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1.
Nanotoxicology ; : 1-15, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941019

RESUMO

Ambient air pollution is a leading cause of non-communicable disease in the world. PM2.5 has the potential to change the miRNAs profiles, which in turn causes cardiovascular effects. Hypoxia-inducible factor (HIF)-1 plays a critical role in the development of atherosclerosis. Yet, the possible role of miR-939-5p/HIF-1α in PM2.5-induced endothelial injury remains elusive. Therefore, the study aims to investigate the effects of miR-939-5p and HIF-1α on PM2.5-triggered endothelial injury. The results from immunofluorescence, qRT-PCR, LSCM, and western blot assays demonstrated that PM2.5 increased the levels of HIF-1α, inflammation and apoptosis in human aortic endothelial cells (HAECs). Yet, the inflammatory response and mitochondrial-mediated apoptosis pathway were effectively inhibited in HIF-1α knockdown HAECs lines. The expression of miR-939-5p was significantly down-regulated in HAECs after exposed to PM2.5. The luciferase reporter, qRT-PCR and western blot results demonstrated that miR-939-5p could directly targeted HIF-1α. And the miR-939-5p overexpression restricted PM2.5-triggered decreases in cell viability and increases in lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and inflammation. In addition, miR-939-5p overexpression remarkably suppressed PM2.5-triggered BcL-2/Bax ratio reduction and Cytochrome C, Cleaved Caspase-9 and Cleaved Caspase-3 expression increase, revealed that miR-939-5p hampered PM2.5-induced endothelial apoptosis through mitochondrial-mediated apoptosis pathway. Our results demonstrated that PM2.5 increased the expression of HIF-1α followed by a pro-inflammatory and apoptotic response in HAECs. The protective effect of miR-939-5p on PM2.5-triggered endothelial cell injury by negatively regulating HIF-1α. miR-939-5p might present a new therapeutic target for PM2.5 induced endothelial injury.

2.
Nature ; 592(7855): 551-557, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33883734

RESUMO

Solid-state lithium (Li)-air batteries are recognized as a next-generation solution for energy storage to address the safety and electrochemical stability issues that are encountered in liquid battery systems1-4. However, conventional solid electrolytes are unsuitable for use in solid-state Li-air systems owing to their instability towards lithium metal and/or air, as well as the difficulty in constructing low-resistance interfaces5. Here we present an integrated solid-state Li-air battery that contains an ultrathin, high-ion-conductive lithium-ion-exchanged zeolite X (LiX) membrane as the sole solid electrolyte. This electrolyte is integrated with cast lithium as the anode and carbon nanotubes as the cathode using an in situ assembly strategy. Owing to the intrinsic chemical stability of the zeolite, degeneration of the electrolyte from the effects of lithium or air is effectively suppressed. The battery has a capacity of 12,020 milliamp hours per gram of carbon nanotubes, and has a cycle life of 149 cycles at a current density of 500 milliamps per gram and at a capacity of 1,000 milliamp hours per gram. This cycle life is greater than those of batteries based on lithium aluminium germanium phosphate (12 cycles) and organic electrolytes (102 cycles) under the same conditions. The electrochemical performance, flexibility and stability of zeolite-based Li-air batteries confer practical applicability that could extend to other energy-storage systems, such as Li-ion, Na-air and Na-ion batteries.

3.
Adv Mater ; 33(18): e2100333, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33792083

RESUMO

The development of highly efficient, multifunctional, and biocompatible sonosensitizer is still a priority for current sonodynamic therapy (SDT). Herein, a defect-rich Ti-based metal-organic framework (MOF) (D-MOF(Ti)) with greatly improved sonosensitizing effect is simply constructed and used for enhanced SDT. Compared with the commonly used sonosensitizer TiO2 , D-MOF(Ti) results in a superior reactive oxygen species (ROS) yield under ultrasound (US) irradiation due to its narrow bandgap, which principally improves the US-triggered electron-hole separation. Meanwhile, due to the existence of Ti3+ ions, D-MOF(Ti) also exhibits a high level of Fenton-like activity to enable chemodynamic therapy. Particularly, US as the excitation source of SDT can simultaneously enhance the Fenton-like reaction to achieve remarkably synergistic outcomes for oncotherapy. More importantly, D-MOF(Ti) can be degraded and metabolized out of the body after completion of its therapeutic functions without off-target toxicity. Overall, this work identifies a novel Ti-familial sonosensitizer harboring great potential for synergistic sonodynamic and chemodynamic cancer therapy.

