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1.
J Trauma Nurs ; 29(5): 240-251, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36095271

RESUMO

BACKGROUND: Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio are reported to reflect the inflammation and immune status in critically ill patients, but their role in severe trauma patients with persistent critical illness remains to be elucidated. OBJECTIVE: We aimed to evaluate the relationship of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio with persistent critical illness in severe trauma patients. METHODS: In a single-center retrospective cohort study, persistent critical illness was defined as intensive care unit length of stay of more than 10 days. Monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were computed individually and categorized into 3 tertiles. Logistic regression analysis was used to assess the relationship of monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with persistent critical illness. Receiver operating characteristic curves and the Youden index were used to evaluate the discriminatory threshold of persistent critical illness. RESULTS: A total of 851 eligible patients were enrolled in the study: 328 patients with persistent critical illness and 523 without. The median levels of maximum neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio during intensive care unit stay were all higher in patients with persistent critical illness than in those without (11.46 vs. 9.13, p < .001 and 0.62 vs. 0.46, p < .001). Multivariate analysis revealed that the second (≥0.385, <0.693) and third (≥0.693) maximum monocyte-to-lymphocyte ratio tertiles were significantly associated with persistent critical illness after adjusting for confounding factors (odds ratio: 1.89, 95% confidence interval: 1.10-3.26, p = .021 and odds ratio 2.69, 95% confidence interval: 1.44-5.02, p = .002, respectively), whereas maximum neutrophil-to-lymphocyte ratio was not significantly correlated with persistent critical illness. The area under the curve for the maximum monocyte-to-lymphocyte ratio was 0.63 (95% confidence interval: 0.59-0.67), and the optimal cutoff was 0.65 for persistent critical illness. CONCLUSION: A high maximum monocyte-to-lymphocyte ratio during intensive care unit stay was independently related to persistent critical illness following severe trauma, although with limited sensitivity and specificity.


Assuntos
Estado Terminal , Neutrófilos , Humanos , Linfócitos , Monócitos , Estudos Retrospectivos
2.
Small ; : e2204360, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36135778

RESUMO

Dynamic sequential control of photoluminescence by supramolecular approaches has become a great issue in supramolecular chemistry. However, developing a systematic strategy to construct polychromatic photoluminescent supramolecular self-assemblies for improving the efficiency and sensitivity of artificial light-harvesting systems still remains a challenge. Here, a series of amphiphilicity-controlled supramolecular self-assemblies with polychromatic fluorescence based on lower-rim hexyl-modified sulfonatocalix[4]arene (SC4A6) and N-alkyl-modified p-phenylene divinylpyridiniums (PVPn, n = 2-7) as efficient light-harvesting platforms is reported. PVPn shows wide ranges of polychromatic fluorescence by co-assembling with SC4A6, whose emission trends significantly depend on the modified alkyl-chains of PVPn. The formed PVPn-SC4A6 co-assemblies as light-harvesting platforms are extremely sensitive for transferring the energy to two near-infrared emissive acceptors, Nile blue (NiB) and Rhodamine 800. After optimizing the amphiphilicity of PVPn-SC4A6 systems, the PVPn-SC4A6-NiB light-harvesting systems achieve an ultrasensitive working concentration for NiB (2 nm) and an ultrahigh antenna effect up to 91.0. Furthermore, the two different kinds of light-harvesting nanoparticles exhibit good performance on near-infrared imaging in the Golgi apparatus and mitochondria, respectively.

