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1.
Small ; : e2402314, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38708815

RESUMO

Topology serves as a blueprint for the construction of reticular structures such as metal-organic frameworks, especially for those based on building blocks with highly symmetrical shapes. However, it remains a challenge to predict the topology of the frameworks from less symmetrical units, because their corresponding vertex figures are largely deformed from the perfect geometries with no "default" net embedding. Furthermore, vertices involving flexible units may have multiple shape choices, and the competition among their designated topologies makes the structure prediction in large uncertainty. Herein, the deformation index is proposed to characterize the symmetry loss of the vertex figure by comparing it with its ideal geometry. The mathematical index is employed to predict the shapes of two in situ formed Co-based metalloligands (pseudo-tetrahedron and pseudo-square), which further dictate the framework topology (flu and scu) when they are joined with the [Zr6O8]-based cuboid units. The two frameworks with very similar constituents provide an ideal platform to investigate how the pore shapes and interconnectivity influence the gas separation. The net with cylindrical channels outperforms the other with discreate cages in C3H8/C2H6/CH4 separation, benefiting from the facile accessibility of its interaction sites to the guests imposed by the specific framework topology.

2.
Water Res ; 252: 121230, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38330714

RESUMO

Although the biotoxicity of heavy metals has been widely studied, there are few reports on the recovery strategy of the inhibited bio-system. This study proposed a combined promoter-I (Primary promoter: l-cysteine, biotin, and cytokinin + Electron-shuttle: PMo12) to recover the denitrification suppressed by Cr(VI). Compared with self-recovery, combined promoter-I shortened the recovery time of 28 cycles, and the recovered reactor possessed more stable long-term operation performance with >95 % nitrogen removal. The biomass increased by 7.07 mg VSS/(cm3 carrier) than self-recovery due to the promoted bacterial reproduction, thereby reducing the toxicity load of chromium per unit biomass. The combined promoter-I strengthened the toxicity remediation by promoting 92.84 % of the intracellular chromium release and rapidly activating anti-oxidative stress response. During toxicity remediation, ROS content quickly decreased, and the PN/PS value was 2.27 times that of self-recovery. PMo12 relieved Cr(VI) inhibition on NO3--N reduction by increasing NAR activity. The enhanced intracellular and intercellular electron transmission benefited from the stimulated NADH, FMN, and Cyt.c secretion by the primary promoter and the improved transmembrane electron transmission by Mo. PMo12 and the primary promoter synergized in regulating community structure and improving microbial richness. This study provided practical approaches for microbial toxicity remediation and maintaining high-efficiency denitrification.


Assuntos
Desnitrificação , Metais Pesados , Elétrons , Cromo/toxicidade , Cromo/química
3.
Asian J Surg ; 47(2): 1285-1286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040512

Assuntos
Ovos , Neoplasias , Humanos
4.
Angew Chem Int Ed Engl ; 63(1): e202313336, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37983653

RESUMO

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

5.
J Am Chem Soc ; 145(48): 26169-26178, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37988478

RESUMO

Imaging-guided chemodynamic therapy is widely considered a promising modality for personalized and precision cancer treatment. Combining both imaging and chemodynamic functions in one system conventionally relies on the hybrid materials approach. However, the heterogeneous, ill-defined, and dissociative/disintegrative nature of the composites tends to complicate their action proceedings in biological environments and thus makes the treatment imprecise and ineffective. Herein, a strategy to employ two kinds of inorganic units with different functions─reactive oxygen species generation and characteristic emission─has achieved two single-crystalline metal-organic frameworks (MOFs), demonstrating the competency of reticular chemistry in creating multifunctional materials with atomic precision. The multinary MOFs could not only catalyze the transformation from H2O2 to hydroxyl radicals by utilizing the redox-active Cu-based units but also emit characteristic tissue-penetrating near-infrared luminescence brought by the Yb4 clusters in the scaffolds. Dual functions of MOF nanoparticles are further evidenced by pronounced cell imaging signals, elevated intracellular reactive oxygen species levels, significant cell apoptosis, and reduced cell viabilities when they are taken up by the HeLa cells. In vivo NIR imaging is demonstrated after the MOF nanoparticles are further functionalized. The independent yet interconnected modules in the intact MOFs could operate concurrently at the same cellular site, achieving a high spatiotemporal consistency. Overall, our work suggests a new method to effectively accommodate both imaging and therapy functions in one well-defined material for precise treatment.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Humanos , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/química , Células HeLa , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Fototerapia , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
6.
Sci Total Environ ; 903: 166626, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-37643709

