RESUMEN

Alkaline ferri/ferro-cyanide-based flow batteries are well suited for energy storage because of their features of high electrochemical activity, good kinetics and low material cost. However, they suffer from low energy density and poor temperature adaptability. The ferri/ferro-cyanide catholyte exhibits low solubility (~0.4 M at 25 °C) in NaOH- or KOH-based supporting electrolyte and can easily form precipitates below room temperature. Here we report a lithium-based supporting electrolyte that significantly enhances the solubility of ferrocyanide. The use of LiOH intensifies the ion-dipole interaction between water molecules and solutes and cripples polarization among ferrocyanide ions. Thus, we have achieved a ferrocyanide-based catholyte of 1.7 M at 25 °C and of 0.8 M at -10 °C. A zinc-ferricyanide flow battery based on the lithium-based supporting electrolyte demonstrates a steady charge energy of ~72 Wh L-1catholyte at 25 °C for ~4200 cycles (~4200 hours). Furthermore, it remains stable for ~800 cycles (~800 hours) at -10 °C.

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ETHNOPHARMACOLOGICAL RELEVANCE: Thesium chinense Turcz., a traditional Chinese herbal medicine, displays good therapeutic efficiency against respiratory diseases (e.g. pneumonia, pharyngitis) in clinical applications, however, its effects on COPD and the mechanism of action are still unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic effect of the ethyl acetate fraction of Thesium chinense Turcz. (TCEA) on COPD and reveal the underlying mechanism. MATERIALS AND METHODS: A cigarette smoke (CS)-induced mouse COPD model was established, and the efficacy of TCEA was evaluated using peripheral blood testing, HE and Masson staining, qRT-PCR and ELISA assays. TCEA was analyzed for chemical composition by LC-MS/MS and HPLC. Prediction of major signaling pathways and potential targets was performed by network pharmacology. The molecular mechanism of TCEA was explored by immunoblotting, immunofluorescence staining, flow cytometry, and ubiquitination assay. Finally, potential active small molecules in TCEA were identified by molecular virtual screening. RESULTS: TCEA treatment significantly inhibited the secretion of pro-inflammatory factors and attenuated pathological emphysema. The main chemical constituents of TCEA were identified as flavonoids by UPLC-MS/MS. Network pharmacology analysis enriched the Nrf2 signaling pathway closely related to oxidative stress. Our results suggested that TCEA inhibited ferroptosis by activating Nrf2/SLC7A11/GPX4 axis and inhibiting lipid metabolism-related proteins, ACSL4, ALOX5 and COX2 in vivo and in vitro. Noteworthily, the beneficial impact of TCEA on regulation of SLC7A11 and GPX4 vanished after silencing Nrf2. Moreover, Nrf2 ubiquitination was inhibited by TCEA treatment. Finally, several flavonoids modulating Nrf2 were identified by molecular virtual screening. CONCLUSIONS: TCEA significantly alleviated COPD progression by inhibiting ferroptosis primarily through activation of Nrf2/SLC7A11/GPX4 signaling. Flavonoids are the main active components that exert their effects. These findings shed light on the mechanism of action of TCEA and its potential active components, providing a feasible approach for the treatment of COPD.

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Caffeoyl-coenzyme 3 A-O-methyltransferase (CCoAOMT) plays a crucial role in the lignin synthesis in many higher plants. In this study, nine PbCCoAOMT genes in total were identified from pear, and classified into six categories. We treated pear fruits with hormones abscisic acid (ABA) and methyl jasmonate (MeJA) and salicylic acid (SA) and observed differential expression levels of these genes. Through qRT-PCR, we also preliminarily identified candidate PbCCoAOMT gene, potentially involved in lignin synthesis in pear fruits. Additionally, the overexpression of PbCCoAOMT1/2 in Arabidopsis and pear fruits increased in lignin content. Enzymatic assays showed that recombinant PbCCoAOMT1/2 proteins have similar enzymatic activity in vitro. The Y1H (Yeast one-hybrid) and dual luciferase (dual-LUC) experiments demonstrated that PbMYB25 can bind to the AC elements in the promoter region of the PbCCoAOMT1 gene. Our findings suggested that the PbCCoAOMT1 and PbCCoAOMT2 genes may contribute to the synthesis of lignin and provide insights into the mechanism of lignin biosynthesis and stone cell development in pear fruits.

