Decoding sunitinib resistance in ccRCC: Metabolic-reprogramming-induced ABAT and GABAergic system shifts.

Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

Novel chitosan-modified biochar prepared from a Chinese herb residue for multiple heavy metals removal: Characterization, performance and mechanism.

In this study, the sorption properties of Cr(VI), As(III), and Pb(II) on chitosan-modified magnetic biochar (CMBC) derived from residues of Ligusticum chuanxiong Hort. were investigated. CMBC was found to be a valuable material for removing three heavy metals from water simultaneously. Kinetic analysis suggested Cr(VI), As(III), and Pb(II) were chemisorbed onto CMBC, while isotherm data conformed well to Langmuir model, the maximum adsorption capacity of CMBC was found to be 65.74 mg/g for Cr(VI), 49.32 mg/g for As(III), and 69.45 mg/g for Pb(II). Experiments, characterization, and density functional theory (DFT) calculations were employed to explore the mechanisms. Furthermore, CMBC demonstrated excellent removal rates of over 95% for Cr(VI), 99% for As(III) and Pb(II) from contaminated water bodies. This work shows that CMBC holds significant potential for wastewater treatment of heavy metals and provides an effective solution for the utilization of Chinese herb residues in environmental remediation.

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.

BACKGROUND: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. METHODS: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. RESULTS: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. CONCLUSION: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

Kinetic reaction mechanism of lignocellulosic biomass oxidative pyrolysis based on combined kinetics.

The kinetics knowledge of lignocellulosic biomass decomposition is essential to develop efficient thermochemical conversion technology. However, the simplification of reaction mechanisms in existing oxidative pyrolysis studies largely compromises the application of kinetic models. To explore more exact kinetic parameters and reaction mechanism of lignocellulosic biomass oxidative pyrolysis, an updated oxidative pyrolysis kinetic model (seven-step reaction combined kinetics model) coupled with an optimization algorithm is proposed. Based on a series of thermogravimetric experiments in an air atmosphere, the extra oxidative pyrolysis kinetic parameters are obtained by the Shuffled Complex Evolution method. The proposed kinetic model is validated based on the degradation process of each component (hemicellulose, cellulose, and lignin). Furthermore, the obtained kinetic parameters are applied to predict the oxidative pyrolysis behavior, and the predicted mass loss rate is in good agreement with the experimental data. Eventually, according to the key combined kinetics parameters, it is found that the oxidative pyrolysis mechanisms of hemicellulose, cellulose, and lignin correspond to the power law, nucleation & growth, and chemical reaction order, respectively, while the combustion of char corresponds to the reaction order mechanism.

Determination of ochratoxin A in licorice extract based on modified immunoaffinity column clean-up and HPLC analysis.

Contamination of ochratoxin A (OTA) is a common concern for the quality and safety of licorice and its derivatives, while their complex sample matrices always restrict the monitoring and regulation of OTA. Taking the much more concentrated and complicated licorice extract as the representative, a modified analysis method was established for OTA by HPLC. Parameters were comprehensively investigated based on liquid-liquid extraction and immunoaffinity column clean-up. In comparison to other methods, the developed method achieved effective clean-up efficiency and selectivity without tedious procedures and specialized instrumentation. Good linearity (R2 ≥0.9995), low LOD/LOQ (0.10 µg/kg/0.33 µg/kg), and satisfactory recovery (90.0%-96.4%, RSDs <7.0%) indicated the satisfactory sensitivity and reliability of the method. In addition, the applicability and robustness of the method was demonstrated by the analysis of large numbers of licorice extract samples. It is noteworthy that 66.5% of 176 samples were contaminated with OTA, while the concentrations of 9.1% of samples exceeded the maximum limit (ML, 80 µg/kg) defined by the EU. On account of the high contamination frequency and broad concentration range of OTA, the daily intake limit of licorice extract was preliminarily determined to be 123.18-123.93 g/day (chronic exposure) and 24.24 g/day (acute exposure), indicating a potential of acute risk through daily exposure. This calls for improved supervision and regulation for OTA contamination in licorice samples. This study suggests a prospective option for the efficient determination and routine monitoring of OTA in licorice and its derivatives, simultaneously providing a valuable data base for its health risk assessment.

Lignans from the root of Valeriana jatamansi and their biological evaluation.

Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 µg/ml, respectively.

