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1.
Adv Anesth ; 40(1): 131-147, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36333043

RESUMO

The number of electrophysiology (EP) procedures being performed has dramatically increased in recent years. This escalation necessitates a full understanding by the general anesthesiologist as to the risks, specific considerations, and comorbidities that accompany these now common procedures. Procedures reviewed in this article include atrial fibrillation and flutter ablation, supraventricular tachycardia ablation, ventricular tachycardia ablation, electrical cardioversion, pacemaker insertion, implantable cardioverter-defibrillator (ICD) insertion, and ICD lead extraction. General anesthetic considerations as well as procedure-specific concerns are discussed. Knowledge of these procedures will add to the anesthesiologist's armamentarium in safely caring for patients in the EP laboratory.


Assuntos
Anestésicos , Fibrilação Atrial , Ablação por Cateter , Desfibriladores Implantáveis , Humanos , Ablação por Cateter/métodos , Fibrilação Atrial/cirurgia , Eletrofisiologia Cardíaca
2.
Eur Radiol ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418619

RESUMO

OBJECTIVES: To establish a breast lesion risk stratification system using ultrasound images to predict breast malignancy and assess Breast Imaging Reporting and Data System (BI-RADS) categories simultaneously. METHODS: This multicenter study prospectively collected a dataset of ultrasound images for 5012 patients at thirty-two hospitals from December 2018 to December 2020. A deep learning (DL) model was developed to conduct binary categorization (benign and malignant) and BI-RADS categories (2, 3, 4a, 4b, 4c, and 5) simultaneously. The training set of 4212 patients and the internal test set of 416 patients were from thirty hospitals. The remaining two hospitals with 384 patients were used as an external test set. Three experienced radiologists performed a reader study on 324 patients randomly selected from the test sets. We compared the performance of the DL model with that of three radiologists and the consensus of the three radiologists. RESULTS: In the external test set, the DL model achieved areas under the receiver operating characteristic curve (AUCs) of 0.980 and 0.945 for the binary categorization and six-way categorizations, respectively. In the reader study set, the DL BI-RADS categories achieved a similar AUC (0.901 vs. 0.933, p = 0.0632), sensitivity (90.98% vs. 95.90%, p = 0.1094), and accuracy (83.33% vs. 79.01%, p = 0.0541), but higher specificity (78.71% vs. 68.81%, p = 0.0012) than those of the consensus of the three radiologists. CONCLUSIONS: The DL model performed well in distinguishing benign from malignant breast lesions and yielded outcomes similar to experienced radiologists. This indicates the potential applicability of the DL model in clinical diagnosis. KEY POINTS: • The DL model can achieve binary categorization for benign and malignant breast lesions and six-way BI-RADS categorizations for categories 2, 3, 4a, 4b, 4c, and 5, simultaneously. • The DL model showed acceptable agreement with radiologists for the classification of breast lesions. • The DL model performed well in distinguishing benign from malignant breast lesions and had promise in helping reduce unnecessary biopsies of BI-RADS 4a lesions.

3.
Genes (Basel) ; 13(11)2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36360298

RESUMO

MAPKAPK2 (MK2) is an important regulator of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, which is involved in a plethora of cellular processes concluding the development of gamete cells in meiosis and resisting pathogenic bacterial infestation. Hyriopsis cumingii is a significant mussel resource in China and a good material for pearl breeding. To explore the role of MK2 in H. cumingii, MK2 was identified and cloned, whose full-length cDNA was 1568 bp, including 87 bp in 5' UTR, 398 bp in 3' UTR, and 1083 bp in the open reading frame (ORF) region, encoding 360 amino acids. The expression of MK2 was the highest in the gills. Meanwhile, there was a significant difference in the gonads. After Aeromonas hydrophila and Lipopolysaccharide (LPS) infestation, the transcript level of the MK2 was upregulated in the gills. It indicated that MK2 might be involved in the innate immune response of H. cumingii after a pathogenic attack. After quantifying H. cumingii of different ages, it was found that the expression of MK2 was highest at 1 year old. In situ hybridization (ISH) results showed that the blue-purple hybridization signal was very significant in the oocytes and egg membranes of the female gonads of H. cumingii. The expression of MK2 increased gradually at the age of 1 to 5 months and showed a downward trend at the age of 5 to 8 months. It was suggested that MK2 might play an important role in the formation of primitive germ cells in H. cumingii. To sum up, MK2 might not only be involved in the immune response against pathogenic bacterial infection but also might play an important role in the development of the gonads in H. cumingii.