Asunto(s)

Arabidopsis , Regulación de la Expresión Génica de las Plantas , Lignina , Metiltransferasas , Pyrus , Lignina/metabolismo , Lignina/biosíntesis , Metiltransferasas/genética , Metiltransferasas/metabolismo , Pyrus/genética , Pyrus/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Frutas/genética , Frutas/metabolismo , Ácido Salicílico/metabolismo , Regiones Promotoras Genéticas , Plantas Modificadas Genéticamente/genética , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Acetatos/metabolismo

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In chicken, primordial germ cells (PGC) are crucial for the preservation and manipulation of genetic resources in poultry production. The HiS and FAcs culture systems are two important methods for the in vitro cultivation of chicken PGCs. The purpose of this study was to compare and analyze the two cultivation systems for PGCs (His and FAcs culture systems) to assess their efficacy and applicability in supporting PGC growth, maintaining PGC characteristics, and lineage transmission ability. The study found that both HiS and FAcs culture systems could maintain the basic biological characteristics of chicken PGCs, including the simultaneous expression of pluripotency and reproductive marker genes, as well as the presence of abundant glycogen granules. Subsequently, we identified 2,145 differentially expressed genes (DEG) through RNA sequencing. GO and KEGG analysis revealed a large number of DEGs enriched in the cell adhesion and calcium ion binding pathways, and the analysis found that these genes maintained a higher level in HiS-PGCs. Further personalized analysis found that the regulatory genes for maintaining PGC pluripotency were highly expressed in HiS-PGCs, while germ cell-related genes showed similar expression in both systems. Additionally, through RNA sequencing data and cell proliferation ability, it was found that PGCs in the FAcs system had a higher proliferation rate and a faster cell cycle. Finally, it was discovered that the expression of cell migration-related genes was maintained at a higher level in HiS-PGCs, but the migration efficiency of HiS-PGCs did not show a significant difference compared to FAcs-PGCs. These results suggest that both HiS and FAcs culture systems can maintain the proliferation and basic characteristics of chicken PGCs, but differences exist in cell proliferation, pluripotency regulation, and cell adhesion. These findings provide new information for optimizing PGC cultivation systems and are important for the preservation and genetic improvement of chicken PGCs.

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Glycolic acid is an important chemical product widely used in various fields, including cosmetics, detergents, textiles, and more. Currently, microbial production of glycolic acid has disadvantages such as poor genetic stability, low yield, and high cost. Additionally, whole-cell catalytic production of glycolic acid typically requires the addition of relatively expensive sorbitol as a carbon source, which limits its industrial production. To develop an industrially applicable method for glycolic acid production, this study used ethylene glycol as a substrate to screen the glycolic acid-producing strains through whole-cell catalysis, obtaining a Rhodotorula sp. capable of producing glycolic acid. The strain was then subjected to UV mutagenesis and high throughput screening, and the positive mutant strain RMGly-20 was obtained. After optimization in shake flasks, the glycolic acid titer of RMGly-20 reached 17.8 g/L, a 10.1-fold increase compared to the original strain. Using glucose as the carbon source and employing a fed-batch culture in a 5 L fermenter, strain RMGly-20 produced 61.1 g/L of the glycolic acid. This achievement marks the preliminary breeding of a genetically stable glycolic acid-producing strain using a cheap carbon source, providing a new host for the biosynthesis of glycolic acid and promoting further progress toward industrial production.

