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High-grade serous ovarian cancer has a high degree of malignancy, and at detection, it is prone to infiltration of surrounding soft tissues, as well as metastasis to the peritoneum and lymph nodes, peritoneal seeding, and distant metastasis. Whether recurrence occurs becomes an important reference for surgical planning and treatment methods for this disease. Current recurrence prediction models do not consider the potential pathological relationships between internal tissues of the entire ovary. They use convolutional neural networks to extract local region features for judgment, but the accuracy is low, and the cost is high. To address this issue, this paper proposes a new lightweight deep learning algorithm model for predicting recurrence of high-grade serous ovarian cancer. The model first uses ghost convolution (Ghost Conv) and coordinate attention (CA) to establish ghost counter residual (SCblock) modules to extract local feature information from images. Then, it captures global information and integrates multi-level information through proposed layered fusion Transformer (STblock) modules to enhance interaction between different layers. The Transformer module unfolds the feature map to compute corresponding region blocks, then folds it back to reduce computational cost. Finally, each STblock module fuses deep and shallow layer depth information and incorporates patient's clinical metadata for recurrence prediction. Experimental results show that compared to the mainstream lightweight mobile visual Transformer (MobileViT) network, the proposed slicer visual Transformer (SlicerViT) network improves accuracy, precision, sensitivity, and F1 score, with only 1/6 of the computational cost and half the parameter count. This research confirms that the proposed algorithm model is more accurate and efficient in predicting recurrence of high-grade serous ovarian cancer. In the future, it can serve as an auxiliary diagnostic technique to improve patient survival rates and facilitate the application of the model in embedded devices.
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Algoritmos , Aprendizaje Profundo , Recurrencia Local de Neoplasia , Redes Neurales de la Computación , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Metadatos , Cistadenocarcinoma Seroso/patologíaRESUMEN
Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Disulfuros , Glicoproteínas Hemaglutininas del Virus de la Influenza , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Anticuerpos Antivirales/inmunología , Ratones , Disulfuros/química , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Anticuerpos Neutralizantes/inmunología , Femenino , Protección Cruzada/inmunología , Reacciones Cruzadas , Humanos , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/virología , Epítopos/inmunología , Epítopos/genética , Epítopos/química , Multimerización de Proteína , Virus de la Influenza B/inmunología , Virus de la Influenza B/genética , Virus de la Influenza B/químicaRESUMEN
The relationship between co-exposure to multiple metals and gestational diabetes mellitus (GDM) and the mechanisms involved are poorly understood. In this nested case-control study, 228 GDM cases and 456 matched controls were recruited, and biological samples were collected at 12-14 gestational weeks. The urinary concentrations of 10 metals and 8-hydroxydeoxyguanosine (8-OHdG) as well as the serum levels of malondialdehyde (MDA) and advanced glycation end products (AGEs) were determined to assess the association of metals with GDM risk and the mediating effects of oxidative stress. Urinary Ti concentration was significantly and positively associated with the risk of GDM (odds ratio [OR]:1.45, 95 % confidence interval [CI]: 1.12, 1.88), while Mn and Fe were negatively associated with GDM risk (OR: 0.67, 95 % CI: 0.50, 0.91 or OR: 0.61, 95 % CI: 0.47, 0.80, respectively). A significant negative association was observed between Mo and GDM risk, specifically in overweight and obese pregnant women. Bayesian kernel machine regression showed a significant negative joint effect of the mixture of 10 metals on GDM risk. The adjusted restricted cubic spline showed a protective role of Mn and Fe in GDM risk (P < 0.05). A significant negative association was observed between essential metals and GDM risk in quantile g-computation analysis (P < 0.05). Mediation analyses showed a mediating effect of MDA on the association between Ti and GDM risk, with a proportion of 8.7 % (P < 0.05), and significant direct and total effects on Ti, Mn, and Fe. This study identified Ti as a potential risk factor and Mn, Fe, and Mo as potential protective factors against GDM, as well as the mediating effect of lipid oxidation.
