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1.
Acc Chem Res ; 56(16): 2225-2240, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37535829

RESUMO

ConspectusCO2 conversion to valuable chemicals is effective at reducing CO2 emissions. We previously proposed valorization strategies and developed efficient catalysts to address thermodynamic stability and kinetic inertness issues related to CO2 conversion. Earlier, we developed molecular capture reagents and catalysts to integrate CO2 capture and conversion, i.e., in situ transformation. Based on the mechanistic understanding of CO2 capture, activation, and transformation at a molecular level, we set out to develop heterogeneous catalysts by incorporating catalytic units into nanomaterials via the immobilization of active molecular catalysts onto nanomaterials and designing nanomaterials with intrinsic catalytic sites.In thermocatalytic CO2 conversion, carbonaceous and metal-organic framework (MOF)-based catalysts were developed for nonreductive and reductive CO2 conversion. Novel Cu- and Zn-based MOFs and carbon-supported Cu catalysts were prepared and successfully applied to the cycloaddition, carboxylation, and carboxylative cyclization reactions with CO2, generating cyclic carbonates, carboxyl acids, and oxazolidinones as respective target products. Reductive conversion of CO2, especially reductive functionalization with CO2, is a promising transformation strategy to produce valuable chemicals, alleviating chemical production that relies on petrochemistry. We explored the hierarchical reductive functionalization of CO2 using organocatalysts and proposed strategies to regulate the CO2 reduction level, triggering heterogeneous catalyst investigation. Introducing multiple active sites into nanomaterials opens possibilities to develop novel CO2 transformation strategies. CO2 capture and in situ conversion were realized with an N-doped carbon-supported Zn complex and MOF materials as CO2 adsorbents and catalysts. These nanomaterial-based catalysts feature high stability and excellent efficiency and act as shape-selective catalysts in some cases due to their unique pore structure.Nanomaterial-based catalysts are also appealing candidates for photocatalytic CO2 reduction (PCO2RR) and electrocatalytic CO2 reduction (ECO2RR), so we developed a series of hybrid photo-/electrocatalysts by incorporating active metal complexes into different matrixes such as porous organic polymers (POPs), metal-organic layers (MOLs), micelles, and conducting polymers. By introducing Re-bipyridine and Fe-porphyrin complexes into POPs and regulating the structure of the polymer chain, catalyst stability and efficiency increased in PCO2RR. PCO2RR in aqueous solution was realized by designing the Re-bipyridine-containing amphiphilic polymer to form micelles in aqueous solution and act as nanoreactors. We prepared MOLs with two different metallic centers, i.e., the Ni-bipyridine site and Ni-O node, to improve the efficiency for PCO2RR due to the synergistic effect of these metal centers. Sulfylphenoxy-decorated cobalt phthalocyanine (CoPc) cross-linked polypyrrole was prepared and used as a cathode, achieving the electrocatalytic transformation of diluted CO2 benefiting from the CO2 adsorption capability of polypyrrole. We fabricated immobilized 4-(t-butyl)-phenoxy cobalt phthalocyanine and Bi-MOF as cathodes to promote the paired electrolysis of CO2 and 5-hydroxymethylfurfural (HMF) and obtained CO2 reductive products and 2,5-furandicarboxylic acid (FDCA) efficiently.

2.
Anticancer Drugs ; 35(1): 93-96, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37449979

RESUMO

Third-generation EGFR-TKIs can be used to treat advanced non-small cell lung cancer patients with T790M resistance mutation induced by first- or second-generation EGFR-TKIs. However, it will also result in drug resistance, and the resistance mechanisms of third-generation EGFR-TKIs are complex. Here we reported a patient diagnosed with advanced lung adenocarcinoma and EGFR positive in September 2016. Following first-line targeted therapy with gefitinib, genetic testing showed EGFR T790M positive, which resulted in a change to osimertinib targeted therapy. In May 2021, troponin and creatinine levels were elevated, and the tumor hyperprogressed to severe lung cancer. Repeated genetic testing revealed that EGFR genotype converted to a non-classical mutation and EGFR T790M turned negative, which caused third-generation EGFR-TKI resistance. As a result, afatinib combined with anlotinib was selected to stabilize the patient's condition. We were inspired by the case that it reflects the significance and necessity of exploring the resistance mechanism and dynamically detecting genetic status throughout the course of treatment, which may help realize individualized precision therapy, and maximize the potential of patient.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Afatinib/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Mutação , Resistencia a Medicamentos Antineoplásicos
3.
Diabetes Obes Metab ; 26(6): 2082-2091, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409633

