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1.
Environ Pollut ; : 124736, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147222

RESUMO

Tire wear particles (TWPs) in stormwater runoff have been widely detected and were generally classified into microplastics (MPs). TWPs and conventional MPs can be intercepted and accumulated in stormwater filtration systems, but their impacts on filtration, adsorption and microbial degradation processes of conventional pollutants (organic matters, nitrate and ammonium) have not been clarified. TWPs are different from MPs in surface feature, chemical components, adsorption ability and leaching of additives, which might lead to their different impacts on conventional pollutants removal. In this study, five different levels of aged polyethylene MPs (PEMPs) and aged TWPs contamination in stormwater filtration systems were simulated using thirty-three filtration columns. Results showed that ultraviolet aging treatment was less influential for the aging of TWPs than that of PEMPs, the specific surface area of aged PEMPs (1.603 m2/g) was over two times of unaged TWPs (0.728 m2/g) in the same size. Aged PEMPs and aged TWPs had different impacts on conventional pollutants removal performance and microbial communities, and the difference might be enlarged with exposure duration. The intensified aged PEMPs contamination generally promoted conventional pollutants removal, whereas aged TWPs showed an opposite trend. Mild contamination (0.01% and 0.1%, wt%) of aged PEMP/TWPs was beneficial to the richness and diversity of microbial communities, whereas higher contamination of aged PEMPs/TWPs was harmful. Aged PEMPs and TWPs had different impact on microbial community structure. Overall, the study found that TWPs were more detrimental than PEMPs in filtration systems. The research underscores the need for more comprehensive investigation into the occurrence, effects and management strategies of TWPs, as well as the importance of distinguishing between TWPs and MPs in future studies.

2.
J Imaging Inform Med ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150595

RESUMO

Primary diffuse central nervous system large B-cell lymphoma (CNS-pDLBCL) and high-grade glioma (HGG) often present similarly, clinically and on imaging, making differentiation challenging. This similarity can complicate pathologists' diagnostic efforts, yet accurately distinguishing between these conditions is crucial for guiding treatment decisions. This study leverages a deep learning model to classify brain tumor pathology images, addressing the common issue of limited medical imaging data. Instead of training a convolutional neural network (CNN) from scratch, we employ a pre-trained network for extracting deep features, which are then used by a support vector machine (SVM) for classification. Our evaluation shows that the Resnet50 (TL + SVM) model achieves a 97.4% accuracy, based on tenfold cross-validation on the test set. These results highlight the synergy between deep learning and traditional diagnostics, potentially setting a new standard for accuracy and efficiency in the pathological diagnosis of brain tumors.

3.
Mar Biotechnol (NY) ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136869

RESUMO

Spotted knifejaw (Oplegnathus punctatus) is a significant marine fish species that exhibits pronounced sexual dimorphism, with males generally exhibiting greater weight and growth rates than females. Therefore, the farming of O. punctatus with a high proportion of males is beneficial for improving the quality and efficiency of the O. punctatus aquaculture industry. Furthermore, the development of a rapid technique in sexing O. punctatus fry will facilitate the selection and breeding of superior male varieties of O. punctatus. In this study, genome-wide scanning, comparative genomics, and structural variation analysis methods were employed to identify and extract the homologous region of the inter-alpha-trypsin inhibitor heavy chain 4 (itih4b) gene on the X and Y chromosomes from the complete genome sequence of O. punctatus. This analysis revealed the presence of a large segment of DNA insertion markers on the Y chromosome in the region. Itih4b plays an important role in the mechanisms that regulate inflammatory and immune responses in multicellular organisms. The method described here involved the design of a pair of primers to amplify two bands of 532 bp and 333 bp in males (individuals with DNA insertion variants in the intron of the itih4b gene). In females (individuals without DNA insertion), only one band of 333 bp could be distinguished by agarose gel electrophoresis. This method shortened the time required to accurately characterize intronic DNA insertion variants and genetic sexes in O. punctatus, thereby improving detection efficiency. This study has significant value for the large-scale breeding of O. punctatus all-male seedlings and provides a reference point for the study of intron variation regulation and RNA shearing in the itih4b gene.

