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1.
Bioresour Technol ; 412: 131359, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39197663

RESUMO

5-hydroxyvalerate (5-HV) is a crucial C5 platform chemical with versatile applications, yet its efficient production remains a challenge. The Raip, gabT, and yahK genes were integrated into the E. coli LE genome, deleted gabD, and enhanced gabP expression, resulting in the QluMG strain. Additionally, the impact of ethanol and H2O2 on 5-HV production was investigated. Further enhancement was achieved by incorporating an NADPH supplementation system, resulting in the QluMG strain. In the 5 L fermenter, the QluMGD strain produced 21.7 g/L of 5-HV from 50 g/L glucose, with a conversion rate of 43.4 %. The successful integration of the RaiP pathway into the E. coli genome significantly enhanced 5-HV production. The QluMG strain achieved the highest reported yield from glucose in engineered E. coli to date. This study provides a new strategy for the efficient production of 5-HV and other chemicals using 5-HV as a precursor, demonstrating potential for industrial application.


Assuntos
Escherichia coli , Engenharia Metabólica , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Metabólica/métodos , Glucose/metabolismo , Fermentação , Oxigenases de Função Mista/metabolismo , Oxigenases de Função Mista/genética , Etanol/metabolismo , Peróxido de Hidrogênio/metabolismo
2.
Int J Mol Sci ; 25(16)2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39201665

RESUMO

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1-/-) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1-/-) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1-/- mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.


Assuntos
Capsaicina , Inflamação , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Obesidade , Canais de Cátion TRPV , Receptor 4 Toll-Like , Animais , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Capsaicina/farmacologia , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Humanos , Camundongos , Receptor 4 Toll-Like/metabolismo , Células CACO-2 , Camundongos Knockout , Dieta Hiperlipídica/efeitos adversos , Masculino , Ocludina/metabolismo , Ocludina/genética , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos
3.
ACS Synth Biol ; 13(9): 2948-2959, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39158285

RESUMO

5-Aminovalerate (5-AVA), 5-hydroxyvalerate (5-HV), and 1,5-pentanediol (1,5-PDO) are l-lysine derivatives with extensive applications in the production of materials such as polyesters, polyurethane, plasticizers, inks, and coatings. However, their large-scale production is limited by the lack of efficient synthetic pathways. Here, we aimed to construct multiple synthetic pathways by screening the key enzymes involved in the synthesis of these compounds in Escherichia coli. The engineered pathway utilizing RaiP demonstrated a superior catalytic efficiency. The LER strain that overexpressed only raiP successfully synthesized 9.70 g/L 5-HV and 8.31 g/L 5-AVA, whereas the strain LERGY that overexpressed raiP, gabT, and yahK accumulated 9.72 g/L 5-HV and 7.95 g/L 5-AVA from 20 g/L glucose. The introduction of exogenous transaminases and dehydrogenases enhanced cell growth and fermentation efficiency with respect to 5-HV synthesis, albeit without significantly impacting the yield. Strain LE05, incorporating only two exogenous enzymes, RaiP and CaR, produced 1.87 g/L 1,5-PDO, 3.85 g/L 5-HV, and 4.78 g/L 5-hydroxyglutaraldehyde from 20 g/L glucose after 6 days. The strain LE02G, fortified with transaminase, dehydrogenase, and NADPH regeneration system, accumulated 7.82 g/L 1,5-PDO, whereas the aldp-knock out LE02G2 synthesized 10.98 g/L 1,5-PDO from 50 g/L glucose in fed-batch fermentation after 6 days, yielding 0.22 g/g glucose (0.37 mol/mol). Introducing the NADPH regeneration pathway and deleting the NADPH-consuming pathways increased the 1,5-PDO yield and decreased the precursor concentration. The proposed pathways and engineering strategies presented in this study can prove instrumental in developing biological routes for the practical production of 5-AVA, 5-HV, and 1,5-PDO.


