohorts (n=20). We identified three distinct phosphoproteomic AML subtypes amongst long-term survivors. The subtypes showed similar duration of MIC response, but different modulation of AML-implicated pathways, and exhibited distinct, highly-predictive biomarkers of MIC response. Using these biomarkers, we built a phosphoproteomics-based predictive model of MIC response, which we called MPhos. When applied to two retrospective real-world patient test cohorts (n=20), MPhos predicted MIC response with 83% sensitivity and 100% specificity (log-rank p<7∗10-5, HR=0.005 [95% CI: 0-0.31]). In validation, MPhos outperformed the currently-used FLT3-based stratification method. Our findings have the potential to transform clinical decision-making, and highlight the important role that phosphoproteomics is destined to play in precision oncology. This work was funded by Innovate UK grants (application numbers: 22217 and 10054602) and by Kinomica Ltd.

Metabolomics and chemometrics-driven valorisation of mango leaves: Unveiling putative α-amylase and α-glycosidase inhibitory metabolites

This study presents a comprehensive investigation into the metabolite composition of various mango leaf samples using Ultra Performance Liquid Chromatography-High Resolution Mass Spectrometry (UPLC-HRMS). A total of 103 chromatographic peaks representing diverse metabolite groups were annotated, revealing significant variations in chemical composition among different mango varieties. Polyphenols emerged as the most abundant class, with mangiferin being the major polyphenol detected in most varieties, including Awis, Sukari, Sinara, Sedika, and Alfonse. Trihydroxybenzoyl mangiferin was predominant in Sedika and Alfonse varieties. Flavonoids, such as flavanone glycosides and flavone glycosides, were also prominent. O-methylnaringenin pentoside was the major flavanone glycoside detected in Awis, Sukari, and Sinara varieties, while naringenin-O-hexoside was predominant in Alfonse. Phenolic acids were detected across all varieties, with protocatechuic acid and gallic acid being major components. Protocatechuic acid was identified in all varieties except Sedika and Naomi, where gallic acid dominated. Kaempferol and di-O-methylquercetin were exclusively detected in the Naomi variety. In-vitro enzyme inhibition assays against α-amylase and α-glycosidase enzymes revealed dose-dependent inhibitory effects of mango leaf extracts, with variations in potency among varieties. The most potent inhibitors of α-amylase activity were found in extracts from Sukari and Alfonse leaves, while those from Sukari and Sedika leaves showed the strongest inhibition of α-glycosidase activity. Interestingly, the extracts that exerted the highest inhibition of α-amylase activity did not necessarily inhibit α-glycosidase activity significantly. Additionally, glucose uptake promotion assays identified Awis and Sedika leaves as the most potent promoters of glucose uptake.

Molecular characterization on the fractionation of organic phosphorus induced by iron oxide adsorption using ESI-FT-ICR MS

The interaction between organic phosphorus (OP) and iron oxide significantly influences the phosphorus cycle in the natural environment. In shallow lakes, intense oxidation-reduction fluctuations constantly alter the existing form of iron oxides, but little is known about their impact on the adsorption and fractionation of OP molecules. In this study, electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS) was used to investigate the fractionation of OP from alkali-extracted sediment induced by crystalline goethite and amorphous ferrihydrite adsorption at a molecular scale. The results showed that ferrihydrite and goethite both exhibited high OP adsorption, and the adsorption amount decreased as the pH increased. The adsorption kinetics matched the pseudo-second-order equation. The ESI-FT-ICR MS analysis showed that 91 P-containing formulas were detected in the alkaline-extracted sediment solution. Ferrihydrite and goethite adsorbed 51 and 24 P-containing formulas, respectively, with adsorption rates of 56.0 % and 26.4 %. Ferrihydrite could adsorb more OP compounds than goethite, but no obvious molecular species selectivity was observed during the adsorption. The P-containing compounds, including unsaturated hydrocarbons-, lignin/carboxyl-rich alicyclic molecule (CRAM)-, tannin-, and carbohydrate-like molecular compounds, were more suitable for iron oxide adsorption. The double bond equivalence (DBE) is a valuable parameter that indicates OP fractionation during adsorption, and P-containing compounds with lower DBE values such as lipid- and protein-like molecular were prone to remain in the solution after adsorption. These research results provide insights into the biogeochemical cycling process of P in the natural environment.

