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1.
Development ; 149(21)2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36205097

RESUMO

Lymphangiogenesis is a dynamic process that involves the directed migration of lymphatic endothelial cells (LECs) to form lymphatic vessels. The molecular mechanisms that underpin lymphatic vessel patterning are not fully elucidated and, to date, no global regulator of lymphatic vessel guidance is known. In this study, we identify the transmembrane cell signalling receptor Plexin D1 (Plxnd1) as a negative regulator of both lymphatic vessel guidance and lymphangiogenesis in zebrafish. plxnd1 is expressed in developing lymphatics and is required for the guidance of both the trunk and facial lymphatic networks. Loss of plxnd1 is associated with misguided intersegmental lymphatic vessel growth and aberrant facial lymphatic branches. Lymphatic guidance in the trunk is mediated, at least in part, by the Plxnd1 ligands, Semaphorin 3AA and Semaphorin 3C. Finally, we show that Plxnd1 normally antagonises Vegfr/Erk signalling to ensure the correct number of facial LECs and that loss of plxnd1 results in facial lymphatic hyperplasia. As a global negative regulator of lymphatic vessel development, the Sema/Plxnd1 signalling pathway is a potential therapeutic target for treating diseases associated with dysregulated lymphatic growth.


Assuntos
Vasos Linfáticos , Semaforinas , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Células Endoteliais/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Linfangiogênese/genética , Vasos Linfáticos/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Proteínas de Transporte/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
2.
Nanotechnology ; 34(46)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37567159

RESUMO

The random disposal and immature recycling of post-consumer polyethylene terephthalate (PET) packages lead to a severe threaten to the ecological system owing to slow natural degradation kinetics of PET plastic, and meanwhile cause a waste of carbon resources stored in PET plastics. Many methods have been developed to recycle PET plastics, such as mechanical recycling, which induces a reduced quality relative to the virgin PET. In recent years, the photocatalytic conversion of PET plastic wastes into chemicals has received considerable attention due to their unique advantages, including mild conditions, less energy consumption, and simple operation. In this review, we have summarized the latest achievements in photoreforming of PET plastics into value-added chemicals. Primarily, we described the mechanism for bond cleavage during PET photoreforming, the emerging pretreatment methodologies for PET plastics, and the advantages of photocatalytic PET plastics conversion. Then, we introduced electro-/bio-assisted photocatalysis technologies for PET disposal and commented their strengths and limitations. Finally, we put forward the challenges and potential advances in the domain of photocatalytic PET plastics conversion.

3.
Appl Opt ; 62(10): 2403-2409, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132787

RESUMO

The photon sieve has had the problem of low diffraction efficiency since it was proposed. Dispersion from different waveguide modes in the pinholes also reduces the quality of focusing. To overcome the above drawbacks, we propose a kind of photon sieve working in the terahertz band. In a metal square-hole waveguide, the effective index is determined by the side length of the pinhole. We adjust the optical path difference by changing the effective indices of those pinholes. When the thickness of the photon sieve is fixed, the optical path in a zone is set to be a multilevel distribution from 0 to λ. In this way, the optical path differences caused by the waveguide effect of pinholes are used to compensate for those caused by the positions of pinholes. We also derive the focusing contribution of an individual square pinhole. The simulated example shows a 60 times increase in intensity than that of the equal-side-length single-mode waveguide photon sieve.

