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The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.
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Técnicas Eletroquímicas , Espectroscopia de Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Tecnologia sem FioRESUMO
BACKGROUND: Endoplasmic reticulum stress plays a crucial role in the pathogenesis of neuroinflammation and chronic pain. This study hypothesized that PRKR-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme type 1 (IRE1) regulate lipocalin-2 (LCN2) and Nod-like receptor family pyrin domain containing 3 (NLRP3) expression in astrocytes, thereby contributing to morphine tolerance and hyperalgesia. METHODS: The study was performed in Sprague-Dawley rats and C57/Bl6 mice of both sexes. The expression of LCN2 and NLRP3 was assessed by Western blotting. The tail-flick, von Frey, and Hargreaves tests were used to evaluate nociceptive behaviors. Chromatin immunoprecipitation was conducted to analyze the binding of activating transcription factor 4 (ATF4) to the promoters of LCN2 and TXNIP. Whole-cell patch-clamp recordings were used to evaluate neuronal excitability. RESULTS: Pharmacologic inhibition of PERK and IRE1 attenuated the development of morphine tolerance and hyperalgesia in male (tail latency on day 7, 8.0 ± 1.13 s in the morphine + GSK2656157 [10 µg] group vs. 5.8 ± 0.65 s in the morphine group; P = 0.04; n = 6 rats/group) and female (tail latency on day 7, 6.0 ± 0.84 s in the morphine + GSK2656157 [10 µg] group vs. 3.1 ± 1.09 s in the morphine group; P = 0.0005; n = 6 rats/group) rats. Activation of PERK and IRE1 upregulated expression of LCN2 and NLRP3 in vivo and in vitro. Chromatin immunoprecipitation analysis showed that ATF4 directly bound to the promoters of the LCN2 and TXNIP. Lipocalin-2 induced neuronal hyperexcitability in the spinal cord and dorsal root ganglia via melanocortin-4 receptor. CONCLUSIONS: Astrocyte endoplasmic reticulum stress sensors PERK and IRE1 facilitated morphine tolerance and hyperalgesia through upregulation of LCN2 and NLRP3 in the spinal cord.
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Inflamassomos , Morfina , Ratos , Camundongos , Masculino , Feminino , Animais , Morfina/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Astrócitos/metabolismo , Hiperalgesia/metabolismo , Roedores/metabolismo , Regulação para Cima , Lipocalina-2/metabolismo , Ratos Sprague-Dawley , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Medula Espinal/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMO
Cyclic GMP-AMP synthase (cGAS) is a major cytosolic DNA sensor that plays a significant role in innate immunity. Upon binding to double stranded DNA (dsDNA), cGAS utilizes GTP and ATP to synthesize the second messenger cyclic GMP-AMP (cGAMP). The cGAMP then binds to the adapter protein stimulator of interferon genes (STING) in the endoplasmic reticulum, resulting in the activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent induction of type I interferon. An important question is how cGAS distinguishes between self and non-self DNA. While cGAS binds to the phosphate backbone of DNA without discrimination, its activation is influenced by physical features such as DNA length, inter-DNA distance, and mechanical flexibility. This suggests that the recognition of DNA by cGAS may depend on these physical features. In this article we summarize the recent progress in research on cGAS-STING pathway involved in antiviral defense, cellular senescence and anti-tumor response, and focus on DNA recognition mechanisms based on the physical features.
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Acute myeloid leukemia (AML) is the most frequently diagnosed acute leukemia, and its incidence increases with age. Although the etiology of AML remains unknown, exposure to genotoxic agents or some prior hematologic disorders could lead to the development of this condition. The pathogenesis of AML involves the development of malignant transformation of hematopoietic stem cells that undergo successive genomic alterations, ultimately giving rise to a full-blown disease. From the disease biology perspective, AML is considered to be extremely complex with significant genetic, epigenetic, and phenotypic variations. Molecular and cytogenetic alterations in AML include mutations in those subsets of genes that are involved in normal cell proliferation, maturation and survival, thus posing significant challenge to targeting these pathways without attendant toxicity. In addition, multiple malignant cells co-exist in the majority of AML patients. Individual subclones are characterized by unique genetic and epigenetic abnormalities, which contribute to the differences in their response to treatment. As a result, despite a dramatic progress in our understanding of the pathobiology of AML, not much has changed in therapeutic approaches to treat AML in the past four decades. Dose and regimen modifications with improved supportive care have contributed to improved outcomes by reducing toxicity-related side effects. Several drug candidates are currently being developed, including targeted small-molecule inhibitors, cytotoxic chemotherapies, monoclonal antibodies and epigenetic drugs. This review summarizes the current state of affairs in the pathobiological and therapeutic aspects of AML.
