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In this editorial we comment on the article by Huffaker et al published in a recent issue of the World Journal of Clinical Cases. We focus on cardiac tumors linked to genetic syndromes and the differential diagnosis of cardiac masses. As cardiomyocytes lack the ability to actively divide, primary cardiac tumors are extremely rare across all ethnicities and age groups. Once they occur, these tumors are often associated with genetic mutations and, occasionally, genetic syndromes. This underscores the importance of considering genetic mutations and syndromes when encountering these cases. The more common growths in the heart are thrombi and vegetations, which can mimic tumors, further making the differential diagnosis challenging. Among the imaging techniques, contrast-enhanced cardiac magnetic resonance imaging has the highest sensitivity for differential diagnosis. To aid in the differential diagnosis of cardiac masses, especially thrombi, appropriate utilization of biomarkers (i.e. D-dimer level) may provide pivotal clinical implications. Employing a multidisciplinary approach that integrates personal history, epidemiological insights, imaging findings, genetic markers, and biomarkers is therefore critical in the diagnostic process of cardiac masses.
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Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized primarily by airflow obstruction, significantly impacting patients' quality of life. Traditional mind-body exercises, as a non-pharmacological intervention for COPD, have become a new research focus. Objective: To assess the impact of traditional mind-body exercises (Tai Chi, Qigong, Yoga) on pulmonary function, exercise capacity, and quality of life in COPD patients. Additionally, to identify the most suitable form of traditional mind-body exercise for different indicators. Methods: Searches were conducted in databases such as Web of Science, PubMed, EBSCOhost, CNKI, etc., to collect randomized controlled trials (RCTs) evaluating the intervention of traditional mind-body exercises (Tai Chi, Yoga, Qigong) in COPD. The Cochrane evaluation tool was applied for methodological quality assessment of the included literature. Statistical analysis and sensitivity analysis were performed using Revman 5.4 software, while publication bias was assessed using R software. Results: This study included 23 studies with a total of 1862 participants. Traditional mind-body exercises improved patients' FEV1% index (WMD = 4.61, 95%CI [2.99, 6.23]), 6-min walk distance (SMD = 0.83, 95%CI [0.55, 1.11]), and reduced patients' SGRQ score (SMD = -0.79, 95%CI [-1.20, -0.38]) and CAT score (SMD = -0.79, 95%CI [-1.20, -0.38]). Qigong showed the most significant improvement in FEV1% and 6MWT, while Tai Chi primarily improved 6MWT, and the effect of Yoga was not significant. Sensitivity analysis indicated stable and reliable research conclusions. Conclusion: Traditional mind-body exercises are effective rehabilitation methods for COPD patients, significantly improving pulmonary function, exercise capacity, and quality of life. They are suitable as complementary interventions for standard COPD treatment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display-record.php?ID=CRD42023495104], identifier [CRD42023495104].
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Kushneria phosphatilytica YCWA18T (= CGMCC 1.9149T = NCCB 100306T) was isolated from sediment collected in a saltern on the eastern coast of Yellow Sea in China. The genome was sequenced and comprised of one circular chromosome with the size of 3,624,619 bp and DNA G + C content of 59.13%. A total of 3267 protein-coding genes, 64 tRNA genes and 12 rRNA genes were obtained. Genomic annotation indicated that the genome of K. phosphatilytica YCWA18T had 34 genes involved in phosphorus (P) solubilization/metabolism, e.g., gdh, pqq, phoA, phoD and phoX, which products can convert insoluble P-containing compounds to more bio-available dissolved inorganic P. Comparative genomic analysis of Kushneria strains revealed that gdh, pqq, phoA, phoD and phoX were widely distributed in these strains, indicating the genus Kushneria may play an important role in the P cycle. Additionally, a multitude of salt tolerance genes were detected in the genome of K. phosphatilytica YCWA18T. This study and the genome sequence data will be available for further research and will provide insights into potential biotechnological and agricultural applications of Kushneria strains.
