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1.
Sci Total Environ ; 932: 173038, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38719055

RESUMEN

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

2.
Scand J Immunol ; 99(6): e13366, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38720518

RESUMEN

Antiphospholipid syndrome is a rare autoimmune disease characterized by persistent antiphospholipid antibodies. Immunoglobulin G plays a vital role in disease progression, with its structure and function affected by glycosylation. We aimed to investigate the changes in the serum immunoglobulin G glycosylation pattern in antiphospholipid syndrome patients. We applied lectin microarray on samples from 178 antiphospholipid syndrome patients, 135 disease controls (including Takayasu arteritis, rheumatoid arthritis and cardiovascular disease) and 100 healthy controls. Lectin blots were performed for validation of significant differences. Here, we show an increased immunoglobulin G-binding level of soybean agglutinin (p = 0.047, preferring N-acetylgalactosamine) in antiphospholipid syndrome patients compared with healthy and disease controls. Additionally, the immunoglobulin G from antiphospholipid syndrome patients diagnosed with pregnancy events had lower levels of fucosylation (p = 0.001, recognized by Lotus tetragonolobus) and sialylation (p = 0.030, recognized by Sambucus nigra I) than those with simple thrombotic events. These results suggest the unique serum immunoglobulin G glycosylation profile of antiphospholipid syndrome patients, which may inform future studies to design biomarkers for more accurate diagnosis of antiphospholipid syndrome and even for the prediction of clinical symptoms in patients.


Asunto(s)
Síndrome Antifosfolípido , Inmunoglobulina G , Humanos , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Glicosilación , Femenino , Masculino , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Adulto , Persona de Mediana Edad , Embarazo , Lectinas/sangre , Lectinas/metabolismo , Lectinas/inmunología , Biomarcadores/sangre , Análisis por Matrices de Proteínas/métodos , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Lectinas de Plantas/metabolismo , Lectinas de Plantas/inmunología , Anciano , Glicoproteínas
3.
Arch Toxicol ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722348

RESUMEN

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4+T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38709407

RESUMEN

Peatlands records can be used to reconstruct and understand the history of environmental evolution, as well as a more accurate reflection of human activities. The black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) are ideal natural archives of anthropogenic activities. To identify the information of anthropogenic activities recorded by peatlands in the middle and high latitudes of the alpine mountains in the arid and semi-arid regions of China. this study analyzed the concentrations of BC, δ13C ratios of BC, PAHs, and molecular diagnostic ratios of PHAs (including Benzo(a) anthracene (BaA), Chrysene (Chr), fluoranthene (Flt), anthracene (Ant), phenanthrene (Phe), Benzo(a) pyrene (BaP), and pyrene (Pyr) in a 30-cm peat profile from the Altay Mountain, northwestern China. Our results revealed concentrations of BC from 11.71 to 67.5 mg·g-1, and PAHs from 168.09 to 263.53 ng·g-1. The δ13CBC value ranged from - 31.37 to - 26.27‰, with an average of - 29.54‰, indicating that the BC mainly comes from biomass combustion. The ratios of BaA/(BaA + Chr), Flt/(Flt + Pyr), and Ant/(Ant + Phe) exceeded 0.35, 0.5, and 0.1, respectively, revealing that the PAHs pollutants mainly originated from the combustion of biomass and fossil fuel burning. Furthermore, based on these findings and our knowledge of social development in Altay, industrial transport and tourism have influenced the emission, transport, and deposition of BC and PAH in peatlands in the Altay mountains since the 1980s. After 1980, pollutant concentrations decreased with the implementation of environmental policies. The results not only reveal the influence of anthropogenic activities on the sedimentary characteristics of peatlands in the Altay Mountains, but also provide an important theoretical basis for the conservation of fragile mountain peatlands.

