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Background: Liver cirrhosis, as the terminal phase of chronic liver disease fibrosis, is associated with high morbidity and mortality. Traditional methods for assessing liver function, such as clinical scoring systems, offer only a global evaluation and may not accurately reflect regional liver function variations. This study aimed at evaluating the diagnostic potential of whole-liver histogram analysis of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) for predicting the progression of cirrhosis. Methods: In this retrospective study, 265 consecutive patients with cirrhosis admitted to the Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University from August 2012 to September 2019 were enrolled. After the exclusion criteria were applied, 117 patients (84 males and 33 females) were divided into Child-Pugh A cirrhosis (n=43), Child-Pugh B cirrhosis (n=49), and Child-Pugh C cirrhosis (n=25). After correction for liver signal intensity with the spleen was completed, 19 histogram features of the whole liver were extracted and modeled to evaluate liver function, with the Child-Pugh class being incorporated as a clinical parameter. Receiver operating characteristic (ROC) curves were used to assess the diagnosis capability and determine the optimal cutoffs after a mean follow-up of 42.3±19.1 (range, 8-93) months. The association between significant histogram features and the cumulative incidence of hepatic insufficiency was analyzed with the adjusted Kaplan-Meier curve model. Results: Among 117 patients (12%), 14 developed hepatic insufficiency through a period of follow-up. Five features, including the median (P<0.01), 90th percentile (P<0.01), root mean squared (P<0.01), mean (P<0.01), and 10th percentile (P<0.05), were significantly different between the groups with and without hepatic insufficiency according to the Kruskal-Wallis test; in the ROC curve analysis, the area under the curve (AUC) of these features was 0.723 [95% confidence interval (CI): 0.653-0.793], 0.722 (95% CI: 0.652-0.792), 0.722 (95% CI: 0.652-0.792), 0.721 (95% CI: 0.651-0.791), and 0.674 (95% CI: 0.600-0.748) after correction, respectively (all P values <0.05). Median, 90th percentile, root mean squared, and mean were found to be significant factors in predicting liver insufficiency. The adjusted Kaplan-Meier curves revealed that patients with a feature level less than the cutoff, as compared to those with a level above the cutoff, showed a statistically shorter progression-free survival and higher incidences of hepatic insufficiency for significant features of median (cutoff =26.001; 21.28% versus 5.71%; P=0.02), 90th percentile (cutoff =86.263; 20.41% versus 5.88%; P<0.01), root mean squared (cutoff =1,028.477; 19.15% versus 7.14%; P=0.049), and mean (cutoff =27.484; 19.15% versus 7.14%; P=0.049). Patients with a 10th percentile less than -39.811 also showed a higher cumulative incidence of hepatic insufficiency than did those with a value higher than the cutoff (0.18% versus 7.46%; P=0.22). Conclusions: Whole-liver histogram analysis of Gd-BOPTA-enhanced MRI may serve as a noninvasive analytical method to predict hepatic insufficiency in patients with cirrhosis.
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Migrasome is a newly discovered organelle composed of small vesicular structures enclosed in membrane structures. Since its discovery in 2014, migrasome has attracted increasing attention in cell biology due to its critical role in multiple disease processes. Its pivotal role in various disease processes, including cell migration, intercellular communication, removal of damaged mitochondria, embryogenesis localization, immune cell chemotaxis, and virus transmission, underscores its significance in biological systems. With research on migrasome steadily increasing, it becomes a unique resource for undergraduate cell biology education. For deeper understanding of migrasome, we applied a bibliometric approach. Here we conducted a comprehensive analysis of migrasome research by retrieving relevant literature from databases such as Web of Science, Scopus, and PubMed using the keywords "migrasome" or "migrasomes." Employing CiteSpace software and Prism, we analyzed annual publication trends, identified core authors and institutions, assessed national contributions, examined keywords, and scrutinized highly cited literature related to migrasome research. This study presents a comprehensive overview of migrasome research, elucidating its literature characteristics, key contributors, research hotspots, and emerging trends. By shedding light on the current status and future trajectories of migrasome research, we aim to provide valuable insights for teachers in cell biology education. We propose for the integration of migrasome research into undergraduate curricula to enhance the understanding of cell biology among premedical, medical, and biomedical students, thereby fostering a deeper appreciation for the intricate mechanisms governing cellular behavior and disease processes.