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Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Epigênese Genética , Epigenômica , Humanos , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/genética , Terapia de Alvo MolecularRESUMO
Our and in vitro studies had confirmed that mechanosensitive ATP release and accumulation in acupoints was elicited by acupuncture (AP), which might be a pivotal step for triggering AP analgesia. But to date, the dynamics of extracellular ATP (eATP) in the interstitial space during AP process was poorly known, mainly due to the low temporal resolution of the current detection approach. This study attempted to capture rapid eATP signals in vivo in the process of needling, and further explored the role of this eATP mobilization in initiating AP analgesic effect. Ipsilateral 20-min needling was applied on Zusanli acupoint (ST36) of complete Freund's adjuvant (CFA)-induced ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in the interstitial space was microdialyzed and real-time quantified by luciferin-luciferase assay at 1-min interval with the aid of the microfluid chip. We revealed in behavioral tests that modulation of eATP levels in ST36 influenced AP analgesic effect on ankle arthritis. A transient eATP accumulation was induced by needling that started to mobilize at 4 min, climbed to the peak of 11.21 nM within 3.25 min and gradually recovered. Such AP-induced eATP mobilization was significantly impacted by ankle inflammation, needling depth, needle manipulation, and the presence of local ecto-nucleotidases. This work reveals that needling elicits a transient eATP mobilization in acupoints, which contributes to initiating AP analgesia. This study will help us better understand the peripheral mechanism of AP analgesia and guide clinicians to optimize the needle manipulations to improve AP efficacy.
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Analgesia por Acupuntura , Terapia por Acupuntura , Artrite , Ratos , Animais , Pontos de Acupuntura , Analgésicos , Trifosfato de AdenosinaRESUMO
The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervical intraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.
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Predisposição Genética para Doença/genética , Infecções por Papillomavirus/genética , Telomerase/genética , Telômero/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Epitélio/metabolismo , Epitélio/virologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Polimorfismo de Nucleotídeo Único , Telomerase/metabolismo , Telômero/enzimologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/metabolismo , Adulto JovemRESUMO
Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.
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Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Ratos , Canais de Potássio Ativados por Cálcio de Condutância Alta , Traumatismo por Reperfusão/tratamento farmacológico , Superóxido Dismutase , Isquemia Encefálica/tratamento farmacológicoRESUMO
The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process and the detection of CTCs has been widely used clinically. In addition, cancer stem cells (CSCs) are the source of distant metastasis. However, the relationship between CTCs and CSCs in nasopharyngeal carcinoma (NPC) patients was largely unknown. A total of 93 NPC patients were enrolled in this study. The CTCs in the peripheral blood were detected. The expression of ALDH1A1 in the tumor tissues of the corresponding patients was detected using immunohistochemistry (IHC). The prognostic value of CTCs level and the correlation with the expression of ALDH1A1 was evaluated. Data showed that the detection of CTCs was positively correlated with metastasis (p<0.001). The positive detection of CTCs was also associated with poor overall survival (p=0.025). CTCs ≥2 demonstrated good specificity and sensitivity in predicting distant metastasis, while CTCs ≥8 demonstrated better specificity and sensitivity in predicting prognosis than CTCs ≥2. Furthermore, we found that there was a positive relationship between the detection of CTCs and the expression of ALDH1A1 (p=0.001). The prognosis analysis also demonstrated that high ALDH1A1 expression was correlated with poor overall survival (p=0.006). Our study demonstrated a positive correlation between the CTCs and the expression of CSCs, both were positively correlated with metastasis and poor prognosis. These results indicated that the CTCs might indirectly reflect the expression of CSCs.
