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1.
Plant Cell ; 34(10): 3899-3914, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35775944

RESUMO

In eukaryotes, the STRUCTURAL MAINTENANCE OF CHROMOSOME 5/6 (SMC5/6) complex is critical to maintaining chromosomal structures around double-strand breaks (DSBs) in DNA damage repair. However, the recruitment mechanism of this conserved complex at DSBs remains unclear. In this study, using Arabidopsis thaliana as a model, we found that SMC5/6 localization at DSBs is dependent on the protein scaffold containing INVOLVED IN DE NOVO 2 (IDN2), CELL DIVISION CYCLE 5 (CDC5), and ALTERATION/DEFICIENCY IN ACTIVATION 2B (ADA2b), whose recruitment is further mediated by DNA-damage-induced RNAs (diRNAs) generated from DNA regions around DSBs. The physical interactions of protein components including SMC5-ADA2b, ADA2b-CDC5, and CDC5-IDN2 result in formation of the protein scaffold. Further analysis indicated that the DSB localization of IDN2 requires its RNA-binding activity and ARGONAUTE 2 (AGO2), indicating a role for the AGO2-diRNA complex in this process. Given that most of the components in the scaffold are conserved, the mechanism presented here, which connects SMC5/6 recruitment and small RNAs, will improve our understanding of DNA repair mechanisms in eukaryotes.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quebras de DNA de Cadeia Dupla , Dano ao DNA/genética , Reparo do DNA/genética , DNA de Plantas/metabolismo , RNA/genética , Fatores de Transcrição/metabolismo
2.
Ann Surg Oncol ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222298

RESUMO

BACKGROUND: Gastrectomy is one of the main treatment modalities for gastric cancer (GC) and induces pathophysiological changes that significantly affect patients' postoperative recovery. In this study, we investigated the relationships between altered insulin resistance (IR), inflammation, and gut microbiota associated with gastrectomy. PATIENTS AND METHODS: This study was a single-center prospective cohort investigation involving 60 patients with GC who underwent gastrectomy between May 2023 and April 2024. Monitoring encompassed IR, inflammation, and nutrition-related markers via blood assays, while gut microbiota analysis employed high-throughput sequencing, and short-chain fatty acids (SCFAs) were examined through targeted metabolomics. The study is registered under the number ChiCTR2300075653. RESULTS: The patients exhibited a significant increase in post-gastrectomy IR markers (P < 0.001), accompanied by elevated inflammation markers (P < 0.001), and also showed decreased nutrition-related indicators (P < 0.001). Notable alterations were observed in the gut microbiota, including reductions in Bifidobacterium and Faecalibacterium, an increase in Streptococcus, and a noteworthy decrease in fecal butyrate. Patients with postoperative IR exhibited poorer inflammation markers (P < 0.05), nutritional indicators (P < 0.05), and postoperative recovery parameters (P < 0.05). Furthermore, significant negative correlations were observed between IR and Bifidobacterium, Faecalibacterium, as well as butyrate. CONCLUSIONS: Patients with GC post-gastrectomy displayed heightened IR, exacerbated inflammation, and compromised nutritional status. Disturbed gut microbiota and reduced fecal butyrate were observed. Gut microbiota and metabolite butyrate production may be predictors of postoperative IR and short-term outcomes in patients with GC.

