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1.
J Cell Sci ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622921

RESUMO

Cardiac looping and trabeculation are key processes during cardiac chamber maturation. However, the underlying mechanisms remain incompletely understood. Here, we report the isolation, cloning, and characterization of the proprotein convertase furina from the cardiovascular mutant loft in zebrafish. loft is an ethylnitrosourea-induced mutant and has evident defects in the cardiac outflow tract, heart looping and trabeculation, the craniofacial region, and pharyngeal arch arteries. Positional cloning revealed that furina mRNA was barely detectable in loft mutants, and loft failed to complement the TALEN-induced furina mutant pku338, confirming that furina is responsible for the loft mutant phenotypes. Mechanistic studies demonstrated that Notch reporter Tg(tp1:mCherry) signals were largely eliminated in mutant hearts, while over-expression of NICD partially rescued the mutant phenotypes, probably due to the lack of Furina-mediated cleavage processing of Notch1b proteins, the only Notch receptor expressed in the heart. Together, our data suggest a potential post-translational modification of Notch1b proteins via the proprotein convertase Furina in the heart and unveil the function of the Furina-Notch1b axis in cardiac looping and trabeculation in zebrafish and possibly in other organisms.

2.
Chem Soc Rev ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34611682

RESUMO

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) systems have revolutionized biological and biomedical sciences in many ways. The last few years have also seen tremendous interest in deploying the CRISPR-Cas toolbox for analytical and diagnostic assay development because CRISPR-Cas is one of the most powerful classes of molecular machineries for the recognition and manipulation of nucleic acids. In the short period of development, many CRISPR-enabled assays have already established critical roles in clinical diagnostics, biosensing, and bioimaging. We describe in this review the recent advances and design principles of CRISPR mediated analytical tools with an emphasis on the functional roles of CRISPR-Cas machineries as highly efficient binders and molecular scissors. We highlight the diverse engineering approaches for molecularly modifying CRISPR-Cas machineries and for devising better readout platforms. We discuss the potential roles of these new approaches and platforms in enhancing assay sensitivity, specificity, multiplexity, and clinical outcomes. By illustrating the biochemical and analytical processes, we hope this review will help guide the best use of the CRISPR-Cas toolbox in detecting, quantifying and imaging biologically and clinically important molecules and inspire new ideas, technological advances and engineering strategies for addressing real-world challenges such as the on-going COVID-19 pandemic.

3.
Appl Opt ; 60(29): 9180-9187, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624000

RESUMO

A single-pixel neural network object classification scenario in the sub-Nyquist ghost imaging system is proposed. Based on the neural network, objects are classified directly by bucket measurements without reconstructing images. Classification accuracy can still be maintained at 94.23% even with only 16 measurements (less than the Nyquist limit of 1.56%). A parallel computing scheme is applied in data processing to reduce the object acquisition time significantly. Random patterns are used as illumination patterns to illuminate objects. The proposed method performs much better than existing methods for both binary and grayscale images in the sub-Nyquist condition, which is also robust to environment noise turbulence. Benefiting from advantages of ghost imaging, it may find applications for target recognition in the fields of remote sensing, military defense, and so on.

4.
Nat Commun ; 12(1): 5385, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508094

RESUMO

At the nanoscale, elastic strain and crystal defects largely influence the properties and functionalities of materials. The ability to predict the structural evolution of catalytic nanocrystals during the reaction is of primary importance for catalyst design. However, to date, imaging and characterising the structure of defects inside a nanocrystal in three-dimensions and in situ during reaction has remained a challenge. We report here an unusual twin boundary migration process in a single platinum nanoparticle during CO oxidation using Bragg coherent diffraction imaging as the characterisation tool. Density functional theory calculations show that twin migration can be correlated with the relative change in the interfacial energies of the free surfaces exposed to CO. The x-ray technique also reveals particle reshaping during the reaction. In situ and non-invasive structural characterisation of defects during reaction opens new avenues for understanding defect behaviour in confined crystals and paves the way for strain and defect engineering.