4.
Database (Oxford) ; 20242024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001614

RESUMO

The significance of entomological evidence in inferring the time, location and cause of death has been demonstrated both theoretically and practically. With the advancement of sequencing technologies, reports have emerged on necrophagous insects' nuclear genomes, transcriptomes, proteomes and mitochondrial genomes. However, within the field of forensic entomology, there is currently no available database that can integrate, store and share the resources of necrophagous insects. The absence of a database poses an inconvenience to the application of entomological evidence in judicial practice and hampers the development of the forensic entomology discipline. Given this, we have developed the Home Of Forensic Entomology database, encompassing 10 core functional modules: Home, Browse, Mitochondria, Proteome, JBrowse, Search, BLAST, Tools, Case base and Maps. Notably, the 'Tools' module enables multiple sequence alignment analysis (Muscle), homologous protein prediction (Genewise), primer design (Primer), large-scale genomic analysis (Lastz), Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, as well as expression profiling (PCA Analysis, Hcluster and Correlation Heatmap). In addition, the present database also works as an interactive platform for researchers by sharing forensic entomological case reports and uploading data and material. This database provides potential visitors with a comprehensive function for multi-omics data analysis, offers substantial references to researchers and criminal scene investigators and facilitates the utilization of entomological evidence in court. Database URL: http://ihofe.com/.


Assuntos
Entomologia Forense , Animais , Insetos/genética , Bases de Dados Factuais , Bases de Dados Genéticas
5.
Gigascience ; 132024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-39028586

RESUMO

BACKGROUND: The use of sex-specific molecular markers has become a prominent method in enhancing fish production and economic value, as well as providing a foundation for understanding the complex molecular mechanisms involved in fish sex determination. Over the past decades, research on male and female sex identification has predominantly employed molecular biology methodologies such as restriction fragment length polymorphism, random amplification of polymorphic DNA, simple sequence repeat, and amplified fragment length polymorphism. The emergence of high-throughput sequencing technologies, particularly Illumina, has led to the utilization of single nucleotide polymorphism and insertion/deletion variants as significant molecular markers for investigating sex identification in fish. The advancement of sex-controlled breeding encounters numerous challenges, including the inefficiency of current methods, intricate experimental protocols, high costs of development, elevated rates of false positives, marker instability, and cumbersome field-testing procedures. Nevertheless, the emergence and swift progress of PacBio high-throughput sequencing technology, characterized by its long-read output capabilities, offers novel opportunities to overcome these obstacles. FINDINGS: Utilizing male/female assembled genome information in conjunction with short-read sequencing data survey and long-read PacBio sequencing data, a catalog of large-segment (>100 bp) insertion/deletion genetic variants was generated through a genome-wide variant site-scanning approach with bidirectional comparisons. The sequence tagging sites were ranked based on the long-read depth of the insertion/deletion site, with markers exhibiting lower long-read depth being considered more effective for large-segment deletion variants. Subsequently, a catalog of bulk primers and simulated PCR for the male/female variant loci was developed, incorporating primer design for the target region and electronic PCR (e-PCR) technology. The Japanese parrotfish (Oplegnathus fasciatus), belonging to the Oplegnathidae family within the Centrarchiformes order, holds significant economic value as a rocky reef fish indigenous to East Asia. The criteria for rapid identification of male and female differences in Japanese parrotfish were established through agarose gel electrophoresis, which revealed 2 amplified bands for males and 1 amplified band for females. A high-throughput identification catalog of sex-specific markers was then constructed using this method, resulting in the identification of 3,639 (2,786 INS/853 DEL, ♀ as reference) and 3,672 (2,876 INS/833 DEL, ♂ as reference) markers in conjunction with 1,021 and 894 high-quality genetic sex identification markers, respectively. Sixteen differential loci were randomly chosen from the catalog for validation, with 11 of them meeting the criteria for male/female distinctions. The implementation of cost-effective and efficient technological processes would facilitate the rapid advancement of genetic breeding through expediting the high-throughput development of sex genetic markers for various species. CONCLUSIONS: Our study utilized assembled genome information from male and female individuals obtained from PacBio, in addition to data from short-read sequencing data survey and long-read PacBio sequencing data. We extensively employed genome-wide variant site scanning and identification, high-throughput primer design of target regions, and e-PCR batch amplification, along with statistical analysis and ranking of the long-read depth of the variant sites. Through this integrated approach, we successfully compiled a catalog of large insertion/deletion sites (>100 bp) in both male and female Japanese parrotfish.


