Publications by authors named "Lei Shi"

2,523 Publications

  • Page 1 of 1

Roles of Aryl-hydrocarbon Receptor in metabolism and proliferative behaviors of Bone Marrow MSCs: Implications for targeted therapy.

Curr Top Med Chem 2021 Jun 11. Epub 2021 Jun 11.

Department of Hematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Background: Mesenchymal stromal cells (MSCs) due to convenient isolation and ex vivo expansion, multipotent differentiation, and migrating capacity into the inflammation sites and tumor microenvironments are interesting candidates in precise medicine. MSCs, as an important component of bone marrow microenvironment, can regulate hematopoiesis and immunity via direct contact or secretion of adhesion factors and hematopoietic chemokines. Recent evidence showed that aryl-hydrocarbon receptor (AHR) signal pathway plays a crucial role in hematopoiesis and immunity. However, the roles and mechanisms of actions of AHR and its activation in bone marrow MCSs (BMMCs) are still largely unclear.

Objective: The present study aimed to investigate the effects and mechanisms of action of AHR activation on the metabolism of BMMSCs and its proliferative behaviors.

Methods: Bone marrow mononuclear cells (BMMNCs) were isolated from fresh bone marrow using Ficoll-Paque Plus. The HS-27A cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum and 5% penicillin-streptomycin at 37°C in a humidified atmosphere with 5% CO2. The mitochondrial membrane potential (MMP) detection kit (JC-1) was used to determine the MMP. Hs-27a cells in the logarithmic growth phase were digested with 0.25% trypsin, following the cells were centrifuged for 5 min at 1000 rpm. Cell suspension was prepared. Cell apoptosis was detected using an Annexin V-FITC kit (BD Life Sciences-Biosciences, San Diego, USA). The ModFit software was used to analyze the data.

Results And Discussion: This study showed that AHR activation resulted in decreased cell viability and the proliferation of BMMSCs. In contrary, AHR inhibition promoted cell viability and proliferation. Activation of AHR enhanced the function of mitochondria (including mitochondrial membrane potential and mitochondrial dehydrogenase) which was concomitant with the decrease of metabolic acid. Nonetheless, inhibition of AHR decreased the mitochondrial function. Furthermore, while activation of AHR signal blocked the BMMSCs in G1 phase, inhibition of AHR promoted the BMMSCs to S phase of the cell cycle.

Conclusion: Taken together, these findings demonstrated that activation of AHR signaling pathway reshaped the metabolism in BMMSCs and consequently inhibited their proliferation.
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http://dx.doi.org/10.2174/1568026621666210611163043DOI Listing
June 2021

Visible-light-driven spirocyclization of epoxides dual titanocene and photoredox catalysis.

Chem Sci 2019 Dec 9;11(3):839-844. Epub 2019 Dec 9.

Zhang Dayu School of Chemistry, State Key Laboratory of Fine Chemicals, Dalian University of Technology Dalian 116024 China

We describe the synergistic utilization of titanocene/photoredox dual catalysis driven by visible light for the radical opening/spirocyclization of easily accessible epoxyalkynes. This environmentally benign process uses the organic donor-acceptor fluorophore 2,4,5,6-tetra(9-carbazol-9-yl)isophthalonitrile (4CzIPN) as a photocatalyst and Hantzsch ester (HE) as an electron donor instead of stoichiometric metallic reductants. The photocatalytic conditions showed exceptionally high reactivity for the synthesis of privileged and synthetically challenging spirocycles featuring a spiro all-carbon quaternary stereocenter. Cyclic voltammetry (CV) studies suggest that CpTiCl is the catalytically active species.
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http://dx.doi.org/10.1039/c9sc05601gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146098PMC
December 2019

Expression-EEG Bimodal Fusion Emotion Recognition Method Based on Deep Learning.

Comput Math Methods Med 2021 25;2021:9940148. Epub 2021 May 25.

Department of Electrical & Information Engineering, Sichuan Engineering Technical College, Deyang, Sichuan 618000, China.

As one of the key issues in the field of emotional computing, emotion recognition has rich application scenarios and important research value. However, the single biometric recognition in the actual scene has the problem of low accuracy of emotion recognition classification due to its own limitations. In response to this problem, this paper combines deep neural networks to propose a deep learning-based expression-EEG bimodal fusion emotion recognition method. This method is based on the improved VGG-FACE network model to realize the rapid extraction of facial expression features and shorten the training time of the network model. The wavelet soft threshold algorithm is used to remove artifacts from EEG signals to extract high-quality EEG signal features. Then, based on the long- and short-term memory network models and the decision fusion method, the model is built and trained using the signal feature data extracted under the expression-EEG bimodality to realize the final bimodal fusion emotion classification and identification research. Finally, the proposed method is verified based on the MAHNOB-HCI data set. Experimental results show that the proposed model can achieve a high recognition accuracy of 0.89, which can increase the accuracy of 8.51% compared with the traditional LSTM model. In terms of the running time of the identification method, the proposed method can effectively be shortened by about 20 s compared with the traditional method.
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http://dx.doi.org/10.1155/2021/9940148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172283PMC
May 2021

Repression of transcription factor AtWRKY47 confers tolerance to boron toxicity in Arabidopsis thaliana.