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Biologia Celular , Humanos , Organelas/metabolismo , Aprendizagem/fisiologia , Animais , Movimento CelularRESUMO
The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer's disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.
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Mechanically interlocked molecules, such as rotaxanes, have drawn significant attention within supramolecular chemistry. Although a variety of macrocycles have been thoroughly explored in rotaxane synthesis, metal-organic macrocycles remain relatively under-investigated. Aluminum molecular rings, with their inner cavities and numerous binding sites, present a promising option for constructing rotaxanes. Here, we introduce an innovative "ring-donor···axle-acceptor" motif utilizing Al8 molecular rings, enabling the stepwise assembly of molecules, complexes, and polymers through tailored coordination chemistry. This novel approach can not only be applied to macrocycle-based systems like catenanes but also enhance specific functionalities progressively.
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Due to the limited maximum output power of the pulsers based on avalanche transistors, high-power ultrawideband (UWB) radiation systems usually synthesize plenty of modules simultaneously to achieve a high peak effective potential (rEp). However, this would lead to an increased aperture size as well as a narrower beam, which would limit their applications in intentional electromagnetic interference fields. In this paper, a high-power UWB radiation system with beam broadening capacity is developed. To achieve beam broadening in the time domain, a power-law time delay distribution method is proposed and studied by simulation, and then the relative excitation time delays of the modules are optimized to achieve higher rEp and avoid beam splitting in the beam broadening mode. In order to avoid false triggering of the pulser elements when implementing the beam broadening, the mutual coupling effect in the system is analyzed and suppressed by employing onboard high-pass filters, since the mutual coupling effect is much more severe in the low-frequency range. Finally, a radiation system with 36 modules is developed. Measuring results indicate that in the high-rEp mode, the developed system could achieve a maximum effective potential rEp of 313.6 kV and a maximum pulse-repetition-rate of 20 kHz. In the beam broadening mode, its half-peak-power beam width in the H-plane is broadened from the original value of 3.9° to 7.9°, with a maximum rEp of 272.9 kV. The polarization direction of the system could be flexibly adjusted by a built-in motor.
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Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS-C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue-specific enrichment analysis indicate that the protective effect of PGS-C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high-cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS-C.
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Disfunção Cognitiva , Humanos , Disfunção Cognitiva/genética , Masculino , Idoso , Feminino , Personalidade/genética , Fatores de Proteção , Herança Multifatorial/genética , Cognição/fisiologia , Imageamento por Ressonância Magnética/métodos , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed amygdalin content of P. sibirica is an interesting question. Mandelonitrile is known as one key intermediate of amygdalin metabolism, but which mandelonitrile lyase (MDL) family member essential for its dissociation destined to low amygdalin accumulation in P. sibirica seeds still remains enigmatic. An integration of our recent 454 RNA-seq data, amygdalin and mandelonitrile content detection, qRT-PCR analysis and function determination is described as a critical attempt to determine key MDL and to highlight its function in governing mandelonitrile catabolism with low amygdalin accumulation in Prunus sibirica seeds for better developing edible oil and biodiesel in China. RESULTS: To identify key MDL and to unravel its function in governing seed mandelonitrile catabolism with low amygdalin accumulation in P. sibirica. Global identification of mandelonitrile catabolism-associated MDLs, integrated with the across-accessions/developing stages association of accumulative amount of amygdalin and mandelonitrile with transcriptional level of MDLs was performed on P. sibirica seeds of 5 accessions to determine crucial MDL2 for seed mandelonitrile catabolism of P. sibirica. MDL2 gene was cloned from the seeds of P. sibirica, and yeast eukaryotic expression revealed an ability of MDL2 to specifically catalyze the dissociation of mandelonitrile with the ideal values of Km (0.22 mM) and Vmax (178.57 U/mg). A combination of overexpression and mutation was conducted in Arabidopsis. Overexpression of PsMDL2 decreased seed mandelonitrile content with an increase of oil accumulation, upregulated transcript of mandelonitrile metabolic enzymes and oil synthesis enzymes (involving FA biosynthesis and TAG assembly), but exhibited an opposite situation in mdl2 mutant, revealing a role of PsMDL2-mediated regulation in seed amygdalin and oil biosynthesis. The PsMDL2 gene has shown as key molecular target for bioengineering high seed oil production with low amygdalin in oilseed plants. CONCLUSIONS: This work presents the first integrated assay of genome-wide identification of mandelonitrile catabolism-related MDLs and the comparative association of transcriptional level of MDLs with accumulative amount of amygdalin and mandelonitrile in the seeds across different germplasms and developmental periods of P. sibirica to determine MDL2 for mandelonitrile dissociation, and an effective combination of PsMDL2 expression and mutation, oil and mandelonitrile content detection and qRT-PCR assay was performed to unravel a mechanism of PsMDL2 for controlling amygdalin and oil production in P. sibirica seeds. These findings could offer new bioengineering strategy for high oil production with low amygdalin in oil plants.
