RESUMEN
GLS1 orchestrates glutaminolysis and promotes cell proliferation when glutamine is abundant by regenerating TCA cycle intermediates and supporting redox homeostasis. CB-839, an inhibitor of GLS1, is currently under clinical investigation for a variety of cancer types. Here, we show that GLS1 facilitates apoptosis when glutamine is deprived. Mechanistically, the absence of exogenous glutamine sufficiently reduces glutamate levels to convert dimeric GLS1 to a self-assembled, extremely low-Km filamentous polymer. GLS1 filaments possess an enhanced catalytic activity, which further depletes intracellular glutamine. Functionally, filamentous GLS1-dependent glutamine scarcity leads to inadequate synthesis of asparagine and mitogenome-encoded proteins, resulting in ROS-induced apoptosis that can be rescued by asparagine supplementation. Physiologically, we observed GLS1 filaments in solid tumors and validated the tumor-suppressive role of constitutively active, filamentous GLS1 mutants K320A and S482C in xenograft models. Our results change our understanding of GLS1 in cancer metabolism and suggest the therapeutic potential of promoting GLS1 filament formation.
Asunto(s)
Glutaminasa , Glutamina , Apoptosis , Asparagina/genética , Glutaminasa/genética , Glutaminasa/metabolismo , Glutamina/metabolismo , Humanos , Especies Reactivas de OxígenoRESUMEN
Protein lysine acetylation is a dynamic post-translational modification (PTM) that regulates a wide spectrum of cellular events including aging. General control nonderepressible 5 (GCN5) is a highly conserved lysine acetyltransferase (KAT). However, the acetylation substrates of GCN5 in vivo remain poorly studied, and moreover, how lysine acetylation changes with age and the contribution of KATs to aging remain to be addressed. Here, using Drosophila, we perform label-free quantitative acetylomic analysis, identifying new substrates of GCN5 in the adult and aging process. We further characterize the dynamics of protein acetylation with age, which exhibits a trend of increase. Since the expression of endogenous fly Gcn5 progressively increases during aging, we reason that, by combining the substrate analysis, the increase in acetylation with age is triggered, at least in part, by GCN5. Collectively, our study substantially expands the atlas of GCN5 substrates in vivo, provides a resource of protein acetylation that naturally occurs with age, and demonstrates how individual KAT contributes to the aging acetylome.
Asunto(s)
Proteínas de Drosophila , Histona Acetiltransferasas , Lisina Acetiltransferasas , Animales , Acetilación , Drosophila , Histona Acetiltransferasas/metabolismo , Lisina/metabolismo , Lisina Acetiltransferasas/metabolismo , Proteínas de Drosophila/metabolismoRESUMEN
Cyclodehydrogenation reactions in the on-surface synthesis of graphene nanoribbons (GNRs) usually involve a series of Csp2-Csp2 and/or Csp2-Csp3 couplings and just happen on uncovered metal or metal oxide surfaces. It is still a big challenge to extend the growth of second-layer GNRs in the absence of necessary catalytic sites. Here, we demonstrate the direct growth of topologically nontrivial GNRs via multistep Csp2-Csp2 and Csp2-Csp3 couplings in the second layer by annealing designed bowtie-shaped precursor molecules over one monolayer on the Au(111) surface. After annealing at 700 K, most of the polymerized chains that appear in the second layer covalently link to the first-layer GNRs that have partially undergone graphitization. Following annealing at 780 K, the second-layer GNRs are formed and linked to the first-layer GNRs. Benefiting from the minimized local steric hindrance of the precursors, we suggest that the second-layer GNRs undergo domino-like cyclodehydrogenation reactions that are remotely triggered at the link. We confirm the quasi-freestanding behaviors in the second-layer GNRs by measuring the quasiparticle energy gap of topological bands and the tunable Kondo resonance from topological end spins using scanning tunneling microscopy/spectroscopy combined with first-principles calculations. Our findings pave the avenue to diverse multilayer graphene nanostructures with designer quantum spins and topological states for quantum information science.
