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1.
Pestic Biochem Physiol ; 204: 106083, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277396

RESUMEN

Eleusine indica is one of the most troublesome weeds in farmland worldwide, especially in Citrus Orchard of China. Glufosinate, as an efficient non-selective broad-spectrum herbicide, has been widely utilized for the control of E. indica in Citrus Orchard. The E. indica resistant population (R) was collected from a Citrus Orchard in Yichang City in Hubei province, China. Bioassay experiments showed that the R plants exhibited 3-fold resistance to glufosinate compared with the E. indica susceptible population (S). No known glutamine synthetase (GS) gene mutation associated with glufosinate resistance was found in R plants. And there was also no significant difference in GS activity between R and S plants. Those results indicated that the resistance to glufosinate in R did not involve target-site resistance. However, glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) plus glufosinate gave a better control of R plants compared with glufosinate treatment alone. Moreover, both before and after glufosinate treatment, the GST activity in R plants was significantly higher than that in S plants. By RNA-seq, the expression of GSTU6 and GST4 up-regulated in R plants relative to S plants with or without glufosinate treatment. They were also significantly up-regulated expression in E. indica field resistant populations compared with S population. In summary, the study elucidated that R plants developed metabolic resistance to glufosinate involving GST. And GSTU6 and GST4 genes may play an important role in this glufosinate metabolic resistance. The research results provide a theoretical basis for a deeper understanding of resistance mechanism to glufosinate in E. indica.


Asunto(s)
Aminobutiratos , Eleusine , Resistencia a los Herbicidas , Herbicidas , Aminobutiratos/farmacología , Herbicidas/farmacología , Resistencia a los Herbicidas/genética , Eleusine/genética , Eleusine/metabolismo , Eleusine/efectos de los fármacos , Glutatión Transferasa/metabolismo , Glutatión Transferasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Glutamato-Amoníaco Ligasa/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Brief Bioinform ; 25(5)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39293803

RESUMEN

As more and more protein structures are discovered, blind protein-ligand docking will play an important role in drug discovery because it can predict protein-ligand complex conformation without pocket information on the target proteins. Recently, deep learning-based methods have made significant advancements in blind protein-ligand docking, but their protein features are suboptimal because they do not fully consider the difference between potential pocket regions and non-pocket regions in protein feature extraction. In this work, we propose a pocket-guided strategy for guiding the ligand to dock to potential docking regions on a protein. To this end, we design a plug-and-play module to enhance the protein features, which can be directly incorporated into existing deep learning-based blind docking methods. The proposed module first estimates potential pocket regions on the target protein and then leverages a pocket-guided attention mechanism to enhance the protein features. Experiments are conducted on integrating our method with EquiBind and FABind, and the results show that their blind-docking performances are both significantly improved and new start-of-the-art performance is achieved by integration with FABind.


Asunto(s)
Descubrimiento de Drogas , Ligandos , Proteínas , Algoritmos , Sitios de Unión , Biología Computacional/métodos , Aprendizaje Profundo , Simulación del Acoplamiento Molecular , Unión Proteica , Conformación Proteica , Proteínas/química , Proteínas/metabolismo
3.
Adv Sci (Weinh) ; : e2405945, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39229956

RESUMEN

Realizing spin transport between heavy metal and two-dimensional (2D) magnetic materials at high Curie temperature (TC) is crucial to advanced spintronic information storage technology. Here, environmentally stable 2D nonlayered Fe3O4 nanosheets are successfully synthesized using a reproducible process and found that they exhibit vortex magnetic domains at room temperature. A Verwey phase transition temperature (TV) of ≈110 K is identified for ≈3 nm thick nanosheet through Raman characterization and spin Hall device measurement of the Pt/Fe3O4 bilayer. The anisotropic magnetoresistance ratio decreases near TV, while both the spin Hall magnetoresistance ratio and spin mixing conductance (Gr) increase at TV. As the temperature approaches 112 K, the anomalous Hall effect ratio tends to become zero. The maximum Gr reaches ≈5 × 1015 Ω-1m-2 due to the clean and flat interface between Pt and 2D nanosheet. The observed spin transport behavior in Pt/Fe3O4 spin Hall devices indicates that 2D Fe3O4 nanosheets possess potential for high-power micro spintronic storage devices applications.