Asunto(s)

Fermentación , Glicolatos , Rhodotorula , Glicolatos/metabolismo , Rhodotorula/metabolismo , Rhodotorula/genética , Microbiología Industrial/métodos , Glicol de Etileno/metabolismo , Mutagénesis

RESUMEN

China's local chicken breeds are rich in resources, and have formed different germplasm characteristics in the process of long-term selection and evolution. Scientific assessment of population genetic diversity and identification of inter-breed genetic structure are of great value to the protection and innovative utilization of local chicken breed resource. In order to evaluate the application effectiveness of 23K SNP chip "Youxin-1" in the analysis of genetic diversity and genetic structure of local chickens, we used RADseq to identify genomic genetic variation of 21 local chicken breeds and developed 23K chip "Youxin-1". The genetic statistics of each variety were calculated based on two sets of SNP data, and correlation, fitting and phylogenetic analysis were carried out to evaluate the application effectiveness of the chip. The results showed that the observed heterozygosity (Ho), polymorphism information content (PIC), inbred coefficient (FROH) and genetic differentiation coefficient (Fst) calculated based on the two SNP data sets were basically consistent in the 21 local chicken breeds. The genetic diversity of Langya chicken (LA), Piao chicken (PJ) and Wenchang chicken (WC) was relatively rich. The genetic diversity of Bian chickens (BJ), Langshan chickens (LS), Gushi chickens (GS), Dongxiang blue-eggshell chickens (DX) and Beijing fatty chickens (BY) was relatively poor, and the correlation coefficients of Ho, PIC, FROH and average Fst in the two groups were 0.794, 0.901, 0.926 and 0.984, respectively, all reaching extremely significant levels (P<0.01) with a high degree of fit (P<0.001) and R2 were 0.644, 0.827, 0.916 and 0.927. For the two sets of SNP data, the evolutionary tree constructed by neighbor-joining (NJ) method and maximum likelihood (ML) method was reasonable, and the 21 local chicken breeds were generally divided into six categories, which was consistent with the formation history and geographical distribution of the varieties. The 23K chip also realized reasonable clustering of the five new varieties without individual deviation. There are some differences in the estimation of genetic statistics using SNP with different densities, and data standardization is needed. 23K chip has good efficacy in the analysis of genetic diversity and structure of local chickens.

Asunto(s)

Pollos , Variación Genética , Polimorfismo de Nucleótido Simple , Animales , Pollos/genética , Filogenia , Cruzamiento , China , Análisis de Secuencia por Matrices de Oligonucleótidos

RESUMEN

Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes.

Asunto(s)

Histidina , Procesamiento Proteico-Postraduccional , Dedos de Zinc , Histidina/metabolismo , Metilación , Humanos , Epigenoma , Células HEK293 , Metiltransferasas/metabolismo , Metiltransferasas/genética

RESUMEN

Formaldehyde (HCHO) is an important source for driving tropospheric ozone (O3) formation. This study investigated the combined effects of anthropogenic and biogenic emission on O3 formation in the Guanzhong Basin (GZB), Central China, providing useful information into the mechanisms of O3 formation due to the interaction between anthropogenic and biogenic volatile organic compounds (VOCs). A severe O3 pollution episode in summer of 2017 was simulated using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to examine the impacts of ambient HCHO on ground-level O3. Results showed secondary HCHO dominated ambient levels, peaking in the afternoon (up to 86 %), while primary emissions contributed 14 % on average. This enhanced O3 production by 7.7 % during the morning rush hour and 24.3 % in the afternoon. In addition, HCHO concentration peaked before that of O3, suggesting it plays significant role in O3 formation. Biogenic emission oxidation contributed 3.1 µg m-3 (53.1 %) of HCHO and 5.2 pptv (40.1 %) of hydroperoxyl radicals (HO2) in average urban areas, where the downwind regions of the forests had high nitrogen oxides (NOx) levels and favorable conditions for O3 production (17.3 µg m-3, 20.5 %). In forested regions, sustained isoprene oxidation led to elevated oxidized VOCs including HCHO and acetaldehyde downwind, which practiced further photolysis of O3 formation with anthropogenic NOx in urban areas. Sensitivity experiments recommend controlling industrial and traffic NOx emissions, with regional joint prevention and regulation, which are essential to reduce O3 pollution.