4.
BMC Med Inform Decis Mak ; 21(Suppl 1): 134, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888098

RESUMO

BACKGROUND: Deep learning algorithms significantly improve the accuracy of pathological image classification, but the accuracy of breast cancer classification using only single-mode pathological images still cannot meet the needs of clinical practice. Inspired by the real scenario of pathologists reading pathological images for diagnosis, we integrate pathological images and structured data extracted from clinical electronic medical record (EMR) to further improve the accuracy of breast cancer classification. METHODS: In this paper, we propose a new richer fusion network for the classification of benign and malignant breast cancer based on multimodal data. To make pathological image can be integrated more sufficient with structured EMR data, we proposed a method to extract richer multilevel feature representation of the pathological image from multiple convolutional layers. Meanwhile, to minimize the information loss for each modality before data fusion, we use the denoising autoencoder as a way to increase the low-dimensional structured EMR data to high-dimensional, instead of reducing the high-dimensional image data to low-dimensional before data fusion. In addition, denoising autoencoder naturally generalizes our method to make the accurate prediction with partially missing structured EMR data. RESULTS: The experimental results show that the proposed method is superior to the most advanced method in terms of the average classification accuracy (92.9%). In addition, we have released a dataset containing structured data from 185 patients that were extracted from EMR and 3764 paired pathological images of breast cancer, which can be publicly downloaded from http://ear.ict.ac.cn/?page_id=1663 . CONCLUSIONS: We utilized a new richer fusion network to integrate highly heterogeneous data to leverage the structured EMR data to improve the accuracy of pathological image classification. Therefore, the application of automatic breast cancer classification algorithms in clinical practice becomes possible. Due to the generality of the proposed fusion method, it can be straightforwardly extended to the fusion of other structured data and unstructured data.


Assuntos
Neoplasias da Mama , Algoritmos , Mama , Neoplasias da Mama/diagnóstico por imagem , Registros Eletrônicos de Saúde , Humanos , Redes Neurais de Computação
6.
Reprod Domest Anim ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33738852

RESUMO

Glycine is a well-known free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. Excessive fluoride exposure is associated with multiple types of cellular damage in humans and animals. The objective of the present study was to investigate the protective effects of glycine on sodium fluoride (NaF) exposure and the possible underlying mechanisms in a porcine testicular Sertoli cell line model. Cellular viability and proliferation were examined following NaF exposure and glycine supplementation, and glycine dramatically ameliorated the decreases in NaF-induced porcine testicular Sertoli cell viability and proliferation. Further investigations revealed that glycine decreased NaF-induced intracellular reactive oxygen species production, DNA fragment accumulation and the apoptosis incidence in the porcine testicular Sertoli cell line; in addition, glycine improved mitochondrial function and ATP production. Notably, results of the SPiDER-ß-Gal analysis suggested that glycine alleviated NaF-induced cellular senescence and downregulated P53, P21, HMGA2 and P16INK4a gene expression in the porcine testicular Sertoli cell line. Collectively, the beneficial effects of glycine alleviate NaF-induced oxidative stress, apoptosis and senescence, and together with our previous findings, support the hypothesis that glycine plays an important role in protecting against NaF exposure-induced impairments in the porcine testicular Sertoli cell line.

