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1.
ACS Appl Mater Interfaces ; 13(45): 53915-53924, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726379

RESUMO

Owing to the scarcity of Pt, low-cost, stable, and efficient nonprecious metal-based electrocatalysts that can be applied in a wide pH range for the hydrogen evolution reaction (HER) are urgently required. Herein, a highly efficient and robust HER catalyst that is applicable at all pH values is fabricated, containing isolated Co-single atomic sites anchored in the self-supported WO3 arrays grown on Cu foam. At a current density of 10 mA cm-2, the HER overpotentials are 117, 105, and 149 mV at pH values of 0, 7, and 14, respectively, which are significantly lower than those of the undoped WO3, suggesting superior electrocatalytic H2-evolution activity at all pH values. The catalyst also exhibits long-term stability over a wide pH range, particularly in an acidic medium over 24 h, owing to the excellent anticorrosion properties of WO3. Density functional theory calculations prove that the enhanced HER activity is attributed to the isolated Co sites because these optimize the adsorption energy of H* species on WO3. Moreover, the high electrical conductivity of Co-doped WO3 and the three-dimensional array structure supported on the porous metal support afford a catalyst with suitable HER kinetics to enhance the catalytic performance.

2.
Molecules ; 26(21)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34771158

RESUMO

Catalytic asymmetric [2 + 4] cycloadditions of 3-vinylindoles with ortho-quinone methides and their precursors were carried out in the presence of chiral phosphoric acid to afford a series of indole-containing chroman derivatives with structural diversity in overall high yields (up to 98%), good diastereoselectivities (up to 93:7 dr) and moderate to excellent enantioselectivities (up to 98% ee). This approach not only enriches the chemistry of catalytic asymmetric cycloadditions involving 3-vinylindoles but is also useful for synthesizing chiral chroman derivatives.

3.
Brain Res Bull ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34728230

RESUMO

Internet gaming disorder (IGD) has become an increasing mental health issue worldwide. Previous studies indicated that IGD was related to maladaptive risk-taking behavior. However, the relationship among risk-taking behavior, reflection level, and resting-state functional connectivity (rsFC) between brain regions in IGD individuals remains unclear. The current study combined resting-state fMRI and the Devil task to investigate this issue. The behavioral results suggested that IGD participants exhibited increased risk-taking behavior in the Devil task than healthy controls. Moreover, IGD participants' risk-taking behavior was positively correlated with their reflection level. As for fMRI results, IGD participants showed stronger rsFC between orbitofrontal cortex (OFC) and inferior frontal gyrus (IFG) than healthy controls. Additionally, the mediation analyses revealed that, among IGD participants, the rsFC between OFC and IFG fully mediated the relationship between reflection level and risk-taking behavior. Together, the current study highlighted that the altered rsFC between OFC and IFG in IGD individuals modified the relationship between their reflection level and risk-taking behavior, which might contribute to the understanding of neural mechanisms underlying risk-taking behavior in IGD individuals.

4.
Sci Total Environ ; : 151615, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34774954

RESUMO

The extensive use of quaternary ammonium compounds (QACs) has raised concerns regarding their environmental fate and potential risks to the ecosystem. As sensitive pollution indicators, green microalgae could readily monitor the aquatic toxicity of QACs as reflective of the changes in cell viability. Recent microfluidic-based systems have been designed for environmental biomonitoring and ecotoxicity studies while overall information of cell viability cannot be directly visualized under flowing conditions. In the present study, we developed a multifunctional microfluidic platform with the integration of analytical techniques including laser speckle contrast imaging and fluorescence spectroscopy for monitoring algal activity in response to QAC treatment. The biocidal efficiency of a representative QAC benzalkonium bromide (BAB) on a typical aquatic algae Chlorella vulgaris was determined by collecting the bio-speckles and chlorophyll autofluorescence in real-time, where dose-dependent and time-dependent decrease of algal growth was found with the increase of BAB concentration and interaction time. The integrated system was capable of rapid detection of the aquatic toxicity of QACs along with macroscopical visualization of algal activities under flowing conditions in time-course, which could be extended to future implementation for broad ecotoxicity analysis of versatile environmental samples.