3.
Front Immunol ; 13: 954440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059510

RESUMO

The development of immunotherapy has changed the treatment landscape of advanced kidney renal clear cell carcinoma (KIRC), offering patients more treatment options. Cuproptosis, a novel cell death mode dependent on copper ions and mitochondrial respiration has not yet been studied in KIRC. We assembled a comprehensive cohort of The Cancer Genome Atlas (TCGA)-KIRC and GSE29609, performed cluster analysis for typing twice using seven cuproptosis-promoting genes (CPGs) as a starting point, and assessed the differences in biological and clinicopathological characteristics between different subtypes. Furthermore, we explored the tumor immune infiltration landscape in KIRC using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) and the potential molecular mechanisms of cuproptosis in KIRC using enrichment analysis. We constructed a cuproptosis score (CUS) using the Boruta algorithm combined with principal component analysis. We evaluated the impact of CUS on prognosis, targeted therapy, and immunotherapy in patients with KIRC using survival analysis, the predictions from the Cancer Immunome Atlas database, and targeted drug susceptibility analysis. We found that patients with high CUS levels show poor prognosis and efficacy against all four immune checkpoint inhibitors, and their immunosuppression may depend on TGFB1. However, the high-CUS group showed higher sensitivity to sunitinib, axitinib, and elesclomol. Sunitinib monotherapy may reverse the poor prognosis and result in higher progression free survival. Then, we identified two potential CPGs and verified their differential expression between the KIRC and the normal samples. Finally, we explored the effect of the key gene FDX1 on the proliferation of KIRC cells and confirmed the presence of cuproptosis in KIRC cells. We developed a targeted therapy and immunotherapy strategy for advanced KIRC based on CUS. Our findings provide new insights into the relationship among cuproptosis, metabolism, and immunity in KIRC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Humanos , Imunoterapia , Rim/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Sunitinibe
4.
J Org Chem ; 87(16): 10928-10936, 2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35921205

RESUMO

The Cu(OTf)2/NBS-mediated tandem reaction of 1-cinnamyl alcohol-o-carboranes for the synthesis of C-alkenyl-o-carboranes has been developed. Mechanism studies demonstrated that the Cu(OTf)2-promoted ring opening of oxetane with electron-rich arenes as soft nucleophiles was involved and was the key step for the transformation. This work provided an alternative strategy for the synthesis of C-alkenyl-o-carboranes, which has an important reference for the synthesis of o-carborane derivatives with diversity.


Assuntos
Boranos , Éteres Cíclicos , Propanóis
5.
An. bras. dermatol ; 97(4): 458-466, July-Aug. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1383604

RESUMO

Abstract Background: UVB irradiation can cause acute damage such as sunburn, or photoaging and melanoma, all of which are major health threats. Objective: This study was designed to investigate the mechanism of skin photoaging induced by UVB radiation in mice through the analysis of the differential expression of miRNAs. Methods: A UVB irradiation photoaging model was constructed. HE and Masson special stains were used to examine the modifications in the epidermis and dermis of mice. The miRNA expression profiles of the mouse skin model exposed to UVB radiation and the normal skin of mice were analyzed using miRNA-sequence analysis. GO and Pathway analysis were employed for the prediction of miRNA targets. Results: A total of 23 miRNAs were evaluated for significantly different expressions in comparison to normal skin. Among them, 7 miRNAs were up-regulated and 16 were down-regulated in the skin with photoaging of mice exposed to UVB irradiation. The differential expression of miRNA is related to a variety of signal transduction pathways, among which mmu-miR-195a-5p and mitogen-activated protein kinase (MAPK) signal pathways are crucial. There was a significant differential expression of miRNA in the skin of normal mice in comparison with the skin with photoaging induced by UVB irradiation. Study limitations: Due to time and energy constraints, the specific protein level verification, MAPK pathway exploration, and miR-195a-5p downstream molecular mechanism need to be further studied in the future. Conclusions: UVB-induced skin photoaging can be diagnosed and treated using miRNA.