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Diabetes Gestacional , Humanos , Diabetes Gestacional/epidemiología , Femenino , Embarazo , Estudios Prospectivos , Adulto , Estudios de Casos y Controles , Metales/orina , Metales/sangre , Factores de Riesgo , Estrés Oxidativo , Exposición Materna/estadística & datos numéricosRESUMEN
Macrolide antibiotics, pivotal in clinical therapeutics, are confronting resistance challenges mediated by enzymes like macrolide esterases, which are classified into Ere-type and the less studied Est-type. In this study, we provide the biochemical confirmation of EstX, an Est-type macrolide esterase that initially identified as unknown protein in the 1980s. EstX is capable of hydrolyzing four 16-membered ring macrolides, encompassing both veterinary (tylosin, tidipirosin, and tilmicosin) and human-use (leucomycin A5) antibiotics. It uses typical catalytic triad (Asp233-His261-Ser102) from alpha/beta hydrolase superfamily for ester bond hydrolysis. Further genomic context analysis suggests that the dissemination of estX is likely facilitated by mobile genetic elements such as integrons and transposons. The global distribution study indicates that bacteria harboring the estX gene, predominantly pathogenic species like Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae, are prevalent in 74 countries across 6 continents. Additionally, the emergence timeline of the estX gene suggests its proliferation may be linked to the overuse of macrolide antibiotics. The widespread prevalence and dissemination of Est-type macrolide esterase highlight an urgent need for enhanced monitoring and in-depth research, underlining its significance as an escalating public health issue.
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Esterasas , Esterasas/genética , Esterasas/metabolismo , Esterasas/química , Antibacterianos/farmacología , Antibacterianos/metabolismo , Macrólidos/metabolismo , Humanos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Filogenia , Hidrolasas/genética , Hidrolasas/metabolismo , Hidrolasas/químicaRESUMEN
INTRODUCTION: Maternal height has been shown to be associated with adverse outcomes in women with gestational diabetes mellitus (GDM). The aim of this study is to evaluate the association between maternal height and adverse outcomes stratified for gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) in women with GDM. METHODS: We conducted a retrospective study that included 2048 women diagnosed with GDM during 24-28 gestational weeks from July 1, 2017, to June 30, 2018, in Zhejiang Province, China. Demographic data, maternal characteristics and pregnancy complications were extracted from medical records. Maternal height was divided into three categories by tertiles. Chi-square was used to evaluate categorical data while one-way ANOVA was utilized to analyze continuous variables. The relationship between maternal height and adverse outcomes was examined using logistic regression. RESULTS: We found that shorter women had higher rates of low birth weight (LBW) (p = 0.003) and primary cesarean section (primary CS) (p < 0.001) while taller women had higher rates of abnormal neonatal ponderal index (p < 0.001), postpartum hemorrhage (p = 0.044) and macrosomia (p < 0.001). In taller women who had excess GWG, maternal height was positively associated with the risk of macrosomia (aOR 1.97, 95% CI 0.95-4.10). In shorter women who had inadequate GWG, maternal height was significantly associated with LBW (aOR 2.20, 95% CI 1.13-4.29) and primary CS (aOR 2.08, 95% CI 1.38-3.12). Maternal height was a protective factor of postpartum hemorrhage (aOR 0.15, 95% CI 0.03-0.72) in shorter women with excess GWG. In women with normal pre-pregnancy BMI, maternal height was positively associated with LBW (aOR 2.00, 95% CI 1.15-3.49) and primary CS (aOR 1.71, 95% CI 1.28-2.28) in shorter women while it was negatively associated with the risk of abnormal neonatal ponderal index in both shorter and taller women compared to average height women (aOR 0.71, 95% CI 0.55-0.92; aOR 0.66, 95% CI 0.51-0.85). CONCLUSION: The association between maternal height and adverse pregnancy outcomes varies with pre-pregnancy BMI and GWG in GDM women. Taking maternal height, pre-pregnancy BMI and GWG into account and using personalized prenatal management may reduce the risk of adverse pregnancy outcomes in GDM.
