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BACKGROUND: People with schizophrenia often face challenges such as lower psychological resilience, reduced self-worth, and increased social stigma, hindering their recovery. Mindfulness-Based Cognitive Therapy (MBCT) has shown promise in boosting psychological resilience and self-esteem while diminishing stigma. However, MBCT demands professional involvement and substantial expenses, adding to the workload of professionals and the financial strain on patients. Mixed-mode Mindfulness-Based Cognitive Therapy (M-MBCT) integrates both "face-to-face" and "self-help" approaches to minimize staff effort and costs. This study aims to assess the impact of M-MBCT on the psychological resilience, self-esteem, and stigma in schizophrenia patients. METHODS: This randomized, controlled, parallel-group, assessor-blinded clinical trial enrolled 174 inpatients with schizophrenia. Participants were randomly assigned to either the experimental or control group. The experimental group underwent an 8-week M-MBCT intervention, while the control group received standard treatment. Data collection employed the Connor-Davidson Resilience Scale (CD-RISC), Internalized Stigma of Mental Illness Scale (ISMI), and Rosenberg Self-Esteem Scale (RSES) before and after the intervention. Post-intervention, significant differences in ISMI, CD-RISC, and RSES scores were observed between the experimental and control groups. RESULTS: In the experimental group, ISMI scores notably decreased, while CD-RISC and RSES scores significantly increased (P < 0.05). Multiple linear regression analysis identified age, education, and family history of mental illness as significant factors related to stigma (P < 0.05). Additionally, correlation analysis indicated a significant negative relationship between the reduction in CD-RISC scores and the reduction in ISMI scores (P < 0.05). CONCLUSION: M-MBCT effectively enhanced psychological resilience and self-esteem while diminishing stigma in individuals with schizophrenia. M-MBCT emerges as a promising treatment option for schizophrenia sufferers. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 03/06/2023 ( www.chictr.org.cn ; ChiCTR ID: ChiCTR2300069071).
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Terapia Cognitivo-Conductual , Atención Plena , Pruebas Psicológicas , Resiliencia Psicológica , Esquizofrenia , Humanos , Esquizofrenia/terapia , Estigma Social , Pacientes Internos , AutoimagenRESUMEN
BACKGROUND: Okra contains flavonoids and vitamin C as antioxidants and it contains polysaccharides as immunomodulators. Flavonoids regulate the inflammatory response in mice and may be related to gut microbiota. This study therefore aimed to investigate the impact of okra extract (OE) on inflammation in mice and to elucidate its underlying mechanism. METHOD: Forty male Kunming (KM) mice were categorized into four groups: the control (CON) group, the lipopolysaccharide stimulation (LPS) group, the 5 mg mL-1 OE intervention (LPS + OE) group, and the 5 mg mL-1 OE supplementation plus mixed antibiotics (LPS + OE + ABX) group. RESULTS: The results showed that, compared with the OE group, the expression of inflammatory signaling pathway genes was upregulated and gut barrier genes were inhibited in the OE + ABX group. The Fxr receptor was activated and the abundance of Akkermansia was increased after OE supplementation, whereas the effect was reversed in the OE + ABX group. Meanwhile, Fxr was correlated positively with Akkermansia. CONCLUSION: The OE supplementation alleviated the inflammatory response in mice under LPS stimulation, accompanied by changes in gut microbiota and bile acid receptors, whereas the addition of antibiotics caused a disturbance to the gut microbiota in the OE group, thus reducing the effect of OE in alleviating the inflammatory response. © 2024 Society of Chemical Industry.
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Abelmoschus , Ácidos y Sales Biliares , Microbioma Gastrointestinal , Inflamación , Lipopolisacáridos , Extractos Vegetales , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Lipopolisacáridos/efectos adversos , Ratones , Masculino , Abelmoschus/química , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Ácidos y Sales Biliares/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Bacterias/clasificación , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Animales no ConsanguíneosRESUMEN
The extremely high species diversity of soil bacterial community has fascinated and puzzled community ecologists. Although theory predicts that fluctuations in environments can facilitate diversity maintenance, the effects of fluctuating temperature on species diversity have rarely been investigated in species-rich microbial communities. Here, we examined whether fluctuating temperature had positive effects on species diversity relative to constant temperatures in soil bacterial communities, and investigated the effects of fluctuating temperature on bacterial performances (changes in relative abundance). We performed a temperature manipulation experiment with soils collected from temperate and subtropical zones, where the soils were subjected to constant high, low or fluctuating temperatures. We found that fluctuating temperatures showed significant positive effects on species diversity. The time-averaged effect of fluctuating temperatures (i.e., averaging out the differences between species in their environment-dependent performances) appeared to delay species loss in both the temperate and the subtropical communities. In addition, we found that the performances of temperature-responsive species at fluctuating temperatures significantly deviated from their time-weighted average performances at constant high and low temperatures, which was defined as fluctuation-dependent effects in our study. Intriguingly, fluctuation-dependent effects beyond time-averaged effect led to an opposite trend: differences in temperature-responsive species' performances decreased in the temperate communities, but increased in the subtropical communities. Our findings provide new insights into diversity maintenance in soil bacterial communities, and imply that the effects of fluctuating temperature on species diversity in soil bacterial community might vary across latitude.
