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1.
Adv Mater ; : e2211363, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626679

RESUMO

Fast and accurate detection of microbial cells in clinical samples is highly valuable but remains a challenge. Here, a simple, culture-free diagnostic system is developed for direct detection of pathogenic bacteria in water, urine and serum samples using an optical colorimetric biosensor. It consists of printed nanoarrays chemically conjugated with specific antibodies that exhibits distinct color changes after capturing target pathogens. By utilizing the internal capillarity inside an evaporating droplet, target preconcentration is achieved within a few minutes to enable rapid identification and more efficient detection of bacterial pathogens. More importantly, the scattering signals of bacteria can be significantly amplified by the nanoarrays due to strong near-field localization, which supports a visualizable analysis of the growth, reproduction and cell activity of bacteria at the single-cell level. Finally, in addition to high selectivity, this nanoarray-based biosensor is also capable of accurate quantification and continuous monitoring of bacterial load on food over a broad linear range, with a detection limit of 10 CFU mL-1 . This work provides an accessible and user-friendly tool for point-of-care testing of pathogens in many clinical and environmental applications, and possibly enables a breakthrough in early prevention and treatment. This article is protected by copyright. All rights reserved.

2.
Nano Lett ; 23(2): 685-693, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36594847

RESUMO

While tuning the electronic structure of Pt can thermodynamically alleviate CO poisoning in direct methanol fuel cells, the impact of interactions between intermediates on the reaction pathway is seldom studied. Herein, we contrive a PtBi model catalyst and realize a complete inhibition of the CO pathway and concurrent enhancement of the formate pathway in the alkaline methanol electrooxidation. The key role of Bi is enriching OH adsorbates (OHad) on the catalyst surface. The competitive adsorption of CO adsorbates (COad) and OHad at Pt sites, complementing the thermodynamic contribution from alloying Bi with Pt, switches the intermediate from COad to formate that circumvents CO poisoning. Hence, 8% Bi brings an approximately 6-fold increase in activity compared to pure Pt nanoparticles. This notion can be generalized to modify commercially available Pt/C catalysts by a microwave-assisted method, offering opportunities for the design and practical production of CO-tolerance electrocatalysts in an industrial setting.

3.
Plants (Basel) ; 12(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36679087

RESUMO

The genus Orychophragmus in the Brassicaceae family includes the types with 2n = 20, 22, 24, and 48. The species O. violaceus (L.) O. E. Schulz has 2n = 24 and is widely cultivated as an ornamental plant in China. This review summarizes the research progress of its genome structure and evolution in the context of cytogenetics and genome sequencing. This species has a large genome size of ~1 Gb and longer chromosomes than those of Brassica species, which is attributable to the burst of TE insertions. Even more, one tetraploidization event from about 600-800 million years ago is elucidated to occur during its genome evolution, which is consistent with the polyploidy nature of its genome revealed by the meiotic pairing patterns. Its chromosomes are still characterized by a larger size and deeper staining than those from Brassica species in their intergeneric hybrids, which is likely related to their inherent differences between genome structures and cytology. Its genome is dissected by the development of additional alien lines, and some traits are located on individual chromosomes. Due to the abundant dihydroxy fatty acids in its seed oil with superior lubricant properties and wide environmental adaptations, this plant promises to be utilized as one new oil crop in the future.

