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Developing highly active electrocatalysts is crucial for the application of electrocatalytic water splitting. In this study, we prepared vanadium oxide-graphene carbon nanocomposites (VxOy/C) with abundant defects using a carbon- and oxygen-rich hexavanadate derivative Na2[V6O7{(OCH2)3CCH3}4] as a precursor without the addition of an extra carbon source. Subsequently, the VxOy/C was used as a catalyst support to load a small amount of Ir, forming the Ir/VxOy/C nanoelectrocatalyst. This catalyst exhibited low hydrogen evolution overpotentials of only 18.90 and 13.46 mV at a working current density of 10 mA cm-2 in 1.0 M KOH and 0.5 M H2SO4 electrolyte systems, outperforming the commercial Pt/C catalysts. Additionally, the catalyst showed excellent chemical stability and long-term durability. This work provides a new strategy for the design and synthesis of highly active electrocatalysts for water splitting.
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To explore, highly active electrocatalysts are essential for water splitting materials. Polyoxometalates (POMs) have drawn interesting attention in recent years due to their abundant structure and unique electrocatalytic properties. In this study, by using a POM-based precursor Co2Mo10, novel bimetallic sulfide (CoS2-MoS2) nanocomposites are rationally designed and synthesized under hydrothermal conditions. The incorporation of Co2+ to the host electrocatalyst could effectively increase the exposure of active sites of MoS2. Compared to pure MoS2, the CoS2-MoS2 nanocomposite exhibited a perfect hydrogen evolution reaction (HER) ability, for it merely requires overpotentials of 120 and 153 mV for 10 mA cm-2 working current density toward the HER in 1 M KOH and 0.5 M H2SO4 electrolyte systems, respectively. Additionally, the nanocomposite exhibited outstanding chemical stability and long-term durability. This study presents a novel strategy that utilizes POMs to enrich the exposed edge sites of MoS2, resulting in the preparation of efficient electrocatalysts.
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Developing inexpensive, efficient, and stable catalysts is crucial for reducing the cost of electrolytic hydrogen production. Recently, polyoxometalates (POMs) have gained attention and widespread use due to their excellent electrocatalytic properties. This study designed and synthesized three composite materials, NF/PMonW12-n, by using phosphomolybdic-tungstic heteropolyacids as precursors to grow in situ on nickel foam via the hydrothermal process and subsequent calcination. Then, their catalytic performances are systematically investigated. This work demonstrates that the NF/PMonW12-n catalysts generate more low valent oxides under the synergistic effect of Mo and W, further enhancing activity for hydrogen evolution reaction (HER). Among these electrocatalysts, NF/PMo6W6 exhibits the perfect HER performance, η10 is only 74 mV. It also shows great stability during long-term electrolysis. The current study introduces a fresh approach for producing electrocatalysts that are both cost-effective and highly efficient.
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BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.
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BACKGROUND: Acute pancreatitis is an acute inflammatory disorder of the pancreas, and severe acute pancreatitis is associated with high mortality. Early assessment the severity of AP has an important significance for improving clinical outcomes. Our object aimed to develop a nomogram with high simplicity and rapidity for predicting the severity of acute pancreatitis. METHODS: Patients admitted to the Hunan Provincial People's Hospital within 72 h from onset of AP from January 2010 and December 2020 were enrolled to establish a nomogram. Independent predictors were determined using univariate and multivariate analysis and then assembled to construct a predicting nomogram. The performance of proposed nomogram was evaluated by Brier score and Harrell's concordance index (C-index). Meanwhile, clinical data of AP patients from January 2021 to January 2022 were collected for external validation. RESULTS: Album (OR 0.891, 95%CI 0.867-0.917), calcium (OR 0.151, 95%CI 0.084-0.273), neutrophil to lymphocyte ratio (OR 1.055, 95%CI 1.023-1.088) and systemic inflammatory response syndrome (OR 6.292, 95%CI 4.459-8.879) were identified as independent factors of SAP after univariate and multivariate analysis (p < .05). A predictive nomogram was accordingly established using these four independent variables. The internally verified C-index was 0.796 (95% CI 0.773-0.818), Brier score was 0.138. The externally verified C index was 0.820 (95% CI 0.754-0.887). CONCLUSION: A nomogram for predicting the severity of AP was well developed, it may be of great significance for clinicians to quickly assess the progress of AP and choose more-targeted strategies.