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Agarooligosaccharides have great potential in food industry because of their various bio-activities, while the limited availability and diversity of α-agarases hinder agarooligosaccharides' broader application. To overcome this limitation, a computer-assisted method was used to screen and identify novel agarases. Firstly, one novel α-agarase, AgaB, with an N-terminal CBM2 domain (the first report of this domain in agarases), was discovered. Purified agarases only exhibited activity against agarose, with optimum activity at 40â and pH 8.0. Analysis of hydrolysis products indicated that AgaB is an endo-type α-agarase, producing agarotetraose and agarohexaose. Secondly, AgaB truncated CBM2 showed increased Km values, suggesting that CBM2 aids in substrate binding. Thirdly, E468 and D333 are possibly catalytic amino acids, which was supported by molecular docking results and mutants. Biochemical characterization of first reported CBM2-containing agarase and catalytic mechanism study lay the foundation for the exploration and development of α-agarases in the future.
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BACKGROUND: A training system that allows the trainee to perform laparoscopic suturing in a realistic environment and measures the force applied to the tissue would be invaluable. This study aims to establish the construct and content validity of the training system we developed for the objective assessment of surgeons' skills. METHODS: Ten novices, 6 residents, and 6 experts performed the suturing and knot-tying task using the training system. Ten force-related parameters were used to analyse the system's construct validity. Experts were invited to evaluate the content validity with questionnaires. RESULTS: Eight parameters showed significant differences between the three groups. The construct validity results demonstrated that the system could distinguish the tissue handling ability of operators. The experts agreed that the system had excellent content validity with an average score of 4.71/5. CONCLUSIONS: The training system is likely valid for surgical training. It can realistically simulate surgical scenarios and evaluate the tissue handling ability of trainees.
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Bio-based pentamethylene diisocyanate (PDI) is a new type of sustainable isocyanate, which has important applications in coatings, foams, and adhesives. Technical-economic analysis of the PDI distillation process can promote the industrialization of PDI. The thermal analysis of PDI facilitates the smooth running of the simulation process. A new PDI heat capacity prediction method was established. The distillation processes of a crude PDI solution by conventional distillation and double-effect distillation were studied. Countercurrent double-effect distillation showed the best energy-saving effects in all double-effect distillation. However, combined with total annual charge (TAC), parallel double-effect distillation was the optimal method for PDI purification. Parallel double-effect distillation can significantly reduce the TAC of production PDI, which is 33.39% lower than that of the conventional distillation. The study demonstrates a clear economic incentive for reducing the cost of PDI purification by parallel double-effect distillation.
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Photodynamic therapy (PDT) utilizing Hematoporphyrin Derivative (HpD) injection has been demonstrated as an efficacious treatment for various conditions, including Bowen's disease, subtypes of basal cell carcinomas, and actinic keratosis. While surgical resection is considered the primary treatment option for extramammary Paget's disease (EMPD), some patients may not be suitable candidates for surgical intervention. ALA-PDT may have some benefits in treating EMPD in select patients, while Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) has demonstrated promising potential as a cancer treatment. We present one case of vulvar extramammary Paget's disease (EMPD), that is a female patient with lesions in the vulva and involving the urethra. Due to advanced age, underlying diseases, the extensive affected area, and the specific location of the vulvar lesion, the patients were unable to undergo surgical treatment. Therefore, the patient declined traditional wide local excision and instead opted for hematoporphyrin photodynamic therapy. Treatment eliminated the tumor, but it recurred locally after 1.5 years of follow-up. Localized small-scale recurrence at the affected site can be treated with surgical resection or photodynamic therapy to achieve complete clearance of the lesion. However, the patient refuses further examination and treatment. EMPD has a high recurrence rate, but we propose that hematoporphyrin photodynamic therapy is an effective alternative to conventional surgery for treating this condition, even in case of recurrence.