6.
Materials (Basel) ; 15(15)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35955310

RESUMO

Sodium carbonate (Na2CO3), an environmentally friendly activator, has been shown to have vast potential for the development of sustainable alkali-activated slag mortars. However, Na2CO3-activated slag mortars exhibit a delayed reaction process and limited early-age strength development, restricting their wider application. In this work, the recycled concrete fines were calcined at a temperature of 800 °C for 1 h and then used as an auxiliary activator to improve the reaction kinetics of Na2CO3-activated slag mortars. The impact of the calcined recycled concrete fines (CRCF) dosage and Na2CO3 concentration on the compressive strength, hydration kinetics, and phase assemblage of mortars was evaluated. The results show that CRCF can react directly with Na2CO3 in the early stages, swiftly removing the CO32- in aqueous solution and providing an alkaline environment suitable for the dissolution of slag. This promotes the development of C-(A)-S-H, hydrotalcite, hemicarbonate, and monocarbonate. The hydration process and strength-giving phase of mortars can be improved further, as an increase in Na2CO3 concentration increases the initial alkaline content. Additionally, the most remarkable compressive strength value of 39.2 MPa was observed at 28 days in the mortar with 6% sodium oxide equivalent (Na2O-E) of Na2CO3 and 15% CRCF because of the synergistic effect of CRCF and Na2CO3.

7.
Front Genet ; 13: 900911, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035145

RESUMO

Glioblastoma (GBM) is the most common brain tumor, with rapid proliferation and fatal invasiveness. Large-scale genetic and epigenetic profiling studies have identified targets among molecular subgroups, yet agents developed against these targets have failed in late clinical development. We obtained the genomic and clinical data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and performed the least absolute shrinkage and selection operator (LASSO) Cox analysis to establish a risk model incorporating 17 genes in the CGGA693 RNA-seq cohort. This risk model was successfully validated using the CGGA325 validation set. Based on Cox regression analysis, this risk model may be an independent indicator of clinical efficacy. We also developed a survival nomogram prediction model that combines the clinical features of OS. To determine the novel classification based on the risk model, we classified the patients into two clusters using ConsensusClusterPlus, and evaluated the tumor immune environment with ESTIMATE and CIBERSORT. We also constructed clinical traits-related and co-expression modules through WGCNA analysis. We identified eight genes (ANKRD20A4, CLOCK, CNTRL, ICA1, LARP4B, RASA2, RPS6, and SET) in the blue module and three genes (MSH2, ZBTB34, and DDX31) in the turquoise module. Based on the public website TCGA, two biomarkers were significantly associated with poorer OS. Finally, through GSCALite, we re-evaluated the prognostic value of the essential biomarkers and verified MSH2 as a hub biomarker.

8.
J Inflamm Res ; 15: 4573-4583, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35982758

RESUMO

Background: Acne is a common inflammatory skin disease, while cannabidiol (CBD) is a representative non-psychoactive phytocannabinoid which has been proved to exert universal anti-inflammatory properties. This study aimed to explore the effect of CBD on acne inflammation induced by Cutibacterium acnes-derived extracellular vesicles (CEVs) in keratinocytes and reveal the underlying mechanisms. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated by CEVs in the presence of CBD or vehicle. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels were examined by RT-PCR and ELISA. The expression of cannabinoid type-2 (CB2) receptor and transient receptor potential vanilloid type-1 (TRPV1) was detected by Western blotting. TNF-α levels in the presence of CB2 receptor antagonist (AM630) or TRPV1 antagonist (Capsazepine) were detected by RT-PCR. The activation of MAPK and NF-κB signaling pathways and the nuclear translocation of NF-κB p65 upon CBD treatment were analyzed by Western blotting and immunofluorescence assay, respectively. Results: The expression of inflammatory cytokines (IL-6, IL-8 and TNF-α) in CEVs-stimulated NHEKs was suppressed by CBD. CB2 receptor expression was upregulated by CBD, whereas CEVs-promoted TRPV1 expression was downregulated by CBD. AM630 reversed TNF-α levels inhibited by CBD. Capsazepine exerted an inhibitory effect on CEVs-induced inflammation and had synergistic effect with CBD. The phosphorylation of ERK1/2 and NF-κB p65 and nuclear translocation of NF-κB p65 were induced by CEVs but reduced by CBD. Conclusion: The results indicated that CBD could inhibit inflammation induced by CEVs in NHEKs, which was mediated by activation of CB2 receptor and enhanced by the TRPV1 antagonist, through inactivation of the MAPK and NF-κB signaling pathways. CBD might be a potential novel strategy for acne treatment in the future.