3.
Ann Surg Oncol ; 31(8): 5240-5251, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38739239

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) for radical distal gastrectomy needs to be improved urgently. We investigated the effects of probiotic compounds (including Lactobacillus plantarum, L. rhamnosus, L. acidophilus, and Bifidobacterium animalis subsp.lactis) on enhance recovery after gastrectomy. METHODS: The patients in this prospective study were divided into probiotic group (PG group, n = 36) and placebo group (CG group, n = 38), taking corresponding capsule according to the protocol during the perioperative period. We compared the trends in perioperative hematologic findings and the postoperative outcomes. Patients' feces were collected for bacterial 16S rRNA sequencing. Patients were followed up at 1 month postoperatively. RESULTS: After the application of probiotics, the patients' postoperative inflammatory response level was reduced, and the trend of postoperative NLR decrease was significantly faster in the patients of the PG group than in the CG group (P = 0.047, partial η2 = 0.054). The trend of postoperative increase in serum albumin concentration in the patients of the PG group was significantly better than that in the CG group (P = 0.016, partial η2 = 0.078). In addition, patients in the PG group met discharge criteria earlier postoperatively and had fewer medical expenses. The quality of life of PG group was improved postoperatively. Postoperative inflammation-related markers, including the ratio of Firmicutes/Bacteroidetes, were increasing in untreated patients. In addition, the postoperative microbial diversity and abundance in the PG group remained stable. CONCLUSIONS: Probiotic compounds can reduce the inflammatory response after gastrectomy and enhance the recovery of the DGC patients by maintaining the stability of the gut microbiota.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Gastrectomia , Probióticos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Probióticos/uso terapêutico , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Seguimentos , Qualidade de Vida , Complicações Pós-Operatórias , Microbioma Gastrointestinal/efeitos dos fármacos , Prognóstico
4.
Inflamm Res ; 73(1): 47-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38147126

RESUMO

OBJECTIVE: NLRP3 inflammasome-mediated pyroptosis of macrophage acts essential roles in the progression of sepsis-induced acute lung injury (ALI). Tangeretin (TAN), enriched in citrus fruit peel, presents anti-oxidative and anti-inflammatory effects. Here, we aimed to explore the potentially protective effect of TAN on sepsis-induced ALI, and the underlying mechanism of TAN in regulating NLRP3 inflammasome. MATERIAL AND METHODS: The effect of TAN on sepsis-induced ALI and NLRP3 inflammasome-mediated pyroptosis of macrophage were examined in vivo and in vitro using a LPS-treated mice model and LPS-induced murine macrophages, respectively. The mechanism of TAN regulating the activation of NLRP3 inflammasome in sepsis-induced ALI was investigated with HE staining, Masson staining, immunofluorescent staining, ELISA, molecular docking, transmission electron microscope detection, qRT-PCR, and western blot. RESULTS: TAN could evidently attenuate sepsis-induced ALI in mice, evidenced by reducing pulmonary edema, pulmonary congestion and lung interstitial fibrosis, and inhibiting macrophage infiltration in the lung tissue. Besides, TAN significantly suppressed inflammatory cytokine IL-1ß and IL-18 expression in the serum or bronchoalveolar lavage fluid (BALF) samples of mice with LPS-induced ALI, and inhibited NLRP3 inflammasome-mediated pyroptosis of macrophages. Furthermore, we found TAN inhibited ROS production, preserved mitochondrial morphology, and alleviated excessive mitochondrial fission in LPS-induced ALI in mice. Through bioinformatic analysis and molecular docking, Polo-like kinase 1 (PLK1) was identified as a potential target of TAN for treating sepsis-induced ALI. Moreover, TAN significantly inhibited the reduction of PLK1 expression, AMP-activated protein kinase (AMPK) phosphorylation, and Dynamin related protein 1 (Drp1) phosphorylation (S637) in LPS-induced ALI in mice. In addition, Volasertib, a specific inhibitor of PLK1, abolished the protective effects of TAN against NLRP3 inflammasome-mediated pyroptosis of macrophage and lung injury in the cell and mice septic models. CONCLUSION: TAN attenuates sepsis-induced ALI by inhibiting ROS-mediated NLRP3 inflammasome activation via regulating PLK1/AMPK/DRP1 signaling axis, and TAN is a potentially therapeutic candidate against ALI through inhibiting pyroptosis.


Assuntos
Lesão Pulmonar Aguda , Sepse , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Lesão Pulmonar Aguda/induzido quimicamente , Sepse/complicações , Sepse/tratamento farmacológico , Camundongos Endogâmicos C57BL
5.
Scand J Gastroenterol ; 59(1): 52-61, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37632275