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Enfermedad de Paget Extramamaria , Fotoquimioterapia , Neoplasias Cutáneas , Neoplasias de la Vulva , Humanos , Femenino , Fármacos Fotosensibilizantes/uso terapéutico , Ácido Aminolevulínico , Fotoquimioterapia/métodos , Derivado de la Hematoporfirina/uso terapéutico , Hematoporfirinas/uso terapéutico , Enfermedad de Paget Extramamaria/patología , Neoplasias de la Vulva/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
OBJECTIVE: To explore the factors related to cesarean scar pregnancy (CSP) treatment failure under different treatment strategies. METHODS: This is a cohort study that consecutively included 1637 patients with CSP. Characteristics including age, gravidity, parity, previous uterine curettages, time since the last cesarean section, gestational age, mean sac diameter, initial serum ß-human chorionic gonadotropin, distance between gestational sac and serosal layer, CSP subtype, classification of blood flow abundance, fetal heartbeat presence, and intraoperative bleeding were recorded. Four strategies were performed separately on these patients. Binary logistic regression analysis was used to analyze the risk factors for initial treatment failure (ITF) under the different treatment strategies. RESULTS: The treatment methods failed in 75 CSP patients, and succeeded in 1298 patients. The analysis found that the presence of a fetal heartbeat was significantly associated with ITF of strategy 1, 2 and 4 (P < 0.05); sac diameter was associated with ITF of strategy 1 and 2 (P < 0.05); gestational age was associated with initial treatment failure of strategy 2 (P < 0.05). CONCLUSION: There was no difference of the failure rate between ultrasound-guided evacuation and hysteroscopy-guided evacuation for CSP treatment with or without uterine artery embolization pretreatment. Sac diameter, fetal heartbeat presence, and gestational age were all associated with CSP initial treatment failure.
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Cesárea , Cicatriz , Humanos , Embarazo , Femenino , Cesárea/efectos adversos , Cicatriz/complicaciones , Cicatriz/terapia , Estudios de Cohortes , Factores de Riesgo , Número de EmbarazosRESUMEN
Bidirectional communication between central nervous system (CNS) and intestine is mediated by nerve, endocrine, immune and other pathways in gut-brain axis. Many diseases of CNS disturb the homeostasis of intestine and gut microbiota. Similarly, the dysbiosis of intestinal and gut microbiota also promotes the progression and deterioration of CNS diseases. IL-23/IL-17 axis is an important inflammatory axis which is widely involved in CNS diseases such as experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), and ischemic stroke (IS). Attributing to the long anatomically distances between ischemic brain and gut, previous studies on IL-23/IL-17 axis in IS are rarely focused on intestinal tissues. However, recent studies have found that IL-17+T cells in CNS mainly originate from intestine. The activation and migration of IL-17+T cells to CNS is likely to be affected by the altered intestinal homeostasis. These studies promoted the attention of IL-23/IL-17 axis and gut-brain axis. IS is difficult to treat because of its extremely complex pathological mechanism. This review mainly discusses the relationship between IL-23/IL-17 axis and IS from the perspective of gut-brain axis. By analyzing the immune pathways in gut-brain axis, the activation of IL-23/IL-17 axis, the roles of IL-23/IL-17 axis in gut, CNS and other systems after stoke, this review is expected to provide new enlightenments for the treatment strategies of IS. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".