RESUMEN
High temperature (HT) causes male sterility and decreases crop yields. Our previous works have demonstrated that sugar and auxin signaling pathways, Gossypium hirsutum Casein kinase I (GhCKI), and DNA methylation are all involved in HT-induced male sterility in cotton. However, the signaling mechanisms leading to distinct GhCKI expression patterns induced by HT between HT-tolerant and HT-sensitive cotton anthers remain largely unknown. Here, we identified a GhCKI promoter (ProGhCKI) region that functions in response to HT in anthers and found the transcription factor GhMYB4 binds to this region to act as an upstream positive regulator of GhCKI. In the tapetum of early-stage cotton anthers, upregulated expression of GhMYB4 under HT and overexpressed GhMYB4 under normal temperature both led to severe male sterility phenotypes, coupled with enhanced expression of GhCKI. We also found that GhMYB4 interacts with GhMYB66 to form a heterodimer to enhance its binding to ProGhCKI. However, GhMYB66 showed an expression pattern similar to GhMYB4 under HT but did not directly bind to ProGhCKI. Furthermore, HT reduced siRNA-mediated CHH DNA methylations in the GhMYB4 promoter, which enhanced the expression of GhMYB4 in tetrad stage anthers and promoted the formation of the GhMYB4/GhMYB66 heterodimer, which in turn elevated the transcription of GhCKI in the tapetum, leading to male sterility. Overall, we shed light on the GhMYB66-GhMYB4-GhCKI regulatory pathway in response to HT in cotton anthers.
Asunto(s)
Gossypium , Infertilidad Masculina , Quinasa de la Caseína I/genética , Quinasa de la Caseína I/metabolismo , Regulación de la Expresión Génica de las Plantas , Gossypium/metabolismo , Calor , Humanos , Masculino , TemperaturaRESUMEN
The pollen wall exine provides a protective layer for the male gametophyte and is largely composed of sporopollenin, which comprises fatty acid derivatives and phenolics. However, the biochemical nature of the external exine is poorly understood. Here, we show that the male sterile line 1355A of cotton mutated in NO SPINE POLLEN (GhNSP) leads to defective exine formation. The GhNSP locus was identified through map-based cloning and confirmed by genetic analysis (co-segregation test and allele prediction using the CRISPR/Cas9 system). In situ hybridization showed that GhNSP is highly expressed in tapetum. GhNSP encodes a polygalacturonase protein homologous to AtQRT3, which suggests a function for polygalacturonase in pollen exine formation. These results indicate that GhNSP is functionally different from AtQRT3, the latter has the function of microspore separation. Biochemical analysis showed that the percentage of de-esterified pectin was significantly increased in the 1355A anthers at developmental stage 8. Furthermore, immunofluorescence studies using antibodies to the de-esterified and esterified homogalacturonan (JIM5 and JIM7) showed that the Ghnsp mutant exhibits abundant of de-esterified homogalacturonan in the tapetum and exine, coupled with defective exine formation. The characterization of GhNSP provides new understanding of the role of polygalacturonase and de-esterified homogalacturonan in pollen exine formation.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Poligalacturonasa , Fertilidad , Pectinas/metabolismo , Polen/genética , Polen/metabolismo , Poligalacturonasa/genética , Poligalacturonasa/metabolismoRESUMEN
Evolution of pest resistance reduces the efficacy of insecticidal proteins from the gram-positive bacterium Bacillus thuringiensis (Bt) used widely in sprays and transgenic crops. Better understanding of the genetic basis of resistance is needed to more effectively monitor, manage, and counter pest resistance to Bt toxins. Here we used CRISPR/Cas9 gene editing to clarify the genetics of Bt resistance and the associated effects on susceptibility to other microbial insecticides in one of the world's most damaging pests, the cotton bollworm (Helicoverpa armigera). We discovered that CRISPR-mediated knockouts of ATP-binding cassette (ABC) transporter genes HaABCC2 and HaABCC3 together caused >15,000-fold resistance to Bt toxin Cry1Ac, whereas knocking out either HaABCC2 or HaABCC3 alone had little or no effect. Inheritance of resistance was autosomal and recessive. Bioassays of progeny from interstrain crosses revealed that one wild type allele of either HaABCC2 or HaABCC3 is sufficient to sustain substantial susceptibility to Cry1Ac. In contrast with previous results, susceptibility to two insecticides derived from bacteria other than Bt (abamectin and spinetoram), was not affected by knocking out HaABCC2, HaABCC3, or both. The results here provide the first evidence that either HaABCC2 or HaABCC3 protein is sufficient to confer substantial susceptibility to Cry1Ac. The functional redundancy of these two proteins in toxicity of Cry1Ac to H. armigera is expected to reduce the likelihood of field-evolved resistance relative to disruption of a toxic process where mutations affecting a single protein can confer resistance.