5.
BMC Genomics ; 22(1): 690, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551715

RESUMO

BACKGROUND: Miscanthus sinensis Andersson is a perennial grass that exhibits remarkable lignocellulose characteristics suitable for sustainable bioenergy production. However, knowledge of the genetic resources of this species is relatively limited, which considerably hampers further work on its biology and genetic improvement. RESULTS: In this study, through analyzing the transcriptome of mixed samples of leaves and stems using the latest PacBio Iso-Seq sequencing technology combined with Illumina HiSeq, we report the first full-length transcriptome dataset of M. sinensis with a total of 58.21 Gb clean data. An average of 15.75 Gb clean reads of each sample were obtained from the PacBio Iso-Seq system, which doubled the data size (6.68 Gb) obtained from the Illumina HiSeq platform. The integrated analyses of PacBio- and Illumina-based transcriptomic data uncovered 408,801 non-redundant transcripts with an average length of 1,685 bp. Of those, 189,406 transcripts were commonly identified by both methods, 169,149 transcripts with an average length of 619 bp were uniquely identified by Illumina HiSeq, and 51,246 transcripts with an average length of 2,535 bp were uniquely identified by PacBio Iso-Seq. Approximately 96 % of the final combined transcripts were mapped back to the Miscanthus genome, reflecting the high quality and coverage of our sequencing results. When comparing our data with genomes of four species of Andropogoneae, M. sinensis showed the closest relationship with sugarcane with up to 93 % mapping ratios, followed by sorghum with up to 80 % mapping ratios, indicating a high conservation of orthologs in these three genomes. Furthermore, 306,228 transcripts were successfully annotated against public databases including cell wall related genes and transcript factor families, thus providing many new insights into gene functions. The PacBio Iso-Seq data also helped identify 3,898 alternative splicing events and 2,963 annotated AS isoforms within 10 function categories. CONCLUSIONS: Taken together, the present study provides a rich data set of full-length transcripts that greatly enriches our understanding of M. sinensis transcriptomic resources, thus facilitating further genetic improvement and molecular studies of the Miscanthus species.


Assuntos
Saccharum , Transcriptoma , Processamento Alternativo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Poaceae/genética
6.
Trials ; 22(1): 566, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34521466

RESUMO

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with a high incidence and no effective treatment. At present, the targeted therapy of intestinal microbes for NAFLD is highly valued. Lycium barbarum polysaccharide (LBP), as the main active ingredient of Lycium barbarum, is considered to be a new type of prebiotic substance, which can improve NAFLD by regulating the gut microbiota. The purpose of this study is to evaluate the safety and efficacy of LBP supplementation in modulating gut microbiota for NAFLD patients. METHODS: This randomized, double-blind, placebo-control study will be conducted in the physical examination center of the Ningxia Hui Autonomous Region People's Hospital. A total of 50 patients with NAFLD confirmed by abdominal ultrasound, laboratory tests, and questionnaire surveys will be recruited and randomly assigned into the control group (maltodextrin placebo capsules) and the intervention group (LBP supplementation capsules) for 3 months. Neither patients, nor investigators, nor data collectors will know the contents in each capsule and the randomization list. The primary outcome measure is the level of ALT concentration relief after the intervention. Secondary outcomes include gut microbiota abundance and diversity, intestinal permeability, patient's characteristic demographic data and body composition, adverse effects, and compliance from patients. DISCUSSION: LBPs are potential prebiotics with the property of regulating host gut microbiota. Our previous studies have documented that LBP supplement can improve the liver damage and the gut microflora dysbiosis in NAFLD rats. This treatment would provide a more in-depth understanding of the effect of this LBP supplementation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000034740 . Registered on 17 July 2020.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Suplementos Nutricionais , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos
7.
Front Cell Infect Microbiol ; 11: 691092, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490138

