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Precise identification and quantification of amino acids is crucial for many biological applications. Here we report a copper(II)-functionalized Mycobacterium smegmatis porin A (MspA) nanopore with the N91H substitution, which enables direct identification of all 20 proteinogenic amino acids when combined with a machine-learning algorithm. The validation accuracy reaches 99.1%, with 30.9% signal recovery. The feasibility of ultrasensitive quantification of amino acids was also demonstrated at the nanomolar range. Furthermore, the capability of this system for real-time analyses of two representative post-translational modifications (PTMs), one unnatural amino acid and ten synthetic peptides using exopeptidases, including clinically relevant peptides associated with Alzheimer's disease and cancer neoantigens, was demonstrated. Notably, our strategy successfully distinguishes peptides with only one amino acid difference from the hydrolysate and provides the possibility to infer the peptide sequence.
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Nanoporos , Aminoácidos/química , Peptídeos/química , Sequência de Aminoácidos , Porinas/química , Porinas/metabolismoRESUMO
CRISPR-Cas systems with dual functions offer precise sequence-based recognition and efficient catalytic cleavage of nucleic acids, making them highly promising in biosensing and diagnostic technologies. However, current methods encounter challenges of complexity, low turnover efficiency, and the necessity for sophisticated probe design. To better integrate the dual functions of Cas proteins, we proposed a novel approach called CRISPR-Cas Autocatalysis Amplification driven by LNA-modified Split Activators (CALSA) for the highly efficient detection of single-stranded DNA (ssDNA) and genomic DNA. By introducing split ssDNA activators and the site-directed trans-cleavage mediated by LNA modifications, an autocatalysis-driven positive feedback loop of nucleic acids based on the LbCas12a system was constructed. Consequently, CALSA enabled one-pot and real-time detection of genomic DNA and cell-free DNA (cfDNA) from different tumor cell lines. Notably, CALSA achieved high sensitivity, single-base specificity, and remarkably short reaction times. Due to the high programmability of nucleic acid circuits, these results highlighted the immense potential of CALSA as a powerful tool for cascade signal amplification. Moreover, the sensitivity and specificity further emphasized the value of CALSA in biosensing and diagnostics, opening avenues for future clinical applications.
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Técnicas Biossensoriais , Sistemas CRISPR-Cas , DNA de Cadeia Simples , Oligonucleotídeos , Humanos , Oligonucleotídeos/química , Oligonucleotídeos/genética , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/química , Técnicas Biossensoriais/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , DNA/química , DNA/genética , Linhagem Celular Tumoral , CatáliseRESUMO
Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.
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Lesão Pulmonar , Pancreatite , Masculino , Camundongos , Animais , Receptor Toll-Like 9/metabolismo , Doença Aguda , NF-kappa B/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismoRESUMO
BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics. METHODS: We screened SALL1 and DACT1 variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS. RESULTS: We identified five novel and two reported pathogenic/likely pathogenic (P/LP) SALL1 variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between SALL1 variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring. CONCLUSION: This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.
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Anormalidades Múltiplas , Anus Imperfurado , Perda Auditiva Neurossensorial , Polegar/anormalidades , Fatores de Transcrição , Humanos , Mutação , Fatores de Transcrição/genética , Síndrome , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Fenótipo , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal/genéticaRESUMO
Plasmodium falciparum, the deadliest causal agent of malaria, caused more than half of the 229 million malaria cases worldwide in 2019. The emergence and spreading of frontline drug-resistant Plasmodium strains are challenging to overcome in the battle against malaria and raise urgent demands for novel antimalarial agents. The P. falciparum formate-nitrite transporter (PfFNT) is a potential drug target due to its housekeeping role in lactate efflux during the intraerythrocytic stage. Targeting PfFNT, MMV007839 was identified as a lead compound that kills parasites at submicromolar concentrations. Here, we present 2 cryogenic-electron microscopy (cryo-EM) structures of PfFNT, one with the protein in its apo form and one with it in complex with MMV007839, both at 2.3 Å resolution. Benefiting from the high-resolution structures, our study provides the molecular basis for both the lactate transport of PfFNT and the inhibition mechanism of MMV007839, which facilitates further antimalarial drug design.
