A cross-sectional analysis of the relationship between the non-high density to high density lipoprotein cholesterol ratio (NHHR) and kidney stone risk in American adults.

BACKGROUND: Recent interest in the Non-High Density to High Density Lipoprotein Cholesterol ratio (NHHR) has emerged due to its potential role in metabolic disorders. However, the connection between NHHR and the development of kidney stones still lacks clarity. The primary goal of this research is to explore how NHHR correlates with kidney stone incidence. METHODS: An analysis was conducted on the data collected by the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, focusing on adults over 20 years diagnosed with kidney stones and those with available NHHR values. Employing weighted logistic regression and Restricted Cubic Spline (RCS) models, NHHR levels' correlation with kidney stone risk was examined. Extensive subgroup analyses were conducted for enhanced reliability of the findings. RESULTS: The findings indicate a heightened kidney stone risk for those at the highest NHHR levels relative to those at the lowest (reference group). A notable non-linear correlation of NHHR with kidney stone incidence has been observed, with a significant P-value (< 0.001), consistent across various subgroups. CONCLUSION: A clear link exists between high NHHR levels and increased kidney stone risk in the American adult population. This study highlights NHHR's significance as a potential indicator in kidney stone formation.

Association between kidney stones and life's essential 8: a population-based study.

BACKGROUND: Kidney stones exhibit a robust correlation with cardiovascular disease (CVD). The objective of this research is to investigate the correlation between kidney stones and Life's Essential 8 (LE8), a newly updated assessment of cardiovascular health (CVH), among adults in the United States. METHODS: In this study, which analyzed data from the 2007-2018 National Health and Nutrition Examination Survey, we employed LE8 scores (ranging from 0 to 100) as the independent variable, classifying them into low, moderate, and high CVH categories. The research examined the relationship between LE8 scores and kidney stones by using multivariate logistic regression and restricted cubic spline models, with kidney stones as the dependent variable. RESULTS: Out of the 14,117 participants in this research, the weighted mean LE8 score was 69.70 ± 0.27. After accounting for confounding factors, there was an inverse association between higher LE8 scores and the likelihood of developing kidney stones (OR of 0.81 per 10-point increase, with a 95% confidence interval of 0.77-0.85), demonstrating a non-linear dose-response pattern. Similar patterns were observed for health behaviors, health factor scores, and kidney stones. Stratified analyses demonstrated a stable negative correlation between LE8 scores and kidney stones across different subgroups. CONCLUSION: LE8 and its subscale scores exhibited a robust and inverse correlation with the occurrence of kidney stones. Encouraging adherence to optimal CVH levels has the potential to serve as an effective strategy in preventing and minimizing the occurrence of kidney stones.

Survival nomogram for high-grade bladder cancer patients after surgery based on the SEER database and external validation cohort.

Background: The aim of this study was to develop a comprehensive and effective nomogram for predicting overall survival (OS) rates in postoperative patients with high-grade bladder urothelial carcinoma. Methods: Patients diagnosed with high-grade urothelial carcinoma of the bladder after radical cystectomy (RC) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. We randomly split (7:3) these patients into the primary cohort and the internal validation cohort. Two hundred eighteen patients from the First Affiliated Hospital of Nanchang University were collected as the external validation cohort. Univariate and multivariate Cox regression analyses were carried out to seek prognostic factors of postoperative patients with high-grade bladder cancer (HGBC). According to these significant prognostic factors, a simple-to-use nomogram was established for predicting OS. Their performances were evaluated using the concordance index (C-index), the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The study included 4,541 patients. Multivariate Cox regression analysis demonstrated that T stage, positive lymph nodes (PLNs), age, chemotherapy, regional lymph nodes examined (RLNE), and tumor size were correlated with OS. The C-index of the nomogram in the training cohort, internal validation cohort, and external validation cohort were 0.700, 0.717, and 0.681, respectively. In the training, internal validation, and external validation cohorts, the ROC curves showed that the 1-, 3-, and 5-year areas under the curve (AUCs) were higher than 0.700, indicating that the nomogram had good reliability and accuracy. The results of calibration and DCA showed good concordance and clinical applicability. Conclusion: A nomogram was developed for the first time to predict personalized 1-, 3-, and 5-year OS in HGBC patients after RC. The internal and external validation confirmed the excellent discrimination and calibration ability of the nomogram. The nomogram can help clinicians design personalized treatment strategies and assist with clinical decisions.