4.
Phytochem Anal ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233523

RESUMEN

INTRODUCTION: Insight into comparing key active ingredients of Radix Bupleuri (RB) based on different processing technologies is a key step to reveal the material basis of drug efficacy and a challenging task for developing traditional Chinese medicine (TCM). OBJECTIVE: This work aims to establish a comprehensive comparative analysis method of TCM and its processed products, which can be used to analyze the changing trend of active components of RB before and after processing. METHODS: First, RB was processed with rice vinegar, rice wine, and honey. Then, ultra-high-performance liquid chromatography (UHPLC) and gas chromatography (GC) coupled with mass spectrometry (MS) technology as well as multiple statistical analyses were used to comprehensively evaluate the compositional variation of polar and volatile compounds in RB under different processing processes. Meanwhile, in UHPLC-MS, a sequential window acquisition of all theoretical fragment ion spectral and information-dependent acquisition mutual authentication (SIMA) was developed. RESULTS: A total of 30 polar components and 33 volatile components were identified as chemical markers (mainly type II saikosaponins, terpenes, and fatty acid esters). These may be the material basis for giving unique pharmacological activities to RB and its processed products. CONCLUSIONS: These findings provided a solid foundation for the differentiated clinical application of RB, and the SIMA method held great potential for achieving accurate analysis of TCM processing ingredients.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39246140

RESUMEN

BACKGROUND: Reduced PALMD expression is strongly associated with the development of calcified aortic valve stenosis; however, the role of PALMD in vascular calcification remains unknown. METHODS: Calcified arteries were collected from mice to detect PALMD expression. Heterozygous Palmd knockout (Palmd+/-) mice were established to explore the role of PALMD in subtotal nephrectomy-induced vascular calcification. RNA sequencing was applied to detect molecular changes in aortas from Palmd+/- mice. Primary Palmd+/- vascular smooth muscle cells (VSMCs) or PALMD silenced VSMCs by short interfering RNA (siRNA) were used to analyze PALMD function in phenotypic changes and calcification. RESULTS: PALMD haploinsufficiency aggravated subtotal nephrectomy-induced vascular calcification. RNA sequencing analysis showed that loss of PALMD disturbed the synthesis and degradation of the extracellular matrix (ECM) in aortas, including collagens and matrix metalloproteinases (Col6a6, Mmp2, Mmp9, etc.). In vitro experiments revealed that PALMD deficient VSMCs were more susceptible to high phosphate induced calcification. Downregulation of SMAD6 expression and increased levels of p-SMAD2 were detected in Palmd+/- VSMCs, suggesting that TGF-ß signaling may be involved in PALMD haploinsufficiency-induced vascular calcification. CONCLUSION: Our data revealed that PALMD haploinsufficiency causes ECM dysregulation in VSMCs and aggravates vascular calcification. Our findings suggest reduced PALMD expression is also linked to vascular calcification, and PALMD maybe a potential therapeutic target for this disease.

6.
ACS Nano ; 18(39): 26614-26630, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39174015

RESUMEN

Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.


Asunto(s)
Materiales Biomiméticos , Plaquetas , Membrana Eritrocítica , Insuficiencia Cardíaca , Nanopartículas , Triazoles , Animales , Nanopartículas/química , Insuficiencia Cardíaca/tratamiento farmacológico , Ratones , Membrana Eritrocítica/química , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Triazoles/química , Triazoles/farmacología , Azepinas/química , Azepinas/farmacología , Fibrosis , Ratones Endogámicos C57BL , Masculino , Sistemas de Liberación de Medicamentos , Humanos
7.
J Gen Appl Microbiol ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39135242