Ecotoxicol Environ Saf 2021 Sep 10;220:112406. Epub 2021 Jun 10.

National Key Laboratory of Crop Genetic Improvement, and Microelement Research Centre, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

Boron (B) excess gives rise to a serious agricultural problem. In this study, we identified a B toxicity responsive transcription factor AtWRKY47 in Arabidopsis thaliana. The T-DNA insertion mutants Atwrky47 showed enhanced tolerance to B toxicity with better growth parameters under high B conditions compared to wild-type Col-0 plants. Quantitative analysis of AtWRKY47 mRNA abundance indicated that it was down-regulated under B toxicity conditions. Fluorescently labeled AtWRKY47 protein was localized in nucleus. In contrast to the phenotype of Atwrky47 mutants, overexpression of AtWRKY47 in Col-0 background resulted in lower biomass, less chlorophyll content, and increased sensitivity to B toxicity. More importantly, the B concentration in shoots was higher in the overexpression lines and lower in the Atwrky47 mutants than in Col-0 plants, respectively. These results demonstrate that AtWRKY47 gene plays a key role in regulating plant tolerance to B toxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112406DOI Listing
September 2021

Quantitative detection of trace VBNC Cronobacter sakazakii by immunomagnetic separation in combination with PMAxx-ddPCR in dairy products.

Food Microbiol 2021 Oct 19;99:103831. Epub 2021 May 19.

Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

One immunomagnetic separation (IMS) assay based on immunomagnetic beads (IMBs) has been evaluated as a potential pretreatment tool for the separation and enrichment of target bacteria. In this study, we successfully immobilized antibodies onto magnetic bead surfaces to form IMBs through biotin and a streptavidin (SA) system to capture viable but nonculturable (VBNC) Cronobacter sakazakii (C. sakazakii) from dairy products. Various parameters that affected the capture efficiency (CE) of IMS, including the number of antibodies, IMBs dose, incubation time, magnetic separation time, and immunoreaction temperature, were systematically investigated. We further determined the optimal enrichment conditions for different dairy substrates to ensure maximum enrichment of target pathogens in the system. An IMS technique combining improved propidium monoazide (PMAxx) and droplet digital PCR (ddPCR) was established to detect the pathogenic VBNC C. sakazakii. The IMS-PMAxx-ddPCR method after IMBs enrichment showed higher accuracy when the VBNC C. sakazakii was under 1 Log copies/g. The detection limit for this method in a background of powdered infant formula (PIF) was 5.6 copies/g. In summary, the developed IMS-PMAxx-ddPCR method has great potential for the analysis and detection of VBNC bacteria in food.
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http://dx.doi.org/10.1016/j.fm.2021.103831DOI Listing
October 2021

MicroRNA-146b-3p regulates the dysfunction of vascular smooth muscle cells via repressing phosphoinositide-3 kinase catalytic subunit gamma.

Bioengineered 2021 Dec;12(1):2627-2638

Department of Cardiac Surgery, Dalian Municipal Center Hospital, Dalian Liaoning, China.

MicroRNAs are crucial regulators in the phenotype switch of vascular smooth muscle cells (VSMCs). Nonetheless, the role of miR-146b-3p in VSMCs remains unclear. In the present study, platelet-derived growth factor-BB (PDGF-BB) at different concentrations was employed to stimulate VSMCs for different times, to establish the model of VSMC dysfunction. The relative expression of miR-146b-3p was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was measured by BrdU assay. Flow cytometry analysis was employed for the analysis of cell cycle. VSMC migration was detected by Transwell assay. Phosphoinositide-3 kinase catalytic subunit-gamma (PIK3CG) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC, and Calponin were examined employing Western blot. The targeting relationship between miR-146b-3p and PIK3CG 3'-UTR was affirmed by dual-luciferase gene assay. We report that the reduction of miR-146b-3p expression was induced by PDGF-BB in a time-dependent and dose-dependent manner ( < 0.05). The overexpression of miR-146b-3p counteracted the effects of PDGF-BB on the proliferation and migration of VSMCs and increased the expressions of differentiation markers ( < 0.05). Additionally, PIK3CG expression was negatively regulated by miR-146b-3p, and the restoration of PIK3CG partly eliminated the effects of miR-146b-3p on VSMCs ( < 0.05). In summary, miR-146b-3p represses the proliferation, migration, and phenotype switch of VSMCs induced by PDGF-BB via targeting PIK3CG. Therefore, miR-146b-3p/PIK3CG may be a potential target for the treatment of atherosclerosis.
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http://dx.doi.org/10.1080/21655979.2021.1937904DOI Listing
December 2021

Diffusionless transformation of soft cubic superstructure from amorphous to simple cubic and body-centered cubic phases.