RESUMO

PURPOSE: The aim of this study was to develop and externally validate a nomogram to accurately predict the overall survival (OS) of patients with gastric adenocarcinoma who underwent radical gastrectomy. MATERIALS AND METHODS: A total of 3492 patients with gastric adenocarcinoma who underwent radical gastrectomy from 2012 to 2017 were included as the training cohort. Survival analysis was performed via Kaplan Meier method and log-rank test. Independent postoperative prognostic factors in patients with gastric adenocarcinoma were analyzed using univariate and multifactorial COX analysis methods. The prognosis nomogram was established in the training cohort and verified externally in the Surveillance, Epidemiology and End Results (SEER) database. RESULTS: According to the univariate and multifactorial COX analyses, metastatic lymph node ratio (MLNR) and five other independent prognostic factors (age at surgery, type of gastrectomy, tumor size, T stage, and pathological grade) were included in the prognostic nomogram. The nomogram had better prognostic predictive ability than the American Joint Committee on Cancer (AJCC) TNM staging in both the training (C-index: 0.736 VS. 0.668) and external validation cohort (C-index: 0.712 VS. 0.627). The calibration plots showed that the predicted survival rate was in good agreement with the actual survival rate. And the decision curve analysis (DCA) curves revealed that nomogram showed stronger ability in predicting 1-year, 3-year, and 5-year OS. CONCLUSION: This study estimated the excellent prognostic predictive power and clinical application potential of the MLNR-based nomogram, which may be used to facilitate postoperative clinical treatment decisions and potentially improve patient survival outcomes.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Nomogramas , Adenocarcinoma/cirurgia , Bases de Dados Factuais , Gastrectomia , Período Pós-Operatório , Neoplasias Gástricas/cirurgia , Prognóstico
6.
Environ Res ; 259: 119536, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38964577

RESUMO

The acidification of the marginal seawater was a more intricate process than the ocean. Although some studies have been done on seasonal acidification in the bottom water of Chinese marginal seas, research on surface water acidification has still been insufficient. We analyzed the acidification properties and controlling factors in the Bohai Sea (BS) and Yellow Sea (YS) surface water during April 2023. The observation showed that the average surface water pH of the BS, North Yellow Sea (NYS), and South Yellow Sea (SYS) were 8.09 ± 0.06, 8.13 ± 0.05, and 8.15 ± 0.05. Phytoplankton significantly impacted pH and Ωarag, while riverine inputs and biological activity played a vital role in controlling DIC and TA. The Yellow River significantly impacted the BS. The North Yellow Sea Cold Water Mass had a limited impact on acidification, while the South Yellow Sea Cold Water Mass significantly affected the SYS. Regarding seasonal fluctuations, Ωarag was significantly higher in summer than in other seasons. DIC and TA showed different patterns in both the BS and YS, with a minimal fluctuation in pH. Over the last two decades, the pH in the BS showed a slight annual decline, and the rate of change was (-1.45 ± 2.19) × 10-5 yr-1. In contrast, the NYS and SYS have slightly risen, with rates of change of (2.39 ± 1.24) × 10-5 and (1.23 ± 0.76) × 10-5 yr-1. We believed that surface water acidification in the BS and YS did not follow the expected trend of significant acidification observed in open oceanic regions. Instead, the acidification process in these marginal seas was dominated by local factors such as riverine inputs, biological activity, and cold water masses, resulting in minimal pH changes over the last two decades.


Assuntos
Estações do Ano , Água do Mar , Concentração de Íons de Hidrogênio , Água do Mar/química , China , Oceanos e Mares , Fitoplâncton , Monitoramento Ambiental
7.
Brief Bioinform ; 22(3)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32510555

RESUMO

Next-generation sequencing (NGS) technology has revolutionised human cancer research, particularly via detection of genomic variants with its ultra-high-throughput sequencing and increasing affordability. However, the inundation of rich cancer genomics data has resulted in significant challenges in its exploration and translation into biological insights. One of the difficulties in cancer genome sequencing is software selection. Currently, multiple tools are widely used to process NGS data in four stages: raw sequence data pre-processing and quality control (QC), sequence alignment, variant calling and annotation and visualisation. However, the differences between these NGS tools, including their installation, merits, drawbacks and application, have not been fully appreciated. Therefore, a systematic review of the functionality and performance of NGS tools is required to provide cancer researchers with guidance on software and strategy selection. Another challenge is the multidimensional QC of sequencing data because QC can not only report varied sequence data characteristics but also reveal deviations in diverse features and is essential for a meaningful and successful study. However, monitoring of QC metrics in specific steps including alignment and variant calling is neglected in certain pipelines such as the 'Best Practices Workflows' in GATK. In this review, we investigated the most widely used software for the fundamental analysis and QC of cancer genome sequencing data and provided instructions for selecting the most appropriate software and pipelines to ensure precise and efficient conclusions. We further discussed the prospects and new research directions for cancer genomics.