RESUMO

The formation of biofilm determines the performance and stability of biofilm system. Increasing the hydrophilicity of the carrier surface could efficiently accelerate the attachment and growth of microorganisms. Here, the surface of polypropylene (PP) fiber carrier was modified with polydopamine (PDA) and calcium (Ca(II)) to enhance microbial attachment and toxicity resistance. The results of surface characteristic confirmed the self-polymerization of PDA and the chelation mechanism of Ca(II). Subsequently, the biofilm formation experiments were conducted in sequencing batch biofilm reactors using both normal and chromium-containing wastewater. The biofilm on the surface of the modified carrier exhibited better nitrogen removal and Cr(VI) reduction ability. The biomass of the modified carrier was significantly increased, and the maximum microbial attachment amounts in normal wastewater and chrome-containing wastewater were 1153.34 and 511.78 mg/g carrier, respectively. Furthermore, the confocal laser scanning microscope (CLSM) indicated that the modified carrier coated with PDA and Ca(II) were both biocompatible, and the cell activity was significantly increased. 16S rRNA sequencing results showed that the modified carrier efficiently enriched both denitrification bacteria (Thauera and Flavobacterium) and chrome-reducing bacteria (Simplicispira and Arenimonas) to improve system stability and Cr(VI) resistance. Microbial phenotype prediction based on BugBase analysis further verified the enrichment effect of modified carriers on microorganisms responsible for biofilm formation and oxidative stress resistance. Overall, this work proposed a novel functional carrier that could provide references for advancing the application of biofilm systems in wastewater treatment.

7.
Cancers (Basel) ; 15(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36980687

RESUMO

A significant burden is placed on the lives of females due to cervical cancer, which is currently the leading cause of cancer death among women. Preferentially expressed antigen in melanoma (PRAME) belongs to the CTA gene family and was found to be abnormally expressed among different types of cancers. Our previous research also indicated that PRAME was highly expressed in cervical cancer compared with normal tissues. However, the roles and detailed mechanisms of PRAME have not been explored in cervical cancer. In the present study, the expression of PRAME in cervical tissues and cells was detected by immunohistochemistry (IHC), qRT-PCR, and Western blotting. Additionally, CCK-8, BrdU, scratch, transwell, and flow cytometry assays were conducted to explore the function of PRAME in regulating the malignant biological behaviors of cervical cancer cells. Nude mice were used to confirm the role of PRAME in tumor growth in vivo. Furthermore, the Wnt inhibitor MSAB was used to verify the role of PRAME in regulating the Wnt/ß-catenin pathway both in vitro and in vivo. The results of IHC, qRT-PCR, and Western blotting showed that PRAME was highly expressed in cervical cancer tissues and cells. PRAME knockdown attenuated cell growth, migration, and invasion; induced G0/G1 arrest; and increased cell apoptosis in C33A and SiHa cells through Wnt/ß-catenin signaling regulation. However, the upregulation of PRAME exhibited the opposite effects accordingly, which could be partly reversed via MSAB treatment. The growth rate of xenograft tumors was enhanced when PRAME was overexpressed via Wnt/ß-catenin signaling activation. Taken together, PRAME is associated with cervical cancer occurrence and progression mediated by Wnt/ß-catenin signaling, suggesting that PRAME might be a factor in manipulating cervical carcinogenesis and a potential therapeutic target.

8.
Angew Chem Int Ed Engl ; 62(11): e202216878, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36651564

RESUMO

Here, we report the first example of Ni-catalyzed asymmetric hydrosilylation of 1,1-disubstituted allenes with high level of regioselectivities and enantioselectivities. The key to achieve this stereoselective hydrosilylation reaction was the development of the SPSiOL-derived bisphosphite ligands (SPSiPO). This protocol features broad substrate scope, excellent functional group, and heterocycle tolerance, thus provides a versatile method for the construction of enantioenriched tertiary allylsilanes in a straightforward and atom-economic manner. DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity.