9.
ACS Appl Mater Interfaces ; 14(32): 36980-36986, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35916606

RESUMO

Confined ionic liquids in hydrophilic porous media have disrupted lattices and can be divided into two layers: An immobile ion layer adheres to the pore surfaces, and an inner layer exhibits faster mobility than the bulk. In this work, we report the first study of ionic liquids confined in block copolymer-based porous carbon fibers (PCFs) synthesized from polyacrylonitrile-block-polymethyl methacrylate (PAN-b-PMMA). The PCFs contain a network of unimodal mesopores of 13.6 nm in diameter and contain more hydrophilic surface functional groups than previously studied porous carbon. Elastic neutron scattering shows no freezing point for 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) confined in PCFs down to 20 K. Quasi-elastic neutron scattering (QENS) is used to measure the diffusion of [BMIM]BF4 confined in PCFs, which, surprisingly, is 7-fold faster than in the bulk. The unprecedentedly high ion diffusion remarks that PCFs hold exceptional potential for use in electrochemical catalysis, energy conversion, and storage.

11.
Front Oncol ; 12: 876360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35785179

RESUMO

Increasing evidence has implicated the modification of 7-methylguanosine (m7G), a type of RNA modification, in tumor progression. However, no comprehensive analysis to date has summarized the predicted role of m7G-related gene signatures in lung adenocarcinoma (LUAD). Herein, we aimed to develop a novel prognostic model in LUAD based on m7G-related gene signatures. The LUAD transcriptome profiling data and corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus datasets. After screening, we first obtained 29 m7G-related genes, most of which were upregulated in tumor tissues and negatively associated with overall survival (OS). According to the expression similarity of m7G-related genes, the combined samples from the TCGA-LUAD and GSE68465 datasets were further classified as two clusters that exhibit distinct OS rates and genetic heterogeneity. Then, we constructed a novel prognostic model involving four genes by using 130 differentially expressed genes among the two clusters. The combined samples were randomly divided into a training cohort and an internal validation cohort in a 1:1 ratio, and the GSE72094 dataset was used as an external validation cohort. The samples were divided into high- and low-risk groups. We demonstrated that a higher risk score was an independent negative prognostic factor and predicted poor OS. A nomogram was further constructed to better predict the survival of LUAD patients. Functional enrichment analyses indicated that cell cycle and DNA replication-related biological processes and pathways were enriched in the high-risk group. More importantly, the low-risk group had greater infiltration and enrichment of most immune cells, as well as higher ESTIMATE, immune, and stromal scores. In addition, the high-risk group had a lower TIDE score and higher expressions of most immune checkpoint-related genes. We finally noticed that patients in the high-risk group were more sensitive to chemotherapeutic agents commonly used in LUAD. In conclusion, we herein summarized for the first time the alterations and prognostic role of m7G-related genes in LUAD and then constructed a prognostic model based on m7G-related gene signatures that could accurately and stably predict survival and guide individualized treatment decision-making in LUAD patients.