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Genoma Bacteriano , Fósforo , Secuenciación Completa del Genoma , Fósforo/metabolismo , ChinaRESUMEN
The direction variation of the fundamental wave in the same nonlinear photonic crystal would cause different pattern of harmonics generation. In a 2D/3D crystal with dense reciprocal lattice vectors, there will be large numbers of conical harmonic beams evolving with direction change of the fundamental wave. By rearranging the Ewald sphere and superposing it into the Ewald shell, we have a hybrid Ewald construction. It becomes a simple but useful geometric method to comprehensively depict the distribution of these quasi-phase-matching second harmonics and their conical form evolution. It presents conical second harmonic beams by their related reciprocal lattice vectors and simplifies the beams' distribution according to spatial arrangement of those reciprocal lattice vectors. It finds that the conical beams will create, annihilate, or get enhanced in specific order when fundamental waves change incident directions. We applied the method on a periodically poled 2D LiTaO3 crystal and all observed phenomena, meet the method's predictions. In our experiment, we observed that the conical beams distorted along the optic axis of the sample due to anisotropy, which was generally overlooked by earlier researches. The eccentricities of their ring projections suggest a potential auxiliary approach for crystal dispersion measurement.
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The frontal branch of middle meningeal artery (MMA) can easily be damaged during revascularization surgery. To precise locate it and minimize its injury, we propose a set of modified craniotomy procedures combined with simple virtual reality (VR) technology based on three-dimensional (3D) Slicer simply, economically, and efficiently. Patients with Moyamoya disease (MMD) and internal carotid artery occlusion (ICAO) who received revascularization from January 2015 to December 2022 were divided into two groups based on the methods used to locate the MMA: traditional methods and precise MMA locating with VR technology. Patient demographics and clinical characteristics were analyzed to compare the preservation rates of MMA. The distances between this artery and bony anatomical landmarks were also measured to better understand its localization. There was no significant difference in baseline characteristics between the two groups. The precise MMA locating group exhibited a significantly higher preservation rate of the frontal branch of MMA (p = 0.037, 91.7% vs. 68.2%). Over 77% of patients had their frontal branch of MMA partially or completely surrounded by bony structures to varying degrees. Therefore, the combination of modified craniotomy procedures, 3D Slicer, and simple VR technology represents an economical, efficient, and operationally simple strategy.
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Craneotomía , Enfermedad de Moyamoya , Realidad Virtual , Humanos , Craneotomía/métodos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedad de Moyamoya/cirugía , Arterias Meníngeas/cirugía , Revascularización Cerebral/métodos , Imagenología Tridimensional/métodos , Adolescente , Adulto Joven , Niño , AncianoRESUMEN
Despite intensive search over the past decades, only a few small-molecule DNA fluorescent dyes were found with large Stokes shifts. These molecules, however, are often too toxic for widespread usage. Here, we designed DNA-specific fluorescent dyes rooted in benzimidazole architectures with a hitherto unexplored molecular framework based on thiazole-benzimidazole scaffolding. We further incorporated a pyrazole ring with an extended sidechain to prevent cell penetration. These novel benzimidazole derivatives were predicted by quantum calculations and subsequently validated to have large Stokes shifts ranging from 135 to 143 nm, with their emission colors changed from capri blue for the Hoechst reference compound to iguana green. These readily-synthesized compounds, which displayed improved DNA staining intensity and detection limits along with a complete loss of capability for cellular membrane permeation and negligible mutagenic effects as designed, offer a safer alternative to the existing high-performance small-molecule DNA fluorescent dyes.
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Bencimidazoles , ADN , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , ADN/química , Bencimidazoles/química , Humanos , Diseño de Fármacos , Mutágenos/química , Mutágenos/toxicidad , Daño del ADNRESUMEN
The Motor tic, Obsessions and Compulsions, Vocal tic Evaluation Survey (MOVES) is a widely used screening tool for Tourette syndrome (TS) and associated comorbidities. This study evaluated its applicability for children in China using 7,125 participants from the National Center for Children's Health (Beijing). Psychometric evaluations included exploratory and confirmatory factor analysis, yielding a 16-item, four-factor model that explained 55.11% of the variance and demonstrated good internal consistency (Cronbach's alpha = 0.88) and test-retest reliability (ICC = 0.86). The scale showed strong convergent, discriminant, and criterion-related validity and was significantly correlated with other established TS scales. The results affirm the reliability and validity of the MOVES for screening TS in Asian contexts, addressing a crucial gap in the region's TS assessment tools.