Assuntos
Escherichia coli , Lisina , Engenharia Metabólica , Engenharia Metabólica/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Lisina/metabolismo , Fermentação , Glucose/metabolismo , Transaminases/metabolismo , Transaminases/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Aminoácidos Neutros
4.
Sci Data ; 11(1): 773, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003335

RESUMO

Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998-2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED's monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944-0.995), Bias (-0.68-0.53), and Root Mean Square Error (5.50-15.59 mm). Additionally, TPRED's monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED's annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.

5.
Acad Radiol ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38824087

RESUMO

OJECTIVES: Low-grade glioma (LGG) is associated with increased mortality owing to recrudescence and the tendency for malignant transformation. Therefore, it is imperative to discover novel prognostic biomarkers as existing traditional prognostic biomarkers of glioma, including clinicopathological features and imaging examinations, are unable to meet the clinical demand for precision medicine. Accordingly, we aimed to evaluate the prognostic value of cyclin D1 (CCND1) expression levels and construct radiomic models to predict these levels in patients with LGG MATERIALS AND METHODS: A total of 412 LGG cases from The Cancer Genome Atlas (TCGA) were used for gene-based prognostic analysis. Using magnetic resonance imaging (MRI) images stored in The Cancer Imaging Archive with genomic data from TCGA, 149 cases were selected for radiomics feature extraction and model construction. After feature extraction, the radiomic signature was constructed using logistic regression (LR) and support vector machine (SVM) analyses. RESULTS: CCND1 was identified as a prognosis-related gene with differential expression in tumor and normal samples and plays a role in regulating both the cell cycle and immune response. Landmark analysis revealed that high-expression levels of CCND1 were beneficial for survival (P < 0.05) in advanced LGG. Four optimal radiomics features were selected to construct radiomics models. The performance of LR and SVM achieved areas under the curve of 0.703 and 0.705, as well as 0.724 and 0.726 in the training and validation sets, respectively. CONCLUSION: Elevated levels of CCND1 expression could impact the prognosis of patients with LGG. MRI-based radiomics, especially the AUC values, can serve as a novel tool for predicting CCND1 expression and understanding the correlation between elevated CCND1 expression and prognosis. AVAILABILITY OF DATA AND MATERIALS: The datasets analyzed during the current study are available in the TCGA, TCIA, UCSC XENA and GTEx repository, https://portal.gdc.cancer.gov/, https://www.cancerimagingarchive.net/, https://xenabrowser.net/datapages/, https://www.gtexportal.org/home/.

6.
JAMA Neurol ; 81(7): 741-751, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38805216

RESUMO

Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.


Assuntos
Atorvastatina , Inibidores de Hidroximetilglutaril-CoA Redutases , Ataque Isquêmico Transitório , AVC Isquêmico , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Método Duplo-Cego , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/prevenção & controle , Atorvastatina/uso terapêutico , Atorvastatina/administração & dosagem , Ataque Isquêmico Transitório/tratamento farmacológico , Adulto , Isquemia Encefálica/tratamento farmacológico , Idoso de 80 Anos ou mais , Prevenção Secundária/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem
7.
Neurobiol Aging ; 140: 122-129, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38776615

RESUMO

Brain biological age, which measures the aging process in the brain using neuroimaging data, has been used to assess advanced brain aging in neurodegenerative diseases, including Parkinson disease (PD). However, assuming that whole brain degeneration is uniform may not be sufficient for assessing the complex neurodegenerative processes in PD. In this study we constructed a multiscale brain age prediction models based on structural MRI of 1240 healthy participants. To assess the brain aging patterns using the brain age prediction model, 93 PD patients and 91 healthy controls matching for sex and age were included. We found increased global and regional brain age in PD patients. The advanced aging regions were predominantly noted in the frontal and temporal cortices, limbic system, basal ganglia, thalamus, and cerebellum. Furthermore, region-level rather than global brain age in PD patients was associated with disease severity. Our multiscale brain age prediction model could aid in the development of objective image-based biomarkers to detect advanced brain aging in neurodegenerative diseases.