Asunto(s)
Bacillus thuringiensis , Proteínas Bacterianas , Endotoxinas , Proteínas Hemolisinas , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Animales , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Endotoxinas/genética , Endotoxinas/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Mariposas Nocturnas , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Control Biológico de VectoresRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an approved treatment for various cancers; however, only a small proportion of the population is responsive to such treatment. We aimed to develop and validate a plain CT-based tool for predicting the response to ICI treatment among cancer patients. METHODS: Data for patients with solid cancers treated with ICIs at two centers from October 2019 to October 2021 were randomly divided into training and validation sets. Radiomic features were extracted from pretreatment CT images of the tumor of interest. After feature selection, a radiomics signature was constructed based on the least absolute shrinkage and selection operator regression model, and the signature and clinical factors were incorporated into a radiomics nomogram. Model performance was evaluated using the training and validation sets. The Kaplan-Meier method was used to visualize associations with survival. RESULTS: Data for 122 and 30 patients were included in the training and validation sets, respectively. Both the radiomics signature (radscore) and nomogram exhibited good discrimination of response status, with areas under the curve (AUC) of 0.790 and 0.814 for the training set and 0.831 and 0.847 for the validation set, respectively. The calibration evaluation indicated goodness-of-fit for both models, while the decision curves indicated that clinical application was favorable. Both models were associated with the overall survival of patients in the validation set. CONCLUSIONS: We developed a radiomics model for early prediction of the response to ICI treatment. This model may aid in identifying the patients most likely to benefit from immunotherapy.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Tomografía Computarizada por Rayos X , Inmunoterapia , Calibración , Nomogramas , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
Spin field-effect transistors (SFETs) based on the Rashba effect could manipulate the spin of electrons electrically, while seeking desirable Rashba semiconductors with large Rashba constant and strong electric-field response, to preserve spin coherence remains a key challenge. Herein, we propose a series of 2D Rashba semiconductors with two-atom-thick buckled honeycomb structure (BHS) according to high-throughput first-principles density functional theory calculations. BHS semiconductors show large Rashba constants that are favorable to be integrated into nanodevices superior to conventional bulk materials, and they can be fabricated by mechanical exfoliation or chemical vapor deposition. In particular, 2D AlBi monolayer has the largest Rashba constant (2.77 eVÅ) of all 2D Rashba materials. Furthermore, 2D BiSb monolayer is a promising candidate for SFETs due to its large Rashba constant (1.94 eVÅ) and strong electric field response (0.92 eÅ2). Our designed 2D-BiSb-SFET shows shorter spin channel length (42 nm with strain) than conventional SFETs (2-5 µm).