5.
Cell Death Dis ; 12(10): 929, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635635

RESUMO

Cervical adenocarcinoma is an important disease that affects young women and it has a high mortality and poor prognosis. Denticleless E3 ubiquitin protein ligase homolog (DTL) gene with oncogenic function has been evaluated in several cancers. Through this study, we aimed to clarify the clinical and molecular characteristics of cervical adenocarcinoma involving overexpression of DTL and elucidate its molecular mechanism. Bioinformatics analysis was performed through multiple databases. RNA sequencing was used to obtain differentially expressed genes after DTL was overexpressed in cells. The role of DTL in cervical adenocarcinoma was explored through in vitro and in vivo experiments. We found that DTL has an unfavorable prognostic implication for patients with cervical adenocarcinoma. Overexpression of DTL induced the migration and invasion of tumor cells in vitro and promoted intra-pulmonary metastasis in vivo. In addition, DTL activated JNK through RAC1 and upregulated FOXO1 to induce epithelial-mesenchymal transition, and the migration and invasion of tumor cells. Therefore, we conclude that overexpression of DTL enhanced cell motility and promoted tumor metastasis of cervical adenocarcinoma by regulating the RAC1-JNK-FOXO1 axis. These results suggest that DTL may become a potential therapeutic target for antitumor metastasis of cervical adenocarcinoma.

6.
Cell Death Dis ; 12(10): 932, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642295

RESUMO

Glioblastoma (GBM) is a brain malignancy characterized by invasiveness to the surrounding brain tissue and by stem-like cells, which propagate the tumor and may also regulate invasiveness. During brain development, polarity proteins, such as Par3, regulate asymmetric cell division of neuro-glial progenitors and neurite motility. We, therefore, studied the role of the Par3 protein (encoded by PARD3) in GBM. GBM patient transcriptomic data and patient-derived culture analysis indicated diverse levels of expression of PARD3 across and independent from subtypes. Multiplex immunolocalization in GBM tumors identified Par3 protein enrichment in SOX2-, CD133-, and NESTIN-positive (stem-like) cells. Analysis of GBM cultures of the three subtypes (proneural, classical, mesenchymal), revealed decreased gliomasphere forming capacity and enhanced invasiveness upon silencing Par3. GBM cultures with suppressed Par3 showed low expression of stemness (SOX2 and NESTIN) but higher expression of differentiation (GFAP) genes. Moreover, Par3 silencing reduced the expression of a set of genes encoding mitochondrial enzymes that generate ATP. Accordingly, silencing Par3 reduced ATP production and concomitantly increased reactive oxygen species. The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.

7.
Front Psychol ; 12: 688376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630204

RESUMO

Objective: To explore the characteristics of expression recognition and spontaneous activity of the resting state brain in major depressive disorder (MDD) patients to find the neural basis of expression recognition and emotional processing. Methods: In this study, two of the six facial expressions (happiness, sadness, anger, fear, aversion, and surprise) were presented in quick succession using a short expression recognition test. The differences in facial expression recognition between MDD patients and healthy people were compared. Further, the differences in ReHo values between the two groups were compared using a resting-state functional magnetic resonance imaging (fMRI) scan to investigate the characteristics of spontaneous brain activity in the resting state and its relationship with clinical symptoms and the accuracy of facial expression recognition in patients with MDD. Results: (1) The accuracy of facial expression recognition in patients with MDD was lower than that of the HC group. There were differences in facial expression recognition between the two groups in sadness-anger (p = 0.026), surprise-aversion (p = 0.038), surprise-happiness (p = 0.014), surprise-sadness (p = 0.019), fear-happiness (p = 0.027), and fear-anger (p = 0.009). The reaction time for facial expression recognition in the patient group was significantly longer than that of the HC group. (2) Compared with the HC group, the ReHo values decreased in the left parahippocampal gyrus, left thalamus, right putamen, left putamen, and right angular gyrus, and increased in the left superior frontal gyrus, left middle temporal gyrus, left medial superior frontal gyrus, and right medial superior frontal gyrus in the patient group. (3) Spearman correlation analysis showed no statistical correlation between ReHo and HAMD-17 scores in MDD patients (p > 0.05). The ReHo value of the left putamen was negatively correlated with the recognition of fear-surprise (r = -0.429, p = 0.016), the ReHo value of the right angular gyrus was positively correlated with the recognition of sadness-anger (r = 0.367, p = 0.042), and the ReHo value of the right medial superior frontal gyrus was negatively correlated with the recognition of fear-anger (r = -0.377, p = 0.037). Conclusion: In view of the different performance of patients with MDD in facial expression tasks, facial expression recognition may have some suggestive effect on the diagnosis of depression and has clinical guiding significance. Many brain regions, including the frontal lobe, temporal lobe, striatum, hippocampus, and thalamus, in patients with MDD show extensive ReHo abnormalities in the resting state. These brain regions with abnormal spontaneous neural activity are important components of LCSPT and LTC circuits, and their dysfunctional functions cause disorder of emotion regulation. The changes in spontaneous activity in the left putamen, right angular gyrus, and right medial superior frontal gyrus may represent the abnormal pattern of spontaneous brain activity in the neural circuits related to emotion perception and may be the neural basis of facial expression recognition.

