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1.
Chem Commun (Camb) ; 60(38): 5038-5041, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38630532

RESUMO

The slow Li+ transport rate in the thick sulfur cathode of the Li-S battery affects its capacity and cycling performance. Herein, Fe-doped highly ordered mesoporous silica material (Fe-HSBA-15) as a sulfur carrier of the Li-S battery shows high ion conductivity (1.10 mS cm-1) and Li+ transference number (0.77). The Fe-HSBA-15/S cell has an initial capacity of up to 1216.7 mA h g-1 at 0.2C and good stability. Impressively, at a high sulfur load of 4.34 mg cm-2, the Fe-HSBA-15/S cell still maintains an area specific capacity of 4.47 mA h cm-2 after 100 cycles. This is because Fe-HSBA-15 improves the Li+ diffusion behavior through the ordered mesoporous structure. Theoretical calculations also confirmed that the doping of iron enhances the adsorption of polysulfides, reduces the band gap and makes the catalytic activity stronger.

2.
J Colloid Interface Sci ; 666: 57-65, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583210

RESUMO

Modification of oxygen evolution co-catalyst (OEC) on the surface of bismuth vanadate (BiVO4) can effectively improve the kinetics of water oxidation, but it is still limited by the small hole extraction driving force at the BiVO4/OEC interface. Modulating the BiVO4/OEC interface with a hole transfer layer (HTL) is expected to facilitate hole transport from BiVO4 to the OEC surface. Herein, a copper(I) thiocyanate (CuSCN) HTL is inserted between BiVO4 and NiFeOx OEC to create BiVO4/CuSCN/NiFeOx photoanode, resulting in a significant enhancement of photoelectrochemical (PEC) water splitting performance. From electrochemical analyses and density functional theory (DFT) simulations, the markedly enhanced PEC performance is attributed to the insertion of CuSCN as an HTL, which promotes the extraction of holes from BiVO4 surface and boosts the water oxidation kinetics. The optimal photoanode achieves a photocurrent density of 5.6 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (vs. RHE) and an impressive charge separation efficiency of 96.2 %. This work offers valuable insights into the development of advanced photoanodes for solar energy conversion and emphasizes the importance of selecting an appropriate HTL to mitigate recombination at the BiVO4/OEC interface.

3.
Clin Epigenetics ; 16(1): 1, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167534

RESUMO

BACKGROUND: The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250-300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. RESULTS: Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. CONCLUSION: While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Ratos , Masculino , Animais , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Glicemia , Metionina/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico , Creatinina/metabolismo , Creatinina/farmacologia , Creatinina/uso terapêutico , Ratos Wistar , Metilação de DNA , Rim/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacologia , Albuminas/metabolismo
4.
BMC Plant Biol ; 23(1): 542, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37924000

RESUMO

BACKGROUND: Henan is the province with the greatest wheat production in China. Although more than 100 cultivars are used for production, many cultivars are still insufficient in quality, disease resistance, adaptability and yield potential. To overcome these limitations, it is necessary to constantly breed new cultivars to maintain the continuous and stable growth of wheat yield and quality. To improve breeding efficiency, it is important to evaluate the genetic diversity and population genetic structure of its cultivars. However, there are no such reports from Henan Province. Therefore, in this study, single nucleotide polymorphism (SNP) markers were used to study the population genetic structure and genetic diversity of 243 wheat cultivars included in a comparative test of wheat varieties in Henan Province, aiming to provide a reference for the utilization of backbone parents and the selection of hybrid combinations in the genetic improvement of wheat cultivars. RESULTS: In this study, 243 wheat cultivars from Henan Province of China were genotyped by the Affymetrix Axiom Wheat660K SNP chip, and 21 characteristics were investigated. The cultivars were divided into ten subgroups; each subgroup had distinct characteristics and unique utilization value. Furthermore, based on principal component analysis, Zhoumai cultivars were the main hybrid parents, followed by Aikang 58, high-quality cultivars, and Shandong cultivars. Genetic diversity analysis showed that 61.3% of SNPs had a high degree of genetic differentiation, whereas 33.4% showed a moderate degree. The nucleotide diversity of subgenome B was relatively high, with an average π value of 3.91E-5; the nucleotide diversity of subgenome D was the lowest, with an average π value of 2.44E-5. CONCLUSION: The parents used in wheat cross-breeding in Henan Province are similar, with a relatively homogeneous genetic background and low genetic diversity. These results will not only contribute to the objective evaluation and utilization of the tested cultivars but also provide insights into the current conditions and existing challenges of wheat cultivar breeding in Henan Province, thereby facilitating the scientific formulation of breeding objectives and strategies to improve breeding efficiency.