Nat Commun 2021 Jun 9;12(1):3477. Epub 2021 Jun 9.

CAS Key Laboratory of Bio-inspired Materials and Interfaces Sciences, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China.

In a narrow temperature window in going from the isotropic to highly chiral orders, cholesteric liquid crystals exhibit so-called blue phases, consisting of different morphologies of long, space-filling double twisted cylinders. Those of cubic spatial symmetry have attracted considerable attention in recent years as templates for soft photonic materials. The latter often requires the creation of monodomains of predefined orientation and size, but their engineering is complicated by a lack of comprehensive understanding of how blue phases nucleate and transform into each other at a submicrometer length scale. In this work, we accomplish this by intercepting nucleation processes at intermediate stages with fast cross-linking of a stabilizing polymer matrix. We reveal using transmission electron microscopy, synchrotron small-angle X-ray diffraction, and angle-resolved microspectroscopy that the grid of double-twisted cylinders undergoes highly coordinated, diffusionless transformations. In light of our findings, the implementation of several applications is discussed, such as temperature-switchable QR codes, micro-area lasing, and fabrication of blue phase liquid crystals with large domain sizes.
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http://dx.doi.org/10.1038/s41467-021-23631-wDOI Listing
June 2021

Enhancement of Transmitting Sensitivity of Piezoelectric Micromachined Ultrasonic Transducers By Electrode Design.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Jun 9;PP. Epub 2021 Jun 9.

This paper investigates the dependence of transmitting sensitivity on the top electrode design of piezoelectric micromachined ultrasonic transducers (PMUTs). Two typical top electrodes, namely inner electrode (IE) and outer electrode (OE), are designed and fabricated. The measured transmitting velocities of the fabricated PMUTs at resonance under a drive voltage of 5 Vp-p (peak-to-peak) are 15.36 mm/s for the IE design and 20.67 mm/s for the OE design with a circular diaphragm, and 16.62 mm/s for the IE design and 22.18 mm/s for the OE design with a hexagonal diaphragm, respectively. The OE design demonstrates a transmitting velocity improvement of 34.57% for the circular diaphragm and 33.45% for the hexagonal diaphragm. The improvement is due to the fact that the OE design shows higher quality factor (Q) than the IE counterpart. Moreover, the resonant frequency of the OE design is higher compared to the IE design, which results in a larger acoustic pressure output and hence higher transmitting sensitivity. This work highlights an effective and simple approach for PMUTs to achieve high transmitting sensitivity, which is an important parameter in the applications that require large sound pressures, such as fingerprint imaging, gesture recognition and ranging.
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http://dx.doi.org/10.1109/TUFFC.2021.3087741DOI Listing
June 2021

Study on the effect of percutaneous intervertebral foraminoscopic discectomy in the treatment of lumbar disc herniation.

Medicine (Baltimore) 2021 May;100(19):e25345

First Ward of Orthopedics Department.

Abstract: This study explored the effect of percutaneous intervertebral foraminoscopic discectomy (PIFD) in the treatment of lumbar disc herniation (LDH).This retrospective study collected a total of 88 patient cases for inclusion. Epidemiological and clinical data of patients with LDH at the First Affiliated Hospital of Jiamusi University between May 2017 and January 2020 were retrospectively analyzed. Of those, 44 patients received PIFD and were allocated to an intervention group. The other 44 patients administrated fenestration discectomy (FD), and were assigned to a control group. We compared surgery time (minute), incision length (cm), duration of hospital stay after surgery (day), pain intensity (as checked by Visual Analogue Scale (VAS), health-related quality of life (as examined by Oswestry Disability Index, ODI), and complications between 2 groups.There were not significant differences in surgery time (minute) (P = .56), VAS (P = .33) and ODI (P = .46) after surgery between 2 groups. However, there were significant differences in incision size (cm) (P < .01) and length of hospital stay (day) (P < .01) after surgery between 2 groups. When compared before the surgery, patients in both groups had significant improvements in VAS (P < .01) and ODI (P < .01) after the surgery. Moreover, both groups had similar safety profiles (P > .05).The findings of this study showed that both PIFD and FD benefit patients with LDH. However, PIFD can benefit patients more than FD in the incision size and duration of hospital stay after surgery.
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http://dx.doi.org/10.1097/MD.0000000000025345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133092PMC
May 2021

Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells.