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Microbiota , Suelo , Temperatura , Bacterias/genética , Microbiota/genética , Microbiología del SueloRESUMEN
BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia. METHODS: We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence. RESULTS: A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05). CONCLUSION: The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future.
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Antipsicóticos , Esquizofrenia , Humanos , Risperidona/efectos adversos , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Many essential cellular functions are carried out by multi-protein complexes that can be characterized by their protein-protein interactions. The interactions between protein subunits are critically dependent on the strengths of their interactions and their cellular abundances, both of which span orders of magnitude. Despite many efforts devoted to the global discovery of protein complexes by integrating large-scale protein abundance and interaction features, there is still room for improvement. Here, we integrated >7000 quantitative proteomic samples with three published affinity purification/co-fractionation mass spectrometry datasets into a deep learning framework to predict protein-protein interactions (PPIs), followed by the identification of protein complexes using a two-stage clustering strategy. Our deep-learning-technique-based classifier significantly outperformed recently published machine learning prediction models and in the process captured 5010 complexes containing over 9000 unique proteins. The vast majority of proteins in our predicted complexes exhibited low or no tissue specificity, which is an indication that the observed complexes tend to be ubiquitously expressed throughout all cell types and tissues. Interestingly, our combined approach increased the model sensitivity for low abundant proteins, which amongst other things allowed us to detect the interaction of MCM10, which connects to the replicative helicase complex via the MCM6 protein. The integration of protein abundances and their interaction features using a deep learning approach provided a comprehensive map of protein-protein interactions and a unique perspective on possible novel protein complexes.
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Aprendizaje Profundo , Proteómica/métodos , Subunidades de Proteína , Aprendizaje Automático , Espectrometría de MasasRESUMEN
Acquired resistance to MAPK inhibitors limits the clinical efficacy in melanoma treatment. We and others have recently shown that BRAF inhibitor (BRAFi)-resistant melanoma cells can develop a dependency on the therapeutic drugs to which they have acquired resistance, creating a vulnerability for these cells that can potentially be exploited in cancer treatment. In drug-addicted melanoma cells, it was shown that this induction of cell death was preceded by a specific ERK2-dependent phenotype switch; however, the underlying molecular mechanisms are largely lacking. To increase the molecular understanding of this drug dependency, we applied a mass spectrometry-based proteomic approach on BRAFi-resistant BRAFMUT 451Lu cells, in which ERK1, ERK2, and JUNB were silenced separately using CRISPR-Cas9. Inactivation of ERK2 and, to a lesser extent, JUNB prevents drug addiction in these melanoma cells, while, conversely, knockout of ERK1 fails to reverse this phenotype, showing a response similar to that of control cells. Our analysis reveals that ERK2 and JUNB share comparable proteome responses dominated by reactivation of cell division. Importantly, we find that EMT activation in drug-addicted melanoma cells upon drug withdrawal is affected by silencing ERK2 but not ERK1. Moreover, transcription factor (regulator) enrichment shows that PIR acts as an effector of ERK2 and phosphoproteome analysis reveals that silencing of ERK2 but not ERK1 leads to amplification of GSK3 kinase activity. Our results depict possible mechanisms of drug addiction in melanoma, which may provide a guide for therapeutic strategies in drug-resistant melanoma.