RESUMO

AIM: The wealth of data generated by continuous glucose monitoring (CGM) provides new opportunities for revealing heterogeneities in patients with type 2 diabetes mellitus (T2DM). We aimed to develop a method using CGM data to discover T2DM subtypes and investigate their relationship with clinical phenotypes and microvascular complications. METHODS: The data from 3119 patients with T2DM who wore blinded CGM at an academic medical centre was collected, and a glucose symbolic pattern (GSP) metric was created that combined knowledge-based temporal abstraction with numerical vectorization. The k-means clustering was applied to GSP to obtain subgroups of patients with T2DM. Clinical characteristics and the presence of diabetic retinopathy and albuminuria were compared among the subgroups. The findings were validated in an independent population comprising 773 patients with T2DM. RESULTS: By using GSP, four subgroups were identified with distinct features in CGM profiles and parameters. Moreover, the clustered subgroups differed significantly in clinical phenotypes, including indices of pancreatic ß-cell function and insulin resistance (all p < .001). After adjusting for confounders, group C (the most insulin resistant) had a significantly higher risk of albuminuria (odds ratio = 1.24, 95% confidence interval: 1.03-1.39) relative to group D, which had the best glucose control. These findings were confirmed in the validation set. CONCLUSION: Subtyping patients with T2DM using CGM data may help identify high-risk patients for microvascular complications and provide insights into the underlying pathophysiology. This method may help refine clinically meaningful stratification of patients with T2DM and inform personalized diabetes care.


Assuntos
Albuminúria , Automonitorização da Glicemia , Glicemia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Glicemia/metabolismo , Glicemia/análise , Albuminúria/sangue , Idoso , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Resistência à Insulina , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Adulto , Monitoramento Contínuo da Glicose
4.
Am J Respir Crit Care Med ; 208(3): 280-289, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37167549

RESUMO

Rationale: Genome-wide association studies have identified common variants of lung cancer. However, the contribution of rare exome-wide variants, especially protein-coding variants, to cancers remains largely unexplored. Objectives: To evaluate the role of human exomes in genetic predisposition to lung cancer. Methods: We performed exome-wide association studies to detect the association of exomes with lung cancer in 30,312 patients and 652,902 control subjects. A scalable and accurate implementation of a generalized mixed model was used to detect the association signals for loss-of-function, missense, and synonymous variants and gene-level sets. Furthermore, we performed association and Bayesian colocalization analyses to evaluate their relationships with intermediate exposures. Measurements and Main Results: We systematically analyzed 216,739 single-nucleotide variants in the human exome. The loss-of-function variants exhibited the most notable effects on lung cancer risk. We identified four novel variants, including two missense variants (rs202197044TET3 [Pmeta (P values of meta-analysis) = 3.60 × 10-8] and rs202187871POT1 [Pmeta = 2.21 × 10-8]) and two synonymous variants (rs7447927TMEM173 [Pmeta = 1.32 × 10-9] and rs140624366ATRN [Pmeta = 2.97 × 10-9]). rs202197044TET3 was significantly associated with emphysema (odds ratio, 3.55; Pfdr = 0.015), whereas rs7447927POT1 was strongly associated with telomere length (ß = 1.08; Pfdr (FDR corrected P value) = 3.76 × 10-53). Functional evidence of expression of quantitative trait loci, splicing quantitative trait loci, and isoform expression was found for the four novel genes. Gene-level association tests identified several novel genes, including POT1 (protection of telomeres 1), RTEL1, BSG, and ZNF232. Conclusions: Our findings provide insights into the genetic architecture of human exomes and their role in lung cancer predisposition.