RESUMO

Oral microbiota is constantly changing with the host state, whereas the oral microbiome of chronic erythematous candidiasis remains poorly understood. The aim of this study was to compare oral microbial signatures and functional profiling between chronic erythematous candidiasis and healthy subjects. Using shotgun metagenomic sequencing, we analyzed the microbiome in 12 chronic erythematous candidiasis, 12 healthy subjects, and 2 chronic erythematous candidiasis cured by antifungal therapy. We found that the salivary microbiota of chronic erythematous candidiasis was significantly different from that of healthy subjects. Among them, Rothia mucilaginosa and Streptococcus mitis were the most abundant disease-enriched species (Mann-Whitney U-test, P < 0.05). In addition, co-occurrence network analysis showed that C. albicans formed densely connected modules with oral bacterial species and was mainly positive connected to Streptococcus species. Furthermore, we investigated the functional potentials of the microbiome and identified a set of microbial marker genes associated with chronic erythematous candidiasis. Some of these genes enriching in chronic erythematous candidiasis are involved in eukaryotic ribosome, putative glutamine transport system, and cytochrome bc1 complex respiratory unit. Altogether, this study revealed the changes of oral microbial composition, the co-occurrence between C. albicans and oral bacteria, as well as the changes of microbial marker genes during chronic erythematous candidiasis, which provides evidence of oral microbiome as a target for the treatment and prevention of chronic erythematous candidiasis.


Assuntos
Candidíase Bucal , Microbiota , Micrococcaceae , Humanos , Metagenômica
8.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34558637

RESUMO

Parkinson's disease (PD), a common multifactorial neurodegenerative disease, is characterized by irreversible loss of dopaminergic neurons in the substantia nigra. In­depth study of the pathogenesis of PD is of great importance. High­mobility group AT­hook 2 (HMGA2) has been proposed to be implicated with neuronal differentiation and impairment of cognitive function. However, whether HMGA2 plays a role in PD is rarely explored. In the present study, N­methyl­4­phenyl­1,2,3,6­tetrahydropyridine (MPTP)­treated PD mice models and N­methyl­4­ phenylpyridinium (MPP+)­treated SH­SY5Y cell models were established. Reverse transcription­quantitative PCR showed that HMGA2 displayed low levels in brain tissues of MPTP­treated mice and MPP+­treated SH­SY5Y cells. Moreover, HMGA2 overexpression suppressed SH­SY5Y cell apoptosis. Additionally, let­7b­5p bound with HMGA2 3' untranslated region (UTR), and its expression was negatively correlated with HMGA2 level. Moreover, let­7b­5p presented high levels in brain tissues of PD mice and MPP+­treated SH­SY5Y cells, and knockdown of let­7b­5p inhibited SH­SY5Y cell apoptosis. Rescue assays illustrated that HMGA2 neutralized the promotive effects of let­7b­5p mimics on SH­SY5Y cell apoptosis. In conclusion, the present study demonstrated that let­7b­5p contributes to cell apoptosis in PD by targeting HMGA2, which offers a potential theoretical basis for the study of effective therapy in PD.

9.
mBio ; 12(4): e0227221, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465026

RESUMO

How cells exposed to one stress are later able to better survive other types of stress is not well understood. In eukaryotic organisms, physiological and pathological stresses can disturb endoplasmic reticulum (ER) function, resulting in "ER stress." Here, we found that exposure to tunicamycin, an inducer of ER stress, resulted in the acquisition of a specific aneuploidy, chromosome 2 trisomy (Chr2x3), in Candida albicans. Importantly, the resulting aneuploidy also conferred cross-tolerance to caspofungin, a first-line echinocandin antifungal, as well as to hydroxyurea, a common chemotherapeutic agent. Exposure to a range of tunicamycin concentrations induced similar ER stress responses. Extra copies of one Chr2 gene, MKK2, affected both tunicamycin and caspofungin tolerance, while at least 3 genes on chromosome 2 (ALG7, RTA2, and RTA3) affected only tunicamycin and not caspofungin responses. Other Chr2 genes (RNR1 and RNR21) affected hydroxyurea tolerance but neither tunicamycin nor caspofungin tolerance. Deletion of components of the protein kinase C (PKC) or calcineurin pathways affected tolerance to both tunicamycin and caspofungin, supporting the idea that the ER stress response and echinocandin tolerance are regulated by overlapping stress response pathways. Thus, antifungal drug tolerance can arise rapidly via ER stress-induced aneuploidy. IMPORTANCE Candida albicans is a prevalent human fungal commensal and also a pathogen that causes life-threatening systemic infections. Treatment failures are frequent because few therapeutic antifungal drug classes are available and because drug resistance and tolerance limit drug efficacy. We found that C. albicans rapidly overcomes the cellular stress induced by the drug tunicamycin by duplicating chromosome 2. Also, chromosome 2 duplication confers tolerance not only to tunicamycin but also to the following two unrelated drugs: caspofungin, an antifungal drug, and hydroxyurea, a chemotherapeutic. Cross tolerance to the three drugs involves different sets of genes, although some genetic pathways affect the tolerance to two of these three drugs. This work highlights a serious concern, namely, that changes in whole chromosome copy number can occur in response to one type of stress, and yet, they may facilitate the emergence of tolerance to multiple drugs, including the few antifungal drug classes available to treat Candida infections.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34523225