4.
ISME J ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690780

RESUMO

Exploring wild reservoirs of pathogenic viruses is critical for their long-term control and for predicting future pandemic scenarios. Here, a comparative in vitro infection analysis was first performed on 83 cell cultures derived from 55 mammalian species using pseudotyped viruses bearing S proteins from SARS-CoV-2, SARS-CoV, and MERS-CoV. Cell cultures from Thomas's horseshoe bats, king horseshoe bats, green monkeys, and ferrets were found to be highly susceptible to SARS-CoV-2, SARS-CoV, and MERS-CoV pseudotyped viruses. Moreover, five variants (del69-70, D80Y, S98F, T572I, and Q675H), that beside spike receptor-binding domain can significantly alter the host tropism of SARS-CoV-2. An examination of phylogenetic signals of transduction rates revealed that closely related taxa generally have similar susceptibility to MERS-CoV but not to SARS-CoV and SARS-CoV-2 pseudotyped viruses. Additionally, we discovered that the expression of 95 genes, e.g., PZDK1 and APOBEC3, were commonly associated with the transduction rates of SARS-CoV, MERS-CoV, and SARS-CoV-2 pseudotyped viruses. This study provides basic documentation of the susceptibility, variants, and molecules that underlie the cross-species transmission of these coronaviruses.

5.
Behav Sci (Basel) ; 13(1)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36661629

RESUMO

The sustainable development of infrastructure construction projects heavily depends on favorable cooperation of all parties and ethical code of conduct, while Un-ethical pro-organizational behavior (UPB) may undermine the mutual efforts and cause serious consequences. UPB has aroused wide interest of researchers, but what may trigger construction employees to engage in UPB at team-level has not been elucidated completely. With information asymmetry and huge uncertainty, the behaviors of employees in temporary project teams are marked by environmental and personal characters. The study discusses the influences of collective moral judgement focus on self (CMJS) and Machiavellianism on UPB. Through a moderated mediation analysis conducted on a set of survey data from Chinese construction projects, the empirical results of the two-level hierarchical linear model indicate that CMJS positively impacts UPB directly, and meanwhile Machiavellianism acts as a partial mediator in the relationship between CMJS and UPB. The findings also reveal that performance-avoidance goal orientation (PAGO) and motivation to learn (MTL) moderate and strengthen the relationship between Machiavellianism and UPB. The study offers practical suggestions for both project managers and policymakers of construction projects.

6.
Acc Chem Res ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688822

RESUMO

ConspectusThe use of quaternary stereocenters during lead candidate optimization continues to grow because of improved physiochemical and pharmacokinetic profiles of compounds with higher sp3 fraction. Pd-catalyzed redox-neutral alkene difunctionalization involving carbopalladation of alkenes followed by nucleophilic-trapping σ-alkyl-palladium intermediates has been developed as an efficient method to construct quaternary stereocenters. However, the low chemoselectivity and air sensitivity of organometallic nucleophiles, as well as their low availability and accessibility, limit the scope of application of this elegant strategy. Recently, Ni-catalyzed reductive cross-coupling has evolved into a privileged strategy to easily construct valuable C(sp3)-C bonds. Despite great progress, the enantioselective coupling of C(sp3) electrophiles still relies on activated or functionalized alkyl precursors, which are often unstable and require multiple steps to prepare. Therefore, Ni-catalyzed reductive difunctionalization of alkenes via selective cyclization/cross-coupling was developed. This strategy not only offers a robust and practical alternative for traditional redox-neutral alkene difunctionalization but also provides strategic complementarity for reductive cross-coupling of activated alkyl electrophiles. In this Account, we summarize the latest results from our laboratory on this topic. These findings mainly include our explorations in modulating the enantioselectivity and cyclization mode of reductive cyclization/cross-couplings.We will first discuss Ni-catalyzed enantioselective reductive cyclization/cross-coupling to construct valuable chiral heterocycles with quaternary stereocenters and focus on the effects of ligands, reductants, and additives and their roles in reductive cross-coupling. A wide range of electrophiles have been explored, including aryl halides, vinyl halides, alkynyl halides, gem-difluoroalkenes, CO2, trifluoromethyl alkenes, and cyano electrophiles. The synthetic potential of this approach has also been demonstrated in the synthesis of biologically active natural products and drug molecules. Second, we will detail how to tune the steric effects of nickel catalysts by modifying bipyridine ligands for regiodivergent cyclization/cross-couplings. Specifically, the use of bidentate ligands favors exo-selective cyclization/cross-coupling, while the use of a carboxylic acid-modified bipyridine ligand permits endo-selective cyclization/cross-coupling. We will also show how to activate the amide substrate by altering the electronic and steric properties of substituents on the nitrogen, thereby enabling the nucleophilic addition of aryl halides to amide carbonyls. Further investigation of ligand properties has led to tunable cyclization/cross-couplings (addition to the amide carbonyl vs 7-endo-cyclization) for the divergent synthesis of pharmacologically important 2-benzazepine frameworks. Finally, we serendipitously discover that modifying the ligands of nickel catalysts and changing the oxidation state of nickel can control the migratory aptitude of different groups, thus providing a switchable skeletal rearrangement strategy. This transformation is of high synthetic value because it represents a conceptually unprecedented new approach to C-C bond activation. Thus, this Account not only summarizes synthetic methods that allow the formation of valuable chiral heterocycles with quaternary stereocenters using a wide variety of electrophiles but also provides insight into the relationship between ligand structure, substrate, and cyclization selectivity.

