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1.
ACS Nano ; 18(33): 22139-22152, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39110572

RESUMO

Periodontitis, with its persistent nature, causes significant distress for most sufferers. Current treatments, such as mechanical cleaning and surgery, often fail to fully address the underlying overactivation of fibroblasts that drives this degradation. Targeting the post-transcriptional regulation of fibroblasts, particularly at the 3'-untranslated regions (3'UTR) of pathogenic genes, offers a therapeutic strategy for periodontitis. Herein, we developed a DNA nanorobot for this purpose. This system uses a dynamic DNA nanoframework to incorporate therapeutic microRNAs through molecular recognition and covalent bonds, facilitated by DNA monomers modified with disulfide bonds. The assembled-DNA nanoframework is encapsulated in a cell membrane embedded with a fibroblast-targeting peptide. By analyzing the 3'UTR regions of pathogenic fibroblast genes FOSB and JUND, we identified the therapeutic microRNA as miR-1-3p and integrated it into this system. As expected, the DNA nanorobot delivered the internal components to fibroblasts by the targeting peptide and outer membrane that responsively releases miR-1-3p under intracellular glutathione. It resulted in a precise reduction of mRNA and suppression of protein function in pathogenic genes, effectively reprogramming fibroblast behavior. Our results confirm that this approach not only mitigates the inflammation but also promotes tissue regeneration in periodontal models, offering a promising therapeutic avenue for periodontitis.


Assuntos
Regiões 3' não Traduzidas , DNA , Fibroblastos , MicroRNAs , Periodontite , Periodontite/genética , Periodontite/patologia , Fibroblastos/metabolismo , Regiões 3' não Traduzidas/genética , DNA/química , DNA/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Animais , Camundongos
2.
Fundam Res ; 4(2): 291-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38933506

RESUMO

The photogenerated charge carrier separation and transportation of inside photocathodes can greatly influence the performance of photoelectrochemical (PEC) H2 production devices. Coupling TiO2 with p-type semiconductors to construct heterojunction structures is one of the most widely used strategies to facilitate charge separation and transportation. However, the band position of TiO2 could not perfectly match with all p-type semiconductors. Here, taking antimony selenide (Sb2Se3) as an example, a rational strategy was developed by introducing a viologen electron transfer mediator (ETM) containing polymeric film (poly-1,1'-dially-[4,4'-bipyridine]-1,1'-diium, denoted as PV2+) at the interface between Sb2Se3 and TiO2 to regulate the energy band alignment, which could inhibit the recombination of photogenerated charge carriers of interfaces. With Pt as a catalyst, the constructed Sb2Se3/PV2+/TiO2/Pt photocathode showed a superior PEC hydrogen generation activity with a photocurrent density of -18.6 mA cm-2 vs. a reversible hydrogen electrode (RHE) and a half-cell solar-to-hydrogen efficiency (HC-STH) of 1.54% at 0.17 V vs. RHE, which was much better than that of the related Sb2Se3/TiO2/Pt photocathode without PV2+ (-9.8 mA cm-2, 0.51% at 0.10 V vs. RHE).

3.
Chem Commun (Camb) ; 60(24): 3319-3322, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38433668

RESUMO

For photoelectrochemical NADH regeneration, an electrode-supported "lipid bilayer membrane" photocathode based on a p-Si semiconductor, an electron transport mediator (OBV2+), and a [Rh(Cp*)(bpy)Cl]+ catalyst was constructed by self-assembly. Mechanistic study shows that OBV2+ can enhance the charge transfer between the semiconductor and catalyst, leading to a significant improvement of the NADH photo-regeneration rate.

4.
ACS Nano ; 17(23): 23679-23691, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37983051

RESUMO

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.


Assuntos
Cicatrização , Infecção dos Ferimentos , Animais , Materiais Biocompatíveis , Antibacterianos/farmacologia , Proteínas de Insetos/farmacologia , Insetos , Hidrogéis
5.
Curr Pharm Des ; 29(27): 2161-2176, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37694785

RESUMO

BACKGROUND: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. OBJECTIVE: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. METHODS: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. RESULTS: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. CONCLUSION: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