Fe3O4@PDA/MIL-101(Cr) as magnetic solid-phase extraction sorbent for mycotoxins in licorice prior to ultrahigh-performance liquid chromatography-tandem mass spectrometry analysis.

Magnetic solid-phase extraction (MSPE) strategy based on the Fe3O4@PDA/MIL-101(Cr) has been proposed to separate and purify five common mycotoxins in licorice, including aflatoxin B1, aflatoxin G1, sterigmatocystin, zearalenone, and ochratoxin A. Integrating the MSPE and solid-liquid extraction/partitioning, a modified QuEChERS was established to adapt to the complex licorice samples. The Fe3O4@PDA/MIL-101(Cr) was successfully synthesized and characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption-desorption isotherms. Sorbents with superior advantages for exclusion of matrix interference and extraction of target analytes in a short time were obtained, according to their ability of magnetic separation, high surface area (287.75 m2/g), large pore volume (0.61 cm3/g), and nanosized structure with mesopores. Prior to analysis with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), several key parameters that would affect the sorbents' extraction efficiency were extensively investigated. Under the optimized conditions, the practicality of the developed method for analysis of mycotoxins in licorice samples was confirmed by adequate linearity (R 2 ≥ 0.9967), high sensitivity (LODs and LOQs, respectively, in the ranges 0.01-0.09 and 0.02-0.30 µg/kg), acceptable recovery (78.53%-116.28%), satisfactory reusability, and good interbatch precision of the sorbents (RSDs in the ranges 6.70%-11.20% and 6.02%-10.35%, respectively). The results indicated that the established method was feasible and reliable for the environment-friendly and rapid screening of mycotoxins in complex licorice samples.

Occurrence and exposure risk assessment of phthalate esters in edible plant oils with a high-frequency import rate in west China.

Phthalate esters (PAEs) are ubiquitous pollutants in the environment with toxicological and epidemiological effects for humans. As one of the daily necessities, edible plant oil is an important exposure source of PAEs, due to the inevitable contact with PAE-containing materials and the intrinsic lipid solubility of PAEs. However, limited information is currently available on the exposure risk of PAEs in commercial plant oil. This study was aimed at investigating the occurrence and risk assessment of PAEs in plant oils with a high-frequency import rate in west China. The analysis method was referenced to the Chinese national standard for the determination of PAEs in food. Results indicated that PAEs (mainly including DBP and DEHP) were ubiquitous contaminants in imported plant oils with the detectable rate being up to 56.83% in 366 samples. The detected concentrations were in the range of 0.10-3.20 mg kg-1 (median 0.28 mg kg-1) for dibutyl phthalate (DBP) and 0.25-1.95 mg kg-1 (median 0.44 mg kg-1) for bis(2-ethylhexyl)phthalate (DEHP). Based on an integrated probabilistic analysis method, the values of non-carcinogenic risk were lower than 1 in all cases, indicating that there would be an unlikely incremental non-carcinogenic risk to humans. Generally, the carcinogenic risk of DEHP was lower than the upper acceptable carcinogenic risk level (<10-4), while 50.40% of the carcinogenic risk exceeded the lower acceptable carcinogenic risk level (>10-6). Besides, diverse health risks were obviously shown and discussed for different categories of plant oils. The obtained results in this study could provide valuable information to understand the contamination status and health risk of PAEs in plant oil and improve the relative supervision and regulation. And the proposed strategy suggests a potential application for health risk assessment of other contaminants in food or even environments.

Solid-phase extraction techniques based on nanomaterials for mycotoxin analysis: An overview for food and agricultural products.

Mycotoxin contamination is a globally concerned problem for food and agricultural products since it may directly or indirectly induce severe threats to human health. Sensitive and selective screening is an efficient strategy to prevent or reduce human and animal exposure to mycotoxins. However, enormous challenges exist in the determination of mycotoxins, arising from complex sample matrices, trace-level analytes, and the co-occurrence of diverse mycotoxins. Appropriate sample preparation is essential to isolate, purify, and enrich mycotoxins from complicated matrices, thus decreasing sample matrix effects and lowering detection limits. With the cross-disciplinary development, new solid-phase extraction strategies have been exploited and integrated with nanotechnology to meet the challenges of mycotoxin analysis. This review summarizes the advance and progress of solid-phase extraction techniques as the methodological solutions for mycotoxin analysis. Emphases are paid on nanomaterials fabricated as trapping media of solid-phase extraction techniques, including carbonaceous nanoparticles, metal/metal oxide-based nanoparticles, and nanoporous materials. Advantages and limitations are discussed, along with the potential prospects.

