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1.
Plant Physiol Biochem ; 216: 109131, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39305558

RESUMEN

Node Inception (NIN) plays a crucial role in legume symbiosis by participating in both infection and nodule formation processes. However, its specific function in mungbean (Vigna radiata) remains poorly understood. This study aimed to functionally characterize the VrNIN1 gene in mungbean through an enhanced hairy root transformation approach. Examination of proVrNIN1: GUS hairy roots via GUS staining indicated the expression of VrNIN1 in later root promodia, nodule primordia, and nodules. Phenotypic evaluation revealed that overexpression or silencing of VrNIN1 led to a significant reduction in nodule numbers in hairy roots compared to controls. Additionally, interaction between VrNIN1 and VrNNC1 was confirmed through yeast two-hybrid, luciferase complementation and Co-immunoprecipitation assays. VrNNC1 expression was observed in the vascular bundle and cortex of roots and root nodules, where it notably suppressed nodule formation in transgenic hairy roots. Furthermore, gene expression analysis demonstrated the involvement of VrNIN1 and VrNNC1 in regulating root nodulation by modulating the expression of VrRIC1 and VrEDOD40. This study not only optimized the genetic transformation system for hairy roots in mungbean, but also provided mechanistic insights into the regulatory role of VrNIN1 in root nodule symbiosis in mungbean.

2.
Adv Healthc Mater ; : e2402916, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39344873

RESUMEN

Large segmental bone defects often lead to nonunion and dysfunction, posing a significant challenge for clinicians. Inspired by the intrinsic bone defect repair logic of "vascularization and then osteogenesis", this study originally reports a smart implantable hydrogel (PDS-DC) with high mechanical properties, controllable scaffold degradation, and timing drug release that can proactively match different bone healing cycles to efficiently promote bone regeneration. The main scaffold of PDS-DC consists of polyacrylamide, polydopamine, and silk fibroin, which endows it with superior interfacial adhesion, structural toughness, and mechanical stiffness. In particular, the adjustment of scaffold cross-linking agent mixing ratio can effectively regulate the in vivo degradation rate of PDS-DC and intelligently satisfy the requirements of different bone defect healing cycles. Ultimately, PDS hydrogel loaded with free desferrioxamine (DFO) and CaCO3 mineralized ZIF-90 loaded bone morphogenetic protein-2 (BMP-2) to stimulate efficient angiogenesis and osteogenesis. Notably, DFO is released rapidly by free diffusion, whereas BMP-2 is released slowly by pH-dependent layer-by-layer disintegration, resulting in a significant difference in release time, thus matching the intrinsic logic of bone defect repair. In vivo and in vitro results confirm that PDS-DC can effectively realize high-quality bone generation and intelligently regulate to adapt to different demands of bone defects.

3.
Anal Sci ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300044

RESUMEN

Recently, the misuse of organic arsenic feed additives, such as roxarsone (ROX), has increasingly jeopardized both human health and the environment. In response, a unique electron-rich pyrazine-cored fluorescent covalent organic framework (COF) nanosheet, named as COF-TMP, was synthesized using an alkali-catalyzed reaction between 2, 3, 5, 6-tetramethylpyrazine (TMP) and terephthalaldehyde (TPA). Characterization demonstrated that COF-TMP boasted high porosity, pronounced fluorescence, and an abundance of (E)-2-styrylpyrazine (SPA) groups. These attributes render it an exceptional fluorescent sensor for the ultrahigh sensitivity detection of electron-deficient ROX molecules. The limit of detection (LOD) for COF-TMP in detecting ROX was found to be 0.015 ppb through fluorescence-quenching titration experiments-surpassing all previously reported fluorescent sensors. A combination of experimental results and theoretical calculations suggests that the extraordinary detection capability of COF-TMP for ROX arises from a static quenching mechanism. This study paves the way not only for a novel pyrazine-based fluorescent COF nanosheet with high porosity, exceptional fluorescent capabilities, and abundant SPA groups suitable for highly sensitive and selective ROX detection but also hints at its potential application as a fluorescent sensor for environmental pollution management and related domains.