Asunto(s)

Contaminantes Atmosféricos , Monitoreo del Ambiente , Formaldehído , Ozono , Compuestos Orgánicos Volátiles , Formaldehído/análisis , Contaminantes Atmosféricos/análisis , China , Ozono/análisis , Compuestos Orgánicos Volátiles/análisis , Bosques , Contaminación del Aire/estadística & datos numéricos

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As the important hub of many cellular signaling networks, KRAS (Kirsten rat sarcoma viral oncogene homologue) has been identified as a tumor biomarker. It is the frequently mutated oncogene in human cancers, and KRAS protein activation caused by mutations, such as G12D, has been found in many human tumors tissues. Although, there are two specific allosteric sites (AS1 and AS2) on the KRAS protein that can be used as the targets for inhibitor development, the difference of regulatory mechanisms between two individual allosteric sites still not be reported. Here, using molecular dynamics simulations combined with molecular mechanics generalized born surface area (MM/GBSA) analysis, we found that both of the inhibitors, located at AS1 and AS2, were able to reduce the binding free energy between wild type, mutant KRAS (G12/D/V/S/C) and GTP remarkably, however the effect of inhibitors on the binding free energy between wild type, mutant KRAS and GDP was limited. In addition, the degree of decrease of binding free energy between KRAS and GTP caused by inhibitors at AS2 was significantly greater than that caused by inhibitors at AS1. Further analysis revealed that both inhibitors at AS1 and AS2 were able to regulate the fluctuation of Switch Ⅰ and Switch Ⅱ to expand the pocket of the orthosteric site (GTP binding site), thereby reducing the binding of KRAS to GTP. Noteworthy there was significant differences in the regulatory preferences on Switch Ⅰ and Switch Ⅱ between two type inhibitor. The inhibitor at AS2 mainly regulated Switch Ⅱ to affect the pocket of the orthosteric site, while the inhibitor at AS1 mainly expand the pocket of the orthosteric site by regulating the fluctuation of Switch Ⅰ. Our study compared the differences between two type inhibitors in regulating the KRAS protein activity and revealed the advantages of the AS2 as the small molecule drug target, aiming to provide theoretical guidance for the research of novel KRAS protein inhibitors.

Asunto(s)

Sitio Alostérico , Simulación de Dinámica Molecular , Mutación , Proteínas Proto-Oncogénicas p21(ras) , Proteínas Proto-Oncogénicas p21(ras)/química , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Humanos , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/química , Regulación Alostérica , Unión Proteica , Guanosina Difosfato/metabolismo , Guanosina Difosfato/química

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Accumulation of ß-amyloid (Aß) in the brain has been recognized as a key factor in the onset and progression of Alzheimer's disease (AD).The accumulation of Aß in the brain catalyzes the production of reactive oxygen species (ROS), which in turn triggers oxidative damage to cellular components such as DNA, lipids, and proteins. In the present study, we investigated the protective effect of Ganoderic acid A (GA.A) against Aß42-induced apoptosis in PC12 cells. Changes in mitochondrial membrane potential indicated that GA.A treats mitochondrial dysfunction by decreasing Aß42 deposition and inhibiting neural protofiber tangle formation. Changes in intracellular Ca2+ and caspase-3 indicated that GA.A reduced mitochondrial damage by Aß42 in PC12 cells, thereby decreasing ROS accumulation and reducing Aß protofiber-induced cytotoxicity. These features suggest that GA.A has great potential as an effective neuroprotective drug in the treatment of Alzheimer's disease.

Asunto(s)

Péptidos beta-Amiloides , Apoptosis , Lanosterol , Potencial de la Membrana Mitocondrial , Mitocondrias , Fármacos Neuroprotectores , Fragmentos de Péptidos , Especies Reactivas de Oxígeno , Animales , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/metabolismo , Células PC12 , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fragmentos de Péptidos/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Apoptosis/efectos de los fármacos , Lanosterol/farmacología , Lanosterol/análogos & derivados , Calcio/metabolismo , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Ácidos Heptanoicos

RESUMEN

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call non B cell-derived Igs (non B Igs), has been documented by growing studies. It has been demonstrated that non B-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, non B-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of non B-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.