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Neoplasias Nasofaríngeas , Células Neoplásicas Circulantes , Biomarcadores Tumorais/metabolismo , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/patologia , Células Neoplásicas Circulantes/metabolismo , Células-Tronco Neoplásicas/patologia , PrognósticoRESUMO
Introduction: The diagnosis of pulmonary infection and the identification of pathogens are still clinical challenges in immunocompromised patients. Metagenomic next-generation sequencing (mNGS) has emerged as a promising infection diagnostic technique. However, its diagnostic value in immunocompromised patients needs further exploration. Purposes: This study was to evaluate the diagnostic value of mNGS compared with comprehensive conventional pathogen tests (CTs) in the etiology of pneumonia in immunocompromised patients and immunocompetent patients. Methods: We retrospectively reviewed 53 patients who were diagnosed with pneumonia from May 2019 to June 2021. There were 32 immunocompromised patients and 21 immunocompetent patients with pneumonia who received both mNGS and CTs. The diagnostic performance was compared between mNGS and CTs in immunocompromised patients, using the composite diagnosis as the reference standard. And, the diagnostic value of mNGS for mixed infections was further analyzed. Results: Compared to immunocompetent patients, the most commonly pathogens, followed by Cytomegalovirus, Pneumocystis jirovecii and Klebsiella pneumoniae in immunocompromised patients. Furthermore, more mixed infections were diagnosed, and bacterial-fungal-virus coinfection was the most frequent combination (43.8%). mNGS can detect more types of pathogenic microorganisms than CTs in both groups (78.1% vs. 62.5%, P = 0.016and 57.1% vs. 42.9%, P = 0.048). The overall diagnostic positive rate of mNGS for pathogens was higher in immunocompromised patients (P = 0.002). In immunocompromised patients, a comparable diagnostic accuracy of mNGS and CTs was found for bacterial, fungal, and viral infections and coinfection. mNGS had a much higher sensitivity for bacterial infections (92.9% vs. 50%, P < 0.001) and coinfections (68.8% vs. 48.3%, P < 0.05), and it had no significant advantage in the detection of fungal infections, mainly due to the high sensitivity for Pneumocystis jirovecii in both groups. Conclusion: mNGS is more valuable in immunocompromised patients and exhibits apparent advantages in detecting bacterial and mixed infections. It may be an alternative or complementary diagnostic method for the diagnosis of complicated infections in immunocompromised patients.
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The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.
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Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Ácido Succínico/farmacologia , Animais , Ciclo do Ácido Cítrico/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Cadeias Pesadas de Miosina/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague-Dawley rats underwent acute inflammatory pain by injecting Complete Freund's Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.
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Terapia por Acupuntura/métodos , Trifosfato de Adenosina/metabolismo , Articulação do Tornozelo/metabolismo , Artrite Experimental/metabolismo , Líquido Extracelular/metabolismo , Gânglios Sensitivos/metabolismo , Trifosfato de Adenosina/antagonistas & inibidores , Analgesia/métodos , Animais , Artrite Experimental/patologia , Artrite Experimental/terapia , Gânglios Sensitivos/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
There has been an explosion of interest in the use of nanomaterials for biosensing applications, and carbonaceous nanomaterials in particular are at the forefront of this explosion. Carbon dots (CDs), a new type of carbon material, have attracted extensive attention due to their fascinating properties, such as small particle size, tunable optical properties, good conductivity, low cytotoxicity, and good biocompatibility. These properties have enabled them to be highly promising candidates for the fabrication of various high-performance biosensors. In this review, we summarize the top-down and bottom-up synthesis routes of CDs, highlight their modification strategies, and discuss their applications in the fields of photoluminescence biosensors, electrochemiluminescence biosensors, chemiluminescence biosensors, electrochemical biosensors and fluorescence biosensors. In addition, the challenges and future prospects of the application of CDs for biosensors are also proposed.
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Técnicas Biossensoriais , Nanoestruturas , Carbono , Tamanho da PartículaRESUMO
BACKGROUND: The pathogen detection rate of traditional ink staining procedure (TISP) is low. METHODS: A modified ink staining procedure (MISP) was created to accumulate pathogen by using cell slide centrifuge. Items of RBC, WBC, and cryptococcus were observed. RESULTS: There were 79.98 ± 54.94 RBC and 126.98 ± 36.39 WBC in one MISP microscopic field whereas there were only 3.35 ± 2.41 RBC and 6.15 ± 1.85 WBC in one TISP microscopic field in the same sample (*200). There was statistical difference between those two methods (p = 0.000). There were 40.78 ± 13.23 mL cryptococcus in CSF processed by MISP whereas there were only 2.10 ± 1.10 mL cryptococcus in the same CSF processed by TISP. There was statistical difference between those two methods. CONCLUSIONS: The modified ink staining procedure contributes to the separation of cells and pathogens (such as cryptococcus).