9.
Aesthet Surg J ; 43(5): 582-592, 2023 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-36446744

RESUMO

BACKGROUND: Preoperative planning for liposuction is vital to ensure safe practice and patient satisfaction. However, current standards of fat assessment before surgery are guided by subjective methods such as visual inspection, skin-pinch tests, and waist circumference measurements. OBJECTIVES: This study aimed to develop an inexpensive software-based tool that utilizes ultrasound (US) imaging and an online platform to accurately simulate regional subcutaneous adipose tissue (SAT) distribution and safe volume estimation for liposuction procedures. METHODS: The authors present a web-based platform with integrated 2-dimensional (2D) and 3-dimensional (3D) simulations of SAT to support liposuction planning and execution. SAT-Map was constructed using multiple sub-applications linked with the python framework programming language (Wilmington, DE). RESULTS: The SAT-Map interface provides an intuitive and fluid means of generating patient-specific models and volumetric data. To further accommodate this, an operational manual was prepared to achieve consistent visualization and examination of estimated SAT content. The system currently supports static 2D heatmap simulation and 3D interactive virtual modelling of the SAT distribution. Supplementary clinical studies are needed to evaluate SAT-Map's clinical performance and practicality. CONCLUSIONS: SAT-Map revolutionizes the concept of preoperative planning for liposuction by developing the first combined web-based software that objectively simulates fat distribution and measures safe liposuction volume. Our software approach presents a cost-efficient, accessible, and user-friendly system offering multiple advantages over current SAT assessment modalities. The immediacy of clinically accurate 3D virtual simulation provides objective support to surgeons towards improving patient conversation, outcomes, and satisfaction in liposuction procedures.


Assuntos
Lipectomia , Humanos , Lipectomia/métodos , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/cirurgia , Distribuição da Gordura Corporal , Software , Internet
10.
Front Pharmacol ; 13: 861319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903325

RESUMO

The abnormal neointima formation caused by the phenotypic switching of vascular smooth cells (VSMCs) into a synthetic state plays a key role in the pathogenesis of various vascular diseases, including atherosclerosis and postangioplasty restenosis. Theaflavin-3,3'-digallate (TF3) in black tea has been reported to exert antiinflammatory and anticancer effects, but its role in neointima formation remains unclear. Here, we delineated a remarkable effect of TF3 in suppressing neointima formation of VSMCs in vivo as well as the ability of primary rat aortic smooth cells (RASMCs) to proliferate and migrate in vitro. Further study confirmed that the effects of TF3 on PDGF-BB-induced RASMCs were due to reduced phosphorylation of PDGFRß, which led to the repression of downstream pathways. We concluded that TF3 may act as a repressor in the progression of neointima formation and serve as a potential therapeutic candidate for excessive phenotypic switching of VSMCs.

11.
J Immunol Res ; 2022: 7375879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832649

RESUMO

Prostate cancer (PCa) is the most common cancer affecting men, with increasing global mortality and morbidity rates. Despite the progress in the diagnosis and treatment of PCa, patient outcomes remain poor, and novel therapeutic targets for PCa are urgently needed. Recently, circular RNAs (circRNAs) have been studied in-depth as potential biomarkers for many diseases. In this study, circRNA microarrays using four pairs of PCa tissues were utilized to show that circGFRA1 was upregulated in PCa tumor tissues. CircGFRA1 is suggested to play an oncogene role in PCa progression as the silencing of circGFRA1 inhibited the proliferation, migration, and immune escape activity of PCa cells. Furthermore, by utilizing bioinformatics analysis, RIP, RNA pull-down, and luciferase reporter assays, our results showed that LMX1B could bind to the GFRA1 promoter and regulate circGFRA1 expression in PCa cells and circGFRA1 upregulated HECTD1 expression through sponging miR-3064-5p. This novel LMX1B/circGFRA1/miR-3064-5p/HECTD1 axis identified in PCa provides new insights for developing novel therapeutic strategies for PCa.


Assuntos
MicroRNAs , Neoplasias da Próstata , RNA Circular , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , Proteínas com Homeodomínio LIM , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Circular/genética , RNA Circular/metabolismo , Fatores de Transcrição , Evasão Tumoral
12.
J Clin Nurs ; 31(15-16): 2271-2286, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34523181

