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The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.
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Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Células A549 , Animais , Criança , Pré-Escolar , Feminino , Mutação com Ganho de Função/genética , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos , Células-Tronco Embrionárias Murinas , Mutação/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Transdução de Sinais , Domínios de Homologia de src/genéticaRESUMO
Pericytes and endothelial cells (ECs) constitute the fundamental components of blood vessels. While the role of ECs in tumor angiogenesis and the tumor microenvironment is well appreciated, pericyte function in tumors remains underexplored. In this study, we used pericyte-specific deletion of the nitric oxide (NO) receptor, soluble guanylate cyclase (sGC), to investigate via single-cell RNA sequencing how pericytes influence the vascular niche and the tumor microenvironment. Our findings demonstrate that pericyte sGC deletion disrupts EC-pericyte interactions, impairing Notch-mediated intercellular communication and triggering extensive transcriptomic reprogramming in both pericytes and ECs. These changes further extended their influence to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Inhibition of pericyte sGC has minimal impact on quiescent vessels but significantly increases the vulnerability of angiogenic tumor vessels to conventional anti-angiogenic therapy. In conclusion, our findings elucidate the role of pericytes in shaping the tumor vascular niche and tumor microenvironment and support pericyte sGC targeting as a promising strategy for improving anti-angiogenic therapy for cancer treatment.
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Neoplasias , Pericitos , Humanos , Pericitos/patologia , Pericitos/fisiologia , Guanilil Ciclase Solúvel , Células Endoteliais/fisiologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neoplasias/genética , Neoplasias/patologia , Guanilato Ciclase , Microambiente TumoralRESUMO
Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease mouse models, mapping populations, and sensitized backgrounds for engineered mutations. The genome sequences of inbred strains, along with dense genotypes from others, enable integrated analysis of trait-variant associations across populations, but these analyses are hampered by the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense variant resource by harmonizing multiple data sets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extendable to other model organisms. The result is a web- and programmatically accessible data service called GenomeMUSter, comprising single-nucleotide variants covering 657 strains at 106.8 million segregating sites. Interoperation with phenotype databases, analytic tools, and other resources enable a wealth of applications, including multitrait, multipopulation meta-analysis. We show this in cross-species comparisons of type 2 diabetes and substance use disorder meta-analyses, leveraging mouse data to characterize the likely role of human variant effects in disease. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.
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Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Filogenia , Genótipo , Camundongos Endogâmicos , Fenótipo , Mutação , Variação GenéticaRESUMO
Primary cilia are nearly ubiquitous organelles that transduce molecular and mechanical signals. Although the basic structure of the cilium and the cadre of genes that contribute to ciliary formation and function (the ciliome) are believed to be evolutionarily conserved, the presentation of ciliopathies with narrow, tissue-specific phenotypes and distinct molecular readouts suggests that an unappreciated heterogeneity exists within this organelle. Here, we provide a searchable transcriptomic resource for a curated primary ciliome, detailing various subgroups of differentially expressed genes within the ciliome that display tissue and temporal specificity. Genes within the differentially expressed ciliome exhibited a lower level of functional constraint across species, suggesting organism and cell-specific function adaptation. The biological relevance of ciliary heterogeneity was functionally validated by using Cas9 gene-editing to disrupt ciliary genes that displayed dynamic gene expression profiles during osteogenic differentiation of multipotent neural crest cells. Collectively, this novel primary cilia-focused resource will allow researchers to explore longstanding questions related to how tissue and cell-type specific functions and ciliary heterogeneity may contribute to the range of phenotypes associated with ciliopathies.
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Ciliopatias , Osteogênese , Humanos , Cílios/genética , Cílios/metabolismo , Ciliopatias/genética , Desenvolvimento Embrionário/genética , Diferenciação Celular/genéticaRESUMO
NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. However, the underlying mechanisms in oncogenesis that involve various N-terminal fusion partners of NTRK fusions remain elusive. Here, we show that NTRK fusion proteins form liquid-like condensates driven by their N-terminal fusion partners. The kinase reactions are accelerated in these condensates where the complexes for downstream signaling activation are also concentrated. Our work demonstrates that the phase separation driven by NTRK fusions is not only critical for TRK activation, but the condensates formed through phase separation serve as organizational hubs for oncogenic signaling.