5.
Cogn Neurodyn ; 18(2): 659-671, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38699610

RESUMEN

Automatic modulation classification (AMC) is a challenging topic in the development of cognitive radio, which can sense and learn surrounding electromagnetic environments and help to make corresponding decisions. In this paper, we propose to complete the real-time AMC through constructing a lightweight neural network MobileViT driven by the clustered constellation images. Firstly, the clustered constellation images are transformed from I/Q sequences to help extract robust and discriminative features. Then the lightweight neural network called MobileViT is developed for the real-time constellation image classification. Experimental results on the public dataset RadioML 2016.10a with edge computing platform demonstrate the superiority and efficiency of MobileViT. Furthermore, the extensive ablation tests prove the robustness of the proposed method to the learning rate and batch size. To the best of our knowledge, this is the first attempt to deploy the deep learning model to complete the real-time classification of modulation schemes of received signals at the edge.

6.
Biomed Pharmacother ; 175: 116687, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38701568

RESUMEN

World Drug Report 2023 concluded that 296 million people abused drugs, 39.5 million became addiction and 494,000 died as a direct or indirect result of addiction. Addiction has become a growing problem that affects individuals, their families, societies, countries and even the world. However, treatment for addiction is only limited to some developed countries because of the high cost, difficult implementation, and time consuming. Therefore, there is an urgent need to develop a low-cost, effective drug for the development of addiction treatment in more countries, which is essential for the stability and sustainable development of the world. In this review, it provided an overview of the abuse of common addictive drugs, related disorders, and current therapeutic regimen worldwide, and summarized the mechanisms of drug addiction as reward circuits, neuroadaptation and plasticity, cognitive decision-making, genetics, and environment. According to their chemical structure, 43 natural products and 5 herbal combinations with potential to treat addiction were classified, and their sources, pharmacological effects and clinical trials were introduced. It was also found that mitragine, ibogine, L-tetrahydropalmatine and crocin had greater potential for anti-addiction.

7.
Plant Phenomics ; 6: 0171, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694449

RESUMEN

Stay-green (SG) in wheat is a beneficial trait that increases yield and stress tolerance. However, conventional phenotyping techniques limited the understanding of its genetic basis. Spectral indices (SIs) as non-destructive tools to evaluate crop temporal senescence provide an alternative strategy. Here, we applied SIs to monitor the senescence dynamics of 565 diverse wheat accessions from anthesis to maturation stages over 2 field seasons. Four SIs (normalized difference vegetation index, green normalized difference vegetation index, normalized difference red edge index, and optimized soil-adjusted vegetation index) were normalized to develop relative stay-green scores (RSGS) as the SG indicators. An RSGS-based genome-wide association study identified 47 high-confidence quantitative trait loci (QTL) harboring 3,079 single-nucleotide polymorphisms associated with SG and 1,085 corresponding candidate genes. Among them, 15 QTL overlapped or were adjacent to known SG-related QTL/genes, while the remaining QTL were novel. Notably, a set of favorable haplotypes of SG-related candidate genes such as TraesCS2A03G1081100, TracesCS6B03G0356400, and TracesCS2B03G1299500 are increasing following the Green Revolution, further validating the feasibility of the pipeline. This study provided a valuable reference for further quantitative SG and genetic research in diverse wheat panels.

8.
Theranostics ; 14(6): 2544-2559, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646641

RESUMEN

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Diferenciación Celular , Condrocitos , Curación de Fractura , Osteogénesis , Células Madre , Canales Catiónicos TRPP , Animales , Curación de Fractura/fisiología , Ratones , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , Condrocitos/metabolismo , Células Madre/metabolismo , Osteogénesis/fisiología , Ratones Noqueados , Condrogénesis/fisiología , Periostio/metabolismo , Osteoblastos/metabolismo , Osteoblastos/fisiología , Modelos Animales de Enfermedad , Masculino
9.
Cell Death Dis ; 15(4): 271, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632264

RESUMEN

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.


Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus , Exosomas , Células Madre Mesenquimatosas , Humanos , Exosomas/metabolismo , Complicaciones de la Diabetes/metabolismo , Comunicación Celular , Células Madre Mesenquimatosas/metabolismo , Resultado del Tratamiento , Diabetes Mellitus/metabolismo
10.
Oncol Lett ; 27(6): 247, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38638842

RESUMEN

Colon cancer is a common gastrointestinal malignant tumor. In addition to conventional treatment, thoughtful and comprehensive aftercare should be given to patients. The present study aimed to explore the effects of explain-simulate-practice-communication-support (ESPCS) model nursing on the surgical tolerance, gastrointestinal recovery and self-management efficacy of patients with colon cancer. The clinical data of 136 patients with colon cancer diagnosed and treated at the Second Affiliated Hospital of Harbin Medical University (Harbin, China) from June 2020 to April 2022 were retrospectively analyzed and a total of 84 patients met the inclusion criteria. A total of 42 patients who underwent conventional nursing were included in the conventional nursing group and 42 patients who underwent ESPCS model nursing were included in the ESPCS model nursing group. Surgical tolerance, gastrointestinal recovery, self-management efficacy (Cancer Self-Management Efficacy Scale), quality of life (Comprehensive Quality of Life Inventory-74) and nursing satisfaction were analyzed. Slightly higher proportions of excellent and good surgical tolerance were found in the ESPCS model nursing group (97.62%) compared with those in the conventional nursing group (85.71%); however, no significant difference was shown (P>0.05). Compared with the conventional nursing group, the time needed for gastric tube removal, bowel sound recovery, anal exhaust, first defecation, general food intake and the time until getting out of bed was significantly shorter in the ESPS model nursing group (all P<0.05). Before the intervention, no statistically significant difference was found between the indicators in the Cancer Self-Management Efficacy Scale of the two groups (all P>0.05). After the intervention, the ESPCS model nursing group had significantly higher scores for positive attitude, stress relief and self-determination than the conventional nursing group (all P<0.05). Before intervention, there was no statistically significant difference in the indicators of CQOLI-74 between the two groups (P>0.05). After the intervention, the ESPCS model nursing group also had significantly higher scores for social function, psychological function, life state and somatic function compared with the conventional nursing group (all P<0.05). Higher satisfaction of patients was found in the ESPCS mode group (95.24%) compared with that in the conventional nursing group (78.57%) (P<0.05). Overall, ESPCS mode nursing could effectively elevate the surgical tolerance of patients with colon cancer, promote the recovery of gastrointestinal function, increase self-management efficacy, and improve the quality of life and nursing satisfaction, which is certainly worthy of clinical promotion.

11.
PLoS One ; 19(4): e0302292, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38626181

RESUMEN

Proteins containing domain of unknown function (DUF) are prevalent in eukaryotic genome. The DUF1216 proteins possess a conserved DUF1216 domain resembling to the mediator protein of Arabidopsis RNA polymerase II transcriptional subunit-like protein. The DUF1216 family are specifically existed in Brassicaceae, however, no comprehensive evolutionary analysis of DUF1216 genes have been performed. We performed a first comprehensive genome-wide analysis of DUF1216 proteins in Brassicaceae. Totally 284 DUF1216 genes were identified in 27 Brassicaceae species and classified into four subfamilies on the basis of phylogenetic analysis. The analysis of gene structure and conserved motifs revealed that DUF1216 genes within the same subfamily exhibited similar intron/exon patterns and motif composition. The majority members of DUF1216 genes contain a signal peptide in the N-terminal, and the ninth position of the signal peptide in most DUF1216 is cysteine. Synteny analysis revealed that segmental duplication is a major mechanism for expanding of DUF1216 genes in Brassica oleracea, Brassica juncea, Brassica napus, Lepidium meyneii, and Brassica carinata, while in Arabidopsis thaliana and Capsella rubella, tandem duplication plays a major role in the expansion of the DUF1216 gene family. The analysis of Ka/Ks (non-synonymous substitution rate/synonymous substitution rate) ratios for DUF1216 paralogous indicated that most of gene pairs underwent purifying selection. DUF1216 genes displayed a specifically high expression in reproductive tissues in most Brassicaceae species, while its expression in Brassica juncea was specifically high in root. Our studies offered new insights into the phylogenetic relationships, gene structures and expressional patterns of DUF1216 members in Brassicaceae, which provides a foundation for future functional analysis.