4.
Heliyon ; 10(14): e34396, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39130457

RESUMEN

Xijiao Huojiu (Xijiao), an ancient Chinese rice wine (ACRW), is produced using traditional methods, which involve biological-ageing-like process and result in distinctive sensory profiles. However, its aroma composition is still unclear. In this study, the aroma characteristics of three samples with varying ageing times were examined. Xijiao_SCT, with a short cellar time, exhibited a strong fruity and floral aroma and a less grain-like aroma. Conversely, Xijiao_LCT, which had a long cellar time, had a deep cocoa- and caramel-like aroma. A total of 27 key odorants that greatly influenced the aroma characteristics of Xijiao were identified. Comparative studies were used to identify 12 key odorants that distinguish Xijiao from modern Chinese rice wine (MCRW) and grape wines (GW). Additionally, 13 dominant latent ageing markers differentiated Xijiao_SCT from Xijiao_LCT. Our results suggested that ACRW and MCRW have overlapping but distinct volatile metabolomic profiles, highlighting the characteristics of ACRW during ageing process.

6.
Plant Cell ; 36(10): 4557-4575, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39102897

RESUMEN

Identifying the essential factors and underlying mechanisms regulating plant heat stress (HS) responses is crucial for mitigating the threat posed by HS on plant growth, development, distribution, and productivity. In this study, we found that the Arabidopsis (Arabidopsis thaliana) super-killer2 (ski2) dicer-like4 (dcl4) mutant, characterized by RNA processing defects and the accumulation of abundant 22-nt small interfering RNAs derived from protein-coding transcripts, displayed significantly increased expression levels of HS-responsive genes and enhanced thermotolerance. These traits primarily resulted from the suppression of SMAX1-LIKE4 (SMXL4) and SMXL5, which encode 2 putative transcriptional regulators that belong to the SMXL protein family. While smxl4 and smxl5 single mutants were similar to wild type, the smxl4 smxl5 double mutant displayed substantially heightened seedling thermotolerance. Further investigation demonstrated that SMXL4 and SMXL5 repressed the transcription of HEAT-SHOCK TRANSCRIPTION FACTOR A2 (HSFA2), encoding a master regulator of thermotolerance, independently of ethylene-response factor-associated amphiphilic repression motifs. Moreover, SMXL4 and SMXL5 interacted with HSFA1d and HSFA1e, central regulators sensing and transducing HS stimuli, and antagonistically affected their transactivation activity. In addition, HSFA2 directly bound to the SMXL4 and SMXL5 promoters, inducing their expression during recovery from HS. Collectively, our findings elucidate the role of the SMXL4/SMXL5-HSFA2 regulatory module in orchestrating plant thermotolerance under HS.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción del Choque Térmico , Termotolerancia , Arabidopsis/genética , Arabidopsis/fisiología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Termotolerancia/genética , Factores de Transcripción del Choque Térmico/genética , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Respuesta al Choque Térmico/genética , Mutación/genética , Transcripción Genética , Plantas Modificadas Genéticamente
7.
Heliyon ; 10(14): e34432, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39104482

RESUMEN

Background: Moyamoya disease (MMD), characterized by chronic cerebrovascular pathology, poses a rare yet significant clinical challenge, associated with elevated rates of mortality and disability. Despite intensive research endeavors, the exact biomarkers driving its pathogenesis remain enigmatic. Methods: The expression patterns of GSE189993 and GSE141022 were retrieved from the Gene Expression Omnibus (GEO) repository to procure differentially expressed genes (DEGs) between samples afflicted with MMD and those under control conditions. The Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine with Recursive Feature Elimination (SVM-RFE), and Random Forest (RF) algorithms were employed for identifying candidate diagnostic genes associated with MMD. Subsequently, these candidate genes underwent validation in an independent cohort (GSE157628). The CMAP database was ultimately employed to forecast drugs pertinent to MMD for clinical translation. Results: A collective of 240 DEGs were discerned. Functional enrichment scrutiny unveiled the enrichment of the cholesterol metabolism pathway, salmonella infection pathway, and allograft rejection pathway within the MMD cohort. EPDR1, DENND3, and NCSTN emerged as discerned diagnostic biomarkers for MMD. The CMAP database was ultimately employed to scrutinize the ten most auspicious pharmaceutical compounds for managing MMD. Finally, after validation through in vitro experiments, EPDR1, DENND3, and NCSTN were identified as the key genes. Conclusion: EPDR1, DENND3, and NCSTN have emerged as potential novel biomarkers for MMD. The involvement of T lymphocytes, neutrophilic granulocytes, dendritic cells, natural killer cells, and plasma cells could be pivotal in the pathogenesis and advancement of MMD.