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Recombinant human erythropoietin (rhEPO) is a glycoprotein that acts as the main hormone involved in regulating red blood cell production to treat anemia caused by chronic kidney disease or chemotherapy, which has three N-glycosylation sites and one O-glycosylation site. It contains a variety of different glycosylation modifications, such as sialyation, O-acetylation on sialic acids, etc., which causes a big challenge for the glycosylation analysis of rhEPO. In this study, a liquid chromatography-mass spectrometry (LC-MS) method combined with electron-activated dissociation (EAD) technology was used in qualitative and quantitative characterization of rhEPO N-glycosylation and O-glycosylation in just one injection. The usage of EAD not only generated abundant MS/MS fragment ions of glycopeptides and improved the MS/MS sequence coverage but also preserved the glycan structures in the MS/MS fragment ions and the integrity of the glycosidic bond between the glycans and peptides. Three N-glycosylation sites (N24, N38, and N83) and one O-glycosylation site (S126) of rhEPO samples were successfully identified. Among them, the glycosylation ratios of N24, N38, and N83 sites were 82.7%, 100%, and 100% respectively, and 15, 10, and 12 different N-glycans could be identified at the glycopeptide level. The total average number of sialic acids, N-hydroxyacetylneuraminoic acid, and O-acetylation on sialic acid were 7.28, 4.21, and 0.66 at the intact protein level, respectively. For O-glycosylation site S126, O-glycosylation ratios analyzed at the intact protein level and the glycopeptide level were 80.2% and 80.3%, respectively, and two O-glycans were identified, including Core1_S1 and Core1_S2. This study also compared the difference of the glycans and their relative contents in batch-to-batch rhEPO samples. The results proved that the workflow using EAD fragmentation in LC-MS method could be effectively applied for characterizing the glycosylation analysis of rhEPO samples and batch-to-batch consistency analysis, which would help to reasonably guide the optimization of rhEPO production process.
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Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.
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Fatty acids (FAs) are essential molecules in all organisms and are involved in various physiological and pathophysiological processes. Pentafluorobenzyl bromide (PFBBr) is commonly used for FA derivatization for gas chromatography-mass spectrometry (GC-MS) quantification by chemical ionization (CI). While CI is the conventional ionization mode for PFBBr derivatization, the electron ionization (EI) source has also demonstrated efficacy in achieving satisfactory analytical performance for the analysis of PFB esters. In this study, we present a novel approach utilizing PFBBr-derivatization on a GC-EI-MS platform to quantitatively analyze a comprehensive range of 44 fatty acids (FAs) spanning from C2 to C24. The method's sensitivity, precision, accuracy, linearity, recovery, and matrix effect were rigorously validated against predetermined acceptance criteria. In comparison to the conventional CI ionization mode, the utilization of PFBBr-derivatization in GC-EI-MS exhibits a wider range of applications and achieves comparable sensitivity levels to the conventional CI platform. By using this method, we successfully quantified 44 FAs in plasma and feces samples from the mice with deoxynivalenol (DON)-induced kidney injury. Among these, the levels of most FA species were increased in the DON-exposure group compared with the control group. The orthogonal partial least squares discriminant analysis (OPLS-DA) of all the tested FAs showed a visual separation of the two groups, indicating DON exposure resulted in a disturbance of the FA profile in mice. These results indicate that the established method by integration of GC-MS with PFBBr derivatization is an efficient approach to quantify the comprehensive FA profile, which includes short-, medium- and long-chain FAs. In addition, our study provides new insights into the mechanism underlying DON exposure-induced kidney injury.
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Electrones , Ácidos Grasos , Fluorobencenos , Fluorocarburos , Animales , Ratones , Cromatografía de Gases y Espectrometría de Masas/métodos , Ácidos Grasos/análisis , Heces/químicaRESUMEN
In nuclear radiation detection, some measured radiation counts are lost due to dead time. Estimation of dead time is necessary to restore the counting information in quantitative analysis. This study aims to propose a method for estimating dead time at high counting rate. First of all, a measurement system of pulse interval distribution was used to estimate the true input counting rate of the detection system and implemented in FPGA. Then, a digital pole-zero cancellation technique was introduced in the measurement system to decrease the decay time constant of pulse. This was aimed at mitigating the impact of pile-up on the pulse interval distribution spectrum, especially at high counting rate. The feasibility of this measurement system at high counting rate was verified by the experimental platform of EDXRF. The dead time was calculated using the measured counting rate and the estimated true input counting rate. The accuracy of the dead time relies on the precision of the estimated true count rate. When the counting rate reaches 600 kCPS, the relative error between the theoretical counting rate and the estimated true input counting rate is less than 5%.