RESUMO

An O2 -assisted, four-component reaction has been developed to synthesize a wide range of syn-1,3-amino alcohols in one step. The reaction proceeds by oxygenation of vinyl magnesium bromide (component-I) with O2 (component-II) to give a magnesium enolate of acetaldehyde, which undergoes addition to a chiral N-tert-butanesulfinyl imine (component-III) followed by a sequential addition with excess vinyl magnesium bromide (component-IV). The approach allows diastereoselective synthesis of anti/syn- and syn/syn-3-amino-1,5-diols in good yields with high diastereoselectivity. The method was illustrated in an efficient, four-step synthesis of piperidine alkaloid (-)-2'-epi-ethylnorlobelol.

11.
Microbiol Spectr ; : e0072321, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585947

RESUMO

The high morbidity and mortality of cryptococcal meningitis is due to the limited range of therapeutic options: only three classes of antifungal drugs are available (polyenes [amphotericin B], azoles [fluconazole], and pyrimidine analogues [flucytosine]). Fluconazole is the most widely used antifungal drug in sub-Saharan Africa, where cryptococcal meningitis is a major cause of death in patients infected with HIV. In this study, we found that exposure to fluconazole, even for short times (48 h) at subinhibitory concentrations, drove rapid adaptation of Cryptococcus neoformans serotype A strain H99 via the acquisition of different aneuploid chromosomes. These aneuploidies conferred heteroresistance to fluconazole. Importantly, most of the adaptors were cross-tolerant to flucytosine. Some of the aneuploid adaptors were not heteroresistant to fluconazole but were tolerant to amphotericin B. Thus, exposure to one antifungal drug class can promote adaptation to two antifungal drug classes, highlighting the plasticity of the C. neoformans genome and raising concerns about the rapid reduction in the range of treatment options for cryptococcal infections. IMPORTANCE Cryptococcosis is a globally distributed invasive fungal infection caused by infections with Cryptococcus neoformans or Cryptococcus gattii. Only three classes of therapeutic drugs are clinically available for treating cryptococcosis: polyenes (amphotericin B), azoles (fluconazole), and pyrimidine analogues (flucytosine). Fluconazole is the primary drug available in resource-limited countries. Aneuploidy is a genomic state due to the gain or loss of chromosomes. We found that C. neoformans rapidly adapted to fluconazole by acquiring diverse aneuploidies and that specific aneuploidies enabled improved growth of isolates susceptible (tolerance) to amphotericin B and/or cross-tolerance to both fluconazole and flucytosine. Therefore, aneuploidy is an underlying mechanism of drug tolerance that not only arises rapidly during growth in fluconazole but can also confer tolerance to other antifungal drugs without prior exposure to those drugs. Resistant isolates have high MICs, and all cells grow similarly in medium with the drug, while tolerant isolates test as susceptible and grow slowly at drug concentrations above the MIC.