Fabrication of porous ionic liquid polymer as solid-phase microextraction coating for analysis of organic acids by gas chromatography - mass spectrometry.

A kind of porous ionic liquid polymer was designed as coating material for solid-phase microextraction (SPME) fibers to extract polar organic acids. The synthesized ionic liquids (1-vinyl-3-(4-vinyl-benzyl)imidazolium chloride) were polymerized in the presence of azobisisobutyronitrile (AIBN), and subsequently coated on stainless steel wires with physical adhesion. To guarantee the adhesion between coating and the surface of stainless steel wires, micro-wave induced plasma was applied to modify the stainless steel wires. The derivatives of extracted organic acids were analyzed by gas chromatography combined with mass spectrometry (GC-MS) with N-tert-Butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) as the derivatization reagent. Under the optimal condition, a calibration study was carried out to evaluate the performance of the SPME fibers. The calibration curves were linear (R2>0.99) in the range from 0.01µg/ml to 1µg/ml for six organic acids. Detection limits were detected down to 0.07ng/ml. To further validate the extraction efficiency of the fibers, experiments were conducted in comparison with commercial fibers. Lower LOD and LOQ values were obtained by the in-house fabricated fibers especially for polyatomic acids. Good repeatability (RSD≤16%) and fiber-to-fiber reproducibility (RSD≤20%) were obtained. The acceptable recovery of the spiked grape wine samples ranged from 78.19% to 98.11%. Additionally, long lifetime and good durability of the fibers have been demonstrated. The performance of the established SPME-GC-MS method for analysis of organic acids was shown to be greatly improved in comparison to the direct HPLC/CE method or other SPME materials as reported in the literature. In summary, a feasible and effective approach has been demonstrated to fabricate the in-house fabricated fibers based on porous ionic liquid polymers, which were proved to be advantageous and sensitive for extraction of polar organic acids. Simultaneously, application of the SPME derivatization GC-MS method for analysis of organic acids has been successfully verified as feasible and reliable.

Preliminary construction of integral analysis for characteristic components in complex matrices by in-house fabricated solid-phase microextraction fibers combined with gas chromatography-mass spectrometry.

Integral analysis plays an important role in study and quality control of substances with complex matrices in our daily life. As the preliminary construction of integral analysis of substances with complex matrices, developing a relatively comprehensive and sensitive methodology might offer more informative and reliable characteristic components. Flavoring mixtures belonging to the representatives of substances with complex matrices have now been widely used in various fields. To better study and control the quality of flavoring mixtures as additives in food industry, an in-house fabricated solid-phase microextraction (SPME) fiber was prepared based on sol-gel technology in this work. The active organic component of the fiber coating was multi-walled carbon nanotubes (MWCNTs) functionalized with hydroxyl-terminated polydimethyldiphenylsiloxane, which integrate the non-polar and polar chains of both materials. In this way, more sensitive extraction capability for a wider range of compounds can be obtained in comparison with commercial SPME fibers. Preliminarily integral analysis of three similar types of samples were realized by the optimized SPME-GC-MS method. With the obtained GC-MS data, a valid and well-fit model was established by partial least square discriminant analysis (PLS-DA) for classification of these samples (R2X=0.661, R2Y=0.996, Q2=0.986). The validity of the model (R2=0.266, Q2=-0.465) has also approved the potential to predict the "belongingness" of new samples. With the PLS-DA and SPSS method, further screening out the markers among three similar batches of samples may be helpful for monitoring and controlling the quality of the flavoring mixtures as additives in food industry. Conversely, the reliability and effectiveness of the GC-MS data has verified the comprehensive and efficient extraction performance of the in-house fabricated fiber.

GC-Based Techniques for Breath Analysis: Current Status, Challenges, and Prospects.

Breath analysis is a noninvasive diagnostic method that profiles a person's physical state by volatile organic compounds in the breath. It has huge potential in the field of disease diagnosis. In order to offer opportunities for practical applications, various GC-based techniques have been investigated for on-line breath analysis since GC is the most preferred technique for mixed gas separation. This article reviews the development of breath analysis and GC-based techniques in basic breath research, involving sampling methods, preconcentration methods, conventional GC-based techniques, and newly developed GC techniques for breath analysis. The combination of GC and newly developed detection techniques takes advantages of the virtues of each. In addition, portable GC or micro GC are poised to become field GC-based techniques in breath analysis. Challenges faced in GC-based techniques for breath analysis are discussed candidly. Effective cooperation of experts from different fields is urgent to promote the development of breath analysis.