The Pharmacokinetic Interaction of Tirabrutinib with Voriconazole, Itraconazole, and Fluconazole in SD Rats by UPLC-MS/MS.

Tirabrutinib is an orally effective, approved, and highly selective second-generation Bruton's tyrosine kinase (BTK) inhibitor for the treatment of recurrent or refractory primary central nervous system lymphoma (PCNSL). This study aimed to develop an ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) method for the determination of tirabrutinib concentration in rat plasma, where zanubrutinib was used as an internal standard (IS). This method was also applied to study whether tirabrutinib would interact with voriconazole, itraconazole, and fluconazole in rats, providing a reference value for clinical medication guidance. In the current study, the organic solvent protein precipitation method was used to treat plasma samples, which is simple and reproducible. Tirabrutinib (m/z 455.32 → 320.21) and zanubrutinib (m/z 472.13 → 455.04) were separated on a Waters Acquity BEH C18 column (2.1 × 50 mm, 1.7 μm) and detected by multiple reaction monitoring (MRM) in positive ionization mode. The method showed good linearity in the range of 5-3000 ng/mL for tirabrutinib with the lower limit of quantification (LLOQ) of 5 ng/mL. The recovery and matrix effects were 85.7-91.0% and 102.0-113.3%, respectively. The accuracy, precision, stability, and carry-over effect were also acceptable. The method could also be used for determining the pharmacokinetic interaction of tirabrutinib in rats. The results showed AUC0→∞ of tirabrutinib to be increased by 139.3% and 83.9% in the presence of voriconazole and fluconazole, respectively, while itraconazole had little effect. It is necessary to monitor the concentration of tirabrutinib in patients when it is combined with voriconazole and fluconazole to achieve a better therapeutic effect and reduce the risk of adverse reaction. Further research should be conducted in the future.

Molecular characterization of nontarget brominated disinfection byproducts formed during the ozonation in the presence of bromide and ammonium and their potential toxicity implications

While there is extensive literature covering byproducts formed during various water treatment processes, there is limited research focusing on the generation of brominated disinfection byproducts (Br-DBPs) specifically during ozonation in the presence of bromide (Br−) and ammonium (NH4+). This study used Orbitrap mass spectrometry and a custom halogen extraction code to selectively pinpoint 109 Br-DBPs generated during the ozonation of Suwannee River natural organic matter (SRNOM) containing Br− and NH4+. The Br-DBPs are predominantly distributed ranging from m/z 190 to 320, with elemental compositions consisting of CHOBr and CHONBr. They mainly fell within the H/C (0.5–1.5) and O/C (0.2–1.0) zones, with 16 % being aromatic compounds. NH4+ suppressed Br-DBP formation in CHOBr1-2 subgroups but promoted it in CHONBr1-2 subgroups compared to Br−-containing SRNOM ozonation. Kendrick mass defect diagram revealed 64 identical Br-DBP formulas in the CHOBr1-2 subgroups in both systems, and among them, 13 brominated carboxylic acids were identified, whose formation was suppressed by the addition of NH4+. Moreover, bromonitrophenol and bromobenzonitrile were identified in CHONBr1-2 subgroups, and their formation pathways were proposed. Nitrogen-containing Br-DBPs, especially the aromatic nitrogen-containing ones, exhibited higher toxicity. Caution is necessary to minimize toxic Br-DBPs formation during Br− and NH4+-involved ozonation. This study offers insights into Br-DBP characterization, formation mechanisms and toxicity, guiding enhanced water treatment strategies.

Caspase-3 interactins with calpain and cathepsin L: implications for protein stability and quality in fish fillets during postmortem storage

The degradation of structural proteins during fish postmortem storage is a critical factor affecting meat quality, leading to economic losses in the seafood industry. The complex interplay between caspase-3 and structural protein stability during fish postmortem storage remains largely unexplored. By treating grass carp fillets with a caspase-3 inhibitor, we establish a model for inhibiting apoptosis, delineating the role of caspase-3 in protein degradation. The effect of caspase-3 on grass carp proteins following postmortem storage and its cascade interaction with calpain and cathepsin L was further investigated. The result demonstrated that the destabilisation of the mitochondrial membrane during apoptosis led to modifications in the B-cell lymphoma (Bcl) family proteins, subsequently triggered the activation of caspase-9/caspase-3. Additionally, caspase-3 reduced the expression of the calpastatin and lysosomal membrane protein 1 (LAMP-1) gene, resulting in increased calpain and cathepsin L activity. SDS-PAGE and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis indicated that caspase-3 inhibitor treatment reduced actin fractures and preserved critical structural proteins. This investigation unveils the molecular mechanisms through which caspase-3 affects protein degradation in fish fillets during storage, providing valuable insights into the postmortem degradation processes.