6.
Nat Commun ; 14(1): 4491, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495582

RESUMO

Electrocatalytic urea synthesis is an emerging alternative technology to the traditional energy-intensive industrial urea synthesis protocol. Novel strategies are urgently needed to promote the electrocatalytic C-N coupling process and inhibit the side reactions. Here, we report a CuWO4 catalyst with native bimetallic sites that achieves a high urea production rate (98.5 ± 3.2 µg h-1 mg-1cat) for the co-reduction of CO2 and NO3- with a high Faradaic efficiency (70.1 ± 2.4%) at -0.2 V versus the reversible hydrogen electrode. Mechanistic studies demonstrated that the combination of stable intermediates of *NO2 and *CO increases the probability of C-N coupling and reduces the potential barrier, resulting in high Faradaic efficiency and low overpotential. This study provides a new perspective on achieving efficient urea electrosynthesis by stabilizing the key reaction intermediates, which may guide the design of other electrochemical systems for high-value C-N bond-containing chemicals.

7.
Animals (Basel) ; 13(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37443959

RESUMO

pH was one of the important meat quality traits, which was an important factor affecting the storage/shelf life and quality of meat in meat production. In order to find a way to extend the storage/shelf life, the pH values (pH45min, pH24h, pH48h and pH72h) of the longissimus dorsi muscles in F2 individuals of 462 Texel sheep × Altay sheep were determined, genotyping was performed using Illumina Ovine SNP 600 K BeadChip and whole genome resequencing technology, a genome-wide association analysis (GWAS) was used to screen the candidate genes and molecular markers for pH values related to the quality traits of mutton, and the effects of population stratification were detected by Q-Q plots. The results showed that the pH population stratification analysis did not find significant systemic bias, and there was no obvious population stratification effect. The results of the association analysis showed that 28 SNPs significantly associated with pH reached the level of genomic significance. The candidate gene associated with pH45min was identified as the CCDC92 gene by gene annotation and a search of the literature. Candidate genes related to pH24h were KDM4C, TGFB2 and GOT2 genes. The candidate genes related to pH48h were MMP12 and MMP13 genes. The candidate genes related to pH72h were HILPDA and FAT1 genes. Further bioinformatics analyses showed 24 gene ontology terms and five signaling pathways that were significantly enriched (p ≤ 0.05). Many terms and pathways were related to cellular components, processes of protein modification, the activity of protein dimerization and hydrolase activity. These identified SNPs and genes could provide useful information about meat and the storage/shelf life of meat, thereby extending the storage/shelf life and quality of meat.

8.
J Hazard Mater ; 457: 131763, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37311294

RESUMO

Antibiotic resistance is a pressing global health issue, leading to increased illnesses and fatalities. The contribution of viruses to the acquisition, preservation, and dissemination of antibiotic resistance genes (ARGs) is not yet fully understood. By using a high-throughput functional gene-based microarray (GeoChip 5.0), this study examines the prevalence and relative abundance of bacteriophage and eukaryotic viral genes in swine manure, compost, compost-amended agricultural soil, and unamended soil from suburban regions of Beijing, China. Our findings reveal a significantly elevated presence of biomarker viral genes in compost-amended soils compared to unamended soils, suggesting potential health risks associated with compost fertilization. We also observed stronger ecological interactions between ARGs and viral genes in manure and compost than in soils. Network analysis identified arabinose efflux permeases and EmrB/QacA resistance genes, linked to CRISPR encoding sequences, as keystone nodes, indicating possible ARG acquisition via virus infections. Moreover, positive correlations were found between viral genes, antibiotic concentrations, and ARG diversity in manure, compost, and compost-amended soils, highlighting a likely pathway for virus-mediated ARG transfer. In summary, our results indicate that use of compost as a fertilizer in agricultural settings could facilitate the spread of ARGs through viral mechanisms, allowing for time-delayed genetic exchanges over broader temporal and spatial scales than ARGs within bacterial genomes.


Assuntos
Antibacterianos , Compostagem , Animais , Suínos , Antibacterianos/farmacologia , Viroma , Genes Bacterianos , Esterco/microbiologia , Solo , Microbiologia do Solo , Fertilização
9.
Aging Dis ; 14(5): 1555-1582, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196112