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Melanoma , Preparaciones Farmacéuticas , Línea Celular Tumoral , Resistencia a Antineoplásicos , Glucógeno Sintasa Quinasa 3 , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteómica , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
BACKGROUND: Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with an abnormal immune response. Accumulating evidence has demonstrated that aquaporin 1 (AQP1) prevents kidney tissue injury in LPS-induced AKI by mediating immune response. However, the underlying mechanisms remain obscure. Macrophages as immune cells with multiple phenotypes are important mediators in tissue homeostasis and host defense. We propose that macrophage polarization is implicated in AQP1-mediated immune response. METHODS: Herein we established sepsis-induced AKI model rats through intraperitoneal injection of LPS into Wistar rats to reveal immune mechanism of damage. We also used LPS-induced mouse RAW264.7 cells to elucidate the molecular mechanism of macropage polarization. RESULTS: Histopathology showed that renal tubular epithelial cells in the model group were swollen, inflammatory exudation was obvious and the inflammatory factors, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were increased. Western blotting showed PI3K was upregulated in the model group. Serum creatinine and urea nitrogen increased after LPS injection. Renal AQP1 mRNA is downregulated and serum AQP1 protein increased first and then decreased in LPS-induced AKI rats. M2 macrophage markers (Arg-1, CD206) were increased in repair stage. In addition, treatment of murine macrophages (RAW264.7) with AQP1 siRNA resulted in decreased PI3K activation and M2 polarization, but increased IL-6 and TNF-α. Moreover, inhibiting PI3K with wortmannin imitated the results of AQP1 silencing. CONCLUSIONS: Macrophage M2 polarization is likely the cellular mechanism underlying the anti-AKI property of AQP1, and PI3K activation is involved in the AQP1-induced M2 phenotype switch.
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Lesión Renal Aguda/inmunología , Acuaporina 1/inmunología , Macrófagos/inmunología , Fosfatidilinositol 3-Quinasas/inmunología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Animales , Acuaporina 1/sangre , Acuaporina 1/genética , Interleucina-6/inmunología , Riñón/patología , Lipopolisacáridos , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo II/inmunología , Células RAW 264.7 , Ratas Wistar , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVE: This study was designed to investigate the role of AQP1 in the development of LPS-induced AKI and its potential regulatory mechanisms in the inflammatory responses of macrophages. METHODS: Male Wistar rats were injected intraperitoneally with LPS, and biochemical and histological renal damage was assessed. The levels of inflammatory mediators, macrophage markers and AQP1 in blood and kidney tissues were assessed by ELISA. RTPCR was used to assess changes in the relative levels of AQP1 mRNA induced by LPS. Western blot and immunofluorescence analyses were performed to assay the activation of the p38 MAPK and NF-κB pathways, respectively. The same detection methods were used in vitro to determine the regulatory mechanisms underlying AQP1 function. RESULTS: AQP1 mRNA levels were dramatically decreased in AKI rats following the increased expression of inflammatory factors. In vitro experiments demonstrated that silencing the AQP1 gene increased inflammatory mediator secretion, altered the classical activation of macrophages, greatly enhanced the phosphorylation of p38 and accelerated the translocation of NF-κB. Furthermore, these results were blocked by doramapimod, a p38 inhibitor. Therefore, these effects were mediated by the increased phosphorylation of p38 MAPK. CONCLUSION: Our results suggest that altered AQP1 expression may be associated with the development of inflammation in AKI. AQP1 plays a protective role in modulating acute renal injury and can attenuate macrophage-mediated inflammatory responses by downregulating p38 MAPK activity in LPS-induced RAW264.7 cells. The pharmacological targeting of AQP1-mediated p38 MAPK signalling may provide a novel treatment approach for AKI.
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Lesión Renal Aguda/inmunología , Acuaporina 1/inmunología , Macrófagos/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/inmunología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Acuaporina 1/sangre , Acuaporina 1/genética , Citocinas/sangre , Riñón/patología , Lipopolisacáridos , Masculino , Ratones , FN-kappa B/inmunología , Células RAW 264.7 , Ratas WistarRESUMEN
BACKGROUND: Inflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1ß (IL-1ß) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory effects. This study aims to investigate the effects of diacerein on endotoxemia-induced AKI. METHODS: Male C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/kg) for 24 h prior to diacerein treatment (15 mg/kg/day) for another 48 h. Mice were examined by histological, molecular and biochemical approaches. RESULTS: LPS administration showed a time-dependent increase of IL-1ß expression and secretion in kidney tissues. Diacerein treatment normalized urine volume and osmolarity, reduced blood urea nitrogen (BUN), fractional excretion of sodium (FENa), serum creatinine and osmolarity, and protected renal function in an endotoxemic AKI mice model. In the histopathologic study, diacerein also improved renal tubular damage such as necrosis of the tubular segment. Moreover, diacerein inhibited LPS-induced increase of inflammatory cytokines, such as IL-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1 and nitric oxide synthase 2. In addition, LPS administration markedly decreased aquaporin 1 (AQP1), AQP2, AQP3, Na,K-ATPase α1, apical type 3 Na/H exchanger and Na-K-2Cl cotransporter expression in the kidney, which was reversed by diacerein treatment. We also found that diacerein or IL-1ß inhibition prevented the secretion of inflammatory cytokines and the decrease of AQP and sodium transporter expression induced by LPS in HK-2 cells. CONCLUSION: Our study demonstrates for the first time that diacerein improves renal function efficiently in endotoxemic AKI mice by suppressing inflammation and altering tubular water and sodium handing. These results suggest that diacerein may be a novel therapeutic agent for the treatment of endotoxemic AKI.