Assuntos
Perciformes , Análise para Determinação do Sexo , Animais , Feminino , Masculino , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação INDEL , Perciformes/genética , Polimorfismo de Nucleotídeo Único , Análise para Determinação do Sexo/métodos
6.
PeerJ ; 12: e17325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832044

RESUMO

The azalea (Rhododendron simsii Planch.) is an important ornamental woody plant with various medicinal properties due to its phytochemical compositions and components. However little information on the metabolite variation during flower development in Rhododendron has been provided. In our study, a comparative analysis of the flavonoid profile was performed in Rhododendron pulchrum sweet at three stages of flower development, bud (stage 1), partially open flower (stage 2), and full bloom (stage 3). A total of 199 flavonoids, including flavone, flavonol, flavone C-glycosides, flavanone, anthocyanin, and isoflavone were identified. In hierarchical clustering analysis (HCA) and principal component analysis (PCA), the accumulation of flavonoids displayed a clear development stage variation. During flower development, 78 differential accumulated metabolites (DAMs) were identified, and most were enriched to higher levels at the full bloom stage. A total of 11 DAMs including flavone (chrysin, chrysoeriol O-glucuronic acid, and chrysoeriol O-hexosyl-O-pentoside), isoflavone (biochanin A), and flavonol (3,7-di-O-methyl quercetin and isorhamnetin) were significantly altered at three stages. In particular, 3,7-di-O-methyl quercetin was the top increased metabolite during flower development. Furthermore, integrative analyses of metabolomic and transcriptomic were conducted, revealing that the contents of isoflavone, biochanin A, glycitin, and prunetin were correlated with the expression of 2-hydroxyisoflavanone dehydratase (HIDH), which provide insight into the regulatory mechanism that controls isoflavone biosynthesis in R. pulchrum. This study will provide a new reference for increasing desired metabolites effectively by more accurate or appropriate genetic engineering strategies.


Assuntos
Flavonoides , Flores , Rhododendron , Rhododendron/metabolismo , Rhododendron/genética , Rhododendron/crescimento & desenvolvimento , Flores/metabolismo , Flores/crescimento & desenvolvimento , Flores/genética , Flavonoides/metabolismo , Flavonoides/análise
7.
Sci Rep ; 14(1): 13854, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879631

RESUMO

Gemini-type imidazoline quaternary ammonium salt is a new type of environmentally friendly corrosion inhibitor has been widely used in engineering materials. However, most of them are hazardous/toxic compounds derived from petroleum-based products, which did harm to environment. In this work, an environmentally friendly Gemini-shaped imidazoline quaternary ammonium salt corrosion inhibitor (G211) was synthesized using cheap fatty acid recycled from dimer acid industry as feedstock. The corrosion inhibition effects of G211 on Q235 steel in 1 M HCl solution were investigated through weight loss experiments, potential polarization curves, and alternating current impedance spectroscopy experiments. The results show that the inhibition rate of G211 as a mixed-type inhibitor is up to 94.4% and the concentration drop as low as 500 ppm at 25 â„ƒ. The adsorption of G211 on Q235 surface follows Langmuir adsorption isothermal curve. The chemical composition of the Q235 steel surface was analyzed through scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Furthermore, the possible corrosion inhibition mechanism of G211 on the surface of Q235 steel is proposed. This article not only presents an outstanding solution for safeguarding Q235 steel against corrosion but also introduces a feasible method for high-value utilization of monomer acid (MA).