RESUMEN

Naphthalene is a persistent environmental pollutant for its potential teratogenic, carcinogenic and mutagenic effects. In this study, 10 strains of bacteria capable of degrading naphthalene were isolated from crude-oil contaminated soil. Among them, Pseudomonas plecoglossicida 2P exhibited prominent growth with 1000 mg/L naphthalene as the sole carbon source and degraded 94.15% of naphthalene in 36 h. Whole genome sequencing analysis showed that P. plecoglossicida 2P had a total of 22 genes related to naphthalene degradation, of which 8 genes were related to the salicylic acid pathway only, 5 genes were related to the phthalic acid pathway only, 8 genes were common in both the salicylic acid and phthalic acid pathways, and 1 gene was related to the gentisic acid pathway. P. plecoglossicida 2P was applied in a two-phase partition bioreactor (TPPB) to degrade naphthalene in wastewater. The optimal operating conditions of the reactor were obtained through response surface optimization: initial naphthalene concentration (C0) =1600 mg/L, bacterial liquid concentration (OD600) = 1.3, and polymer-to-wastewater mass ratio (PWR) = 2%. Under these conditions, the naphthalene degradation rate was 98.36% at 24 h. The degradation kinetics were fitted using the Haldane equation with a high coefficient of determination (R2=0.94). The present study laid foundations for naphthalene degradation mechanism of genus Pseudomonas and its potential application in TPPB.

8.
Polymers (Basel) ; 16(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39125205

RESUMEN

Adenosine is an endogenous molecule that plays a vital role in biological processes. Research indicates that abnormal adenosine levels are associated with a range of diseases. The development of sensors capable of detecting adenosine is pivotal for early diagnosis of disease. For example, elevated adenosine levels are closely associated with the onset and progression of cancer. In this study, we designed a novel DNA biosensor utilizing chaperone copolymer-assisted catalytic hairpin assembly for highly sensitive detection of adenosine. The functional probe comprises streptavidin magnetic beads, an aptamer, and a catalytic chain. In the presence of adenosine, it selectively binds to the aptamer, displacing the catalytic chain into the solution. The cyclic portion of H1 hybridizes with the catalytic strand, while H2 hybridizes with the exposed H1 fragment to form an H1/H2 complex containing a G-quadruplex. Thioflavin T binds specifically to the G-quadruplex, generating a fluorescent signal. As a nucleic acid chaperone, PLL-g-Dex expedites the strand exchange reaction, enhancing the efficiency of catalytic hairpin assembly, thus amplifying the signal and reducing detection time. The optimal detection conditions were determined to be a temperature of 25 °C and a reaction time of 10 min. Demonstrating remarkable sensitivity and selectivity, the sensor achieved a lowest limit of detection of 9.82 nM. Furthermore, it exhibited resilience to interference in complex environments such as serum, presenting an effective approach for rapid and sensitive adenosine detection.

9.
Nat Cardiovasc Res ; 3(1): 28-45, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-39195894

RESUMEN

Cardiac resident MerTK+ macrophages exert multiple protective roles after ischemic injury; however, the mechanisms regulating their fate are not fully understood. In the present study, we show that the GAS6-inducible transcription factor, activating transcription factor 3 (ATF3), prevents apoptosis of MerTK+ macrophages after ischemia-reperfusion (IR) injury by repressing the transcription of multiple genes involved in type I interferon expression (Ifih1 and Ifnb1) and apoptosis (Apaf1). Mice lacking ATF3 in cardiac macrophages or myeloid cells showed excessive loss of MerTK+ cardiac macrophages, poor angiogenesis and worse heart dysfunction after IR, which were rescued by the transfer of MerTK+ cardiac macrophages. GAS6 administration improved cardiac repair in an ATF3-dependent manner. Finally, we showed a negative association of GAS6 and ATF3 expression with the risk of major adverse cardiac events in patients with ischemic heart disease. These results indicate that the GAS6-ATF3 axis has a protective role against IR injury by regulating MerTK+ cardiac macrophage survival and/or proliferation.


Asunto(s)
Factor de Transcripción Activador 3 , Apoptosis , Proliferación Celular , Supervivencia Celular , Modelos Animales de Enfermedad , Péptidos y Proteínas de Señalización Intercelular , Macrófagos , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica , Tirosina Quinasa c-Mer , Animales , Factor de Transcripción Activador 3/metabolismo , Factor de Transcripción Activador 3/genética , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Macrófagos/metabolismo , Tirosina Quinasa c-Mer/metabolismo , Tirosina Quinasa c-Mer/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Humanos , Masculino , Ratones Noqueados , Transducción de Señal , Ratones , Células Cultivadas
10.
Cancer Cell ; 42(8): 1386-1400.e8, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39137727

RESUMEN

Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.