7.
Aging (Albany NY) ; 13(6): 8454-8466, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33714197

RESUMO

In this study, we investigated the beneficial effects of high endogenous levels of n-3 polyunsaturated fatty acids (PUFAs) on skeletal muscle repair and regeneration using a mouse cardiotoxin (CTX, 20 µM/200 µL) -induced gastrocnemius muscle injury model. Transgenic fat-1 mice expressing the Caenorhabditis elegans fat-1 gene, encoding n-3 fatty acid desaturase, showed higher n-3 PUFA levels and lower n-6/n-3 PUFA ratios in gastrocnemius muscle tissues. Hematoxylin and eosin and Masson's trichrome staining of gastrocnemius sections revealed increased muscle fiber size and reduced fibrosis in fat-1 mice on days 7 and 14 after CTX injections. Gastrocnemius muscle tissues from fat-1 mice showed reduced inflammatory responses and increased muscle fiber regeneration reflecting enhanced activation of satellite cells on day 3 after cardiotoxin injections. Gastrocnemius muscle tissues from cardiotoxin-treated fat-1 mice showed reduced levels of pro-apoptotic proteins (Caspase 3 and Bax) and increased levels of anti-apoptotic proteins (Bcl-2 and Survivin). Moreover, eicosapentaenoic acid (EPA) reduced the incidence of apoptosis among cardiotoxin-treated C2C12 mouse myoblasts. These findings demonstrate that higher endogenous n-3 PUFA levels in fat-1 mice enhances skeletal muscle repair and regeneration following cardiotoxin-induced injury.

8.
Theriogenology ; 167: 67-76, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33774368

RESUMO

Cypermethrin (CYP) is a widely used insecticide that may be harmful to nontarget species. However, the toxicity of CYP to porcine Sertoli cells (SCs) and its associated mechanism is not known. We investigated the toxicity of CYP and showed that CYP induced cytotoxicity in porcine SCs in a dose-dependent manner. Mechanistic investigations revealed that CYP induced oxidative stress and DNA damage in porcine SCs, which provoked mitochondria-associated apoptosis. CYP also stimulated the phosphorylation of c-Jun N-terminal kinase (JNK) to induce porcine SC apoptosis and inhibited cell proliferation via the inhibition of nuclear factor kappa B (NFκB) expression. The natural antioxidant melatonin had an obvious protective effect against CYP-induced porcine SC toxicity. Overall, our results reveal that the mechanism underlying CYP-induced toxicity in porcine SCs involves oxidative stress, DNA damage, and apoptosis and suggest that melatonin may be used as a highly effective protective agent against oxidative stress.

9.
Sci Total Environ ; 770: 144761, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33736424

RESUMO

Intensified Mn redox cycling could enhance nutrient removal in constructed wetlands (CWs). In this study, Mn oxides (birnessite-coated sand) were used as the matrix in horizontal flow CWs (HFCWs) with a microbial electrolysis cell (MEC) (E-B-CW) or without an MEC (B-CW). The model CWs were developed to investigate the capacities and mechanisms of nitrogen removal with increased Mn redox cycling. The results showed that E-B-CW had the highest average removal efficiencies for NH4-N, NO3-N and TN, followed by B-CW and control HFCW (C-CW). The Mn(III) oxides (MnOOH or Mn2O3) and the Mn(IV) oxide (MnO2) were all detected in E-B-CW and B-CW, while the matrix in E-B-CW had much more Mn(IV) oxides than B-CW. Interestingly, clustering heat map showed that ammonification and nitrate reduction were related to Mn-oxidizing bacteria and the relative abundance of Mn-oxidizing bacteria in E-B-CW was highest due to the re-oxidation of Mn(II) by the MEC.


Assuntos
Nitrogênio , Áreas Alagadas , Desnitrificação , Eletrólise , Compostos de Manganês , Óxidos , Eliminação de Resíduos Líquidos , Águas Residuárias
10.
Sci Total Environ ; 778: 146203, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33711594

RESUMO

Vertical flow constructed wetlands (VF CWs) are widely applied for treating eutrophic water due to prominent advantages in economy and ecology. Natural inorganic particles are ubiquitous in contaminated water and the accumulation of inorganic particles takes place spontaneously in VF CWs. To reveal how the accumulation of inorganic particles affects the transport and transformation of phosphorus (P) and nitrogen (N) in VF CWs, column experiments with and without inorganic particle loading were conducted for over 180 days. The morphology and mass balance of P and N, microbial community structure and hydraulic characteristics of VF CWs were investigated. The average total phosphorus (TP) and total nitrogen (TN) removal efficiencies in VF CWs with inorganic particle loading were steady at 90.4 ± 1.9% and 87.8 ± 2.3%, respectively. Inorganic particle accumulation improved TP removal mainly via adsorption and plant uptake, while enhanced TN removal was mainly attributed to higher plant uptake and microbial degradation. Of particular interest was that plant biomass production was doubled by the concentrated nutrients (e.g., bioavailable P and N) in the rhizosphere, accompanied by the accumulation of inorganic particles up to 9.5 g L-1. Accumulated particles increased the bacterial abundance by 7.7-fold, and the diversity of the bacterial community associated with P and N transformations was significantly enhanced (p < 0.05). 31P NMR and P fractionation revealed that the elevated P proportion in the substrate was mainly in the form of iron-bound inorganic P. Moreover, inorganic particle accumulation decreased the substrate hydraulic conductivity, while it showed limited effect on the reduction of the hydraulic retention time.