RESUMO

AIMS AND OBJECTIVES: To investigate the characteristics and prevalence of demoralisation syndrome among heart transplantation patients in Taiwan. BACKGROUND: Patients with end-stage heart failure who have undergone cardiac transplantation are at risk of demoralisation syndrome. Demoralisation syndrome has been studied in cancer populations, but our understanding of the syndrome among heart transplant recipients is limited. DESIGN AND METHODS: The study adopted a cross-sectional design and analysed the baseline data from a longitudinal study with cardiac transplant patients at a heart centre in northern Taiwan. A structured questionnaire, namely the Demoralization Scale-Mandarin Version (DS-MV), was used to assess demoralisation syndrome. Hierarchical regression was applied to determine the predictors of demoralisation. Reporting was consistent with the STROBE checklist. RESULTS: There were a total of 84 participants with an average age of 51.9 years and a time since heart transplantation of around 4.1 years. Among them, the prevalence of demoralisation syndrome was 35.8%, and 57.1% coped well with stress. In addition, on the DS-MV, participants tended to choose sentences with positive rather than negative wording. Our data showed that cardiac transplant recipients with stress have higher possibility suffering from demoralisation syndrome; poor renal function and those who cannot relive from stress are predictors for loss of meaning. CONCLUSIONS: Chinese individuals tend to hide their weaknesses; nevertheless, demoralisation syndrome among cardiac transplant recipients, as related to stress status and kidney function, is still remarkable. RELEVANCE TO CLINICAL PRACTICE: Since demoralisation is preventable, further research on this phenomenon in the cardiac transplant population is warranted and needs to be developed.


Assuntos
Desmoralização , Transplante de Coração , Estudos Transversais , Transplante de Coração/efeitos adversos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Inquéritos e Questionários , Síndrome
13.
Sci Rep ; 11(1): 19652, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608241

RESUMO

Traumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn't been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.


Assuntos
Biomarcadores , Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/metabolismo , Circulação Cerebrovascular , Choque Hemorrágico/complicações , Nervo Trigêmeo/fisiologia , Animais , Biópsia , Encéfalo , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/fisiopatologia , Suscetibilidade a Doenças , Imunofluorescência , Hemodinâmica , Imuno-Histoquímica , Mediadores da Inflamação , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Prognóstico , Ratos
14.
Ann Palliat Med ; 10(9): 9984-9992, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628922

RESUMO

BACKGROUND: The long protocol has been recognized as the gold standard in controlled ovarian hyperstimulation (COH). However, the full dose of gonadotropin-releasing hormone agonist (GnRH-a) under the prolonged protocol has become increasingly popular in China. This study sought to compare pregnancy outcomes among the following 3 groups: a long protocol group, and 2 types of improved prolonged protocol groups. METHODS: A retrospective cohort study was conducted of 550 patients undergoing fresh embryo transfer (ET). Patients were treated either with the improved prolonged protocol in the follicular phase (Group 1; n=288) or the mid-luteal phase (Group 2; n=143), or the long protocol (Group 3; n=119). The clinical and laboratory outcomes of the 3 groups were compared. RESULTS: The general characteristics of the women in the 3 groups were comparable. On the day on which gonadotropin (Gn) was first administered and on the day on which human chorionic gonadotropin (hCG) was administered, the luteinizing hormone (LH) levels of patients in both Groups 1 and 2 were lower than those of patients in Group 3. The number of oocytes retrieved, fertilized, and cleaved, and the number of high-quality embryos in the 3 procedures were similar. However, the number of transferred embryos, the rate of blastocyst progression, and the rate of implantation differed. The clinical pregnancy rates (CPRs)were significantly higher in the prolonged protocol groups (62.5% and 61.5%) than the long protocol group (48.7%). Further, statistically significant differences in the live-birth rates (LBRs) (56.9% vs. 57.3% vs. 42.9%) were observed. However, no differences in early abortion rates were found. CONCLUSIONS: As a result of pituitary downregulation with GnRH-a, the prolonged groups had better CPRs and LBRs than the long protocol group. The prolonged protocol in the mid-luteal phase was equally effective as that in the early follicular phase in fresh in-vitro fertilization (IVF)/intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. High LH levels on the day of hCG may be a predictor of adverse clinical outcomes.


Assuntos
Coeficiente de Natalidade , Indução da Ovulação , Regulação para Baixo , Feminino , Hormônio Liberador de Gonadotropina , Humanos , Gravidez , Estudos Retrospectivos
15.
J Immunol Res ; 2021: 1782728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527749

