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Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.
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Coma , Humanos , Femenino , Coma/etiología , Trastornos de Conversión/complicaciones , Trastornos de Conversión/diagnóstico , Electroencefalografía , Cataplejía/diagnóstico , Cataplejía/complicaciones , Orexinas/líquido cefalorraquídeoRESUMEN
Perioperative neurocognitive disorders (PND) are intractable, indistinct, and considerably diminish the postoperative quality of life of patients. It has been proved that Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was involved in neurodegenerative diseases by regulating mitochondrial biogenesis. The underlying mechanisms of PGC-1α and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in PND are not well understood. In this study, we constructed a model of laparotomy in aged mice, and then examined the cognition changes with novel object recognition tests and fear condition tests. The protein levels of PGC-1α and NLRP3 in the hippocampus were detect after surgery. Our results showed that NLRP3 and downstream PI3K/AKT pathway expressions were augmented in the hippocampus after surgery, whereas, the expressions of PGC-1α/estrogen-related receptor α (ERRα)/Unc-51-like autophagy activating kinase 1 (ULK1) pathway were diminished after surgery. In addition, we found that NLRP3 was mainly co-localized with neurons in the hippocampus, and synaptic-related proteins were reduced after surgery. At the same time, transmission electron microscopy (TEM) showed that mitochondria were impaired after surgery. Pharmacological treatment of MCC950, a selective NLRP3 inhibitor, effectively alleviated PND. Activation of PGC-1α with ZLN005 significantly ameliorated PND by enhancing the PGC-1α/ERRα/ULK1 signaling pathway, and further suppressing NLRP3 activation. As a result, we conclude that suppression of the PGC-1α/ERRα/ULK1 signaling pathway is the primary mechanism of PND which caused mitochondrial dysfunction, and activated NLRP3 inflammasome and downstream PI3K/AKT pathway, eventually improved cognitive dysfunction.
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Metal-organic frameworks (MOFs), recognized as advanced catalyst carriers due to their adjustable porous, diverse structure and highly exposed active sites, have earned increasing attention for their potential to address the longevity of catalytic centers. In this manuscript, we have devised and synthesized a multifunctional amino-pyridine benzoic acid (APBA) ligand to replace the modulator ligand of the MOF-808 and disperse the palladium catalytic centers atomically on the MOF-APBA. The resulting single-site catalytic system, Pd@MOF-APBA, demonstrates preeminent efficiency and stability, as evidenced by a high average turnover number (95000) and a low metal residue (4.8 ppm) in the Heck reaction. This catalyst has exhibited recyclability for multiple runs without significant loss of reactivity for gram-scale reactions. The catalyst's high activity and efficiency can be attributed to the suitable electrical properties and structures of the N, N'-bidentate ligand for the catalytic palladium ions, postponing their deactivations, including leaching and agglomeration.
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Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that commonly manifests cardiovascular complications. We aimed to assess the prevalence of FD in a Chinese population with left ventricular hypertrophy (LVH) whilst implementing a gender-specific screening approach. Methods: Patients with LVH, defined as a maximum thickness of the left ventricular septal/posterior wall ≥ 13 mm, were considered eligible. All patients with hypertrophic cardiomyopathy (HCM) were excluded. Plasma α-galactosidase (α-GLA) enzyme activity was assessed using a dried blood spot test. Males with low enzyme activity underwent genetic testing to confirm a diagnosis of FD whereas females were screened for both α-GLA and globotriaosylsphingosine concentration and underwent genetic analysis of the GLA gene only if testing positive for ≥1 parameter. Results: 426 unrelated patients (age = 64.6 ± 13.0 years; female: male = 113:313) were evaluated. FD was diagnosed in 3 unrelated patients (age = 69.0 ± 3.5 years, female: male = 1:2) and 1 related female subject (age = 43 years). Genetic analyses confirmed the late-onset cardiac variant GLA c.640-801G>A (n = 3) and the missense variant c.869T>C associated with classic FD (n = 1). Cardiac complications were the only significant findings associated with the late-onset c.640-801G>A mutation, manifesting as mild or severe concentric LVH. In contrast, the classic c.869T>C mutation FD exhibited multisystemic manifestations in addition to severe concentric LVH. Conclusions: The prevalence of FD is lower in Chinese patients with LVH when HCM is excluded. The pathological variant c.640-801G>A remains the most common cause of late-onset FD, while the detection of FD in females can be improved by utilizing a gender-specific screening method.
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PURPOSE: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators. METHODS: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy. RESULTS: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females. CONCLUSIONS: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.
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Ingestión de Energía , Estado Nutricional , Diálisis Renal , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Anciano , Proteínas en la Dieta/administración & dosificación , Adulto , Modelos Lineales , Fallo Renal Crónico/terapia , Fallo Renal Crónico/fisiopatología , Fuerza de la Mano , Registros de Dieta , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/dietoterapia , Insuficiencia Renal Crónica/fisiopatologíaRESUMEN
BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.