Modulation of metagenomic, biochemical, and histo-morphological features in the termite Odontotermes formosanus through nanoemulsion treatment

A biotechnological technique that involves creating novel pesticides is the nanotechnology of natural compounds, like essential oils. With a lower threat to the environment and public health, these rational approaches provide a more sustainable choice. The present work sought to create novel nanoemulsions of ginger essential oil (G-EO) (Zingiber officinale) and basil essential oil (B-EO) (Ocimum basilicum) to control Odontotermes formosanus (O. formosanus). Stabilization of the ginger nano-emulsion (G-NE) and basil nano-emulsion (B-NE) was assessed by dynamic light scattering (DLS), zeta potential (ZP), and PH measurement, and the characterization was verified by transmission electron microscopy, UV-Vis, energy dispersive spectroscopy, and scanning electron microscopy. Furthermore, a chemical investigation utilizing gas chromatography and mass spectrometers revealed the main components of B-NE, B-EO, G-NE, and G-EO. In addition to assessing the essential oil's termiticidal abilities against O. formosanus in bulk and nanoemulsion formulations. When G-NE and G-EO were both at 17.5 mg/mL, the mortality rates were 100% and 42.87%, respectively. B-EO appeared to have a 45.33% death rate, while B-NE displayed a 100% mortality rate at a dose of 0.273 mg/mL. According to the termiticide appraisal, nanoemulsions have a greater effect on suppressing O. formosanus than essential oils. Additional research was conducted on the impact of G-NE and B-NE on the level of total protein, detoxification enzymes (carboxylesterase, acid, alkaline phosphatase, and acetylcholinesterase), and antioxidant enzyme (peroxidase). It was found that there was a significant change in biochemical activities when compared to the control. Additionally, changes in morphology and histology were seen after exposure to G-NE and B-NE. Moreover, when contrasted to the untreated group, the current study's analysis of the fungal community after exposure to B-NE revealed a high degree of diversity. This work stressed the potential of G-NE and B-NE as natural plant-derived termiticides and suggested a novel technique for sustainability and environmental friendliness in controlling O. formosanus.

Structural characterization and screening of chemical markers of alkaloids in Aconiti lateralis radix Praeparata and its processed products by UHPLC/Q-TOF-MS/MS and GNPS combining multivariate statistical methods based on the clinic.

Aconiti Lateralis Radix Praeparata (AC) is a traditional Chinese medicine with a long history of use. However, the current research on the material basis of AC and its processed products is still not comprehensive, especially the changes in lipo-diterpenoid alkaloids (LDAs) that can be hydrolyzed into diester-diterpenoid alkaloids in AC before and after processing. This study aimed to provide material basis guidance for the clinical use of AC and its processed products by comprehensively analyzing the changes in substances between AC and its processed products. An ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) approach was optimized to chemical profiling. The MS data were processed using molecular networking combined with the in-house library database to fast characterize the compounds. Multivariate statistical methods were adopted to determine the dissimilarities of components in AC and its processed products. A total of 310 compounds were tentatively identified from AC, including 109 potential new alkaloids, of which 98 were potential novel LPAs. A metabolomics approach was applied to find the characteristic marker components. As a result, 52 potential chemical markers were selected to distinguish the AC samples of different extraction methods and 42 potential chemical markers for differentiating between AC and its processed products were selected. The results indicate that UHPLC/Q-TOF-MS/MS and Global Natural Products Social Molecular Networking coupled with multivariate analysis strategies was a powerful tool to rapidly identify and screen the chemical markers of alkaloids between the AC samples and its processed products. These results also indicate that the toxicity of water extracts of AC and its processed products were decreased. This research not only guides the clinical safe use of AC and its processed products, but also extends the application of the molecular networking strategy in traditional herbal medicine.