Assuntos
Genoma , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias/genética , Controle de Qualidade , Biologia Computacional/métodos , Humanos , Anotação de Sequência Molecular , Software
8.
Vascular ; : 17085381231214720, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940108

RESUMO

OBJECTIVE: The objective is to compare the characteristics of clinical data, imaging data, and treatment methods of young and old patients with acute type B aortic dissection (ABAD). METHODS: ABAD patients admitted to the Department of Vascular Surgery of the First Affiliated Hospital of Anhui Medical University from January 2012 to December 2018 were retrospectively reviewed. Patient demographics, such as gender, age, diabetes, hypertension, presenting symptoms, imaging characteristics, laboratory data on admission, hemodynamics on admission and in-hospital management, and mortality of different age groups were compared and analyzed. Categorical variables were compared using χ2 tests or Fisher's exact test. Continuous variables were compared using Student's t-test or Mann-Whitney U-test. RESULTS: A total of 141 ABAD patients were included in this study. Old ABAD patients were more likely to have a prior history of hypertension (88.6% vs 70.4%, p = 0.037) and atherosclerosis (29.8% vs 7.4%, p = 0.016). In the young group, Marfan syndrome was significantly higher (14.8% vs 0.9%; p = 0.005). Compared with the old group, the number of distal tears in the young group was significantly higher (62.3% vs 39.5%, p = 0.027). The proportion of patients with malperfusion of lower limbs in the young group was significantly higher than that in the old group (22.2% vs 6.1%, p = 0.026). There was no significant difference in the treatment methods and in-hospital mortality between the two groups. CONCLUSION: Compared with old ABAD patients, young ABAD patients had more distal tears and a higher proportion of lower limbs malperfusion.

9.
Scand J Gastroenterol ; 57(7): 832-841, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35293268

RESUMO

BACKGROUND: The objective of this study was to evaluate the prognostic value of Metastatic lymph node ratio (MLNR) after curative gastrectomy in patients with gastric cancer (GC) and the potential for new indicators to strengthen the current guidelines. METHODS: We retrospectively researched 3864 GC patients with curative gastrectomy between February 2011 and February 2016. The following clinical data were collected from the included patients: gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, TNM stage, survival time and survival status. Patients were divided into low-MLNR (L-MLNR), and high-MLNR (H-MLNR) groups based on adjusted the X-tile cutoff-value of 0.25 for MLNR, the survival rates and clinicopathological characteristics of each group were compared. For the assessment of significant associations between clinicopathological characteristics and patients' survival, univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazards analysis. The log-rank test was used to examine the statistical significance of differences among different survival curves. Clinicopathological features significantly associated with MLNR were assessed by the Chi-square test and multinomial logistic regression. The discriminative ability was measured by calculating the Bayesian Information Criterion (BIC) values for each category. Assessment of the effect of clinicopathological features on MLNR for predicting prognosis of GC patients used stratum analysis through Kaplan-Meier analysis and Cox proportional risk Analysis. RESULTS: Survival analysis indicated that MLNR was negatively associated with overall survival (OS) (p < .001) and was an independent prognostic predictor in 3864 GC patients (p < .001). MLNR had significant prognostic significance in various subgroups with clinicopathological characteristics (gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, and TNM stage) (p < .001). CONCLUSIONS: The MLNR may become a new indicator to assess the prognosis of GC patients who underwent curative gastrectomy. The results may have potential clinical implications that should be considered when developing clinical practice guidelines or the design of the future investigation.