8.
ACS Omega ; 6(40): 26773-26781, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34661031

RESUMO

Carbon dioxide (CO2) levels outside of the physiological range are frequently encountered in the tumor microenvironment and laparoscopic pneumoperitoneum during clinical cancer therapy. Controversies exist regarding the biological effects of hypercapnia on tumor proliferation and metastasis concerning time frame, CO2 concentration, and cell type. Traditional control of gaseous microenvironments for cell growth is conducted using culture chambers that allow for a single gas concentration at a time. In the present paper, Hela cells were studied for their response to varying levels of CO2 in an aerogel-based gas gradient-generating apparatus capable of delivering a stable and quantitative linear CO2 profile in spatial and temporal domains. Cells cultured in the standard 96-well plate sandwiched in between the device were interfaced with the gas gradient generator, and the cells in each row were exposed to a known level of CO2 accordingly. Both the ratiometric pH indicator and theoretical modeling have confirmed the efficient mass transport of CO2 through the air-permeable aerogel monolith in a short period of time. Tumor cell behaviors in various hypercapnic microenvironments with gradient CO2 concentrations ranging from 12 to 89% were determined in terms of viability, morphology, and mitochondrial metabolism under acute exposure for 3 h and over a longer cultivation period for up to 72 h. A significant reduction in cell viability was noticed with increasing CO2 concentration and incubation time, which was closely associated with intracellular acidification and elevated cellular level of reactive oxygen species. Our modular device demonstrated full adaptability to the standard culture systems and high-throughput instruments, which provide the potential for simultaneously screening the responses of cells under tunable gaseous microenvironments.

9.
AMIA Jt Summits Transl Sci Proc ; 2021: 152-160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457129

RESUMO

Models predicting health complications are increasingly attempting to reflect the temporally changing nature of patient status. However, both the practice of medicine and electronic health records (EHR) have yet to provide a true longitudinal representation of a patient's medical history as relevant data is often asynchronous and highly missing. To match the stringent requirements of many static time models, time-series data has to be truncated, and missing values in samples have to be filled heuristically. However, these data preprocessing procedures may unconsciously misinterpret real-world data, and eventually lead into failure in practice. In this work, we proposed an augmented gated recurrent unit (GRU), which formulate both missingness and timeline signals into GRU cells. Real patient data of post-operative bleeding (POB) after Colon and Rectal Surgery (CRS) was collected from Mayo Clinic EHR system to evaluate the effectiveness of proposed model. Conventional models were also trained with imputed dataset, in which event missingness or asynchronicity were approximated. The performance of proposed model surpassed current state-of-the-art methods in this POB detection task, indicating our model could be more eligible to handle EHR datasets.