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Neoplasias , Proteínas de Fusão Oncogênica , Humanos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais/genética , Neoplasias/genética , Neoplasias/metabolismo , Fusão Gênica , Receptor trkA/genética , Receptor trkA/metabolismo , Inibidores de Proteínas QuinasesRESUMO
The Mouse Phenome Database (MPD; https://phenome.jax.org; RRID:SCR_003212), supported by the US National Institutes of Health, is a Biomedical Data Repository listed in the Trans-NIH Biomedical Informatics Coordinating Committee registry. As an increasingly FAIR-compliant and TRUST-worthy data repository, MPD accepts phenotype and genotype data from mouse experiments and curates, organizes, integrates, archives, and distributes those data using community standards. Data are accompanied by rich metadata, including widely used ontologies and detailed protocols. Data are from all over the world and represent genetic, behavioral, morphological, and physiological disease-related characteristics in mice at baseline or those exposed to drugs or other treatments. MPD houses data from over 6000 strains and populations, representing many reproducible strain types and heterogenous populations such as the Diversity Outbred where each mouse is unique but can be genotyped throughout the genome. A suite of analysis tools is available to aggregate, visualize, and analyze these data within and across studies and populations in an increasingly traceable and reproducible manner. We have refined existing resources and developed new tools to continue to provide users with access to consistent, high-quality data that has translational relevance in a modernized infrastructure that enables interaction with a suite of bioinformatics analytic and data services.
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Bases de Dados Genéticas , Fenômica , Camundongos , Animais , Camundongos Endogâmicos , Fenótipo , GenótipoRESUMO
Trust propensity (TP) relies more on social than economic rationality to transform the perceived probability of betrayal into positive reciprocity expectations in older adults with normal cognition. While deficits in social rationality have been observed in older adults with mild cognitive impairment (MCI), there is limited research on TP and its associated resting-state functional connectivity (RSFC) mechanisms in this population. To measure TP and related psychological functions (affect, motivation, executive cognition, and social cognition), MCI (n = 42) and normal healthy control (NHC, n = 115) groups completed a one-shot trust game and additional assessments of related psychological functions. RSFC associated with TP was analyzed using connectome-based predictive modeling (CPM) and lesion simulations. Our behavioral results showed that the MCI group trusted less (i.e., had lower TP) than the NHC group, with lower TP associated with higher sensitivity to the probability of betrayal in the MCI group. In the MCI group, only negative CPM models (RSFC negatively correlated with TP) significantly predicted TP, with a high salience network (SN) contribution. In contrast, in the NHC group, positive CPM models (RSFC positively correlated with TP) significantly predicted TP, with a high contribution from the default mode network (DMN). In addition, the total network strength of the NHC-specific positive network was lower in the MCI group than in the NHC group. Our findings demonstrated a decrease in TP in the MCI group compared to the NHC group, which is associated with deficits in social rationality (social cognition, associated with DMN) and increased sensitivity to betrayal (affect, associated with SN) in a trust dilemma. In conclusion, our study contributes to understanding MCI-related alterations in trust and their underlying neural mechanisms.
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Disfunção Cognitiva , Conectoma , Imageamento por Ressonância Magnética , Confiança , Humanos , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Masculino , Idoso , Conectoma/métodos , Feminino , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologiaRESUMO
During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.
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Doenças dos Peixes , Peixes , Yersiniose , Yersinia ruckeri , Yersiniose/veterinária , Yersiniose/microbiologia , Yersiniose/epidemiologia , Animais , China/epidemiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/epidemiologia , Yersinia ruckeri/genética , Peixes/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Farmacorresistência BacterianaRESUMO
The emerging field of nanoscale infrared (nano-IR) offers label-free molecular contrast, yet its imaging speed is limited by point-by-point traverse acquisition of a three-dimensional (3D) data cube. Here, we develop a spatial-spectral network (SS-Net), a miniaturized deep-learning model, together with compressive sampling to accelerate the nano-IR imaging. The compressive sampling is performed in both the spatial and spectral domains to accelerate the imaging process. The SS-Net is trained to learn the mapping from small nano-IR image patches to the corresponding spectra. With this elaborated mapping strategy, the training can be finished quickly within several minutes using the subsampled data, eliminating the need for a large-labeled dataset of common deep learning methods. We also designed an efficient loss function, which incorporates the image and spectral similarity to enhance the training. We first validate the SS-Net on an open stimulated Raman-scattering dataset; the results exhibit the potential of 10-fold imaging speed improvement with state-of-the-art performance. We then demonstrate the versatility of this approach on atomic force microscopy infrared (AFM-IR) microscopy with 7-fold imaging speed improvement, even on nanoscale Fourier transform infrared (nano-FTIR) microscopy with up to 261.6 folds faster imaging speed. We further showcase the generalization of this method on AFM-force volume-based multiparametric nanoimaging. This method establishes a paradigm for rapid nano-IR imaging, opening new possibilities for cutting-edge research in materials, photonics, and beyond.
