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1.
Front Immunol ; 14: 1142539, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122754

RESUMO

As an important mediator of information transfer between cells, exosomes play a unique role in regulating tumor growth, supporting vascular proliferation, tumor invasion, and metastasis. Exosomes are widely present in various body fluids, and therefore they can be used as a potential tool for non-invasive liquid biopsy. The present study reviews the role of exosomes in liquid biopsy, tumor microenvironment formation, and epithelial-mesenchymal transition in non-small cell lung cancer (NSCLC). By targeting epidermal growth factor receptor (EGFR) therapy as a first-line treatment for patients with NSCLC, this study also briefly describes the occurrence of EGRF+ exosomes and the role of exosomes and their contents in non-invasive detection and potential therapeutic targets in EGFR-mutated lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Exossomos/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Microambiente Tumoral/genética
2.
PLoS One ; 18(5): e0285363, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37141339

RESUMO

PURPOSE: The study aimed to investigate how two English as a Foreign Language (EFL) teachers integrated their teacher and researcher identities to achieve sustainable professional growth in the context of a changing academic landscape. METHODS: Using purposive sampling, two EFL teachers from a non-elite public university in China were selected as participants for this qualitative study. Data were collected and triangulated from multiple sources, including semi-structured interviews, narrative frames, document analysis, and the academic profiles of the participants. A qualitative, inductive thematic approach was employed in the data analysis. Adopting "identity" as an analytical lens, this study examined how the two participants underwent different identity trajectories to develop into teacher-researchers under the influence of their personal values and beliefs, as well as contextual factors such as institutional research policy. FINDINGS: Throughout their identity construction process, the two participants encountered identity deficits and tensions between multiple professional roles, leading to their struggles with identity and complex identity (re)construction. While the participants underwent interactions between various forms of identity throughout their careers, they enacted agency to take actions and draw on available resources to address their identity deficits and conflicts, ultimately resolving them by pursuing a sustainable career path as teacher-researchers in their situated socio-institutional environment. CONCLUSION: Despite their different identity trajectories, the construction of the participants' teacher-researcher identity facilitated their continuing professional development. This study contributes to our understanding of the complexities of EFL teachers' identity (re)construction when seeking to establish sustainable career paths in a changing academic context. This study also has implications for both EFL academics and university management on how to assist EFL teachers in integrating teacher and researcher identities to achieve sustainable professional development in higher education.


Assuntos
Pessoal de Educação , Idioma , Humanos , China , Análise de Dados , Análise Documental
3.
Methods Mol Biol ; 2666: 149-155, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37166663

RESUMO

Ribosomal profiling is a widely used technique for deep sequencing of ribosome-protected mRNA and for measuring ribosome status in cells. It is a powerful method that is typically employed for monitoring and measuring protein translation status and ribosome activity. Also, it has been used for monitoring the ribosomal stress-responsive events in the ribosome activity. Furthermore, this approach enables understanding of translational regulation, which is invisible in most proteomic approaches. Moreover, this method is known as an important approach for biological discovery such as identification of translation products. Hence, this methodology will be useful for studying cellular events engaging in ribosome assembly, ribosome biogenesis, ribosome activity, translation during the cell cycle, cell proliferation, and growth as well as the ribosomal stress response in mammalian cells.


Assuntos
Proteômica , Proteínas Ribossômicas , Animais , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , Proliferação de Células , Mamíferos/metabolismo
4.
Heliyon ; 9(5): e15737, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37180886

RESUMO

Anesthesia management of Totally thoracoscopic cardiac surgery (TTCS) has been the subject of much debate and discussion. In this single center retrospective study, we summarize the experience of clinical anesthesia management for TTCS by review the medical records of our medical center and look forward to its future development. In this retrospective study, 103 patients (49 male and 54 female) were enrolled, the mean age was 56.7 ± 14.4 years old. The participants underwent Mitral Valve Replacement (MVR) + Tricuspid Valve Annuloplasty (TVA) (42, 40.8%), Mitral Valve Annuloplasty (MVA) + TVA (38, 36.9%), MVA (21, 20.4%), and MVR (2, 1.9%),respectively. Intraoperative hypoxemia, radiographic pulmonary infiltrates, and pneumonia were observed in 19 (18.4%), 84 (81.6%), and 13 (12.6%) patients, respectively. The LOS of ICU and POD were as follows: MVR + TVA (55.1 ± 25h, 9.9 ± 3.5 d), MVA + TVA (56.5 ± 28.4h, 9.4 ± 4.2d), MVA (37.9 ± 21.9h, 8.1 ± 2.3d) and MVR (48 ± 4.2h, 7.5 ± 2.1d). No reintubation, reoperations, postoperative cognitive dysfunction, 30-day mortality were observed in the present study. The present study demonstrated that applying this anesthesia management for TTCS associated with acceptable morbidity, intensive care unit and postoperative hospital lengths of stay. The finding from the present study might provide some new approach for Anesthesia management of TTCS.