Assuntos
Neoplasias Gástricas , Teorema de Bayes , Gastrectomia , Humanos , Razão entre Linfonodos , Linfonodos/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
10.
Vasc Med ; 27(3): 239-250, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35164613

RESUMO

Introduction: Femoropopliteal artery in-stent restenosis (ISR) remains a challenging treatment. We performed a network meta-analysis (NWM) for femoropopliteal artery ISR to explore the safety and efficacy of endovascular therapeutic strategies. Methods: The MEDLINE, Embase, Web of Science, and Cochrane databases were used as data sources. The network meta-analysis (NWM) approach used random-effects models based on the frequentist framework. We compared technical success rate, primary patency, target lesion revascularization (TLR), and major amputation at the 12-month follow-up for femoropopliteal artery ISR. Results: In total, 14 eligible studies (10 prospective and four retrospective; 1348 patients; and eight treatment modalities - standard balloon angioplasty (SBA), drug-coated balloon (DCB), peripheral cutting balloon angioplasty (PCBA), Viabahn endoprosthesis (VBE), directional atherectomy (DA), excimer laser atherectomy (ELA), and combinations - were included. The primary patency rates (at 6 months) were significantly higher for DCB and ELA+DCB than for SBA and ELA+SBA. ELA+DCB had higher primary patency rates (at 12 months) than ELA+SBA and SBA. The technical success rates were significantly lower for DCB and SBA than for VBE. The major amputation rates were significantly lower for ELA+DCB than for DCB. Based on the surface values under the cumulative ranking curve (SUCRA), ELA+DCB was considered the best treatment in terms of primary patency at 6 months (SUCRA = 91.1), primary patency at 12 months (SUCRA = 82.3), and TLR (SUCRA = 83.4). Conclusion: ELA+DCB showed positive encouraging results in primary patency (6, 12 months), TLR, and major amputation in femoropopliteal ISR. The efficacy and safety of ELA+DCB are worthy of further investigation. PROSPERO Registration No.: CRD42021246674.


Assuntos
Angioplastia com Balão , Reestenose Coronária , Doença Arterial Periférica , Angioplastia com Balão/efeitos adversos , Materiais Revestidos Biocompatíveis , Constrição Patológica , Artéria Femoral/diagnóstico por imagem , Humanos , Metanálise em Rede , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/terapia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular
11.
Sensors (Basel) ; 20(11)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471047

RESUMO

:Electroencephalogram (EEG) signals have been widely used in emotion recognition. However, the current EEG-based emotion recognition has low accuracy of emotion classification, and its real-time application is limited. In order to address these issues, in this paper, we proposed an improved feature selection algorithm to recognize subjects' emotion states based on EEG signal, and combined this feature selection method to design an online emotion recognition brain-computer interface (BCI) system. Specifically, first, different dimensional features from the time-domain, frequency domain, and time-frequency domain were extracted. Then, a modified particle swarm optimization (PSO) method with multi-stage linearly-decreasing inertia weight (MLDW) was purposed for feature selection. The MLDW algorithm can be used to easily refine the process of decreasing the inertia weight. Finally, the emotion types were classified by the support vector machine classifier. We extracted different features from the EEG data in the DEAP data set collected by 32 subjects to perform two offline experiments. Our results showed that the average accuracy of four-class emotion recognition reached 76.67%. Compared with the latest benchmark, our proposed MLDW-PSO feature selection improves the accuracy of EEG-based emotion recognition. To further validate the efficiency of the MLDW-PSO feature selection method, we developed an online two-class emotion recognition system evoked by Chinese videos, which achieved good performance for 10 healthy subjects with an average accuracy of 89.5%. The effectiveness of our method was thus demonstrated.


Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Emoções/classificação , Algoritmos , Humanos , Máquina de Vetores de Suporte
12.
Int J Neuropsychopharmacol ; 22(2): 157-164, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407505