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Caries Dental , Placa Dental , Humanos , Placa Dental/microbiología , Caries Dental/microbiología , Caries Dental/terapia , Preescolar , Masculino , Femenino , Microbiota , Anestesia General , ARN Ribosómico 16SRESUMEN
The heat shock protein 70 family contains the stress proteins ubiquitous in plants. These proteins are involved in the responses to different abiotic stress conditions and have highly conserved gene sequences. However, little is known about the molecular mechanisms of Fritillaria cirrhosa in response to high-temperature stress. Here, 26 HSP70s, FcHSP70-1 to FcHSP70-26, were identified from the transcriptome data of root, bulb, stem, leaf, and fruit samples of F. cirrhosa. The proteins encoded by FcHSP70s had the lengths ranging from 560 aa to 944 aa, with the molecular weight of 61.64-100.01 kDa and the theoretical isoelectric point between 5.00 and 6.59. The secondary structural elements of HSP70s were mainly random coils and α-helixes. Subcellular localization prediction revealed that FcHSP70s were distributed in mitochondria, chloroplasts, nuclei, endoplasmic reticulum, and cytoplasm. The phylogenetic tree showed that 7 members of the HSP70 family belonged to the Dnak subfamily and 19 members belonged to the HSP110/SSE subfamily. In addition, the qRT-PCR results showed that the expression of FcHSP70-5, FcHSP70-8, FcHSP70-17, FcHSP70-18, and FcHSP70-23 in F. cirrhosa was significantly up-regulated at 35 â, which indicated that these genes might play a role in the response to high temperature stress. In addition, compared with other tissues, stems and leaves were sensitive to high temperature stress, with the expression of 18 genes up-regulated by 18.18 and 8.03 folds on average, respectively. These findings provide valuable information about the molecular mechanism of HSP70s of F. cirrhosa in response to high temperature stress.
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Fritillaria , Regulación de la Expresión Génica de las Plantas , Proteínas HSP70 de Choque Térmico , Filogenia , Proteínas de Plantas , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Fritillaria/genética , Fritillaria/química , Calor , Estrés Fisiológico/genética , Perfilación de la Expresión Génica , Familia de MultigenesRESUMEN
White adipose tissue accumulation and inflammation contribute to obesity by inducing insulin resistance. Herein, we aimed to screen the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for the treatment of insulin resistance and explore the potential synergistic mechanisms. Enzyme-linked immunosorbent assay and quantitative PCR were used to detect expression levels of inflammatory genes in vitro and in vivo. Western blotting and immunohistochemistry were performed to detect protein levels of the insulin signaling pathway and macrophage markers. The effects on obesity-induced insulin resistance were verified using a diet-induced obesity (DIO) mouse model. Interactions between macrophage and adipocyte were assessed using a cellular supernatant transfer assay. Berberine (BBR) and isoliquiritigenin (ISL) alleviated mRNA levels and secretion of inflammatory genes in vitro and in vivo. Furthermore, BBR acted synergistically with ISL to ameliorate obesity and dyslipidemia in DIO mice. Meanwhile, the combination treatment significantly improved glucose intolerance and insulin resistance and decreased M1-macrophage accumulation and infiltration in the adipose tissue. Mechanistically, co-treatment with BBR and ISL upregulated the protein expression of the IRS1-PI3K-Akt insulin signaling pathway, enhanced glucose uptake in adipocyte, and suppressed the interaction between macrophage and adipocyte. BBR and ISL were identified as the synergistic components of the herbal pair Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma for treating insulin resistance. The synergistic combination of BBR with ISL can be a promising and effective strategy for improving obesity-induced adipose inflammation and insulin resistance.
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Berberina , Chalconas , Inflamación , Resistencia a la Insulina , Ratones Endogámicos C57BL , Obesidad , Animales , Berberina/farmacología , Obesidad/tratamiento farmacológico , Chalconas/farmacología , Ratones , Masculino , Inflamación/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Adipocitos/efectos de los fármacos , Sinergismo Farmacológico , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Tejido Adiposo/efectos de los fármacos , Glycyrrhiza/química , Dieta Alta en Grasa/efectos adversos , Medicamentos Herbarios Chinos/farmacología , Células 3T3-L1 , Células RAW 264.7RESUMEN
BACKGROUND: It is unclear whether alternating placements during clinical clerkship, without an explicit emphasis on clinical competencies, would bring about optimal educational outcomes. METHODS: This is an explanatory sequential mixed-methods research. We enrolled a convenience sample of 41 eight-year programme medical students in Sun Yat-sen University who received alternating placements during clerkship. The effects of competence-based approach (n = 21) versus traditional approach (n = 20) to clerkship teaching were compared. In the quantitative phase, course satisfaction was measured via an online survey and academic performance was determined through final scores on summative assessment. Then, in the qualitative phase, students were invited for semi-structured interviews about their learning experiences, and the transcripts were used for thematic analysis. RESULTS: Quantitative findings showed that students in the study group rated high course satisfaction and performed significantly better in their final scores compared with those in the control group. Qualitative findings from thematic analysis showed that students were relatively neutral about their preference on placement models, but clearly perceived, capitalised, and appreciated that their competencies were being cultivated by an instructor who was regarded as a positive role model. CONCLUSION: A competence-based approach to clerkship teaching resulted in better course satisfaction and academic performance, and was perceived, capitalised, and appreciated by students.