7.
Theranostics ; 13(2): 639-658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632228

RESUMO

Rationale: Hepatic lymphatics are essential for liver homeostasis and immune function. However, the 3D structure and spatial distribution of hepatic lymphatic vessels (LVs) need to be confirmed. Moreover, the molecular information of hepatic lymphatic endothelial cells (LyECs) needs to be further studied. The bottleneck is the lack of specific markers or labeling methods for hepatic lymphatic endothelial cells (LyECs) Methods: Here, we proposed a method for the spatiotemporal sequential injection of antibodies (STSI-Ab) to selectively label hepatic LyECs in vivo. In addition, we also developed an efficient hepatic LyEC sorting method and performed deep transcriptome sequencing on hepatic LyECs. Results: The STSI-Ab method achieved selective labeling of the mouse hepatic lymphatic network. Three-dimensional fluorescence imaging results of the STSI-Ab mouse liver lobe clearly showed that hepatic LVs entangled with the portal vein but were not present in the central vein. The imaging data inspired a novel hepatic lobule structure model with an added set of LVs in the portal area. Furthermore, deep transcriptome sequencing of isolated hepatic LyECs and Masson's trichrome staining results suggested that hepatic LyECs might be an important source of collagen fibers deposited in the portal area during the process of liver fibrosis and bile duct ligation (BDL). Conclusions: We proposed an STSI-Ab method for selectively labeling hepatic LVs, distinguishing the hepatic LVs from other vessels, and mapping their 3D structure. This study opens an avenue for understanding hepatic lymphatic structure and it will be very beneficial to the study of hepatic LyEC functions.


Assuntos
Células Endoteliais , Vasos Linfáticos , Camundongos , Animais , Fígado/patologia , Vasos Linfáticos/diagnóstico por imagem , Cirrose Hepática/patologia , Perfilação da Expressão Gênica
8.
EMBO Rep ; : e55762, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36597993

RESUMO

N6 -Methyladenosine (m6 A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m6 A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m6 A homeostasis remain elusive. Here, we show that METTL14 stability is regulated by the competitive interaction of METTL3 with the E3 ligase STUB1. STUB1 directly interacts with METTL14 to mediate its ubiquitination at lysine residues K148, K156, and K162 for subsequent degradation, resulting in a significant decrease in total m6 A levels. The amino acid regions 450-454 and 464-480 of METTL3 are essential to promote METTL14 stabilization. Changes in STUB1 expression affect METTL14 protein levels, m6 A modification and tumorigenesis. Collectively, our findings uncover an ubiquitination mechanism controlling METTL14 protein levels to fine-tune m6 A homeostasis. Finally, we present evidence that modulating STUB1 expression to degrade METTL14 could represent a promising therapeutic strategy against cancer.