Assuntos
Polimorfismo de Nucleotídeo Único , Triticum , Triticum/genética , Polimorfismo de Nucleotídeo Único/genética , Melhoramento Vegetal/métodos , China , Nucleotídeos , Variação Genética
5.
Mol Plant ; 16(12): 1893-1910, 2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37897037

RESUMO

Despite recent progress in crop genomics studies, the genomic changes brought about by modern breeding selection are still poorly understood, thus hampering genomics-assisted breeding, especially in polyploid crops with compound genomes such as common wheat (Triticum aestivum). In this work, we constructed genome resources for the modern elite common wheat variety Aikang 58 (AK58). Comparative genomics between AK58 and the landrace cultivar Chinese Spring (CS) shed light on genomic changes that occurred through recent varietal improvement. We also explored subgenome diploidization and divergence in common wheat and developed a homoeologous locus-based genome-wide association study (HGWAS) approach, which was more effective than single homoeolog-based GWAS in unraveling agronomic trait-associated loci. A total of 123 major HGWAS loci were detected using a genetic population derived from AK58 and CS. Elite homoeologous haplotypes (HHs), formed by combinations of subgenomic homoeologs of the associated loci, were found in both parents and progeny, and many could substantially improve wheat yield and related traits. We built a website where users can download genome assembly sequence and annotation data for AK58, perform blast analysis, and run JBrowse. Our work enriches genome resources for wheat, provides new insights into genomic changes during modern wheat improvement, and suggests that efficient mining of elite HHs can make a substantial contribution to genomics-assisted breeding in common wheat and other polyploid crops.


Assuntos
Pão , Triticum , Triticum/genética , Haplótipos/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Poliploidia , Genoma de Planta/genética
6.
Cancer Cell Int ; 23(1): 242, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37840147

RESUMO

Epigenetic modifications have long been recognized as an essential level in transcriptional regulation linking behavior and environmental conditions or stimuli with biological processes and disease development. Among them, methylation is the most abundant of these reversible epigenetic marks, predominantly occurring on DNA, RNA, and histones. Methylation modification is intimately involved in regulating gene transcription and cell differentiation, while aberrant methylation status has been linked with cancer development in several malignancies. Early detection and precise restoration of dysregulated methylation form the basis for several epigenetics-based therapeutic strategies. In this review, we summarize the current basic understanding of the regulation and mechanisms responsible for methylation modification and cover several cutting-edge research techniques for detecting methylation across the genome and transcriptome. We then explore recent advances in clinical diagnostic applications of methylation markers of various cancers and address the current state and future prospects of methylation modifications in therapies for different diseases, especially comparing pharmacological methylase/demethylase inhibitors with the CRISPRoff/on methylation editing systems. This review thus provides a resource for understanding the emerging role of epigenetic methylation in cancer, the use of methylation-based biomarkers in cancer detection, and novel methylation-targeted drugs.

7.
J Org Chem ; 88(17): 12808-12815, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37589566

RESUMO

A palladium-catalyzed decarbonylative annulation of 2-arylbenzoic acids with internal alkynes via C(sp2)-H activation has been developed. A series of phenanthrenes were produced in moderate to good yield with good functional group tolerance. The mechanism study indicated that the C(sp2)-H activation should be the rate-determining step during the reaction.