11.
Sci Total Environ ; 780: 146637, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33774296

RESUMO

Pharmaceuticals and personal care products (PPCPs) cause ongoing water pollution and consequently have attracted wide attention. Constructed wetlands (CWs) show good PPCP removal performance through combined processes of substrates, plants, and microorganisms; however, most published research focuses on the role of substrates and microorganisms. This review summarizes the direct and indirect roles of wetland plants in PPCP removal, respectively. These direct effects include PPCP precipitation on root surface iron plaque, and direct absorption and degradation by plants. Indirect effects, which appear more significant than direct effects, include enhancement of PPCP removal through improved rhizosphere microbial activities (more than twice as much as bulk soil) stimulated by radial oxygen loss and exudate secretions, and the formation of supramolecular ensembles from PPCPs and humic acids from decaying plant materials which improving PPCPs removal efficiency by up to four times. To clarify the internal mechanisms of PPCP removal by plants in CWs, factors affecting wetland plant performance were reviewed. Based on this review, future research needs have been identified.

12.
Chin J Nat Med ; 19(3): 181-187, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33781451

RESUMO

Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi, are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron mollefruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2-O-methylrhodojaponin (3), and 5'-ß-D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg-1·d-1) significantly alleviated the symptoms of rheumatoid arthritis, similar to tripterygium polyglycosides, an effective RA therapy. Preliminary mechanism studies indicated that diterpenoid fraction significantly inhibited the abnormal proliferation of T and B lymphocytes, and remarkably reduced the levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α. Overall, our findings may provide a more effective and safe alternative treatment for RA using common clinical Chinese medicines like tripterygium polyglycosides.

13.
Sci Rep ; 11(1): 5846, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712668

RESUMO

Ambulatory blood pressure monitoring (ABPM) can produce many variables, of which the lowest nocturnal systolic blood pressure (LNSBP) currently used in calculating morning surge is occasionally overlooked in recent kidney studies compared with other ABPM parameters. We explored the clinical effects of LNSBP in elderly patients with chronic kidney disease (CKD) in a multicenter, observational cohort study. A total of 356 elderly patients with CKD from 19 clinics were included in this analysis. We used multiple logistic regression and survival analyses to assess the associations between the lowest nocturnal systolic blood pressure and heavy proteinuria and kidney disease outcomes, respectively. The median age was 66 years, and 66.6% were men. The median eGFR was 49.2 ml/min/1.73 m2. Multivariate logistic regression analysis demonstrated that LNSBP (OR 1.24; 95% CI 1.10-1.39; P < 0.001; per 10 mmHg) was associated with heavy proteinuria. During the median follow-up of 23 months, 70 patients (19.7%) had a composite outcome; of these, 25 initiated dialysis, 25 had 40% eGFR loss, and 20 died. Cox analysis showed that the renal risk of LNSBP for CKD outcomes remained significant even after adjusting for background factors, including age, sex, medical history of hypertension and diabetes, smoking status, eGFR, 24-h proteinuria, and etiology of CKD (HR 1.18; 95% CI 1.06-1.32; P = 0.002; per 10 mmHg). Concentrating on LNSBP could be valuable in guiding antihypertensive treatment to control heavy proteinuria and improve renal prognosis in elderly CKD patients.

14.
Waste Manag ; 126: 247-257, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33780704

RESUMO

Accurate waste classification is key to successful waste management. However, most current studies have focused exclusively on single-label waste classification from images, which goes against common sense. In this paper, we move beyond single-label waste classification and propose a benchmark for evaluating the multi-label waste classification and localization tasks to advance waste management via deep learning-based methods. We propose a multi-task learning architecture (MTLA) based on a convolutional neural network, which can be used to simultaneously identify and locate wastes in images. The MTLA comprises a backbone network with proposed attention modules, a novel multi-level feature pyramid network, and a group of joint learning multi-task subnets. To achieve joint optimization of waste identification and location, we designed the loss functions according to the concepts of focusing and joint. The proposed MTLA achieved performance similar to that of experts and had high scores for multiple tasks related to waste management. Its F1 score exceeded 95.50% (95.12% to 95.88%, with a 95% confidence interval) on the multi-label waste classification task, and the average precision score was over 81.50% (@IoU = 0.5) on the waste localization task. To improve interpretation, heatmaps were used to visualize the salient features extracted by the MTLA. The proposed MTLA is a promising auxiliary tool that can improve the automation of waste management systems.