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BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Carcinoma Hepatocelular , Proliferación Celular , Ferroptosis , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , MicroARNs , Proteínas de Neoplasias , ARN Circular , Animales , Femenino , Humanos , Masculino , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Ferroptosis/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , MicroARNs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Circular/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3â nM.
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Aureobasidium , Óxido Nítrico , Animales , Ratones , Aureobasidium/química , Aureobasidium/metabolismo , Línea Celular , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Conformación Molecular , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , LactonasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.
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Enfermedad Coronaria , Fibrinolíticos , Simulación del Acoplamiento Molecular , Farmacología en Red , Trichosanthes , Animales , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Fibrinolíticos/química , Enfermedad Coronaria/tratamiento farmacológico , Ratas , Masculino , Trichosanthes/química , Pez Cebra , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Medicina Tradicional China/métodosRESUMEN
BACKGROUND: This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure. CASE SUMMARY: Here, we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital. We also detected the whole-exon gene of the patient's spouse and parents, and conducted bioinformatics analysis to determine the pathogenesis of the gene. CONCLUSION: A novel mutant of the TUBB8 gene [c.602G>T(p.C201F)] was identified, and this mutant provided new data on the genotype-phenotype relationships of related diseases.
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The main problem addressed in this paper is the task-space bipartite formation tracking problem of uncertain heterogeneous Euler-Lagrange systems in predefined time. To solve this problem, an effective hierarchical predefined-time control algorithm is designed. This algorithm utilizes a non-singular sliding surface, allowing for the adjustment of the upper bound of the settling time as a flexible parameter. Key components of the proposed approach include an estimator for the leader's states and a controller tailored to the formation problem. To mitigate the effects of dynamic uncertainties in the system, the radial basis function neural network is integrated into the methodology. Finally, the effectiveness and validity of the proposed algorithm are demonstrated through numerical simulations, showcasing their practical applicability and efficacy.
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This work proposes a microwave resonator built from gallium arsenide using integrated passive device (IPD) technology. It consists of a three-layered interlaced spiral structure with airbridges and inner interdigital structures. For integrated systems, IPD technology demonstrated outstanding performance, robustness, and a tiny size at a low cost. The airbridges were made more compact, with overall dimensions of 1590 × 800 µm2 (0.038 × 0.019 λg2). The designed microwave resonator operated at 1.99 GHz with a return loss of 39 dB, an insertion loss of 0.07 dB, and a quality factor of 1.15. Additionally, an experiment was conducted on the properties of the airbridge and how they affected resistance, inductance, and S-parameters in the construction of the resonator. To investigate the impact of airbridges on the structure, E- and H-field distributions of the resonator were simulated. Furthermore, its use in sensing applications was explored. Various concentrations of glucose solutions were used in the experiment. The proposed device featured a minimum detectable concentration of 0.2 mg/mL; high sensitivity, namely, 14.58 MHz/mg·mL-1, with a linear response; and a short response time. Thus, this work proposes a structure that exhibits potential in integrated systems and real-time sensing systems with high sensitivity.
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ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. AIM OF THE STUDY: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. MATERIALS AND METHODS: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. RESULTS: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1ß, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1ß, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. CONCLUSION: Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1ß, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.