8.
ACS Appl Mater Interfaces ; 15(26): 32047-32056, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37345757

RESUMO

Microsphere arrays have significant applications and broad development prospects in various fields and disciplines. The simple, efficient, low-cost, automatic, and controllable preparation of microsphere arrays in multiple dimensions and morphologies is still a significant challenge. Here, a novel microsphere array direct writing technology was developed using a low-cost portable droplet microfluidic device and a high-precision XY movable platform. The proposed technology provided a powerful platform for the direct-writing preparation of microsphere arrays and was successfully applied to the precise and controllable fabrication of microsphere arrays with different sizes, shapes, structures, and arrangements. Additionally, gel microsphere arrays with metal ion patterns were fabricated using the microsphere arrays as templates and exhibited excellent performance in the visual analytical detection of heavy metal ions. Moreover, the simulated microsphere arrays offer a promising platform for rapidly generating high-viability and uniform 3D tumor spheroids. Therefore, given the superiority of this technology and the great potential of microsphere arrays, this simple high-speed microsphere array direct writing technology has a promising application in the multidisciplinary intersection of chemical, biological, and material sciences.

9.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37373363

RESUMO

Crop genetic diversity is essential for adaptation and productivity in agriculture. A previous study revealed that poor allele diversity in wheat commercial cultivars is a major barrier to its further improvement. Homologs within a variety, including paralogs and orthologs in polyploid, account for a large part of the total genes of a species. Homolog diversity, intra-varietal diversity (IVD), and their functions have not been elucidated. Common wheat, an important food crop, is a hexaploid species with three subgenomes. This study analyzed the sequence, expression, and functional diversity of homologous genes in common wheat based on high-quality reference genomes of two representative varieties, a modern commercial variety Aikang 58 (AK58) and a landrace Chinese Spring (CS). A total of 85,908 homologous genes, accounting for 71.9% of all wheat genes, including inparalogs (IPs), outparalogs (OPs), and single-copy orthologs (SORs), were identified, suggesting that homologs are an important part of the wheat genome. The levels of sequence, expression, and functional variation in OPs and SORs were higher than that of IPs, which indicates that polyploids have more homologous diversity than diploids. Expansion genes, a specific type of OPs, made a great contribution to crop evolution and adaptation and endowed crop with special characteristics. Almost all agronomically important genes were from OPs and SORs, demonstrating their essential functions for polyploid evolution, domestication, and improvement. Our results suggest that IVD analysis is a novel approach for evaluating intra-genomic variations, and exploitation of IVD might be a new road for plant breeding, especially for polyploid crops, such as wheat.


Assuntos
Domesticação , Triticum , Triticum/genética , Melhoramento Vegetal , Poliploidia , Agricultura , Genoma de Planta , Evolução Molecular
10.
Genes (Basel) ; 14(2)2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36833242

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate several pathway intermediates and affect the skeletal muscle development in mice, pigs, sheep, and cattle. However, to date, only a small number of miRNAs have been reported in the muscle development of goats. In this report, the longissimus dorsi transcripts of one- and ten-month-old goats were analyzed by sequencing RNAs and miRNAs. The results showed that the ten-month-old Longlin goats had 327 up- and 419 down-regulated differentially expressed genes (DEGs) compared with the one-month-old. In addition, 20 co-up-regulated and 55 co-down-regulated miRNAs involved in the muscle fiber hypertrophy of goats were identified in ten-month-old Longlin and Nubian goats compared with one-month-old. Five miRNA-mRNA pairs (chi-let-7b-3p-MIRLET7A, chi-miR193b-3p-MMP14, chi-miR-355-5p-DGAT2, novel_128-LOC102178119, novel_140-SOD3) involved in the goat skeletal muscle development were identified by miRNA-mRNA negative correlation network analysis. Our results provided new insight into the functional roles of goat muscle-associated miRNAs, allowing a deeper understanding of the transformation of miRNA roles during mammalian muscle development.


Assuntos
MicroRNAs , Suínos , Animais , Bovinos , Camundongos , Ovinos/genética , MicroRNAs/genética , Perfilação da Expressão Gênica , RNA Mensageiro/genética , Cabras/genética , Fibras Musculares Esqueléticas/metabolismo , Hipertrofia
11.
Nat Commun ; 13(1): 3145, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672415

