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BACKGROUND: Intraoperative conversion to open surgery is an adverse event during minimally invasive distal pancreatectomy (MIDP), associated with poor postoperative outcomes. The aim of this study was to develop a model capable of predicting conversion in patients undergoing MIDP. METHODS: A total of 352 patients who underwent MIPD were included in this retrospective analysis and randomly assigned to training and validation cohorts. Potential risk factors related to open conversion were identified through a literature review, and data on these factors in our cohort was collected accordingly. In the training cohort, multivariate logistic regression analysis was performed to adjust the impact of confounding factors to identify independent risk factors for model building. The constructed model was evaluated using the receiver operating characteristics curve, decision curve analysis (DCA), and calibration curves. RESULTS: Following an extensive literature review, a total of ten preoperative risk factors were identified, including sex, BMI, albumin, smoker, size of lesion, tumor close to major vessels, type of pancreatic resection, surgical approach, MIDP experience, and suspicion of malignancy. Multivariate analysis revealed that sex, tumor close to major vessels, suspicion of malignancy, type of pancreatic resection (subtotal pancreatectomy or left pancreatectomy), and MIDP experience persisted as significant predictors for conversion to open surgery during MIDP. The constructed model offered superior discrimination ability compared to the existing model (area under the curve, training cohort: 0.921 vs. 0.757, P < 0.001; validation cohort: 0.834 vs. 0.716, P = 0.018). The DCA and the calibration curves revealed the clinical usefulness of the nomogram and a good consistency between the predicted and observed values. CONCLUSION: The evidence-based prediction model developed in this study outperformed the previous model in predicting conversions of MIDP. This model could contribute to decision-making processes surrounding the selection of surgical approaches and facilitate patient counseling on the conversion risk of MIDP.
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BACKGROUNDS: Major depressive disorder (MDD) is a pervasive mental and mood disorder with complicated and heterogeneous etiology. Mitophagy, a selective autophagy of cells, specifically eliminates dysfunctional mitochondria. The mitochondria dysfunction in the astrocytes is regarded as a critical pathogenetic mechanism of MDD. However, studies on the mitophagy of astrocytes in MDD are scarce. To explore the impact of mitophagy on the astrocytes, we used bioinformatic methods to analyze the correlation between astrocyte-related genes and mitophagy-related genes in MDD. METHODS: The microarray dataset of MDD was downloaded from the Gene Expression Omnibus database and identified astrocyte- and mitophagy-related differentially expressed genes (AMRDEGs). We used three machine learning algorithms to identify hub AMRDEGs and constructed a diagnostic prediction model. Also, we analyzed transcription factor-gene and gene-microRNA interaction networks, and the immune infiltration in MDD and healthy controls. Besides, we performed consensus clustering analysis, immune infiltration analysis, and gene set variation analysis of MDD samples. RESULTS: The present research identified 3 hub AMRDEGs (GRN, NDUFAF4, and SNCA), and a good diagnostic model with potential clinical applications was constructed and validated. Besides, we identified 6 transcription factors and 14 microRNAs. The immune infiltration analysis showed that MDD was closely related to immune cells. Gene set variant analysis showed that MDD was related to immune and mitochondrial metabolism and inflammatory signaling pathways. CONCLUSIONS: We identified 3 hub AMRDEGs, new biomarkers for treating and diagnosing MDD and associated with immuno-inflammation. Our research provides new insights into the early diagnosis and treatment of MDD.
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Despite improvements in the early intervention of myocardial infarction (MI) in recent decades, left ventricular aneurysms (LVA) remain a major health concern, particularly in developing nations. The progression of MI can lead to the thinning of the myocardial wall and the formation of a ventricular wall bulge, characteristic of an LVA. Furthermore, cardiac magnetic resonance (CMR) has emerged as the gold standard for LVA diagnosis due to its superior imaging capabilities. Notably, surgical ventricular reconstruction (SVR) is an effective treatment for LVA, aiming to restore the normal volume and structure of the left ventricle, thereby improving cardiac function. However, the criteria for selecting patients for SVR treatment remains a subject of debate. This review focuses on the current understanding of surgical indications, procedures, and prognostic risk factors that influence outcomes in left ventricular reconstruction, highlighting the need for precise patient selection to optimize surgical benefits.
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Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.