RESUMO

Bone is a tissue that is active throughout the lifespan, and its physiological activities, such as growth, development, absorption, and formation, are always ongoing. All types of stimulation that occur in sports play an important role in regulating the physiological activities of bone. Here, we track the latest research progress locally and abroad, summarize the recent, relevant research results, and systematically summarize the effects of different types of exercise on bone mass, bone strength and bone metabolism. We found that different types of exercise have different effects on bone health due to their unique technical characteristics. Oxidative stress is an important mechanism mediating the exercise regulation of bone homeostasis. Excessive high-intensity exercise does not benefit bone health but induces a high level of oxidative stress in the body, which has a negative impact on bone tissue. Regular moderate exercise can improve the body's antioxidant defense ability, inhibit an excessive oxidative stress response, promote the positive balance of bone metabolism, delay age-related bone loss and deterioration of bone microstructures and have a prevention and treatment effect on osteoporosis caused by many factors. Based on the above findings, we provide evidence for the role of exercise in the prevention and treatment of bone diseases. This study provides a systematic basis for clinicians and professionals to reasonably formulate exercise prescriptions and provides exercise guidance for patients and the general public. This study also provides a reference for follow-up research.

10.
Biomolecules ; 13(2)2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36830672

RESUMO

BACKGROUND: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. METHODS: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. RESULTS: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). CONCLUSIONS: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.


Assuntos
Biologia Computacional , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Estimativa de Kaplan-Meier , Neoplasias de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Microambiente Tumoral
11.
Clin Exp Med ; 23(6): 2341-2356, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36242643

RESUMO

Breast cancer was the fourth leading cause of cancer-related death worldwide, and early mammography screening could decrease the breast cancer mortality. Artificial intelligence (AI)-assisted diagnose system based on machine learning (ML) methods can help improve the screening accuracy and efficacy. This study aimed to systematically review and make a meta-analysis on the diagnostic accuracy of mammography diagnosis of breast cancer through various ML methods. Springer Link, Science Direct (Elsevier), IEEE Xplore, PubMed and Web of Science were searched for relevant studies published from January 2000 to September 2021. The study was registered with the PROSPERO International Prospective Register of Systematic Reviews (protocol no. CRD42021284227). A Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess the included studies, and reporting was evaluated using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The pooled summary estimates for sensitivity, specificity, the area under the receiver operating characteristic curve (AUC) for three ML methods (convolutional neural network [CNN], artificial neural network [ANN], support vector machine [SVM]) were calculated. A total of 32 studies with 23,804 images were included in the meta-analysis. The overall pooled estimate for sensitivity, specificity and AUC was 0.914 [95% CI 0.868-0.945], 0.916 [95% CI 0.873-0.945] and 0.945 for mammography diagnosis of breast cancer through three ML methods. The pooled sensitivity, specificity and AUC of CNN were 0.961 [95% CI 0.886-0.988], 0.950 [95% CI 0.924-0.967] and 0.974. The pooled sensitivity, specificity and AUC of ANN were 0.837 [95% CI 0.772-0.886], 0.894 [95% CI 0.764-0.957] and 0.881. The pooled sensitivity, specificity and AUC of SVM were 0.889 [95% CI 0.807-0.939], 0.843 [95% CI 0.724-0.916] and 0.913. Machine learning methods (especially CNN) show excellent performance in mammography diagnosis of breast cancer screening based on retrospective studies. More rigorous prospective studies are needed to evaluate the longitudinal performance of AI.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Inteligência Artificial , Estudos Retrospectivos , Detecção Precoce de Câncer , Mamografia/métodos , Aprendizado de Máquina
12.
Zhonghua Nan Ke Xue ; 29(5): 387-392, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-38602753

RESUMO

OBJECTIVE: To investigate the expression of Zfx gene in spermatogenic cells. METHODS: The testes of d6, d8, d17 and adult mice were collected, single cell suspension was prepared by combinatorial enzyme digestion, spermatogenic cells were isolated by BSA density gradient method, and Zfx expression was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western Blot (WB). RESULTS: Single cell suspension prepared by combination enzyme digestion method and density gradient method laid with BSA can obtain various types of spermatogenic cells with purity>85%; The expression level of the Zfx gene is low in primitive type A spermatogonia, type A spermatogonia, and type B spermatogonia, whereas it is high in preleptotene spermatocytes, pachytene spermatocytes, and round spermatid cells. It is not expressed in elongating spermatids and mature sperm. CONCLUSION: Zfx gene exhibits periodic expression in various levels of spermatogenic cells and may be an important transcription factor involved in regulating meiosis in spermatogenic cells.