4.
BMC Anesthesiol ; 23(1): 144, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37118673

RESUMO

BACKGROUND: Pain intensity may be varied during the needle advancing through different skin layers, injection into the intradermal layer may exclude mixed pain from deeper planes. This study aimed to investigate whether compressing a three-dimensional (3D)-printed disk against the skin may relieve pain associated with intradermal injection of local anesthetic which mimics the skin test procedure. METHODS: After institutional review board approval, 3D-printed disks with projections were designed for this study. Enrolled patients were randomized to receive either a disk compressing against the axillary skin during the intradermal injection of local anesthesia (compressing disk group) or an intradermal injection of local anesthesia without any compression (no compressing disk group). The primary outcomes were pain intensity (100-mm visual analog scale) and satisfaction (5-point Likert scale) as assessed by patients. RESULTS: Ninety patients with American Society of Anesthesiologists I-II physical status receiving intradermal local anesthesia prior to an ultrasound-guided axillary approach were included. Eighty-seven patients completed the study, with 44 and 43 patients in disk and no disk groups, respectively. Pain scores were significantly different (P < 0.001) in compressing disk (median, 10; IQR, 5-20) and no compressing disk (median, 30; IQR, 20-40) groups. The median satisfaction score was 5 in both groups. No complications occurred during follow-up. CONCLUSION: Compressing a 3D-printed disk against the skin may reduce intradermal needle pain and offers an effective alternative for nerve block induction.


Assuntos
Anestesia Local , Lidocaína , Humanos , Anestesia Local/métodos , Anestésicos Locais , Dor/etiologia , Impressão Tridimensional
5.
BMC Musculoskelet Disord ; 24(1): 126, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36793065

RESUMO

BACKGROUND: The preoperative flexibility of the scoliotic spine is a key aspect of surgical planning, as it provides information on the rigidity of the curve, the extent of structural changes, the levels to be fused and the amount of correction. The purpose of this study was to assess whether supine flexibility can be used to predict postoperative correction in patients with adolescent idiopathic scoliosis (AIS) by determining the correlation between these two characteristics. METHODS: A total of 41 AIS patients who underwent surgical treatment between 2018 and 2020 were retrospectively enrolled for analysis. Preoperative and postoperative standing radiographs and preoperative CT images of the entire spine were collected and used to measure supine flexibility and the postoperative correction rate. T tests were used to analyse the differences in supine flexibility and postoperative correction rate between groups. Pearson's product-moment correlation analysis was performed, and regression models were established to determine the correlation between supine flexibility and postoperative correction. Thoracic curves and lumbar curves were analysed independently. RESULTS: Supine flexibility was found to be significantly lower than the correction rate but showed a strong correlation with the postoperative correction rate, with r values of 0.68 for the thoracic curve group and 0.76 for the lumbar curve group. The relationship between supine flexibility and postoperative correction rate could be expressed by linear regression models. CONCLUSION: Supine flexibility can be used to predict postoperative correction in AIS patients. In clinical practice, supine radiographs may be used in place of existing flexibility test techniques.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Radiografia , Fusão Vertebral/métodos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia
6.
BMC Musculoskelet Disord ; 24(1): 935, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38042803

RESUMO

BACKGROUND: Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome. METHODS: Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group. RESULTS: All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures. CONCLUSION: Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.


Assuntos
Síndrome do Túnel Carpal , Gota , Humanos , Dedos , Punho , Gota/complicações , Gota/cirurgia , Tendões/cirurgia , Tendões/fisiologia
7.
J Acoust Soc Am ; 154(5): 3344-3353, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37988374

RESUMO

Channel equalization plays a crucial role in single-carrier underwater acoustic (UWA) communications. Recently, a frequency-domain turbo equalization (FDTE) scheme enabled by the vector approximate message passing (VAMP) algorithm, was proposed, and it outperformed classic linear minimum mean square error FDTE at acceptable complexity cost. The operation of the VAMP-FDTE requires knowledge of noise power, which is predetermined before the equalization starts. In practice, however, it is difficult to obtain prior knowledge of noise power due to factors of unknown channel estimation errors and dynamic underwater environments. Motivated by this fact, we propose an enhanced VAMP-FDTE scheme, which learns the noise power knowledge during the equalization process via the expectation-maximization (EM) algorithm. The EM-based noise power estimation makes use of intermediate results of the VAMP-FDTE and, thus, only incurs a small extra computational overhead. The improved VAMP-FDTE, named EM-VAMP-FDTE, was tested by experimental data collected in shallow-sea horizontal UWA communication trials with MIMO configuration. It showed better performance than the existing VAMP-FDTE scheme, attributed to the online noise power learning.