Assuntos
Unionidae , Feminino , Animais , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Unionidae/genética , Unionidae/microbiologia
4.
Healthcare (Basel) ; 10(11)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36360490

RESUMO

Background: Sepsis commonly causes acute respiratory distress syndrome (ARDS), and ARDS contributes to poor prognosis in sepsis patients. Early prediction of ARDS for sepsis patients remains a clinical challenge. This study aims to develop and validate chest computed tomography (CT) radiomic-based signatures for early prediction of ARDS and assessment of individual severity in sepsis patients. Methods: In this ambispective observational cohort study, a deep learning model, a sepsis-induced acute respiratory distress syndrome (SI-ARDS) prediction neural network, will be developed to extract radiomics features of chest CT from sepsis patients. The datasets will be collected from these retrospective and prospective cohorts, including 400 patients diagnosed with sepsis-3 definition during a period from 1 May 2015 to 30 May 2022. 160 patients of the retrospective cohort will be selected as a discovering group to reconstruct the model and 40 patients of the retrospective cohort will be selected as a testing group for internal validation. Additionally, 200 patients of the prospective cohort from two hospitals will be selected as a validating group for external validation. Data pertaining to chest CT, clinical information, immune-associated inflammatory indicators and follow-up will be collected. The primary outcome is to develop and validate the model, predicting in-hospital incidence of SI-ARDS. Finally, model performance will be evaluated using the area under the curve (AUC) of receiver operating characteristic (ROC), sensitivity and specificity, using internal and external validations. Discussion: Present studies reveal that early identification and classification of the SI-ARDS is essential to improve prognosis and disease management. Chest CT has been sought as a useful diagnostic tool to identify ARDS. However, when characteristic imaging findings were clearly presented, delays in diagnosis and treatment were impossible to avoid. In this ambispective cohort study, we hope to develop a novel model incorporating radiomic signatures and clinical signatures to provide an easy-to-use and individualized prediction of SI-ARDS occurrence and severe degree in patients at early stage.

5.
Commun Biol ; 5(1): 1239, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371560

RESUMO

Engineering microbes to produce plant-derived natural products provides an alternate solution to obtain bioactive products. Here we report a systematic approach to sequentially identify the rate-limiting steps and improve the biosynthesis of the cannabinoid precursor olivetolic acid (OLA) in Yarrowia lipolytica. We find that Pseudomonas sp LvaE encoding a short-chain acyl-CoA synthetase can efficiently convert hexanoic acid to hexanoyl-CoA. The co-expression of the acetyl-CoA carboxylase, the pyruvate dehydrogenase bypass, the NADPH-generating malic enzyme, as well as the activation of peroxisomal ß-oxidation pathway and ATP export pathway are effective strategies to redirect carbon flux toward OLA synthesis. Implementation of these strategies led to an 83-fold increase in OLA titer, reaching 9.18 mg/L of OLA in shake flask culture. This work may serve as a baseline for engineering cannabinoids biosynthesis in oleaginous yeast species.


Assuntos
Canabinoides , Yarrowia , Yarrowia/genética , Canabinoides/metabolismo , Engenharia Metabólica , Salicilatos/metabolismo
6.
Angew Chem Int Ed Engl ; : e202214235, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36259368

RESUMO

The non-heme iron ergothioneine synthase (EgtB) is a sulfoxide synthase that catalyzes oxidative C-S bond formation in the synthesis of ergothioneine, which plays roles against oxidative stress in cells. Despite extensive experimental and computational studies of the catalytic mechanisms of EgtB, the root causes for the selective C-S bond formation remain elusive. Using quantum mechanics/molecular mechanics (QM/MM) calculations, we show herein that a coordination switch of the sulfoxide intermediate is involved in the catalysis of the non-heme iron EgtB. This coordination switch from the S to the O atom is driven by the S/π electrostatic interactions, which efficiently promotes the observed stereoselective C-S bond formation while bypassing cysteine dioxygenation. The present mechanism is in agreement with all available experimental data, including regioselectivity, stereoselectivity and KIE results. This match underscores the critical role of coordination switching in the catalysis of non-heme enzymes.