Asunto(s)

Inmunoglobulinas , Humanos , Animales , Inmunoglobulinas/genética , Inmunoglobulinas/metabolismo , Inmunoglobulinas/inmunología , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/citología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/inmunología , Células Mieloides/inmunología , Células Mieloides/metabolismo

RESUMEN

Salinization is a global problem affecting agricultural productivity and sustainability. The application of exogenous microbial fertilizer harbors great potential for improving saline-alkali soil conditions and increasing land productivity. Yet the responses to microbial fertilizer application rate in terms of rhizosphere soil biochemical characteristics, soil microbial community, and crop yield and their interrelationships and underlying mechanisms are still unclear. Here, we studied changes to rhizosphere soil-related variables, soil enzyme activity (catalase, sucrase, urease), microbial community diversity, and sweet sorghum (Sorghum bicolor (L.) Moench) yield under four fertilization concentration levels (0, 0.12, 0.24, and 0.36 kg m-2) in a saline-alkali ecosystem (Shandong, China). Our results showed that the best improvement effect on soil when the microbial fertilizer was applied at a rate of 0.24 kg m-2. Compared with the control (sweet sorghum + no fertilizer), it significantly increased soil organic carbon (21.50 %), available phosphorus (26.14 %), available potassium (36.30 %), and soil urease (38.46 %), while significantly reducing soil pH (2.21 %) and EC (12.04 %). Meanwhile, the yield of sweet sorghum was increased by 24.19 %. This is mainly because microbial fertilizers enhanced the diversity and the network complexity of bacterial and fungal communities, and influenced catalase (CAT), urease (UE), and sucrase (SC), thereby facilitating nutrient release in the soil, enhancing soil fertility, and indirectly influencing sweet sorghum productivity. Among them, Gemmatimonadota and Verrucomicrobiota may be the key microbial factors affecting sweet sorghum yield, while available potassium, soil urease and available phosphorus are the main soil factors. These findings provide valuable theoretical insights for preserving the health of coastal saline-alkali soils and meeting the agricultural demand for increased yield per unit of land area.

Asunto(s)

Fertilizantes , Microbiología del Suelo , Suelo , Sorghum , Fertilizantes/análisis , Suelo/química , China , Hongos , Salinidad , Productos Agrícolas , Bacterias , Agricultura/métodos , Microbiota , Rizosfera

RESUMEN

Background: The rate at which the anticancer drug paclitaxel is cleared from the body markedly impacts its dosage and chemotherapy effectiveness. Importantly, paclitaxel clearance varies among individuals, primarily because of genetic polymorphisms. This metabolic variability arises from a nonlinear process that is influenced by multiple single nucleotide polymorphisms (SNPs). Conventional bioinformatics methods struggle to accurately analyze this complex process and, currently, there is no established efficient algorithm for investigating SNP interactions. Methods: We developed a novel machine-learning approach called GEP-CSIs data mining algorithm. This algorithm, an advanced version of GEP, uses linear algebra computations to handle discrete variables. The GEP-CSI algorithm calculates a fitness function score based on paclitaxel clearance data and genetic polymorphisms in patients with nonsmall cell lung cancer. The data were divided into a primary set and a validation set for the analysis. Results: We identified and validated 1184 three-SNP combinations that had the highest fitness function values. Notably, SERPINA1, ATF3 and EGF were found to indirectly influence paclitaxel clearance by coordinating the activity of genes previously reported to be significant in paclitaxel clearance. Particularly intriguing was the discovery of a combination of three SNPs in genes FLT1, EGF and MUC16. These SNPs-related proteins were confirmed to interact with each other in the protein-protein interaction network, which formed the basis for further exploration of their functional roles and mechanisms. Conclusion: We successfully developed an effective deep-learning algorithm tailored for the nuanced mining of SNP interactions, leveraging data on paclitaxel clearance and individual genetic polymorphisms.