RESUMO

Background: Rhodomyrtone is one of the main active compounds derived from Rhodomyrtus tomentosa, which belongs to the Myrtaceae family. In the current study, we investigated the properties of rhodomyrtone as a potential drug candidate for the treatment of stress-caused depression. Methods: We assessed the function of rhodomyrtone in chronic unpredictable mild stress, a well-validated depression model in mice. Depression-like behavior tests, including a sucrose performance test, social interaction test, and forced swimming test, were used to validate the antidepressant effects of rhodomyrtone. The Morris water maze was used to evaluate the mice's learning and memory ability. Spine density, glycogen synthase kinase-3ß, brain-derived neurotrophic factor, postsynaptic density protein 95, and apoptosis-associated protein were detected to reveal the underlying mechanism. Results: Rhodomyrtone was found to prevent source consumption decrease, decreased social behaviors, and increase immobility in the forced swimming test, suggesting a protective effect of rhodomyrtone against depression-like behaviors. Additionally, rhodomyrtone prevented the impairment of spatial memory in mice exposed to chronic unpredictable mild stress. Rhodomyrtone administration also reversed dendritic spine density defects in chronic unpredictable mild stress. Furthermore, rhodomyrtone inhibited the increase of glycogen synthase kinase-3ß activity and reversed the decrease of brain-derived neurotrophic factor and postsynaptic density protein 95 in chronic unpredictable mild stress mice. Elevated expression of apoptosis-associated protein Bax and cleaved-caspase 3 was also reversed by rhodomyrtone treatment. Conclusions: These results suggested that the antidepressant effect of rhodomyrtone involves the regulation of neurogenesis, neuronal survival, and synaptic plasticity in the hippocampus.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Estresse Psicológico/complicações , Xantonas/farmacologia , Animais , Doença Crônica , Espinhas Dendríticas/patologia , Depressão/etiologia , Modelos Animais de Doenças , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
13.
Proteins ; 86(6): 621-628, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29493006

RESUMO

The secondary structure transitions of regenerated silk fibroin (RSF) under different external perturbations have been studied extensively, except for pressure. In this work, time-resolved infrared spectroscopy with the attenuated total reflectance (ATR) accessory was employed to follow the secondary structure transitions of RSF in its wet film under low pressure. It has been found that pressure alone is favorable only to the formation of ß-sheet structure. Under constant pressure there is an optimum amount of D2 O in the wet film (D2 O : film = 2:1) so as to provide the optimal condition for the reorganization of the secondary structure and to have the largest formation of ß-sheet structure. Under constant amount of D2 O and constant pressure, the secondary structure transitions of RSF in its wet film can be divided into three stages along with time. In the first stage, random coil, α-helix, and ß-turn were quickly transformed into ß-sheet. In the second stage, random coil and ß-turn were relatively slowly transformed into ß-sheet and α-helix, and the content of α-helix was recovered to the value prior to the application of pressure. In the third and final stage, no measurable changes can be found for each secondary structure. This study may be helpful to understand the secondary structure changes of silk fibroin in silkworm's glands under hydrostatic pressure.


Assuntos
Bombyx/química , Fibroínas/química , Pressão , Animais , Cinética , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Plant Physiol ; 173(3): 1574-1582, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28115583

RESUMO

Chromatin remodeling is essential for gene expression regulation in plant development and response to stresses. Brahma (BRM) is a conserved ATPase in the SWI/SNF chromatin remodeling complex and is involved in various biological processes in plant cells, but the regulation mechanism on BRM protein remains unclear. Here, we report that BRM interacts with AtMMS21, a SUMO ligase in Arabidopsis (Arabidopsis thaliana). The interaction was confirmed in different approaches in vivo and in vitro. The mutants of BRM and AtMMS21 displayed a similar defect in root development. In the mms21-1 mutant, the protein level of BRM-GFP was significantly lower than that in wild type, but the RNA level of BRM did not change. Biochemical evidence indicated that BRM was modified by SUMO3, and the reaction was enhanced by AtMMS21. Furthermore, overexpression of wild-type AtMMS21 but not the mutated AtMMS21 without SUMO ligase activity was able to recover the stability of BRM in mms21-1 Overexpression of BRM in mms21-1 partially rescued the developmental defect of roots. Taken together, these results supported that AtMMS21 regulates the protein stability of BRM in root development.