Assuntos
Envelhecimento , Encéfalo , Imageamento por Ressonância Magnética , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Envelhecimento/patologia , Pessoa de Meia-Idade , Idoso
8.
Angew Chem Int Ed Engl ; 63(14): e202318609, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38345594

RESUMO

The fabrication of a multimodal phototheranostic platform on the basis of single-component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full of challenges. The emergence of aggregation-induced emission luminogens (AIEgens), particularly those emit fluorescence in the second near-infrared window (NIR-II), provides a powerful tool for cancer treatment by virtue of adjustable pathway for radiative/non-radiative energy consumption, deeper penetration depth and aggregation-enhanced theranostic performance. Although bulky thiophene π-bridges such as ortho-alkylated thiophene, 3,4-ethoxylene dioxythiophene and benzo[c]thiophene are commonly adopted to construct NIR-II AIEgens, the subtle differentiation on their theranostic behaviours has yet to be comprehensively investigated. In this work, systematical investigations discovered that AIEgen BT-NS bearing benzo[c]thiophene possesses acceptable NIR-II fluorescence emission intensity, efficient reactive oxygen species generation, and high photothermal conversion efficiency. Eventually, by using of BT-NS nanoparticles, unprecedented performance on NIR-II fluorescence/photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal elimination of tumors was demonstrated. This study thus offers useful insights into developing versatile phototheranostic systems for clinical trials.


Assuntos
Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanopartículas/uso terapêutico , Medicina de Precisão , Linhagem Celular Tumoral
9.
Luminescence ; 39(1): e4675, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38286603

RESUMO

The coronavirus disease-2019 pandemic reflects the underdevelopment of point-of-care diagnostic technology. Nuclei acid (NA) detection is the "gold standard" method for the early diagnosis of the B.1.1.529 (Omicron) variant of severe acute respiratory syndrome-coronavirus disease-2. Polymerase chain reaction is the main method for NA detection but requires considerable manpower and sample processing taking ≥ 3 h. To simplify the operation processes and reduce the detection time, exonuclease III (Exo III)-aided MoS2 /AIE nanoprobes were developed for rapid and sensitive detection of the oligonucleotides of Omicron. Molybdenum disulfide (MoS2 ) nanosheets with excellent optical absorbance and distinguishable affinity to single-strand and duplex DNAs were applied as quenchers, and aggregation-induced emission (AIE) molecules with high luminous efficiency were designed as donor in fluorescence resonance energy transfer-based nanoprobes. Exo III with catalytic capability was used for signal amplification to increase the sensitivity of detection. The composite nanoprobes detected the mutated nucleocapsid (N)-gene and spike (S)-gene oligonucleotides of Omicron within 40 min with a limit of detection of 4.7 pM, and showed great potential for application in community medicine.


Assuntos
Técnicas Biossensoriais , COVID-19 , Exodesoxirribonucleases , Humanos , Oligonucleotídeos , SARS-CoV-2/genética , Molibdênio , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico
10.
N Engl J Med ; 389(26): 2413-2424, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38157499

RESUMO

BACKGROUND: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS: A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).


Assuntos
Aspirina , Clopidogrel , AVC Isquêmico , Inibidores da Agregação Plaquetária , Humanos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/etiologia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
11.
BMJ Open ; 13(6): e069663, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37355272

RESUMO

OBJECTIVE: Previous studies linking Triglyceride Glucose (TyG) Index to carotid plaque have yielded inconsistent results. Moreover, related studies on the population of Japan are rare. This study aims to provide further results. DESIGN: A hospital-based cross-sectional study. SETTING: The Shin Takeo Hospital. PARTICIPANTS: We assessed 1904 Japanese participants (988 men and 916 women) whose mean age was 57±11.9 years, and those participants underwent health check-ups at Shinbuf Hospital at Shin Takeo Hospital from 1 April 2016 to 31 October 2017. METHODOLOGY: Carotid plaque, triglyceride and fasting glucose and other relevant indicators were collected. We used ultrasonography to evaluate carotid plaque. A multivariable logistic regression model and generalised additive model were used to evaluate the association between the TyG Index and carotid plaque. Subgroup and interaction analyses were validated for the consistency of these correlations. RESULTS: Following the adjustment of traditional carotid plaque risk factors, the non-linear relationship between the TyG Index and carotid plaque was investigated. Using a two-piecewise regression model, we calculated the inflection point to be 9.06. The OR and 95% CIs for the inflection points on the left and right sides were 1.70 (1.27 to 2.29) and 0.88 (0.52 to 1.47), respectively. According to the variables tested, the interactions between the TyG Index and all subgroup factors were analysed and significant interactions were not observed. CONCLUSION: In individuals who underwent a comprehensive check-up in Japan, the relationship between the TyG Index and carotid plaque is non-linear. When the TyG Index is less than 9.06, it is associated with carotid plaque.