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Cryptococcus , Centrifugação , Líquido Cefalorraquidiano , Tinta , Coloração e RotulagemRESUMO
We aimed to investigate the impact of apigenin on LOX-1, Bcl-2, and Bax expression in hyperlipidemia rats and explore the possible molecular pathological mechanism of apigenin in improving hyperlipidemia and preventing atherosclerosis. In hyperlipidemia models, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and the LOX-1 protein expression were apparently increased (P<0.01), while the high-density lipoprotein cholesterol (HDL-c) levels and the ratio of Bcl-2/Bax were reduced significantly (P<0.01) in comparison with the standard control group. After the treatment of apigenin, the levels of TC, TG, LDL-c, and the LOX-1 protein expression were noticeably decreased (P<0.01), while the levels of HDL-c and the Bcl-2/Bax ratio were increased (P<0.01). The intima was thickened and had protrusions in the hyperlipidemia model group compared to the normal control group. In comparison with the atherosclerosis model group, the degree of aortic lesions in the low-dose, middle-dose, high-dose groups was alleviated. Apigenin can reduce the level of blood lipid, improve hyperlipidemia, and prevent atherosclerosis in hyperlipidemia rats. The molecular mechanism may be related to inhibiting LOX-1 gene expression and increasing the Bcl-2/Bax ratio.
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Apigenina/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Depuradores Classe E/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Apigenina/uso terapêutico , Colesterol/sangue , Modelos Animais de Doenças , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/patologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Sprague-Dawley , Receptores Depuradores Classe E/genética , Triglicerídeos/sangue , Proteína X Associada a bcl-2/genéticaRESUMO
KEY MESSAGE: Os4BGlu14, a monolignol ß-glucosidase, plays a negative role in seed longevity by affecting primary metabolism during seed development and aging. Seed longevity is a crucial trait in agriculture and in the conservation of germplasm resources. ß-Glucosidases (BGlus) are multifunctional enzymes that affect plant growth and their adaptation to the environment. The function of rice BGlus in seed longevity, however, remains unknown. We report here that Os4BGlu14, a rice ß-Glucosidase, negatively affected seed longevity during accelerated aging. Os4BGlu14 was highly expressed in rice embryos and induced by accelerated aging. Compared to the wild type, rice lines overexpressing Os4BGlu14 had significantly greater grain length, but smaller grain width and thickness. Overexpressing (OE) lines also showed lower starch but higher glucose contents. After accelerated aging treatment, OE lines displayed a significantly lower germination percentage than the wild type. Additionally, these lines had higher lignin accumulation before and after accelerated aging. Metabolome analysis detected 217 metabolites in untreated and aged rice seeds. Comparison of the differential metabolites between WT and OE5 revealed that ten key metabolites, four of which (e.g., uridine 5'-diphosphoglucose-glucose, UDPG) were increased, while the other six (e.g., γ-aminobutyric acid and methionine) were decreased, might be the crucial factors that lead to seed deterioration. Further analysis confirmed higher UDPG levels and more severe programmed cell death in OE lines than in the wild type. Furthermore, OE lines presented a lower germination rate after abscisic acid and paclobutrazol treatment during germination, compared to the wild type. Our study provides a basis for understanding the function of Os4BGlu14 in seed longevity in rice.
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Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Sementes/fisiologia , beta-Glucosidase/genética , Ácido Abscísico/farmacologia , Morte Celular , Regulação da Expressão Gênica de Plantas , Germinação/efeitos dos fármacos , Lignina/genética , Lignina/metabolismo , Metaboloma , Estresse Oxidativo/fisiologia , Células Vegetais/fisiologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Sementes/metabolismo , Uridina Difosfato Glucose/metabolismo , beta-Glucosidase/metabolismoRESUMO
BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) and childhood acute lymphoblastic leukemia (ALL) is inconsistent. OBJECTIVE: To explore the relationship between MTHFR-C677T polymorphism and susceptibility to childhood ALL. METHODS: PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP, and other databases were searched from the establishment of the database to November 2019, and all the case-control studies that met the inclusion criteria were collected. Stata 15.0 was used for meta-analysis, with calculation of the odds ratio (OR) of the relationship between MTHFR-C677T polymorphism and childhood ALL susceptibility. Ethnicity was analyzed by subgroup analysis. RESULTS: A total of 26 studies were included in this meta-analysis, including 4,682 children with ALL and 7144 controls. The results showed that there was no significant difference in the comparison of population of allele model, dominant gene model, recessive gene model, homozygous gene model, heterozygous gene model, and the comparison of Caucasian children. The results of the Asian child analysis suggested that the combined OR of the dominant gene model (CC + CT versus TT), homozygous model (CC versus TT) and heterozygous model (CT versus TT) was 1.32 (95% confidence interval [CI]: 1.03-1.70), 1.37 (95% CI: 1.02-1.84), and 1.27 (95% CI: 1.01-1.59), respectively, with statistically significant differences. However, there was no significant difference between the allele model and recessive gene model among Asian children. CONCLUSION: The MTHFR C677T polymorphism is related to ALL in children, especially in Asian children. CC + CT, CC, and CT genotypes can increase the risk of ALL, but no association has been found in Caucasian children.