Assuntos
Registros Eletrônicos de Saúde , Diagnóstico Precoce , Humanos
10.
AMIA Jt Summits Transl Sci Proc ; 2021: 410-419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457156

RESUMO

HL7 Fast Healthcare Interoperability Resources (FHIR) is one of the current data standards for enabling electronic healthcare information exchange. Previous studies have shown that FHIR is capable of modeling both structured and unstructured data from electronic health records (EHRs). However, the capability of FHIR in enabling clinical data analytics has not been well investigated. The objective of the study is to demonstrate how FHIR-based representation of unstructured EHR data can be ported to deep learning models for text classification in clinical phenotyping. We leverage and extend the NLP2FHIR clinical data normalization pipeline and conduct a case study with two obesity datasets. We tested several deep learning-based text classifiers such as convolutional neural networks, gated recurrent unit, and text graph convolutional networks on both raw text and NLP2FHIR inputs. We found that the combination of NLP2FHIR input and text graph convolutional networks has the highest F1 score. Therefore, FHIR-based deep learning methods has the potential to be leveraged in supporting EHR phenotyping, making the phenotyping algorithms more portable across EHR systems and institutions.


Assuntos
Aprendizado Profundo , Algoritmos , Registros Eletrônicos de Saúde , Humanos , Obesidade , Projetos Piloto
11.
AMIA Jt Summits Transl Sci Proc ; 2021: 624-633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457178

RESUMO

Lack of standardized representation of natural language processing (NLP) components in phenotyping algorithms hinders portability of the phenotyping algorithms and their execution in a high-throughput and reproducible manner. The objective of the study is to develop and evaluate a standard-driven approach - CQL4NLP - that integrates a collection of NLP extensions represented in the HL7 Fast Healthcare Interoperability Resources (FHIR) standard into the clinical quality language (CQL). A minimal NLP data model with 11 NLP-specific data elements was created, including six FHIR NLP extensions. All 11 data elements were identified from their usage in real-world phenotyping algorithms. An NLP ruleset generation mechanism was integrated into the NLP2FHIR pipeline and the NLP rulesets enabled comparable performance for a case study with the identification of obesity comorbidities. The NLP ruleset generation mechanism created a reproducible process for defining the NLP components of a phenotyping algorithm and its execution.


Assuntos
Registros Eletrônicos de Saúde , Processamento de Linguagem Natural , Algoritmos , Comorbidade , Humanos , Idioma
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(7): 704-710, 2021 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34382586

RESUMO

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.


Assuntos
Pacientes Internados , Lúpus Eritematoso Sistêmico , Idoso , Glucocorticoides/efeitos adversos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Prednisona , Fatores de Risco
13.
Aging (Albany NY) ; 13(15): 19475-19485, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388114

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of malignant tumor in the kidney. With numbers of patients whose physical condition or tumor stage not suitable for radical surgery, they only have a narrow choice of using VEGF/mTOR targeted drugs to control their tumors, but ccRCC often shows resistance to these drugs. Therefore, identifying a new therapeutic target is of urgent necessity. In this study, for the first time, we concluded from bioinformatics analyses and in vitro research that FK506 binding protein 10 (FKBP10), together with its molecular partner Lysyl hydroxylase 2 (LH2/PLOD2), participate in the process of type I collagen synthesis in ccRCC via regulating crosslinking of pro-collagen chains. Our findings may provide a potential therapeutic target to treat ccRCC in the future.

14.
Front Cell Dev Biol ; 9: 724172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414195

RESUMO

Cervical cancer as a common gynecological malignancy threatens the health and lives of women. Resistance to radiotherapy is the primary cause of treatment failure and is mainly related to difference in the inherent vulnerability of tumors after radiotherapy. Here, we investigated signature genes associated with poor response to radiotherapy by analyzing an independent cervical cancer dataset from the Gene Expression Omnibus, including pre-irradiation and mid-irradiation information. A total of 316 differentially expressed genes were significantly identified. The correlations between these genes were investigated through the Pearson correlation analysis. Subsequently, random forest model was used in determining cancer-related genes, and all genes were ranked by random forest scoring. The top 30 candidate genes were selected for uncovering their biological functions. Functional enrichment analysis revealed that the biological functions chiefly enriched in tumor immune responses, such as cellular defense response, negative regulation of immune system process, T cell activation, neutrophil activation involved in immune response, regulation of antigen processing and presentation, and peptidyl-tyrosine autophosphorylation. Finally, the top 30 genes were screened and analyzed through literature verification. After validation, 10 genes (KLRK1, LCK, KIF20A, CD247, FASLG, CD163, ZAP70, CD8B, ZNF683, and F10) were to our objective. Overall, the present research confirmed that integrated bioinformatics methods can contribute to the understanding of the molecular mechanisms and potential therapeutic targets underlying radiotherapy resistance in cervical cancer.