Asunto(s)
Adenoma , Biomarcadores de Tumor , Neoplasias Colorrectales , Progresión de la Enfermedad , Heces , Metabolómica , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Heces/química , Adenoma/metabolismo , Adenoma/diagnóstico , Adenoma/patología , Adenoma/sangre , Metabolómica/métodos , Animales , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/sangre , Ratones , Masculino , Femenino , Detección Precoz del Cáncer/métodos , Metaboloma , Persona de Mediana Edad , Ácido Oléico/metabolismo , Ácido Oléico/sangre , Anciano
11.
J Pathol ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39161125

RESUMEN

Testicular tumors represent the most common malignancy among young men. Nevertheless, the pathogenesis and molecular underpinning of testicular tumors remain largely elusive. We aimed to delineate the intricate intra-tumoral heterogeneity and the network of intercellular communication within the tumor microenvironment. A total of 40,760 single-cell transcriptomes were analyzed, encompassing samples from six individuals with seminomas, two patients with mixed germ cell tumors, one patient with a Leydig cell tumor, and three healthy donors. Five distinct malignant subclusters were identified in the constructed landscape. Among them, malignant 1 and 3 subclusters were associated with a more immunosuppressive state and displayed worse disease-free survival. Further analysis identified that APP-CD74 interactions were significantly strengthened between malignant 1 and 3 subclusters and 14 types of immune subpopulations. In addition, we established an aberrant spermatogenesis trajectory and delineated the global gene alterations of somatic cells in seminoma testes. Sertoli cells were identified as the somatic cell type that differed the most from healthy donors to seminoma testes. Cellular communication between spermatogonial stem cells and Sertoli cells is disturbed in seminoma testes. Our study delineates the intra-tumoral heterogeneity and the tumor immune microenvironment in testicular tumors, offering novel insights for targeted therapy. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

12.
Adv Sci (Weinh) ; 11(35): e2405299, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39037903

RESUMEN

During the process of muscle regeneration post-injury in adults, muscle stem cells (MuSCs) function is facilitated by neighboring cells within the pro-regenerative niche. However, the precise mechanism triggering the initiation of signaling in the pro-regenerative niche remains unknown. Using single-cell RNA sequencing, 14 different muscle cells are comprehensively mapped during the initial stage following injury. Among these, macrophages and fibro-adipogenic progenitor cells (FAPs) exhibit the most pronounced intercellular communication with other cells. In the FAP subclusters, the study identifies an activated FAP phenotype that secretes chemokines, such as CXCL1, CXCL5, CCL2, and CCL7, to recruit macrophages after injury. Il1rl1, encoding the protein of the interleukin-33 (IL-33) receptor, is identified as a highly expressed signature surface marker of the FAP phenotype. Following muscle injury, autocrine IL-33, an alarmin, has been observed to activate quiescent FAPs toward this inflammatory phenotype through the IL1RL1-MAPK/NF-κB signaling pathway. Il1rl1 deficiency results in decreased chemokine expression and recruitment of macrophages, accompanied by impaired muscle regeneration. These findings elucidate a novel mechanism involving the IL-33/IL1RL1 signaling pathway in promoting the activation of FAPs and facilitating muscle regeneration, which can aid the development of therapeutic strategies for muscle-related disorders and injuries.


Asunto(s)
Interleucina-33 , Regeneración , Interleucina-33/metabolismo , Interleucina-33/genética , Animales , Ratones , Regeneración/fisiología , Músculo Esquelético/metabolismo , Músculo Esquelético/lesiones , Células Madre/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal , Macrófagos/metabolismo
13.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2920-2929, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39041151