Assuntos
Glicemia , Doenças das Artérias Carótidas , Placa Aterosclerótica , Triglicerídeos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Glicemia/análise , Estudos Transversais , População do Leste Asiático , Glucose , Resistência à Insulina , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Fatores de Risco , Triglicerídeos/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem
12.
Front Neurosci ; 17: 1125281, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37274215

RESUMO

Background: Alzheimer's disease (AD), a neurodegenerative disorder with progressive symptoms, seriously endangers human health worldwide. AD diagnosis and treatment are challenging, but molecular biomarkers show diagnostic potential. This study aimed to investigate AD biomarkers in the peripheral blood. Method: Utilizing three microarray datasets, we systematically analyzed the differences in expression and predictive value of mitophagy-related hub genes (MRHGs) in the peripheral blood mononuclear cells of patients with AD to identify potential diagnostic biomarkers. Subsequently, a protein-protein interaction network was constructed to identify hub genes, and functional enrichment analyses were performed. Using consistent clustering analysis, AD subtypes with significant differences were determined. Finally, infiltration patterns of immune cells in AD subtypes and the relationship between MRHGs and immune cells were investigated by two algorithms, CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). Results: Our study identified 53 AD- and mitophagy-related differentially expressed genes and six MRHGs, which may be potential biomarkers for diagnosing AD. Functional analysis revealed that six MRHGs significantly affected biologically relevant functions and signaling pathways such as IL-4 Signaling Pathway, RUNX3 Regulates Notch Signaling Pathway, IL-1 and Megakaryocytes in Obesity Pathway, and Overview of Leukocyteintrinsic Hippo Pathway. Furthermore, CIBERSORT and ssGSEA algorithms were used for all AD samples to analyze the abundance of infiltrating immune cells in the two disease subtypes. The results showed that these subtypes were significantly related to immune cell types such as activated mast cells, regulatory T cells, M0 macrophages, and neutrophils. Moreover, specific MRHGs were significantly correlated with immune cell levels. Conclusion: Our findings suggest that MRHGs may contribute to the development and prognosis of AD. The six identified MRHGs could be used as valuable diagnostic biomarkers for further research on AD. This study may provide new promising diagnostic and therapeutic targets in the peripheral blood of patients with AD.

13.
Discov Med ; 35(176): 312-320, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37272098

RESUMO

OBJECTIVES: Although probiotics have been shown to improve several mental-related diseases, their association with post-stroke depression (PSD) remains unclear. This research aimed to investigate the effect of combined live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus cereus tablets on PSD and serum inflammatory factors. METHODS: A total of 400 stroke patients treated from January 2020 to March 2022 in Shuyang Hospital were included and randomly divided into two groups: The observation group (n = 200) and the control group (n = 200). The control group was treated with conventional therapy, while the observation group was given combined live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus cereus tablets on the basis of conventional therapy. The Hamilton Depression Scale score was used to assess the degree and incidence of depression in the two groups. Recurrence and complications of PSD in stroke patients after treatment were followed up. In addition, ELISA (enzyme-linked immunosorbent assay) was employed for the detection of serum levels of nuclear factor kappa light chain enhancer of activated B cells (NF-κB), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and logistics regression analysis was also performed for the correlation between the occurrence of PSD and NF-κB, IL-1ß, and TNF-α levels. RESULTS: The analysis of clinical baseline data showed that the two groups of patients were comparable. After treatment, the Hamilton Depression Scale score in the observation group was significantly lower than in the control group (p < 0.05), and the observation group had a lower incidence rate of PSD, follow-up recurrence rate and complications (p < 0.05). In addition, the observation group showed a significant decrease in the serum levels of NF-κB, IL-1ß and TNF-α compared with the control group (p < 0.05). Further logistics regression analysis indicated that the levels of NF-κB (OR (odds ratio) = 3.337, p < 0.001), IL-1ß (OR = 2.411, p < 0.001) and TNF-α (OR = 1.557, p < 0.001) were risk factors for the development of PSD. CONCLUSIONS: Combined live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus cereus tablets can promote neurological recovery and remission of depression in stroke patients. Such effects may be achieved by regulating the levels of NF-κB, IL-1ß and TNF-α.