7.
Front Bioeng Biotechnol ; 10: 1006925, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185456

RESUMO

In this work, hydrothermal pretreatment (autohydrolysis) was coupled with endo-xylanase enzymatic hydrolysis for bamboo shoot shell (BSS) to produce glucose and valuable xylooligosaccharides (XOS) rich in xylobiose (X2) and xylotriose (X3). Results showed that the enzymatic hydrolysis efficiency of pretreated BSS residue reached 88.4% with addition of PEG during the hydrolysis process. To enrich the portions of X2-X3 in XOS, endo-xylanase was used to hydrolyze the XOS in the prehydrolysate, which was obtained at the optimum condition (170°C, 50 min). After enzymatic hydrolysis, the yield of XOS reached 25.6%, which contained 76.7% of X2-X3. Moreover, the prehydrolysate contained a low concentration of fermentation inhibitors (formic acid 0.7 g/L, acetic acid 2.6 g/L, furfural 0.7 g/L). Based on mass balance, 32.1 g of glucose and 6.6 g of XOS (containing 5.1 g of X2-X3) could be produced from 100.0 g of BSS by the coupled technology. These results indicate that BSS could be an economical feedstock for the production of glucose and XOS.

8.
Front Cardiovasc Med ; 9: 992284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277786

RESUMO

The purpose of the present article is to identify intrinsic genes across general hypertension (HT), hypertension with left ventricular remodeling (HT-LVR), and uncontrolled hypertension (UN-HT). In total, four microarray datasets (GSE24752, GSE75360, GSE74144, and GSE71994) were downloaded from the GEO database and were used to identify differentially expressed genes (DEGs), respectively. Furthermore, gene set enrichment analysis (GSEA) was utilized to screen for significantly enriched biological pathways across the four datasets above, respectively. Furthermore, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were applied to screen out gene modules of interest and potential biological functions, respectively. Finally, a Metascape-based multiple gene list meta-analysis was used to investigate intrinsic genes at different stages of the progression of hypertension. A total of 75 DEGs (63 upregulated genes and 12 downregulated genes, GSE24752) and 23 DEGs (2 upregulated genes and 21 downregulated genes, GSE74144) were identified. However, there were few DEGs identified in GSE75360, GSE71994, and part of the GSE74144 datasets. GSEA and functional enrichment of gene module of interest have indicated that "Heme metabolism," "TNF alpha/NFkB," and "interferon alpha response signaling," and MYC target v1/v2 were enriched significantly in different stages of hypertension progression. Significantly, findings from the multiple gene list meta-analysis suggested that FBXW4 and other 13 genes were unique to the hypertension group, and TRIM11 and other 40 genes were mainly involved in hypertension with the left ventricular remodeling group, while the other 18 genes including F13A1 significantly enriched in uncontrolled hypertension. Collectively, the precise switch of the "immune-metabolic-inflammatory" loop pathway was the most significant hallmark across different stages of hypertension, thereby providing a potential therapeutic target for uncontrolled hypertension treatment.

9.
10.
Front Physiol ; 13: 961773, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091389

RESUMO

The process of spermatogenesis is complex and controlled by many genes. In mammals, Testis-expressed gene 11 (Tex11) and meiosis expressed gene 1 (Meig1) are typical spermatogenesis-related genes. In this study, we obtained the full length cDNAs for Tex11 (3143bp) and Meig1 (1649bp) in Hyriopsis cumingii by cloning. Among them, Hc-Tex11 contains 930 amino acids and Hc-Meig1 contains 91 amino acids. The protein molecular masses (MW) of Hc-Tex11 and Hc-Meig1 were 105.63 kDa and 10.95 kDa, respectively. Protein secondary structure analysis showed that Hc-TEX11 protein has three TPR domains. The expression of Hc-Tex11 and Hc-Meig1 in different tissues showed higher levels in testes. At different ages, the expression of Hc-Tex11 and Hc-Meig1 was higher levels in 3-year-old male mussels. During spermatogenesis, the mRNA levels of Hc-Tex11, Hc-Meig1 gradually increased with the development of spermatogonia and reached a peak during sperm maturation. Hc-Tex11 and Hc-Meig1 mRNA signals were detected on spermatogonia and spermatocytes by in situ hybridization. In addition, RNA interference (RNAi) experiments of Hc-Tex11 caused a down-regulated of Dmrt1, KinaseX, Tra-2 and Klhl10 genes and an up-regulated of ß-catenin gene. Based on the above experimental results, it can be speculated that Hc-Tex11 and Hc-Meig1 are important in the development of the male gonadal and spermatogenesis in H. cumingii, which can provide important clues to better comprehend the molecular mechanism of Tex11 and Meig1 in regulating spermatogenesis of bivalves.