RESUMO

BACKGROUND: Chimeric antigen receptor-modified T cell (CAR-T) therapy has great potential for treating malignant tumors, especially hematological malignancies. However, the therapeutic effect of solid tumors is limited. One of the most important factors is the homing of CAR-T cells to tumor tissues in vivo. METHOD: a recombinant adeno-associated virus 2 (AAV2) subtype carrying the CCL19 gene was used to pretreat the tumor before the Glypican-3 (GPC3) CAR-T treatment. The tumor tissue continuously expressed CCL19 and analyzed the tumor-suppressive effect of AAV-CCL19 on GPC3 CAR-T by in vitro and in vivo experiments. RESULT: Under the chemotaxis of CCL19, CAR-T cells had a significant increase in the degree of tumor tissue infiltration; also, the antitumor effect in vitro was significantly enhanced. AAV-CCL19 combined with GPC3 CAR-T significantly increased the survival time of mice. The aforementioned results showed that the combination of AAV-CCL19 and GPC3 CAR-T cells effectively increased the ability of CAR-T cells to go home into the tumor tissue, making the CAR-T cell treatment more effective. CONCLUSION: This study is expected to solve the dilemma in treating CAR-T cell solid tumors and achieve better clinical results.


Assuntos
Carcinoma Hepatocelular/terapia , Quimiocina CCL19/genética , Glipicanas/genética , Imunoterapia Adotiva , Neoplasias Hepáticas/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/metabolismo , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Quimiotaxia/imunologia , Dependovirus/genética , Modelos Animais de Doenças , Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Memória Imunológica , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Camundongos , Receptores de Antígenos Quiméricos/genética , Linfócitos T/imunologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
16.
ACS Sens ; 6(6): 2403-2410, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34081429

RESUMO

Various volatile aerosols have been associated with adverse health effects; however, characterization of these aerosols is challenging due to their dynamic nature. Here, we present a method that directly measures the volatility of particulate matter (PM) using computational microscopy and deep learning. This method was applied to aerosols generated by electronic cigarettes (e-cigs), which vaporize a liquid mixture (e-liquid) that mainly consists of propylene glycol (PG), vegetable glycerin (VG), nicotine, and flavoring compounds. E-cig-generated aerosols were recorded by a field-portable computational microscope, using an impaction-based air sampler. A lensless digital holographic microscope inside this mobile device continuously records the inline holograms of the collected particles. A deep learning-based algorithm is used to automatically reconstruct the microscopic images of e-cig-generated particles from their holograms and rapidly quantify their volatility. To evaluate the effects of e-liquid composition on aerosol dynamics, we measured the volatility of the particles generated by flavorless, nicotine-free e-liquids with various PG/VG volumetric ratios, revealing a negative correlation between the particles' volatility and the volumetric ratio of VG in the e-liquid. For a given PG/VG composition, the addition of nicotine dominated the evaporation dynamics of the e-cig aerosol and the aforementioned negative correlation was no longer observed. We also revealed that flavoring additives in e-liquids significantly decrease the volatility of e-cig aerosol. The presented holographic volatility measurement technique and the associated mobile device might provide new insights on the volatility of e-cig-generated particles and can be applied to characterize various volatile PM.


Assuntos
Aprendizado Profundo , Sistemas Eletrônicos de Liberação de Nicotina , Aerossóis , Microscopia , Propilenoglicol
17.
Metabolism ; 118: 154730, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33607194

RESUMO

BACKGROUND: Human differentiated embryonic chondrocyte expressed gene 1 (DEC1) has been implicated in enhancing osteogenesis, a desirable outcome to counteract against deregulated bone formation such as retarded bone development, osteopenia and osteoporosis. METHODS AND RESULTS: DEC1 knockout (KO) and the age-matched wild-type (WT) mice were tested for the impact of DEC1 deficiency on bone development and osteopenia as a function of age. DEC1 deficiency exhibited retarded bone development at the age of 4 weeks and osteopenic phenotype in both 4- and 24-week old mice. However, the osteopenia was more severe in the 24-week age groups. Mechanistically, DEC1 deficiency downregulated the expression of bone-enhancing genes such as Runx2 and ß-catenin accompanied by upregulating DKK1, an inhibitor of the Wnt/ß-catenin signaling pathway. Consistently, DEC1 deficiency favored the attenuation of the integrated PI3KCA/Akt/GSK3ß signaling, a pathway targeting ß-catenin for degradation. Likewise, the attenuation was greater in the 24-week age group. These changes, however, were reversed by in vivo treatment with lithium chloride, a stabilizer of ß-catenin, and confirmed by gain-of-function study with DEC1 transfection into DEC1 KO bone marrow mesenchymal stem cells and loss-of-function study with siDEC1 lentiviral infection into the corresponding WT cells. CONCLUSION: DEC1 is a positive regulator with a broad activity spectrum in both bone development and maintenance, and the osteopenic phenotype accelerated by DEC1 deficiency is achieved by enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3ß signaling.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Desenvolvimento Ósseo , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/patologia , Diferenciação Celular , Progressão da Doença , Humanos , Camundongos , Camundongos Knockout , Osteoblastos/citologia , beta Catenina/metabolismo
18.
Angew Chem Int Ed Engl ; 59(46): 20399-20404, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32744375