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Estudos de Associação Genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , População Branca/genéticaRESUMO
Lysine 2-hydroxyisobutyrylation (Khib) is a newly discovered post-translational modification (PTM) across eukaryotes and prokaryotes in recent years, which plays a significant role in diverse cellular functions. Accurate prediction of Khib sites is a first-crucial step to decipher its molecular mechanism and urgently needed. In this work, based on a large benchmark datasets in multi-species, a novel online species-specific prediction tool, namely KhibPred, was developed to identify Khib sites. Four types of feature strategies, including sequence-based information, physicochemical properties and evolutionary-derived information, were applied to represent a wide range of protein sequences, and the random forest was used to build the optimal feature datasets. Moreover, six representative machine learning (ML) methods were trained and comprehensively discussed and compared for each organism. Data analyses suggested that the unique protein sequence preferences were discovered for each species. When evaluated on independent test datasets, the area under the receiver operating characteristic curves (AUCs) achieved 0.807, 0.781, 0.825 and 0.831 for Saccharomyces cerevisiaes, Physcomitrella patens, Rice Seeds and HeLa cells, respectively. The satisfactory results imply that KhibPred is a promising computational tool. The online predictor can be freely available at: http://bioinfo.ncu.edu.cn/KhibPred.aspx.
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Hidroxibutiratos/metabolismo , Lisina/metabolismo , Aprendizado de Máquina , Bryopsida/química , Bryopsida/metabolismo , Células HeLa , Humanos , Hidroxibutiratos/química , Lisina/química , Oryza/química , Oryza/metabolismo , Processamento de Proteína Pós-Traducional , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , Sementes/química , Sementes/metabolismo , Especificidade da EspécieRESUMO
In recent years, deep learning models have achieved remarkable successes in various applications, such as pattern recognition, computer vision, and signal processing. However, high-performance deep architectures are often accompanied by a large storage space and long computational time, which make it difficult to fully exploit many deep neural networks (DNNs), especially in scenarios in which computing resources are limited. In this paper, to tackle this problem, we introduce a method for compressing the structure and parameters of DNNs based on neuron agglomerative clustering (NAC). Specifically, we utilize the agglomerative clustering algorithm to find similar neurons, while these similar neurons and the connections linked to them are then agglomerated together. Using NAC, the number of parameters and the storage space of DNNs are greatly reduced, without the support of an extra library or hardware. Extensive experiments demonstrate that NAC is very effective for the neuron agglomeration of both the fully connected and convolutional layers, which are common building blocks of DNNs, delivering similar or even higher network accuracy. Specifically, on the benchmark CIFAR-10 and CIFAR-100 datasets, using NAC to compress the parameters of the original VGGNet by 92.96% and 81.10%, respectively, the compact network obtained still outperforms the original networks.
Assuntos
Análise por Conglomerados , Compressão de Dados , Redes Neurais de Computação , Neurônios , AlgoritmosRESUMO
China National GeneBank DataBase (CNGBdb) is a data platform aiming to systematically archiving and sharing of multi-omics data in life science. As the service portal of Bio-informatics Data Center of the core structure, namely, "Three Banks and Two Platforms" of China National GeneBank (CNGB), CNGBdb has the advantages of rich sample resources, data resources, cooperation projects, powerful data computation and analysis capabilities. With the advent of high throughput sequencing technologies, research in life science has entered the big data era, which is in the need of closer international cooperation and data sharing. With the development of China's economy and the increase of investment in life science research, we need to establish a national public platform for data archiving and sharing in life science to promote the systematic management, application and industrial utilization. Currently, CNGBdb can provide genomic data archiving, information search engines, data management and data analysis services. The data schema of CNGBdb has covered projects, samples, experiments, runs, assemblies, variations and sequences. Until May 22, 2020, CNGBdb has archived 2176 research projects and more than 2221 TB sequencing data submitted by researchers globally. In the future, CNGBdb will continue to be dedicated to promoting data sharing in life science research and improving the service capability. CNGBdb website is: https://db.cngb.org/.
Assuntos
Bases de Dados Genéticas , Big Data , China , Genômica , Disseminação de InformaçãoRESUMO
Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.