Development of solid-phase microextraction fibers based on multi-walled carbon nanotubes for pre-concentration and analysis of alkanes in human breath.

In this work, a laboratory preparation method based on sol-gel technology was proposed to develop a new kind of SPME (solid phase microextraction) fibers. Multi-walled carbon nanotubes (MWCNT) were selected as sol-gel active organic component. Stainless steel wires were used as the substrate of the fibers. Instead of traditional modification methods, microwave induced plasma was used to modify the stainless steel wire surface, resulting in a significant improvement in chemical adhesion of the fiber substrate and coating. The MWCNT coating exhibited several good properties. Acceptable fiber-to-fiber reproducibility (RSD≤13%) and repeatability (RSD<7%) were obtained. End-tidal breath of 10 normal humans were collected by Bio-VOC(®) sampler and assayed by the optimized SPME-GC-MS method. The calibration curves were all linear (R(2)≥0.994) in the range from 0.03 to 403.3ppbv for five alkanes. Detection limits (down to 0.001ppbv) were about one order of magnitude better than those of commercial PDMS fibers. The recovery of the spiked alkanes in real breath sample at 1ppbv ranged from 89.71 to 101.08% and the relative standard deviations were less than 8%. These results demonstrated the feasibility and practicality of the proposed preparation procedure. Applications of the in-house fabricated fibers for human breath analysis were successfully verified.

Breath analysis: technical developments and challenges in the monitoring of human exposure to volatile organic compounds.

At present, there is a growing concern about human quality of life. In particular, there is an awareness of the impact of volatile organic compounds (VOCs) on the environment and human health, so the monitoring of human exposure to VOCs is an increasingly urgent need. Biomonitoring is theoretically more accurate compared with traditional ambient air monitoring, and it plays an essential role in human environmental exposure assessment. Breath analysis is a biomonitoring method with many advantages, which is applicable to assessments of human exposure to a large number of VOCs. Techniques are being developed to improve the sensitivity and precision of breath analysis based on in-direct and direct measurements which will be reviewed in this paper. This paper briefly reviews the frequently used methods in both of these categories, specifically highlighting some promising new techniques. Furthermore, this review also provides theoretical background knowledge about the use of breath analysis as a biomonitoring tool for human exposure assessment. A review of the application of breath analysis to human exposure monitoring during last two decades is also provided according to occupational/non-occupational exposure. Obstacles and potential challenges in this field are also summarized. Based on the gradual improvements in the theoretical basis and technology reviewed in this paper, breath analysis is an enormous potential approach for the monitoring of human exposure to VOCs.

Investigation of potential breath biomarkers for the early diagnosis of breast cancer using gas chromatography-mass spectrometry.

BACKGROUND: Breast cancer (BC) remains the most commonly diagnosed malignancy in women. We investigated 4 straight aldehydes in the exhaled breath as potential early BC diagnostic biomarkers. METHODS: End-tailed breath were collected by Bio-VOC® sampler and assayed by gas chromatography-mass spectrometry. Kruskal-Wallis one-way analysis of variance test and binary logistic regression were used for data analysis. The diagnostic accuracies were evaluated by receiver operating characteristic curves. A predictive model/equation was generated using the 4 biomarkers and validated by leave-one-out cross-validation. RESULTS: All four potential biomarkers demonstrated significant differences in concentrations between BC and healthy controls (HC) (p<0.05). The areas under the curves (AUCs) in HC vs BCI-II model using hexanal, heptanal, octanal, and nonanal were 0.816, 0.809, 0.731, and 0.830, respectively. The AUC for their combined use was 0.934 (sensitivity 91.7%, specificity 95.8%) in the early diagnosis of BC. The predictive model/equation exhibited good sensitivity (72.7%) and specificity (91.7%) in distinguishing between HC and BC (cross-validation: sensitivity 68.2% and specificity 91.7%). CONCLUSIONS: The diagnostic values of 4 exhaled straight aldehydes as early diagnostic biomarkers for BC were successfully verified and the diagnostic accuracy improved in their combined use.