15.
J Anim Sci ; 99(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33687436

RESUMO

Mitochondria play an important role in controlling oocyte developmental competence. Our previous studies showed that glycine (Gly) can regulate mitochondrial function and improve oocyte maturation in vitro. However, the mechanisms by which Gly affects mitochondrial function during oocyte maturation in vitro have not been fully investigated. In this study, we induced a mitochondrial damage model in oocytes with the Bcl-2-specific antagonist ABT-199. We investigated whether Gly could reverse the mitochondrial dysfunction caused by ABT-199 exposure and whether it is related to calcium regulation. Our results showed that ABT-199 inhibited cumulus expansion, decreased the oocyte maturation rate and the intracellular glutathione (GSH) level, caused mitochondrial dysfunction, which was confirmed by decreased mitochondrial membrane potential (ΔΨm) and the expression of mitochondrial function-related genes PGC-1α, and increased reactiveoxygenspecies (ROS) levelsand the expression of apoptosis-associated genes Bax, Caspase-3, and Cyto C.More importantly, ABT-199-treated oocytes showed an increase in the intracellular free calcium concentration ([Ca2+]i) and had impaired cortical type 1 inositol 1,4,5-trisphosphate receptors (IP3R1) distribution. Nevertheless, treatment with Gly significantly ameliorated mitochondrial dysfunction, oxidative stress, and apoptosis, and Gly also regulated [Ca2+]i levels and IP3R1 cellular distribution, which further protects oocyte maturation in ABT-199-induced porcine oocytes.Taken together, our results indicate that Gly has a protective action against ABT-199-induced mitochondrial dysfunction in porcine oocytes.


Assuntos
Glicina , Oócitos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Glicina/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Mitocôndrias , Oócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sulfonamidas , Suínos
16.
J Clin Hypertens (Greenwich) ; 23(4): 823-830, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33523570

RESUMO

Our study aimed to explore the intercorrelations of brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI), ambulatory arterial stiffness index (AASI), 24-hour mean pulse pressure (24-h   PP), and augmentation index (AIx, AIx@75, the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49-65) years and 50.5 (35.5-84.1) ml/min/1.73 m2 , respectively. In Pearson correlation analysis, baPWV was significantly associated with 24-h  PP (r = .531, p < .001), AIx@75 (r = .306, p < .001). Additionally, 24-h  PP was associated with AASI (r = .507, p < .001) and AIx@75 (r = .217, p = .019). During follow-up for a median of 25 months, 26.5% (n = 31) of patients had a composite outcome; of these, 10 initiated dialysis, 17 had 40% eGFR loss, and 4 died. Increased AASI, 24-h  PP, and baPWV were associated with poor renal outcomes in a univariate Cox analysis. After adjusting for age, sex, MAP, eGFR, and 24 hours proteinuria, 1-SD increase in AASI and 24-h  PP was associated with renal outcomes. The ROC analysis yielded the largest area under the curve (AUC) of 0.727 (95% CI: 0.624 to 0.831; p < .001) for 24  -h PP. When the Youden's index was at its maximum, the 24-h PP value was 52 mmHg. In conclusion, 24-h  PP, baPWV, and AIx@75 were linked well to one another. Arterial stiffness is a target for delaying the decline in kidney function. The use of 24-h  PP as an arterial stiffness marker should be valued in CKD clinical practice.