15.
JAMIA Open ; 4(3): ooab070, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34423261

RESUMO

Objective: With COVID-19, there was a need for a rapidly scalable annotation system that facilitated real-time integration with clinical decision support systems (CDS). Current annotation systems suffer from a high-resource utilization and poor scalability limiting real-world integration with CDS. A potential solution to mitigate these issues is to use the rule-based gazetteer developed at our institution. Materials and Methods: Performance, resource utilization, and runtime of the rule-based gazetteer were compared with five annotation systems: BioMedICUS, cTAKES, MetaMap, CLAMP, and MedTagger. Results: This rule-based gazetteer was the fastest, had a low resource footprint, and similar performance for weighted microaverage and macroaverage measures of precision, recall, and f1-score compared to other annotation systems. Discussion: Opportunities to increase its performance include fine-tuning lexical rules for symptom identification. Additionally, it could run on multiple compute nodes for faster runtime. Conclusion: This rule-based gazetteer overcame key technical limitations facilitating real-time symptomatology identification for COVID-19 and integration of unstructured data elements into our CDS. It is ideal for large-scale deployment across a wide variety of healthcare settings for surveillance of acute COVID-19 symptoms for integration into prognostic modeling. Such a system is currently being leveraged for monitoring of postacute sequelae of COVID-19 (PASC) progression in COVID-19 survivors. This study conducted the first in-depth analysis and developed a rule-based gazetteer for COVID-19 symptom extraction with the following key features: low processor and memory utilization, faster runtime, and similar weighted microaverage and macroaverage measures for precision, recall, and f1-score compared to industry-standard annotation systems.

16.
J Cell Physiol ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34350982

RESUMO

The role of liver kinase B1 (LKB1) in glioblastoma (GBM) development remains poorly understood. LKB1 may regulate GBM cell metabolism and has been suggested to promote glioma invasiveness. After analyzing LKB1 expression in GBM patient mRNA databases and in tumor tissue via multiparametric immunohistochemistry, we observed that LKB1 was localized and enriched in GBM tumor cells that co-expressed SOX2 and NESTIN stemness markers. Thus, LKB1-specific immunohistochemistry can potentially reveal subpopulations of stem-like cells, advancing GBM patient molecular pathology. We further analyzed the functions of LKB1 in patient-derived GBM cultures under defined serum-free conditions. Silencing of endogenous LKB1 impaired 3D-gliomasphere frequency and promoted GBM cell invasion in vitro and in the zebrafish collagenous tail after extravasation of circulating GBM cells. Moreover, loss of LKB1 function revealed mitochondrial dysfunction resulting in decreased ATP levels. Treatment with the clinically used drug metformin impaired 3D-gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. The IC50 of temozolomide in the GBM cultures was significantly decreased in the presence of metformin. This combinatorial effect was further enhanced after LKB1 silencing, which at least partially, was due to increased apoptosis. The expression of genes involved in the maintenance of tumor stemness, such as growth factors and their receptors, including members of the platelet-derived growth factor (PDGF) family, was suppressed after LKB1 silencing. The defect in gliomasphere growth caused by LKB1 silencing was bypassed after supplementing the cells with exogenous PFDGF-BB. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D-gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread.

17.
Materials (Basel) ; 14(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361478

RESUMO

The main concern of this work is to evaluate the influences of supplementary cementitious materials (fly ash, slag) and a new type of polycarboxylate superplasticizer containing viscosity modifying agents (PCE-VMA) on the performance of self-compacting concrete (SCC). The workability, hydration process, mechanical property, chloride permeability, degree of hydration and pore structure of SCC were investigated. Results indicate that the addition of fly ash and slag slows down early hydration and decreases the hydration degree of SCC, and thus leads to a decline in compressive strengths, especially within the first 7 days. The addition of slag refines pore structure and contributes to lower porosity, and thus the chloride permeability of SCC is decreased during the late hydration stage. Additionally, a new factor of calculated water-binder ratio is put forward, which can directly reflect the free water content of concrete mixture after mixing, and guide the mix proportion design of SCC.