RESUMEN
Anther indehiscence and pollen sterility caused by high temperature (HT) stress have become a major problem that decreases the yield of cotton. Pollen- and anther-specific genes play a critical role in the process of male reproduction and the response to HT stress. In order to identify pollen-specific genes that respond to HT stress, a comparative transcriptome profiling analysis was performed in the pollen and anthers of Gossypium hirsutum HT-sensitive Line H05 against other tissue types under normal temperature (NT) conditions, and the analysis of a differentially expressed gene was conducted in the pollen of H05 under NT and HT conditions. In total, we identified 1111 pollen-specific genes (PSGs), 1066 anther-specific genes (ASGs), and 833 pollen differentially expressed genes (DEGs). Moreover, we found that the late stage of anther included more anther- and pollen-specific genes (APSGs). Stress-related cis-regulatory elements (CREs) and hormone-responsive CREs are enriched in the promoters of APSGs, suggesting that APSGs may respond to HT stress. However, 833 pollen DEGs had only 10 common genes with 1111 PSGs, indicating that PSGs are mainly involved in the processes of pollen development and do not respond to HT stress. Promoters of these 10 common genes are enriched for stress-related CREs and MeJA-responsive CREs, suggesting that these 10 common genes are involved in the process of pollen development while responding to HT stress. This study provides a pathway for rapidly identifying cotton pollen-specific genes that respond to HT stress.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Gossypium , Flores/metabolismo , Perfilación de la Expresión Génica , Gossypium/metabolismo , Polen/genética , Temperatura , TranscriptomaRESUMEN
Poultry eggs, the basic foodstuffs of human society, have been extensively consumed for domestic and industrial uses. A large amount of eggshell waste is generated and discarded every year, resulting in a waste of natural resources and a threat to the environment. In this context, the reutilization of eggshell waste has gained increasing attentions. Meanwhile, the overuse of antibiotics has led to the emergence of many drug-resistant bacteria, which greatly endangers public health. Therefore, manufacturing new materials with strong antimicrobial activities has become the focus of many researchers. Recent studies have revealed that eggshells can be applied as solid substances, the raw materials for calcium oxide, and the calcium source for synthesizing hydroxyapatite or other materials with antimicrobial activities. Herein, the preparation methods, antibacterial mechanisms and the applications of these eggshell waste-derived antibacterial materials are summarized in this review. Finally, the current challenges and future directions in this field are discussed.
Asunto(s)
Cáscara de Huevo , Aves de Corral , Animales , Antibacterianos/farmacología , Huevos , Humanos , ResiduosRESUMEN
This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from Delphinium brunonianum. Four novel diterpenoid alkaloids, brunodelphinine B-E, were isolated from D. brunonianum together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids-brunodelphinine E (4), delbruline (5), lycoctonine (7), delbrunine (8), and sharwuphinine A (12)-exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A (12) displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of D. brunonianum and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.
Asunto(s)
Alcaloides , Delphinium , Diterpenos , Alcaloides/química , Alcaloides/farmacología , Delphinium/química , Diterpenos/química , Diterpenos/farmacología , Hepatocitos , Lípidos , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
The double-recessive genic male-sterile (ms) line ms5 ms6 has been used to develop cotton (Gossypium hirsutum) hybrids for many years, but its molecular-genetic basis has remained unclear. Here, we identified the Ms5 and Ms6 loci through map-based cloning and confirmed their function in male sterility through CRISPR/Cas9 gene editing. Ms5 and Ms6 are highly expressed in stages 7-9 anthers and encode the cytochrome P450 mono-oxygenases CYP703A2-A and CYP703A2-D. The ms5 mutant carries a single-nucleotide C-to-T nonsense mutation leading to premature chain termination at amino acid 312 (GhCYP703A2-A312aa ), and ms6 carries three nonsynonymous substitutions (D98E, E168K, and G198R) and a synonymous mutation (L11L). Enzyme assays showed that GhCYP703A2 proteins hydroxylate fatty acids, and the ms5 (GhCYP703A2-A312aa ) and ms6 (GhCYP703A2-DD98E,E168K,G198R ) mutant proteins have decreased enzyme activities. Biochemical and lipidomic analyses showed that in ms5 ms6 plants, C12-C18 free fatty acid and phospholipid levels are significantly elevated in stages 7-9 anthers, while stages 8-10 anthers lack sporopollenin fluorescence around the pollen, causing microspore degradation and male sterility. Overall, our characterization uncovered functions of GhCYP703A2 in sporopollenin formation and fertility, providing guidance for creating male-sterile lines to facilitate hybrid cotton production and therefore exploit heterosis for improvement of cotton.