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Astrocitos , Conexina 43 , Trastorno Depresivo Mayor , Plasticidad Neuronal , Humanos , Astrocitos/metabolismo , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/fisiopatología , Plasticidad Neuronal/fisiología , Animales , Conexina 43/metabolismo , Transmisión Sináptica/fisiología , Ácido Glutámico/metabolismo , Neuroglía/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Sinapsis/metabolismo , Sinapsis/fisiologíaRESUMEN
Sensing platforms with high interference immunity and low power consumption are crucial for the co-detection of dual oxidative stress biomarkers and clinical diagnosis of periodontitis. Herein, we constructed a bifunctional nanozyme to identify hydrogen peroxide (H2O2) and ascorbic acid (AA) with low crosstalk at zero or low bias voltage. To target H2O2 and AA, Fe(III) meso-tetra(4-carboxyphenyl) porphine (TCPP(Fe)) and Pt nanoclusters were selected as active sites respectively, and titanium carbide nanosheets were additionally introduced as a sensitizer. Due to their highly efficient catalytic properties, self-powered detection of H2O2 without bias voltage and distinguishable AA detection at 0.45 V were successfully achieved. Density functional theory calculations further confirmed the binding sites for target molecules and elucidated the sensing mechanism. On this basis, a dual-channel screen-printed electrode was fabricated to further ensure the discriminative detection of dual biomarkers at the device level. The constructed flexible, low-power consumption sensing platform was successfully applied to raw clinical samples, effectively distinguishing between healthy individuals and patients with varying degrees of periodontitis. This work is expected to provide new insights into the design of highly specific nanozymes and low-power consumption electrochemical sensing systems, which will contribute to the accurate and convenient diagnosis of periodontitis.
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Ácido Ascórbico , Biomarcadores , Técnicas Biosensibles , Técnicas Electroquímicas , Peróxido de Hidrógeno , Estrés Oxidativo , Periodontitis , Humanos , Técnicas Biosensibles/métodos , Biomarcadores/análisis , Periodontitis/diagnóstico , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Ácido Ascórbico/química , Ácido Ascórbico/análisis , Técnicas Electroquímicas/métodos , Titanio/química , Platino (Metal)/química , Nanoestructuras/química , Compuestos Inorgánicos de Carbono/química , Porfirinas/químicaRESUMEN
The incidence of herpes zoster (HZ) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is significantly higher than that of the general public. Although routine antiviral prophylaxis is recommended, late-onset HZ has been highlighted, yet limited information is known about its clinical features and predictors. Here, we conducted a retrospective nested case-control study to identify patients with late-onset HZ, defined as a diagnosis of HZ after 1 year of transplantation, among allo-HSCT recipients between 2012 and 2017 at Peking University People's Hospital. Three controls were matched for each patient. A total of 201 patients developed late-onset HZ. Age over 20 years, absence of neutrophil engraftment by 14 days, mental disorders, immunosuppressant use at 1 year, and a peripheral CD4+/CD8+ ratio ≥0.5 at 1 year were independent risk factors, among which the CD4+/CD8+ ratio demonstrated good discriminative power for predicting late-onset HZ. For patients with a CD4+/CD8+ ratio <0.5, patient age, neutrophil engraftment time, mental disorders, and immunosuppressant use were potential risk factors. A stratification algorithm was accordingly established, classifying the transplant recipients into three risk groups. Whether the algorithm could facilitate the administration of posttransplant antiviral prophylaxis merits further validation.
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Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/virología , Herpes Zóster/epidemiología , Herpes Zóster/diagnóstico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estudios de Casos y Controles , Trasplante Homólogo/efectos adversos , Adulto Joven , Medición de Riesgo , Antivirales/uso terapéutico , Incidencia , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Relación CD4-CD8 , Adolescente , Factores de Tiempo , Anciano , Herpesvirus Humano 3/inmunologíaRESUMEN
Cell death constitutes a critical component of the pathophysiology of cardiovascular diseases. A growing array of non-apoptotic forms of regulated cell death (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified and is intimately linked to various cardiovascular conditions. These forms of RCD are governed by genetically programmed mechanisms within the cell, with epigenetic modifications being a common and crucial regulatory method. Such modifications include DNA methylation, RNA methylation, histone methylation, histone acetylation, and non-coding RNAs. This review recaps the roles of DNA methylation, RNA methylation, histone modifications, and non-coding RNAs in cardiovascular diseases, as well as the mechanisms by which epigenetic modifications regulate key proteins involved in cell death. Furthermore, we systematically catalog the existing epigenetic pharmacological agents targeting novel forms of RCD and their mechanisms of action in cardiovascular diseases. This article aims to underscore the pivotal role of epigenetic modifications in precisely regulating specific pathways of novel RCD in cardiovascular diseases, thus offering potential new therapeutic avenues that may prove more effective and safer than traditional treatments.