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PURPOSE: Air leaks are common after pulmonary surgery. Prolonged air leaks (PALs) may persist through discharge and often are managed with one-way valve devices (OWD). We sought to determine the course and complications of patients discharged with OWDs, risk factors for complications, and to evaluate the utility of clamp trials before chest tube (CT) removal. METHODS: Single-institution, retrospective review of patients discharged with a OWD after pulmonary surgery between 2008 and 2022. Charts were examined for the presence of complications and CT duration. Differences in CT duration were compared by using the Wilcoxon rank-sum test. RESULT: Sixty-four of 1917 (3.3%) pulmonary surgeries resulted in OWD use. Twelve of 64 (19%) patients discharged with a OWD suffered a complication. Nine of 64 (14%) had a CT-related readmission, and seven of 64 (11%) required PAL intervention. Patients sustaining a complication demonstrated longer CT durations before complication compared with duration in patients without complications, with median days of 13 [IQR 6-21] vs. 7 [IQR 6-12], p = 0.04). Five (7.8%) OWD patients developed an empyema; only one (20%) occurred before a CT duration of 14 days. Sixteen of 64 (25%) patients underwent a clamp trial before CT removal. One of ten (10%) failed even with no air leak present, whereas one of six (17%) failed with a present/questionable air leak. CONCLUSIONS: One-way valve device use has a substantial complication rate, and chest tube duration is a risk factor. In-hospital interventions might benefit patients with larger leaks that likely require prolonged OWD use. Because clamp trials occasionally fail, we contend that a clamp trial is the safest course before CT removal.
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Tubos Torácicos , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Masculino , Feminino , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Idoso , Seguimentos , Pneumotórax/etiologia , Pneumotórax/terapia , Prognóstico , Neoplasias Pulmonares/cirurgia , Fatores de Risco , Procedimentos Cirúrgicos Pulmonares/efeitos adversos , Procedimentos Cirúrgicos Pulmonares/métodos , Pacientes Ambulatoriais , Pneumonectomia/efeitos adversosRESUMO
BACKGROUND: Choosing the appropriate treatment for elderly patients with esophageal cancer remains a contentious issue. While surgery is still a valid option, we aimed to identify predictors and outcomes in elderly esophagectomy patients with esophageal cancer. PATIENTS AND METHODS: We analyzed characteristics, surgical outcomes, survival rates, cause-specific mortality, and recurrence in 120 patients with stage I-IV esophageal cancer. Univariate and multivariate analyses were used to identify risk factors for event-free survival (EFS) and overall survival (OS). RESULTS: The median follow-up period was 31 months, with 5-year overall survival (OS) and event-free survival (EFS) rates standing at 45.2% and 41.5%, respectively. Notably, lower body mass index (BMI ≤ 22 kg/m2) and reduced preoperative albumin levels (pre-ALB < 40 g/L) led to a significant decrease in OS rates. Postoperative pulmonary complications resulted in higher in-hospital and 90-day mortality rates. After about 31 months post-surgery, the rate of cancer-specific deaths stabilized. The most common sites for distant metastasis were the lungs, supraclavicular lymph nodes, liver, and bone. The study identified lower BMI, lower pre-ALB levels, and postoperative pulmonary complications as independent risk factors for poorer EFS and OS outcomes. CONCLUSIONS: Esophagectomy remains a safe and feasible treatment for elderly patients, though the prevention of postoperative pulmonary infection is crucial. Factors such as lower BMI, lower pre-ALB levels, advanced tumor stage, postoperative pulmonary complications, and certain treatment modalities significantly influence the outcomes in elderly esophagectomy patients. These findings provide critical insights into the characteristics and outcomes of this patient population.
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Neoplasias Esofágicas , Esofagectomia , Humanos , Idoso , Prognóstico , Esofagectomia/métodos , Estadiamento de Neoplasias , Neoplasias Esofágicas/patologia , Linfonodos/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Complicações Pós-Operatórias/patologiaRESUMO
BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.
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Neoplasias Pulmonares , Estadiamento de Neoplasias , Programa de SEER , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Feminino , Carcinoma de Pequenas Células do Pulmão/cirurgia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Pessoa de Meia-Idade , Masculino , Taxa de Sobrevida , Idoso , Prognóstico , Seguimentos , Pneumonectomia/mortalidade , Estudos de CoortesRESUMO
BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.