5.
Prev Chronic Dis ; 20: E37, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37167553

RESUMO

INTRODUCTION: Local data are increasingly needed for public health practice. County-level data on disabilities can be a valuable complement to existing estimates of disabilities. The objective of this study was to describe the county-level prevalence of disabilities among US adults and identify geographic clusters of counties with a higher or lower prevalence of disabilities. METHODS: We applied a multilevel logistic regression and poststratification approach to geocoded 2018 Behavioral Risk Factor Surveillance System data, Census 2018 county-level population estimates, and American Community Survey 2014-2018 poverty estimates to generate county-level estimates for 6 functional disabilities and any disability type. We used cluster-outlier spatial statistical methods to identify clustered counties. RESULTS: Among 3,142 counties, median estimated prevalence was 29.5% for any disability and differed by type: hearing (8.0%), vision (4.9%), cognition (11.5%), mobility (14.9%), self-care (3.7%), and independent living (7.2%). The spatial autocorrelation statistic, Moran's I, was 0.70 for any disability and 0.60 or greater for all 6 types of disability, indicating that disabilities were highly clustered at the county level. We observed similar spatial cluster patterns in all disability types except hearing disability. CONCLUSION: The results suggest substantial differences in disability prevalence across US counties. These data, heretofore unavailable from a health survey, may help with planning programs at the county level to improve the quality of life for people with disabilities.


Assuntos
Pessoas com Deficiência , Qualidade de Vida , Humanos , Adulto , Estados Unidos/epidemiologia , Pobreza , Censos , Modelos Logísticos
6.
ACS Appl Mater Interfaces ; 15(20): 24346-24353, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37184859

RESUMO

Precise electronic state regulation through coordination environment optimization by metal-support interaction is a promising strategy to facilitate catalysis reaction, while the limited density of functional groups in the bulk substrate restricts the regulation degree. Herein, different sizes of Ti3C2Tx MXene with hydroxyl (-OH) terminal including the MXene layer (ML-OH, 3 µm), the MXene nanosheet (MNS-OH, 600 nm), and the MXene quantum dot (MQD-OH, 8 nm) were prepared to anchor CoPc, and the effect of -OH density on the performance of electrochemical CO2 reduction was systematically investigated. Notably, a linear relationship was established by plotting reactivity vs hydroxyl density. With the highest -OH density, CoPc/MQD-OH exhibits a superior Faradaic efficiency for CO formation (FECO) of ∼100% at -0.9 to -1.0 V vs RHE and a high FECO of >90% over a wide potential window from -0.8 to -1.4 V. The mechanism exploration shows that the axial coordination interaction of the -OH terminal with Co increases the electron density of the Co site, thus promoting the adsorption and activation of CO2. This work provides a new insight into designing of molecular catalysts with high efficiency and tunable structure for other electrochemical conversions.

7.
BMC Surg ; 23(1): 118, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170233

RESUMO

BACKGROUND: Locking plates are commonly used in the treatment of comminuted metaphyseal distal femoral fractures. However, locking plates form a strong structure and promote asymmetrical callus formation, which is not conducive for rapid fracture healing and may increase fracture risk. To overcome this, we designed a micromotion-balancing fixation system based on locking plates. METHODS: Six healthy pigs (Bama miniature pigs) were used to establish a model of bilateral comminuted distal femoral fracture (AO/ASIF: 33-C2). Standard drilling was performed on one of each pig's hind limbs (control group), whereas eccentric drilling was performed on the other hind limb (experimental group). Both femurs were fixed with a 3-hole locking compression plate using 5-mm-diameter screws. At 12 postoperative weeks, all pigs were euthanized and the femurs with compression plates were radiographically examined. The level of fracture healing and loosening/internal fixation failure were recorded. Bone mineral density, number of trabeculae, trabecular morphology, and calcification precipitations were assessed. RESULTS: All pigs survived, and the fractures healed. No complications related to fracture healing, such as infection and internal fixation failure, were noted. The bone mineral density of the near and far cortical calli, number of the near and far cortical callus trabeculae, and difference in bone mineral density between the near and far cortical calli in the experimental group were significantly higher than those in the control group (p < 0.01). However, the difference in the number of trabeculae between the near and far cortical calli was significantly lower in the experimental group than in the control group (p < 0.01). CONCLUSION: This newly designed system provides stable fixation for comminuted distal femoral fracture, increases the overall strain at the fracture site, and balances the strains at the near and far cortices to achieve uniform callus growth and fracture healing.