8.
BMC Cancer ; 24(1): 961, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107726

RESUMEN

BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients. METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated. RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa. CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.


Asunto(s)
Biomarcadores de Tumor , Exosomas , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/patología , Exosomas/genética , Exosomas/metabolismo , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Regulación Neoplásica de la Expresión Génica , Anciano , Perfilación de la Expresión Génica/métodos , Curva ROC , Antígeno CA-19-9/sangre
9.
Technol Cancer Res Treat ; 23: 15330338241272043, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39149934

RESUMEN

PURPOSE: Research on bone metastasis in esophageal cancer (EC) is relatively limited. Once bone metastasis occurs in patients, their prognosis is poor, and it severely affects their quality of life. Currently, there is a lack of convenient tumor markers for early identification of bone metastasis in EC. Our research aims to explore whether neutrophil-lymphocyte ratio (NLR) can predict bone metastasis in patients with EC. METHODS: Retrospective analysis of clinical indicators was performed on 604 patients with EC. They were divided into groups based on whether or not there was bone metastasis, and the patients' coagulation-related tests, blood routine, tumor markers and other indicators were collected. The receiver operating characteristic curve (ROC) were used to determine the predictive ability of parameters such as NLR for bone metastasis in EC, and univariate and multivariate logistic regression analyses were conducted to determine the impact of each indicator on bone metastasis. Using binary logistic regression to obtain the predictive probability of NLR combined with tumor markers. RESULTS: ROC curves analysis suggested that the area under the curve (AUC) of the NLR was 0.681, with a sensitivity of 79.2% and a specificity of 52.6%, which can be used as a predictive factor for bone metastasis in EC. Multivariate logistic regression analysis showed that high NLR (odds ratio [OR]: 2.608, 95% confidence interval [CI]: 1.395-4.874, P = 0.003) can function as an independent risk factor for bone metastasis in patients with EC. Additionally, high PT, high APTT, high FDP, high CEA, high CA724, low hemoglobin, and low platelet levels can also predict bone metastasis in EC. When NLR was combined with tumor markers, the area under the curve was 0.760 (95% CI: 0.713-0.807, P < 0.001), significantly enhancing the predictability of bone metastasis in EC. CONCLUSION: NLR, as a convenient, non-invasive, and cost-effective inflammatory indicator, could predict bone metastasis in EC. Combining NLR with tumor markers can significantly improve the diagnostic accuracy of bone metastasis in EC.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Óseas , Neoplasias Esofágicas , Linfocitos , Neutrófilos , Curva ROC , Humanos , Neutrófilos/patología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/sangre , Neoplasias Óseas/secundario , Neoplasias Óseas/sangre , Femenino , Masculino , Linfocitos/patología , Persona de Mediana Edad , Pronóstico , Anciano , Estudios Retrospectivos , Biomarcadores de Tumor/sangre , Adulto , Recuento de Linfocitos , Recuento de Leucocitos
10.
Animals (Basel) ; 14(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38998106

RESUMEN

Janus kinase 2 (JAK2) plays a critical role in myoblast proliferation and fat deposition in animals. Our previous RNA-Seq analyses identified a close association between the JAK2 gene and muscle development. To date, research delving into the relationship between the JAK2 gene and growth traits has been sparse. In this study, we sought to investigate the relationship between novel mutations within the JAK2 gene and goat growth traits. Herein, two novel InDel (Insertion/Deletion) polymorphisms within the JAK2 gene were detected in 548 goats, and only two genotypes were designated as ID (Insertion/Deletion) and DD (Deletion/Deletion). The results indicate that the two InDels, the del19008 locus in intron 2 and del72416 InDel in intron 6, showed significant associations with growth traits (p < 0.05). Compared to Nubian and Jianzhou Daer goats, the del72416 locus displayed a more pronounced effect in the Fuqing breed group. In the Nubian breed (NB) group, both InDels showed a marked influence on body height (BH). There were strong linkages observed for these two InDels between the Fuqing (FQ) and Jianzhou (JZ) populations. The DD-ID diplotype was associated with inferior growth traits in chest width (ChW) and cannon circumference (CaC) in the FQ goats compared to the other diplotypes. In the NB population, the DD-DD diplotype exhibited a marked negative impact on BH and HuWI (hucklebone width index), in contrast to the other diplotypes. In summary, our findings suggest that the two InDel polymorphisms within the JAK2 gene could serve as valuable molecular markers for enhancing goat growth traits in breeding programs.