11.
Lancet Reg Health West Pac ; 29: 100576, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36065174

RESUMO

Background: With the growing demand for breast screening in public health services and clinical care, ultrasound departments in China are facing tremendous challenges. Methods: A cross-sectional nationwide survey was conducted in 5,460 departments providing ultrasound diagnoses in mainland China from 2020 to 2021. The survey included general information about the ultrasound department, the characteristics of sonologists, the use of Breast Imaging Reporting and Data System (BI-RADS) templates, and the diagnostic accuracy rate of breast cancer ultrasound. Findings: There were on average 2.25 sonologists per 10,000 patients in mainland China per year. The average utilization rate of BI-RADS in Chinese hospitals was 87.02%. The GDP per capita of the province (P = 0.008), whether the hospital was specialized (P = 0.002) or a Tier 3 facility (P < 0.001), the percentage of doctors with master's and doctoral degrees (P < 0.001) and doctors ≤35 years (P = 0.005) were significantly and independently associated with the utilization rate of BI-RADS. The average diagnostic accuracy rate of breast cancer ultrasound in Chinese hospitals was 73.64%, and we observed significant positive associations between GDP per capita (P = 0.02), BI-RADS utilization rate (P = 0.019), and breast cancer ultrasound diagnostic accuracy. Interpretation: The utilization of BI-RADS templates effectively improved the diagnostic accuracy of ultrasound. Moreover, the survey summarized the current situation of departments and sonologists providing breast ultrasound diagnosis in mainland China, which helped monitor the development of the discipline and provide information for administrators to meet the growing demand. Funding: This work was supported by Natural Science Foundation of Beijing (7202156) and Foundation of ihecc (2019-C-0646-2).

12.
Appl Microbiol Biotechnol ; 106(18): 6125-6137, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36056198

RESUMO

The combination of Escherichia coli BL21 (DE3) and the pET expression system is used extensively for the expression of various recombinant proteins (RPs). However, RP overexpression often introduces a growth burden for the host, especially in the case of toxic proteins. The key to solving this problem is to reduce the host burden associated with protein overproduction, which is often achieved by regulating the expression or activity of T7 RNAP or growth-decoupled systems. However, these strategies mainly relieve or interrupt the robbing of host resources, and do not eliminate other types of host burdens in the production process. In this study, we constructed a production system based on a dynamic equilibrium to precisely relieve the host burden and increase the RP production. The system is composed of three modules, including the overexpression of basic growth-related genes (rRNA, RNAP core enzyme, sigma factors), prediction and overexpression of key proteins using the enzyme-constrained model ec_iECBD_1354, and dynamic regulation of growth-related and key protein expression intensity based on a burden-driven promoter. Using this system, the production of many high-burden proteins, including autolysis protein and E. coli membrane proteins, was increased to varying degrees. Among them, the cytosine transporter protein (CodB) was most significantly improved, with a 4.02-fold higher production compared to the wild strain. This system can effectively reduce the optimizing costs, and is suitable for developing various types of RP expression hosts rapidly. KEY POINTS: • The basic growth-related resources can relieve the host burden from recombinant protein. • The enzyme-constrained model can accurately predict key genes to improve yield. • The expression intensity can be dynamically adjusted with changes in burden.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Proteínas de Transporte/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regiões Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
13.
Water Res ; 224: 119108, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122448

RESUMO

Heavy metals and pesticides (HMPs) are common contaminants due to their extensive use worldwide. Diffusive gradients in thin films (DGT) are a good method for measuring the bioavailable concentration of pollutants. This study represents the first evaluation of HMP toxicity in aquatic biota using the DGT technique in sediments. Zhelin Bay was selected as the case study site because it has been contaminated by pollutants. Nonmetric multidimensional scaling (NMS) analysis reveals that a diverse range of pollutants (V, Cr, Ni, Cu, Zn, As, Se, InHg, Mo, Cd, Sb, W, Pb, CLP, PYR) are mainly influenced by sediment characteristics. Assessment of single HMP toxicity found that the risk quotient (RQ) values for Mn, Cu, inorganic Hg (InHg), chlorpyrifos (CLP) and diuron (DIU) are significantly higher than 1, indicating that the adverse effects of these single HMPs should not be ignored. The combined toxicity of HMP mixtures based on probabilistic ecotoxicological risk assessment shows that Zhelin Bay surface sediments had a medium probability (54.6%) of toxic effects to aquatic biota.