Development and validation of a ubiquitin-proteasome system gene signature for prognostic prediction and immune microenvironment evaluation in hepatocellular carcinoma.

BACKGROUND: The ubiquitin proteasome has a major role in the development of many tumors. However, the prognostic importance of ubiquitin proteasome-system genes (UPSGs) in hepatocellular carcinoma (HCC) is not fully defined. METHODS: The TCGA and ICGC datasets were utilized to obtain transcriptional profiling data as well as clinicopathological information about HCC. The 3-UPSGs signature for the TCGA cohort was developed via univariate and LASSO Cox regression analyses. Differential expression of genes was demonstrated by qRT-PCR and immunohistochemistry (IHC). Biological pathways were studied using GSVA and GSEA. Six algorithms were used to compare immune infiltration between the two risk groups. Furthermore, drug sensitivity was measured using the "pRRophetic" R package. The predictive capacity of the 3-UPSGs signature for sensitivity to immunotherapy was also explored. Moreover, we performed a pan-cancer analysis of the 3-UPSGs signature. RESULTS: A risk model containing 3 UPSGs (DCAF13, CDC20 and PSMB5) was developed. IHC and qRT-PCR results showed that signature genes were significantly overexpressed in HCC tissues. The high-risk group had a worse prognosis, with a higher clinicopathological grade, higher levels of tumor mutation burden (TMB), elevated levels of immune checkpoint (IC) expression, as well as increased sensitivity to immunotherapy. The two risk groups also differ in their sensitivity to chemotherapeutic drugs. Furthermore, the three UPSGs may play crucial roles in the progression of multiple types of cancers. CONCLUSION: We created a 3-UPSGs signature to estimate the prognosis of HCC and to assist in individualized treatment.

Development and validation of a vesicle-mediated transport-associated gene signature for predicting prognosis and immune therapy response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with a poor prognosis. The progression of numerous malignancies has been linked to abnormal vesicle-mediated transport-related gene (VMTRG) expression. The prognostic importance of VMTRGs in HCC is uncertain nonetheless. METHODS: Utilizing HCC data from TCGA and ICGC, we employed univariate cox analysis, unsupervised clustering, and lasso analysis to construct molecular subtypes and prognostic signature of HCC based on the prognostic-associated VMTRGs expression levels. Subsequently, we validated the expression levels of the signature genes. We investigated the probable pathways using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Six methods were utilized to compare immune cell infiltration between two risk groups. Moreover, the "pRRophetic" algorithm was utilized to test the drug sensitivity of both groups. RESULTS: We identified two distinct subtypes with divergent biological behaviors and immune functionality through unsupervised clustering. Subtype C1 demonstrated a poorer prognosis. A prognostic signature incorporating two VMTRGs (KIF2C and RAC1) was formulated. Immunohistochemistry and qRT-PCR analyses unveiled a significant upregulation of these pivotal genes within HCC tissues. The prognosis was worse for the high-risk group, which also had a higher clinicopathological grade, higher levels of tumor mutation burden (TMB), a higher immunological infiltration of CD8 + T cells, a higher expression of immune checkpoints, and enhanced immunotherapy efficacy. These two risk groups also have varied chemotherapy drug sensitivities. CONCLUSIONS: Based on VMTRGs, we have developed a signature that assists in accurate prognosis prediction and formulating personalized treatment strategies for HCC patients.

Corrigendum: Machine learning in non-small cell lung cancer radiotherapy: a bibliometric analysis.

[This corrects the article DOI: 10.3389/fonc.2023.1082423.].

Machine learning in non-small cell lung cancer radiotherapy: A bibliometric analysis.