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Enfermedad Coronaria , Medicamentos Herbarios Chinos , Humanos , Animales , Ratas , Apigenina , Luteolina/farmacología , Luteolina/uso terapéutico , Peróxido de Hidrógeno , Interleucina-6 , Ácido Linoleico , Simulación del Acoplamiento Molecular , Farmacología en Red , Quercetina , Especies Reactivas de Oxígeno , Factor de Necrosis Tumoral alfa , Enfermedad Coronaria/tratamiento farmacológico , Interleucina-1beta , FenilalaninaRESUMEN
Halogenated organic contaminants, such as chlorinated and brominated polycyclic aromatic hydrocarbons (Cl/Br-PAHs), are some of the most important emerging environmental pollutants. However, empirical data on Cl/Br-PAHs in estuarine and marine ecosystems are limited, rendering assessments of Cl/Br-PAH contamination in estuarine and offshore environments uncertain. Here the occurrence, sources, and ecological risks of 7 Cl-PAHs and 18 Br-PAHs were determined in surface sediments of the Yangtze River Estuary (YRE), a highly urbanized and industrialized area, and its adjacent marine area. The concentrations of Cl-PAHs ranged from 4.50 to 18.38 ng g-1 (average 7.19 ng g-1), while those of Br-PAHs ranged from 4.80 to 61.18 ng g-1 (average 14.11 ng g-1). The dominant Cl-PAH and Br-PAH in surface sediment were 9-chlorofluorene (17.79%) and 9-bromofluorene (58.49%), respectively. The distributions and compositions of Cl/Br-PAHs in the surface sediments varied considerably due to complex hydrodynamic and depositional conditions in the YRE and its adjacent marine area, as well as differences in physicochemical properties of different Cl/Br-PAHs. Positive matrix factorization revealed that the primary sources of Cl/Br-PAHs in the study area were e-waste dismantling (33.6%), waste incineration (23.2%), and metal smelting (11.0%). According to the risk quotient, the Cl/Br-PAHs in sediments posed no toxic risk to aquatic organisms.
Asunto(s)
Monitoreo del Ambiente , Estuarios , Sedimentos Geológicos , Hidrocarburos Policíclicos Aromáticos , Ríos , Contaminantes Químicos del Agua , Sedimentos Geológicos/análisis , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/análisis , China , Ríos/química , Hidrocarburos Policíclicos Aromáticos/análisis , Agua de Mar/química , Agua de Mar/análisisRESUMEN
Cu(II) supramolecular assemblies [Cu2(tipe)2(H2O)2](NO3)4·2.5H2O (CuN4) and [Cu2Cl4(tipe)(CH3CN)]·H2O (CuN2Cl2) (tipe = 1,1,2,2-tetrakis(4-(imidazole-1-yl)phenyl)ethene) were synthesized and utilized for photocatalytic CO2 reduction. CuN4 exhibits CO production of up to 891 µmol gcat-1 with a selectivity of 79.9%, while CuN2Cl2 gives low CO production of 206 µmol gcat-1 but with a high selectivity of >99.9% in 5 h. The experimental and DFT calculation results indicate that the coordination environment and non-covalent interactions within the assemblies have a great impact on the photocatalytic CO2 reduction behavior. This work provides useful insights on Cu(II) assembly catalyzed CO2 photoreduction.
RESUMEN
Cyclin-dependent kinases (CDKs) play an important role in the regulation of cell proliferation, and many CDK inhibitors were developed. However, pan-CDK inhibitors failed to be approved due to intolerant toxicity or low efficacy and the use of selective CDK4/6 inhibitors is limited by resistance. Protein degraders have the potential to increase selectivity, efficacy and overcome resistance, which provides a novel strategy for regulating CDKs. In this review, we summarized the function of CDKs in regulating the cell cycle and transcription, and introduced the representative CDK inhibitors. Then we made a detailed introduction about four types of CDKs degraders, including their action mechanisms, research status and application prospects, which could help the development of novel CDKs degraders.
Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Quinasas Ciclina-Dependientes , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Puntos de Control del Ciclo Celular , Ciclo Celular , Neoplasias/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Quinasa 2 Dependiente de la CiclinaRESUMEN
Tree growth is the consequence of developmental interactions between above- and below-ground compartments. However, a comprehensive view of the genetic architecture of growth as a cohesive whole is poorly understood. We propose a systems biology approach for mapping growth trajectories in genome-wide association studies viewing growth as a complex (phenotypic) system in which above- and below-ground components (or traits) interact with each other to mediate systems behavior. We further assume that trait-trait interactions are controlled by a genetic system composed of many different interactive genes and integrate the Lotka-Volterra predator-prey model to dissect phenotypic and genetic systems into pleiotropic and epistatic interaction components by which the detailed genetic mechanism of above- and below-ground co-growth can be charted. We apply the approach to analyze linkage mapping data of Populus euphratica, which is the only tree species that can grow in the desert, and characterize several loci that govern how above- and below-ground growth is cooperated or competed over development. We reconstruct multilayer and multiplex genetic interactome networks for the developmental trajectories of each trait and their developmental covariation. Many significant loci and epistatic effects detected can be annotated to candidate genes for growth and developmental processes. The results from our model may potentially be useful for marker-assisted selection and genetic editing in applied tree breeding programs. The model provides a general tool to characterize a complete picture of pleiotropic and epistatic genetic architecture in growth traits in forest trees and any other organisms.