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Pancreatitis , Enfermedad Aguda , Humanos , Nomogramas , Pancreatitis/diagnóstico , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Modern breeding in the poultry industry mainly aims to produce high-performance poultry lines and breeds in two main directions of productivity, meat and eggs. To understand more about the productive potential of lowly selected Chinese native chicken populations, we selected 14 representative SNP markers strongly associated with growth traits or carcass traits and 14 SNP markers strongly associated with egg laying traits through previous reports. By using the MassArray technology, we detected the genotype frequency distributions of these 28 SNP markers in seven populations including four lowly selected as well as one moderately selected Sichuan native chicken populations, one commercial broiler line and one commercial layer line. RESULTS: Based on the genotype frequency distributions of these 28 SNP markers in 5 native chicken populations and 2 commercial lines, the results suggested that these Chinese indigenous chicken populations have a relatively close relationship with the commercial broiler line but a marked distinction from the commercial layer line. Two native chicken breeds, Shimian Caoke Chicken and Daheng Broilers, share similar genetic structure with the broiler line. CONCLUSIONS: Our observations may help us to better select and breed superior domestic chickens and provide new clues for further study of breeding programs in local chicken populations.
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Pollos/genética , Marcadores Genéticos , Genotipo , Polimorfismo de Nucleótido Simple , Animales , China , Análisis por Conglomerados , Frecuencia de los Genes , Genética de Población , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Reproducción/genéticaRESUMEN
Precise regulation of glucose metabolism-related genes is essential for early embryonic development. Although previous research has yielded detailed information on the biochemical processes, little is yet known of the dynamic gene expression profiles in glucose metabolism of preimplantation embryos at a single-cell resolution. In the present study, we performed integrated analysis of single-cell RNA sequencing (scRNA-seq) data of human preimplantation embryos that had been cultured in sequential medium. Different cells in the same embryo have similar gene expression patterns in glucose metabolism. During the switch from the cleavage to morula stage, the expression of glycolysis-related genes, such as glucose transporter genes (solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) and solute carrier family 2 (facilitated glucose transporter), member 3 (SLC2A3) and genes encoding hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, is increased. The genes involved in the pentose phosphate pathway are highly expressed at the cleavage stage, generating the reducing power to balance oxidative stress derived from biosynthesis. Expression of the genes involved in the biosynthesis of glycerophospholipids is increased after the morula stage. Nevertheless, the expression of tricarboxylic acid-related genes remains relatively unchanged during the preimplantation stages. In conclusion, we discovered that the gene expression profiles are dynamic according to glucose utilisation in the embryos at different stages, which contributes to our understanding of regulatory mechanisms of glucose metabolism-related genes in human preimplantation embryos.
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Blastocisto/metabolismo , Metabolismo de los Hidratos de Carbono/genética , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , Glucosa/metabolismo , Bases de Datos Genéticas , Técnicas de Cultivo de Embriones , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/genética , Transportador de Glucosa de Tipo 3/metabolismo , Hexoquinasa/genética , Hexoquinasa/metabolismo , Humanos , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Fosfofructoquinasa-1/genética , Fosfofructoquinasa-1/metabolismo , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
Broodiness is a behavior commonly occurring in the poultry industry, which is characterized by inappetence, egg-laying cessation and incubation. Different from laying fowls, the ovary and oviduct of broodiness fowls is degenerate. Broodiness is a low heritability trait, which is controlled by multiple genes in autosomes and influenced by three factors, including environment, endocrine and genetics. In addition to the observation of behavioral characteristics, the current research of broodiness focuses on evaluating the genetic mode, endocrine factors, nesting candidate genes and their polymorphisms in poultry. Given the rapid development of high-throughput sequencing, the joint analyses of genomics, transcriptomics and proteomics have been used to screen out the candidate genes, pathways and molecular mechanism of broodiness. In this review, we summarize the candidate genes, microRNAs and pathways involved in broodiness to provide a reference for further research on poultry broodiness.