Background: Machine learning is now well-developed in non-small cell lung cancer (NSCLC) radiotherapy. But the research trend and hotspots are still unclear. To investigate the progress in machine learning in radiotherapy NSCLC, we performed a bibliometric analysis of associated research and discuss the current research hotspots and potential hot areas in the future. Methods: The involved researches were obtained from the Web of Science Core Collection database (WoSCC). We used R-studio software, the Bibliometrix package and VOSviewer (Version 1.6.18) software to perform bibliometric analysis. Results: We found 197 publications about machine learning in radiotherapy for NSCLC in the WoSCC, and the journal Medical Physics contributed the most articles. The University of Texas MD Anderson Cancer Center was the most frequent publishing institution, and the United States contributed most of the publications. In our bibliometric analysis, "radiomics" was the most frequent keyword, and we found that machine learning is mainly applied to analyze medical images in the radiotherapy of NSCLC. Conclusion: The research we identified about machine learning in NSCLC radiotherapy was mainly related to the radiotherapy planning of NSCLC and the prediction of treatment effects and adverse events in NSCLC patients who were under radiotherapy. Our research has added new insights into machine learning in NSCLC radiotherapy and could help researchers better identify hot research areas in the future.

Lower attenuation and higher kurtosis of coronary artery calcification associated with vulnerable plaque - an agatston score propensity-matched CT radiomics study.

BACKGROUND: Coronary artery calcification (CAC) burden assessed by Agatston score (AS) is currently recommended to stratify patients at risk for future acute coronary syndrome (ACS). Besides the CAC burden, the biostructure of CAC may also play a vital role in the vulnerability of CAC, which CT radiomics could reveal. Propensity-score matching of the traditional risk factors and CAC burden between the ACS and asymptomatic groups could radically remove biases and allow the exploration of characteristic features of CAC in ACS. METHODS: We retrospectively identified 77 patients with ACS who had a CAC scan before percutaneous coronary intervention between 2016 and 2019. These 77 patients were one-to-two propensity-score matched for traditional risk factors of ACS and AS ranks to select 154 subjects from 2890 asymptomatic subjects. A validation cohort of 30 subjects was also enrolled. Radiomics features of each plaque were extracted and averaged in each person. Conditional logistic regression and area-under-curve analysis were used for statistical analysis. RESULTS: A higher number of coronary segments involved, lower mean, median, first quartile, and standard deviation of attenuation, and increased kurtosis of attenuation of CAC were associated with the ACS group compared to the control group (p < 0.05 for all). Multivariable analysis showed that the lower median attenuation (OR = 0.969, p < 0.001) and higher Kurtosis (OR = 18.7, p < 0.001) were associated with the ACS group. The median attenuation and kurtosis significantly increase across AS ranks 1 to 4 (p = 0.001). The AUC of kurtosis (0.727) and median attenuation (0.66) were both significantly higher than that of the standard AS (AUC = 0.502) and the number of TRF (AUC = 0.537). The best cut-off of kurtosis at 2.74 yielded an accuracy of 74%, and the cut-off of median attenuation at 196 yielded an accuracy of 68%. The accuracy of kurtosis was 64%, and the accuracy of median attenuation was 55% in the validation cohort. CONCLUSION: After propensity-matching traditional risk factors and CAC burden, CT radiomics highlighted that lower median attenuation and higher kurtosis were the CAC characteristics of vulnerable plaques. These features improve the understanding of the biomechanics of CAC evolution and enhance the value of CAC scan in ACS risk assessment.

Effects of ultrasonic-assisted pH shift treatment on physicochemical properties of electrospinning nanofibers made from rapeseed protein isolates.

Electrospinning nanofibers (NFs) made from natural proteins have drawn increasing attention recently. Rapeseed meal is a by-product that rich in protein but not fully utilized due to poor properties. Therefore, modification of rapeseed protein isolates (RPI) is necessary to expand applications. In this study, pH shift alone or ultrasonic-assisted pH shift treatment was adopted, the solubility of RPI, along with the conductivity and viscosity of the electrospinning solution were detected. Moreover, the microstructure and functional characteristics of the electrospinning NFs, as well as the antibacterial activity of clove essential oil loaded-NFs were investigated. The tested parameters were remarkably improved after different treatments compared with the control, and synergistic effects were observed, especially under alkaline conditions. Hence, pH12.5 + US showed the maximum value of solubility, conductivity, and viscosity, which was more than 7-fold, 3-fold, and almost 1-fold higher than the control respectively. Additionally, SEM and AFM images showed a finer and smoother surface of NFs after treatments, and the finest diameter of 216.7 nm was obtained after pH12.5 + US treatment in comparison with 450.0 nm in control. FTIR spectroscopy of NFs demonstrated spatial structure changes of RPI, and improved thermal stability and mechanical strength of NFs were achieved after different treatments. Furthermore, an inhibition zone with a diameter of 22.8 mm was observed from the composite NFs. This study indicated the effectiveness of ultrasonic-assisted pH shift treatment on the physicochemical properties improvement and functional enhancement of NFs made from RPI, as well as the potential antibacterial application of the composite NFs in the future.