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Antimaláricos/química , Antimaláricos/farmacologia , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Microscopia Crioeletrônica , Formiatos , Ácido Láctico/metabolismo , Malária Falciparum , Transportadores de Ácidos Monocarboxílicos/química , Nitritos , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Relação Estrutura-AtividadeRESUMO
Peptide detection methods with facility and high sensitivity are essential for diagnosing disease associated with peptide biomarkers. Nanopore sensing technology had emerged as a low cost, high-throughput, and scalable tool for peptide detection. The omptins family proteins which can form ß-barrel pores have great potentials to be developed as nanopore biosensor. However, there are no study about the channel properties of E. coli OmpT and the development of OmpT as a nanopore biosensor. In this study, the OmpT biological nanopore channel was constructed with a conductance of 1.49 nS in 500 mM NaCl buffer and a three-step gating phenomenon under negative voltage higher than 100 mV and then was developed as a peptide biosensor which can detect peptide without the interfere of ssDNA and dNTPs. The OmpT constructed in this study has potential application in peptide detection, and also provides a new idea for the detection of peptides using the specific binding ability of protease.
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Proteínas de Escherichia coli , Nanoporos , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Peptídeos/metabolismoRESUMO
PURPOSE: To develop a model to identify risk factors and predictors of acute pancreatitis in children with pancreaticobiliary maljunction (PBM). METHODS: We screened consecutive PBM patients treated at two centers between January, 2015 and July, 2021. For machine learning, the cohort was divided randomly at a 6:4 ratio to a training dataset and a validation dataset. Three parallel models were developed using logistic regression (LR), a support vector machine (SVM), and extreme gradient boosting (XGBoost), respectively. Model performance was judged primarily based on the area under the receiver operating curves (AUC). RESULTS: A total of 99 patients were included in the analysis, 17 of whom suffered acute pancreatitis and 82 did not. The XGBoost (AUC = 0.814) and SVM (AUC = 0.813) models produced similar performance in the validation dataset; both outperformed the LR model (AUC = 0.805). Based on the SHapley Additive exPlanation values, the most important variable in both the XGBoost and SVM models were age, protein plugs, and white blood cell count. CONCLUSIONS: Machine learning models, especially XGBoost and SVM, could be used to predict acute pancreatitis in children with PBM. The most important contributing factor to the models were age, protein plugs, and white blood cell count.
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Má Junção Pancreaticobiliar , Pancreatite , Criança , Humanos , Doença Aguda , Aprendizado de Máquina , Fatores de RiscoRESUMO
Biological nanopores are proteins with transmembrane pore that can be embedded in lipid bilayer. With the development of single-channel current measurement technologies, biological nanopores have been reconstituted into planar lipid bilayer and used for single-molecule sensing of various analytes and events such as single-molecule DNA sensing and sequencing. To improve the sensitivity for specific analytes, various engineered nanopore proteins and strategies are deployed. Here, we introduce the origin and principle of nanopore sensing technology as well as the structure and associated properties of frequently used protein nanopores. Furthermore, sensing strategies for different applications are reviewed, with focus on the alteration of buffer condition, protein engineering, and deployment of accessory proteins and adapter-assisted sensing. Finally, outlooks for de novo design of nanopore and nanopore beyond sensing are discussed.
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Nanoporos , DNA/química , Bicamadas Lipídicas/química , Proteínas/químicaRESUMO
The quantum-classical coexistence can be implemented based on wavelength division multiplexing (WDM), but due to Raman noise, the wavelength spacing between quantum and classical signals and launch power from classical channels are restricted. Space division multiplexing (SDM) can now be availably achieved by multicore fiber (MCF) to reduce Raman noise, thereby loosening the restriction for coexistence in the same band and obtaining a high communication capacity. In this paper, we realize the quantum-classical coexistence over a 7-core MCF. Based on the SDM, the highest launch power of 25 dBm is achieved which has been extended nearly 19 times in previous work. Moreover, both the quantum and classical channels are allocated in the C-band and the minimum wavelength spacing between them is only 1.6 nm. The coexistence system eliminates the need for adding a narrowband filter.