9.
Sci Total Environ ; 858(Pt 3): 159916, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36356727

RESUMO

In the production process of industrial products, different product structures, batches, and the selection of different production methods directly affect the resource utilization, distribution, consumption, and carbon emission generation in the production process. In this study, a strategy to select low carbon production methods for product structure and batch is proposed to advance resource management and carbon emission reduction in manufacturing production processes. Specifically, taking a typical casting industry as an example, we analyze the two factors of product structures and batches on the resource consumption and environmental impact of the production process to establish a production process carbon emission model; using forty casting products as the research objects, the clustering algorithm and multiple linear regression analysis method are used to establish the influence relationship between product structure, batch, and production carbon emissions. Based on the characteristics of product structure and batch, a strategy is proposed for selecting a low carbon production method. The study shows that in sand casting production, the 3D printing method is more low carbon for small volumes, reducing 56.057 % of carbon emissions. However, traditional technology is more low carbon for large volumes, which can reduce at least 6.778 % of carbon emissions. In addition, as the number of casting batches increases, the advantage of low carbon in traditional casting technology will rise. The results of this study may provide a new way to help the manufacturing industry develop and optimize the environmental impact of the product manufacturing process.


Assuntos
Carbono , Poluição Ambiental , Indústria Manufatureira , Poluição Ambiental/prevenção & controle
10.
Water Res ; 229: 119499, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549186

RESUMO

Erosion is the most widespread form of soil degradation and an important pathway of carbon transfer from land into aquatic systems, with significant impact on water quality and carbon cycle. However, it remains debatable whether erosion induces a carbon source or sink, and the fate of eroded soil carbon in aquatic systems remains poorly constrained. Here, we collect 41 representative soils from seven erosion-influenced basins and conduct microcosm simulation experiments to examine the fate of soil carbon under three different scenarios. We showed that soil carbon mineralization was generally promoted (by up to 10 times) in water under turbulence relative to in soils, but suppressed under static conditions upon entering into aquatic systems. Moreover, the enhancement of mineralization in turbulent systems is primarily related to soil aggregate content, while suppression in static systems positively relates to macromolecule abundance, indicating that soil geochemistry affects the magnitude of hydrodynamic effects on carbon mineralization. Random forest model further predicts that erosion may induce significant carbon sources in basins dominated by turbulent waters and aggregate-rich soils. Our findings demonstrate hydrodynamic and geochemical controls on soil carbon mineralization upon delivery into aquatic systems, which is a non-negligible part of the boundless carbon cycle and must be considered when making region-specific conservation strategies to reduce CO2 emissions from inland waters.


Assuntos
Carbono , Solo , Solo/química , Carbono/química , Hidrodinâmica , Ciclo do Carbono , Qualidade da Água
11.
Bioinformatics ; 39(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36477791

RESUMO

MOTIVATION: DNA methylation within gene body and promoters in cancer cells is well documented. An increasing number of studies showed that cytosine-phosphate-guanine (CpG) sites falling within other regulatory elements could also regulate target gene activation, mainly by affecting transcription factors (TFs) binding in human cancers. This led to the urgent need for comprehensively and effectively collecting distinct cis-regulatory elements and TF-binding sites (TFBS) to annotate DNA methylation regulation. RESULTS: We developed a database (CanMethdb, http://meth.liclab.net/CanMethdb/) that focused on the upstream and downstream annotations for CpG-genes in cancers. This included upstream cis-regulatory elements, especially those involving distal regions to genes, and TFBS annotations for the CpGs and downstream functional annotations for the target genes, computed through integrating abundant DNA methylation and gene expression profiles in diverse cancers. Users could inquire CpG-target gene pairs for a cancer type through inputting a genomic region, a CpG, a gene name, or select hypo/hypermethylated CpG sets. The current version of CanMethdb documented a total of 38 986 060 CpG-target gene pairs (with 6 769 130 unique pairs), involving 385 217 CpGs and 18 044 target genes, abundant cis-regulatory elements and TFs for 33 TCGA cancer types. CanMethdb might help biologists perform in-depth studies of target gene regulations based on DNA methylations in cancer. AVAILABILITY AND IMPLEMENTATION: The main program is available at https://github.com/chunquanlipathway/CanMethdb. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Metilação de DNA , Neoplasias , Humanos , Fatores de Transcrição/metabolismo , Genoma , Sequências Reguladoras de Ácido Nucleico , Regiões Promotoras Genéticas , Neoplasias/genética , DNA/metabolismo , Ilhas de CpG
12.
Adv Clin Exp Med ; 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36530029