8.
Sci Data ; 11(1): 616, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866804

RESUMO

The development and aging of the brain constitute a lifelong dynamic process, marked by structural and functional changes that entail highly coordinated cellular differentiation and epigenetic regulatory mechanisms. Chromatin accessibility serves as the foundational basis for genetic activity. However, the holistic and dynamic chromatin landscape that spans various brain regions throughout development and ageing remains predominantly unexplored. In this study, we employed single-nucleus ATAC-seq to generate comprehensive chromatin accessibility maps, incorporating data from 69,178 cells obtained from four distinct brain regions - namely, the olfactory bulb (OB), cerebellum (CB), prefrontal cortex (PFC), and hippocampus (HP) - across key developmental time points at 7 P, 3 M, 12 M, and 18 M. We delineated the distribution of cell types across different age stages and brain regions, providing insight into chromatin accessible regions and key transcription factors specific to different cell types. Our data contribute to understanding the epigenetic basis of the formation of different brain regions, providing a dynamic landscape and comprehensive resource for revealing gene regulatory programs during brain development and aging.


Assuntos
Envelhecimento , Encéfalo , Cromatina , Animais , Cromatina/metabolismo , Camundongos , Envelhecimento/genética , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Epigênese Genética , Hipocampo/metabolismo , Hipocampo/crescimento & desenvolvimento , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/crescimento & desenvolvimento
9.
Molecules ; 29(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893402

RESUMO

The use of vegetable oil-dervied plasticizers to enhance the flexibility of polylactic acid (PLA) has received much attention due to their renewability, inexpensiveness and biodegradation. However, the double bonds in vegetable oil-based plasticizers limit their compatibility with PLA, resulting in PLA-derived products with reduced flexibility. Herein, we examined soybean oil-derived hydrogenated dimer acid-based polyethylene glycol methyl ether esters (HDA-2n, 2n = 2, 4, 6 or 8, referring to the ethoxy units) developed via the direct esterification of saturated hydrogenated dimer acid and polyethylene glycol monomethyl ethers. The resulting HDA-2n was first used as a plasticizer for PLA, and the effects of the ethoxy units in HDA-2n on the overall performance of the plasticized PLA were systematically investigated. The results showed that, compared with PLA blended with dioctyl terephthalate (DOTP), the PLA plasticized by HDA-8 with the maximum number of ethoxy units (PLA/HDA-8) exhibited better low-temperature resistance (40.1 °C vs. 15.3 °C), thermal stability (246.8 °C vs. 327.6 °C) and gas barrier properties. Additionally, the biodegradation results showed that HDA-8 could be biodegraded by directly burying it in soil. All results suggest that HDA-8 could be used as green alternative to the traditional petroleum-based plasticizer DOTP, which is applied in the PLA industry.