Assuntos
Acidente Vascular Cerebral , Fator de Necrose Tumoral alfa , Humanos , NF-kappa B , Bacillus cereus , Depressão/etiologia , Depressão/terapia , Enterococcus , Lactobacillus , Bifidobacterium , Inflamação , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia
14.
Enzyme Microb Technol ; 168: 110259, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37245327

RESUMO

D-Allose is a rare cis-caprose with a wide range of physiological functions, which has a wide range of applications in medicine, food, and other industries. L-Rhamnose isomerase (L-Rhi) is the earliest enzyme found to catalyze the production of D-allose from D-psicose. This catalyst has a high conversion rate, but its specificity for substrates is limited; thus, it cannot fulfill the requirements of industrial production of D-allose. In this study, L-Rhi derived from Bacillus subtilis was employed as the research subject, and D-psicose as the conversion substrate. Two mutant libraries were constructed through alanine scanning, saturation mutation, and rational design based on the analysis of the secondary structure, tertiary structure, and interactions with ligands of the enzyme. The yield of D-allose produced by these mutants was assessed; it was found that the conversion rate of mutant D325M to D-allose was increased by 55.73 %, and the D325S improved by 15.34 %, while mutant W184H increased by 10.37 % at 55 °C, respectively. According to modeling analysis, manganese (Mn2+) had no significant effect on the production of D-psicose from D-psicose by L-Rhi. The results of molecular dynamics simulation demonstrated that the mutants W184H, D325M, and D325S had more stable protein structures while binding with the substrate D-psicose, as evidenced by its root mean square deviation (RMSD), root mean square fluctuation (RMSF), and binding free energy values. It was more conducive to binding D-psicose and facilitating its conversion to D-allose, providing the basis for the production of D-allose.


Assuntos
Aldose-Cetose Isomerases , Glucose , Glucose/metabolismo , Frutose/metabolismo , Aldose-Cetose Isomerases/metabolismo , Mutação
15.
Sci Total Environ ; 856(Pt 2): 159201, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36202353

RESUMO

On the alpine areas such as Tianshan Mountains, snow and glaciers are widely distributed, which are sensitive to temperature changes. However, due to high altitude and scarcity of observed stations, the temperature changes and their causes in Tianshan are unclear. To address this issue, this study integrated Thiel-Sen trend test, Pearson correlation, and wavelet analysis methods to analyze the driving factors of temperature changes in Tianshan. We draw the following conclusions: (1) In the past 40 years, Tianshan warmed at a rate of 0.30 °C/decade. Seasonally, the temperature increased the most in spring and summer; spatially, the east Tianshan experienced the most warming. (2) Climate change has affected significant warming in the Tianshan. (3) The large-scale climate teleconnections found to be associated with warming in the Tianshan include North Pacific pattern, Atlantic Multidecadal Variability (AMV), North Atlantic Oscillation, and Western Hemisphere Warm Pool (WHWP). During the study period, the temperature changes lagged AMV and WHWP by 1.5 months, North Tropical Atlantic Index and Tropical Northern Atlantic Index by 3 months, and Arctic Oscillation by 4 months. This research contributes to understanding the response of dry mountains to global warming and atmospheric circulation changes.