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BACKGROUND: Endometriosis is a common chronic gynecological condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to chronic inflammation, pelvic nodules and masses, pelvic pain, and infertility. Acupuncture has been shown to improve pain associated with endometriosis by modulating abnormal levels of prostaglandins, ß-endorphins, dynorphins, electrolytes, and substance P. This review aims to evaluate the clinical efficacy of acupuncture in treating endometriosis, specifically focusing on its efficacy in relieving pain associated with endometriosis. METHODS: A comprehensive search was conducted in eight databases (PubMed, EMBASE, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), the China Biology Medicine (CBM), Wanfang, and Weipu database) to identify randomized controlled trials (RCTs) published from database inception to December 16, 2022, which investigated the use of acupuncture for endometriosis-related pain. Two researchers independently screened articles, extracted data, and assessed methodological quality using the Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using Stata statistical software. RESULTS: A total of 1991 articles were identified, and ultimately, 14 studies involving 793 patients (387 in the acupuncture group and 359 in the control group) were included. The control interventions in the included studies included placebo, traditional Chinese medicine (TCM), and Western medicine treatments. Meta-analysis results showed that compared to the control group, acupuncture treatment for pain associated with endometriosis demonstrated significant reductions in pain severity [SMD = - 1.10, 95% CI (- 1.45, - 0.75), P < 0.001], improved response rate [RR = 1.25, 95% CI (1.09, 1.44), P = 0.02], and decreased serum CA-125 levels [SMD = - 0.62, 95% CI (- 1.15, - 0.08), P = 0.024]. Furthermore, subgroup analysis revealed that electroacupuncture and auricular acupuncture were superior to the control group in reducing pain severity, while auricular acupuncture and warm needling showed greater clinical efficacy compared to the control group. However, there were no significant differences between electroacupuncture or fire needling and the control group in terms of pain relief. The findings suggest that acupuncture is effective in improving pain associated with endometriosis. CONCLUSIONS: In conclusion, acupuncture is effective in alleviating dysmenorrhea and pelvic pain associated with endometriosis, reducing serum CA-125 levels, decreasing the size of nodules, improving patients' quality of life, and lowering the recurrence rate. However, it should be noted that the current evidence is limited by the design and quality flaws of the original studies, as well as a lack of research specifically focusing on subtypes of acupuncture. Therefore, caution should be exercised when interpreting the results.
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Terapia por Acupuntura , Endometriosis , Dolor Pélvico , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Endometriosis/complicaciones , Endometriosis/terapia , Femenino , Dolor Pélvico/terapia , Dolor Pélvico/etiología , Resultado del Tratamiento , Manejo del Dolor/métodos , Dimensión del DolorRESUMEN
Direct copper-to-copper (Cu-Cu) bonding is a promising technology for advanced electronic packaging. Nanocrystalline (NC) Cu receives increasing attention due to its unique ability to promote grain growth across the bonding interface. However, achieving sufficient grain growth still requires a high thermal budget. This study explores how reducing grain size and controlling impurity concentration in NC Cu leads to substantial grain growth at low temperatures. The fabricated NC Cu has a uniform nanograin size of around 50 nm and a low impurity level of 300 ppm. To prevent ungrown NC and void formation caused by impurity aggregation, we propose a double-layer (DL) structure comprising a normal coarse-grained (CG) layer underneath the NC layer. The CG layer, with a grain size of 1 µm and an impurity level of 3 ppm, acts as a sink, facilitating impurity diffusion from the NC layer to the CG layer. Thanks to sufficient grain growth throughout the entire NC layer, cross-interface Cu-Cu bonding becomes possible under a low thermal budget, either at 100 °C for 60 min or at 200 °C for only 5 min.