RESUMO

Knowledge gaps remain on how nucleosome organization and dynamic reorganization are governed by specific pioneer factors in a genome-wide manner. In this study, we generate over three billons of multi-omics sequencing data to exploit dynamic nucleosome landscape governed by pioneer factors (PFs), FOXA1 and GATA2. We quantitatively define nine functional nucleosome states each with specific characteristic nucleosome footprints in LNCaP prostate cancer cells. Interestingly, we observe dynamic switches among nucleosome states upon androgen stimulation, accompanied by distinct differential (gained or lost) binding of FOXA1, GATA2, H1 as well as many other coregulators. Intriguingly, we reveal a noncanonical pioneer model of GATA2 that it initially functions as a PF binding at the edge of a nucleosome in an inaccessible crowding array. Upon androgen stimulation, GATA2 re-configures an inaccessible to accessible nucleosome state and subsequently acts as a master transcription factor either directly or recruits signaling specific transcription factors to enhance WNT signaling in an androgen receptor (AR)-independent manner. Our data elicit a pioneer and master dual role of GATA2 in mediating nucleosome dynamics and enhancing downstream signaling pathways. Our work offers structural and mechanistic insight into the dynamics of pioneer factors governing nucleosome reorganization.


Assuntos
Nucleossomos , Neoplasias da Próstata , Androgênios , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo , Humanos , Masculino , Nucleossomos/genética , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais
12.
Food Chem ; 389: 133120, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35526288

RESUMO

This work proposed a cost-effective, simple, and highly sensitive magnetic molecularly imprinted particles (MMIPs) electrochemical sensor to indirectly detect kanamycin (KAN), tobramycin (TOB), and gentamicin (GEN). The MMIPs electrochemical sensor was prepared by a complex of metal ions and the MMIPs of rebinding the template, which modified on the magnetic glassy carbon electrode surface. Here, metal ions were used as the signal tracers and amplifiers of the MMIPs electrochemical sensor. Then the response peak currents of metal re-oxidized to metal ion was recorded by differential pulse voltammetry and used to monitor the level of aminoglycoside antibiotics. Under the optimal conditions, the MMIPs electrochemical sensors showed a high sensitivity toward KAN, TOB, and GEN with detection limits of 4.88, 1.28, and 1.07 nmol/L, respectively. Furthermore, the MMIPs electrochemical sensors showed high selectivity for determining KAN, TOB, and GEN, and they were successfully used to detect KAN, TOB, and GEN in milk.


Assuntos
Leite , Impressão Molecular , Animais , Antibacterianos/análise , Técnicas Eletroquímicas , Eletrodos , Íons , Canamicina , Limite de Detecção , Fenômenos Magnéticos , Leite/química , Tobramicina
13.
Front Med (Lausanne) ; 9: 830484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433742

RESUMO

COVID-19 is spreading widely, and the pandemic is seriously threatening public health throughout the world. A comprehensive study on the optimal sampling types and timing for an efficient SARS-CoV-2 test has not been reported. We collected clinical information and the values of 55 biochemical indices for 237 COVID-19 patients, with 37 matched non-COVID-19 pneumonia patients and 131 healthy people in Inner Mongolia as control. In addition, the results of dynamic detection of SARS-CoV-2 using oropharynx swab, pharynx swab, and feces were collected from 197 COVID-19 patients. SARS-CoV-2 RNA positive in feces specimen was present in approximately one-third of COVID-19 patients. The positive detection rate of SARS-CoV-2 RNA in feces was significantly higher than both in the oropharynx and nasopharynx swab (P < 0.05) in the late period of the disease, which is not the case in the early period of the disease. There were statistically significant differences in the levels of blood LDH, CRP, platelet count, neutrophilic granulocyte count, white blood cell number, and lymphocyte count between COVID-19 and non-COVID-19 pneumonia patients. Finally, we developed and compared five machine-learning models to predict the prognosis of COVID-19 patients based on biochemical indices at disease onset and demographic characteristics. The best model achieved an area under the curve of 0.853 in the 10-fold cross-validation.