11.
ChemSusChem ; : e202400899, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39010791

RESUMEN

The selective conversion of biomass fermentation derived from an acetone-butanol-ethanol (ABE) mixture into high-value biofuels is of paramount importance for industrial applications. However, challenges persist in effectively controlling the selectivity of long carbon chain ketones in elevated ABE conversion. In this research, a Ca-doped Ni-CaO-SiO2 catalyst was designed and employed to achieve a remarkable conversion of 89.9% into ketone products from the extracted ABE mixture. The selectivity for C8+ ketones reaches 41.8%, demonstrating exceptional performance. The reversible phase transition between Ca2SiO4 and CaCO3 enhances the recyclability, thereby improving the sustainability of the process. Additionally, the trace intermediate 3-hepten-2-one was successfully detected using two-dimensional GC×GC-MS, elucidating the conversion pathway in the catalytic upgrading of the ABE mixture. This finding offers a potential route for the efficient utilization of biomass and the highly selective production of value-added chemicals.

12.
Animals (Basel) ; 14(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38929389

RESUMEN

In this study, we measured the growth performance and intramuscular fat (IMF) content of the Longissimus dorsi (LD) of Fuqing goats (FQs) and Nubian goats (NBYs), which exhibit extreme phenotypic differences in terms of their production and meat quality traits. RNA-Seq analysis was performed, and transcriptome data were obtained from the LD tissue of 3-month fetuses (E3), 0-month lambs (0M), 3-month lambs (3M), and 12-month lambs (12M) to reveal the differences in the molecular mechanisms regulating the muscle development and IMF deposition between FQs and NBYs. The results showed that a higher body weight and average daily gain were observed in the NBYs at three developmental stages after birth, whereas a higher IMF content was registered in the FQs at 12M. Additionally, transcriptome profiles during the embryonic period and after birth were completely different for both FQs and NBYs. Moreover, DEGs (KIF23, CCDC69, CCNA2, MKI67, KIF11, RACGAP1, NUSAP1, SKP2, ZBTB18, NES, LOC102180034, CAPN6, TUBA1A, LOC102178700, and PEG10) significantly enriched in the cell cycle (ko04110) at E3 (FQs vs. NBYs), and DEGs (MRPS7, RPS8, RPL6, RPL4, RPS11, RPS10, RPL5, RPS6, RPL8, RPS13, RPS24, RPS15, RPL23) significantly enriched in ribosomes (ko03010) at 0M (FQs vs. NBYs) related to myogenic differentiation and fusion were identified. Meanwhile, the differences in glucose and lipid metabolism began at the E3 timepoint and continued to strengthen as growth proceeded in FQs vs. NBYs. DEGs (CD36, ADIROQR2, ACACA, ACACB, CPT1A, IGF1R, IRS2, LDH-A, PKM, HK2, PFKP, PCK1, GPI, FASN, FADS1, ELOVL6, HADHB, ACOK1, ACAA2, and ACSL4) at 3M (FQs vs. NBYs) and 12M (FQs vs. NBYs) significantly enriched in the AMPK signaling pathway (ko04152), insulin resistance (ko04931), the insulin signaling pathway (ko04910), fatty acid metabolism (ko01212), and glycolysis/gluconeogenesis (ko00010) related to IMF deposition were identified. Further, the results from this study provide the basis for future studies on the mechanisms regulating muscle development and IMF deposition in different breeds of goats, and the candidate genes identified could be used in the selection process.

13.
Front Neurosci ; 18: 1394234, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872940

RESUMEN

Computer aided diagnosis methods play an important role in Attention Deficit Hyperactivity Disorder (ADHD) identification. Dynamic functional connectivity (dFC) analysis has been widely used for ADHD diagnosis based on resting-state functional magnetic resonance imaging (rs-fMRI), which can help capture abnormalities of brain activity. However, most existing dFC-based methods only focus on dependencies between two adjacent timestamps, ignoring global dynamic evolution patterns. Furthermore, the majority of these methods fail to adaptively learn dFCs. In this paper, we propose an adaptive spatial-temporal neural network (ASTNet) comprising three modules for ADHD identification based on rs-fMRI time series. Specifically, we first partition rs-fMRI time series into multiple segments using non-overlapping sliding windows. Then, adaptive functional connectivity generation (AFCG) is used to model spatial relationships among regions-of-interest (ROIs) with adaptive dFCs as input. Finally, we employ a temporal dependency mining (TDM) module which combines local and global branches to capture global temporal dependencies from the spatially-dependent pattern sequences. Experimental results on the ADHD-200 dataset demonstrate the superiority of the proposed ASTNet over competing approaches in automated ADHD classification.