Asunto(s)
Gossypium , Infertilidad Vegetal , Aminoácidos/metabolismo , Codón sin Sentido/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Fertilidad/genética , Regulación de la Expresión Génica de las Plantas/genética , Gossypium/genética , Gossypium/metabolismo , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Nucleótidos/metabolismo , Fosfolípidos/metabolismo , Infertilidad Vegetal/genéticaRESUMEN
The GW approximation is an effective way to accurately describe the single-electron excitations of molecules and the quasiparticle energies of solids. However, a perceived drawback of the GW calculations is their high computational cost and large memory usage, which limit their applications to large systems. Herein, we demonstrate an accurate and effective low-rank approximation to accelerate non-self-consistent GW (G0W0) calculations under the static Coulomb hole plus screened exchange (COHSEX) approximation for periodic systems. Our approach is to adopt the interpolative separable density fitting (ISDF) decomposition and Cauchy's integral to construct low-rank representations of the dielectric matrix ϵ and self-energy matrix Σ. This approach reduces the number of floating point operations from O(Ne4) to O(Ne3) and requires a much smaller memory footprint. Two methods are used to select the interpolation points in ISDF, including the standard QR factorization with column pivoting (QRCP) procedure and the machine learning K-means clustering (K-means) algorithm. We demonstrate that these two methods can yield similar accuracy for both molecules and solids at much lower computational cost. In particular, K-means clustering can significantly reduce the computational cost of selecting the interpolation points by an order of magnitude compared to QRCP, resulting in an overall speedup factor of about ten times ISDF accelerated the static COHSEX calculations compared with conventional COHSEX approximation.
RESUMEN
The impact of iron plaque (IP) on bioavailability of heavy metals to plants has been well documented, but the role of zinc (Zn) in modulating the associated processes remains elusive. We took Iris pseudacorus used in wetland for remediating Cd-contaminated water as an example and systematically studied the combined influence of Cd and Zn concentration on formation of IP and its consequence for immobilization and plant uptake of Cd. The experiment was conducted in hydroponic culture and in each treatment, we measured the physiological traits, activity of antioxidant enzymes (SOD, POD, CAT), mass of the IP, as well as the Cd content in both plant tissues and IP. The results showed that increasing Cd concentration resulted in a steady reduction in IP while the impact of zinc on IP was complicated and appeared to be coupled with Cd. When the Cd concentration was low (0.5 mg L-1 measured as CdCl2 2·5H2O) increasing Zn concentration reduced IP, while when the Cd concentration was increased to 5 mg L-1 increasing zinc concentration led to an increase in IP mass first followed by a decline after Zn concentration exceeded 100 mg L-1 (measured as ZnSO4·7H2O). The change in IP as affected by Zn had a strong consequence for immobilization and plant uptake of Cd. When Cd concentration was low, the IP was comparatively abundant and hence adsorbed most Cd. In contrast, when Cd concentration was high, the IP reduced and the amount of Cd taken up by plant roots and translocated to shoots and leaves increased. Both Cd immobilization and its plant uptake were modulated by Zn concentration. At low Cd concentration the combined Cd immobilized and taken up by plant peaked when the Zn concentration was 50 mg L-1, while at high Cd concentration the combined Cd reached maxima when theZn concentration was 100 mg L-1. The activity of the antioxidant enzymes changed significantly with Zn rather than with Cd. Regardless of Cd concentration, the activity of all three antioxidant enzymes increased first with zinc concentration before declining when the Zn concentration exceeded approximately 100 mg L-1 in all treatments, comparable with the change in immobilization and plant uptake of Cd as the Zn concentration increased. SEM analysis did prove the formation and variation of IP on the root surface of Iris pseudacorus in different treatments. We also found that the plant developed a survival strategy by scarifying its leaves with high Cd content. The results presented in this paper has wide implications as it revealed that care needs to be taken in applying Zn to enhance Cd immobilization and its plant uptake as exceeding the optimal application rate might reduce remediating efficiency rather than increase it.