RESUMO

BACKGROUND: Liver cancer, the vast majority of cases being hepatocellular carcinoma (HCC), is now the most malignant tumor in the world. Recurrence and metastasis remain the major obstacles on the way to the successful treatment of HCC. In recent years, the vital function of microRNAs (miRNAs) in human health and disease have been demonstrated. Large amounts of evidence demonstrate that miRNAs play an important role in the occurrence and progression of HCC. OBJECTIVES: To find new targets for improving the early diagnosis, treatment and clinical prognosis of liver cancer. MATERIAL AND METHODS: We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to analyze the expression of miR-29a-5p. A cell counting kit-8 (CCK-8) assay was used to measure the proliferation of liver cancer cells. Wound healing and transwell assays were used to detect migration and invasion in vitro. Western blot was used to detect the expression of the related protein. RESULTS: The miR-29a-5p was identified as a tumor-related miRNA. It is upregulated in HCC. The overexpression of miR-29a-5p contributes to the proliferation, invasion and metastasis of HCC cells. Furthermore, the downregulation of miR-29a-5p inhibited the growth, migration and invasion of HCC cells in vitro. Subsequently, we used bioinformatics methods to predict that AT-rich interaction domain 2 (ARID2) is the downstream target gene of miR-29a-5p. The downregulation of ARID2 could reverse the tumor suppressive effect caused by the knockdown of miR-29a-5p. Similarly, the epithelial-mesenchymal transition (EMT)-related protein epithelial marker E-cadherin expression increased and the mesenchymal marker Vimentin decreased when we downregulated the expression of miR-29a-5p. Interestingly, the knockdown of ARID2 could reverse this phenomenon. CONCLUSIONS: Our study demonstrated that miRNA-29a-5p was overexpressed in HCC cells. It promotes the progression of HCC by targeting ARID2 in an EMT manner.

13.
Nutr Metab (Lond) ; 19(1): 77, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348493

RESUMO

BACKGROUND: As a cardiometabolic disease, hypertension has shown an obvious upward trend, becoming a global epidemic chronic disease. Lifestyle intervention is a fundamental method for lowering blood pressure. This systematic review and meta-analysis aimed to evaluate the effects of time-restricted eating (TRE) on blood pressure. METHODS: Studies were retrieved from the PubMed, Embase, Cochrane Library, and Web of Science databases to evaluate the effects of TRE on blood pressure. The time frame of search was from the start of database construction until July 14, 2022.There were no language restrictions. Meta-analysis and meta-regression were performed using Stata version 16. The weighted mean difference with 95% CI was used to assess the effect of TRE on blood pressure, heart rate, weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. The main ending of this article were blood pressure and heart rate, while the secondary ending were weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. RESULTS: Ten randomized controlled trials involving 694 patients were identified. TRE significantly reduced systolic blood pressure (SBP) (mean difference = -4.15; 95% CI: -6.73, -2.30; P < 0.0001), but had no significant effect on diastolic blood pressure (DBP) (mean difference = -2.06; 95% CI: -4.16, 0.02; P = 0.053) and no beneficial effect on heart rate (mean difference = 0.36; 95% CI: -2.83, 3.54; P = 0.0825). TRE promoted weight loss (mean difference = -1.63; 95% CI: -2.61, -0.64; P = 0.001) and decreased blood glucose levels (mean difference = -2.80; 95% CI: -4.64, -0.96; P = 0.003), but had no significant effect on total cholesterol (mean difference = 0.03, 95% CI: -10.01, 10.08; P = 0.995), HDL-C (mean difference = 0.85, 95% CI: -1.80, 3.49; P = 0.531), LDL-C (mean difference = -0.86, 95% CI: -6.47, 4.76; P = 0.764), or triglycerides (mean difference = -3.524, 95% CI: -9.49, 2.45; P = 0.248). In a separate meta-regression analysis, the degree of SBP change was related to weight loss (P = 0.044) but not to glucose improvement (P = 0.867). CONCLUSIONS: The present meta-analysis suggests that TRE significantly reduced SBP, while no effect of reducing DBP was seen. The observed lower blood pressure may be attributed to significant weight loss. The effects of TRE on heart rate and blood lipid levels were not apparent.