15.
Front Genet ; 12: 730519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777467

RESUMO

Illumina is the leading sequencing platform in the next-generation sequencing (NGS) market globally. In recent years, MGI Tech has presented a series of new sequencers, including DNBSEQ-T7, MGISEQ-2000 and MGISEQ-200. As a complex application of NGS, cancer-detecting panels pose increasing demands for the high accuracy and sensitivity of sequencing and data analysis. In this study, we used the same capture DNA libraries constructed based on the Illumina protocol to evaluate the performance of the Illumina Nextseq500 and MGISEQ-2000 sequencing platforms. We found that the two platforms had high consistency in the results of hotspot mutation analysis; more importantly, we found that there was a significant loss of fragments in the 101-133 bp size range on the MGISEQ-2000 sequencing platform for Illumina libraries, but not for the capture DNA libraries prepared based on the MGISEQ protocol. This phenomenon may indicate fragment selection or low fragment ligation efficiency during the DNA circularization step, which is a unique step of the MGISEQ-2000 sequence platform. In conclusion, these different sequencing libraries and corresponding sequencing platforms are compatible with each other, but protocol and platform selection need to be carefully evaluated in combination with research purpose.

16.
Front Microbiol ; 12: 729455, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650534

RESUMO

Objectives: COVID-19 is highly infectious and has been widely spread worldwide, with more than 159 million confirmed cases and more than 3 million deaths as of May 11, 2021. It has become a serious public health event threatening people's lives and safety. Due to the rapid transmission and long incubation period, shortage of medical resources would easily occur in the short term of discovering disease cases. Therefore, we aimed to construct an artificial intelligent framework to rapidly distinguish patients with COVID-19 from common pneumonia and non-pneumonia populations based on computed tomography (CT) images. Furthermore, we explored artificial intelligence (AI) algorithms to integrate CT features and laboratory findings on admission to predict the clinical classification of COVID-19. This will ease the burden of doctors in this emergency period and aid them to perform timely and appropriate treatment on patients. Methods: We collected all CT images and clinical data of novel coronavirus pneumonia cases in Inner Mongolia, including domestic cases and those imported from abroad; then, three models based on transfer learning to distinguish COVID-19 from other pneumonia and non-pneumonia population were developed. In addition, CT features and laboratory findings on admission were combined to predict clinical types of COVID-19 using AI algorithms. Lastly, Spearman's correlation test was applied to study correlations of CT characteristics and laboratory findings. Results: Among three models to distinguish COVID-19 based on CT, vgg19 showed excellent diagnostic performance, with area under the curve (AUC) of the receiver operating characteristic (ROC) curve at 95%. Together with laboratory findings, we were able to predict clinical types of COVID-19 with AUC of the ROC curve at 90%. Furthermore, biochemical markers, such as C-reactive protein (CRP), LYM, and lactic dehydrogenase (LDH) were identified and correlated with CT features. Conclusion: We developed an AI model to identify patients who were positive for COVID-19 according to the results of the first CT examination after admission and predict the progression combined with laboratory findings. In addition, we obtained important clinical characteristics that correlated with the CT image features. Together, our AI system could rapidly diagnose COVID-19 and predict clinical types to assist clinicians perform appropriate clinical management.

17.
Front Oncol ; 11: 700781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527578

RESUMO

Nuclear protein of the testis (NUT) carcinoma is a very rare and aggressive carcinoma characterized by chromosomal rearrangement. NUT-midline carcinoma (NMC) can occur anywhere in the body, but most of the tumors are found in the midline anatomic structure or mediastinum. Pulmonary-originated NMC is extremely rare and often difficult to be distinguished from other poorly differentiated tumors, making the diagnosis awfully challenged in clinical practice. There are less than 100 cases of NUT carcinoma reported so far. In this study, the diagnosis and molecular mechanisms of reported NUT carcinoma cases were reviewed. Furthermore, a case of primary pulmonary NUT-midline carcinoma and its pathological features was reported. The process of pathological identification and genomic analysis for establishing the diagnosis was discussed. We found that NUT carcinoma could be identified by combining CT, H&E staining, immunohistochemistry (IHC), and molecular tests. The development of NUT carcinoma might be associated with mutation of MYC, p63, and MED24 genes and the Wnt, MAPK, and PI3K signaling pathways. Our study provided a detailed molecular mechanistic review on NMC and established a procedure to identify pulmonary NMC.