Nat Commun 2021 06 7;12(1):3330. Epub 2021 Jun 7.

Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA.

Human pluripotent stem cell (hPSC)-derived pancreatic β cells are an attractive cell source for treating diabetes. However, current derivation methods remain inefficient, heterogeneous, and cell line dependent. To address these issues, we first devised a strategy to efficiently cluster hPSC-derived pancreatic progenitors into 3D structures. Through a systematic study, we discovered 10 chemicals that not only retain the pancreatic progenitors in 3D clusters but also enhance their potentiality towards NKX6.1+/INS+ β cells. We further systematically screened signaling pathway modulators in the three steps from pancreatic progenitors toward β cells. The implementation of all these strategies and chemical combinations resulted in generating β cells from different sources of hPSCs with high efficiency. The derived β cells are functional and can reverse hyperglycemia in mice within two weeks. Our protocol provides a robust platform for studying human β cells and developing hPSC-derived β cells for cell replacement therapy.
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http://dx.doi.org/10.1038/s41467-021-23525-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184986PMC
June 2021

Protective effect of pogostone on murine norovirus infected-RAW264.7 macrophages through inhibition of NF-κB/NLRP3-dependent pyroptosis.

J Ethnopharmacol 2021 Jun 2;278:114250. Epub 2021 Jun 2.

Institute of Cardiovascular Disease of Integrated Traditional Chinese Medicine and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:

Ethnopharmacological Relevance: Pogostemon cablin, the dry overground parts of Pogostemon cablin (Blanco) Benth, has been widely used in the treatment of gastrointestinal dysfunction, such as nausea, diarrhea, headaches and fever. Pogostone (PO) is a major component of Pogostemon cablin which has a variety of pharmacological properties, including antiinflammatory, and immunosuppressive activities, and antioxidant. However, the effect of PO on norovirus gastroenteritis and the underlying molecular mechanism remain unclear.

Aim Of The Study: The purpose of our study is to investigate the effects of PO against MNV infection using RAW264.7 cells and to elucidate its active mechanisms.

Materials And Methods: The cell viability was assessed using Cell Counting Kit-8 (CCK-8) assay and Fluorescein diacetate (FDA) staining. The activation of nuclear factor kappa B (NF-κB) signaling and NOD-like receptor 3 (NLRP3) inflammasome was evaluated by assessing the level of phospho-NF-κB p65, interleukin (IL)-6, TNF-α, NLRP3, cleaved caspase-1, IL-18, IL-1β using Western blot and quantitative real-time PCR (qPCR), respectively. The number of infected cells were determined by immunofluorescence microscopic assay.

Results: PO did not possess a cytotoxic effect toward RAW264.7 cells. The cytotoxic damage caused by MNV infection in RAW264.7 cells decreased significantly in the presence of PO. Cell viability assays showed that pyroptosis is the major mechanism of death in MNV-infected RAW264.7 cells. PO could decreased the expression levels of p-p65, IL-6, TNF-α, NLRP3, cleaved caspase-1, IL-1β, and IL-18.

Conclusions: These results demonstrate that PO decreases MNV-induced RAW264.7 macrophages death and MNV replication through repressing NF-κB/NLRP3-dependent pyroptosis. Therefore PO may be considered as a potential therapeutic agent for preventing and treating norovirus gastroenteritis.
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http://dx.doi.org/10.1016/j.jep.2021.114250DOI Listing
June 2021

Deep learning for predicting subtype classification and survival of lung adenocarcinoma on computed tomography.

Transl Oncol 2021 Jun 1;14(8):101141. Epub 2021 Jun 1.

Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, No. 37 Guo Xue Alley, Chengdu 610041, China. Electronic address:

Objectives: The subtype classification of lung adenocarcinoma is important for treatment decision. This study aimed to investigate the deep learning and radiomics networks for predicting histologic subtype classification and survival of lung adenocarcinoma diagnosed through computed tomography (CT) images.

Methods: A dataset of 1222 patients with lung adenocarcinoma were retrospectively enrolled from three medical institutions. The anonymised preoperative CT images and pathological labels of atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma, invasive adenocarcinoma (IAC) with five predominant components were obtained. These pathological labels were divided into 2-category classification (IAC; non-IAC), 3-category and 8-category. We modeled the classification task of histological subtypes based on modified ResNet-34 deep learning network, radiomics strategies and deep radiomics combined algorithm. Then we established the prognostic models in lung adenocarcinoma patients with survival outcomes. The accuracy (ACC), area under ROC curves (AUCs) and C-index were primarily performed to evaluate the algorithms.