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Enfermedades del Sistema Nervioso Central , Encefalomielitis Autoinmune Experimental , Accidente Cerebrovascular Isquémico , Animales , Humanos , Eje Cerebro-Intestino , Interleucina-17 , Encéfalo , Interleucina-23RESUMEN
This study aims to use a deep learning method to develop a signature extract from preoperative magnetic resonance imaging (MRI) and to evaluate its ability as a non-invasive recurrence risk prognostic marker in patients with advanced high-grade serous ovarian cancer (HGSOC). Our study comprises a total of 185 patients with pathologically confirmed HGSOC. A total of 185 patients were randomly assigned in a 5:3:2 ratio to a training cohort (n = 92), validation cohort 1 (n = 56), and validation cohort 2 (n = 37). We built a new deep learning network from 3839 preoperative MRI images (T2-weighted images and diffusion-weighted images) to extract HGSOC prognostic indicators. Following that, a fusion model including clinical and deep learning features is developed to predict patients' individual recurrence risk and 3-year recurrence likelihood. In the two validation cohorts, the consistency index of the fusion model was higher than both the deep learning model and the clinical feature model (0.752, 0.813 vs. 0.625, 0.600 vs. 0.505, 0.501). Among the three models, the fusion model had a higher AUC than either the deep learning model or the clinical model in validation cohorts 1 or 2 (AUC = was 0.986, 0.961 vs. 0.706, 0.676/0.506, 0.506). Using the DeLong method, the difference between them was statistically significant (p < 0.05). The Kaplan-Meier analysis distinguished two patient groups with high and low recurrence risk (p = 0.0008 and 0.0035, respectively). Deep learning may be a low-cost, non-invasive method for predicting risk for advanced HGSOC recurrence. Deep learning based on multi-sequence MRI serves as a prognostic biomarker for advanced HGSOC, which provides a preoperative model for predicting recurrence in HGSOC. Additionally, using the fusion model as a new prognostic analysis means that can use MRI data can be used without the need to follow-up the prognostic biomarker.
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For medical image retrieval task, deep hashing algorithms are widely applied in large-scale datasets for auxiliary diagnosis due to the retrieval efficiency advantage of hash codes. Most of which focus on features learning, whilst neglecting the discriminate area of medical images and hierarchical similarity for deep features and hash codes. In this paper, we tackle these dilemmas with a new Multi-scale Triplet Hashing (MTH) algorithm, which can leverage multi-scale information, convolutional self-attention and hierarchical similarity to learn effective hash codes simultaneously. The MTH algorithm first designs multi-scale DenseBlock module to learn multi-scale information of medical images. Meanwhile, a convolutional self-attention mechanism is developed to perform information interaction of the channel domain, which can capture the discriminate area of medical images effectively. On top of the two paths, a novel loss function is proposed to not only conserve the category-level information of deep features and the semantic information of hash codes in the learning process, but also capture the hierarchical similarity for deep features and hash codes. Extensive experiments on the Curated X-ray Dataset, Skin Cancer MNIST Dataset and COVID-19 Radiography Dataset illustrate that the MTH algorithm can further enhance the effect of medical retrieval compared to other state-of-the-art medical image retrieval algorithms.
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COVID-19 , Neoplasias Cutáneas , Humanos , Algoritmos , Aprendizaje , SemánticaRESUMEN
BACKGROUND: Colorectal cancer is the most common cause of cancer-related death worldwide. Magnetic resonance imaging (MRI) has become a promising alternative method for staging the cancer. PURPOSE: To evaluate parameters of intravoxel incoherent motion (IVIM) and their relationships with clinical-pathologic factors in rectal cancers. MATERIAL AND METHODS: A total of 51 patients with histopathologically proven rectal cancer who underwent preoperative pelvic MRI were prospectively enrolled. Parameters (ADC, D, D*, and f) derived from IVIM-diffusion-weighted imaging (DWI) were independently measured by two radiologists. Student's t-test, receiver operating characteristic curves, and Spearman correlation were used for statistical analysis. RESULTS: ADC, D, and D* were significantly higher in pT1-2 tumors than in pT3-4 tumors (1.108 ± 0.233 vs. 0.950 ± 0.176, 0.796 ± 0.199 vs. 0.684 ± 0.114, 0.013 ± 0.005 vs. 0.008 ± 0.003, respectively; P < 0.05). D* exhibited a strong correlation with the tumor stage (r = -0.675, P < 0.001). In poorly differentiated cluster (PDC) grading, ADC, D*, and f were significantly lower in high-grade tumors than in low-grade tumors (0.905 ± 0.148 vs. 1.064 ± 0.200, 0.008 ± 0.002 vs. 0.011 ± 0.005, and 0.252 ± 0.032 vs. 0.348 ± 0.058, respectively; P < 0.05). The f value exhibited a significantly strong correlation with the PDC grades (r = -0.842, P < 0.001), and higher sensitivity and specificity (95.2% and 75.9%) than those shown by the ADC, D, and D* values. CONCLUSION: IVIM parameters, especially f, demonstrated a strong correlation with histologic grades and showed a better performance in differentiating between high- and low-grade rectal cancers. These parameters would be helpful in predicting tumor aggressiveness and prognosis.