Assuntos
Sêmen , Espermatozoides , Animais , Masculino , Camundongos , Western Blotting , Meiose , Espermátides
13.
Neurochem Res ; 47(12): 3647-3658, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35790697

RESUMO

The mechanism underlying moderate ethanol (EtOH)-preconditioning (PC) against ischemic brain injury remains unclear. We evaluated the role of large conductance calcium-sensitive potassium (BKCa) channels in EtOH-PC. Almost one hundred and ninety normal adult SD rats (8 to 10 weeks, 320-350 g) were enrolled in this study. Ischemic/reperfusion (I/R) brain injury was induced in rats by middle cerebral artery occlusion for 2 h followed by reperfusion for 24 h. EtOH or the BKCa channel opener, NS11021, was administered 24 h before I/R with or without pre-treatment with the BKCa channel blocker, paxilline. Infarct volumes were measured by tissue staining and imaging, and neurological functions were assessed by a scoring system. The expression of BKCa channel subunit α was detected by Western blotting, and cell apoptosis was assessed using staining. Prior (24 h) administration of ethanol that produced a peak plasma concentration of ~ 45 mg/dl in rats would offer neuroprotection after cerebral I/R. In addition, the expression of BKCa channel α-subunit was significantly increased 24 h after EtOH-PC (n = 10; control: 2.00 ± 0.09, EtOH: 1.00 ± 0.06; P < 0.5). Compared to I/R, EtOH-PC enhanced the expression of BKCa channel α-subunit both in the penumbra (n = 10; 24 h: I/R: 1.25 ± 0.10, EtOH-PC + I/R: 1.99 ± 0.12; P < 0.01; 4 h: I/R: 1.03 ± 0.03, EtOH-PC + I/R: 1.49 ± 0.05; P < 0.001) and infarct core (n = 10; 4 h: I/R: 1.04 ± 0.04, EtOH-PC + I/R: 1.42 ± 0.05; P < 0.001), improved the neurological function (n = 10; I/R: 14.00 (12.75-15.00), EtOH-PC + I/R: 7.00 (4.75-8.25); P < 0.001), attenuated the apoptosis (n = 10; I/R: 26.80 ± 0.69, EtOH-PC + I/R: 8.46 ± 0.31; P < 0.001), and decreased the infarct volume (n = 10; I/R: 244.00 ± 26.24, EtOH-PC + I/R: 70.09 ± 14.69; P < 0.001) after experimental cerebral I/R. These changes were reversed by paxilline administration. The moderate EtOH-PC protects against I/R-induced brain damage dependent on the upregulation BKCa channels.


Assuntos
Lesões Encefálicas , Canais de Potássio Ativados por Cálcio de Condutância Alta , Ratos , Animais , Etanol/toxicidade , Ratos Sprague-Dawley , Reperfusão , Infarto da Artéria Cerebral Média
14.
Dis Markers ; 2022: 8602068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35726234

RESUMO

Glioblastoma multiforme (GBM) is a prevalent intracranial brain tumor associated with a high rate of recurrence and treatment difficulty. The prediction of novel molecular biomarkers through bioinformatics analysis may provide new clues into early detection and eventual treatment of GBM. Here, we used data from the GTEx and TCGA databases to identify 1923 differentially expressed genes (DEGs). GO and KEGG analyses indicated that DEGs were significantly enriched in immune response and coronavirus disease-COVID-19 pathways. Survival analyses revealed a significant correlation between high expression of C1R, CCL2, and TNFRSF1A in the coronavirus disease-COVID-19 pathway and the poor survival in GBM patients. Cell experiments indicated that the mRNA expression levels of C1R, CCL2, and TNFRSF1A in GBM cells were very high. Immune infiltration analysis revealed a significant difference in the proportion of immune cells in tumor and normal tissue, and the expression levels of C1R, CCL2, and TNFRSF1A were associated with immune cell infiltration of GBM. Additionally, the protein-protein interaction networks of C1R, CCL2, and TNFRSF1A involved a total of 65 nodes and 615 edges. These results suggest that C1R, CCL2, and TNFRSF1A may be used as molecular biomarkers of prognosis and immune infiltration in GBM patients in the future.