Results: This study included a training set (n = 802) and two validation cohorts (internal, n = 196; external, n = 224). The ACC of deep radiomics algorithm in internal validation achieved 0.8776, 0.8061 in the 2-category, 3-category classification, respectively. Even in 8 classifications, the AUC ranged from 0.739 to 0.940 in internal set. Further, we constructed a prognosis model that C-index was 0.892(95% CI: 0.846-0.937) in internal validation set.

Conclusions: The automated deep radiomics based triage system has achieved the great performance in the subtype classification and survival predictability in patients with CT-detected lung adenocarcinoma nodules, providing the clinical guide for treatment strategies.
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http://dx.doi.org/10.1016/j.tranon.2021.101141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184655PMC
June 2021

Photosynthetic acclimation during low-light-induced leaf senescence in post-anthesis maize plants.

Photosynth Res 2021 Jun 4. Epub 2021 Jun 4.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

Low light conditions not only induce leaf senescence, but also photosynthetic acclimation. This study aimed to determine whether plants exhibit photosynthetic acclimation during low-light-induced leaf senescence. The influences of shading on leaf senescence and photosynthetic acclimation were explored in post-anthesis maize plants. The results showed that whole shading (WS) of maize plants accelerated leaf senescence, whereas partial shading (PS) slowed leaf senescence. WS led to larger decreases in the photosynthetic rate (P) and stomatal conductance (G) compared to those of the PS treatment. Interestingly, chlorophyll a fluorescence (ChlF) demonstrated that the absorption flux (ABS/CS) and trapped energy flux (TR/CS) per cross section in leaves remained relatively stable under WS, whereas significant decreases in the active PSII reaction centers (RC/CS) resulted in considerable increases in absorption (ABS/RC) and trapped energy flux (TR/RC) per reaction center. ABS/CS, TR/CS, ABS/RC, and TR/RC increased markedly under PS, whereas there were slight decreases in RC/CS and electron transport activity. These results suggest that the PS treatment resulted in obvious improvements in the absorption and capture of light energy in shaded leaves. Further analysis demonstrated that both the WS and PS treatments resulted in a greater decrease in the activity of Rubisco compared to that of phosphoenolpyruvate carboxylase (PEPC). Moreover, PEPC activity in PS was maintained at a high level. Consequently, the current study proposed that the improvement of the absorption and capture of light energy and the maintenance of PEPC activity of mesophyll cells were due to photosynthetic acclimation of low-light-induced leaf senescence in maize plants. In addition, the rate of senescence of vascular bundle cells in maize leaves exceeded that of mesophyll cells under low light, showing obvious tissue specificity.
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http://dx.doi.org/10.1007/s11120-021-00851-1DOI Listing
June 2021

An ultrasensitive LC-MS/MS method and application to clinical dose-range finding for glycopyrrolate via an e-Nebulizer.

Bioanalysis 2021 Jun 4;13(12):959-968. Epub 2021 Jun 4.

Sunovion Pharmaceuticals Inc., 84 Waterford Drive, Marlborough, MA 01752, USA.

Glycopyrrolate (GLY) has been widely used to treat chronic obstructive pulmonary disease (COPD). Recent technical advancement significantly improves the drug delivery efficiency. In a clinical dose-range determination study via electronic nebulizer, the starting dose was as low as 3-μg, thus, a bioanalytical method capable of measuring down to sub-pg/ml or fg/ml level was required to characterize pharmacokinetics of GLY. A straightforward solid-phase extraction coupled with reversed-phase LC-MS/MS method was successfully developed to quantify plasma GLY concentrations of 0.500-250 pg/mL. MS/MS detection was at ESI+ by monitoring 318.3→116.1 for GLY and 321.3→119.1 for the internal standard GLY-d. The method was validated with adequate selectivity, intra- and inter-assay precision and accuracy, dilution linearity, and sufficient stability for measuring GLY in human plasma. This method has been used for sample analysis of a clinical dose-range finding study (3-50 µg twice daily doses via an electronic nebulizer). The assay exhibited good precision, accuracy, and robustness. Pharmacokinetic analysis showed good dose proportionality over the studied dose range, where C was found to be Y = 1.354*X + 1.968 (r = 0.9984), and AUC was Y = 4.661*X + 23.32 (r = 0.9976). The study clearly demonstrated the importance of an ultrasensitive (500 fg/ml LLOQ) method.
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http://dx.doi.org/10.4155/bio-2021-0037DOI Listing
June 2021

Using the Delphi Method to Construct a Promotion Plan for Clinical Nurse Specialists.

Clin Nurse Spec 2021 Jul-Aug 01;35(4):188-198

Author Affiliations: School of Nursing, Southern Medical University (Zhao and Dr Shi); Nursing Department, Guangzhou General Hospital of the People's Liberation (Li); and ICU Department, Sun Yat-sen University First Affiliated Hospital (Gao), Guangzhou, China.