10.
Mar Biotechnol (NY) ; 26(4): 687-695, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38874827

RESUMO

Spotted knifejaw (Oplegnathus punctatus) is a marine economic fish with high food and ecological value, and its growth process has obvious male and female sexual dimorphism, with males growing significantly faster than females. However, the current sex identification technology is not yet mature, which will limit the growth rate of O. punctatus aquaculture and the efficiency of separate sex breeding, so the development of efficient sex molecular markers is imperative. This study identified a 926 bp DNA insertion fragment in the cdkn1/srsf3 intergenic region of O. punctatus males through whole-genome scanning, comparative genomics, and structural variant analysis. A pair of primers was designed based on the insertion information of the Y chromosome intergenic region in male individuals. Agarose gel electrophoresis revealed the amplification of two DNA fragments, 1118 bp and 192 bp, in male O. punctatus individuals. The 926 bp fragment was identified as the insertion in the intergenic region of cdkn1/srsf3 in males, while only a single 192 bp DNA fragment was amplified in females. The biological sex of the individuals identified in this manner was consistent with their known phenotypic sex. In this study, we developed a method to detect DNA insertion variants in the intergenic region of O. punctatus. Additionally, we introduced a new DNA marker for the rapid identification of the sex of O. punctatus, which enhances detection efficiency. The text has important reference significance and application value in sex identification, all-male breeding, and lineage selection. It provides new insights into the regulation of variation in the intergenic region of cdkn1/srsf3 genes and the study of RNA shearing.


Assuntos
DNA Intergênico , Animais , Masculino , Feminino , DNA Intergênico/genética , Marcadores Genéticos , Análise para Determinação do Sexo/métodos , Análise para Determinação do Sexo/veterinária , Perciformes/genética , Proteínas de Peixes/genética
11.
ACS Omega ; 9(20): 22186-22195, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38799369

RESUMO

Developing a highly efficient multifunctional epoxy adhesive is still an enormous challenge, which can rapidly cure at room temperature and has excellent low-temperature resistance performance and is crucial for the epoxy adhesive and electrical sealing fields during severe cold seasons. Herein, diglycidyl phthalate (DP) was synthesized with phthalic anhydride (PA) and epichlorohydrin (ECH) to enhance the curing rate and low-temperature resistance of bisphenol A diglycidyl ether (DGEBA) adhesive. The modified DP/DGEBA adhesives were systematically analyzed by gel time, mechanical properties, and aging resistance (time, temperature, and dry/wet treatment). The results showed that DP with highly active ester groups significantly accelerates the curing speed of DP/DGEBA. DP's rigid aromatic ring-benzene ring and flexible group-ester group gave the adhesive better low-temperature resistance. When the addition of DP was 10 wt % (based on the mass of DGEBA), the gel time of DP/DGEBA epoxy adhesives was reduced by 58 min compared to unmodified DGEBA epoxy adhesive, and after aging at low temperature (-20 °C) for 7 days, the tensile shear strengths of polyvinyl chloride (PVC) and aluminum plate increased by 76.2 and 80.6%, respectively. The results of non-isothermal curing kinetics and dynamic mechanical analysis suggested that when the amount of DP was 10 wt %, the reaction activation energy of DP/DGEBA epoxy adhesive decreased by 4.0%, and the cross-linking density increased by 8.9%. Moreover, the toughness of the modified adhesive was also improved. This study opens up a feasible way for the development of a low temperature-resistant epoxy adhesive cured rapidly at room temperature in practical application.

12.
Appl Microbiol Biotechnol ; 108(1): 324, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713211

RESUMO

Laccase, a copper-containing polyphenol oxidase, is an important green biocatalyst. In this study, Laccase Lcc5 was homologous recombinantly expressed in Coprinopsis cinerea and a novel strategy of silencing chitinase gene expression was used to enhance recombinant Lcc5 extracellular yield. Two critical chitinase genes, ChiEn1 and ChiE2, were selected by analyzing the transcriptome data of C. cinerea FA2222, and their silent expression was performed by RNA interference (RNAi). It was found that silencing either ChiEn1 or ChiE2 reduced sporulation and growth rate, and increased cell wall sensitivity, but had no significant effect on mycelial branching. Among them, the extracellular laccase activity of the ChiE2-silenced engineered strain Cclcc5-antiChiE2-5 and the control Cclcc5-13 reached the highest values (38.2 and 25.5 U/mL, respectively) at 250 and 150 rpm agitation speeds, corresponding to productivity of 0.35 and 0.19 U/mL·h, respectively, in a 3-L fermenter culture. Moreover, since Cclcc5-antiChiE2-5 could withstand greater shear forces, its extracellular laccase activity was 2.6-fold higher than that of Cclcc5-13 when the agitation speed was all at 250 rpm. To our knowledge, this is the first report of enhanced recombinant laccase production in C. cinerea by silencing the chitinase gene. This study will pave the way for laccase industrial production and accelerate the development of a C. cinerea high-expression system. KEY POINTS: • ChiEn1 and ChiE2 are critical chitinase genes in C. cinerea FA2222 genome. • Chitinase gene silencing enhanced the tolerance of C. cinerea to shear forces. • High homologous production of Lcc5 is achieved by fermentation in a 3-L fermenter.