Differential Adaptation of Biventricular Myocardial Kinetic Energy in Patients With Repaired Tetralogy of Fallot Assessed by MR Tissue Phase Mapping.

BACKGROUND: The myocardial kinetic energy (KE) and its association with pulmonary regurgitation (PR) have yet to be investigated in repaired tetralogy of Fallot (rTOF) patients. PURPOSE: To evaluate the adaptation of myocardial KE in rTOF patients by tissue phase mapping (TPM). STUDY TYPE: Prospective. POPULATION: A total of 49 rTOF patients (23 ± 5 years old; male = 32), 47 normal controls (22 ± 1 year old; male = 29). FIELD STRENGTH/SEQUENCE: 3-T/2D dark-blood three-directional velocity-encoded gradient-echo sequence. ASSESSMENT: Left and right ventricle (LV, RV) myocardial KE in radial (KEr ), circumferential (KEø ), longitudinal (KEz ) directions. The proportions of KE in each direction to the sum of all KE (KErøz ): %KEr , %KEø , %KEz . PR fraction. STATISTICAL TEST: Student's t test, multivariable regression. Statistical significance: P < 0.05. RESULTS: In rTOF group, LV KEz remained normal in systole (P = 0.565) and diastole (P = 0.210), whereas diastolic LV %KEz (62% ± 14% vs. 72% ± 7%) and systolic LV %KEø (9% ± 6% vs. 20% ± 7%) were significantly decreased. The KEr and %KEr of both ventricles significantly increased in the rTOF group (RV in diastole: 6 ± 3 vs. 3 ± 1 µJ and 54% ± 13% vs. 27% ± 7%). The rTOF group exhibited significantly higher RV/LV ratios of %KEr (systole: 1.3 ± 0.3 vs. 1.0 ± 0.3) and %KEø (systole: 1.6 ± 0.8 vs. 1.0 ± 0.3) and significantly lower ratios of %KEz in systole (0.7 ± 0.2 vs. 1.0 ± 0.1) and diastole (0.5 ± 0.2 vs. 0.9 ± 0.1). In multivariable regression analysis, the RV peak systolic KErøz , RV systolic KEz , and LV diastolic %KEø were independently associated with PR fraction in the rTOF group (adjusted R2  = 0.479). DATA CONCLUSION: In rTOF patients, the adaptation of the KE proportion occurred earlier than that of the KE amplitude, and the biventricular balance of %KE was disrupted. PR may cause differential KE adaptation in RV and LV. TPM-derived KE may be useful in investigation of myocardial adaptation in rTOF patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

The efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of EGFR.

BACKGROUND: The study aims to explore the efficacy of adding hyperthermia to the treatment of advanced NSCLC patients based on the states of epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: We included 205 advanced NSCLC patients who were received hyperthermia plus other treatment (hyperthermia group) or non- hyperthermia and other treatments (non- hyperthermia group). The OS and progression free survival (PFS) were retrospectively estimated. Using Kaplan-Meier and the log-rank test compare the OS and PFS between the groups. RESULTS: The median follow-up was 22 months. The Univariate analysis have shown that 1-year OS and PFSfirst rates in the hyperthermia group and non- hyperthermia group were 83.3% vs 71.5% (P=0.010) and 62.0% vs 42.7% (P=0.001). The subgroup analyses revealed that patients didn't have EGFR mutant who received hyperthermia had significantly higher 1 year OS and PFSfirst rates than those treated with non- hyperthermia (OS: 79.1% vs 65.2% P=0.037, PFS: 64.2% vs 36.5%, P=0.001). For patients with EGFR mutation, there was no significant difference between the two groups. The PFSfirst in first-line and PFSpost in posterior-line was no significant difference between the groups. CONCLUSIONS: This retrospective study revealed that adding hyperthermia to the treatment of NSCLC patients without EGFR mutation had better prognosis than those who did not adding hyperthermia to the regimen. Moreover, adding hyperthermia in first-line or in posterior-line treatment was no significant difference. However, these results need more prospective studies to confirm the conclusions.