Asunto(s)
Cadmio/toxicidad , Género Iris/efectos de los fármacos , Hierro/análisis , Contaminantes Químicos del Agua/toxicidad , Zinc/farmacología , Adsorción , Cadmio/análisis , Cadmio/metabolismo , Hidroponía , Género Iris/crecimiento & desarrollo , Género Iris/metabolismo , Hierro/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Humedales , Zinc/análisis , Zinc/metabolismoRESUMEN
Resistance to apoptosis and uncontrolled proliferation are two hallmarks of cancer cells. p53 is crucial for apoptosis triggered by a broad range of stresses and a well-known gatekeeper for neoplastic transformation. Here we show that oncogenic IDH1 R132H/R132Q mutants robustly inhibit p53 expression and such an effect is attributed to 2-HG production. Mechanistically, 2-hydroxyglutarate (2-HG) stabilizes hypoxia-inducible factor-2α, which in turn activates the expression of miR-380-5p, a characterized microRNA against p53 expression. Rescue expression of p53 can inhibit the proliferation rate and impair the resistance of apoptosis induced by doxorubicin in IDH1 R132Q mouse embryonic fibroblast cells. Furthermore, p53 protein levels correlates negatively with IDH1 R132H levels in human glioma samples. Our results thus shed a new light on how p53 is down-regulated by 2-HG and suggests that impairment of p53-mediated apoptosis contributes to the tumorigenesis driven by IDH1 mutants.
Asunto(s)
Arginina/genética , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Isocitrato Deshidrogenasa/metabolismo , Mutación , Proteína p53 Supresora de Tumor/metabolismo , Animales , Arginina/química , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Carcinogénesis , Proliferación Celular , Glioma/genética , Glioma/metabolismo , Glutaratos/farmacología , Humanos , Isocitrato Deshidrogenasa/genética , Ratones , MicroARNs/genética , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ginseng, the active ingredients of which are ginsenosides, is the most popular herbal medicine and has potential merit in the treatment of cerebral disorders. To better understand the function of Ginseng in the cerebral system, we examined changes in the protein expression profiles of synaptosomes extracted from the cerebral cortical and hippocampal tissues of rats administered a high or low dose of Ginseng for 2 weeks. More than 5000 proteins belonging to synaptosomes were simultaneously identified and quantitated by an approach combining tandem mass tags with 2D liquid chromatography-mass spectrometry (LC-MS). Regarding differentially expressed proteins, downregulated proteins were much more highly induced than upregulators in the cerebral cortical and hippocampal synaptosomes, regardless of the dose of Ginseng. Bioinformatic analysis indicated the majority of the altered proteins to be located in the mitochondria, directly or indirectly affecting mitochondrial oxidative respiration. Further functional experiments using the substrate-uncoupler inhibitor titration approach confirmed that three representative ginsenosides were able to inhibit oxidative phosphorylation in mitochondria. Our results demonstrate that Ginseng can regulate the function of mitochondria and alter the energy metabolism of cells, which may be useful for the treatment of central nervous disorders.
Asunto(s)
Corteza Cerebral/metabolismo , Hipocampo/metabolismo , Mitocondrias/fisiología , Panax/química , Extractos Vegetales/farmacología , Proteómica/métodos , Sinaptosomas/metabolismo , Animales , Respiración de la Célula , Células Cultivadas , Corteza Cerebral/efectos de los fármacos , Biología Computacional , Metabolismo Energético , Regulación de la Expresión Génica , Hipocampo/efectos de los fármacos , Masculino , Mitocondrias/efectos de los fármacos , Fosforilación Oxidativa , Ratas , Ratas Sprague-Dawley , Sinaptosomas/efectos de los fármacosRESUMEN
The antifungal effect of Lactobacillus plantarum C10 on pink rot caused by Trichothecium roseum and its application in muskmelon fruit were investigated. Cell-free supernatant (CFS) produced by Lactobacillus plantarum C10 strongly inhibited the growth of T. roseum and seriously damaged the structures of spores and mycelia of T. roseum. Acid compounds produced by Lb. plantarum C10 were the major antifungal substances and exhibited a narrow pH range from 3.5 to 6.5. Application of the CFS on muskmelon fruit reduced the contamination zone of T. roseum by enhancing the activities of defensive enzymes (phenylalanine ammonialyase, peroxidase and polyphenoloxidase) and promoting the accumulation of phenolics and flavonoids. These results suggested that Lb. plantarum C10 could be used as a biocontrol agent to control pink rot caused by T. roseum in muskmelon fruit.