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Regulación de la Expresión Génica , Comportamiento de Nidificación , Oviposición , Aves de Corral/genética , Animales , Femenino , Aves de Corral/fisiologíaRESUMEN
Innate immunity is an essential line of defense against pathogen invasion which is gained at birth, and the mechanism involved is mainly to identify pathogen-associated molecular patterns through pattern recognition receptors. STING (stimulator of interferon genes) is a signal junction molecule that hosts the perception of viral nucleic acids and produces type I interferon response, which plays a crucial role in innate immunity. However, relatively few studies have investigated the molecular characterization, tissue distribution, and potential function of STING in chickens. In this study, we cloned the full-length cDNA of chicken STING that is composed of 1341 bp. Sequence analyses revealed that STING contains a 1140-bp open-reading frame that probably encodes a 379-amino acid protein. Multiple sequence alignments showed that the similarity of the chicken STING gene to other birds is higher than that of mammals. Real-time polymerase chain reaction (PCR) assays revealed that STING is highly expressed in the spleen, thymus and bursa of fabricious in chickens. Furthermore, we observed that STING expression was significantly upregulated both in vitro and in vivo following infection with Newcastle disease virus (NDV). STING expression was also significantly upregulated in chicken embryo fibroblasts upon stimulation with poly(I:C) or poly(dA:dT). Taken together, these findings suggest that STING plays an important role in antiviral signaling pathways in chickens.
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Proteínas Aviares/genética , Proteínas de la Membrana/genética , Animales , Proteínas Aviares/química , Proteínas Aviares/metabolismo , Células Cultivadas , Embrión de Pollo , Pollos , Clonación Molecular , Interferones/genética , Interferones/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Enfermedad de Newcastle/inmunología , Sistemas de Lectura Abierta , Enfermedades de las Aves de Corral/inmunología , Bazo/metabolismo , Timo/metabolismo , Regulación hacia ArribaRESUMEN
Lung cancer is a common disease with high mortality in China. Recent economic advances have led to improved medical capabilities, while costs associated with treating this disease have increased. Such change contributes to a commonly held belief that healthcare costs are out of control. However, few studies have examined this issue. Here, we use 34,678 hospitalization summary reports from 67 Guangxi hospitals (period 2013-2016) to document costs, temporal trends, and associated factors. Findings from this study are surprising in that they debunk the myth of uncontrolled healthcare costs. In addition, results and experiences from Guangxi are informative for other comparable regions.
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Atención a la Salud/economía , Costos de Hospital , Hospitales , Neoplasias Pulmonares/economía , Neoplasias Pulmonares/terapia , Evaluación de Procesos, Atención de Salud/economía , Adulto , Anciano , Anciano de 80 o más Años , China , Bases de Datos Factuales , Atención a la Salud/tendencias , Femenino , Costos de Hospital/tendencias , Hospitales/tendencias , Humanos , Seguro de Salud/economía , Seguro de Salud/estadística & datos numéricos , Tiempo de Internación/economía , Tiempo de Internación/tendencias , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Ocupaciones/economía , Ocupaciones/tendencias , Evaluación de Procesos, Atención de Salud/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Neuropathic pain responds poorly to drug treatments. Partial relief is achieved in only about half of the patients. Danggui Sini decoction (DSD), an aqueous extract of Angelica sinensis, Ramulus Cinnamomi, and Radix Puerariae, has been used extensively in China to treat inflammatory and ischemic diseases. The current study examined the putative effects of DSD on neuropathic pain. METHOD: We used two commonly-used animal models: chronic constriction injury (CCI) and diabetic neuropathy for the study. And we examined effects of DSD on pain response, activation of microglia and astroglia in spinal dorsal horn, and expression of proinflammatory cytokines in the spinal cord. RESULTS: Consecutive intragastric administration of DSD (25 - 100 mg/kg) for 10 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models, DSD inhibited the over-expression of specific markers for microglia (Iba-1) and astroglia (GFAP) activation in the spinal dorsal horn. DSD also reduced the elevated nuclear NF-κB level and inhibited the up-regulation of proinflammatory cytokines, such as IL-6, IL-1ß, and TNF-α, in the spinal cord. CONCLUSION: DSD can alleviate CCI and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of DSD may be related to the suppression of spinal NF-κB activation and/or cytokines expression.â©.