Asunto(s)
Arabidopsis , Brassicaceae , Brassicaceae/genética , Duplicación de Gen , Filogenia , Evolución Molecular , Genoma de Planta , Arabidopsis/genética , Proteínas de Plantas/genética , Proteínas de Plantas/química , Planta de la Mostaza/genética , Señales de Clasificación de Proteína/genética , Regulación de la Expresión Génica de las Plantas
12.
Artículo en Inglés | MEDLINE | ID: mdl-38571296

RESUMEN

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

13.
Adv Mater ; : e2313946, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582876

RESUMEN

Micro/nanostructured perovskites with spatially graded compositions and bandgaps are promising in filter-free, chip-level multispectral, and hyperspectral detection. However, achieving high-resolution patterning of perovskites with controlled graded compositions is challenging. Here, a programmable mixed electrohydrodynamic printing (M-ePrinting) technique is presented to realize the one-step direct-printing of arbitrary spatially graded perovskite micro/nanopatterns for the first time. M-ePrinting enables in situ mixing and ejection of solutions with controlled composition/bandgap by programmatically varying driving voltage applied to a multichannel nozzle. Composition can be graded over a single dot, line or complex pattern, and the printed feature size is down to 1 µm, which is the highest printing resolution of graded patterns to the knowledge. Photodetectors based on micro/nanostructured perovskites with halide ions gradually varying from Br to I are constructed, which successfully achieve multispectral detection and full-color imaging, with a high detectivity and responsivity of 3.27 × 1015 Jones and 69.88 A W-1, respectively. The presented method provides a versatile and competitive approach for such miniaturized bandgap-tunable perovskite spectrometer platforms and artificial vision systems, and also opens new avenues for the digital fabrication of composition-programmable structures.

14.
ACS Biomater Sci Eng ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597148

RESUMEN

Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.

15.
Bioact Mater ; 37: 222-238, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38549772

RESUMEN

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.

16.
Medicine (Baltimore) ; 103(11): e37504, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489696

RESUMEN

Immune-related cutaneous adverse events (ircAEs) will undermine the patients' quality of lives, and interrupt the antitumor therapy. A clinical proved recipe for external use of clearing heat and removing dampness (Qing-Re-Li-Shi Formula, hereinafter referred to as "QRLSF") is beneficial to the treatment of ircAEs in clinical practice. Our study will elucidate the mechanism of QRLSF against ircAEs based on network pharmacology and molecular docking. The active components and corresponding targets of QRLSF were collected through traditional Chinese medicine systems pharmacology database. GeneCards, online Mendelian inheritance in man, and pharmacogenomics knowledgebase were used to screen the targets of ircAEs. The intersecting targets between drug and disease were acquired by venn analysis. Cytoscape software was employed to construct "components-targets" network. Search tool for the retrieval of interacting genes/proteins database was applied to establish the protein-protein interaction network and then its core targets were identified. Gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed to predict the mechanism. The molecular docking verification of key targets and related phytomolecules was accomplished by AutoDock Vina software. Thirty-nine intersecting targets related to QRLSF against ircAEs were recognized. The analysis of network clarified 5 core targets (STAT3, RELA, TNF, TP53, and NFKBIA) and 4 key components (quercetin, apigenin, luteolin, and ursolic acid). The activity of QRLSF against ircAEs could be attributed to the regulation of multiple biological effects via multi-pathways (PI3K-Akt pathway, cytokine-cytokine receptor interaction, JAK-STAT pathway, chemokine pathway, Th17 cell differentiation, IL-17 pathway, TNF pathway, and Toll-like receptor pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of QRLSF against ircAEs, providing a new strategy for such medical problem.