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OBJECTIVES: To implement a pipeline to automatically segment the ROI and to use a nomogram integrating the MRI-based radiomics score and clinical variables to predict responses to neoadjuvant chemotherapy (NAC) in osteosarcoma patients. METHODS: A total of 144 osteosarcoma patients treated with NAC were separated into training (n = 101) and test (n = 43) groups. After normalisation, ROIs for the preoperative MRI were segmented by a deep learning segmentation model trained with nnU-Net by using two independent manual segmentations as labels. Radiomics features were extracted using automatically segmented ROIs. Feature selection was performed in the training dataset by five-fold cross-validation. The clinical, radiomics, and clinical-radiomics models were built using multiple machine learning methods with the same training dataset and validated with the same test dataset. The segmentation model was evaluated by the Dice coefficient. AUC and decision curve analysis (DCA) were employed to illustrate the model performance and clinical utility. RESULTS: 36/144 (25.0%) patients were pathological good responders (pGRs) to NAC, while 108/144 (75.0%) were non-pGRs. The segmentation model achieved a Dice coefficient of 0.869 on the test dataset. The clinical and radiomics models reached AUCs of 0.636 with a 95% confidence interval (CI) of 0.427-0.860 and 0.759 (95% CI, 0.589-0.937), respectively, in the test dataset. The clinical-radiomics nomogram demonstrated good discrimination, with an AUC of 0.793 (95% CI, 0.610-0.975), and accuracy of 79.1%. The DCA suggested the clinical utility of the nomogram. CONCLUSION: The automatic nomogram could be applied to aid radiologists in identifying pGRs to NAC. KEY POINTS: ⢠The nnU-Net trained by manual labels enables the use of an automatic segmentation tool for ROI delineation of osteosarcoma. ⢠A pipeline using automatic lesion segmentation and followed by a radiomics classifier could aid the evaluation of NAC response of osteosarcoma. ⢠A predictive nomogram composed of clinical variables and MRI-based radiomics score provides support for individualised treatment planning.
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Neoplasias Ósseas , Aprendizado Profundo , Osteossarcoma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante , Nomogramas , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Estudos RetrospectivosRESUMO
The coronavirus disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is spreading around the world,while the specific drugs targeting SARS-CoV-2 are still under development.On the basis of the biological characteristics of SARS-CoV-2 and the key protein(spike protein) for viral replication,this paper introduces the research progress in the action sites of related drugs,providing information for clinical application and ideas for development of anti-SARS-CoV-2 drugs.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
The demand for the integration of quantum key distribution (QKD) and classical optical communication in the same optical fiber medium greatly increases as fiber resources and the flexibility of practical applications are taken into consideration. To satisfy the needs of the mass deployment of ultra-high power required for classical optical networks integrating QKD, we implement the discrete variable quantum key distribution (DV-QKD) under up to 25 dBm launch power from classical channels over 75 km on an ultra-low-loss (ULL) fiber by combining a finite-key security analysis method with the noise model of classical signals. To the best of our knowledge, this is the highest power launched by classical signals on the coexistence of DV-QKD and classical communication. The results exhibit the feasibility and tolerance of our QKD system for use in ultra-high-power classical communications.
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There is an increasing demand for multiplexing of quantum key distribution with optical communications in single fiber in consideration of high costs and practical applications in the metropolitan optical network. Here, we realize the integration of quantum key distribution and an optical transport network of 80 Gbps classical data at 15 dBm launch power over 50 km of the widely used standard (G.652 Recommendation of the International Telecom Union Telecom Standardization Sector) telecom fiber. A secure key rate of 11 Kbps over 20 km is obtained. By tolerating a high classical optical power up to 18 dBm of 160 Gbps classical data on single-mode fiber, our result shows the potential and tolerance of quantum key distribution being used in future large capacity transmission systems, such as metropolitan area networks and data centers. The quantum key distribution system is stable, practical, and insensitive to the polarization disturbance of channels by using a phase coding system based on a Faraday-Michelson interferometer. We also discuss the fundamental limit for quantum key distribution performance in the multiplexing environment.