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Analgésicos/farmacología , Citocinas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Mediadores de Inflamación/metabolismo , Neuralgia/prevención & control , Neuroglía/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Animales , Neuropatías Diabéticas/complicaciones , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ligadura , Masculino , FN-kappa B/metabolismo , Neuralgia/etiología , Neuralgia/metabolismo , Neuralgia/fisiopatología , Neuroglía/metabolismo , Ratas Sprague-Dawley , Nervio Ciático/cirugía , Transducción de Señal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
OBJECTIVE: Determination of the urinary levels of 2.5-hexanedione (2,5-HD) was performed in subjects belonging to the Chinese general population to define the reference value for this metabolite. METHODS: Urine samples were collected from 8235 individuals (4216 men and 4019 women) from the healthy general population who had not been occupationally exposed to n-hexane or methyl-n-butyl ketone. The determination was performed by a gas chromatography mass spectrometry method using an ion-trap mass spectrometer. RESULTS: The result showed that the urinary 2,5-HD median level was 0.159mg/L for the total samples. Males had statistically significant higher excretion of 2,5-HD in urine than females (median 0.171mg/L compared to 0.147mg/L, Z=-8.21, P<0.001). There was a statistically significant difference in urinary 2,5-HD levels among age groups. The excretion of 2,5-HD in urine was related to increasing age (r=-0.160, P<0.05). There was statistically significant difference in urinary 2,5-HD levels among people from difference provinces. The results showed that there was also a statistically significant effect in urinary 2,5-HD levels between current smokers and non-smokers. CONCLUSION: Finding a measurable amount of 2,5-HD in urine does not mean that the level of 2,5-HD causes an adverse health effect. Biomonitoring studies on levels of urinary 2,5-HD can provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of 2,5-HD than are found in the Chinese general population. These data can also provide a foundation for scientists to make a plan for further study.
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Contaminantes Ambientales/orina , Hexanonas/orina , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/orina , Pueblo Asiatico , Niño , Monitoreo del Ambiente , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Fumar/orina , Adulto JovenRESUMEN
Steady progress has been achieved in the medical genetics in China in 2015, as numerous original researches were published in the world's leading journals. Chinese scientists have made significant contributions to various fields of medical genetics, such as pathogenicity of rare diseases, predisposition of common diseases, somatic mutations of cancer, new technologies and methods, disease-related microRNAs (miRNAs), disease-related long non-coding RNAs (lncRNAs), disease-related competing endogenous RNAs (ceRNAs), disease-related RNA splicing and molecular evolution. In these fields, Chinese scientists have gradually formed the tendency, from common variants to rare variants, from single omic analyses to multipleomics integration analyses, from genetic discovery to functional confirmation, from basic research to clinical application. Meanwhile, the findings of Chinese scientists have been drawn great attentions of international peers. This review aims to provide an overall picture of the front in Chinese medical genetics, and highlights the important findings and their research strategy.
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Genética Médica , Metilación de ADN , Evolución Molecular , Predisposición Genética a la Enfermedad , Humanos , MicroARNs/fisiología , Mutación , Neoplasias/genética , Enfermedades Raras/genéticaRESUMEN
Intellectual disability, occurring in 1%-3% of the general population, is a common disease of the nervous system in children. Since diverse genetic and environmental factors contribute to its pathogenesis, the etiological diagnosis of intellectual disability is challenging with respect to the selection of diagnostic tests. It is important to determine the etiology of intellectual disability for the assessment of prognosis, treatment and the family plan. This paper summarizes the research progress in etiology and diagnosis for intellectual disability and introduces the recommended clinical genetics diagnostic approach from the American Academy of Pediatrics.