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Amigdalina , Prunus , Sementes , Amigdalina/metabolismo , Prunus/genética , Prunus/metabolismo , Prunus/enzimologia , Sementes/metabolismo , Sementes/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Óleos de Plantas/metabolismo , Aldeído Liases/metabolismo , Aldeído Liases/genética , Regulação da Expressão Gênica de PlantasRESUMO
Background: Alphaviruses are a diverse group of pathogens that have garnered considerable attention due to their impact on human health. By investigating alphavirus receptors, researchers can elucidate viral entry mechanisms and gain important clues for the prevention and treatment of viral diseases. This study presents an in-depth analysis of the research progress made in the field of alphavirus receptors through bibliometric analysis. Methods: This study encompasses various aspects, including historical development, annual publication trends, author and cited-author analysis, institutional affiliations, global distribution of research contributions, reference analysis with strongest citation bursts, keyword analysis, and a detailed exploration of recent discoveries in alphavirus receptor research. Results: The results of this bibliometric analysis highlight key milestones in alphavirus receptor research, demonstrating the progression of knowledge in this field over time. Additionally, the analysis reveals current research hotspots and identifies emerging frontiers, which can guide future investigations and inspire novel therapeutic strategies. Conclusion: This study provides an overview of the state of the art in alphavirus receptor research, consolidating the existing knowledge and paving the way for further advancements. By shedding light on the significant developments and emerging areas of interest, this study serves as a valuable resource for researchers, clinicians, and policymakers engaged in combating alphavirus infections and improving public health.
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Alphavirus , Bibliometria , Humanos , Receptores Virais/metabolismo , Animais , Internalização do Vírus , Infecções por Alphavirus/virologia , Pesquisa Biomédica/tendênciasRESUMO
Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.
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Aprendizado Profundo , Humanos , Estilbenos/química , Bactérias Gram-Positivas/isolamento & purificação , Corantes Fluorescentes/química , Bactérias Gram-Negativas/isolamento & purificação , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/diagnóstico , Fungos/isolamento & purificaçãoRESUMO
CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.
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Neoplasias da Mama , Proliferação de Células , Proteína-Arginina N-Metiltransferases , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/metabolismo , Feminino , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Camundongos Nus , Camundongos Endogâmicos BALB C , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêuticoRESUMO
Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer's disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.
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Doença de Alzheimer , Demência Frontotemporal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Neurodegenerativas , Fenótipo , Polimorfismo de Nucleotídeo Único , Humanos , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/diagnóstico por imagem , Demência Frontotemporal/genética , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/patologia , Masculino , Feminino , Imagem de Difusão por Ressonância Magnética , Esclerose Múltipla/genética , Esclerose Múltipla/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idoso , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Reino UnidoRESUMO
Rh-catalyzed three-component C(sp3)/C(sp2)-H activation has been achieved through a two-directing group strategy. This protocol provides a convenient and efficient pathway for the construction of diverse 8-alkyl quinoline derivatives in one-pot. Furthermore, mechanistic studies revealed that the first C-H amidation was significantly faster than the sequential C-H alkylation.