Assuntos
Fraturas Femorais Distais , Fraturas Cominutivas , Animais , Suínos , Fixação Interna de Fraturas , Consolidação da Fratura , Fraturas Cominutivas/cirurgia , Placas Ósseas
8.
Langmuir ; 39(18): 6539-6547, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37127842

RESUMO

Attaching polymers, especially polyethylene glycol (PEG), to protein drugs has emerged as a successful strategy to prolong circulation time in the bloodstream. The hypothesis is that the flexible chain wobbles on the protein's surface, thus resisting potential nonspecific adsorption. Such a theoretical framework may be challenged when a helical polyglutamate is used to conjugate with target proteins. In this study, we investigated the structure-activity relationships of polyglutamate-interferon conjugates P(EG3Glu)-IFN using molecular simulations. Our results show that the local crowding effect induced by oligoethylene glycols (i.e., EG3) is the primary driving force for helix formation in P(EG3Glu), and its helicity can be effectively increased by reducing the free volume of the two termini. Furthermore, it was found that the steric hindrance induced by IFN is not conductive to the helicity of P(EG3Glu) but contributes to its dominant orientation relative to interferon. The orientation of IFN relative to the helical P(EG3Glu) can help to protect the protein drug from neutralizing antibodies while maintaining its bioactivity. These findings suggest that the helical structure and its orientation are critical factors to consider when updating the theoretical framework for protein-polymer conjugates.


Assuntos
Interferons , Ácido Poliglutâmico , Interferons/química , Polietilenoglicóis/química , Polímeros/química , Proteínas
9.
Front Mol Biosci ; 10: 1183808, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152902

RESUMO

Chronic liver disease or repeated damage to hepatocytes can give rise to hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation of extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the hepatic parenchyma. Changes in the composition of the ECM lead to the stiffness of the matrix that destroys its inherent mechanical homeostasis, and a mechanical homeostasis imbalance activates hepatic stellate cells (HSCs) into myofibroblasts, which can overproliferate and secrete large amounts of ECM proteins. Excessive ECM proteins are gradually deposited in the Disse gap, and matrix regeneration fails, which further leads to changes in ECM components and an increase in stiffness, forming a vicious cycle. These processes promote the occurrence and development of hepatic fibrosis. In this review, the dynamic process of ECM remodeling of HF and the activation of HSCs into mechanotransduction signaling pathways for myofibroblasts to participate in HF are discussed. These mechanotransduction signaling pathways may have potential therapeutic targets for repairing or reversing fibrosis.

10.
J Org Chem ; 88(9): 5291-5299, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37079904

RESUMO

Fusion selenophene endows the chromophore with more intrinsic and special functions. Herein, nonsymmetric selenophene-fused BODIPYs were designed and synthesized starting from the selenophene unit. The fused ring of selenophene not only maintains the rigid structure of BODIPY but also further modulates its spectral properties. The newly prepared dyes possessed many promising properties including large molar extinction coefficients, low fluorescence quantum yields, and moderate singlet oxygen generation. Quantum calculations affirmed that the smaller singlet-triplet energy gap and larger spin-orbit coupling cause efficient intersystem crossing, thus enhancing the singlet oxygen generation yield. Furthermore, selenophene-fused BODIPY exhibited significant phototoxicity with negligible dark cytotoxicity, based on the fluorescence imaging of the reactive oxygen species detection experiment.

11.
ACS Macro Lett ; 12(5): 555-562, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37041004

RESUMO

The ring-opening (co)polymerization (ROP) of N-carboxyanhydride (NCA) monomers bearing unprotected/reactive side groups is rare and challenging. Here, we report the ROP of a d-penicillamine NCA (Pen-NCA) monomer for the synthesis of tertiary thiol-functionalized (co)polypeptides. Through judicious selection of reaction solvents and the use of benzoic acid as an additive in the ROP, the intramolecular isomerization side reactions of Pen-NCA are suppressed, generating homo- and copolypeptides with improved yield, high molecular weight, and narrow molecular weight distributions. Successful postpolymerization modifications of the d-Pen-containing copolypeptides on the tertiary thiols are achieved with high efficiency through thiol-Michael, SN2, and nitrosylation reactions. This work provides an efficient protection-free approach to generating functional polypeptides and creates a fundamental understanding for Pen-NCA chemistry.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 389-395, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37096510

RESUMO

OBJECTIVE: To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients. METHODS: The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively. RESULTS: A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival. CONCLUSION: In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.