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Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/etiología , Bandeo Cromosómico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Discapacidad Intelectual/genética , Análisis por MicromatricesRESUMEN
Diabetic neuropathy is characterized by progressive degeneration of nerve fibers associated with diabetes mellitus. Antidepressants and anticonvulsants are the mainstay of pharmacological treatment, but are often limited in effectiveness against the core clinical feature of pain. In the current study, we examined the potential effects of koumine, a Gelsemium elegans Benth alkaloid, using a rat model of diabetic neuropathy. Rats were administered intraperitoneally a single dose of streptozocin (60 mg/kg) to induce type 1 diabetes. Koumine was given at a dose range of 0.056-7 mg/kg subcutaneously for one week starting 3 weeks after streptozocin adminstration. Behavioral responses to mechanical stimuli were evaluated every day after streptozocin injection. At 4 weeks after streptozocin injection, sensory nerve conduction velocity (SNCV) and morphological alternation of sciatic nerves were assessed by electron microscopy. Diabetic rats developed mechanical hyperalgesia within 3 weeks after streptozocin injection and exhibited reduced SNCV and impaired myelin/axonal structure. Koumine treatment of diabetic rats decreased neuropathic pain behavior as early as after the first administration. At a dose of 7 mg/kg, koumine was more effective than gabapentin (100 mg/kg), and decreased mechanical sensitivity threshold to a level comparable to healthy control. Repeated treatment of koumine significantly reduced the damage to axon and myelin sheath of the sciatic nerve and increased SNCV, without affecting body weight and blood glucose. These findings encourage the use of koumine in the treatment of diabetic neuropathy.
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Neuropatías Diabéticas/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/uso terapéutico , Degeneración Nerviosa/tratamiento farmacológico , Aminas/uso terapéutico , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/inducido químicamente , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/fisiopatología , Relación Dosis-Respuesta a Droga , Gabapentina , Hiperalgesia/inducido químicamente , Hiperalgesia/complicaciones , Hiperalgesia/patología , Hiperalgesia/fisiopatología , Masculino , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Neuralgia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Dimensión del Dolor/efectos de los fármacos , Ratas , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patología , Nervio Ciático/fisiología , Nervio Ciático/ultraestructura , Células Receptoras Sensoriales/efectos de los fármacos , Células Receptoras Sensoriales/patología , Células Receptoras Sensoriales/fisiología , Células Receptoras Sensoriales/ultraestructura , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
Inflammatory pain and neuropathic pain are major health issues that represent considerable social and economic burden worldwide. In this study we investigated the potential of obtusifolin and gluco-obtusifolin, two anthraquinones found in the seeds of the widely used traditional Chinese medical botanical Cassia obtusifolia, to reduce neuropathic and inflammatory pain. The potential analgesic effects of obtusifolin and gluco-obtusifolin were evaluated by mice formalin test and complete Freund's adjuvant (CFA)-induced nociceptive behaviors in rats. Chronic constriction injury (CCI), L5 spinal nerve ligation (L5 SNL), diabetes, and chemotherapeutics inducing allodynia were used to test whether repeated treatment with obtusifolin and gluco-obtusifolin ameliorated neuropathic pain. Finally, we explored whether obtusifolin and gluco-obtusifolin altered the degree of neuroinflammation in rat spinal cord after CFA administration and CCI induction. Obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reduced licking/biting time in dose-dependent manner in phase 2 of formalin-induced behavior in mice. Furthermore, repeated administration of obtusifolin and gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed mechanical allodynia induced by CFA, CCI, L5 SNL, diabetes, and oxaliplatin in a dose-dependent manner in rats. Levels of activated nuclear factor-kappa B (NF-κB) and proinflammatory cytokines (interleukin (IL)-1ß, IL-6, tumor necrosis factor α (TNF-α)) in lumbar spinal cord were elevated in rats following CFA treatment and CCI induction, and obtusifolin and gluco-obtusifolin significantly inhibited these effects. Our results demonstrate that obtusifolin and gluco-obtusifolin produce significant antinociceptive action in rodent behavioral models of inflammatory/neuropathic pain, and that this activity is associated with modulation of neuroinflammation in spinal cord.