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Introduction: Air pollution is speculated to increase the risk of Coronavirus disease-2019 (COVID-19). Nevertheless, the results remain inconsistent and inconclusive. This study aimed to explore the association between ambient air pollution (AAP) and COVID-19 risks using a meta-analysis with meta-regression modelling. Methods: The inclusion criteria were: original studies quantifying the association using effect sizes and 95 % confidence intervals (CIs); time-series, cohort, ecological or case-crossover peer-reviewed studies in English. Exclusion criteria encompassed non-original studies, animal studies, and data with common errors. PubMed, Web of Science, Embase and Google Scholar electronic databases were systemically searched for eligible literature, up to 31, March 2023. The risk of bias (ROB) was assessed following the Agency for Healthcare Research and Quality parameters. A random-effects model was used to calculate pooled risk ratios (RRs) and their 95 % CIs. Results: A total of 58 studies, between 2020 and 2023, met the inclusion criteria. The global representation was skewed, with major contributions from the USA (24.1 %) and China (22.4 %). The distribution included studies on short-term (43.1 %) and long-term (56.9 %) air pollution exposure. Ecological studies constituted 51.7 %, time-series-27.6 %, cohorts-17.2 %, and case crossover-3.4 %. ROB assessment showed low (86.2 %) and moderate (13.8 %) risk. The COVID-19 incidences increased with a 10 µg/m3 increase in PM2.5 [RR = 4.9045; 95 % CI (4.1548-5.7895)], PM10 [RR = 2.9427: (2.2290-3.8850)], NO2 [RR = 3.2750: (3.1420-3.4136)], SO2 [RR = 3.3400: (2.7931-3.9940)], CO [RR = 2.6244: (2.5208-2.7322)] and O3 [RR = 2.4008: (2.1859-2.6368)] concentrations. A 10 µg/m3 increase in concentrations of PM2.5 [RR = 3.0418: (2.7344-3.3838)], PM10 [RR = 2.6202: (2.1602-3.1781)], NO2 [RR = 3.2226: (2.1411-4.8504)], CO [RR = 1.8021 (0.8045-4.0370)] and O3 [RR = 2.3270 (1.5906-3.4045)] was significantly associated with COVID-19 mortality. Stratified analysis showed that study design, exposure period, and country influenced exposure-response associations. Meta-regression model indicated significant predictors for air pollution-COVID-19 incidence associations. Conclusion: The study, while robust, lacks causality demonstration and focuses only on the USA and China, limiting its generalizability. Regardless, the study provides a strong evidence base for air pollution-COVID-19-risks associations, offering valuable insights for intervention measures for COVID-19.
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A suite of coal samples near a diabase dike was collected to investigate the structural and functional group evolution of a series of carbon materials prepared from thermally altered coals, explore the influence of thermal metamorphism distance on the structure of coal and its carbon material products, and divide the thermally altered zones. Using Fourier transform infrared and Raman studies, it was found that after demineralization, the aromatic parameters f ar H and I of the coal structure slightly increase, while the aliphatic parameters CH2/CH3 and oxidation parameter 'C' slightly decrease, and the degree of order of the coal structure increases. Graphitization can greatly improve aromatic parameters, eliminate aliphatic structures, and enhance orderliness. However, after oxidation and reduction, the aromatic parameters and ordering degree of graphene decrease. Except for the sample closely attached to the dike, the coal-based graphene yield of the other samples first decreases and then stabilizes with the increase of distance from the dike, which is consistent with the trend of changes in the reflectance of raw coal. The thermally altered distance affects the structural changes of coal and carbon material products. The coal attached to the dike has been damaged and polluted, and the aromaticity and orderliness of the prepared carbon material products are relatively poor. The aromaticity and orderliness of coal-based products prepared from other thermally altered coals are relatively high and increase with the closer the thermally altered distance. Based on the characterized parameters of coal samples and products with distance from the dike, the sampling area is divided into four zones, including abnormally altered zone, normal altered zone, transition zone, and original coal zone. Among them, the yield and quality of coal-based graphene prepared from coal in the normal altered zone are the highest, an ideal raw material collection area for making coal-based graphene.
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OBJECTIVE: Studies have shown that electroacupuncture (EA) can alleviate cognitive impairments from Alzheimer's disease (AD) by regulating the expression of adenosine monophosphate-activated protein kinase (AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics. METHODS: The four-month-old transgenic mice with amyloid precursor protein (APP)/presenilin 1 (PS1) and AMPKα1-subunit conditional knockout (AMPKα1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition, chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice. RESULTS: Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway increased pathological amyloid-ß (Aß) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway, specifically by reducing pathological Aß deposition, normalizing energy metabolism, protecting the structure and function of mitochondria, increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout. CONCLUSION: The regulation of hippocampal mitochondrial dynamics and reduction in Aß deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice. Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; Epub ahead of print.