Purpose: The aim of this study was to design a quantitative evaluation of the promotion plan for clinical nurse specialists in China.

Design: The evaluation indexes were selected and established by inquiring 22 experts and using the analytic hierarchy process. The promotion plan was sent to 22 specialized nurses. The reference value was established by comparing the results from predictions made by experts and the self-evaluation of specialized nurses.

Methods: This study used the Delphi method and mixed qualitative and quantitative methods, which not only determined the entry of the promotion plan but also calculated its weight, and obtained the baseline score through a small range of empirical studies.

Results: This promotion plan included basic promotion conditions, 5 primary indicators, 15 secondary indicators, and 61 tertiary indicators and was designed by experts who had a high degree of authority in this field. The self-evaluation results of 19 specialist nurses showed a reference value of 30 points per 3 years using the promotion plan. For clinical nursing managers, it is a management tool to evaluate specialist nurses, which can provide a basis for the promotion of specialist nurses.

Conclusions: The promotion plan for clinical nurse specialists in China formed by this research is quantifiable, scientific, and instructive.
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http://dx.doi.org/10.1097/NUR.0000000000000605DOI Listing
June 2021

Identifying Mismatches of Ecosystem Services Supply and Demand under semi-arid conditions: The Case of the Oasis City Urumqi, China.

Integr Environ Assess Manag 2021 Jun 1. Epub 2021 Jun 1.

Faculty of Forest and Environment, Eberswalde University for Sustainable Development, Eberswalde, 16225, Germany.

Understanding the balance between supply and demand of ecosystem services (ESs) is helpful for sustainable urban management. However, the interactions among multiple ESs supplies and demands remain under-researched, and ESs supply and demand spatial heterogeneity and correlation characteristics at the city level are rarely studied, especially in arid areas. To fill this gap, we established a comprehensive assessment framework of ESs supply and demand through integrating multi-source remote sensing data, social economy and policy objectives. The ESs supply-demand mismatches were revealed at the city level, and the spatial relationship between the ESs supply and demand was analyzed using spatial statistics. The results showed that: (1) The total quantity of supply and demand of food provision, carbon sequestration, PM removal and recreation services in Urumqi all showed that the demand was greater than the supply, the deficits being 16.10× 10 kcal/ha, 6.88 × 10 t/ha, 155.86 kg/ha and 697.26, respectively. (2) The supply and demand assessment of ESs showed spatial differences from the city center to the suburbs, which further indicated that there are neighborhood similarities between the supply and demand of ESs. (3) The matching types of ESs supply and demand present obvious spatial heterogeneity, which can be divided into four types: High-High, High-Low, Low-High and Low-Low. Due to rapid urban development in the inner city, the city center is dominated by Low-High, while the urban-rural ecotone is characterized by High-Low due to the higher elevation and water resource advantages in the suburbs. Based on the analysis of the supply, demand and matching of ESs, economic development and sustainable management policies were proposed for different ecological spaces. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ieam.4471DOI Listing
June 2021

Interleukin IL-5 alleviates sepsis-induced acute lung injury by regulating the immune response in rats.

Bioengineered 2021 Dec;12(1):2132-2139

School of Public Health, Southern Medical University, Guangdong, China.

To study the effect of IL-5 on the immune response and lung injury in rats with sepsis. We constructed a rat model of sepsis by cecal ligation and puncture (CLP). The rats were randomly divided into the control group, the sham group, the CLP group and the IL-5 group, with 6 rats in each group. With the induction of CLP, the lung tissue of rats was severely injured, and the water content of lung tissue was significantly increased. Moreover, the ratio of CD4/CD8 was significantly decreased and Th1/Th2 was significantly increased in the peripheral blood. The content of IL-6, TNF-α, and HMGB1 was found to be increased in the CLP group. However, with the injection of IL-5, the degree of lung tissue injury in CLP rats was alleviated and the water content of lung tissue was significantly reduced. The ratio of CD4/CD8 was increased and Th1/Th2 was significantly down-regulated in the peripheral blood and the levels of IL-6, TNF-α, and HMGB1 in serum were significantly decreased. In conclusion, IL-5 can alleviate lung injury by regulating the immune response and inhibiting the systemic inflammatory response induced by sepsis.
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http://dx.doi.org/10.1080/21655979.2021.1930746DOI Listing
December 2021

Investigating F-FDG PET/CT Parameters as Prognostic Markers for Differentiated Thyroid Cancer: A Systematic Review.

Front Oncol 2021 13;11:648658. Epub 2021 May 13.

Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.