18.
J Org Chem ; 86(15): 10427-10439, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34313431

RESUMO

The first application of 3-alkyl-2-vinylindoles in catalytic asymmetric dearomative cycloadditions was established by chiral phosphoric acid (CPA)-catalyzed (2+3) cycloaddition with azoalkenes, leading to the generation of chiral pyrroloindolines bearing two tetrasubstituted stereogenic centers in good yields (61-96%) and excellent stereoselectivities (all >95:5 dr, 86-99% ee). This reaction has realized the first enantioselective dearomative cycloaddition of 3-alkyl-2-vinylindoles, which brings a new reactivity to this class of vinylindoles and will enrich the chemistry of 3-alkyl-2-vinylindoles. In addition, this approach has provided a useful strategy for the construction of enantioenriched pyrroloindoline skeletons bearing two tetrasubstituted stereogenic centers. More importantly, the bioassay of these chiral pyrroloindolines has revealed that some compounds exhibit strong anti-cancer activity against Hela and MCF-7 cell lines, which will be helpful for discovering anti-cancer drug candidates.


Assuntos
Indóis , Catálise , Reação de Cicloadição , Estereoisomerismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-34211569

RESUMO

Male infertility induced by heat stress has been attracting more and more attention. Heat stress not only causes apoptosis of spermatocytes but also has adverse effects on Sertoli cells, further damaging spermatogenesis. Lycium barbarum polysaccharide (LBP) is the main bioactive component of Lycium barbarum, which has a protective effect on male reproduction, but its mechanism is still unclear. In this study, our results proved that LBP blocked the inhibitory effect on the proliferation activity of Sertoli cells after heat stress, reversed the dedifferentiation of Sertoli cells induced by heat stress, and ameliorated the structural integrity of the blood-testis barrier. In addition, it increased the expression of the androgen receptor and activated Akt signaling pathway to resist heat-stress-induced injury of Sertoli cells.

20.
Kidney Dis (Basel) ; 5: 1-10, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-34192120

RESUMO

Background: The COVID-19 pandemic has brought increased focus on hydroxychloroquine (HCQ), as doctors, the medical community, and policymakers around the world attempt to understand how the risks of HCQ weigh against unknown benefits. We aim to evaluate the effects of HCQ on cardiac conduction, thus contributing to the global understanding of implications of HCQ use. Methods: We reviewed 717 cases of nonmalaria patients treated with HCQ (302) or without HCQ (415) in our hospital from 2008 to 2019, analyzed the cardiac conduction recorded by electrocardiogram (122 vs. 180) including heart rate (HR), PR, and corrected-QT (QTc) intervals, and explored the relationship of cardiac conduction with age, HCQ dosage, HCQ duration, sex, and primary diseases in HCQ users. Results: The all-cause mortality is similar between HCQ and non-HCQ groups (4.0 vs. 4.3%, p = 0.85). Patients aged 45 years or older, not younger ones, have lower HR (80.1 ± 1.7 vs. 85.7 ± 1.8 bpm, p = 0.03) but longer PR (163 ± 3.4 vs. 146.6 ± 4.2 ms, p = 0.003) and QTc (417.8 ± 3.8 vs. 407.7 ± 2.7 ms, p = 0.03) in HCQ than those in non-HCQ. The age in the HCQ group is positively correlated with PR (R = 0.31, p < 0.01) and QTc (R = 0.34, p < 0.01) but not HR. HR, PR, and QTc are not related to HCQ dosage (0.1-0.6 g/day), HCQ duration (0.2-126 months), sex, primary diseases, and repeated exams. Conclusion: Age is the most important risk factor of HCQ on cardiac conduction in nonmalaria patients. Electrocardiogram monitoring is suggested in aged patients due to the effects of HCQ on HR, PR, and QTc.

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