12.
Food Funct ; 13(16): 8676-8684, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35904366

RESUMO

Strenuous exercise is reported to provoke deleterious consequences including cardiac impairments, while the detailed mechanisms and effective interventions remain limited. The current study aims to explore the profitable effects of hydroxytyrosol (HT), one of the most abundant polyphenols derived from olive oil, on strenuous exercise-induced pathological changes in the heart and its underlying mechanisms. Sprague-Dawley male rats at the age of 8-week-old were supplemented with 25 mg kg-1 day-1 of HT 45 min before the beginning of strenuous exercise for a total of 8 weeks. HT treatment obviously improved the heart weight and morphology with lowered serum cardiac hypertrophy markers as well as cardiac oxidative stress. Moreover, the down-regulated mitochondrial biogenesis pathway, impaired mitochondrial complex activity, dysregulated expression of mitochondrial dynamics-related proteins and activated apoptotic pathway induced by Exe were all improved by HT. In vitro, 10 µM HT effectively reduced the reactive oxygen species level, promoted mitochondrial biogenesis, and inhibited apoptosis and cardiomyocyte hypertrophy in an angiotensin II-induced cardiomyocyte hypertrophy model. In addition, knockdown of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha, the key regulator of mitochondrial biogenesis, partially abolished the benefits of HT. Our results demonstrate that the disturbance of mitochondrial homeostasis plays a substantial role in strenuous exercise-induced pathological cardiac hypertrophy, and HT presents as an effective intervention strategy targeting mitochondrial homeostasis for cardiac health.


Assuntos
Mitocôndrias , Proteínas Mitocondriais , Animais , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Homeostase , Masculino , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Álcool Feniletílico/análogos & derivados , Ratos , Ratos Sprague-Dawley
13.
Sci Total Environ ; 848: 157712, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-35908691

RESUMO

Disinfection is essential for the microbial safety of reclaimed water. Traditional chlorine disinfection leads to secondary problems such as disinfection by-products and chlorine-resistant bacteria. Ferrate (Fe(VI)) is a novel green disinfectant. However, research on the disinfection characteristics of Fe(VI) remains insufficient. This study compared the disinfection efficacy between Fe(VI) and chlorine in secondary effluent, including the inactivation efficiency of coliforms and heterotrophic bacteria and the control effect on typical chlorine-resistant bacteria. The results showed that Fe(VI) was more effective than chlorine in inactivating Escherichia coli and total coliforms at low doses, whereas chlorine was more effective than Fe(VI) in inactivating heterotrophic bacteria. A severe trailing phenomenon was observed in Fe(VI) disinfection. Based on bacterial community structure analysis, Fe(VI) was also found to be capable of controlling the relative abundance of some chlorine-resistant bacteria such as Sphingomonas, Bacillus, Mycobacterium and Legionella except for Pseudomonas. The results of this study could have implications in evaluating Fe(VI) disinfection ability and optimizing Fe(VI) dosing for disinfection.


Assuntos
Desinfetantes , Purificação da Água , Bactérias , Cloro/farmacologia , Desinfetantes/química , Desinfecção/métodos , Ferro , Água , Purificação da Água/métodos
14.
Int J Mol Sci ; 23(14)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35886990

RESUMO

Pseudomonas syringae pv. actinidiae (Psa), a bacterial pathogen, is a severe threat to kiwifruit production. To elucidate the species-specific interaction between Psa and kiwifruit, transcriptomic-profiles analyses were conducted, under Psa-infected treatment and mock-inoculated control, on shoots of resistant Maohua (MH) and susceptible Hongyang (HY) kiwifruit varieties. The plant hormone-signal transduction and plant-pathogen interaction were significantly enriched in HY compared with MH. However, the starch and sucrose metabolism, antigen processing and presentation, phagosome, and galactose metabolism were significantly enriched in MH compared with HY. Interestingly, the MAP2 in the pathogen/microbe-associated molecular patterns (PAMPs)-triggered immunity (PTI) was significantly up-regulated in MH. The genes RAR1, SUGT1, and HSP90A in the effector-triggered immunity (ETI), and the NPR1 and TGA genes involved in the salicylic acid signaling pathway as regulatory roles of ETI, were significantly up-regulated in HY. Other important genes, such as the CCRs involved in phenylpropanoid biosynthesis, were highly expressed in MH, but some genes in the Ca2+ internal flow or involved in the reactive oxygen metabolism were obviously expressed in HY. These results suggested that the PTI and cell walls involved in defense mechanisms were significant in MH against Psa infection, while the ETI was notable in HY against Psa infection. This study will help to understand kiwifruit bacterial canker disease and provide important theoretical support in kiwifruit breeding.