14.
Biochem Biophys Res Commun ; 636(Pt 1): 25-32, 2022 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-36332479

RESUMO

This study aimed to evaluate the efficacy of intra-articular delivery of peripheral blood derived mesenchymal stromal cells (PB-MSCs) on the progression of trauma-induced osteoarthritis (OA) in mice. Adult male C57BL/6J mice subjected to destabilization of the medial meniscus surgeries (DMM) were randomly divided into four groups: sham surgery group; vehicle control group (treated with saline), PBMSC-treated group, or adipose tissue derived MSCs (AD-MSC)-treated group (n = 4 per group). PB-MSCs and AD-MSCs were harvested and cultured following previously established protocols, and pre-labeled with BrdU for 48 h before transplantation. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3-5) were intra-articular injected into the right knee joints thrice post-surgery. The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations. PB-MSCs administration significantly reduced subchondral bone volume comparing to the vehicle control group. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which was comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of the PB-MSCs treated group comparing to that of the vehicle control group. Co-expression of BrdU and Sox9 indicated that injected PB-MSCs differentiated in chondrocytes in situ, along with reduced levels of IL-6 within peripheral sera of PB-MSCs- and AD-MSCs-treated mice. Therefore, administration of PB-MSCs or AD-MSCs attenuated trauma-induced OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs are ideal cell source for treating cartilage-associated diseases.


Assuntos
Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite , Animais , Masculino , Camundongos , Bromodesoxiuridina , Cartilagem Articular/metabolismo , Modelos Animais de Doenças , Injeções Intra-Articulares , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Osteoartrite/patologia
15.
Cell Discov ; 8(1): 117, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36316318

RESUMO

Long noncoding RNAs (lncRNAs) are usually 5' capped and 3' polyadenylated, similar to most typical mRNAs. However, recent studies revealed a type of snoRNA-related lncRNA with unique structures, leading to questions on how they are processed and how they work. Here, we identify a novel snoRNA-related lncRNA named LNC-SNO49AB containing two C/D box snoRNA sequences, SNORD49A and SNORD49B; and show that LNC-SNO49AB represents an unreported type of lncRNA with a 5'-end m7G and a 3'-end snoRNA structure. LNC-SNO49AB was found highly expressed in leukemia patient samples, and silencing LNC-SNO49AB dramatically suppressed leukemia progression in vitro and in vivo. Subcellular location indicated that the LNC-SNO49AB is mainly located in nucleolus and interacted with the nucleolar protein fibrillarin. However, we found that LNC-SNO49AB does not play a role in 2'-O-methylation regulation, a classical function of snoRNA; instead, its snoRNA structure affected the lncRNA stability. We further demonstrated that LNC-SNO49AB could directly bind to the adenosine deaminase acting on RNA 1(ADAR1) and promoted its homodimerization followed by a high RNA A-to-I editing activity. Transcriptome profiling shows that LNC-SNO49AB and ADAR1 knockdown respectively share very similar patterns of RNA modification change in downstream signaling pathways, especially in cell cycle pathways. These findings suggest a previously unknown class of snoRNA-related lncRNAs, which function via a manner in nucleolus independently on snoRNA-guide rRNA modification. This is the first report that a lncRNA regulates genome-wide RNA A-to-I editing by enhancing ADAR1 dimerization to facilitate hematopoietic malignancy, suggesting that LNC-SNO49AB may be a novel target in therapy directed to leukemia.