8.
Mikrochim Acta ; 190(10): 401, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37726483

RESUMO

An electrochemical sensor for the detection of uric acid was constructed using cobalt oxide-modified porous carbon@multi-walled carbon nanotube (MWCNTs) composite material for the modification of the electrode. Firstly, ZIF-67 is generated on carbon nanotubes using the surfactant cetylammonium bromide (CTAB) as template. The vesicles generated by CTAB act as nucleation sites for the in situ growth of ZIF-67. Then, cobalt oxide-modified porous carbon was obtained after high-temperature carbonization of ZIF-67, leading to the formation of cobalt oxide-modified porous carbon@MWCNT composite materials. Co-N and Co-O active sites on the composite material can improve the oxidation of uric acid on the electrode surface, leading to enhanced sensitivity and selectivity for uric acid detection. The sensor has a good linear range from 1 to 40 µM for uric acid detection with a detection limit of 0.09 µM. The sensor was utilized for determination of uric acid in actual serum samples.

9.
Ren Fail ; 45(1): 2221130, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37403637

RESUMO

The relationship between serum insulin-like growth factor-1 (IGF-1) levels and anemia in patients undergoing maintenance hemodialysis (MHD) remains unclear. This cross-sectional study included patients who underwent MHD treatment for >3 months at our dialysis center in March 2021. Demographic and clinical data were recorded. Blood samples were collected before the hemodialysis sessions, and general serum biochemical parameters, routine blood markers, and serum IGF-1 levels were measured. Patients were divided into a group without anemia (hemoglobin ≥110 g/L) and a group with anemia (hemoglobin <110 g/L), and multivariable linear and binary logistic regression analyses were performed to study the relationship between the levels of serum IGF-1 and anemia. A total of 165 patients (male/female = 99:66) with MHD were enrolled in the study, with a median age of 66.0 (58.0, 75.0) years and a median dialysis vintage of 27.0 (12.0, 55.0) months. The mean hemoglobin level was 96.38 ± 16.72 g/L, and 126 patients had anemia (76.4%). Compared to patients without anemia, patients with anemia had lower serum IGF-1 and triglyceride levels and higher intravenous iron supplementation on dialysis (all p < 0.05). After adjusting for confounding factors in different models, the nine-model multivariate binary logistic regression analyses also confirmed that lower serum IGF-1 levels and serum IGF-1 < 197.03 ng/ml were both independently associated with anemia in patients undergoing MHD. However, further multicenter studies with larger sample sizes are required to confirm these findings.


Assuntos
Anemia , Falência Renal Crônica , Humanos , Masculino , Feminino , Fator de Crescimento Insulin-Like I , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Estudos Transversais , Diálise Renal/efeitos adversos , Anemia/tratamento farmacológico , Hemoglobinas
10.
J Environ Manage ; 345: 118661, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37515885

RESUMO

Volatile organic compounds (VOCs) evolved from biomass gasification plays a positive role in the formation of PM2.5 and odor pollution. In order to improve the removal rate of various VOCs produced by biomass gasification, a nickel-based supported HZSM-5 cataly st (Ni/HZSM-5 and Ni-Ca-Co/HZSM-5) was prepared by different auxiliary methods, Ni loadings, and pyrolysis temperatures. The catalytic cracking performance of Ni/HZSM-5 catalysts for different VOCs model compounds such as toluene, phenol, furan, acetic acid and cyclohexane were studied in a fixed-bed reactor. The catalysts were further characterized and analyzed by XRD, SEM, XPS and BET. The results showed that the Ni/HZSM--C-Co5 catalyst prepared by ultrasonic-assisted excess impregnation method with Ni loading of 8 wt%, Ca loading of 4 wt%, Co loading of 0.1 wt% had strong catalytic activity for VOCs degradation. With the increase of the cracking temperature, the conversion rate and gas yield of from model compound cracking improved significantly. At 800 °C, the conversion of each model compound was more than 90%, accompanied by the generation of cracking gases such as H2 and CH4. The selectivity of H2 and CH4 from toluene cracking reached 93%, and cyclohexane reached 98%. The models with higher oxygen content and lower bond energy were more likely to undergo reforming reaction to form small molecular gas. Model compounds with large molecular weight and high carbon content provided more carbon sources. Under the conversion degree towards the gas direction was high. This study provides a new idea on the removal of VOCs for the efficient utilization of biomass resources.