Asunto(s)
Medicamentos Herbarios Chinos , Farmacología en Red , Humanos , Simulación del Acoplamiento Molecular , Calor , Quinasas Janus , Fosfatidilinositol 3-Quinasas , Factores de Transcripción STAT , Transducción de Señal , Bases de Datos Genéticas , Medicamentos Herbarios Chinos/efectos adversos , Medicina Tradicional China
17.
Sci Total Environ ; 926: 171995, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38547977

RESUMEN

Dichloroacetonitrile (DCAN) is an emerging disinfection by-product (DBP) that is widespread in drinking water. However, the pathway for DCAN formation from aromatic amino acids remains unclear, leading to a lack of an understanding of its explicit fate during chloramination. In this study, we investigated the specific formation mechanism of DCAN during the chloramination of phenylalanine based on reaction kinetics and chemical thermodynamics. The reason for differences between aldehyde and decarboxylation pathways was explained, and kinetic parameters of the pathways were obtained through quantum chemistry calculations. The results showed that the reaction rate constant of the rate-limiting step of the aldehyde pathway with 1.9 × 10-11 s-1 was significantly higher than that of decarboxylation (3.6 × 10-16 s-1 M-1), suggesting that the aldehyde pathway is the main reaction pathway for DCAN formation during the chloramination of phenylalanine to produce DCAN. Subsequently, theoretical calculations were performed to elucidate the effect of pH on the formation mechanism, which aligned well with the experimental results. Dehydrohalogenation was found to be the rate-limiting step under acidic conditions with reaction rate constants higher than those of the rate-limiting step (expulsion of amines) under neutral conditions, increasing the rate of DCAN formation. This study highlights the differences in DCAN formation between the decarboxylation and aldehyde pathways during the chloramination of precursors at both molecular and kinetic levels, contributing to a comprehensive understanding of the reaction mechanisms by which aromatic free amino acids generate DCAN.


Asunto(s)
Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Fenilalanina , Halogenación , Purificación del Agua/métodos , Desinfección , Acetonitrilos/química , Aldehídos , Contaminantes Químicos del Agua/análisis
18.
Virol Sin ; 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38499155

RESUMEN

The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications, enabling the development of effective therapeutic and preventive strategies. In this study, our initial attempts to introduce a NanoLuc luciferase (NLuc) reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies. We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus. Therefore, we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71 (EV-A71), coxsackievirus A10 (CVA10), coxsackievirus A7 (CVA7), coxsackievirus A16 (CVA16), namely EV-A71-HiBiT, CVA16-HiBiT, CVA10-HiBiT, CVA7-HiBiT, and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency. Notably, the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses. A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics. Moreover, these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages. In addition, the HiBiT-tagged viruses were successfully tested in antiviral drug assays, and the sensitivity of the viruses to drugs was not affected by the HiBiT tag. Ultimately, our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal, convenient, and invaluable method for advancing research in the realm of enterovirus virology. Furthermore, HiBiT-tagged enteroviruses exhibit great potential for diverse applications, including the development of antivirals and the elucidation of viral infection mechanisms.

19.
Molecules ; 29(6)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38543005

RESUMEN

The development of electrode materials with excellent performance serves as the key for researchers to enhance the energy density of supercapacitors. Cobalt molybdate (CoMoO4) nanomaterials have been regarded as one of the most prospective electrode materials for supercapacitors due to their high theoretical capacitance and excellent electrical conductivity. In this paper, three kinds of CoMoO4 nanorods were prepared directly via simple and environmentally friendly solid-phase chemical reactions with solid inorganic salts as raw materials. According to X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) test results, different reagents had certain effects on the size and morphology of CoMoO4, and these affected its electrochemical performance. In particular, the samples prepared with Co(NO3)2·6H2O as raw material took on a more uniform micromorphology, with a better crystallinity. Simultaneously, electrochemical test results showed that the samples synthesized with Co(NO3)2·6H2O presented relatively good electrical conductivity and a large specific capacitance (177 F g-1). This may be due to the nitrates reacting more slowly during the reaction and the crystals having difficulty aggregating during growth. Therefore, the structure of the prepared CoMoO4 nanomaterial was more uniform, and it was resistant to collapse during the charging and discharging process; thus, the capacitor presents the best performance.

20.
Arch Toxicol ; 98(5): 1297-1310, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38498160

RESUMEN

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.


Asunto(s)
Lesión Pulmonar , MicroARNs , Humanos , ARN Circular/genética , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/genética , Lesión Pulmonar/terapia , Pulmón/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores/metabolismo
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