Assuntos
Actinidia , Pseudomonas syringae , Actinidia/metabolismo , Genótipo , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Pseudomonas syringae/fisiologia
15.
Front Physiol ; 13: 921866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800343

RESUMO

Fatty acid (FA) metabolism has been involved in acne vulgaris, a common inflammatory skin disease frequently observed in adolescents and adults, but it remains poorly defined whether the distributions or location of FA in facial sebum and those in the circulation differentially correlate with the disease. In a cohort of 47 moderate acne patients and 40 controls, sebum samples from forehead and chin areas were collected using Sebutape adhesive patches, and erythrocytes were separated from the fasting blood. Total FAs were analyzed by the gas chromatograph-mass spectrometry method. Compared to control female subjects, female patients showed increased levels of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) from both facial areas, whereas decreased levels of polyunsaturated fatty acids (PUFAs) from chin areas were observed. Interestingly, the levels of docosahexaenoic acid (DHA) in the circulating erythrocytes were significantly decreased in male patients compared with control. In addition, DHA levels in erythrocytes were positively correlated with PUFAs from sebum only in male subjects. Furthermore, female patients with moderate acne had more severe sebum abnormity and chin-specific FA profiles, consistent with higher acne incidences than males in adulthood, especially in the chin areas. Importantly, serum insulin-like growth factor 1 (IGF-1) levels were positively correlated with SFAs and MUFAs from sebum only in male subjects. In summary, differential spatial FA distributions in facial sebum and correlation with those in erythrocytes and IGF1 levels in serum may shed some light on the pathology of acne in male and female adults.

16.
Genome Biol ; 23(1): 146, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35788225

RESUMO

BACKGROUND: Plant metabolites reshaped by nature and human beings are crucial for both their lives and human health. However, which metabolites respond most strongly to selection pressure at different evolutionary stages and what roles they undertake on perennial fruit crops such as peach remain unclear. RESULTS: Here, we report 18,052 significant locus-trait associations, 12,691 expression-metabolite correlations, and 294,676 expression quantitative trait loci (eQTLs) for peach. Our results indicate that amino acids accumulated in landraces may be involved in the environmental adaptation of peaches by responding to low temperature and drought. Moreover, the contents of flavonoids, the major nutrients in fruits, have kept decreasing accompanied by the reduced bitter flavor during both domestication and improvement stages. However, citric acid, under the selection of breeders' and consumers' preference for flavor, shows significantly different levels between eastern and western varieties. This correlates with differences in activity against cancer cells in vitro in fruit from these two regions. Based on the identified key genes regulating flavonoid and acid contents, we propose that more precise and targeted breeding technologies should be designed to improve peach varieties with rich functional contents because of the linkage of genes related to bitterness and acid taste, antioxidant and potential anti-cancer activity that are all located at the top of chromosome 5. CONCLUSIONS: This study provides powerful data for future improvement of peach flavor, nutrition, and resistance in future and expands our understanding of the effects of natural and artificial selection on metabolites.


Assuntos
Prunus persica , Domesticação , Frutas/genética , Humanos , Metaboloma , Melhoramento Vegetal , Prunus persica/genética
17.
Nat Commun ; 13(1): 3947, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35803927

RESUMO

Succinate dehydrogenase, which is known as mitochondrial complex II, has proven to be a fascinating machinery, attracting renewed and increased interest in its involvement in human diseases. Herein, we find that succinate dehydrogenase assembly factor 4 (SDHAF4) is downregulated in cardiac muscle in response to pathological stresses and in diseased hearts from human patients. Cardiac loss of Sdhaf4 suppresses complex II assembly and results in subunit degradation and complex II deficiency in fetal mice. These defects are exacerbated in young adults with globally impaired metabolic capacity and activation of dynamin-related protein 1, which induces excess mitochondrial fission and mitophagy, thereby causing progressive dilated cardiomyopathy and lethal heart failure in animals. Targeting mitochondria via supplementation with fumarate or inhibiting mitochondrial fission improves mitochondrial dynamics, partially restores cardiac function and prolongs the lifespan of mutant mice. Moreover, the addition of fumarate is found to dramatically improve cardiac function in myocardial infarction mice. These findings reveal a vital role for complex II assembly in the development of dilated cardiomyopathy and provide additional insights into therapeutic interventions for heart diseases.