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Doença da Artéria Coronariana , Diabetes Mellitus , Hiperglicemia , Humanos , Feminino , Idoso , Masculino , Doença da Artéria Coronariana/diagnóstico , Estudos Retrospectivos , Glicemia/análise , Fatores de RiscoRESUMO
INTRODUCTION: Vascular prosthetic grafts are widely used in vascular surgery; however, graft infection remains a major concern. Silver-coated vascular grafts have demonstrated anti-infection properties in clinical settings; however, whether the silver irons influence foreign body reaction or neointimal hyperplasia remains unclear. METHODS: Sodium alginate and hyaluronic acid (SA/HA) hydrogel patches loaded with rhodamine, with or without silver, were fabricated. Patches were implanted in the subcutaneous or abdominal cavity and inferior vena cava of rats. Samples were harvested on day 14 and examined via immunohistochemical and immunofluorescence analyses. RESULTS: Silver hydrogel was found to decrease the foreign body reaction; after subcutaneous and abdominal cavity implantation in rats, the capsule was found to be thinner in the silver hydrogel group than in the control hydrogel group. The silver hydrogel group had fewer CD68-positive cells and proliferating cell nuclear antigen and interleukin-33 (IL-33) dual-positive cells than the control hydrogel group. Additionally, the silver hydrogel patch reduced the neointimal thickness after patch venoplasty in rats, and the number of IL-33- and IL-1ß-positive cells was lower than that in the control patch. CONCLUSION: Silver-loaded SA/HA hydrogel patches decreased the foreign body reaction and venous neointimal hyperplasia in rats by the inhibition of IL-33 expression.
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Interleucina-33 , Prata , Ratos , Animais , Hiperplasia , Neointima , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/prevenção & controle , HidrogéisRESUMO
Patients with castration-resistant prostate cancer inevitably acquire resistance to antiandrogen therapies in part because of androgen receptor (AR) mutations or splice variants enabling restored AR signaling. Here we show that ligand-activated AR can form transcriptionally active condensates. Both structured and unstructured regions of AR contribute to the effective phase separation of AR and disordered N-terminal domain plays a predominant role. AR liquid-liquid phase separation behaviors faithfully report transcriptional activity and antiandrogen efficacy. Antiandrogens can promote phase separation and transcriptional activity of AR-resistant mutants in a ligand-independent manner. We conducted a phase-separation-based phenotypic screen and identified ET516 that specifically disrupts AR condensates, effectively suppresses AR transcriptional activity and inhibits the proliferation and tumor growth of prostate cancer cells expressing AR-resistant mutants. Our results demonstrate liquid-liquid phase separation as an emerging mechanism underlying drug resistance and show that targeting phase separation may provide a feasible approach for drug discovery.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Receptores Androgênicos/genética , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Ligantes , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
Carboxymethyl Salix psammophila wood powder-imprinted membranes (CMSM-MIPs) were prepared by using wet spinning technology and molecular-imprinting technology for the selective removal of tetracycline from wastewater. Scanning electron microscopy, X-ray diffraction, thermogravimetry, and X-ray photoelectron spectroscopy characterizations demonstrate that CMSM-MIPs retain the membranous structure of Carboxymethyl Salix psammophila wood powder membranes, successfully encapsulate thin layers of imprinted polymers on the membrane surface, and exhibit excellent thermal stability. The adsorption results showed that CMSM-MIPs had the highest selective adsorption capacity for tetracycline, which was 253.8 mg/g. In addition, the adsorption capacities for oxytetracycline and chlortetracycline were 208.8 and 188 mg/g, respectively. It can be observed that CMSM-MIPs not only exhibit a high adsorption capacity for tetracycline but also demonstrate good adsorption capacities for oxytetracycline and chlortetracycline. The experimental results showed that CMSM-MIPs were best fitted with pseudo-second-order kinetics and most consistent with Freundlich fitting. The regeneration experiment showed that CMSM-MIPs still had good regeneration performance after 5 regeneration cycles. In conclusion, the CMSM-MIPs can not only have the natural adsorption performance of Salix psammophila wood powder but also give it higher selectivity through molecular imprinting, so as to achieve efficient removal of target organic pollutants in water.