Assuntos
Exoma , Neoplasias Pulmonares , Humanos , Teorema de Bayes , Exoma/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética
5.
Opt Express ; 31(24): 40190-40201, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041325

RESUMO

Holographic techniques enable precise laser manipulation, but suffer from two considerable limitations: speckle and deterioration of axial distribution. Here, we propose a cylindrical quadratic phase (CQP) method with temporal focusing (TF) to generate speckle-free holographic illumination with high axial resolution. TF-CQP utilizes a superposed cylindrical phase as the initial guess to iteratively optimize phase hologram, realizing speckle-free holographic reconstruction on the target focal plane and eliminating secondary focus on the defocused planes. TF-CQP further disperses defocused beams symmetrically by a blazed grating, placed conjugate to the focal plane, which enhances axial confinement. Simulation and experimental results show that TF-CQP reconstructs speckle-free illumination with arbitrary shapes and <10 µm axial resolution. Compared to TF-GS (Gerchberg-Saxton algorithm), widely used in holographic optogenetics, TF-CQP shows increased uniformity of 200% and improved modulation efficiency of 32.33% for parallel holographic illumination, as well as a 10% increment in axial resolution.

6.
J Org Chem ; 88(8): 4942-4964, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36342846

RESUMO

Carbon dioxide (CO2) is the major greenhouse gas and also an abundant and renewable carbon resource. Therefore, its chemical conversion and utilization are of great attraction for sustainable development. Especially, reductive conversion of CO2 with energy input has become a current hotspot due to its ability to access fuels and various important chemicals. Nowadays, the controllable CO2 hydrogenation to formic acid and alcohols using sustainable H2 resources has been regarded as an appealing solution to hydrogen storage and CO2 accumulation. In addition, photocatalytic CO2 reduction to CO also provides a potential way to utilize this greenhouse gas efficiently. Besides direct CO2 hydrogenation, CO2 reductive functionalization integrates CO2 reduction with subsequent C-X (X = N, S, C, O) bond formation and indirect transformation strategies, enlarging the diverse products derived from CO2 and promoting CO2 reductive conversion into a new stage. In this Perspective, the progress and challenges of CO2 reductive conversion, including hydrogenation, reductive functionalization, photocatalytic reduction, and photocatalytic reductive functionalization are summarized and discussed along with the key issues and future trends/directions in this field. We hope this Perspective can evoke intense interest and inspire much innovation in the promise of CO2 valorization.

7.
BMC Infect Dis ; 23(1): 231, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37059987

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.


Assuntos
Infecções Comunitárias Adquiridas , Legionella pneumophila , Pneumonia Bacteriana , Pneumonia , Humanos , Adulto , Idoso , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Pneumonia Bacteriana/complicações , Estudos Prospectivos , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/etiologia , Streptococcus pneumoniae , Mycoplasma pneumoniae , Vírus Sinciciais Respiratórios , Klebsiella pneumoniae , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etiologia
8.
Sensors (Basel) ; 23(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37448094

RESUMO

The authors wish to make the following corrections to the original paper [...].

9.
Sensors (Basel) ; 23(6)2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36991843

RESUMO

In high dynamic scenes, fringe projection profilometry (FPP) may encounter fringe saturation, and the phase calculated will also be affected to produce errors. This paper proposes a saturated fringe restoration method to solve this problem, taking the four-step phase shift as an example. Firstly, according to the saturation of the fringe group, the concepts of reliable area, shallow saturated area, and deep saturated area are proposed. Then, the parameter A related to the reflectivity of the object in the reliable area is calculated to interpolate A in the shallow and deep saturated areas. The theoretically shallow and deep saturated areas are not known in actual experiments. However, morphological operations can be used to dilate and erode reliable areas to produce cubic spline interpolation areas (CSI) and biharmonic spline interpolation (BSI) areas, which roughly correspond to shallow and deep saturated areas. After A is restored, it can be used as a known quantity to restore the saturated fringe using the unsaturated fringe in the same position, the remaining unrecoverable part of the fringe can be completed using CSI, and then the same part of the symmetrical fringe can be further restored. To further reduce the influence of nonlinear error, the Hilbert transform is also used in the phase calculation process of the actual experiment. The simulation and experimental results validate that the proposed method can still obtain correct results without adding additional equipment or increasing projection number, which proves the feasibility and robustness of the method.