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The "spot sign" is a well-known radiological marker used for predicting hematoma expansion and clinical outcomes in patients with intracerebral hemorrhage (ICH). We performed a meta-analysis to assess the predictive accuracy of spot sign, depending on the criteria used to identify them.We conducted a systematic review of clinical studies that clearly stated their definition of spot sign and that were indexed in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure databases. We collected data on computed tomography (CT) parameters, spot sign diagnostic criteria, hematoma expansion, and clinical outcomes.Based on the eligibility criteria, we included 17 studies in this systematic review. CT imaging modality, type, time from symptom onset to CT, time from contrast infusion to scan, slice thickness, tube current, and tube electric discharge showed variation across studies. Three different definitions of the spot sign were applied: (1) a hyperdense spot within the hematoma; (2) one or more focal areas/regions of contrast pooling of any size and morphology that occurred within a hemorrhage, were discontinuous from the normal or abnormal vasculature adjacent to the hemorrhage, and showed an attenuation rate ≥ 120 UH; or (3) serpiginous or spot-like contrast density on CTA images that occurred within the hematoma margin, showed twice the density of the hematoma background, and did not contact vessels outside the hematoma. Three definitions for the spot sign were identified, all of which were associated with hematoma expansion, mortality, and unfavorable functional outcome. Subgroup analyses based on these definitions showed that spot sign identified using the second definition were more likely to be associated with hematoma expansion (OR 18.31, 95% CI 9.11-36.8) and unfavorable functional outcomes (OR 8.78, 95% CI 3.24-23.79), while those identified using the third definition were associated with increased risk of mortality (OR 6.88, 95% CI 1.43-33.13).Clinical studies identify spot sign using different CT protocols and criteria. These differences affect the ability of spot sign to predict hematoma expansion and clinical outcomes in ICH patients.
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Hemorragia Cerebral , Hematoma , Angiografia Cerebral , Hemorragia Cerebral/diagnóstico por imagem , Bases de Dados Factuais , Hematoma/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios XRESUMO
Human immunodeficiency virus (HIV) infection inflicts significant economic and social burdens on many countries worldwide. Given the substantial morbidity and mortality from HIV infection, there is an urgent need for accurate and early detection of the virus. In this study, immunofluorescence and visual techniques are described that detect the HIV-1 p24 antigen, which relied on selective recognition of Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+ using cadmium telluride quantum dots (CdTe QDs). After the sandwich immunoreactions were accomplished, the alkaline phosphatase (ALP) hydrolyzed L-ascorbic acid 2-phosphate (AAP) to form ascorbic acid (AA) that further reduces Ag+ and Cu2+ to Ag NPs and Cu+, respectively. This method was highly sensitive and selective and could detect as low as 1 pg/mL of p24 antigen by naked eyes and had a good linearity in the concentration range 1-100 pg/mL. When using Ag+ and Cu2+ as media, the limit of detection (LOD) of the new method was 0.3 pg/mL and 0.2 pg/mL, respectively. Compared with clinical electrochemiluminescence immunoassay (ECLIA) results and clinical data, this method demonstrated good consistency for the quantification of HIV-1 p24 antigen in 34 clinical serum samples. In addition, this method could accurately distinguish HIV from other viruses and infections such as hepatitis B virus, systemic lupus erythematosus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, lipemia, and hemolysis. Therefore, our dual-mode analysis method may provide additional solutions to identify clinical HIV infection. An immunofluorescence and visualization dual-mode strategy for the detection of p24 antigen was constructed based on immune recognition reaction and a phenomenon that cadmium telluride quantum dots (CdTe QDs) can selectively recognize Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+.