RESUMEN

Geological modeling is a three-dimensional (3D) representation of comprehensive geological research results in oil fields. In this paper, first, the comprehensive geological research results were fully applied to establish geological models such as matrix, reservoir, and fractures in the study area. Second, in response to the geological characteristics of carbonate fractured and vuggy reservoirs, various data are integrated. Finally, by collecting and organizing various basic data mentioned above, a refined geological model of the oil reservoir in the study area is established. Results show that (a) Due to the complexity of the distribution of cracks and pores, the presence of these unrelated grids also affects the observation of target cracks and pores. (b) There may be multiple adjacent nodes in the initial access node. The strategy of depth-first traversal is to first access the first adjacent node. (c) There is a significant difference between the connected units extracted solely from static data and the connected units reextracted after fine-tuning the crack position considering dynamic data.

RESUMEN

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

RESUMEN

Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p < 0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage Ⅲ/silicosis stage Ⅰ groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.

Asunto(s)

Biomarcadores , Citocinas , Exosomas , Proteómica , Silicosis , Silicosis/sangre , Humanos , Citocinas/sangre , Citocinas/metabolismo , Exosomas/metabolismo , Biomarcadores/sangre , Masculino , Persona de Mediana Edad , Exposición Profesional , Adulto , Estudios de Casos y Controles , Dióxido de Silicio

RESUMEN

At present, research studies on the description of fracture characterization elements in fault solution reservoirs are relatively limited, and further research is needed on contour recognition and characterization methods. In this paper, first, the regional fault system is investigated and the faults are finely identified and characterized. Second, the volume of contour-sensitive attributes of the fault solver is optimized using tensor attributes, amplitude variation, discontinuity detection, and other attributes. Finally, a comprehensive evaluation of the fault solution reservoir is carried out by combining the dynamic production characteristics. Results show that (a) the interior details of fractured reservoirs can be mainly divided into two categories: cave-type reservoirs and fracture-pore-type reservoirs. (b) Fractured and porous reservoirs mainly utilize discontinuous properties and combine well data to calibrate and determine threshold values, ultimately achieving the characterization of interior details of fractured solution bodies. (c) After anisotropic diffusion filtering and fault enhancement, the seismic data was subjected to amplitude gradient disorder detection attribute calculation for multiscale fractures.

RESUMEN

Aim: This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites. Methods: We systematically searched the PubMed, Embase, and Cochrane databases for trials investigating ICI-based therapies published between their inception and August 2023. Results: In total, 147 studies involving 45,855 patients met the inclusion criteria. Among them, patients treated with ICIs reported 39.8% and 14.9% of all-grade and grade ≥3 immune-related adverse events (irAEs), respectively. The most common all-grade irAEs were dermatological and gastrointestinal issues, diarrhea, and pruritus, whereas patients who received ICIs showed most common grade ≥3 irAEs, including gastrointestinal events, diarrhea, increased aspartate aminotransferase and alanine transaminase levels, and hepatic and dermatological events. The overall trAE incidence in patients treated with ICIs was 83.2% for all-grade trAEs and 38.2% for grade ≥3 trAEs. TrAE incidence was highest for patients treated with cytotoxic T lymphocyte antigen-4 inhibitors for all-grade and grade ≥3 trAEs, with incidences of 86.4% and 39.2%, respectively. ICIs combined with targeted therapy showed the highest all-grade and grade ≥3 trAEs, with incidences of 96.3% and 59.4%, respectively. The most common all-grade trAEs were anemia, decrease in white blood cell count, decrease in neutrophil count, nausea, fatigue, diarrhea, and alopecia; patients who received ICIs presented relatively high incidences of grade ≥3 trAEs. Conclusion: This study provided comprehensive data regarding irAEs and trAEs in patients receiving ICIs. These results should be applied in clinical practice to provide an essential reference for safety profiles of ICIs. Systematic review registration: INPLASY platform, identifier INPLASY202380119.