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Lesión Renal Aguda/tratamiento farmacológico , Antraquinonas/uso terapéutico , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/patología , Animales , Citocinas/inmunología , Endotoxemia/complicaciones , Endotoxemia/tratamiento farmacológico , Endotoxemia/inmunología , Endotoxemia/patología , Inflamación/complicaciones , Inflamación/inmunología , Inflamación/patología , Riñón/efectos de los fármacos , Masculino , Ratones Endogámicos C57BLRESUMEN
Drug target interactions (DTIs) are crucial in pharmacology and drug discovery. Presently, experimental determination of compound-protein interactions remains challenging because of funding investment and difficulties of purifying proteins. In this study, we proposed two in silico models based on support vector machine (SVM) and random forest (RF), using 1589 molecular descriptors and 1080 protein descriptors in 9948 ligand-protein pairs to predict DTIs that were quantified by Ki values. The cross-validation coefficient of determination of 0.6079 for SVM and 0.6267 for RF were obtained, respectively. In addition, the two-dimensional (2D) autocorrelation, topological charge indices and three-dimensional (3D)-MoRSE descriptors of compounds, the autocorrelation descriptors and the amphiphilic pseudo-amino acid composition of protein are found most important for Ki predictions. These models provide a new opportunity for the prediction of ligand-receptor interactions that will facilitate the target discovery and toxicity evaluation in drug development.
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Prednisolona/análogos & derivados , Ligandos , Prednisolona/metabolismo , Unión Proteica , Máquina de Vectores de SoporteRESUMEN
A rapid, improved and comprehensive method including high-performance thin-layer chromatography, fingerprint technology and single standard to determine multiple components was developed and validated for the quality evaluation of licorice. In this study, a newly developed high-performance thin-layer chromatography method was first used for authentication of licorice, which achieved simultaneous identification of multiple bands including five bands for known bioactive components by comparing their retention factor values and colors with the standards. For fingerprint analysis, 8 of 16 common peaks were identified. Simultaneously, similarity analysis which showed very similar patterns and hierarchical clustering analysis were performed to discriminate and classify the 27 batches of samples. Additionally, the single standard to determine multiple components method was first successfully achieved to quantify the eight important active markers in licorice including liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquritin, neoisoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid. The easily available glycyrrhizic acid was selected as the reference substance to calculate relative response factors. Compared with the normal external standard method, this alternative method can be used to determine the multiple indices effectively and accurately. The validation result showed that the developed method was specific, accurate, precise, robust and reliable for the overall quality assessment of licorice.
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Técnicas de Química Analítica/métodos , Cromatografía en Capa Delgada , Medicamentos Herbarios Chinos/normas , Glycyrrhiza/química , Técnicas de Química Analítica/normas , Control de Calidad , Reproducibilidad de los ResultadosRESUMEN
High-performance photocatalysts for catalytic reduction of CO2 are largely impeded by inefficient charge separation and surface activity. Reasonable design and efficient collaboration of multiple active sites are important for attaining high reactivity and product selectivity. Herein, Cu-Cu2O and Ag nanoparticles are confined as dual sites for assisting CO2 photoreduction to CH4 on TiO2. The introduction of Cu-Cu2O leads to an all-solid-state Z-scheme heterostructure on the TiO2 surface, which achieves efficient electron transfer to Cu2O and adsorption and activation of CO2. The confined nanometallic Ag further enhances the carrier's separation efficiency, promoting the conversion of activated CO2 molecules to â¢COOH and further conversion to CH4. Particularly, this strategy is highlighted on the TiO2 system for a photocatalytic reduction reaction of CO2 and H2O with a CH4 generation rate of 62.5 µmolâg-1âh-1 and an impressive selectivity of 97.49 %. This work provides new insights into developing robust catalysts through the artful design of synergistic catalytic sites for efficient photocatalytic CO2 conversion.