The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseases.

Leukocyte cell-derived chemotaxin-2 (LECT2 or LECT-2), also called chondromodulin II (ChM-II or CHM2) plays a versatile role in various tissues. It was first identified as a chemotactic factor to promote the migration of neutrophils. It was also reported as a hepatokine to regulate glucose metabolism, obesity, and nonalcoholic fatty liver disease. As a secreted factor, LECT2 binds to several cell surface receptors CD209a, Tie1, and Met to regulate inflammatory reaction, fibrogenesis, vascular invasion, and tumor metastasis in various cell types. As an intracellular molecule, it is associated with LECT2-mediated amyloidosis, in which LECT2 misfolding results in insoluble fibrils in multiple tissues such as the kidney, liver, and lung. Recently, LECT2 was found to be associated with the development of rheumatoid arthritis and osteoarthritis, involving the dysregulation of osteoclasts, mesenchymal stem cells, osteoblasts, chondrocytes, and endothelial cells in the bone microenvironment. LECT2 is implicated in the development of cancers, such as hepatocellular carcinoma via MET-mediated PTP1B/Raf1/ERK signaling pathways and is proposed as a biomarker. The mechanisms by which LECT2 regulates diverse pathogenic conditions in various tissues remain to be fully elucidated. Further research to understand the role of LECT2 in a tissue tropism-dependent manner would facilitate the development of LECT2 as a biomarker for diagnosis and therapeutic target.

Predictive nomograms for early death in metastatic bladder cancer.

Background: Metastatic bladder cancer (MBC) is an incurable malignancy, which is prone to early death. We aimed to establish models to evaluating the risk of early death in patients with metastatic bladder cancer. Methods: The data of 1,264 patients with MBC registered from 2010 to 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We utilized X-tile software to determine the optimal cut-off points of age and tumor size in diagnosis. Univariate and multivariate logistic regression analyses were used to identify significant independent risk factors for total early death and cancer-specific early death, then we construct two practical nomograms. In order to validate our prediction models, we performed calibration plots, receiver operating characteristics (ROCs) curves, decision curve analysis (DCA) and clinical impact curve (CIC). Result: A total of 1,216 patients with MBC were included in this study. 463 patients died prematurely (≤3 months), and among them 424 patients died of cancer-specific early death. The nomogram of total premature death was created by surgery, chemotherapy, tumor size, histological type, liver metastases, and nomogram of cancer-specific early death was based on surgery, race, tumor size, histological type, chemotherapy, and metastases (liver, brain). Through the verify of calibration plots, receiver operating characteristics (ROCs) curves, decision curve analysis (DCA) and clinical impact curve (CIC), we concluded that nomogram were a valid tool with excellent clinical utility to help clinicians predict premature death in MBC patients. Conclusions: The nomograms derived from the analysis of patients with MBC, which can provide refined prediction of premature death and furnish clinicians with useful ideas for patient-specific treatment options and follow-up scheduling.

Inhibition Effect of Ultrasound on the Formation of Lysinoalanine in Rapeseed Protein Isolates during pH Shift Treatment.

pH shift is an effective technique for modifying functional properties of food proteins. However, it can increase lysinoalanine (LAL) content under alkali conditions, thus limiting the use of proteins. This study investigated the inhibition effect of ultrasonic parameters on LAL formation in rapeseed protein isolates (RPI) during pH shift treatment (pH-ST). Results showed that the content of LAL decreased by 49.5% and 74.1%, following the use of ultrasound (28 kHz, 40 W/L, 40 °C, and 30 min) under alkali and acidic treatment, respectively. Structural analysis showed that after ultrasonic irradiation, increased sulfhydryl groups and amino acids reduced the dehydroalanine and, thus, decreased LAL content. Particle size, secondary structure, and microstructure (SEM, AFM) analyses showed relative dispersion in protein distribution, reducing intermolecular or intramolecular cross-linking, thereby lowering the LAL content. Thus, ultrasonic-aided pH-ST may be an operational technique toward minimizing LAL formation in RPI.