RESUMEN
The intricate interplay among extracellular vesicles, cancer stemness properties, and the immune system significantly impacts hepatocellular carcinoma (HCC) progression, treatment response, and patient prognosis. Extracellular vesicles (EVs), which are membrane-bound structures, play a pivotal role in conveying proteins, lipids, and nucleic acids between cells, thereby serving as essential mediators of intercellular communication. Since a lot of current research focuses on small extracellular vesicles (sEVs), with diameters ranging from 30 nm to 200 nm, this review emphasizes the role of sEVs in the context of interactions between HCC stemness-bearing cells and the immune cells. sEVs offer promising opportunities for the clinical application of innovative diagnostic and prognostic biomarkers in HCC. By specifically targeting sEVs, novel therapeutics aimed at cancer stemness can be developed. Ongoing investigations into the roles of sEVs in cancer stemness and immune regulation in HCC will broaden our understanding and ultimately pave the way for groundbreaking therapeutic interventions.
Asunto(s)
Carcinoma Hepatocelular , Progresión de la Enfermedad , Vesículas Extracelulares , Neoplasias Hepáticas , Células Madre Neoplásicas , Humanos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Vesículas Extracelulares/inmunología , Vesículas Extracelulares/metabolismo , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/inmunología , Comunicación Celular/inmunología , Microambiente Tumoral/inmunología , AnimalesRESUMEN
Objective: The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we conducted a prospective observational study to observe serum proteomics differences in PND patients after cardiac valve replacement surgery. Methods: Two hundred and twenty-six patients who underwent cardiac valve surgery were included. They were categorized based on scoring into non-PND group (group non-P) and PND group (group P'). The risk factors associated with PND were analyzed. These patients were further divided into group C and group P by propensity score matching (PSM) to investigate the serum proteome related to the PND by serum proteomics. Results: The postoperative 6-week incidence of PND was 16.8%. Risk factors for PND include age, chronic illness, sufentanil dosage, and time of cardiopulmonary bypass (CPB). Proteomics identified 31 down-regulated proteins and six up-regulated proteins. Finally, GSTO1, IDH1, CAT, and PFN1 were found to be associated with PND. Conclusion: The occurrence of PND can impact some oxidative stress proteins. This study provided data for future studies about PND to general anaesthesia and surgeries.
Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Proteómica , Humanos , Masculino , Estudios Prospectivos , Femenino , Proteómica/métodos , Persona de Mediana Edad , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Factores de Riesgo , Disfunción Cognitiva/sangre , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Anciano , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/sangre , Complicaciones Cognitivas Postoperatorias/diagnóstico , Incidencia , Puntaje de Propensión , AdultoRESUMEN
Plant anthers are composed of different specialized cell types with distinct roles in plant reproduction. High temperature (HT) stress causes male sterility, resulting in crop yield reduction. However, the spatial expression atlas and regulatory dynamics during anther development and in response to HT remain largely unknown. Here, the first single-cell transcriptome atlas and chromatin accessibility survey in cotton anther are established, depicting the specific expression and epigenetic landscape of each type of cell in anthers. The reconstruction of meiotic cells, tapetal cells, and middle layer cell developmental trajectories not only identifies novel expressed genes, but also elucidates the precise degradation period of middle layer and reveals a rapid function transition of tapetal cells during the tetrad stage. By applying HT, heterogeneity in HT response is shown among cells of anthers, with tapetal cells responsible for pollen wall synthesis are most sensitive to HT. Specifically, HT shuts down the chromatin accessibility of genes specifically expressed in the tapetal cells responsible for pollen wall synthesis, such as QUARTET 3 (QRT3) and CYTOCHROME P450 703A2 (CYP703A2), resulting in a silent expression of these genes, ultimately leading to abnormal pollen wall and male sterility. Collectively, this study provides substantial information on anthers and provides clues for heat-tolerant crop creation.