Assuntos
Quitinases , Inativação Gênica , Lacase , Quitinases/genética , Quitinases/metabolismo , Quitinases/biossíntese , Lacase/genética , Lacase/metabolismo , Lacase/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Agaricales/genética , Agaricales/enzimologia , Fermentação , Interferência de RNA , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Micélio/genética , Micélio/crescimento & desenvolvimento , Micélio/enzimologia , Parede Celular/metabolismo , Parede Celular/genética
13.
Int J Immunopathol Pharmacol ; 38: 3946320241249445, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38679570

RESUMO

BACKGROUND AND OBJECTIVES: Metformin, an oral hypoglycemic drug, has been suggested to possess antitumour activity in several types of cancers. Additionally, interleukin-8 (IL-8) has been reported to be involved in the development and metastasis of many cancers. However, the effect of metformin on IL-8 expression in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to investigate whether metformin could inhibit IL-8 expression to exert an inhibitory effect on HCC progression. MATERIALS AND METHODS: The IL-8 levels were measured in the plasma of 159 HCC patients (86 men, 73 women; average age 56 years) and in the culture supernatant of HCC cells (Hep3B and HuH7) using flow cytometry. In addition, the protein expression levels of IL-8 were also validated by the Human Protein Atlas (HPA) database. The prognostic value of IL-8 was evaluated using the Kaplan-Meier Plotter database. The association between IL-8 expression and immune checkpoints was estimated using the TIMER and The Cancer Genome Atlas (TCGA) databases. What's more, bioinformatics analysis, western blotting, and transwell assays were conducted to illustrate the molecular mechanism of metformin (≤1 mM) on IL-8 in HCC. RESULTS: IL-8 expression was found to be increased in the plasma of HCC patients, which is consistent with the expression of IL-8 in HCC cells and tissues. High expression of IL-8 was significantly related to poor prognosis. In addition, IL-8 was positively correlated with immune checkpoints in HCC. Notably, we found that low-dose metformin could inhibit the secretion of IL-8 by HCC cells and the migration of HCC cells. Mechanistically, low-dose metformin significantly suppresses HCC metastasis mainly through the AMPK/JNK/IL-8/MMP9 pathway. CONCLUSION: The results indicate that low-dose metformin can inhibit HCC metastasis by suppressing IL-8 expression. Targeting the AMPK/JNK/IL-8 axis may be a promising treatment strategy for patients with HCC metastasis.


Assuntos
Proteínas Quinases Ativadas por AMP , Carcinoma Hepatocelular , Interleucina-8 , Neoplasias Hepáticas , Metformina , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Interleucina-8/metabolismo , Interleucina-8/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Proteínas Quinases Ativadas por AMP/metabolismo , Idoso , Transdução de Sinais/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Metástase Neoplásica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Hipoglicemiantes/farmacologia
14.
Oncogene ; 43(25): 1900-1916, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38671157