Current research progress in targeted anti-angiogenesis therapy for osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%-70% 5-year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre-clinical and developmental research of targeted anti-angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti-angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti-angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti-angiogenesis therapy in OS.

Fermentation of Saccharomyces cerevisiae in a 7.5 L ultrasound-enhanced fermenter: Effect of sonication conditions on ethanol production, intracellular Ca2+ concentration and key regulating enzyme activity in glycolysis.

In this study, the effect of sonication on the fermentation process of a single-celled fungus was examined. During the experiment, Saccharomyces cerevisiae (S. cerevisiae) was used as the starting strain for ethanol fermentation (batch fermentation) in a 7.5 L automated fermentation tank. The fermentation tank connected with a six-frequency ultrasonic equipment. Non-sonication treatment was set up as the control. Sonication treatment with power density of 280 W/L and 48 h of treatment time were set up as trial groups for investigating the influence of different ultrasound frequency including 20, 23, 25, 28, 33 and 40 kHz on the changes in dry cell-weight, glucose consumption rate, and ethanol yield. The results showed that the dry cell-weight, glucose consumption rate, and ethanol content reached the best results under the ultrasonic condition of 28 kHz ultrasound frequency in comparison with other ultrasound frequency. The dry cell-weight and ethanol content of the 28 kHz ultrasonic treatment group increased by 17.30% and 30.79%, respectively in comparison with the control group The residual sugar content dropped to a lower level within 24 h, which was consistent with the change in ethanol production. Besides, the results found that the glucose consumption rate increased compared to the control. It indicated that ultrasound accelerated glucose consumption contributed to increase the rate of ethanol output. In order to explore the mechanism of sonication enhanced the content of ethanol output by S. cerevisiae, the morphology, permeability of S. cerevisiae and key enzyme activities of ethanol synthesis were investigated before and after sonication treatment. The results showed that after sonication treatment, the extracellular nucleic acid protein content and intracellular Ca2+ concentration increased significantly. The morphology of S. cerevisiae was observed by SEM and found that the surface of the strain had wrinkles and depressions after ultrasonic treatment. furthermore after sonication treatment, the activities of three key enzymes which catalyze three irreversible reactions in glycolysis metabolism, namely, hexokinase, phosphofructokinase and pyruvate kinase increased by 59.02%, 109.05% and 87.27%, respectively. In a word, low-intensity ultrasound enhance the rate of ethanol output by S. cerevisiae might due to enhancing the growth and cell permeability of strains, and increasing the activities of three key enzymes of ethanol biosynthesis.

Advances in sulfur mustard-induced DNA adducts: Characterization and detection.

Sulfur mustard (SM) is a blister chemical warfare agent with severe cytotoxicity and genotoxicity. It can extensively alkylate important macromolecules in organisms, such as proteins, DNA, and lipids, and produce a series of metabolites, among which the characteristic ones can be used as biomarkers. The exact toxicological mechanisms of SM remain unclear but mainly involve the DNA lesions induced by alkylation and oxidative stress caused by glutathione depletion. Various methods have been used to analyze DNA damage caused by SM. Among these methods, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology stands out and makes it possible to observe damage in view of biomarkers induced by SM. Sample preparation is critical for detection by LC-MS/MS and mainly includes DNA isolation, adduct hydrolysis, and adduct purification. Moreover, optimization of chromatographic conditions, selection of MS transitions, and quantitative strategies are also essential. SM-DNA adducts are generally considered to be N7-HETEG, O6-HETEG, N7-BisG, and N3-HETEA. This article proposes some other possibilities of SM-DNA adducts for the identification of SM genotoxicity.

Modification of rapeseed protein by ultrasound-assisted pH shift treatment: Ultrasonic mode and frequency screening, changes in protein solubility and structural characteristics.