12.
Medicine (Baltimore) ; 100(35): e27134, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477162

RESUMO

RATIONALE: Chronic myelogenous leukemia (CML) with thrombocytosis and complex chromosomal translocation is extremely rare in clinical setting. Here, we reported the clinical and pathological characteristics of CML patients, which were characterized by thrombocytosis and complex Philadelphia chromosome translocation. Moreover, we also introduced our therapeutic schedule for this patient as well as review relative literature. PATIENT CONCERNS: A 24-year-old female presented with night sweating, fatigue, and intermittent fever for 1 month. DIAGNOSIS: Fluorescence in situ hybridization results revealed that breakpoint cluster region (BCR)-Abelson (ABL) gene fusion in 62% of the cells and karyotyping showed a complex 3-way 46, XY, t(9;22;11) (q34;q11;q13) [19/20] translocation. This patient was diagnosed with CML complicated with thrombocytosis and complex Philadelphia chromosome translocation. INTERVENTIONS: The patients received continuously oral imatinib mesylate tablets (400 mg) once a day. OUTCOMES: After treatment with imatinib for 3 months, the BCR/ABLIS was less than 0.1% and achieved major molecular response. Moreover, the BCR/ABLIS of this patient achieved major molecular response. The BCR/ABLIS values at 6 months and 12 months were less than 0.01% and 0.0032%, respectively. And no BCR/ABL fusion was detected in the next 2 years follow-up period. LESSONS: Imatinib might represent a preferred therapeutic option for CML patients with rare thrombocytosis and complex chromosomal translocation. In addition, BCR/ABL fusion gene examination in patients with thrombocytosis might represent an effective strategy to avoid the misdiagnosis of this specific CML population.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia , Trombocitose/etiologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Adulto Jovem
13.
J Oral Rehabil ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398484

RESUMO

BACKGROUND: Dental pulp tissues are rich in pain-related afferent nerve fibers, which originate from primary sensory neurons in the trigeminal ganglion (TG). The mechanisms of central nervous system (CNS) underlying ectopic pain following peripheral inflammation have been reported that the macrophages as inflammatory and immunologic mediators in the TG play an important role in the process of pulpitis and hyperalgesia. OBJECTIVE(S): To observe the polarization response and dynamic distribution of macrophages in the TG during the development of dental pulp inflammation. METHODS: A rat model of pulpitis was established using complete Freund's adjuvant (CFA). Hematoxylin-eosin (HE), immunohistochemistry (IHC), immunofluorescence (IF), toluidine blue (TB) staining, and RT-qPCR were performed to observe the expression of macrophage-related factors in the TG. RESULTS: The results of IHC staining showed that M2 macrophages labeled with CD206 were observed in the TG of both the control and CFA groups. The statistical analysis indicated that the number of CD206-positive macrophages in the TG increased significantly at 24 h after CFA-induced pulpitis, reached a peak at 2 weeks, and then returned to the normal level after 6 weeks. The ratio of M2/M1 in the CFA groups was significantly lower than that in the control group from 24 to 72 h, and this pattern was reversed at 2 weeks after CFA-induced pulpitis; then, the ratio increased significantly and was maintained at a high level for 4 weeks. RT-qPCR results showed that the expression of IL-10 in the TG increased significantly from 1 to 4 weeks after CFA-induced pulpitis. CONCLUSION: The trend of M2 macrophages was opposite to that of M1 macrophages in the TG during the process of pulpitis induced by CFA, which is consistent with the expression of macrophage-related cytokines. Macrophage polarization in the TG may participate in the neuroinflammation response induced by dental pulpitis.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34444351

RESUMO

The progress of new media has promoted the development of online health consultations. Previous research has investigated the impact of media richness on user satisfaction; however, little attention has been given to the mixed effects of the nesting of multiple media. The purpose of this study is to analyze the impact and differences of the use of single or mixed media on users' perceived effect from the perspectives of social support and satisfaction by mining user reviews on online health platforms. The data were collected from a professional online psychological counseling platform. We collected data on 48,807 reviews from 11,694 users. Text annotation and sentiment analysis were then used to extract variable eigenvalues from the reviews. One-way analysis of variance (ANOVA) and hierarchical regression analysis were used for statistical analysis. The results show that mixed media with different richness has a significant impact on the users' perceived effects. Among them, compared to "text + audio," using "text + audio + video/face to face" can significantly improve the users' perceived social support and satisfaction. However, compared to single medium, mixed media with higher richness may not necessarily achieve a better effect. We found that the inclusion of "video/face to face" mixed media significantly reduced the users' perceived social support and satisfaction compared to text or audio use alone. These research results complement the blank media richness theory in the field of online health care and provide guidance for improving the personalized customization of online psychological counseling platforms.