Assuntos
Clorpirifos , Mercúrio , Metais Pesados , Praguicidas , Poluentes Químicos da Água , Biota , Cádmio/análise , China , Diurona/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , Isoniazida/análogos & derivados , Chumbo/análise , Mercúrio/análise , Metais Pesados/análise , Praguicidas/análise , Medição de Risco , Poluentes Químicos da Água/análise
14.
Bioresour Technol ; 363: 127907, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36087655

RESUMO

Engineering microbial cell factories to convert CO2-based feedstock into chemicals and fuels provide a feasible carbon-neutral route for the third-generation biorefineries. Ethanol became one of the major products of syngas fermentation by engineered acetogens. The key building block chemical 3-hydroxypropionic acid (3-HP) can be synthesized from ethanol by the malonyl-CoA pathway with CO2 fixation. In this study, the effect of two ethanol consumption pathways on 3-HP synthesis were studied as well as the effect of TCA cycle, gluconeogenesis pathway, and transhydrogenase. And the 3-HP synthesis pathway was also optimized. The engineered strain synthesized 1.66 g/L of 3-HP with a yield of 0.24 g/g. Furthermore, the titer and the yield of 3-HP increased to 13.17 g/L and 0.57 g/g in the whole-cell biocatalysis system. This study indicated that ethanol as feedstock had the potential to synthesize 3-HP, which provided an alternative route for future biorefinery.


Assuntos
Escherichia coli , Engenharia Metabólica , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Etanol/metabolismo , Ácido Láctico/análogos & derivados , Malonil Coenzima A/metabolismo
15.
Microb Cell Fact ; 21(1): 191, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109777

RESUMO

Escherichia coli, one of the most efficient expression hosts for recombinant proteins (RPs), is widely used in chemical, medical, food and other industries. However, conventional expression strains are unable to effectively express proteins with complex structures or toxicity. The key to solving this problem is to alleviate the host burden associated with protein overproduction and to enhance the ability to accurately fold and modify RPs at high expression levels. Here, we summarize the recently developed optimization strategies for the high-level production of RPs from the two aspects of host burden and protein activity. The aim is to maximize the ability of researchers to quickly select an appropriate optimization strategy for improving the production of RPs.


Assuntos
Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes
16.
Eur J Pharmacol ; 934: 175303, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36174667

RESUMO

Increased expression of secreted frizzled related protein 3 (SFRP3) is associated with adverse outcomes of heart failure. The purpose of this study was to investigate the effect of SFRP3 on cardiac remodeling and its mechanism. Cardiac remodeling was induced by angiotensin II (Ang II) infusion in the mice, and in the neonatal rat cardiomyocytes (NRCM) treated with Ang II. The expression decreased in the heart of mice, and NRCM and HL-1 cells with Ang II treatment. Ang II-induced hypertrophy and fibrosis of heart in mice were attenuated by upregulation of SFRP3, and were further deteriorated by downregulation of SFRP3. Ang II-induced hypertrophy of NRCM and HL-1 cells were improved by SFRP3 overexpression, and were further deteriorated by SFRP3 knockdown. The oxidative stress increased in the heart of Ang II-treated mice, and this enhancement was inhibited by overexpressing of SFPR3, and was worsened by downregulation of SFPR3. These outcomes suggested that upregulation of SFPR3 could improve cardiac remodeling via inhibition of oxidative stress.


Assuntos
Angiotensina II , Remodelação Ventricular , Camundongos , Animais , Ratos , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Estresse Oxidativo , Miócitos Cardíacos/metabolismo , Apoptose , Fibrose , Hipertrofia/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Camundongos Endogâmicos C57BL
17.
Sensors (Basel) ; 22(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35957352

RESUMO

Navigation safety is one of the primary operational requirements for unmanned surface vehicles (USVs) in a complex marine environment, mainly guaranteed by a reliable path planning system for collision avoidance. This work proposes a novel weighted sum multi-objective optimisation strategy for USV collision avoidance path planning in restricted waters. In particular, the coefficients of different objectives could be tuned to emphasise the most critical design consideration under varying navigation scenarios. Moreover, in addition to the Convention on the International Regulations for Preventing Collisions at Sea (COLREGs), the terrain and weather constraints were also considered in the path planning system. The proposed USV collision avoidance path planning framework's effectiveness was demonstrated through numerical simulations and hardware-in-the-loop (HIL) tests. The numerical simulation results indicate that the proposed method could avoid collision with dynamic and static obstacles, and it is also adaptive to different navigation restrictions and preferences. Moreover, a USV navigation platform was established by incorporating true Automatic Identification System (AIS) signals, and HIL tests were performed with real-time AIS data in a water channel in the Zhoushan archipelago. The results demonstrate that the proposed USV path planning strategy is applicable in restricted waters with complex terrains and weather constraints.