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Vertical three-dimensional integration of two-dimensional (2D) semiconductors holds great promise, as it offers the possibility to scale up logic layers in the z axis1-3. Indeed, vertical complementary field-effect transistors (CFETs) built with such mixed-dimensional heterostructures4,5, as well as hetero-2D layers with different carrier types6-8, have been demonstrated recently. However, so far, the lack of a controllable doping scheme (especially p-doped WSe2 (refs. 9-17) and MoS2 (refs. 11,18-28)) in 2D semiconductors, preferably in a stable and non-destructive manner, has greatly impeded the bottom-up scaling of complementary logic circuitries. Here we show that, by bringing transition metal dichalcogenides, such as MoS2, atop a van der Waals (vdW) antiferromagnetic insulator chromium oxychloride (CrOCl), the carrier polarity in MoS2 can be readily reconfigured from n- to p-type via strong vdW interfacial coupling. The consequential band alignment yields transistors with room-temperature hole mobilities up to approximately 425 cm2 V-1 s-1, on/off ratios reaching 106 and air-stable performance for over one year. Based on this approach, vertically constructed complementary logic, including inverters with 6 vdW layers, NANDs with 14 vdW layers and SRAMs with 14 vdW layers, are further demonstrated. Our findings of polarity-engineered p- and n-type 2D semiconductor channels with and without vdW intercalation are robust and universal to various materials and thus may throw light on future three-dimensional vertically integrated circuits based on 2D logic gates.
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Several trichomonad species have already been identified in pigs, and their pathogenic potential may not be ruled out. To date, however, no information is available regarding the prevalence of trichomonads in pigs in Shanxi Province, North China. In the present study, a total of 362 fecal samples collected from pigs in three representative counties (Qi, Jishan, and Shanyin) in this province were examined for Tetratrichomonas buttreyi, Tritrichomonas foetus, and Pentatrichomonas hominis using a nested polymerase chain reaction (PCR) with primers targeting the small subunit ribosomal RNA (SSU rRNA) gene. The overall prevalence of T. buttreyi was 49.72%, and region and age were found to be significantly associated with T. buttreyi infection, respectively. Only one pig fecal sample from Qi County was found to be positive for T. foetus, and all samples were negative for P. hominis. Molecular evolutionary analysis revealed that some T. buttreyi isolates showed complete genetic identity with those reported previously, and some T. buttreyi isolates and one T. foetus isolate showed minor allelic variations compared with those reported previously. This is the report of the molecular epidemiology of T. foetus and T. buttreyi in pigs in Shanxi Province, North China. These findings not only enrich the knowledge on the distribution of these trichomonad species in pigs in China but also provide baseline information for planning future research and control strategies.
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The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTSâ¢+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.
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Toxinas Bacterianas , Técnicas Biossensoriais , Técnicas Eletroquímicas , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/análise , Estruturas Metalorgânicas/química , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Peroxidase/metabolismo , Peroxidase/química , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/metabolismoRESUMO
Pyroptosis, a programmed cell death process, is vital for the immune response against microbial infections and internal danger signals. Recent studies have highlighted the importance of protein palmitoylation, a modification that involves attaching palmitate to cysteine residues, in regulating key proteins involved in pyroptosis. Palmitoylation of cGAS at residue C474 by ZDHHC18 affects its enzymatic activity and DNA binding ability. Similarly, ZDHHC9 promotes cGAS activity through palmitoylation at residues C404/405. NLRP3 palmitoylation at residue C844, mediated by ZDHHC12, impacts its stability and interactions with other proteins, crucial for activating the NLRP3 inflammasome and triggering inflammation. However, the role of ZDHHC5 in NLRP3 palmitoylation remains uncertain due to conflicting findings. Palmitoylation at C88/91 is essential for STING activation and induction of type I interferons. It modulates the formation of multimeric complexes and downstream signaling pathways. GSDMD palmitoylation at C191 is necessary for pore formation and membrane translocation, while GSDME palmitoylation at C407/408 is associated with drug-induced pyroptosis. Moreover, palmitoylation of NOD1 and NOD2 influences their membrane recruitment and immune signaling pathways in response to bacterial peptidoglycans, acting as upstream regulators of pyroptosis. This review summarizes the important roles for palmitoylation in regulating the function of key pyroptosis-related proteins, shedding light on the intricate mechanisms governing immune responses and inflammation.