10.
J Sci Food Agric ; 103(10): 5126-5137, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37005496

RESUMO

BACKGROUND: Fragrant rice is increasingly popular with the public owing to its fresh aroma, and 2-acetyl-1-pyrroline (2-AP) is the main characteristic component of the aroma in fragrant rice. Rice-fish co-culture is an environmentally friendly practice in sustainable agriculture. However, the effect of rice-fish co-culture on 2-AP in grains has received little study. A conventional fragrant rice (Meixiangzhan 2) was used, and a related field experiment during three rice growing seasons was conducted to investigate the effects of rice-fish co-culture on 2-AP, as well as the rice quality, yield, plant nutrients, and precursors and enzyme activities of 2-AP biosynthesis in leaves. This study involved three fish stocking density treatments (i.e. 9000 (D1), 15 000 (D2), and 21 000 (D3) fish fries per hectare) and rice monocropping. RESULTS: Rice-fish co-culture increased the 2-AP content in grains by 2.5-49.4% over that of the monocropping, with significant increases in the early and late rice seasons of 2020. Rice-fish co-culture treatments significantly promoted seed-setting rates by 3.39-7.65%, and improved leaf nutrients and rice quality. Notably, the D2 treatment significantly increased leaf total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents and the head rice rate at maturity stage, while significantly decreased chalkiness degree. There was no significant difference in rice yield. CONCLUSION: Rice-fish co-culture had positive effects on 2-AP synthesis, rice quality, seed-setting rates, and plant nutrient contents. The better stocking density of field fish for rice-fish co-culture in this study was 15 000 fish ha-1 . © 2023 Society of Chemical Industry.


Assuntos
Oryza , Animais , Oryza/química , Grão Comestível , Sementes , Pirróis
11.
Anal Chem ; 94(44): 15307-15314, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36301050

RESUMO

Impaired insulin release is the key feature of type 2 diabetes. Insulin secretion, mainly mediated by SNARE proteins, is closely related to the blood glucose level. However, the mechanism underlying how glucose controls SNARE proteins to regulate insulin release is largely unexplained. Herein, we investigated the effects of glucose on the subcellular localization and spatial distribution on the plasma membrane (PM) of t-SNAREs (SNAP-25 and STX-1A) using a live-cell confocal microscope and the single-molecule localization imaging technique. Live-cell confocal and dSTORM imaging first revealed that SNAP-25 was mostly localized to the PM as clusters under the basal glucose concentration condition and demonstrated significant colocalization with STX-1A clusters. Furthermore, our data showed that the elevated glucose concentration increased the expression of SNAP-25 and induced more and larger SNAP-25 clusters on the PM, whereas glucotoxicity severely inhibited SNAP-25 transport to the PM and caused fewer and smaller SNAP-25 clusters on the PM. Additionally, we found that glucotoxicity also had an inhibitory effect on the colocalization between SNAP-25 and STX-1A, indicating a decrease of their interactions. Our study sheds light on the regulatory effects of glucose on the functional organization of t-SNAREs at a subcellular and molecular level, thus providing new insights into the mechanisms by which SNAREs regulate insulin release.


Assuntos
Diabetes Mellitus Tipo 2 , Insulina , Humanos , Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo , Secreção de Insulina , Membrana Celular/metabolismo , Glucose/metabolismo
12.
Sensors (Basel) ; 22(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36502089

RESUMO

An improved three-frequency heterodyne synthesis phase unwrapping method is proposed to improve the measurement accuracy through phase difference and phase sum operations. This method can reduce the effect of noise and increase the equivalent phase frequency. According to the distribution found in the phase difference calculation process, the Otsu segmentation is introduced to judge the phase threshold. The equivalent frequency obtained from the phase sum is more than those of all projected fringe patterns. In addition, the appropriate period combinations are also studied. The simulations and related experiments demonstrate the feasibility of the proposed method and the ability to improve the accuracy of the measurement results further.

13.
Anal Chem ; 93(42): 14113-14120, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34657412

RESUMO

Membrane proteins tend to interact with each other in the cell membranes to form protein clusters and perform the corresponding physiological functions. However, because channel proteins are involved in many biological functions, their distribution and nano-organization in these protein clusters are unclear. To study the distribution patterns and relationships between the different channel proteins, we identified the locations of glucose transporter 1 (Glut1) and Band3 (anion transporter 1) precisely in the topography of the cytoplasmic side of the human red blood cell (hRBC) membranes using combined atomic force microscopy (AFM) and single-molecule localization microscopy (SMLM). The AFM results revealed that membrane proteins interacted with each other and aggregated into protein islands. The SMLM results showed that Glut1 and Band3 tended to form protein clusters in the hRBC membranes, and there was a strong colocalization between the two proteins. The results of the combined AFM and SMLM method indicated that the protein clusters of Glut1 and Band3 were mainly located in the protein islands of topography, and the protein islands in topography also interacted with each other to assemble into larger protein clusters or functional microdomains.