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Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Antígeno B7-H1/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.
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MicroARN Circulante , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Obesidad Mórbida , Niño , Adolescente , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Hígado/patología , MicroARN Circulante/genética , MicroARN Circulante/metabolismo , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Obesidad Mórbida/metabolismo , MicroARNs/metabolismo , Obesidad/complicaciones , Fibrosis , Inflamación/patologíaRESUMEN
Rhenium sulfide (ReS2) has emerged as a promising two-dimensional material, demonstrating broad-spectrum visible absorption properties that make it highly relevant for diverse optoelectronic applications. Manipulating and optimizing the pathway of photogenerated carriers play a pivotal role in enhancing the efficiency of charge separation and transfer in novel semiconductor composites. This study focuses on the strategic construction of a semiconductor heterostructure by synthesizing ZnO on vacancy-containing ReS2 (VRe-ReS2) through chemical bonding processes. The ingeniously engineered built-in electric field within the heterostructure effectively suppresses the recombination of photogenerated electron-hole pairs. A direct and well-established interfacial connection between VRe-ReS2 and ZnO is achieved through a robust Zn-S bond. This distinctive bond configuration leads to enhanced nonlinear optical conversion efficiency, attributed to shortened carrier migration distances and accelerated charge transfer rates. Furthermore, theoretical calculations unveil the superior chemical interactions between Re vacancies and sulfide moieties, facilitating the formation of Zn-S bonds. The photoluminescence (PL) intensity is increased by the formation of VRe-ReS2 and ZnO heterostructure and the PL quantum yield of VRe-ReS2 is improved. The intricate impact of the Zn-S bond on the nonlinear absorption behavior of the VRe-ReS2@ZnO heterostructure is systematically investigated using femtosecond Z-scan techniques. The charge transfer from ZnO to ReS2 defect levels induces a transition from saturable absorption to reverse saturable absorption in the VRe-ReS2@ZnO heterostructure. Transient absorption measurements further confirm the presence of the Zn-S bond between the interfaces, as evidenced by the prolonged relaxation time (τ3) in the VRe-ReS2@ZnO heterostructure. This study offers valuable insights into the rational construction of heterojunctions through tailored interfacial bonding and surface/interface charge transfer pathways. These endeavors facilitate the modulation of electron transfer dynamics, ultimately yielding superior nonlinear optical conversion efficiency and effective charge regulation in optoelectronic functional materials.
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Systematic interface and defect engineering strategies have been demonstrated to be an effective way to modulate the electron transfer and nonlinear absorption properties in semiconductor heterojunctions. However, the role played by defects and interfacial strain in electron transfer at the interface of the MoX2 (X = Se, S, Te)@ZnO heterojunction remains poorly understood. Herein, using the MoX2@ZnO heterojunction, we reveal that vacancies play a critical role in the interfacial electron transfer of heterojunctions. Specifically, we present the defect and interface engineering of the MoX2@ZnO heterojunction for controlled charge transfer and electron excitation-relaxation. The experimental characterization combined with first-principles calculations showed that the presence of defects promoted the transport of photogenerated carriers at the heterojunction interface, thereby inhibiting their rapid recombination. The DFT calculation confirmed that the electron band structure, density of states and charge density distribution in the system changed after the formation of Mo-O bonds. On the basis of defects and interfacial stress and the effective charge transfer, the MoX2@ZnO heterojunction exhibited excellent excitation and emission behaviors. The nonlinear optical regulation behavior of TMDs is expected to be realized with the help of the defects and interface/surface synergistically modulated effect of ZnO nanoparticles. The local strain generation on the MoX2@ZnO heterojunction boundary provides a new method for the design of new heterogeneous materials and will be of great significance to investigate the contact physical behavior and application of metals and two-dimensional (2D) semiconductors. This work provides some inspiration for the construction of heterojunctions with rich defects and surface/interface charge transfer channels to promote tunable electron transfer dynamics, thereby achieving a good nonlinear optical conversion efficiency and efficient charge separation in optoelectronic functional materials.