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Lipoilação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Humanos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Inflamassomos/imunologia , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/imunologia , Inflamação/imunologia , Aciltransferases/imunologiaRESUMO
Pancreatic cancer is a highly malignant and metastatic cancer. Pancreatic cancer can lead to liver metastases, gallbladder metastases, and duodenum metastases. The identification of pancreatic cancer cells is essential for the diagnosis of metastatic cancer and exploration of carcinoma in situ. Organelles play an important role in maintaining the function of cells, the various cells show significant differences in organelle microenvironment. Herein, six probes are synthesized for targeting mitochondria, lysosomes, cell membranes, endoplasmic reticulum, Golgi apparatus, and lipid droplets. The six fluorescent probes form an organelles-targeted sensor array (OT-SA) to image pancreatic metastatic cancer cells and cell spheroids. The homology of metastatic cancer cells brings the challenge for identification of these cells. The residual network (ResNet) model has been proven to automatically extract and select image features, which can figure out a subtle difference among similar samples. Hence, OT-SA is developed to identify pancreatic metastasis cells and cell spheroids in combination with ResNet analysis. The identification accuracy for the pancreatic metastasis cells (> 99%) and pancreatic metastasis cell spheroids (> 99%) in the test set is successfully achieved respectively. The organelles-targeting sensor array provides a method for the identification of pancreatic cancer metastasis in cells and cell spheroids.
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Organelas , Neoplasias Pancreáticas , Esferoides Celulares , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Humanos , Linhagem Celular Tumoral , Organelas/metabolismo , Corantes Fluorescentes/química , Metástase NeoplásicaRESUMO
Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson's disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.
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Córtex Motor , Doença de Parkinson , Ratos , Animais , Hipocinesia , Gânglios da Base , Movimento , Ritmo betaRESUMO
Under conditions of dietary amino acid balance, decreasing the dietary crude protein (CP) level in pigs has a beneficial effect on meat quality. To further elucidate the mechanism, we explored the alteration of muscle fiber characteristics and key regulators related to myogenesis in the skeletal muscle of pigs fed a protein restricted diet. Compared to pigs fed a normal protein diet, dietary protein restriction significantly increased the slow-twitch muscle fiber proportion in skeletal muscle, succinic dehydrogenase (SDH) activity, the concentrations of ascorbate, biotin, palmitoleic acid, and the ratio of s-adenosylhomocysteine (SAM) to s-adenosylhomocysteine (SAH), but the fast-twitch muscle fiber proportion, lactate dehydrogenase (LDH) activity, the concentrations of ATP, glucose-6-phosphate, SAM, and SAH in skeletal muscle, and the ratio of serum triiodothyronine (T3) to tetraiodothyronine (T4) were decreased. In conclusion, we demonstrated that dietary protein restriction induced skeletal muscle fiber remodeling association the regulation of FGF21-ERK1/2-mTORC1 signaling in weaned piglets.
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White light-emitting diode (LED) for night lighting disrupts photoperiod in plants, which affects the plant's photosynthesis. Therefore, it is necessary to find a new type of white LED with little effect on plant photosynthesis. In this study, a series of phosphate phosphors Ca9NaY2/3(PO4)7:Dy3+ (CNYP:Dy3+) were synthesized. Cation Li+ substitute Na+ were used to improve the luminescence properties of CNYP:Dy3+ phosphor. The CNYP:Dy3+ phosphor exhibits visible white light emission with emission peaks at 480 nm (blue light) and 570 nm (yellow light) excited by the near ultraviolet light 350 nm. The optimal concentration of Dy3+ was 0.10 mol, and the mechanism of concentration quenching was evaluated as energy migration among the nearest or next-nearest Dy3+. The substitution of Na+ by Li+ of CNYP:0.10Dy3+ improves the internal quantum efficiency from 30.24 % to 59.05 %, and presents good near-zero thermal quenching performance at 423 K. To assess the suitability of this phosphor for urban ecological lighting, the spectrum resemblance (SR) index between the electroluminescence spectrum of the prepared pc-LED and the absorption spectra of chlorophyll a and b was evaluated as 6.63 % and 18.61 %, respectively. This work exhibits a feasible scheme for the development of urban ecological lighting.