RESUMEN

This study explored the relationship between the appearance traits and internal components of Cinnamomi Ramulus pieces, so as to provide a reference for the quality evaluation and the formulation of grade standards. This study determined the appearance traits and index component contents of 41 batches of Cinnamomi Ramulus pieces in the core producing areas of Guangxi and Guangdongand established the HPLC characteristic map method. The weight of the pieces, the narrowest diameter, and the widest diameter of the tr ansverse section were used as the indices of appearance traits. The content of index components(cinnamic acid and cinnamalde hyde)was determined by the established content determination method. The chromatographic characteristics were determinedon a Waters XBridge C_(18)(4. 6 mm×250 mm, 5 µm) column with a mobile phase consisting of 0. 1% phosphoric acidacetonitrile and gradient elution at the flow rate of 1 mL ·min~(-1). The column temperature was 30 ℃, and the detection wavelength was 254 nm. Cluster analysis, principal component analysis, and other stoichiometric methods were used to analyze the correlation between theap pearance traits and the index/characteristic components of Cinnamomi Ramulus pieces and compare the qu ality differences of the piecesfrom different batches and plac es. The results showed that the larger weight, the narrowest diameter, andthe widest diameter of the tra nsverse section indicated lowercontent of main indexes/characteristic components, and there was a synergistic decreasing trend amongd ifferent components. The overall quality of Cinnamomi Ramulus pieces in Guangdong Province and Guangxi Province was similar, but there were still differences between different origins and different batches of the same origin. It is scientific and feasible to evaluatethe quality of Cinnamomi Ramulus pieces and establish grading standards based on the appearance traits and index/character istic components. The research provides a more scientific and comprehensive basis for the quality control evaluation and standardformulation of Cinnamomi Ramulus.


Asunto(s)
Medicamentos Herbarios Chinos , Control de Calidad , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/normas , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión , Cinnamomum/química , China , Cinnamomum zeylanicum/química
14.
Adv Healthc Mater ; : e2401704, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011795

RESUMEN

A bio-hydrogel is prepared via a low-cost and time-saving strategy and is studied as a self-powered wound dressing for precision medicine and health monitoring. Promoted by a dual self-catalytic pair composed of Fe3+ and catechol, gelation time is dramatically accelerated to 15 s and the hydrogel can be freely modeled at -18 °C without losing flexibility. As smart wound dressing, the required properties such as self-healing, self-adhesion, antibacterial, and sensing stability, are integrated into one hydrogel. TA@CNC offers abundant hydrogen bond and metal-ligand coordination which facilitate the hydrogel with a self-healing efficiency of 91.6%. Owing to the catechol in TA@CNC, hydrogel can adhere to multiple substrates including skin, and show good antibacterial activity. Inspired by a fruit battery, a self-powered wound dressing is fabricated, which exhibits excellent correlation and efficiency in real-time monitoring of body activity and drug release. In vivo experiments prove that efficient drug release of hydrogel dressing significantly accelerate wound healing. Additionally, the dressing exhibits excellent biocompatibility and has no negative impacts on organs. Herein, a smart wound dressing that is different from the traditional way is proposed. As a self-powered device, it can be integrated with wireless devices and is expected to participate in promising applications.

15.
J Clin Invest ; 134(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38950288

RESUMEN

Research advances over the past 30 years have confirmed a critical role for genetics in the etiology of dilated cardiomyopathies (DCMs). However, full knowledge of the genetic architecture of DCM remains incomplete. We identified candidate DCM causal gene, C10orf71, in a large family with 8 patients with DCM by whole-exome sequencing. Four loss-of-function variants of C10orf71 were subsequently identified in an additional group of492 patients with sporadic DCM from 2 independent cohorts. C10orf71 was found to be an intrinsically disordered protein specifically expressed in cardiomyocytes. C10orf71-KO mice had abnormal heart morphogenesis during embryonic development and cardiac dysfunction as adults with altered expression and splicing of contractile cardiac genes. C10orf71-null cardiomyocytes exhibited impaired contractile function with unaffected sarcomere structure. Cardiomyocytes and heart organoids derived from human induced pluripotent stem cells with C10orf71 frameshift variants also had contractile defects with normal electrophysiological activity. A rescue study using a cardiac myosin activator, omecamtiv mecarbil, restored contractile function in C10orf71-KO mice. These data support C10orf71 as a causal gene for DCM by contributing to the contractile function of cardiomyocytes. Mutation-specific pathophysiology may suggest therapeutic targets and more individualized therapy.