14.
Nat Commun ; 15(1): 4474, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796514

RESUMEN

Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.


Asunto(s)
Algoritmos , Inteligencia Artificial , Odorantes , Olfato , Dispositivos Electrónicos Vestibles , Humanos , Olfato/fisiología , Interfaz Usuario-Computador , Adulto , Masculino
15.
Chem Res Toxicol ; 37(6): 944-956, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38771988

RESUMEN

Celastrol (Cel), extracted from Tripterygium wilfordii Hook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol-chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18-19 mg/mL) in water, slower peak time (Tmax = 4 h), and clearance (T1/2 = 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.


Asunto(s)
Fármacos Antiobesidad , Quitosano , Obesidad , Triterpenos Pentacíclicos , Triterpenos , Animales , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/química , Obesidad/tratamiento farmacológico , Masculino , Triterpenos/química , Triterpenos/farmacología , Ratones , Quitosano/química , Quitosano/farmacología , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/química , Ratas , Dieta Alta en Grasa/efectos adversos , Humanos , Ratas Sprague-Dawley , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos , Tripterygium/química
16.
Hepatology ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563629

RESUMEN

BACKGROUND AND AIMS: Fibrosis is the common end point for all forms of chronic liver injury, and the progression of fibrosis leads to the development of end-stage liver disease. Activation of HSCs and their transdifferentiation into myofibroblasts results in the accumulation of extracellular matrix proteins that form the fibrotic scar. Long noncoding RNAs regulate the activity of HSCs and provide targets for fibrotic therapies. APPROACH AND RESULTS: We identified long noncoding RNA TILAM located near COL1A1 , expressed in HSCs, and induced with liver fibrosis in humans and mice. Loss-of-function studies in human HSCs and human liver organoids revealed that TILAM regulates the expression of COL1A1 and other extracellular matrix genes. To determine the role of TILAM in vivo, we annotated the mouse ortholog ( Tilam ), generated Tilam- deficient green fluorescent protein-reporter mice, and challenged these mice in 2 different models of liver fibrosis. Single-cell data and analysis of single-data and analysis of Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Tilam -deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Furthermore, loss of Tilam expression attenuated the development of fibrosis in the setting of in vivo liver injury. Finally, we found that TILAM interacts with promyelocytic leukemia nuclear body scaffold protein to regulate a feedback loop by which TGF-ß2 reinforces TILAM expression and nuclear localization of promyelocytic leukemia nuclear body scaffold protein to promote the fibrotic activity of HSCs. CONCLUSIONS: TILAM is activated in HSCs with liver injury and interacts with promyelocytic leukemia nuclear body scaffold protein to drive the development of fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end-stage liver disease.

17.
Front Vet Sci ; 11: 1354548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38496312

RESUMEN

Mycoplasma synoviae (MS) is an economically important pathogen in the poultry industry. Vaccination is an effective method to prevent and control MS infections. Currently two live attenuated MS vaccines are commercially available, the temperature-sensitive MS-H vaccine strain and the NAD-independent MS1 vaccine strain. Differentiation of vaccine strains from wild-type (WT) strains is crucial for monitoring MS infection, especially after vaccination. In this study, we developed a Taqman duplex real-time polymerase chain reaction (PCR) method to identify MS1 vaccine strains from WT strains. The method was specific and did not cross-react with other avian pathogens. The sensitivity assay indicated that no inhibition occurred between probes or between mixed and pure templates in duplex real-time PCR. Compared with the melt-based mismatch amplification mutation assay (MAMA), our method was more sensitive and rapid. In conclusion, the Taqman duplex real-time PCR method is a useful method for the diagnosis and differentiation of WT-MS and MS1 vaccine strains in a single reaction.