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Salix , Tetraciclina , Madeira , Adsorção , Madeira/química , Tetraciclina/química , Tetraciclina/isolamento & purificação , Salix/química , Pós/química , Membranas Artificiais , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Impressão Molecular/métodos , Antibacterianos/química , Antibacterianos/isolamento & purificaçãoRESUMO
Decay-accelerating factor (DAF) is an essential member of the complement regulatory protein family that plays an important role in immune response and host homeostasis in mammals. However, the immune function of DAF has not been well characterized in bony fish. In this study, a complement regulatory protein named CiDAF was firstly characterized from Ctenopharyngodon idella and its potential roles were investigated in intestine following bacterial infection. Similar to mammalian DAFs, CiDAF has multiple complement control protein (CCP) functional domains, suggesting the evolutionary conservation of DAFs. CiDAF was broadly expressed in all tested tissues, with a relatively high expression level detected in the spleen and kidney. In vivo immune challenge experiments revealed that CiDAF strongly responded to bacterial pathogens (Aeromonas hydrophila and Aeromonas veronii) and PAMPs (lipopolysaccharide (LPS) or muramyl dipeptide (MDP)) challenges. In vitro RNAi experiments indicated that knockdown of CiDAF could upregulate the expression of complement genes (C4b, C5 and C7) and inflammatory cytokines (TNF-α, IL-1ß and IL-8). Moreover, 2000 ng/mL of CiDAF agonist progesterone effectively alleviated LPS- or MDP-induced intestinal inflammation by regulating expression of complement factors, TLR/PepT1 pathway genes and inflammatory cytokines. Overall, these findings revealed that CiDAF may act as a negative regulator of intestinal complement pathway and immune response to bacterial challenge in grass carp.
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Carpas , Doenças dos Peixes , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas , Imunidade Inata , Intestinos , Animais , Carpas/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata/genética , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Intestinos/imunologia , Regulação da Expressão Gênica/imunologia , Filogenia , Perfilação da Expressão Gênica/veterinária , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Alinhamento de Sequência/veterinária , Proteínas do Sistema Complemento/imunologiaRESUMO
The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired by electronegative redox reactions, we designed a nitrogen-oxygen rich pyrazine connected COF (TQY-COF) with multiple redox sites as a platform for extracting uranium via combining superaffinity and enhanced photoinduction. The preorganized bisnitrogen-bisoxygen donor configuration on TQY-COF is entirely matched with the typical geometric coordination of hexavalent uranyl ions, which demonstrates high affinity (tetra-coordination). In addition, the presence of the carbonyl group and pyrazine ring effectively stores and controls electron flow, which efficaciously facilitates the separation of e-/h+ and enhances photocatalytic performance. The experimental results show that TQY-COF removes up to 99.8% of uranyl ions from actual uranium mine wastewater under the light conditions without a sacrificial agent, and the separation coefficient reaches 1.73 × 106 mL g-1 in the presence of multiple metal ions, which realizes the precise separation in the complex environment. Importantly, DFT calculations further elucidate the coordination mechanism of uranium and demonstrate the necessity of the presence of N/O atoms in the photocatalytic adsorption of uranium.
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Oxygen vacancies and heteroatom doping play important role in oxygen reduction activity of metal oxides. Developing efficient modification method is one of the key issues in catalysts research. Room temperature plasma treatment, with the advantages of mild working conditions, no emissions and high efficiency, is a new catalyst modification method developed in recent years. In this work, hydrothermal synthesizedα-MnO2nanorods are treated in NH3plasma at room temperature. In the reducing atmosphere, oxygen vacancies and N doping are achieved simultaneously on the surface. The NH3plasma etched MnO2demonstrate a significant enhanced oxygen reduction activity with half-wave potential of 0.84 V, limiting current density of 6.32 mA cm-2and transferred electrons number of 3.9. The Mg-air battery with N-MnO2display a maximum power density of 76.3 mW cm-2as well as stable discharge performance. This work provides new ideas for preparing efficient and cost-effective method to boost the catalysts activity.
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Liver is an important metabolic organ in human body and is sensitive to toxic chemicals or drugs. Adverse reactions caused by drug hepatotoxicity will damage the liver and hepatotoxicity is the leading cause of removal of approved drugs from the market. Therefore, it is of great significance to identify liver toxicity as early as possible in the drug development process. In this study, we developed a predictive model for drug hepatotoxicity based on histopathological whole slide images (WSI) which are the by-product of drug experiments and have received little attention. To better represent the WSIs, we constructed a graph representation for each WSI by dividing it into small patches, taking sampled patches as nodes and calculating the correlation coefficients between node features as the edges of the graph structure. Then a WSI-level graph convolutional network (GCN) was built to effectively extract the node information of the graph and predict the toxicity. In addition, we introduced a gated attention global context vector (gaGCV) to combine the global context to make node features to contain more comprehensive information. The results validated on rat liver in vivo data from the Open TG-GATES show that the use of WSI for the prediction of toxicity is feasible and effective.