Assuntos
Mídias Sociais , Envio de Mensagens de Texto , Aconselhamento , Humanos , Psicoterapia , Apoio Social
15.
Bioinformatics ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406374

RESUMO

MOTIVATION: Aberrant DNA methylation is strongly associated with heterogeneity in tumors. This study investigated the prognostic value of CpG island methylator phenotype (CIMP) in hepatocellular carcinoma (HCC). RESULTS: A total of 319 HCC samples with 21,121 CpG sites were included in this study and 215 disease-free survival (DFS) and overall survival (OS)-related CpG sites were identified. These CpG sites were divided into 7 clusters by using consensus clustering method. Cluster 4, which constructed the prognostic prediction model as the seed cluster to evaluate survival risk for DFS and OS of HCC patients, had the lowest methylation level with the worse prognosis. The low-risk group patients had a significantly prolonged DFS and OS than the patients in the high-risk group (p = 0.008 and p < 0.001, respectively). A receiver operating characteristic curve results for predicting DFS and OS was 0.691 and 0.695, respectively. These results suggested that the CpG site methylation appears to be an informative prognostic biomarker in HCC. The CpG site methylation-related prognostic model may be an innovative insight to evaluate clinical outcomes for HCC patients. AVAILABILITY: The code of the analysis is available at https://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

16.
Talanta ; 234: 122671, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364472

RESUMO

Traditional cell biology researches on cell populations by their origin, tissue, morphology, and secretions. Because of the heterogeneity of cells, research at the single-cell level can obtain more accurate and comprehensive information that reflects the physiological state and process of the cell, increasing the significance of single-cell analysis. The application of single-cell analysis is faced with the problem of contaminated or damaged cells caused by cell sample transportation. Reversible encapsulation of a single cell can protect cells from the external environment and open the encapsulation shell to release cells, thus preserving cell integrity and improving extraction efficiency of analytes. Meanwhile, microfluidic single cell analysis (MSCA) exhibits integration, miniaturization, and high throughput, which can considerably improve the efficiency of single-cell analysis. The researches on single-cell reversible encapsulation materials, single-cell analysis methods, and the MSCA integration platform are analyzed and summarized in this review. The problems of single-cell viability, network of single-cell signal, and simultaneous detection of multiple biotoxins in food based on single-cell are proposed for future research.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Humanos , Análise de Célula Única
17.
Insect Sci ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347932

RESUMO

Rab proteins constitute the largest family of small GTPases, which play pivotal roles in intracellular membrane trafficking in all eukaryotes. A number of Rab genes have been identified in eukaryotes; however, very little information about these genes has been reported in insects. In the current study, for the first time we identified and characterized 27 Rab family genes from Locusta migratoria. Phylogenetic analysis and comparison of domain architecture indicated that Rab family genes are highly conserved among insect species. Tissue-dependent expression profiles indicated that expression of Rab genes was highest in the ovary, except for LmRab3, which was most highly expressed in hemolymph. The biological function of each Rab gene was investigated using RNA interference (RNAi). Double-stranded RNA targeting each Rab gene was injected into the hemocoel of nymphs and revealed that suppression of two Rab genes (LmRab5 and LmRab11A) caused 100% mortality. In addition, nymphs injected with dsLmRab5 exhibited severe phenotypic defects in the gastric caeca and midgut, while dsLmRab11A arrested the molting process. We then applied the RNAi of RNAi technique to test if silencing either of these two genes would affect the suppression of the lethal giant larvae (LmLgl) reporter gene and found that suppression of LmRab5 diminished the RNAi efficiency of LmLgl, whereas suppression of LmRab11A enhanced RNAi efficiency of LmLgl. These results indicate that Rab genes contribute differently to RNAi efficiency in different tissues. Our study provides a foundation for further functional investigations of Rab genes and their contributions to RNAi efficiency in L. migratoria.