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Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017-1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases.
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Hipersensibilidad , Inmunoglobulina G , Niño , Animales , Humanos , Alérgenos , Inmunoglobulina E , Dieta , Pyroglyphidae , Dermatophagoides pteronyssinus , LecheRESUMEN
INTRODUCTION: Fluorosis is a global public health disease affecting more than 50 countries and 500 million people. Excessive fluoride damages the liver and intestines, yet the mechanisms and therapeutic approaches remain unclear. OBJECTIVES: To explore the mechanisms by which fluoride-induced intestinal-hepatic damage and vitamin B2 alleviation. METHODS: Fluoride and/or vitamin B2-treated IL-17A knockout and wild-type mouse models were established, the morphological and functional changes of liver and gut, total bile acid biosynthesis, metabolism, transport, and regulation of FXR-FGF15 signaling pathways were evaluated, the ileal microbiome was further analyzed by 16S rDNA sequence. Finally, Bifidobacterium supplementation mouse model was designed and re-examined the above indicators. RESULTS: The results demonstrated that fluoride induced hepatointestinal injury and enterohepatic circulation disorder by altering the synthesis, transporters, and FXR-FGF15 pathway regulation of total bile acid. Importantly, the ileum was found to be the most sensitive and fluoride changed ileal microbiome particularly by reducing abundance of Bifidobacterium. While vitamin B2 supplementation attenuated fluoride-induced enterohepatic circulation dysfunction through IL-17A and ileal microbiome, Bifidobacterium supplementation also reversed fluoride-induced hepatointestinal injury. CONCLUSION: Fluoride induces morphological and functional impairment of liver and gut tissues, as well as enterohepatic circulation disorder by altering total bile acid (TBA) synthesis, transporters, and FXR-FGF15 signaling regulation. Vitamin B2 attenuated fluoride-induced enterohepatic circulation disorder through IL-17A knockout and ileal microbiome regulation. The ileum was found to be the most sensitive to fluoride, leading to changes in ileal microbiome, particularly the reduction of Bifidobacterium. Furthermore, Bifidobacterium supplementation reversed fluoride-induced hepatointestinal injury. This study not only elucidates a novel mechanism by which fluoride causes hepatointestinal toxicity, but also provides a new physiological function of vitamin B2, which will be useful in the therapy of fluorosis and other hepatoenterological diseases.
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Image dehazing is a challenging task in computer vision. Currently, most dehazing methods adopt the U-Net architecture that directly fuses the decoding layer with the corresponding scale encoding layer. These methods ignore the effective utilization of different encoding layer information and existing feature information dilute problems, resulting in suboptimal edge details and overall scene aspects of dehazed image restoration. In addition, Squeeze and Excitation (SE) channel attention is widely used in dehazing network. However, the two fully-connected layers of dimensionality reduction operation in SE will negatively affect the weight prediction of feature channels, thus reducing the performance of the dehazing network. To solve the above problems, we propose a Multi-level Feature Interaction and Non-local Information Enhanced Channel Attention (MFINEA) dehazing model. Specifically, a multi-level feature interaction module is proposed to enable the decoding layer to fuse shallow and deep feature information extracted from different encoding layers for better recovery of edge details and the overall scene. Furthermore, an efficient non-local information enhanced channel attention module is proposed to mine more effective feature channel information for the weight assignment of the feature maps. The experimental results on several challenging benchmark datasets show that our MFINEA outperforms the state-of-the-art dehazing methods.