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Neoplasias del Recto , Humanos , Pronóstico , Perfusión , Movimiento (Física) , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Imagen de Difusión por Resonancia Magnética/métodosRESUMEN
Diabetic foot ulcer (DFU) and poor wound healing are chronic complications in patients with diabetes. The increasing incidence of DFU has resulted in huge pressure worldwide. Diagnosing and treating this condition are therefore of great importance to control morbidity and improve prognosis. Finding new markers with potential diagnostic and therapeutic utility in DFU has gathered increasing interest. Wound healing is a process divided into three stages: Inflammation, proliferation, and regeneration. Non-coding RNAs (ncRNAs), which are small protected molecules transcribed from the genome without protein translation function, have emerged as important regulators of diabetes complications. The deregulation of ncRNAs may be linked to accelerated DFU development and delayed wound healing. Moreover, ncRNAs can be used for therapeutic purposes in diabetic wound healing. Herein, we summarize the role of microRNAs, long ncRNAs, and circular RNAs in diverse stages of DFU wound healing and their potential use as novel therapeutic targets.
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Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1ß. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.
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Diabetes Gestacional , MicroARNs , Femenino , Humanos , Embarazo , Diabetes Gestacional/metabolismo , Regulación hacia Abajo/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Venas Umbilicales/metabolismo , Placenta/metabolismo , MicroARNs/metabolismo , Proliferación Celular , Inflamación/patologíaRESUMEN
Ischemic stroke (IS) has complex pathological mechanisms, and is extremely difficult to treat. At present, the treatment of IS is mainly based on intravenous thrombolysis and mechanical thrombectomy, but they are limited by a strict time window. In addition, after intravenous thrombolysis or mechanical thrombectomy, damaged neurons often fail to make ideal improvements due to microcirculation disorders. Therefore, finding suitable pathways and targets from the pathological mechanism is crucial for the development of neuroprotective agents against IS. With the hope of making contributions to the development of IS treatments, this review will introduce (1) how related targets are found in pathological mechanisms such as inflammation, excitotoxicity, oxidative stress, and complement system activation; and (2) the current status and challenges in drug development.
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The extinguishing and re-burning of the closed fire area in an underground coal mine were investigated by laboratory-scale physical simulation. Temperatures in the center of the fire source were recorded, and the typical cooling process was observed to include the rapid cooling stage (900-400 °C) and dilatory cooling stage (400-100 °C). With the increase of coal mass from 20 to 80 kg, the rate of cooling decreases and the time required for fire extinguishing increases by 69.5%-193.2%. At temperatures ranging between 500 and 100 °C, yields of CO and H2 show strong correlation with the attenuation of the coal fire, and the trend in the yield of H2 might be used as the optimal indicator considering the different amounts of coal. A significant difference appears in the concentration of H2 released by samples of different dosages of coal in the early stage of cooling, especially when the temperature exceeds 200 °C. During the extinguishing process, micropores in coal fused into mesopores and macropores, while the content of O-containing groups fluctuated significantly. Variations of elemental C and O also indirectly reflect the combustion state in the fire cooling. Taking the experimental reactor as a physical model, the time required for the fire area from closure to safe re-opening is deduced, that is, t = Cm ln (T 1 - T ∞)/(T 2 - T ∞ ). The calculated results were compared with the changes in measured temperatures, providing a theoretical foundation for the re-opening prediction of mine fire areas.