Assuntos
Compostos Orgânicos Voláteis , Biomassa , Gases/química , Catálise , Carbono , Tolueno/química
11.
Opt Lett ; 47(3): 461-464, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103651

RESUMO

A deep learning channel estimation scheme in orthogonal frequency division multiplexing for X-ray communication (XCOM) is studied. The scheme uses simulated and detected data obtained with different working parameters and numbers of pilots as training and testing data, respectively, for the deep neural network (DNN) model. The bit-error-rate performance of the DNN model under various system operating parameters, numbers of pilot sequences, and channel obstructions is investigated separately. Experiment results showed that the deep-learning-based approach can address the distortion of the air-scintillator channel for XCOM, giving a performance comparable to those of least-squares and minimum-mean-square error estimation methods.


Assuntos
Aprendizado Profundo , Comunicação , Redes Neurais de Computação , Raios X
12.
J Biol Chem ; 295(19): 6741-6753, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32249212

RESUMO

SUMOylation is a posttranslational modification (PTM) at a lysine residue and is crucial for the proper functions of many proteins, particularly of transcription factors, in various biological processes. Zinc finger homeobox 3 (ZFHX3), also known as AT motif-binding factor 1 (ATBF1), is a large transcription factor that is active in multiple pathological processes, including atrial fibrillation and carcinogenesis, and in circadian regulation and development. We have previously demonstrated that ZFHX3 is SUMOylated at three or more lysine residues. Here, we investigated which enzymes regulate ZFHX3 SUMOylation and whether SUMOylation modulates ZFHX3 stability and function. We found that SUMO1, SUMO2, and SUMO3 each are conjugated to ZFHX3. Multiple lysine residues in ZFHX3 were SUMOylated, but Lys-2806 was the major SUMOylation site, and we also found that it is highly conserved among ZFHX3 orthologs from different animal species. Using molecular analyses, we identified the enzymes that mediate ZFHX3 SUMOylation; these included SUMO1-activating enzyme subunit 1 (SAE1), an E1-activating enzyme; SUMO-conjugating enzyme UBC9 (UBC9), an E2-conjugating enzyme; and protein inhibitor of activated STAT2 (PIAS2), an E3 ligase. Multiple analyses established that both SUMO-specific peptidase 1 (SENP1) and SENP2 deSUMOylate ZFHX3. SUMOylation at Lys-2806 enhanced ZFHX3 stability by interfering with its ubiquitination and proteasomal degradation. Functionally, Lys-2806 SUMOylation enabled ZFHX3-mediated cell proliferation and xenograft tumor growth of the MDA-MB-231 breast cancer cell line. These findings reveal the enzymes involved in, and the functional consequences of, ZFHX3 SUMOylation, insights that may help shed light on ZFHX3's roles in various cellular and pathophysiological processes.


Assuntos
Proliferação de Células , Proteínas de Homeodomínio/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/metabolismo , Proteínas Inibidoras de STAT Ativados/metabolismo , Sumoilação , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Animais , Células HEK293 , Células HeLa , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Proteínas de Neoplasias/genética , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Proteínas Inibidoras de STAT Ativados/genética , Estabilidade Proteica , Enzimas Ativadoras de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/genética
13.
Opt Express ; 29(3): 3596-3608, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770956

RESUMO

We experimentally demonstrate an improved orthogonal frequency division multiplexing (OFDM) into the pulse width modulation (PWM) scheme for the X-ray communication (XCOM). The scheme is insensitive to the nonlinearity of the grid-controlled X-ray tube with switching 'on' and 'off' between two points. The dependence of this system's bit-error-rate (BER) performances on the data rates and the working parameters including the anode voltage and filament current of the grid-controlled X-ray tube are studied. The OFDM-PWM scheme reaches the data rate of 360 kbps at a BER of the forward error correction threshold of 3.8 × 10-3 over a 5 cm air channel. In addition, an experiment aided by density-based spatial clustering of applications with noise nonlinear compensation is carried out, and the results demonstrate the improvements in Q-factor by 0.62 dB.