Assuntos
Aquecimento Global , Camada de Gelo , Temperatura , Mudança Climática , Estações do Ano
16.
Adv Mater ; 35(10): e2210085, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36479736

RESUMO

Aggregation-induced emission luminogens (AIEgens) have recently been developed at a tremendous pace in the area of organic luminescent materials by virtue of their superior properties. However, the practical applications of AIEgens still face the challenge of transforming AIEgens from molecules into materials. Till now, many AIEgens have been integrated into fiber, endowing the fiber with prominent fluorescence and/or photosensitizing capacities. AIEgens and fiber complement each other for making progress in flexible smart materials, in which the utilization of AIEgens creates new application possibilities for fiber, and the fiber provides an excellent carrier for AIEgens towards realizing the conversion from molecule to materials and an ideal platform to research the aggregate state of AIEgens in mesoscale and macroscale. This review begins with a brief summary of the recent advances related to some typical AIEgens with various functions and the technology for the fabrication of AIEgen-functionalized fiber. The most representative applications are then highlighted by focusing on energy conversion, personal protective equipment, biomedical, sensor, and fluorescence-related fields. Finally, the challenges, opportunities, and tendencies in future development are discussed in detail. This review hopes to inspire innovation in AIEgens and fiber from the view of mesoscale and macroscale.

18.
BMC Genomics ; 23(1): 745, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348277

RESUMO

BACKGROUND: Plums are one of the most important economic crops of the Rosaceae family and are produced all over the world. China has many local varieties, but the genomic information is limited for genetic studies. Here, we first sequenced, assembled, and analyzed the plastomes of twelve plum cultivars and developed molecular markers to distinguish them. RESULTS: The twelve plastomes of plum cultivars have a circular structure of 157,863-157,952 bp containing a large single-copy region (LSC) of 86,109-86,287 bp, a small copy region (SSC) of 18,927-19,031 bp, and two inverted repeats (IR) of 26,353-26,387 bp each. The plastomes of plum cultivars encode 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. We detected 50, 54, 54, 53, 53, 50, 54, 54, 54, 49, 50, 54 SSRs in the twelve analyzed varieties, respectively. For repeat sequences, we identified 553 tandem repeats, 204 direct repeats, and 270 palindromic repeats. We also analyzed the expansion/contraction of IR regions. The genes rpl22, rps19, rpl2, ycf1, ndhF, and the trnH span on or near the boundary of IR and single-copy regions. Phylogenetic analysis showed that the twelve cultivars were clustered with the P. salicina and P. domestica. We developed eight markers LZ01 to LZ08 based on whole plastomes and nuclear genes and validated them successfully with six repetitions. CONCLUSIONS: The results obtained here could fill in the blanks of the plastomes of these twelve plum cultivars and provide a wider perspective based on the basis of the plastomes of Prunus to the molecular identification and phylogenetic construction accurately. The analysis from this study provides an important and valuable resource for studying the genetic basis for agronomic and adaptive differentiation of the Prunus species.


Assuntos
Prunus domestica , Prunus , Rosaceae , Filogenia , Prunus domestica/genética , Prunus/genética , Rosaceae/genética , Sequência de Bases
20.
Small Methods ; 6(8): e2200393, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35657020

RESUMO

Inspired by the excellent photothermal conversion ability and inherent nanomedicine platform property of MXenes, efficient reactive oxygen species production and prominent fluorescence emission feature of aggregation-induced emission (AIE)-active photosensitizers (PSs), as well as the extending excitation wavelength capability of upconversion nanoparticles (UCNPs), a versatile nanoplatform comprised of Ti3 C2 nanosheets (NSs), AIE-active PSs and UCNPs is intelligently fabricated. This three-pronged strategy takes advantages of each component simultaneously, and realizes fluorescence imaging/photoacoustic imaging/photothermal imaging triple-modal imaging-guided photothermal/photodynamic synergetic therapy under 808 nm laser irradiation. The introduction of UCNPs actualizes the long wavelength-activation of AIE-active PSs, which significantly increases the tissue penetration depth. Spatially isolation of AIE-active PSs and Ti3 C2 NSs is beneficial for suppressing the fluorescence quenching effect of Ti3 C2 NSs, bringing about ultimately brilliant fluorescence. The covalently bonded polymer surface endows the nanoplatform with excellent physiological stability and efficient tumor accumulation. These outputs reveal a win-win cooperation of multiple inorganic/organic nanocomposites for phototheranostics, and present great potential for future clinical translations.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Fármacos Fotossensibilizantes/farmacologia , Polímeros , Medicina de Precisão
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