Assuntos
Neoplasias Encefálicas , COVID-19 , Quimiocina CCL2 , Complemento C1r , Glioblastoma , Receptores Tipo I de Fatores de Necrose Tumoral , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , COVID-19/genética , Quimiocina CCL2/genética , Complemento C1r/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioblastoma/diagnóstico , Glioblastoma/patologia , Humanos , Prognóstico , Receptores Tipo I de Fatores de Necrose Tumoral/genética
15.
Anal Chim Acta ; 1214: 339963, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35649641

RESUMO

Perylene diimide derivatives (PDIs) are suitable ECL luminophore candidates with low triggering potentials and strong ECL signals for fundamental studies and practical applications. However, PDIs tend to aggregate, which affects their optical properties and limits their application in bio-imaging and bio-sensing fields. In this study, an ECL sensor is fabricated based on the layer-by-layer (LBL) assembly of N, N-bis(phosphonomethyl)-3,4,9,10-perylene diimide (PMPDI) and ZrIV ions on the surface of a mesoporous indium tin oxide (ITO) substrate. When six layers of PMPDI are immobilized on ITO, the resulting PMPDI6/ITO electrode shows maximum ECL intensity with K2S2O8 as a co-reactant in the potential range 0 to -0.5 V vs. Ag/AgCl. LBL assembly decreases the aggregation and increases the loading of PMPDI on the mesoporous ITO substrate, which stabilizes and amplifies the ECL signals. The ECL method exhibits excellent sensitivity and selectivity with good stability and reproducibility, when used to detect dopamine (DA) under optimal experimental conditions.


Assuntos
Perileno , Dopamina , Eletrodos , Medições Luminescentes/métodos , Perileno/química , Reprodutibilidade dos Testes
16.
Cell Prolif ; 55(5): e13223, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35437845

RESUMO

OBJECTIVES: This study investigated the ability of immunity- and matrix- regulatory cells (IMRCs) to improve cognitive function in a rat model of vascular cognitive impairment. MATERIALS AND METHODS: A chronic cerebral hypoperfusion (CCH) model was established in rats via permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO). The rats then received intravenous injections of IMRCs or saline. A single injection of different doses of IMRCs (1 × 106 cells/rat, 2 × 106 cells/rat, or 4 × 106 cells/rat) was administered via tail vein 72 h after establishment of the model. To evaluate functional recovery, the rats were subjected to behavioural tests after 30 days of CCH. Imaging, western blotting, immunofluorescence staining, and quantitative real-time PCR were used to analyse neuroinflammation and white matter injury after 14 and 40 days of CCH. RNA sequencing (RNA-seq) was used to profile gene expression changes in copine 1 (CPNE1) in response to IMRCs treatment. RESULTS: Intravenous injection of 4 × 106 IMRCs alleviated white matter damage and ameliorated cognitive deficits in rats subjected to CCH. Immunofluorescence staining suggested that activation of microglia and astrocytes was reduced, and RNA sequencing showed that CPNE1 expression was significantly elevated following treatment with IMRCs. CONCLUSIONS: Intravenous injection of IMRCs protected against CCH-induced white matter injury and cognitive impairment inhibition of microglial activation and regulation of microglia polarization.


Assuntos
Isquemia Encefálica , Disfunção Cognitiva , Substância Branca , Animais , Cognição , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Humanos , Microglia/metabolismo , Ratos , Substância Branca/metabolismo
17.
mLife ; 1(4): 448-459, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38818483

RESUMO

Identification, sorting, and sequencing of individual cells directly from in situ samples have great potential for in-depth analysis of the structure and function of microbiomes. In this work, based on an artificial intelligence (AI)-assisted object detection model for cell phenotype screening and a cross-interface contact method for single-cell exporting, we developed an automatic and index-based system called EasySort AUTO, where individual microbial cells are sorted and then packaged in a microdroplet and automatically exported in a precisely indexed, "One-Cell-One-Tube" manner. The target cell is automatically identified based on an AI-assisted object detection model and then mobilized via an optical tweezer for sorting. Then, a cross-interface contact microfluidic printing method that we developed enables the automated transfer of cells from the chip to the tube, which leads to coupling with subsequent single-cell culture or sequencing. The efficiency of the system for single-cell printing is >93%. The throughput of the system for single-cell printing is ~120 cells/h. Moreover, >80% of single cells of both yeast and Escherichia coli are culturable, suggesting the superior preservation of cell viability during sorting. Finally, AI-assisted object detection supports automated sorting of target cells with high accuracy from mixed yeast samples, which was validated by downstream single-cell proliferation assays. The automation, index maintenance, and vitality preservation of EasySort AUTO suggest its excellent application potential for single-cell sorting.