14.
EMBO Rep ; 20(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30877134

RESUMO

Lymphatic vessels are known to be derived from veins; however, recent lineage-tracing experiments propose that specific lymphatic networks may originate from both venous and non-venous sources. Despite this, direct evidence of a non-venous lymphatic progenitor is missing. Here, we show that the zebrafish facial lymphatic network is derived from three distinct progenitor populations that add sequentially to the developing facial lymphatic through a relay-like mechanism. We show that while two facial lymphatic progenitor populations are venous in origin, the third population, termed the ventral aorta lymphangioblast (VA-L), does not sprout from a vessel; instead, it arises from a migratory angioblast cell near the ventral aorta that initially lacks both venous and lymphatic markers, and contributes to the facial lymphatics and the hypobranchial artery. We propose that sequential addition of venous and non-venous progenitors allows the facial lymphatics to form in an area that is relatively devoid of veins. Overall, this study provides conclusive, live imaging-based evidence of a non-venous lymphatic progenitor and demonstrates that the origin and development of lymphatic vessels is context-dependent.


Assuntos
Vasos Linfáticos/fisiologia , Células-Tronco/fisiologia , Veias/fisiologia , Peixe-Zebra/fisiologia , Animais , Movimento Celular/fisiologia , Células Endoteliais/fisiologia
15.
Mol Divers ; 25(3): 1481-1495, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34160713

RESUMO

DGAT1 plays a crucial controlling role in triglyceride biosynthetic pathways, which makes it an attractive therapeutic target for obesity. Thus, development of DGAT1 inhibitors with novel chemical scaffolds is desired and important in the drug discovery. In this investigation, the multistep virtual screening methods, including machine learning methods and common feature pharmacophore model, were developed and used to identify novel DGAT1 inhibitors from BioDiversity database with 30,000 compounds. 531 compounds were predicted as DGAT1 inhibitors by combination of machine learning methods comprising of SVM, NB and RP models. Then, 12 agents were filtered from 531 compounds by using the common feature pharmacophore model. The 3D chemical structures of the 12 hits coordinated with surface charges and isosurface have been carefully analyzed by the established 3D-QSAR model. Finally, 8 compounds with desired properties were retained from the final hits and have been assigned to another research group to complete the follow-up compound synthesis and biologic evaluation.


Assuntos
Diacilglicerol O-Aciltransferase/química , Descoberta de Drogas/métodos , Inibidores Enzimáticos/química , Aprendizado de Máquina , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade , Algoritmos , Quimioinformática/métodos , Bases de Dados de Compostos Químicos , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Curva ROC , Reprodutibilidade dos Testes
16.
Sleep Breath ; 25(4): 2007-2013, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33666836

RESUMO

PURPOSE: Sleep disturbance is frequently observed in patients on maintenance hemodialysis (MHD), and this population usually presents imbalances in trace elements. We investigated the association between blood trace element levels and sleep quality in patients on MHD. METHODS: This cross-sectional and single-center study was performed in September 2019. Patients regularly undergoing hemodialysis for > 3 months at our center were recruited, and demographic, clinical, and laboratory parameters were recorded. The Pittsburgh Sleep Quality Index (PSQI) was applied to define sleep disturbance. Blood trace element (zinc, manganese, copper, selenium, and lead) levels were measured using an inductively coupled plasma mass spectrometer. RESULTS: In total, 121 patients on MHD (male/female = 68:53) were enrolled in the study (mean age 63.7 ± 13.9 years, median dialysis vintage 38.0 [20.0, 60.0] months). According to PSQI, 56 (46%) patients experienced severe sleep disturbance. These patients were characterized by older age, higher serum parathyroid hormone levels, and lower blood selenium levels (all P < 0.05). No significant differences in blood zinc, manganese, copper, and lead levels were observed between groups. Univariate binary logistic regression showed that lower blood selenium levels were associated with severe sleep disturbance (odds ratio = 0.976, 95% confidence interval: 0.954-0.999, P = 0.038). Multivariate analyses also confirmed the results after adjusting for confounding factors. CONCLUSION: Our study indicated an association between lower blood selenium levels and the occurrence of severe sleep disturbances in patients on MHD. However, a prospective study with a larger sample size and assessing the importance of selenium supplementation are needed to confirm the results.