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Compostos de Cádmio/química , Proteína do Núcleo p24 do HIV/metabolismo , HIV-1/metabolismo , Imunoensaio/métodos , Telúrio/química , Fluorescência , HumanosRESUMO
OBJECTIVE: To explore the efficacy and mechanism of using 3-n-butylphthalide (NBP) in combination with bone marrow mesenchymal stem cells (BMSCs) in the treatment of experimental autoimmune encephalomyelitis (EAE) in mice. METHODS: Myelin oligodendrocyte glycoprotein (MOG35-55) was used for the induction and establishment of the EAE model in C57BL/6 mice. The mice were randomly assigned to the EAE group, which received intraperitoneal injection of phosphate-buffered saline (PBS), the NBP-treated EAE group, or the NBP group, which received intraperitoneal injection of NBP, the BMSCs transplantion EAE group, or the BMSCs group, which received BMSCs injected into the lateral ventricle and intraperitoneal injection of PBS, and the BMSCs and NBP combination treatment EAE group, or the BMSCs+NBP group, which received BMSCs injected into the lateral ventricle and intraperitoneal injection of NBP. Each group had 10 mice, while ten normal mice were used as the blank control group receiving intraperitoneal injection of PBS. The neurological function scores were documented daily. The mice were sacrificed 22 days after EAE induction, and the demyelination state of of the spinal cords was observed through Luxol fast blue (LFB) staining. In addition, the levels of serum interleukin-6 (IL-6), IL-10, IL-17, IL-22 and transforming growth factor-ß (TGF-ß) were examined with ELISA. The levels of glial fibrillary acidic protein (GFAP), microtubule associated protein-2 (MAP-2) and myelin basic protein (MBP) in the brain were examined with immunofluorescence staining. Western blot was used to check the expressions of nuclear factor (NF)-κB pathway, phosphoinositide-3 kinase (PI3K)/protein kinase B (PKB or Akt) pathway, IL-17 and forkhead box P3 (Foxp3) in the spinal cords. RESULTS: The neurological function scores and average scores of each treatment group were significantly lower than those of the EAE group ( P<0.05). The scores of the BMSCs+NBP group decreased more significantly than those of the single treatment groups (the NBP group and the BMSCs group) ( P<0.05). LFB staining results of the spinal cords were consistent with the neurological function scores and the average scores. Compared with the EAE group, the levels of pro-inflammatory cytokines, including IL-6, IL-17 and IL-22, significantly decreased ( P<0.05), and the levels of anti-inflammatory cytokines IL-10 and TGF-ß significantly increased ( P<0.05). The change in cytokine expression was more significant in the BMSCs+NBP group ( P<0.05). The expressions of GFAP, MAP-2 and MBP in the BMSCs+NBP group were significantly higher than those of the BMSCs group ( P<0.05). Compared with the EAE group, the p-NF-κB/NF-κB ratio and the IL-17/Foxp3 ratio in NBP group, BMSCs group and BMSCs+NBP group decreased, while P-IκBα/IκBα, p-pI3k/PI3K and P-Akt/Akt ratios increased, especially in the BMSCs+NBP group( P<0.05). CONCLUSION: The combined treatment of NBP and BMSCs can help alleviate the symptoms of EAE model mice, showing better efficacy than treatment with NBP or BMSCs alone. The mechanism is related to the inhibition of the NF-κB pathway to regulate Th17/Foxp3 ratio and the activation of the PI3K/Akt pathway to promote the neurogenic differentiation of BMSCs.
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Encefalomielite Autoimune Experimental , Células-Tronco Mesenquimais , Animais , Benzofuranos , Encefalomielite Autoimune Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-QuinasesRESUMO
We investigate quantum random number generation based on backward spontaneous Raman scattering in standard single-mode fiber, where the randomness of photon wavelength superposition and arrival time is simultaneously utilized. The experiment uses four avalanche photodiodes working in gated Geiger mode to detect backward Raman scattering photons from four different wavelength channels and a time-to-digital converter placed behind the detectors to record their arrival time. Both information of the wavelength and arrival time interval of photons from different channels are applied to generate random bits. Due to the independence of these two entropy sources, the random number resource of the present system is fully utilized. Five-bit raw data can be obtained for every effective click, which contains 2.87-bit min-entropy. To obtain the optimal generation rate of random bits, appropriate pump power and fiber length are adopted. The post-processing method by the SHA-256 hashing algorithm is used to remove the bias of the raw data, after which the final random bit sequences pass the NIST statistical test.
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There is much interest in developing synthetic analogues of biological membrane channels with high efficiency and exquisite selectivity for transporting ions and molecules. Bottom-up and top-down methods can produce nanopores of a size comparable to that of endogenous protein channels, but replicating their affinity and transport properties remains challenging. In principle, carbon nanotubes (CNTs) should be an ideal membrane channel platform: they exhibit excellent transport properties and their narrow hydrophobic inner pores mimic structural motifs typical of biological channels. Moreover, simulations predict that CNTs with a length comparable to the thickness of a lipid bilayer membrane can self-insert into the membrane. Functionalized CNTs have indeed been found to penetrate lipid membranes and cell walls, and short tubes have been forced into membranes to create sensors, yet membrane transport applications of short CNTs remain underexplored. Here we show that short CNTs spontaneously insert into lipid bilayers and live cell membranes to form channels that exhibit a unitary conductance of 70-100 picosiemens under physiological conditions. Despite their structural simplicity, these 'CNT porins' transport water, protons, small ions and DNA, stochastically switch between metastable conductance substates, and display characteristic macromolecule-induced ionic current blockades. We also show that local channel and membrane charges can control the conductance and ion selectivity of the CNT porins, thereby establishing these nanopores as a promising biomimetic platform for developing cell interfaces, studying transport in biological channels, and creating stochastic sensors.