18.
Curr Alzheimer Res ; 18(14): 1077-1086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34911423

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease that has been characterized by progressive development of long onset early disease with complicated etiology and may cause memory loss, cognitive impairment, and behavioral changes. Physical exercise may play a preventive role in AD. In the present study, we investigated the impact of longer-term physical exercise on the finger tapping of AD patients by comparing the finger tapping of AD patients and healthy controls. METHODS: In this study, 140 subjects aged ≥ 60 years were enrolled. Group A consisted of 70 subjects (27 males and 43 females) without exercise habits who were selected from Yangpu District (Shanghai, China). Group B consisted of 70 subjects (27 males and 43 females) who were selected from Minxing District (Shanghai, China). All the subjects were right-handed as well. The subjects' data, including subjects' age, weight, height, Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and finger tapping frequency, were measured. RESULTS: The subjects were matched in age, weight, and height. The AD subjects' MoCA and MMSE scores were noticeably lower than healthy subjects' scores (P<0.001); besides, AD patients with exercise had significantly lower MoCA and MMSE scores than healthy controls with exercise (P<0.001). The finger tapping of AD subjects' left hands was significantly lower than that of healthy subjects without AD (P<0.01), and AD subjects with exercise tapped significantly slower with their left hand than healthy subjects with exercise (P<0.01). Meanwhile, AD subjects with exercise tapped significantly faster with the left hand than AD subjects (P<0.05). The right hands of AD subjects tapped remarkably less than healthy subjects (P<0.01) with or without exercise. Meanwhile, subjects with exercise tapped significantly faster with their right hand than healthy subjects (P<0.05), and AD subjects with exercise tapped significantly faster with their right hand than AD subjects (P<0.05). CONCLUSION: Long-term physical exercises can improve finger tapping frequency, especially in patients with AD. Finger tapping frequency may be used as an index to monitor the cognitive decline in ageing AD patients.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Doença de Alzheimer/diagnóstico , China , Disfunção Cognitiva/diagnóstico , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
19.
Angew Chem Int Ed Engl ; 60(37): 20331-20341, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34245082

RESUMO

The multimetallic sulfur-framework catalytic site of biological nitrogenases allows the efficient conversion of dinitrogen (N2 ) to ammonia (NH3 ) under ambient conditions. Inspired by biological nitrogenases, a bimetallic sulfide material (FeWSx @FeWO4 ) was synthesized as a highly efficient N2 reduction (NRR) catalyst by sulfur substitution of the surface of FeWO4 nanoparticles. Thus prepared FeWSx @FeWO4 catalysts exhibit a relatively high NH3 production rate of 30.2 ug h-1 mg-1cat and a Faraday efficiency of 16.4 % at -0.45 V versus a reversible hydrogen electrode in a flow cell; these results have been confirmed via purified 15 N2 -isotopic labeling experiments. In situ Raman spectra and hydrazine reduction kinetics analysis revealed that the reduction of undissociated hydrazine intermediates (M-NH2 -NH2 ) on the surface of the bimetallic sulfide catalyst is the rate-determing step for the NRR process. Therefore, this work can provide guidance for elucidating the structure-activity relationship of NRR catalysts.

20.
Research (Wash D C) ; 2021: 9851231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954292

RESUMO

Water oxidation is a vital anodic reaction for renewable fuel generation via electrochemical- and photoelectrochemical-driven water splitting or CO2 reduction. Ruthenium complexes, such as Ru-bda family, have been shown as highly efficient water-oxidation catalysts (WOCs), particularly when they undergo a bimolecular O-O bond formation pathway. In this study, a novel Ru(pda)-type (pda2- =1,10-phenanthroline-2,9-dicarboxylate) molecular WOC with 4-vinylpyridine axial ligands was immobilized on the glassy carbon electrode surface by electrochemical polymerization. Electrochemical kinetic studies revealed that this homocoupling polymer catalyzes water oxidation through a bimolecular radical coupling pathway, where interaction between two Ru(pda)-oxyl moieties (I2M) forms the O-O bond. The calculated barrier of the I2M pathway by density-functional theory (DFT) is significantly lower than the barrier of a water nucleophilic attack (WNA) pathway. By using this polymerization strategy, the Ru centers are brought closer in the distance, and the O-O bond formation pathway by the Ru (pda) catalyst is switched from WNA in a homogeneous molecular catalytic system to I2M in the polymerized film, providing some deep insights into the importance of third coordination sphere engineering of the water oxidation catalyst.

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