16.
FASEB J ; 36(12): e22663, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36421017

RESUMO

Regardless of the improvements in diagnostic and therapeutic methods, the clinical outcomes of hepatocellular carcinoma (HCC) patients remain poor. Although accumulating evidence indicates that lncRNAs (long noncoding RNAs) are essential within the control of tumorigenesis and the metastasis of cancer, the underlying mechanisms remain largely unknown. This work explored the pattern of expression and functional significance of a newly found lncRNA, Ewing sarcoma-associated transcript 1 (EWSAT1), in HCC metastasis. The results indicated that EWSAT1 was upregulated significantly in HCC relative to that in normal tissues and was correlated with an aggressive phenotype and low patient survival. Functional experiments demonstrated that EWSAT1 could promote proliferation and HCC cell metastasis both in vitro and in vivo. Mechanistically, EWSAT1 binds directly to Yes-associated protein (YAP), promotes Sarcoma gene (Src)-induced phosphorylation of YAP, facilitates nuclear translocation of YAP, and consequently, activates the transcription of Hippo-YAP signaling target genes involved in cancer evolution. This study found that EWSAT1 plays a crucial role in HCC metastasis and that it has the potential to be a prognosis biomarker and a target for therapeutics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Sarcoma de Ewing , Humanos , Carcinoma Hepatocelular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sarcoma de Ewing/genética , Neoplasias Hepáticas/metabolismo , Regulação Neoplásica da Expressão Gênica
17.
Hum Cell ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36424471

RESUMO

Cancer-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) can promote tumor progression by delivering microRNA (miRNA). Whether EVs could transfer miR-1228-3p into hepatocellular carcinoma (HCC) cells to affect chemoresistance was discussed in this study. Normal fibroblasts (NFs) and CAFs were isolated from tissue samples of HCC patients. We assessed the functions of HCC cells after co-culturing with NFs and CAFs. miR-1228-3p gain-of-function experiments were conducted. Next, functional assays were carried out to determine the binding of miR-1228-3p to placenta associated 8 (PLAC8). In vivo models were constructed for validation. CAFs-derived EVs exerted promoting effect on proliferative, migrating, invading potential of HCC cells and their resistance to sorafenib. PLAC8 was demonstrated as a direct target of miR-1228-3p. By targeting PLAC8, miR-1228-3p activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. In addition, the transfer of miR-1228-3p from CAFs-derived EVs into HCC cells boosted chemoresistance of HCC cells, which was reversed by restoring PLAC8. All in all, CAF-EV-carried miR-1228-3p strengthens the chemoresistance of HCC through activating PLAC8-mediated PI3K/AKT pathway. This finding contributes to the development of EV-based therapies overcoming the chemoresistance of HCC.

18.
Int J Mol Sci ; 23(19)2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36232615

RESUMO

To study the thermal decomposition behavior of 4,4'-azobis(1,2,4-triazole) (ATRZ), the non-isothermal thermal decomposition kinetics of ATRZ were studied using the thermogravimetric-differential scanning calorimetry (TG-DSC) method. The TG-DSC of ATRZ was analyzed at heating rates of 5, 10, 15, and 20 K·min-1 in an argon atmosphere. The thermal decomposition kinetic parameters at peak temperature (Tp), such as apparent activation energy (Ea) and pre-exponential factor (lgA) of ATRZ, were calculated using the Kissinger, Ozawa, and Satava-Sestak methods. Ea and lgA calculated using the Kissinger, Ozawa, and Satava-Sestak methods are very close, at 780.2 kJ·mol-1/70.5 s-1, 751.1 kJ·mol-1/71.8 s-1, and 762.1 kJ·mol-1/71.8 s-1, respectively. Using a combination of three methods, the reaction mechanism function g(α) of ATRZ was obtained. The results show that the decomposition temperature of ATRZ is about 310 °C, and the decomposition is rapidly exothermic. The pyrolysis path of ATRZ was investigated through a pyrolysis-gas chromatography mass spectrometry (PY-GC/MS) experiment. ATRZ has three different decomposition paths and finally generates N2, HC-N-CH, N≡C-N, and HC=N-C≡N. The laser ignition combustion duration of ATRZ was 0.5033 s and the peak temperature was 1913 °C. The laser ignition combustion duration of ATRZ+CL-20 was 1.0277 s and the peak temperature was 2105 °C. The rapid energy release rate of ATRZ promotes the combustion energy release of CL-20.