RESUMO

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Dano ao DNA , Histona-Lisina N-Metiltransferase , Leucemia Mieloide Aguda , Proteína de Leucina Linfoide-Mieloide , Transdução de Sinais , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/genética , Dano ao DNA/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Transdução de Sinais/genética , Animais , Camundongos , Linhagem Celular Tumoral , Metiltransferases/metabolismo , Metiltransferases/genética , Proteína de Ligação a CREB/metabolismo , Proteína de Ligação a CREB/genética , Rearranjo Gênico , Histonas/metabolismo , Histonas/genética , Fosforilação , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Acetilação
16.
Biosensors (Basel) ; 14(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38667164

RESUMO

Raman flow cytometry (RFC) uniquely integrates the "label-free" capability of Raman spectroscopy with the "high-throughput" attribute of traditional flow cytometry (FCM), offering exceptional performance in cell characterization and sorting. Unlike conventional FCM, RFC stands out for its elimination of the dependency on fluorescent labels, thereby reducing interference with the natural state of cells. Furthermore, it significantly enhances the detection information, providing a more comprehensive chemical fingerprint of cells. This review thoroughly discusses the fundamental principles and technological advantages of RFC and elaborates on its various applications in the biomedical field, from identifying and characterizing cancer cells for in vivo cancer detection and surveillance to sorting stem cells, paving the way for cell therapy, and identifying metabolic products of microbial cells, enabling the differentiation of microbial subgroups. Moreover, we delve into the current challenges and future directions regarding the improvement in sensitivity and throughput. This holds significant implications for the field of cell analysis, especially for the advancement of metabolomics.


Assuntos
Citometria de Fluxo , Análise Espectral Raman , Humanos , Neoplasias , Animais
17.
Analyst ; 149(11): 3169-3177, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38639189

RESUMO

Small extracellular vesicles (sEVs), a form of extracellular vesicles, are lipid bilayered structures released by all cells. Large-scale studies on sEVs from clinical samples are necessary, but a major obstacle is the lack of rapid, reproducible, efficient, and low-cost methods to enrich sEVs. Acoustic microfluidics have the advantage of being label-free and biocompatible, which have been reported to successfully enrich sEVs. In this paper, we present a highly efficient acoustic microfluidic trap that can offer low and large volume compatible ways of enriching sEVs from biological fluids by flexible structure design. It uses the idea of pre-loading larger seed particles in the acoustic trap to enable sub-micron particle capturing. The microfluidic chip is actuated using a piezoelectric plate transducer attached to a silicon-glass bonding plate with circular cavities. Each cavity works as a resonant unit, excited at the frequency of both the half wave resonance in the main plane and inverted quarter wave resonance in the depth direction, which has the ability to strongly trap seed particles at the center, thereby improving the subsequent nanoparticle capture efficiency. Mean trapping efficiencies of 35.62% and 64.27% were obtained using 60 nm and 100 nm nanobeads, respectively. By the use of this technology, we have successfully enriched sEVs from cell culture conditioned media and blood plasma at a flow rate of 10 µL min-1. The isolated sEV subpopulations are characterized by NTA and TEM, and their protein cargo is determined by WB. This acoustic trapping chip provides a rapid and robust method to enrich sEVs from biofluids with high reproducibility and sufficient quantities. Therefore, it can serve as a new tool for biological and clinical research such as cancer diagnosis and drug delivery.


Assuntos
Acústica , Vesículas Extracelulares , Vesículas Extracelulares/química , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Nanopartículas/química , Dispositivos Lab-On-A-Chip , Meios de Cultivo Condicionados/química
18.
IEEE Trans Cybern ; PP2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526908

RESUMO

This article is concerned with the switched control of hybrid terrestrial and aerial quadrotors (HyTAQs) via stochastic hybrid fuzzy system methodology, in which the terrestrial and aerial mode switching is subject to a Markov process with lower-bounded sojourn time. For the first time, the bimodal nonlinear attitude dynamics of HyTAQs is analyzed and modeled based on the Takagi-Sugeno (T-S) fuzzy model, and switched fuzzy controllers are developed to stabilize the hybrid fuzzy system. The characteristic of state dimension switching caused by ground contact is modeled via the singular system presentation with mode-dependent singularity matrices, based on which numerically testable criteria of stability and stabilization in the stochastic sense are derived. Compared with the previous control approaches based on Markov jump systems, the proposed one is able to describe the deterministic dwelling duration in practice and integrate multiple subsystems with algebraic equations of different dimensions, while achieving lower conservatism. Illustrative examples are provided to demonstrate the effectiveness and potential of the designed variable-dimension fuzzy controllers.