18.
Oxid Med Cell Longev ; 2021: 6366254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367463

RESUMO

Evidence suggests that miR-146a is implicated in the pathogenesis of cardiovascular diseases; however, the role of miR-146a in myocardial ischaemia reperfusion (I/R) injury is unclear. The aim of this study was to explore the functional role of miR-146a in myocardial ischaemia reperfusion injury and the underlying mechanism. C57BL/6J mice were subjected to 45 min of ischaemia and 1 week of reperfusion to establish a myocardial I/R injury model. A miR-146a mimic (0.5 mg/kg) was administered intravenously at the beginning of the ischaemia process. Neonatal rat cardiomyocytes were also subjected to hypoxia/reperfusion (H/R). Cells were treated with the miR-146a mimic or antagonist. As a result, the miR-146a mimic attenuated H/R-induced cardiomyocyte injury, as evidenced by increased cell viability and reduced lactate dehydrogenase (LDH) levels. In addition, the miR-146a mimic inhibited oxidative stress in cells suffering from H/R injury. Moreover, the miR-146a antagonist exerted adverse effects in vitro. In mice with myocardial I/R injury, the miR-146a mimic preserved cardiac function and reduced the infarction area and fibrosis. Moreover, the miR-146a mimic decreased the inflammatory response and reactive oxygen species (ROS) accumulation in mouse hearts. Mechanistically, we found that miR-146a directly regulated the transcription of NOX4, which subsequently affected P38 signalling in cardiomyocytes. When we knocked down NOX4, the effects of the miR-146a antagonist in worsening the cell condition were counteracted in in vitro experiments. Taken together, the results suggest that miR-146a protects against myocardial ischaemia reperfusion injury by inhibiting NOX4 signalling. The miR-146a mimic may become a potential therapeutic approach for patients with myocardial ischaemia reperfusion.

19.
Oxid Med Cell Longev ; 2021: 3225439, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413926

RESUMO

Lumbar intervertebral disc degeneration (IDD) has been the major contributor to low back pain (LBP). IDD is an chronic inflammation process, with the activation of plentiful inflammation-related cytokines and ECM degradation-related enzymes. In the past few years, hypertension has been reported to correlate with LBP. In addition, the local tissue renin-angiotensin system (tRAS) has been identified in multiple tissues, including the spinal cord, skin, kidney, heart, and bone. Recently, tRAS has also been established in both bovine and human intervertebral disc tissues, especially in the degenerated disc tissue. However, the exact of tRAS and IDD remains unknown. In this present study, proteomic analysis, molecular biology analysis, and animal model were all used. Firstly, we revealed that tRAS was excessively activated in the human degenerated intervertebral disc tissue via proteomic analysis and molecular biology analysis. Then, in vitro experiment suggested that Ang II could decrease the cell viability of human NP cells and promote NP cell apoptosis, senescence, oxidative stress, and NLRP3 activation in human NP cells. In addition, Ang II could also trigger degeneration and fibrosis phenotype in human NP cells. Finally, the animal model demonstrated that the local activated ACE/Ang II axis in the NP tissue could accelerate IDD in aging spontaneously hypertensive rats (SHR). Collectively, the degenerated intervertebral disc tissue showed excessively activated tRAS, and local activated tRAS could induce NP cell senescence, apoptosis, oxidative stress, and inflammatory reaction to promote IDD. These biological effects of Ang II on human NP cells may provide novel insight into further treatment of IDD.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34462244

RESUMO

BACKGROUND: Whether the characteristics and outcome of secondary acute promyelocytic leukemia (s-APL) are similar to de no APL (dn-APL) remains unknown. PATIENTS AND METHODS: Using the SEER database, we identified 3877 patients with APL diagnosed from 2000 to 2014, including 465 s-APL and 3412 dn-APL. RESULTS: Compared with dn-APL, s-APL werecharacterized by older median age, and a higher early mortality rate. Multivariate Cox model showed s-APL, older age, earlier year of diagnosis, and male gender were independently associated with worse survival. Notably, s-APL had a significantly inferior survival regardless of gender, race, marital status, and year of diagnosis. However, the difference between the 2 cohorts was only evident in younger patients (≤ 65 years) but was lost in older patients (> 65 years). Additionally, the majority of index cancer type was breast and prostate in female and male s-APL, respectively. Latency < 3 years was associated with superior survival in s-APL with breast index cancer. CONCLUSIONS: Inferior survival of s-APL points to the need for treatment improvement.

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