Assuntos
Membrana Eritrocítica , Imagem Individual de Molécula , Citoplasma , Humanos , Proteínas de Membrana , Microscopia de Força Atômica
14.
Anal Chem ; 93(2): 936-945, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33301288

RESUMO

Protein tyrosine kinase-7 (PTK7), as an important membrane receptor, regulates various cellular activities, including cell polarity, movement, migration, and invasion. Although lots of research studies focused on revealing its functions from the aspect of the expression of the gene and protein are present, the relationship between the spatial distribution at the single-molecule level and the function remains unclear. Through combining aptamer probe labeling and super-resolution imaging technology, after verifying the specificity and superiority of the aptamer probe, a more significant clustering distribution of PTK7 is found on the MCF10A cell basal membrane than on the apical membrane, which is thought to be related to their specific functions on different membranes. By exploring the relationship between the assembly of PTK7 and lipid rafts, actin cytoskeleton, and carbohydrate chains on the membrane, the unique distribution of PTK7 on disparate membranes is revealed to be probably because of the varied dominant position of these three factors. These findings present the detailed spatial information of PTK7 and the related potential organization mechanism on the cell membrane, which will facilitate a better understanding of the relationship between the molecular assembly and its function, as well as the overall structure of the cell membrane.


Assuntos
Aptâmeros de Nucleotídeos/química , Moléculas de Adesão Celular/análise , Membrana Celular/química , Receptores Proteína Tirosina Quinases/análise , Células Cultivadas , Humanos , Microscopia de Fluorescência , Processos Estocásticos
15.
Cancer Cell Int ; 21(1): 443, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419073

RESUMO

BACKGROUND: Lung cancer has the highest case fatality rate among cancers because of uncontrolled proliferation and early metastasis of cancer cells in the lung tissue. This study aimed to clarify the role of the non-SMC condensin I complex, subunit G (NCAPG) in lung adenocarcinoma (LUAD), explore the mechanisms of its progression, and lay the foundation for the search for new biological markers. METHODS: We analyzed overlapping differentially expressed genes (DEGs) from three datasets; a protein-protein interaction (PPI) network was subsequently constructed and analyzed using Cytoscape. We then selected NCAPG for validation because of its poor prognosis and because it has not been sufficiently studied in the context of LUAD. Immunohistochemical analysis was used to detect the expression of NCAPG in LUAD tissues, and the relationships between NCAPG and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to verify the role of NCAPG in LUAD. Finally, we studied the specific mechanism of action of NCAPG in LUAD. RESULTS: Through comprehensive analysis of the GSE43458, GSE75037, and The Cancer Genome Atlas databases, we identified 517 overlapping DEGs. Among them, NCAPG was identified as a hub gene. Immunohistochemical analysis revealed that NCAPG was strongly associated with the clinical stage, M-classification, and N-classification. Univariate and multivariate Cox regression analyses indicated that NCAPG was a prognostic risk factor for LUAD, while the in vitro experiments showed that NCAPG overexpression promoted proliferation, migration, invasion, and epithelial-mesenchymal transition. Furthermore, knockdown of NCAPG inhibited LUAD progression, both in vitro and in vivo. Mechanistically, NCAPG overexpression increased p-Smad2 and p-Smad3 expressions in the transforming growth factor ß (TGF-ß) signaling pathway. Additionally, rescue experiments indicated that TGF-ß signaling pathway inhibitors could restore the effect of NCAPG overexpression in LUAD cells. CONCLUSIONS: NCAPG may promote proliferation and migration via the TGF-ß signaling pathway in LUAD.