Assuntos
Diálise Renal , Selênio/sangue , Transtornos do Sono-Vigília/sangue , Oligoelementos/sangue , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente
17.
Am J Respir Cell Mol Biol ; 63(6): 780-793, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32915645

RESUMO

Lung myeloid cells are important in pulmonary immune homeostasis and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Multiparameter immunophenotypic characterization of these cells is challenging because of their autofluorescence and diversity. We evaluated the immunophenotypic landscape of airway myeloid cells in COPD using time of flight mass cytometry. Cells from BAL, which were obtained from never-smokers (n = 8) and smokers with (n = 20) and without (n = 4) spirometric COPD, were examined using a 44-parameter time of flight mass cytometry panel. Unsupervised cluster analysis was used to identify cellular subtypes that were confirmed by manual gating. We identified major populations of CD68+ and CD68- cells with 22 distinct phenotypic clusters, of which 18 were myeloid cells. We found a higher abundance of putative recruited myeloid cells (CD68+ classical monocytes) in BAL from patients with COPD. CD68+ classical monocyte population had distinct responses to smoking and COPD that were potentially related to their recruitment from the interstitium and vasculature. We demonstrate that BAL cells from smokers and subjects with COPD have lower AXL expression. Also, among subjects with COPD, we report significant differences in the abundance of PDL1high and PDL2high clusters and in the expression of PDL1 and PDL2 across several macrophage subtypes suggesting modulation of inflammatory responses. In addition, several phenotypic differences in BAL cells from subjects with history of COPD exacerbation were identified that could inform potential disease mechanisms. Overall, we report several changes to the immunophenotypic landscape that occur with smoking, COPD, and past exacerbations that are consistent with decreased regulation and increased activation of inflammatory pathways.


Assuntos
Antígeno B7-H1/metabolismo , Células Mieloides/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Idoso , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Humanos , Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Fumar/imunologia , Receptor Tirosina Quinase Axl
18.
Ecotoxicol Environ Saf ; 182: 109374, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31254853

RESUMO

Obtaining accurate measurements of the partition coefficients between sorbent materials and water is of major importance for the analysis of the adsorption behavior and dissolved concentrations of organic compounds in the environment. In the passive-sampling approach, polydimethylsiloxane (PDMS) has a wide range of applications. Therefore, we established a poly-parameter linear-free energy relationship (pp-LFER) and a quantitative structure-activity relationship (QSAR) model to predict the log KPDMS-w values for a large dataset of 290 organic chemicals from 11 diverse classes. For the pp-LFER model, E (excess molar refractivity), A (molecular H-bond donor ability), V (McGowan volume), and B (the H-bond acceptor properties) were introduced as the main correlated variables. However, the obtained model is much limited in terms of acquiring available descriptors. For this reason, we developed a QSAR model, and CrippenLogP (Crippen octanol-water partition coefficient), RNCG (Relative negative charge-most negative charge/total negative charge), ATSC4e (Centered Broto-Moreau autocorrelation-lag4/weighted by Sanderson electronegativities) and GATS6p (Geary autocorrelation-lag6/weighted by polarizabilities) were selected as the significant parameters. The predictive power and functional reliability of the presented models were confirmed with validation methods as described in previous studies. The adjusted determination coefficients (R2adj) of 0.851 and 0.922 and leave-one-out cross-validated (Q2LOO) of 0.841 and 0.907 revealed that the models have good predictive power and generalizability. Thus, the proposed models are simple yet accurate tools for predicting the log KPDMS-w values and providing new insights to further understand the adsorption mechanism of organic compounds.


Assuntos
Dimetilpolisiloxanos/química , Modelos Químicos , Água/química , Octanóis/química , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes
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