RESUMEN

In recent years, significant advancements in radiofrequency ablation technology have notably enhanced arrhythmia treatment in cardiology. Technological advancements and increasing clinical adoption have made radiofrequency ablation a key therapy in improving life quality for patients with conditions like atrial fibrillation (AF). Consequently, there has been a marked increase in research output, underscoring the technology's significance and its potential in cardiology. Aims to comprehensively analyze cardiology's radiofrequency ablation research trends, identifying leading countries and institutions in international collaborations, key researchers' contributions, and evolving research hotspots. The study, based on the Web of Science Core Collection database, reviewed the literatures from 2004 to 2023. CiteSpace 6.2.R7 Basic was used for bibliometric analysis, which examined annual publication trends, international collaboration networks, key authors, leading research institutions, major journals, keyword co-occurrence and clustering trends. Analyzing 3423 relevant articles, this study reveals a consistent growth in cardiology radiofrequency ablation research since 2004. The analysis shows that the United States, Germany, and France hold central roles in the international collaboration network, with leading authors from premier US and European institutions. Keyword cluster analysis identifies "atrial flutter" and "ventricular tachycardia" as current research focal points. Cardiology radiofrequency ablation research shows a growth trend, led by the United States and European countries. Research hotspots are concentrated on the diverse applications of radiofrequency ablation technology and the treatment of AF. Future studies may increasingly focus on technological innovation and the deepening of clinical applications.

Asunto(s)

Bibliometría , Cardiología , Ablación por Radiofrecuencia , Humanos , Cardiología/tendencias , Ablación por Radiofrecuencia/estadística & datos numéricos , Ablación por Radiofrecuencia/métodos , Ablación por Radiofrecuencia/tendencias , Investigación Biomédica/tendencias , Investigación Biomédica/estadística & datos numéricos , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Ablación por Catéter/estadística & datos numéricos , Ablación por Catéter/tendencias

RESUMEN

INTRODUCTION: This study examined the prevalence of tobacco exposure and drinking and ascertained the relationships between tobacco exposure, alcohol drinking, concurrent smoking and drinking, and hypertension in rural southwestern China. METHODS: Data were collected from a cross-sectional health interview and examination survey, which included 7572 adults aged ≥35 years, in rural China. Participant demographic characteristics, smoking habits, exposure to secondhand smoke (SHS), and alcohol drinking habits were obtained using a standard questionnaire. Blood pressure (BP), height, weight, and waist circumference were measured for each participant. RESULTS: The overall prevalence of smoking, SHS exposure, drinking, concurrent smoking and drinking, concurrent exposure to SHS and drinking, and hypertension was 37.7%, 27.4%, 16.2%, 12.6%, 1.6%, and 41.3%, respectively. Males had a significantly higher prevalence of smoking (74.1% vs 2.2%, p<0.01), drinking (31.1% vs 1.7%, p<0.01), and concurrent smoking and drinking than females (25.3% vs 0.3%, p<0.01). However, females had a higher prevalence of SHS exposure than males (30.2% vs 20.6%, p<0.01). Ethnic minorities had a higher prevalence of SHS exposure, drinking, and concurrent smoking and drinking, than Han participants (p<0.01). Participants with a higher education level had a higher prevalence of smoking, drinking, and concurrent smoking and drinking than their counterparts (p<0.01). In contrast, participants with a lower education level had a higher prevalence of SHS exposure than their counterparts (p<0.01). Multivariate logistic regression analysis found that smokers (AOR=1.31; 95% CI: 1.13-1.51), individuals exposed to SHS (AOR=1.24; 95% CI: 1.11-1.43), drinkers (AOR=1.31; 95%: CI: 1.15-1.50), and concurrent smokers and drinkers (AOR=1.45; 95% CI: 1.25-1.67) all had a higher probability of having hypertension (p<0.01). Additionally, concurrent smoking and drinking had the strongest association with the prevalence of hypertension (AOR=1.45; 95% CI: 1.25-1.67; p<0.01). CONCLUSIONS: Socioeconomic factors play an important role in influencing the prevalence of smoking, exposure to SHS, and drinking in rural southwest China. Interventions to prevent and reduce hypertension should, in particular, focus on smokers, individuals exposed to SHS, drinkers, and, in particular, concurrent smokers and drinkers.