17.
Pestic Biochem Physiol ; 172: 104766, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518053

RESUMO

According to the pharmacophore binding strategy and principle of bioelectronic isobaric, used the sulfonylurea bridge as the parent structure, a series of novel thiourea compounds containing aromatic-substituted pyrimidines were designed and synthesized. The preliminary herbicidal activity tests showed that some compounds had good herbicidal activity against Digitaria adscendens, Amaranthus retroflexus, especially for compound 4d and 4f. The results showed that compound 4d had an inhibition rate of 81.5% on the root growth of Brassica napus L. at the concentration of 100 mg L-1, and compound 4f had an inhibition rate of 81% on the root growth of Digitaria adscendens at the concentration of 100 mg L-1. Compounds 4d and 4f had higher comparative activity on Echinochloa crus-galli than the commercial herbicide bensulfuron-methyl. The preliminary structure-activity relationship (SAR) was also summarized. We also tested the in vivo AHAS enzyme activity inhibition experiment of 14 compounds at 100 mg L-1, and the results showed that they all have inhibitory activity on the enzyme, with the highest inhibition rate reaching 44.4% (compound 4d). Based on the results of molecular docking to yeast acetohydroxyacid synthase (AHAS), the possible herbicidal activity mechanism of these compounds was evaluated.


Assuntos
Acetolactato Sintase , Herbicidas , Acetolactato Sintase/metabolismo , Herbicidas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Tioureia/farmacologia
18.
Mol Neurobiol ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629272

RESUMO

Alzheimer's disease (AD) is the most common neurodegenerative disease in the older adults. Although much effort has been made in the analyses of diagnostic biomarkers, such as amyloid-ß, tau, and neurofilament light chain, identifying peripheral blood-based biomarkers is in extremely urgent need for their minimal invasiveness and more convenience. Here we characterized the miRNA profile by RNA sequencing in human serum exosomes from AD patients and healthy controls (HC) to investigate its potential for AD diagnosis. Subsequently, Gene Ontology analysis and pathway analysis were performed for the targeted genes from the differentially expressed miRNAs. These basic functions were differentially enriched, including cell adhesion, regulation of transcription, and the ubiquitin system. Functional network analysis highlighted the pathways of proteoglycans in cancer, viral carcinogenesis, signaling pathways regulating pluripotency of stem cells, and cellular senescence in AD. A total of 24 miRNAs showed significantly differential expression between AD and HC with more than ± 2.0-fold change at p value < 0.05 and at least 50 reads for each sample. Logistic regression analysis established a model for AD prediction by serum exosomal miR-30b-5p, miR-22-3p, and miR-378a-3p. Sequencing results were validated using quantitative reverse transcription PCR. The data showed that miR-30b-5p, miR-22-3p, and miR-378a-3p were significantly deregulated in AD, with area under the curve (AUC) of 0.668, 0.637, and 0.718, respectively. The combination of the three miRs gained a better diagnostic capability with AUC of 0.880. This finding revealed a miR panel as potential biomarker in the peripheral blood to distinguish AD from HC.

19.
Cell ; 184(3): 775-791.e14, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33503446

RESUMO

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.


Assuntos
/metabolismo , Regulação da Expressão Gênica , Proteoma/biossíntese , Proteômica , /metabolismo , Autopsia , /terapia , Feminino , Humanos , Masculino , Especificidade de Órgãos
20.
Small ; 17(6): e2005728, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33470521

RESUMO

In order to achieve better antitumor therapeutic efficacy and inhibit tumor metastasis, a multifunctional nanovaccine based on L-arginine (LA)-loaded black mesoporous titania (BMT) is fabricated. In this system, LA is utilized as the exogenous NO supplementation for gas therapy, and BMT is served as acoustic sensitizer for sonodynamic therapy. The ultrasound (US) as the exogenous stimulus can simultaneously trigger BMT and LA to produce singlet oxygen (1 O2 ) and NO gas at tumor sites, respectively. Interestingly, 1 O2 from US-excited BMT can promote the oxidation of LA to produce more NO. The high concentration of 1 O2 and NO in cancer cell can cause intracellular strong oxidative stress level and DNA double-strand breaks to induce cancer cell apoptosis ultimately. The US-triggered BMT@LA "nanovaccine" combining with immune checkpoint inhibitor PD-L1 antibody (αPD-L1) can induce strong antitumor immune response thus effectively killing primary tumors and further inhibiting metastatic tumors. Hence, BMT@LA-based "nanovaccine" combining with αPD-L1 checkpoint blockade treatment can realize synergetic sonodynamic/gas/immunotherapy with enhanced antitumor therapeutic effects.

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