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Hand, foot, and mouth disease is a serious public health problem, and the main pathogen is enterovirus 71 (EV71). Its capsid assembly mechanism including capsid protein processing has been widely studied. Full and empty capsids have different immunological efficacy. Therefore, tracking full/empty capsid ratio throughout the EV71 production process is important to ensure consistent product quality and proper dosing response. The analysis of full/empty capsid ratio of intact virus has been widely reported as well. A variety of techniques have been employed to evaluate the full/empty capsid ratios. However, there has not been a rapid, reproducible, and robust assay to determine the full/empty capsid ratios of final and in-process products. In this study, a novel assay based on capillary zone electrophoresis was established. The separation of full and empty species could be achieved within 10 min and the ratio of peak areas was used to calculate the full/empty capsid ratio directly. The results showed good reproducibility and linearity for the determination of full/empty capsid ratios.
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Enterovirus Humano A , Enterovirus Humano A/metabolismo , Reproducibilidad de los Resultados , Proteínas de la Cápside , Cápside/metabolismo , Procesamiento Proteico-PostraduccionalRESUMEN
AIMS: Deoxynivalenol (DON), namely vomitoxin, is one of the most prevalent fungal toxins in cereal crops worldwide. However, the underlying toxic mechanisms of DON remain largely unknown. MAIN METHODS: DON exposure-caused changes in the murine plasma metabolome and gut microbiome were investigated by an LC-MS/MS-based nontargeted metabolomics approach and sequencing of 16S rRNA in fecal samples, respectively. Cellular models were then used to validate the findings from the metabolomics study. KEY FINDINGS: DON exposure increased intestinal barrier permeability evidenced by its-mediated decrease in colonic Claudin 5 and E-cadherin, as well as increases in colonic Ifn-γ, Cxcl9, Cxcl10, and Cxcr3. Furthermore, DON exposure resulted in a significant increase in murine plasma levels of deoxycholic acid (DCA). Also, DON exposure led to gut microbiota dysbiosis, which was associated with DON exposure-caused increase in plasma DCA. In addition, we found not only DON but also DCA dose-dependently caused a significant increase in the levels of IFN-γ, CXCL9, CXCL10, and/or CXCR3, as well as a significant decrease in the expression levels of Claudin 5 and/or E-cadherin in the human colonic epithelial cells (NCM460). SIGNIFICANCE: DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
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Enfermedades Intestinales , Espectrometría de Masas en Tándem , Humanos , Ratones , Animales , Cromatografía Liquida , ARN Ribosómico 16S , Claudina-5 , Cadherinas , Ácido Desoxicólico/toxicidadRESUMEN
Adeno-associated virus (AAV) has been widely used to treat various human diseases as an important delivery vector for gene therapy due to its low immunogenicity and safety. AAV capsids proteins are comprised of three capsid viral proteins (VP; VP1, VP2, VP3). The capsid proteins play a key role in viral vector infectivity and transduction efficiency. To ensure the safety and efficacy of AAV gene therapy products, the quality of AAV vector capsid proteins during development and production should be carefully monitored and controlled. Microflow liquid chromatography coupled with mass spectrometry provides superior sensitivity and fast analysis capability. It showed significant advantages in the analysis of low- concentration and large numbers of AAV samples. The intact mass of capsid protein can be accurately determined using high-resolution mass spectrometry (MS). And MS also provides highly confident confirmation of sequence coverage and post-translational modifications site identification and quantitation. In this study, we used microflow liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the characterization of AAV2 capsid protein. we obtained nearly 100% sequence coverage of low-concentration AAV2 capsid protein (8 × 1011 GC/mL). More than 30 post-translational modifications (PTMs) sites were identified, the PTMs types included deamidation, oxidation and acetylation. From this study, the proposed microflow LC-MS/MS method provides a sensitive and high throughput approach in the characterization of AAVs and other biological products with low abundance.
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Proteínas de la Cápside , Dependovirus , Humanos , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Cápside/metabolismo , Vectores GenéticosRESUMEN
Ferroptosis is a new form of regulated cell death caused by iron-dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine-glutathione-glutathione peroxidase 4 system (cyst(e)ine-GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH4) system (GCH1/BH4 system), ferroptosis suppressor protein 1/coenzyme Q10 system (FSP1/CoQ10 system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q10 (CoQ10), BH4, hydropersulfides, vitamin K, vitamin E, 7-dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors.
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Quistes , Ubiquinona , Humanos , Ubiquinona/metabolismo , Peroxidación de Lípido , Muerte Celular , Peróxidos Lipídicos/metabolismoRESUMEN
Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.