RESUMO

Reported here is the discovery of a redox-neutral NiII /NiII catalytic cycle which is capable of the linear-selective hydroarylation of unactivated alkenes with arylboronic acids for the first time. This novel catalytic cycle, enabled by the use of an electron-rich diimine ligand, features broad substrate scope, and excellent functional-group and heterocycle compatibility under mild reaction conditions in the absence of additional oxidants and reductants. Mechanistic investigations using kinetic analysis and deuterium-labelling experiments revealed the protonation to be the rate-determining step in this redox-neutral catalysis, and the reversible chain-walking nature of the newly developed diimine-Ni catalyst.

19.
Front Pharmacol ; 11: 601468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33628174

RESUMO

Timosaponin AIII (TAIII), a steroidal saponin, exerts potent anti-tumor activity in various cancers, especially breast cancer. However, the concrete molecular mechanisms of TAIII against breast cancer are still unclear. Here, we find that TAIII triggers DNA damage, leads to G2/M arrest, and ultimately induces apoptosis in breast cancer both in vitro and in vivo. TAIII induced G2/M phase arrest and apoptosis in MDA-MB-231 and MCF7 cells accompanied with down-regulation of CyclinB1, Cdc2 and Cdc25C. Further data showed that the ATM/Chk2 and p38 pathways were activated representing by up-regulated levels of p-H2A.X and p-p38, which indicated an induction of DNA damage by TAIII, leading to cell cycle arrest and apoptosis. The effects of TAIII were further confirmed by employing inhibitors of ATM and p38 pathways. In vivo, TAIII suppressed the growth of subcutaneous xenograft tumor without obvious toxicity, which indicated by Ki67 and TUNEL analysis. Data also showed that TAIII stimulated the ATM/Chk2 and p38 MAPK pathways in vivo, which in consistent with the effects in vitro. Hence, our data demonstrate that TAIII triggers DNA damage and activates ATM/Chk2 and p38 MAPK pathways, and then induces G2/M phase arrest and apoptosis in breast cancer, which provide theoretical evidence for TAIII utilized as drug against breast cancer.

20.
Front Immunol ; 10: 2750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824516

RESUMO

T-helper-17 (Th17) cells are a subset of CD4+ T cells that can produce the cytokine interleukin (IL)-17 and play vital roles in protecting the host from bacterial and fungal infections, especially at the mucosal surface. These are abundant in the small intestinal lamina propria (SILP) and their differentiation are associated with the colonization of the intestinal flora. Segmented filamentous bacteria (SFB) drew the attention of researchers due to their unique ability to drive the accumulation of Th17 cells in the SI LP of mice. Recent work has highlighted that SFB used microbial adhesion-triggered endocytosis (MATE) to transfer SFB antigenic proteins into small intestinal epithelial cells (SI ECs) and modulate host immune homeostasis. However, which components of SFB are involved in this immune response process remains unclear. Here, we examined the roles of SFB flagellins in Th17 cells induction using various techniques, including ELISA, ELISPOT, and RNA-seq in vitro and in vivo. The results show that the immune function of SFB flagellins is similar to SFB, i.e., induces the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the SI LP. Furthermore, treatment of mice with SFB flagellins lead to a significant increase in the expression of genes associated with the IL-17 signaling pathway, such as IL-6, IL-1ß, TNF-α, IL-17A, IL-17F, and IL-22. In addition, SFB flagellins have an intimate relationship with intestinal epithelial cells, influencing the expression of epithelial cell-specific genes such as Nos2, Duox2, Duoxa2, SAA3, Tat, and Lcn2. Thus, we propose that SFB flagellins play a significant role in the involvement of SFB in the induction of intestinal Th17 cells.


Assuntos
Bactérias/imunologia , Flagelina/imunologia , Mucosa Intestinal , Intestino Delgado , Células Th17/imunologia , Animais , Aderência Bacteriana/imunologia , Citocinas/imunologia , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Intestino Delgado/citologia , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Masculino , Camundongos , Células Th17/citologia
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