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Membrana Celular/química , Membrana Celular/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Nanotubos de Carbono , Porinas/metabolismo , Processos Estocásticos , Animais , Transporte Biológico , Células CHO , Sobrevivência Celular , Cricetulus , DNA/metabolismo , Células HEK293 , Humanos , Canais Iônicos/metabolismo , Lipossomos , Nanotubos de Carbono/ultraestrutura , Porinas/químicaRESUMO
203 road dust samples were conducted across China covering 28 provinces from January to Februaryï¼2016 to comprehensively investigates the occurrence, distribution and human exposure of 21 phthalic esters (PAEs). The concentration of Σ21PAEs in road dust ranged from 2.3 to 531 mg/kg, with a mean concentration of 64.1 ± 57.2 mg/kg. DEHP, DnBP and DiBP were the dominant components accounting for 63.3-97.9% (mean: 92.1%) of the Σ21PAEs. Significant Pearson correlation (r = 0.51, p < 0.0001) between Σ21PAEs concentrations and longitude demonstrated a distinguished geographical trend. Higher concentration of PAEs in sidewalk (SW) and trunk road (TR) may reflect influence of human activities such as shoe wear and traffic load. Significant differences were found among different human activities area (urban commercial, urban residential, and suburbs/rural). For total daily intake of Æ©21PAEs via street dust, children had the highest exposure risk followed by teenagers and adults with the median values of 160.8, 43.6, and 37.7 ng/kg-bw/day, respectively. The maximum exposure risk of PAEs calculated based on measurement and simulation were all far below reference values. The sensitivity analysis results demonstrated that concentrations, ingestion rate (IR) and fraction of PAEs absorbed in the skin (AF) were most important parameters on the assessment of exposure risk of PAEs via street dust. Specific parameters based on China and Chinses population is needed to obtain more reliable exposure risk via street dust.
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Poeira , Ácidos Ftálicos , Adolescente , Adulto , Criança , China , Poeira/análise , Ésteres/análise , Atividades Humanas , Humanos , Ácidos Ftálicos/análise , Ácidos Ftálicos/toxicidade , Medição de RiscoRESUMO
BACKGROUND: Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is an exceedingly rare subtype of low-grade central osteosarcoma (LGCO), accounting for up to 10% of cases and making it difficult to diagnose. CMF-OS is frequently misdiagnosed on a radiological examination and biopsy, even after the initial operation. Its treatment is a controversial issue due to its low-grade classification and actual high-grade behavior. CASE PRESENTATION: We retrospectively reviewed the medical charts of more than 2000 osteosarcoma patients between 2008 and 2019; 11 patients with CMF-OS were identified, of which six patients were treated by our institution with complete clinical characteristics, including treatment and prognosis, radiological and pathological features were reviewed. Three males and three females with a median age of 46 (range 22-56) years were pathologically proven to have CMF-OS. The radiological presentation of CMF-OS is variable, thus radiological misdiagnoses are common. However, one must not ignore a malignant radiologic appearance. The most distinctive pathological feature conferring the diagnosis of CMF-OS is the presence of osteoid production directly by the tumor cells under a chondromyxoid fibroma (CMF)-like background. Differential diagnoses based on comprehensive data from CMF, LGCO, chondrosarcoma (CHS), conventional osteosarcoma (COS), etc., are needed. All patients were treated with an operation and chemotherapy, and one patient received additional radiotherapy. Nevertheless, recurrence and metastasis are common in CMF-OS patients. Relatively invasive biological behavior of CMF-OS is against the low-grade classification of this disease. CONCLUSIONS: It is important to recognize CMF-OS and distinguish it from CMF, CHS, COS and other LGCOs. CMF-OS has a relatively poor prognosis despite its low-grade classification.