Assuntos
Nitrogênio , Pirólise , Argônio , Cinética , Termogravimetria , Triazóis
19.
BMC Pregnancy Childbirth ; 22(1): 738, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36184592

RESUMO

OBJECTIVES: To study the correlations between facial profile markers and crown-lump length (CRL) in a Chinese population, and to evaluate the clinical value of these markers for abnormal fetuses during the first trimester (11 to 13+6 gestational weeks).  METHODS: The facial profile markers were as followings: inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA), frontal space (FS) distance and profile line (PL) distance. These markers were measured in facial mid-sagittal section through ViewPoint 6 software. The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic (ROC) curves. RESULTS: According to the first-trimester scanning (FTS) and follow-up, 31 fetuses were enrolled in the abnormal group, including 14 cases of trisomy 21, 7 cases of trisomy 18, 10 cases with cleft lip and palate (CLP), and 1000 normal fetuses were selected. Among the normal fetuses, the IFA, FS distance and PL distance had negative correlations with CRL. The MNM angle and FMA had positive correlations with CRL. The mean IFA values for fetuses with trisomy 21 and trisomy 18 were 74.11° (standard deviation (SD) 7.48) and 69.88° (SD 7.08), respectively, which were significantly smaller than the normal fetuses (p = 0.013; p = 0.003). The mean MNM angle of fetuses with trisomy 18 and CLP were 6.98° (SD 2.61) and 9.41° (SD 2.57), respectively, which were significantly greater than the normal fetuses (p = 0.005; p < 0.001). The mean FMA values of trisomy 18 fetuses were 63.95° (SD 4.77), which was significantly smaller than the normal fetuses (p < 0.001). The mean FS distance of CLP fetuses was -0.22 mm (SD 1.38), which was significantly smaller than the normal fetuses (p < 0.001). The mean PL distance of trisomy 21, trisomy 18 and CLP fetuses were 2.89 mm (SD 0.41), 2.91 mm (SD 0.56) and 2.71 mm (SD 0.37), respectively. The difference with the normal fetuses had no statistical significance (p = 0.56; p = 0.607; p = 0.54). CONCLUSIONS: Fetal facial profile markers had excellent correlations with CRL during the first trimester. IFA had certain clinical significance in detecting trisomy 21. FMA, IFA and MNM angle were reliable indicators for screening trisomy 18. The abnormal MNM angle and FS distance could be used as sensitive indicators for CLP. However, PL distance was not the best markers for trisomy 21, trisomy 18 and CLP.


Assuntos
Fenda Labial , Fissura Palatina , Síndrome de Down , Síndrome de Down/diagnóstico , Feminino , Feto , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Trissomia , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Ultrassonografia Pré-Natal
20.
Dig Liver Dis ; 2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36289024

RESUMO

OBJECTIVE: The risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood. METHODS: Studies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood. RESULTS: Six studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR = 1.17, 95% CI: 1.08-1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR = 1.27, 95% CI: 1.16-1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89-1.11, P = 0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR = 1.17, 95% CI: 1.02-1.33, P = 0.02) and moderate to severe NAFLD (RR = 1.51, 95% CI: 1.16-1.98, P = 0.002). CONCLUSIONS: Foetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine.

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