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Antraquinonas/uso terapéutico , Glucósidos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Mediadores de Inflamación/antagonistas & inhibidores , Neuralgia/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Animales , Antraquinonas/farmacología , Relación Dosis-Respuesta a Droga , Glucósidos/farmacología , Hiperalgesia/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Neuralgia/metabolismo , Dimensión del Dolor/métodos , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
Developing DNA strand displacement reactions (SDRs) offers crucial technical support for regulating artificial nucleic acid circuits and networks. More recently, enzymatic SDR-based DNA circuits have gained significant attention because of their modular design, high orthogonality signaling, and extremely fast reaction rates. Typical enzymatic SDRs are regulated by relatively long primers (20-30 nucleotides) that hybridize to form stable double-stranded structures, facilitating enzyme-initiated events. Implementing more flexible primer-based enzymatic SDR regulations remains challenging due to the lack of convenient and simple primer control mechanism, which consequently limits the development of enzymatic DNA circuits. In this study, we propose an approach, termed primer switching regulation, that implements programmable and flexible regulations of enzymatic circuits by introducing switchable wires into the enzymatic circuits. We applied this method to generate diverse enzymatic DNA circuits, including cascading, fan-in/fan-out, dual-rail, feed-forward, and feedback functions. Through this method, complex circuit functions can be implemented by just introducing additional switching wires without reconstructing the basic circuit frameworks. The method is experimentally demonstrated to provide flexible and programmable regulations to control enzymatic DNA circuits and has future applications in DNA computing, biosensing, and DNA storage.
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Computadores Moleculares , Ácidos Nucleicos , ADN/química , NucleótidosRESUMEN
AIMS: This study aimed to investigate the resting-state functional connectivity and topologic characteristics of brain networks in patients with diabetic optic neuropathy (DON). METHODS: Resting-state functional magnetic resonance imaging scans were performed on 23 patients and 41 healthy control (HC) subjects. We used independent component analysis and graph theoretical analysis to determine the topologic characteristics of the brain and as well as functional network connectivity (FNC) and topologic properties of brain networks. RESULTS: Compared with HCs, patients with DON showed altered global characteristics. At the nodal level, the DON group had fewer nodal degrees in the thalamus and insula, and a greater number in the right rolandic operculum, right postcentral gyrus, and right superior temporal gyrus. In the internetwork comparison, DON patients showed significantly increased FNC between the left frontoparietal network (FPN-L) and ventral attention network (VAN). Additionally, in the intranetwork comparison, connectivity between the left medial superior frontal gyrus (MSFG) of the default network (DMN) and left putamen of auditory network was decreased in the DON group. CONCLUSION: DON patients altered node properties and connectivity in the DMN, auditory network, FPN-L, and VAN. These results provide evidence of the involvement of specific brain networks in the pathophysiology of DON.
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Diabetes Mellitus , Enfermedades del Nervio Óptico , Humanos , Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.
Asunto(s)
Infarto del Miocardio , Tomografía de Coherencia Óptica , Humanos , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Vasos Retinianos/diagnóstico por imagen , Retina/diagnóstico por imagen , Infarto del Miocardio/diagnóstico por imagenRESUMEN
Background: Although gastric adenocarcinoma (GA) related ocular metastasis (OM) is rare, its occurrence indicates a more severe disease. We aimed to utilize machine learning (ML) to analyze the risk factors of GA-related OM and predict its risks. Methods: This is a retrospective cohort study. The clinical data of 3532 GA patients were collected and randomly classified into training and validation sets in a ratio of 7:3. Those with or without OM were classified into OM and non-OM (NOM) groups. Univariate and multivariate logistic regression analyses and least absolute shrinkage and selection operator were conducted. We integrated the variables identified through feature importance ranking and further refined the selection process using forward sequential feature selection based on random forest (RF) algorithm before incorporating them into the ML model. We applied six ML algorithms to construct the predictive GA model. The area under the receiver operating characteristic (ROC) curve indicated the model's predictive ability. Also, we established a network risk calculator based on the best performance model. We used Shapley additive interpretation (SHAP) to identify risk factors and to confirm the interpretability of the black box model. We have de-identified all patient details. Results: The ML model, consisting of 13 variables, achieved an optimal predictive performance using the gradient boosting machine (GBM) model, with an impressive area under the curve (AUC) of 0.997 in the test set. Utilizing the SHAP method, we identified crucial factors for OM in GA patients, including LDL, CA724, CEA, AFP, CA125, Hb, CA153, and Ca2+. Additionally, we validated the model's reliability through an analysis of two patient cases and developed a functional online web prediction calculator based on the GBM model. Conclusion: We used the ML method to establish a risk prediction model for GA-related OM and showed that GBM performed best among the six ML models. The model may identify patients with GA-related OM to provide early and timely treatment.