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In this work, a comparative study of efficient degradation of Rhodamine B (RhB) in CoFe2O4/H2O2 and CoFe2O4/PMS systems was performed. Batch experiments indicated that the RhB degradation rate of CoFe2O4/H2O2 system reached 95.5% at 90 min under the condition of 0.5 g L-1 of CoFe2O4 dosage, 10 mM of H2O2 concentration and 3.0 of initial pH. At certain conditions of initial pH = 7.0, 0.3 g L-1 of CoFe2O4 dosage, 7 mM of PMS concentration, CoFe2O4/PMS system could completely degrade RhB within 90 min. EPR and quenching experiments indicated that â¢OH was the main active species of CoFe2O4/H2O2 system, and â¢OH, SO4â¢-, â¢O2- and 1O2 participated in RhB degradation of CoFe2O4/PMS system. The circulate of Co(II)/Co(III) and Fe(II)/Fe(III) on the CoFe2O4 surface promoted the formation of free radical species in the two system. In CoFe2O4/PMS system, the formed â¢O2- and SO5â¢- realized the generation of non-free radical species (1O2). The LC-MS results indicated that N-de-ethylation, chromophore cleavage, opening rings and mineralization were the main steps for the RhB degradation of the two systems. After five cycles of degradation experiment, the CoFe2O4/H2O2 and CoFe2O4/PMS systems still maintained the high degradation rate (85.2% and 92.4%) and low mass loss (2.7% and 3.09%). In addition, CoFe2O4/PMS system had better potential value for the actual water and multi-pollutant degradation than CoFe2O4/H2O2 system. Finally, the toxicity analysis and cost assessment of the two oxidation systems were preliminarily evaluated.
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Contaminantes Ambientales , Peróxidos , Compuestos Férricos , Compuestos Ferrosos , Peróxido de Hidrógeno , Rodaminas , AguaRESUMEN
Male infertility is a major and growing health problem with an estimated global prevalence of 4.2%. The current therapy is limited by the unknown etiology of MI, emphasizing the critical requirement forward to a more efficient method or medication. Through thousands of years, Traditional Chinese Medicine (TCM) has been shown to be effective in treating MI effectively. However, the components, mechanisms and functions of TCM prescriptions on MI are still obscure, severely limiting its clinical application. In order to discover the molecular mechanism of TCM against MI, our study presents a comprehensive approach integrated data mining, network pharmacology, molecular docking, UHPLC-Q-Orbitrap HRMS, and experimental validation. Here, we begin to acquire 289 clinical TCM prescriptions for MI from a TCM hospital's outpatient department. Then, Core Chinese Materia Medica (CCMM) was then retrieved from the TCM Inheritance Support System (TCMISS), which was utilized to discover the underlying rules and connections in clinical prescriptions. After that, 98 CCMM components and 816 MI targets were obtained from ten distinct databases. Additionally, the network pharmacology methods, including network construction, GO and KEGG pathway enrichment, PPI analysis, were utilized to reveal that kaempferol, quercetin, isorhamnetin, and beta-sitosterol are the core components of CCMM in treating MI. The mechanisms and functions of CCMM against MI are hormone regulation, anti-apoptosis, anti-oxidant stress, and anti-inflammatory. Furthermore, the strong connections between four core components and six key targets were verified using a molecular docking method. Following that, the core components of the CCMM extract were identified using UHPLC-Q-Orbitrap HRMS analysis. Finally, in vivo experiments demonstrated that CCMM and four core components could improve the density, motility, viability of sperm, lecithin corpuscle density, decrease the rate of sperm malformation and testis tissue damage, and regulate the protein expressions of AKT1, MAPK3/1, EGFR, and TNF-α in a mouse model of MI. UHPLC-Q-Orbitrap HRMS analysis and in vivo experiments further validated the results of data mining, network pharmacology, and molecular docking. Our study could uncover the components, mechanisms, and functions of TCM prescriptions against MI and develop a new integrative approach to demonstrate TCM's multi-component, multi-target, and multi-pathway approach to disease treatment.