19.
J Agric Food Chem ; 72(12): 6236-6249, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38484389

RESUMO

Hypercholesterolemia poses a significant cardiovascular risk, particularly in postmenopausal women. The anti-hypercholesterolemic properties of Lactiplantibacillus plantarum ATCC8014 (LP) are well recognized; however, its improving symptoms on postmenopausal hypercholesterolemia and the possible mechanisms have yet to be elucidated. Here, we utilized female ApoE-deficient (ApoE-/-) mice undergoing bilateral ovariectomy, fed a high-fat diet, and administered 109 colony-forming units (CFU) of LP for 13 consecutive weeks. LP intervention reduces total cholesterol (TC) and triglyceride (TG) accumulation in the serum and liver and accelerates their fecal excretion, which is mainly accomplished by increasing the excretion of fecal secondary bile acids (BAs), thereby facilitating cholesterol conversion. Correlation analysis revealed that lithocholic acid (LCA) is an important regulator of postmenopausal lipid abnormalities. LP can reduce LCA accumulation in the liver and serum while enhancing its fecal excretion, accomplished by elevating the relative abundances of Allobaculum and Olsenella in the ileum. Our findings demonstrate that postmenopausal lipid dysfunction is accompanied by abnormalities in BA metabolism and dysbiosis of the intestinal microbiota. LP holds therapeutic potential for postmenopausal hypercholesterolemia. Its effectiveness in ameliorating lipid dysregulation is primarily achieved through reshaping the diversity and abundance of the intestinal microbiota to correct BA abnormalities.


Assuntos
Microbioma Gastrointestinal , Hipercolesterolemia , Lactobacillus plantarum , Humanos , Feminino , Camundongos , Animais , Hipercolesterolemia/metabolismo , Ácidos e Sais Biliares/metabolismo , Pós-Menopausa , Colesterol/metabolismo , Lactobacillus plantarum/metabolismo , Fígado/metabolismo , Apolipoproteínas E/metabolismo , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica
20.
Sensors (Basel) ; 24(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38544113

RESUMO

Cruise ships and other naval vessels include automated Internet of Things (IoT)-based evacuation systems for the passengers and crew to assist them in case of emergencies and accidents. The technical challenges of assisting passengers and crew to safety during emergencies include various aspects such as sensor failures, imperfections in the sound or display systems that are used to direct evacuees, the timely selection of optimum evacuation routes for the evacuees, as well as computation and communication delays that may occur in the IoT infrastructure due to intense activities during an emergency. In addition, during an emergency, the evacuees may be confused or in a panic, and may make mistakes in following the directions offered by the evacuation system. Therefore, the purpose of this work is to analyze the effect of two important aspects that can have an adverse effect on the passengers' evacuation time, namely (a) the computer processing and communication delays, and (b) the errors that may be made by the evacuees in following instructions. The approach we take uses simulation with a representative existing cruise ship model, which dynamically computes the best exit paths for each passenger, with a deadline-driven Adaptive Navigation Strategy (ANS). Our simulation results reveal that delays in the evacuees' reception of instructions can significantly increase the total time needed for passenger evacuation. In contrast, we observe that passenger behavior errors also affect the evacuation duration, but with less effect on the total time needed to evacuate passengers. These findings demonstrate the importance of the design of passenger evacuation systems in a way that takes into account all realistic features of the ship's indoor evacuation environment, including the importance of having high-performance data processing and communication systems that will not result in congestion and communication delays.

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