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The landscape plant, Cinnamomum camphora, is a broad-spectrum insect-repelling tree species, mainly due to a diversity of terpenoids, such as camphor. Despite its formidable chemical defenses, C. camphora is easily attacked and invaded by a monophagous weevil pest, Pagiophloeus tsushimanus. Deciphering the key olfactory signal components regulating host preference could facilitate monitoring and control strategies for this pest. Herein, two host volatiles, camphor and ocimene, induced GC-EAD/EAG reactions in both male and female adult antennae. Correspondingly, Y-tube olfactometer assays showed that the two compounds were attractive to both male and female adults. In field assays, a self-made trap device baited with 5 mg dose d(+)-camphor captured significantly more P. tsushimanus adults than isopropanol solvent controls without sexual bias. The trunk gluing trap device baited with bait can capture adults, but the number was significantly less than that of the self-made trap device and adults often fell after struggling. The cross baffle trap device never trapped adults. Neither ocimene nor isopropanol solvent control captured adults. When used in combination, ocimene did not enhance the attraction of d(+)-camphor to both female and male adults. These results indicate that d(+)-camphor is a key active compound of P. tsushimanus adults for host location. The combination of the host-volatile lure based on d(+)-camphor and the self-made trapping device is promising to monitor and provide an eco-friendly control strategy for this novel pest P. tsushimanus in C. camphora plantations.
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BACKGROUND: Interventional endoscopic ultrasound is clinically used for the treatment of isolated gastric varices (IGVs) owing to its precise visualization. CASE SUMMARY: A 39-year-old man was diagnosed with a large IGV during a routine physical examination. Endoscopic ultrasonography showed gastric varices entwined with an artery, which greatly increased the difficulty of treatment. We successfully treated the patient with endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection. CONCLUSION: Endoscopic ultrasonography-guided coil embolization combined with cyanoacrylate injection was safe and effective for the treatment of an IGV entwined with an artery.
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OBJECTIVES: This study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic-clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE. METHODS: This cross-sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (-) group (n = 37). The FBTCS (+) group was subcategorized into current-FBTCS (n = 31) and remote-FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE. RESULTS: Global efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current-FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (-) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE. INTERPRETATION: Our study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE.
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OBJECTIVE: To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. METHODS: Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. RESULTS: This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. CONCLUSION: The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.
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Perfilación de la Expresión Génica , ARN Largo no Codificante , Tuberculosis de la Columna Vertebral , Humanos , Tuberculosis de la Columna Vertebral/genética , ARN Largo no Codificante/genética , Disco Intervertebral/microbiología , Disco Intervertebral/metabolismo , Disco Intervertebral/patología , Masculino , Transcriptoma , Femenino , Redes Reguladoras de Genes , Adulto , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Clay-based marine sediments have great potential for safe and effective carbon dioxide (CO2) encapsulation by storing enormous amounts of CO2 in solid gas hydrate form. However, the aging of clay with time changes the surface properties of clay and complicates the CO2 hydrate formation behaviors in sediments. Due to the long clay aging period, it is difficult to identify the role of clay aging in the formation of CO2 hydrate in marine sediments. Here, we used ultrasonication and plasma treatment to simulate the breakage and oxidation of clay nanoflakes in aging and investigated the influence of clay aging on CO2 hydrate formation kinetics. We found that the breakage and oxidation of clay nanoflakes would disrupt the siloxane rings and graft hydroxyl on the clay nanoflakes. This decreased the negative charge density of clay nanoflakes and weakened the interfacial interaction of clay nanoflakes with the surrounding water. Therefore, the small clay nanoflakes enriched in hydroxyl would disrupt the surrounding tetrahedral water structure analogous to the CO2 hydrate, resulting in the prolongation of CO2 hydrate nucleation. These results revealed the influence of the structure-function relationship of clay nanoflakes with CO2 hydrate formation and are favorable for the development of hydrate-based CO2 storage.
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OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.
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Araquidonato 5-Lipooxigenasa , Proliferación Celular , Glioma , Inhibidores de la Lipooxigenasa , Simulación del Acoplamiento Molecular , Glioma/tratamiento farmacológico , Glioma/patología , Glioma/metabolismo , Glioma/enzimología , Araquidonato 5-Lipooxigenasa/metabolismo , Humanos , Inhibidores de la Lipooxigenasa/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Calcio/metabolismo , Espectrometría de Masas en TándemRESUMEN
Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.