Asunto(s)
Cardiomiopatía Dilatada , Mutación del Sistema de Lectura , Ratones Noqueados , Miocitos Cardíacos , Organoides , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/metabolismo , Modelos Animales de Enfermedad , Contracción Miocárdica/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Organoides/metabolismo , Organoides/patología
16.
Artículo en Inglés | MEDLINE | ID: mdl-39017669

RESUMEN

A bacterial strain, designated S6T, was isolated from the sandy soil on a rocky mountain in South China. Cells of S6T were Gram-stain-negative, aerobic, non-spore-forming, non-motile and non-prosthecae-producing. 16S rRNA gene sequence analysis revealed the highest similarities to 12 uncultured bacteria, followed by Phenylobacterium sp. B6.10-61 (97.14 %). The closest related validly published strains are Caulobacter henricii ATCC 15253T (96.15 %), Phenylobacterium conjunctum FWC 21T (96.08 %) and Caulobacter mirabilis FWC 38T (96.08 %). Phylogenetic analysis based on 16S rRNA gene, genome and proteome sequences demonstrated that S6T formed a separated lineage in the genus Phenylobacterium. Strain S6T contained Q-10 (97.5 %) as the major ubiquinone and C18 : 1 ω7c and C16 : 0 as the major fatty acids. The polar lipid profile consisted of phosphatidylglycerol, an unknown phosphoglycolipid and three unknown glycolipids. The assembled genome comprises a chromosome with a length of 5.5 Mb and a plasmid of 96 014 bp. The G+C content was 67.6 mol%. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus it is proposed that strain S6T represents a novel species in the genus Phenylobacterium, for which the name Phenylobacterium montanum sp. nov. is proposed. The type strain is S6T (=NBRC 115419T=GCMCC 1.18594T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Microbiología del Suelo , Ubiquinona , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , ADN Bacteriano/genética , China , Fosfolípidos/análisis , Fosfolípidos/química , Genoma Bacteriano , Arena/microbiología
17.
Plant Physiol Biochem ; 214: 108940, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39024781

RESUMEN

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.


Asunto(s)
Cadmio , Pared Celular , Zinc , Cadmio/toxicidad , Zinc/metabolismo , Zinc/toxicidad , Zinc/farmacología , Pared Celular/metabolismo , Pared Celular/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/genética
18.
Antioxidants (Basel) ; 13(7)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39061842

RESUMEN

Heat stress (HS) induces various physiological disorders in poultry, negatively impacting feed intake, feed efficiency, and growth performance. Considering the documented anti-stress and growth-promoting benefits of monochromatic green light in poultry, we aimed to investigate its effects on cyclic chronic HS-induced oxidative stress (OS) and inflammation in geese. We established three treatment groups-geese exposed to white light (W), white light with HS treatment (WH), and green light with HS treatment (GH)-treated over a six-week period with daily HS sessions. The results revealed that cyclic chronic HS induced liver OS and inflammation, leading to hepatocellular injury and reduced growth performance and feed intake. In comparison, the growth performance of geese under green light significantly improved. Additionally, liver index, serum, liver malondialdehyde (MDA), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) levels were reduced. Serum total antioxidant capacity (T-AOC), liver catalase (CAT), and superoxide dismutase (SOD) activity were enhanced, reducing hepatic OS and inflammation. Liver transcriptomic analysis indicated that green light alleviates cyclic chronic HS-induced liver injury and promotes geese growth performance by suppressing NF-κB pathway activation.

19.
Front Plant Sci ; 15: 1380157, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919820

RESUMEN

Fagopyrum dibotrys, belonging to the family Polygonaceae and genus Fagopyrum, is used in traditional Chinese medicine and is rich in beneficial components, such as flavonoids. As its abundant medicinal value has become increasingly recognized, its excessive development poses a considerable challenge to wild germplasm resources, necessitating artificial cultivation and domestication. Considering these factors, a high-quality genome of F. dibotrys was assembled and the evolutionary relationships within Caryophyllales were compared, based on which 58 individual samples of F. dibotrys were re-sequenced. We found that the samples could be categorized into three purebred populations and regions distributed at distinct elevations. Our varieties were cultivated from the parental populations of the subpopulation in central Yunnan. F. dibotrys is speculated to have originated in the high-altitude Tibetan Plateau region, and that its combination with flavonoids can protect plants against ultraviolet radiation; this infers a subpopulation with a high accumulation of flavonoids. This study assembled a high-quality genome and provided a theoretical foundation for the future introduction, domestication, and development of cultivated varieties of F. dibotrys.

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