Assuntos
Adenosina Trifosfatases/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Ligases/genética , Raízes de Plantas/genética , Adenosina Trifosfatases/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Montagem e Desmontagem da Cromatina/genética , Immunoblotting , Ligases/metabolismo , Microscopia Confocal , Modelos Genéticos , Mutação , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Ligação Proteica , Estabilidade Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Anal Chem ; 89(10): 5534-5541, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28406023

RESUMO

Whether the process of protein folding/unfolding is fully cooperative or it contains sequential elements has long been a fundamental issue in protein science. This issue seemingly became straightforward since the appearance of generalized two-dimensional (2D) correlation spectroscopy in 1990s, because 2D correlation analysis has been considered as a convenient and powerful analytical tool to determine the sequential order of events under external physical or chemical perturbations. In this work, the sequential order of the secondary structure transitions of regenerated silk fibroin under thermal treatment from 130 to 220 °C was first studied using generalized 2D correlation spectroscopy, but an apparently doubtful sequential order was obtained; ß-sheet was the first one to change at low temperature, then the random coil, followed by the nonamide C═O and, finally, the α-helix. A subsequent detailed in situ infrared spectral analysis showed that the main secondary structures of silk fibroin, including α-helix, ß-turn, random coil and ß-sheet (high-wavenumber component), all changed with a fully cooperative manner at a relatively low temperature of 150 °C. But the low-wavenumber component of ß-sheet started to change at a higher temperature of 180 °C. Besides, it has also been found that, before 200 °C, the loss of α-helix and random coil was transformed into ß-turn, ß-sheet, and nonamide C═O. After 200 °C, some ß-turn structure was also disruptured and transformed into ß-sheet and nonamide C═O.


Assuntos
Fibroínas/química , Amidas/química , Animais , Bombyx/metabolismo , Temperatura Alta , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier
16.
J Appl Gerontol ; : 7334648241273387, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39165167

RESUMO

The basic premise of this study is that the traditional method to treating all older people as coming from the same distribution misspecifies the true model and ignores potentially important information in wellbeing outcomes of social participation. Using data from the China Longitudinal Aging Social Survey (CLASS), this paper proposes a finite mixture model (FMM) to identify the heterogeneous relationship between volunteer participation and older people's subjective well-being (SWB) and then explore the determinants of wellbeing heterogeneity in volunteer participation. The results reveal that older people can be classified into two latent subgroups, that is the volunteering beneficiary group (accounting for about 42%) and the volunteering non-beneficiary group (accounting for about 58%). The FMM is therefore more appropriate in estimating the complex impact of volunteering. Rural older people with poorer health, weaker social networks, better economic status, and better community environments are more likely to benefit from volunteer participation. Our findings have suggested some practical implications to increase the probability of benefit from volunteer participation.

17.
Front Microbiol ; 15: 1463070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39376709

RESUMO

Global climate warming has led to changes in the suitable habitats for fungi. Colletotrichum acutatum, a common fungus causing anthracnose disease, is widely distributed in southern China. Currently, research on the relationship between C. acutatum and environmental warming was limited. In this study, MaxEnt and ArcGIS software were used to predict the suitable habitats of C. acutatum under current and future climate conditions based on its occurrence records and environmental factors. The optimal MaxEnt model parameters were set as feature combination (FC) = lp and regularization multiplier (RM) = 2.6. Bio15, Bio12, Bio09, and Bio19 were identified as the main environmental factors influencing the distribution of C. acutatum. Under current climate conditions, C. acutatum was distributed across all continents globally, except Antarctica. In China, C. acutatum was primarily distributed south of the Qinling-Huaihe Line, with a total suitable area of 259.52 × 104 km2. Under future climate conditions, the potential suitable habitat area for C. acutatum was expected to increase and spread towards inland China. The results of this study provided timely risk assessment for the distribution and spread of C. acutatum in China and offer scientific guidance for monitoring and timely controlled of its distribution areas.