The aim of this study was to determine whether F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) parameters might be prognostic markers for patients with differentiated thyroid carcinoma (DTC). We searched for eligible articles in PubMed, EMBASE (Ovid), Cochrane Library, and ClinicalTrials.gov from inception to February 2021. We included studies addressing the association between F-FDG PET/CT parameters and clinical outcomes among patients with DTC. Quality assessment was performed using the Quality in Prognosis Studies (QUIPS) tool. A total of 25 studies including 2,954 patients (1,994 females, 67.5%) were included; 2,416 patients (81.8%) had papillary thyroid carcinoma (PTC), and the mean or median follow-up time ranged from 19.1 months to 17.1 years. Thirteen (52.0%) studies were assessed as "unclear" for the domain of study participation. The most common timing of PET/CT scans was after thyroidectomy (in 20 of 25 studies, 80%), especially in patients with an elevated thyroglobulin (Tg) and a negative radioiodine whole-body scan (WBS). The most common PET parameter was FDG uptake. Twelve of 17 (70.6%) and 12 of 12 (100%) studies showed an association between PET/CT parameters and disease progression and survival in patients with DTC, respectively. F-FDG PET/CT parameters alone or combined with other variables can serve as prognostic markers to identify DTC patients with poor outcomes, especially in the setting of an elevated Tg and a negative WBS. Future research is needed to confirm these findings and to examine the prognostic value of PET/CT parameters for DTC patients, considering the heterogeneity in PET/CT parameters, unclear information of patients, and PET/CT-adapted treatment modifications.
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http://dx.doi.org/10.3389/fonc.2021.648658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158293PMC
May 2021

Intratumoral SIRPα-deficient macrophages activate tumor antigen-specific cytotoxic T cells under radiotherapy.

Nat Commun 2021 05 28;12(1):3229. Epub 2021 May 28.

Center of Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA.

Radiotherapy (RT)-induced tumoricidal immunity is severely limited when tumors are well-established. Here, we report that depleting SIRPα on intratumoral macrophages augments efficacy of RT to eliminate otherwise large, treatment-resistant colorectal (MC38) and pancreatic (Pan02 and KPC) tumors, inducing complete abscopal remission and long-lasting humoral and cellular immunity that prevent recurrence. SIRPα macrophages activated by irradiated tumor-released DAMPs exhibit robust efficacy and orchestrate an anti-tumor response that controls late-stage tumors. Upon RT-mediated activation, intratumoral SIRPα macrophages acquire potent proinflammatory features and conduct immunogenic antigen presentation that confer a tumoricidal microenvironment highly infiltrated by tumor-specific cytotoxic T cells, NK cells and inflammatory neutrophils, but with limited immunosuppressive regulatory T cells, myeloid derived suppressor cells and post-radiation wound-healing. The results demonstrate that SIRPα is a master regulator underlying tumor resistance to RT and provide proof-of-principle for SIRPα macrophage-based therapies to treat a broad spectrum of cancers, including those at advanced stages with low immunogenicity and metastases.
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http://dx.doi.org/10.1038/s41467-021-23442-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163884PMC
May 2021

Anti-RSV activities of chicoric acid from echinacea purpurea in vitro.

Minerva Surg 2021 May 28. Epub 2021 May 28.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Shandong, China -

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http://dx.doi.org/10.23736/S2724-5691.21.08925-5DOI Listing
May 2021

Human umbilical cord mesenchymal stromal cell treatment of severe COVID-19 patients: a three-month follow-up study following hospital discharge.

Stem Cells Dev 2021 May 27. Epub 2021 May 27.

Sir Run Run Hospital Nanjing Medical University, 572527, Department of Respiratory Medicine, Nanjing, Jiangsu, China;

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this three-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after three months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88±8.46% and 59.45±27.45% in the hUC-MSC and control groups (P<0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95±8.00% and 58.97±19.16% in the hUC-MSC and control groups, respectively (P<0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25±3.69 vs. 31.9±8.78, P<0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P<0.05). There were no significant differences in CT scores between the two groups (0.60±0.88 vs. 1.00±1.31, P=0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating the relatively safety and preliminary efficacy of this treatment for patients with severe COVID-19.
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http://dx.doi.org/10.1089/scd.2021.0015DOI Listing
May 2021

Emerging roles of ferroptosis in the tumor immune landscape: from danger signals to anti-tumor immunity.

FEBS J 2021 May 27. Epub 2021 May 27.

School of Life Science, Chongqing University, China.