Assuntos
Cardiomiopatia Dilatada , Animais , Cardiomiopatia Dilatada/metabolismo , Fumaratos/metabolismo , Camundongos , Dinâmica Mitocondrial/fisiologia , Mitofagia , Miócitos Cardíacos/metabolismo , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo
18.
Chin J Integr Med ; 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35723812

RESUMO

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

19.
Comput Intell Neurosci ; 2022: 8315442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35655499

RESUMO

In the research of network abnormal traffic detection, in view of the characteristics of high dimensionality and redundancy in traffic data and the loss of original information caused by the pooling operation in the convolutional neural network, which leads to the problem of unsatisfactory detection effect, this paper proposes a network abnormal traffic detection algorithm based on RIC-SC-DeCN to improve the above problems. Firstly, a recursive information correlation (RIC) feature selection mechanism is proposed, which reduces data redundancy through the maximum information correlation feature selection algorithm and recursive feature elimination method. Secondly, a skip-connected deconvolutional neural network model (SC-DeCN) is proposed to reduce the information loss by reconstructing the input signal. Finally, the RIC mechanism and the SC-DeCN model are merged to form a network abnormal traffic detection algorithm based on RIC-SC-DeCN. The experimental results on the CIC-IDS-2017 dataset show that the RIC feature selection mechanism proposed in this paper has the highest accuracy when using MSCNN as the detection model compared to the other three, which can reach 96.22%. Compared with the other five models, the SC-DeCN model has the highest detection accuracy, while the model training time is moderate and can reach 96.55%. Compared with the SC-DeCN model, the RIC-SC-DeCN model reduces the overall training time by 45.50%, while the accuracy rate is increased to 97.68%. It shows that the algorithm proposed in this paper has a good detection effect in the detection of network abnormal traffic.


Assuntos
Algoritmos , Redes Neurais de Computação
20.
Viral Immunol ; 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35675657

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a novel infectious disease caused by bunya virus. The purpose of this study was to investigate the clinical characteristics of SFTS patients and their virus-related immune disorders in vivo. Patients with SFTS admitted to Nanjing Drum Tower Hospital from 2017 to 2020 were retrospectively analyzed, and divided into survival group and death group according to the 28-day survival. Clinical characteristics and laboratory examination results of SFTS patients were recorded, and dynamic changes of immune function and inflammatory factors were statistically analyzed. Prolonged activated prothrombin time (APTT) (p = 0.001), high viral load (p = 0.001), and elevated human leukocyte antigen DR (HLA-DR) level (p = 0.002) were independent prognostic risk factors for SFTS patients. Compared to the survival group, the nonsurvival group was more prone to hemorrhagic and neurological symptoms (p < 0.05). Natural kill (NK) cell count, interleukin-10, interferon-α, and tumor necrosis factor-α scores in the nonsurvival group continued to increase after admission, while CD3+ T, CD4+ T, and CD8+ T cell counts continued to decrease. CD3+ T lymphocyte count was negatively correlated with viral load (R = 0.3883, p < 0.001), CD4+ T lymphocyte count was negatively correlated with viral load (R = 0.28933, p < 0.001), CD8+ T lymphocyte count was negatively correlated with viral load (R = 0.781, p < 0.001), and HLA-DR was positively correlated with viral load (R = 0.489, p < 0.001). High viral load, prolonged APTT time, and elevated HLA-DR level are independent prognostic risk factors for SFTS patients. The T lymphocyte subsets of SFTS patients continue to decrease after infection, and the number of T lymphocyte subsets can reflect the severity of the disease.

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