18.
Genome Biol ; 22(1): 250, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446075

RESUMO

We develop a novel computational method, NucHMM, to identify functional nucleosome states associated with cell type-specific combinatorial histone marks and nucleosome organization features such as phasing, spacing and positioning. We test it on publicly available MNase-seq and ChIP-seq data in MCF7, H1, and IMR90 cells and identify 11 distinct functional nucleosome states. We demonstrate these nucleosome states are distinctly associated with the splicing potentiality of skipping exons. This advances our understanding of the chromatin function at the nucleosome level and offers insights into the interplay between nucleosome organization and splicing processes.


Assuntos
Nucleossomos/metabolismo , Splicing de RNA/genética , Linhagem Celular , Éxons/genética , Genoma Humano , Humanos , Cadeias de Markov
19.
Front Immunol ; 12: 658048, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953720

RESUMO

B cell activation by Tfh cells, i.e., through CD154 engagement of CD40 and IL-21, and survival within GCs are crucial for the T-dependent Ab response. LUBAC, composed of HOIP, SHARPIN, and HOIL-1, catalyzes linear ubiquitination (Linear M1-Ub) to mediate NF-κB activation and cell survival induced by TNF receptor superfamily members, which include CD40. As shown in this study, B cells expressing the Sharpin null mutation cpdm (Sharpincpdm ) could undergo proliferation, CSR, and SHM in response to immunization by a T-dependent Ag, but were defective in survival within GCs, enrichment of a mutation enhancing the BCR affinity, and production of specific Abs. Sharpincpdm B cells stimulated in vitro with CD154 displayed normal proliferation and differentiation, marginally impaired NF-κB activation and survival, but markedly exacerbated death triggered by IL-21. While activating the mitochondria-dependent apoptosis pathway in both Sharpin+/+ and Sharpincpdm B cells, IL-21 induced Sharpincpdm B cells to undergo sustained activation of caspase 9 and caspase 8 of the mitochondria-dependent and independent pathway, respectively, and ultimately caspase 3 in effecting apoptosis. These were associated with loss of the caspase 8 inhibitor cFLIP and reduction in cFLIP Linear M1-Ub, which interferes with cFLIP poly-ubiquitination at Lys48 and degradation. Finally, the viability of Sharpincpdm B cells was rescued by caspase inhibitors but virtually abrogated - together with Linear M1-Ub and cFLIP levels - by a small molecule HOIP inhibitor. Thus, LUBAC controls the cFLIP expression and inhibits the effects of caspase 8 and IL-21-activated caspase 9, thereby suppressing apoptosis of CD40 and IL-21-activated B cells and promoting GC B cell survival.


Assuntos
Apoptose , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígenos CD40/metabolismo , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Interleucinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Formação de Anticorpos/imunologia , Apoptose/efeitos dos fármacos , Biomarcadores , Caspase 8/metabolismo , Caspase 9 , Comunicação Celular , Sobrevivência Celular , Camundongos , Camundongos Transgênicos , Mutação , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ubiquitinas/metabolismo
20.
Biomed Res Int ; 2021: 5559187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33969118

RESUMO

COVID-19 has spread globally with over 90,000,000 incidences and 1,930,000 deaths by Jan 11, 2021, which poses a big threat to public health. It is urgent to distinguish COVID-19 from common pneumonia. In this study, we reported multiple clinical feature analyses on COVID-19 in Inner Mongolia for the first time. We dynamically monitored multiple clinical features of all 75 confirmed COVID-19 patients, 219 pneumonia patients, and 68 matched healthy people in Inner Mongolia. Then, we studied the association between COVID-19 and clinical characteristics, based on which to construct a novel logistic regression model for predicting COVID-19. As a result, among the tested clinical characteristics, WBC, hemoglobin, C-reactive protein (CRP), ALT, and Cr were significantly different between COVID-19 patients and patients in other groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.869 for the logistic regression model using multiple factors associated with COVID-19. Furthermore, the CRP reaction showed five different time-series patterns with one-peak and double-peak modes. In conclusion, our study identified a few clinical characteristics significantly different between COVID-19 patients and others in Inner Mongolia. The features can be used to establish a reliable logistic regression model for predicting COVID-19.


Assuntos
COVID-19/epidemiologia , Pneumonia Viral/epidemiologia , SARS-CoV-2/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , COVID-19/virologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/virologia , Curva ROC , Análise de Sistemas , Adulto Jovem
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