18.
Int Immunopharmacol ; 142(Pt B): 113194, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39305892

RESUMO

Hepatocellular carcinoma (HCC) is a complex disease, further exacerbated by coexisting diabetes. With the rising incidence of HCC-diabetes cases, alternative treatment strategies are urgently needed. Traditional Chinese Medicine (TCM) offers promising options, and quercetin, a bioactive flavonoid, has shown significant antitumor and antidiabetic effects. This study aimed to investigate the efficacy of quercetin in treating HCC with diabetes using bioinformatics and network pharmacology. We constructed a prognostic model for HCC-diabetes using multivariate Cox proportional hazards regression and identified potential targets for quercetin by intersecting quercetin target genes with HCC-diabetes genes. Molecular docking and molecular dynamics simulations screened these potential targets, and in vitro experiments verified quercetin's targets and pathways. The results revealed a prediction model with four essential genes that effectively predict HCC prognosis in diabetic patients. IL6 and MMP9 were identified as potential targets of quercetin through molecular docking and dynamics simulations. In vitro experiments revealed that quercetin promotes apoptosis, inhibits cell proliferation, and suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells under high-glucose conditions by reducing IL6 expression and inhibiting the MEK/ERK pathway. In summary, quercetin may delay the progression of HCC-diabetes by modulating IL6 to inhibit the MEK/ERK signaling pathway, thereby promoting apoptosis and inhibiting the proliferation and EMT of HepG2 cells.


Assuntos
Apoptose , Carcinoma Hepatocelular , Neoplasias Hepáticas , Sistema de Sinalização das MAP Quinases , Simulação de Acoplamento Molecular , Quercetina , Humanos , Quercetina/uso terapêutico , Quercetina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Hep G2 , Interleucina-6/metabolismo , Interleucina-6/genética , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia
19.
Int J Artif Organs ; 47(4): 269-279, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38506302

RESUMO

Centrifugal blood pumps can be used for treating heart failure patients. However, pump thrombosis has remained one of the complications that trouble clinical treatment. This study analyzed the effect of impeller shroud on the thrombosis risk of the blood pump, and predicted areas prone to thrombosis. Multi-constituent transport equations were presented, considering mechanical activation and biochemical activation. It was found that activated platelets concentration can increase with shear stress and adenosine diphosphate(ADP) concentration increasing, and the highest risk of thrombosis inside the blood pump was under extracorporeal membrane oxygenation (ECMO) mode. Under the same condition, ADP concentration and thrombosis index of semi-shroud impeller can increase by 7.3% and 7.2% compared to the closed-shroud impeller. The main reason for the increase in thrombosis risk was owing to elevated scalar shear stress and more coagulation promoting factor-ADP released. The regions with higher thrombosis potential were in the center hole, top and bottom clearance. As a novelty, the findings revealed that impeller shroud can influence mechanical and biochemical activation factors. It is useful for identifying potential risk regions of thrombus formation based on relative comparisons.


Assuntos
Coração Auxiliar , Estresse Mecânico , Trombose , Trombose/etiologia , Trombose/fisiopatologia , Trombose/sangue , Humanos , Coração Auxiliar/efeitos adversos , Ativação Plaquetária , Modelos Cardiovasculares , Difosfato de Adenosina/metabolismo , Desenho de Prótese , Oxigenação por Membrana Extracorpórea/efeitos adversos , Fatores de Risco , Plaquetas/metabolismo
20.
Neural Netw ; 174: 106211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447425

RESUMO

Cross-modal hashing has attracted a lot of attention and achieved remarkable success in large-scale cross-media similarity retrieval applications because of its superior computational efficiency and low storage overhead. However, constructing similarity relationship among samples in cross-modal unsupervised hashing is challenging because of the lack of manual annotation. Most existing unsupervised methods directly use the representations extracted from the backbone of their respective modality to construct instance similarity matrices, leading to inaccurate similarity matrices and resulting in suboptimal hash codes. To address this issue, a novel unsupervised hashing model, named Structure-aware Contrastive Hashing for Unsupervised Cross-modal Retrieval (SACH), is proposed in this paper. Specifically, we concurrently employ both high-dimensional representations and discriminative representations learned by the network to construct a more informative semantic correlative matrix across modalities. Moreover, we design a multimodal structure-aware alignment network to minimize heterogeneous gap in the high-order semantic space of each modality, effectively reducing disparities within heterogeneous data sources and enhancing the consistency of semantic information across modalities. Extensive experimental results on two widely utilized datasets demonstrate the superiority of our proposed SACH method in cross-modal retrieval tasks over existing state-of-the-art methods.


Assuntos
Aprendizagem , Semântica
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