16.
BMC Med Inform Decis Mak ; 21(1): 22, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478490

RESUMO

BACKGROUND: Early alarm of hypoglycemia, detection of asymptomatic hypoglycemia, and effective control of blood glucose fluctuation make a great contribution to diabetic treatment. In this study, we designed a multi-level hypoglycemia early alarm system to mine potential information in Continuous Glucose Monitoring (CGM) time series and improve the overall alarm performance for different clinical situations. METHODS: Through symbolizing the historical CGM records, the Prefix Span was adopted to obtain the early alarm/non-alarm frequent sequence libraries of hypoglycemia events. The longest common subsequence was used to remove the common frequent sequence for achieving the hypoglycemia early alarm in different clinical situations. Then, the frequent sequence pattern libraries with different risk thresholds were designed as the core module of the proposed multi-level hypoglycemia early alarm system. RESULTS: The model was able to predict hypoglycemia events in the clinical dataset of level-I (sensitivity 85.90%, false-positive 23.86%, miss alarm rate 14.10%, average early alarm time 20.61 min), level-II (sensitivity 80.36%, false-positive 17.37%, miss alarm rate 19.63%, average early alarm time 27.66 min), and level-III (sensitivity 78.07%, false-positive 13.59%, miss alarm rate 21.93%, average early alarm time 33.80 min), respectively. CONCLUSIONS: The proposed approach could effectively predict hypoglycemia events based on different risk thresholds to meet different prevention and treatment requirements. Moreover, the experimental results confirm the practicality and prospects of the proposed early alarm system, which reflects further significance in personalized medicine for hypoglycemia prevention.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Glicemia , Automonitorização da Glicemia , Humanos , Hipoglicemia/diagnóstico , Monitorização Ambulatorial
17.
Nano Lett ; 20(12): 8600-8607, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33155820

RESUMO

Rational design of stimuli-responsive polymers for cytosolic protein delivery with robust efficiency is of great importance but remains a challenging task. Here, we reported a bioreducible and amphiphilic dendrimer bearing a fluoroalkyl tail for this purpose. The fluorolipid was conjugated to the focal point of a cysteamine-cored polyamidoamine dendrimer via disulfide bond, while phenylboronic acid moieties were decorated on dendrimer surface for efficient protein binding. The yielding polymer showed high protein binding capability and complex stability and could efficiently release the cargo proteins in a glutathione-responsive manner. The designed polymer was effective in the delivery of various membrane-impermeable proteins into living cells with reserved bioactivities. In addition, the polymer efficiently delivered a toxin protein saporin into 4T1 breast cancer cells and inhibited the tumor growth in vivo after intravenous injection. The developed polymer in this study is a promising vector for the delivery of membrane-impermeable proteins to treat various diseases.


Assuntos
Dendrímeros , Linhagem Celular Tumoral , Citosol , Polímeros , Proteínas
18.
Clin Infect Dis ; 71(15): 713-720, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32129843

RESUMO

BACKGROUND: A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. RESULTS: The median number of intrahost variants was 1-4 in SARS-CoV-2-infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavirus , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave , Betacoronavirus , COVID-19 , Variação Genética , Genômica , Humanos , SARS-CoV-2
19.
Anal Chem ; 92(9): 6555-6563, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32290652

RESUMO

The orderly organelle interaction network is essential for normal biological activity of cells. However, the mechanism of orderly organelle interaction remains elusive. In this report, we analyzed the structure characteristics of the cell membrane, endocytic vesicles, and the Golgi membrane through a high-resolution imaging technique and further comprehensively investigated the vesicle-transport process via epidermal growth factor receptor endocytosis and a recycling pathway using a real-time fluorescence tracing method. Our data suggest that orderly vesicle transport is due to protein protrusion from the outer surface of endocytic vesicles and that full membrane fusion between homotypic endocytic vesicles is a result of the rough outer surface. Finally, the kiss-and-run method, which is utilized by endocytic vesicles to communicate with the trans-Golgi network (TGN) is attributed to a dense protein layer at the outer surface of the TGN. In summary, by combining static structural analysis with dynamic tracing, we elucidate the mechanism of orderly vesicle transport from the overall structural features of the membrane. This work provides insight into the structural mechanisms underlying vital biological processes involving organelle interactions at the molecular level.

20.
Opt Express ; 28(26): 38491-38504, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33379418

RESUMO

We propose an absolute phase retrieval method based on three phase-shifting amount codes (3-PSA-codes) to measure the colored object with one additional pattern. 3-PSA-codes adopt the coding concept of 3-digit-codes, in which the code elements of three consecutive periods are treated as a unique code word for one period. However, to measure the colored object more effectively in the proposed method, each code element is embedded into the PSA domain and retrieved from the phase difference. Fringe patterns for the wrapped phase are artfully employed in the code element retrieval. Hence, for the first time, to the best of our knowledge, the code element related to the phase can be determined by one additional pattern. It breaks the constraint that temporal methods require multiple additional patterns to overcome the adverse effect of the surface color of objects on absolute phase retrieval. Experimental results demonstrate that the proposed 3-PSA-codes have strong robustness in the measurement of the colored object.

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