Assuntos
Neoplasias Hematológicas , Linfoma , Mieloma Múltiplo , Segunda Neoplasia Primária , Humanos , População do Leste Asiático , Neoplasias Hematológicas/complicações , Linfoma/complicações , Mieloma Múltiplo/complicações , Estudos Retrospectivos , Análise de Sobrevida
13.
J Ethnopharmacol ; 311: 116409, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37003401

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with ß-elemene (BE) being its main active compound, along with trace amounts of ß-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. AIM OF THE STUDY: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. MATERIALS AND METHODS: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. RESULTS: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC50 of EE and its main active components, BE and BC, was around 60 µg/mL. Flow cytometry analysis showed that BE and BC blocked the G2/M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. CONCLUSIONS: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Sesquiterpenos , Animais , Camundongos , Caspase 9/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/patologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Apoptose , Glutationa/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
14.
Redox Biol ; 62: 102705, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37087976

RESUMO

The eukaryotic ribosome is essential for cancer cell survival. Perturbation of ribosome biogenesis induces nucleolar stress or ribosomal stress, which restrains cancer growth, as rapidly proliferating cancer cells need more active ribosome biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and associated with poor prognoses. Interestingly, depletion of UTP11 inhibits cancer cell growth in vitro and in vivo through p53-depedednt and -independent mechanisms, whereas UTP11 overexpression promotes cancer cell growth and progression. On the one hand, the ablation of UTP11 impedes 18S rRNA biosynthesis to trigger nucleolar stress, thereby preventing MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins, RPL5 and RPL11. On the other hand, UTP11 deficiency represses the expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced levels of glutathione (GSH) and enhanced ferroptosis. Altogether, our study uncovers a critical role for UTP11 in maintaining cancer cell survival and growth, as depleting UTP11 leads to p53-dependent cancer cell growth arrest and p53-independent ferroptosis.


Assuntos
Ferroptose , Neoplasias , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proliferação de Células/genética , Ribossomos/genética , Ribossomos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo
15.
Ying Yong Sheng Tai Xue Bao ; 34(3): 597-604, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37087641

RESUMO

With the combination of airborne Lidar and panchromatic images in 1981 and 2021, we investigated the canopy height structure of tropical forests in Menglun sub-reserve in the Xishuangbanna National Nature Reserve of Yunnan Province, and analyzed its relationship with environmental factors by using multiple regression tree (MRT) method. The results showed that forests in the Menglun sub-reserve could be clustered into seven types based on canopy height structures, with tropical rainforest, monsoon evergreen broad-leaved forest, secondary forest, and flood plain forest as the main types. The potential solar radiation, altitude, terrain profile curvature, slope and the brightness value of imageries in 1981 and 2021 were main factors that drove the classification. The tropical seasonal rainforest dominated by Pometia pinnata occupied the largest area in valley and low-land. The monsoon evergreen broad-leaved forest dominated by Castanopsis echinocarpa mainly distributed in the ridge and disturbed areas. The secondary forests had homogeneous canopy surface, which was significantly different from the primary forests. The activities of swidden agriculture about three decades ago had legacy impacts on the physiognomy of secondary forests.


Assuntos
Florestas , Floresta Úmida , Altitude , China , Clima Tropical
16.
Heliyon ; 9(4): e14816, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37035389

RESUMO

Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.