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Benchmarking , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Traditional Chinese Medicine (TCM) involves a broad range of empirical testing and refinement and plays an important role in the health maintenance for people all over the world. However, due to the complexity of Chinese herbs, a full understanding of TCM's action mechanisms is still unavailable despite plenty of successful applications of TCM in the treatment of various diseases, including especially cardiovascular diseases (CVD), one of the leading causes of death. Thus in the present work, by incorporating the chemical predictors, target predictors and network construction approaches, an integrated system of TCM has been constructed to systematically uncover the underlying action mechanisms of TCM. From three representative Chinese herbs, i.e., Ligusticum chuanxiong Hort., Dalbergia odorifera T. Chen and Corydalis yanhusuo WT Wang which have been widely used in CVD treatment, by combinational use of drug absorption, distribution, metabolism and excretion (ADME) screening and network pharmacology techniques, we have generated 64 bioactive ingredients and identified 54 protein targets closely associated with CVD, of which 29 are common targets (52.7%) of the three herbs. The result provides new information on the efficiency of the Chinese herbs for the treatment of CVD and also explains one of the basic theories of TCM, i.e., "multiple herbal drugs can treat one disease". The predicted potential targets were then mapped to target-disease and target-signal pathway connections, which revealed the relationships of the active ingredients with their potential targets, diseases and signal systems. This means that for the first time, the action mechanism of these three important Chinese herbs for the treatment of CVD is uncovered, by generating and identifying both their active ingredients and novel targets specifically related to CVD, which clarifies some of the common conceptions in TCM, and thus provides clues to modernize such specific herbal medicines.
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Enfermedades Cardiovasculares/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Biología de Sistemas , Enfermedades Cardiovasculares/metabolismo , Corydalis/química , Corydalis/metabolismo , Dalbergia/química , Dalbergia/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacocinética , Humanos , Ligusticum , Redes y Vías MetabólicasRESUMEN
Kimura disease (KD) is a rare and benign chronic inflammatory disease of unknown cause. It is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil count, and elevated serum IgE. Currently, no definitive treatments are recommended. A 57-year-old Chinese man was diagnosed with KD after 7 years of slow subcutaneous masses growth. The patient underwent treatment of oral glucocorticoids for 1 year, but the masses recurred as the dosage was tapered down. Subsequent anti-IgE therapy of omalizumab administered subcutaneously at 450 mg/day at a 4-week interval did not show improvement. The size of masses and serum IgE and circulating eosinophils did not decrease significantly after 19 cycles of continuous treatment. Ultimately, switched strategy of dupilumab was applied at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. This treatment demonstrated dramatical effects with reduced masses in each area and fast dropdown of eosinophil counts, while the high level of serum IgE remained without changes. Recently, different biologics including anti-IgE, anti-IL-5, and anti-IL-4/IL-13 have been applied to treat KD with satisfied results and help to explore the pathogenesis of this rare disease. To our knowledge, this is the first report that demonstrates the effects of two different biologics in the same patient and reveals the impressive clinical efficacy of dupilumab to treat KD independent of IgE. Therefore, further investigation of the underlying mechanism and the development of diagnosis and treatment of KD is valuable.
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Productos Biológicos , Enfermedad de Kimura , Masculino , Humanos , Persona de Mediana Edad , Enfermedad de Kimura/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Omalizumab/uso terapéutico , Inmunosupresores , Productos Biológicos/uso terapéuticoRESUMEN
Phenotypic plasticity affords invasive plant species the ability to colonize a wide range of habitats, but physiological plasticity of their stems is seldom recognized. Investigation of the stem plasticity of invasive plant species could lead to a better understanding of their invasiveness. We performed pot experiments involving defoliation treatments and isolated culture experiments to determine whether the invasive species Mikania micrantha exhibits greater plasticity in the stems than do three non-invasive species that co-occur in southern China and then explored the mechanism underlying the modification of its stem photosynthesis. Our results showed that the stems of M. micrantha exhibited higher plasticity in terms of either net or gross photosynthetic rate in response to the defoliation treatment. These effects were positively related to an increased stem elongation rate. The enhancement of stem photosynthesis in M. micrantha resulted from the comprehensive action involving increases in the Chl a/b ratio, D1 protein and stomatal aperture, changes in chloroplast morphology and a decrease in anthocyanins. Increased plasticity of stem photosynthesis may improve the survival of M. micrantha under harsh conditions and allow it to rapidly recover from defoliation injuries. Our results highlight that phenotypic plasticity promotes the invasion success of alien plant invaders.
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Two formal syntheses and one total synthesis of fostriecin (1) have been achieved, as well as, the synthesis of its related congener dihydro-dephospho-fostriecin. All the routes use the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 positions and a Leighton allylation to set the C-5 position of the natural product. In the formal syntheses a Noyori transfer hydrogenation of an ynone was used to set the C-11 position while the total synthesis employed a combination of asymmetric dihydroxylation and Pd-π-allyl reduction to set the C-11 position. Finally in the total synthesis, a trans-hydroboration of the C-12/13 alkyne was used in combination with a Suzuki cross coupling to establish the Z,Z,E-triene of fostriecin (1).