We investigated the effect of ultrasound-assisted pH shift treatment on the micro-particle, molecular, and spatial structure of rapeseed protein isolates (RPI). Various ultrasonic frequency modes (fixed, and sweep) was used. Protein characterization by the indexes: particle size, zeta potential, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), scanning electron microscopy (SEM), free sulfhydryl (SH), surface hydrophobicity (Ho), Fourier transform infrared Spectrum (FTIR) and fluorescence intensity was studied to elucidate the changes in solubility and structural attributes of RPI. The results showed that ultrasonic frequency and working modes substantially altered the structure, and modified the solubility of RPI. Ultra + pH mode at fixed frequency of 20 kHz had the best effect on the solubility of RPI. Under the condition of ultra + pH mode, 20 kHz at pH 12.5, solubility, compared to control, increased from 8.90% to 66.84%; and the change in molecular structure of RPI was characterized by smaller particles (from 330.90 to 115.77 nm), high zeta potential (from -17.95 to -14.43 mV, p < 0.05), and increased free sulfhydryl (from 11.63 to 24.50 µmol/g) compared to control. Likewise, surface hydrophobicity increased (from 2053.9 to 2649.4, p < 0.05), whilst ɑ-helix and random coil decreased (p < 0.05), compared to control. The fluorescence spectroscopy and FTIR spectroscopy showed that the secondary and tertiary structure of the RPI were altered. These observations revealed that changes in RPI structure was the direct factor affecting solubility. In conclusion, ultrasound assisted pH shift treatment was proven to be an effective method for the modification of protein, with promising application in food industry.

Lysinoalanine formation and conformational characteristics of rice dreg protein isolates by multi-frequency countercurrent S-type sonochemical action.

The influences of multi-frequency countercurrent S-type ultrasound (MFSU), with various frequency modes, on lysinoalanine (LAL) formation and conformational characteristics of rice dreg protein isolates (RDPI) were investigated. The ultrasonic operating mode with dual-frequency combination (20/40 kHz) indicated lower LAL content and higher protein dissolution rate of RDPI compared with that of other ultrasound operating modes. Under the dual-frequency ultrasound mode of 20/40 kHz, acoustic power density of 60 W/L, time of 20 min, and temperature of 35 °C, the relative reduction rate of LAL of RDPI reached the highest with its value of 26.95%, and the protein dissolution rate was 71.87%. The changes in chemical interactions between protein molecules indicated that hydrophobic interactions and disulfide bonds played a considerable role in the formation of LAL of RDPI, especially the reduction of g-g-g and g-g-t disulfide bond. Alterations in microstructure showed that ultrasonication loosened the protein structure and created more uniform protein fragments of RDPI. In conclusion, using MFSU in treating RDPI was an efficacious avenue for minimizing LAL content and modifying the conformational characteristics of RDPI.

The role of glial cell line-derived neurotrophic factor family member artemin in neurological disorders and cancers.

Artemin (ARTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs), which encompasses family members, GDNF, neurturin (NRTN) and persephin (PSPN). ARTN is also referred to as Enovin or Neublastin, and bears structural characteristics of the TGF-ß superfamily. ARTN contains a dibasic cleavage site (RXXR) that is predicted to be cleaved by furin to yield a carboxy-terminal 113 amino acid mature form. ARTN binds preferentially to receptor GFRα3, coupled to a receptor tyrosine kinase RET, forming a signalling complex for the regulation of intracellular pathways that affect diverse outcomes of nervous system development and homoeostasis. Standard signalling cascades activated by GFLs via RET include the phosphorylation of mitogen-activated protein kinase or MAPK (p-ERK, p-p38 and p-JNK), PI3K-AKT and Src. Neural cell adhesion molecule (NCAM) is an alternative signalling receptor for ARTN in the presence of GFRα1, leading to activation of Fyn and FAK. Further, ARTN also interacts with heparan sulphate proteoglycan syndecan-3 and mediates non-RET signalling via activation of Src kinases. This review discusses the role of ARTN in spinal cord injury, neuropathic pain and other neurological disorders. Additionally, ARTN plays a role in non-neuron tissues, such as the formation of Peyer's patch-like structures in the lymphoid tissue of the gut. The emerging role of ARTN in cancers and therapeutic resistance to cancers is also explored. Further research is necessary to determine the function of ARTN in a tissue-specific manner, including its signalling mechanisms, in order to improve the therapeutic potential of ARTN in human diseases.