18.
Int J Mol Sci ; 25(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38396815

RESUMEN

The gaseous phytohormone ethylene plays a crucial role in plant growth, development, and stress responses. In the ethylene signal transduction cascade, the F-box proteins EIN3-BINDING F-BOX 1 (EBF1) and EBF2 are identified as key negative regulators governing ethylene sensitivity. The translation and processing of EBF1/2 mRNAs are tightly controlled, and their 3' untranslated regions (UTRs) are critical in these regulations. However, despite their significance, the exact mechanisms modulating the processing of EBF1/2 mRNAs remain poorly understood. In this work, we identified the gene DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1), which encodes an endoribonuclease and is induced by ethylene treatment, as a positive regulator of ethylene response. The loss of function mutant dne1-2 showed mild ethylene insensitivity, highlighting the importance of DNE1 in ethylene signaling. We also found that DNE1 colocalizes with ETHYLENE INSENSITIVE 2 (EIN2), the core factor manipulating the translation of EBF1/2, and targets the P-body in response to ethylene. Further analysis revealed that DNE1 negatively regulates the abundance of EBF1/2 mRNAs by recognizing and cleaving their 3'UTRs, and it also represses their translation. Moreover, the dne1 mutant displays hypersensitivity to 1,4-dithiothreitol (DTT)-induced ER stress and oxidative stress, indicating the function of DNE1 in stress responses. This study sheds light on the essential role of DNE1 as a modulator of ethylene signaling through regulation of EBF1/2 mRNA processing. Our findings contribute to the understanding of the intricate regulatory process of ethylene signaling and provide insights into the significance of ribonuclease in stress responses.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Arabidopsis/metabolismo , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Proteínas Nucleares/genética , Etilenos/farmacología , Etilenos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas F-Box/genética
19.
Sci Total Environ ; 917: 170415, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38278276

RESUMEN

Astaxanthin (Axn), a feed additive, can improve growth performance and enhance the environmental stress tolerance of shrimp at all growth stages. High carbonate alkalinity is considered a major stressor that affects the survival, growth, and reproduction of aquatic animals in saline-alkaline waters. In this study, a combined analysis of physiology, transcriptomics, and metabolomics was performed to explore the effected mechanism of Axn on Exopalaemon carinicauda (E. carinicauda) under alkalinity stress. The results revealed that dietary Axn can inhibit oxidative stress damage caused by alkalinity stress and maintain the normal cell structure and mitochondrial membrane potential. Transcriptomic data indicated that differentially expressed genes (DEGs) under alkalinity stress and those under alkalinity stress after Axn feeding were associated with apoptosis. The metabolic data suggested that alkalinity stress has adverse effects on ammonia metabolism, unsaturated fatty acid metabolism, and TCA cycle, and dietary Axn can improve the metabolic processes in E. carinicauda. In addition, transcriptomics and metabolomics analyses showed that Axn could help maintain the cytoskeletal structure and inhibit apoptosis under alkalinity stress; a TUNEL assay further confirmed these effects. Lastly, metabolic responses to alkalinity stress included changes in multiple amino acids and unsaturated fatty acids, and pathways related to energy metabolism were downregulated in the hepatopancreas of E. carinicauda under alkalinity stress. Collectively, all these results provide new insights into the molecular mechanisms underlying alkalinity stress tolerance in E. carinicauda after Axn feeding.


Asunto(s)
Palaemonidae , Animales , Perfilación de la Expresión Génica , Transcriptoma , Estrés Fisiológico , Xantófilas
20.
Adv Sci (Weinh) ; 11(8): e2305608, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38095542

RESUMEN

As a vital project of forward chemical genetic research, target deconvolution aims to identify the molecular targets of an active hit compound. Chemoproteomics, either with chemical probe-facilitated target enrichment or probe-free, provides a straightforward and effective approach to profile the target landscape and unravel the mechanisms of action. Canonical methods rely on chemical probes to enable target engagement, enrichment, and identification, whereas click chemistry and photoaffinity labeling techniques improve the efficiency, sensitivity, and spatial accuracy of target recognition. In comparison, recently developed probe-free methods detect protein-ligand interactions without the need to modify the ligand molecule. This review provides a comprehensive overview of different approaches and recent advancements for target identification and highlights the significance of chemoproteomics in investigating biological processes and advancing drug discovery processes.


Asunto(s)
Descubrimiento de Drogas , Etiquetas de Fotoafinidad , Ligandos , Descubrimiento de Drogas/métodos , Etiquetas de Fotoafinidad/química , Química Clic
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