18.
Nat Commun ; 13(1): 4711, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953472

RESUMO

Innate lymphoid cells (ILCs) exert important roles in host defense, tissue repair and inflammatory diseases. However, how ILC lineage specification is regulated remains largely elusive. Here we identify that circular RNA circTmem241 is highly expressed in group III innate lymphoid cells (ILC3s) and their progenitor cells. CircTmem241 deficiency impairs ILC3 commitment and attenuates anti-bacterial immunity. Mechanistically, circTmem241 interacts with Nono protein to recruit histone methyltransferase Ash1l onto Elk3 promoter in ILC progenitor cells (ILCPs). Ash1l-mediated histone modifications on Elk3 promoter enhance chromatin accessibility to initiate Elk3 transcription. Of note, circTmem241-/-, Nono-/- and Ash1l-/- ILCPs display impaired ILC3 differentiation, while Elk3 overexpression rescues ILC3 commitment ability. Finally, circTmem241-/-Elk3-/- mice show lower numbers of ILC3s and are more susceptible to bacterial infection. We reveal that the circTmem241-Nono-Ash1l-Elk3 axis is required for the ILCP differentiation into ILC3P and ILC3 maturation, which is important to manipulate this axis for ILC development on treatment of infectious diseases.


Assuntos
Imunidade Inata , Linfócitos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-ets/metabolismo , Animais , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase , Linfócitos/metabolismo , Camundongos , RNA Circular , Fatores de Transcrição/metabolismo
19.
Micron ; 161: 103342, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963207

RESUMO

As a critically endangered (CR) fish species, Chinese Bahaba is a unique "Giant Panda" fish species in China and has been listed among the national first-class wildlife protection animals and China's top 10 genetic resources of aquatic products since 2021. This fish species is of high commercial value because its swim bladder is commonly used in traditional Chinese medicine. Its otoliths are the sensory organs immersed in the endolymph for maintaining its balance and hearing. However, rare information has been reported on the sound absorption structure and chambers of otoliths of such "Giant Panda" fish. The big "C" groove was found in the fish's front sagittal otolith with the crystal cluster in the back sagittal otolith, the former of which is a 3D layered structure, that is constructed by elongated prismatic crystals. Besides, there are numerous small holes and adhesion material in this 3D layered structure, where many chambers were also found, indicating that some specific sounds may be captured by this structure and these chambers may then amplify such sounds at a certain wavelength. This finding could be of great importance for protecting and conserving this critically endangered species.


Assuntos
Membrana dos Otólitos , Ursidae , Animais , Microtomografia por Raio-X , Peixes , Audição
20.
Oxid Med Cell Longev ; 2022: 3034150, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958019

RESUMO

Hepatocellular carcinoma (HCC) is one of the dominating tumors causing death due to lack of timely discovery and valid treatment. Abnormal increase of Rac GTPase activating protein 1 (RACGAP1) has been verified to be an oncogene in plenty tumors. The profound mechanism of RACGAP1 was rarely reported in HCC. In this study, we explored the function and mechanism of RACGAP1 in HCC through multiple analysis and experiments. RACGAP1 expression was up-regulated in HCC samples and the high expression of RACGAP1 was an independent prognostic risk factor for HCC patients. Meanwhile, RACGAP1 promoted developments of HCC both in vitro and in vivo. We verified that RACGAP1 promoted proliferation of HCC via PI3K/AKT/CDK2 and PI3K/AKT/GSK3ß/Cyclin D1 signaling pathway. RACGAP1 accelerated the invasion and metastasis of HCC via phosphorylation of GSK3ß and nuclear translocation of ß-catenin. Furthermore, by luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay, we confirmed Recombinant GA Binding Protein Transcription Factor Alpha (GABPA) regulated the transcription of RACGAP1. All these findings revealed that RACGAP1 promotes the progression of HCC through a novel mechanism, which might be a new therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular , Proteínas Ativadoras de GTPase , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/genética
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