17.
Angew Chem Int Ed Engl ; 62(22): e202303483, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-36988074

RESUMO

Electrochemically converting NO3 - into NH3 offers a promising route for water treatment. Nevertheless, electroreduction of dilute NO3 - is still suffering from low activity and/or selectivity. Herein, B as a modifier was introduced to tune electronic states of Cu and further regulate the performance of electrochemical NO3 - reduction reaction (NO3 RR) with dilute NO3 - concentration (≤100 ppm NO3 - -N). Notably, a linear relationship was established by plotting NH3 yield vs. the oxidation state of Cu, indicating that the increase of Cu+ content leads to an enhanced NO3 - -to-NH3 conversion activity. Under a low NO3 - -N concentration of 100 ppm, the optimal Cu(B) catalyst displays a 100 % NO3 - -to-NH3 conversion at -0.55 to -0.6 V vs. RHE, and a record-high NH3 yield of 309 mmol h-1 gcat -1 , which is more than 25 times compared with the pristine Cu nanoparticles (12 mmol h-1 gcat -1 ). This research provides an effective method for conversion of dilute NO3 - to NH3 , which has certain guiding significance for the efficient and green conversion of wastewater in the future.

18.
Cells ; 12(6)2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36980298

RESUMO

Drug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence in late development results in increased costs, human risk, and delayed market availability of novel therapeutics. Therefore, there is an urgent need for biologically relevant, in vitro high-throughput screening assays (HTS) to predict potential risks for drug-induced seizure early in drug discovery. We investigated drug-induced changes in neural Ca2+ oscillations, using fluorescent dyes as a potential indicator of seizure risk, in hiPSC-derived neurons co-cultured with human primary astrocytes in both 2D and 3D forms. The dynamics of synchronized neuronal calcium oscillations were measured with an FDSS kinetics reader. Drug responses in synchronized Ca2+ oscillations were recorded in both 2D and 3D hiPSC-derived neuron/primary astrocyte co-cultures using positive controls (4-aminopyridine and kainic acid) and negative control (acetaminophen). Subsequently, blinded tests were carried out for 25 drugs with known clinical seizure incidence. Positive predictive value (accuracy) based on significant changes in the peak number of Ca2+ oscillations among 25 reference drugs was 91% in 2D vs. 45% in 3D hiPSC-neuron/primary astrocyte co-cultures. These data suggest that drugs that alter neuronal activity and may have potential risk for seizures can be identified with high accuracy using an HTS approach using the measurements of Ca2+ oscillations in hiPSC-derived neurons co-cultured with primary astrocytes in 2D.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Células Cultivadas , Ensaios de Triagem em Larga Escala , Neurônios , Convulsões/induzido quimicamente
20.
Biomed Res Int ; 2023: 5647758, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36733404

RESUMO

Background: Multiple circular RNAs (circRNAs) are implicated in atherosclerosis (AS) pathogenesis. In fact, how circRNA 0026218 (circ_0026218) functions in AS remains unknown, and thus the functions and mechanisms of circ_0026218 in the injury of vascular endothelial cells are to be investigated. Methods: Microarray analysis was employed to screen out differentially expressed circRNAs in AS. A cell model was mimicked by treating Human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL). circ_0026218, microRNA-338-3p (miR-338-3p) and silent information regulator 6 (SIRT6) expressions in HUVECs with ox-LDL treatment were probed by qRT-PCR. The cell proliferative capabilities were exposed by CCK-8 assay. The contents of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and tumor necrosis factor α (TNF-α) were measured by ELISA. Oxidative stress kits were utilized to detect the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA). Flow cytometry was adopted to analyze the level of apoptosis of HUVECs. Dual-luciferase reporter gene assay and RIP assay were leveraged to expose the interplay between miR-338-3p and circ_0026218 or SIRT6 3'-UTR, respectively. In addition, the impacts of circ_0026216 and miR-338-3p on SIRT6 protein expressions were subjected to Western blot. Results: circ_0026218 was greatly depleted in ox-LDL-stimulated HUVECs. circ_0026218 overexpression promoted viability of HUVECs in vitro and inhibited inflammatory response, oxidative stress, and apoptosis. circ_0026218 could adsorb miR-338-3p and positively modulated SIRT6 expressions via sponging miR-338-3p. Upregulation of this miRNA reversed the influence of circ_0026218 overexpression on ox-LDL-caused injury and apoptosis of HUVECs. Conclusion: Collectively, circ_0026218 upregulates SIRT6 expression through decoying miR-338-3p, thereby inhibiting ox-LDL-initiated injury of HUVECs. circ_0026218 is involved in the pathogenesis of AS.


Assuntos
Aterosclerose , MicroRNAs , Sirtuínas , Humanos , RNA Circular/genética , Fator de Necrose Tumoral alfa , Apoptose/genética , Aterosclerose/genética , Proliferação de Células/genética , Glicosiltransferases , Células Endoteliais da Veia Umbilical Humana , Sirtuínas/genética , MicroRNAs/genética , Lipoproteínas LDL
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