Regulated cell death (RCD) is a vital event in various physiological and pathological processes. Ferroptosis is a newly described RCD, which is driven by iron accumulation and unrestricted lipid peroxidation. The interaction between ferroptosis and immunity has been a topic of substantial interest since its discovery in 2012. It has become increasingly evident that ferroptosis is critically involved in the regulation of antitumor immunity and may provide potential strategies in immunotherapy. Ferroptosis could release various damage-associated molecular patterns (DAMPs) or lipid metabolites to regulate the cellular immune response, validating its role as a form of immunogenic cell death (ICD). Specifically, the oxygenated membrane lipids on ferroptotic cells could mediate the phagocytosis by macrophages to maintain the immune responses. Additionally, immune checkpoint inhibitor therapy may sensitize cancer cells to ferroptosis, while ferroptosis might contribute to tumor immune evasion by directly interfering with the function of various immune cells. Based on these insights, we provided a comprehensive review on the interaction patterns between ferroptosis and immunity, which may not only offer insight into the underlying regulatory mechanisms but also facilitating the development of ferroptosis-based antitumor therapeutics.
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http://dx.doi.org/10.1111/febs.16034DOI Listing
May 2021

AMPKα loss promotes KRAS-mediated lung tumorigenesis.

Cell Death Differ 2021 May 26. Epub 2021 May 26.

Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.

AMP-activated protein kinase (AMPK) is a critical sensor of energy status that coordinates cell growth with energy balance. In non-small cell lung cancer (NSCLC) the role of AMPKα is controversial and its contribution to lung carcinogenesis is not well-defined. Furthermore, it remains largely unknown whether long non-coding RNAs (lncRNAs) are involved in the regulation of AMPK-mediated pathways. Here, we found that loss of AMPKα in combination with activation of mutant KRAS increased lung tumour burden and reduced survival in Kras/AMPKα mice. In agreement, functional in vitro studies revealed that AMPKα silencing increased growth and migration of NSCLC cells. In addition, we identified an AMPKα-modulated lncRNA, KIMAT1 (ENSG00000228709), which in turn regulates AMPKα activation by stabilizing the lactate dehydrogenase B (LDHB). Collectively, our study indicates that AMPKα loss promotes KRAS-mediated lung tumorigenesis and proposes a novel KRAS/KIMAT1/LDHB/AMPKα axis that could be exploited for therapeutic purposes.
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http://dx.doi.org/10.1038/s41418-021-00777-0DOI Listing
May 2021

In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche.

Nat Commun 2021 05 25;12(1):3094. Epub 2021 May 25.

Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.

Short-term, systemic expression of the Yamanaka reprogramming factors (Oct-3/4, Sox2, Klf4 and c-Myc [OSKM]) has been shown to rejuvenate aging cells and promote tissue regeneration in vivo. However, the mechanisms by which OSKM promotes tissue regeneration are unknown. In this work, we focus on a specific tissue and demonstrate that local expression of OSKM, specifically in myofibers, induces the activation of muscle stem cells or satellite cells (SCs), which accelerates muscle regeneration in young mice. In contrast, expressing OSKM directly in SCs does not improve muscle regeneration. Mechanistically, expressing OSKM in myofibers regulates the expression of genes important for the SC microenvironment, including upregulation of p21, which in turn downregulates Wnt4. This is critical because Wnt4 is secreted by myofibers to maintain SC quiescence. Thus, short-term induction of the Yamanaka factors in myofibers may promote tissue regeneration by modifying the stem cell niche.
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http://dx.doi.org/10.1038/s41467-021-23353-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149870PMC
May 2021

H synchronization of delayed neural networks via event-triggered dynamic output control.

Neural Netw 2021 May 11;142:231-237. Epub 2021 May 11.

Computer Science and Engineering Department, Yunnan University, Kunming 650091, China.

This paper investigates H exponential synchronization (ES) of neural networks (NNs) with delay by designing an event-triggered dynamic output feedback controller (ETDOFC). The ETDOFC is flexible in practice since it is applicable to both full order and reduced order dynamic output techniques. Moreover, the event generator reduces the computational burden for the zero-order-hold (ZOH) operator and does not induce sampling delay as many existing event generators do. To obtain less conservative results, the delay-partitioning method is utilized in the Lyapunov-Krasovskii functional (LKF). Synchronization criteria formulated by linear matrix inequalities (LMIs) are established. A simple algorithm is provided to design the control gains of the ETDOFC, which overcomes the difficulty induced by different dimensions of the system parameters. One numerical example is provided to demonstrate the merits of the theoretical analysis.
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http://dx.doi.org/10.1016/j.neunet.2021.05.009DOI Listing
May 2021

Case Report: Two Novel Frameshift Mutations in and One Novel Splice Donor Mutation in Associated With Primary Familial Brain Calcification.

Front Genet 2021 7;12:643452. Epub 2021 May 7.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Beijing, China.

Primary familial brain calcification (PFBC, OMIM#213600), also known as Fahr's disease, is characterized by bilateral and symmetric brain calcification in the basal ganglia (globus pallidus, caudate nucleus, and putamen), thalamus, subcortical white matter, and cerebellum. PFBC can be caused by loss-of-function mutations in any of the six known causative genes. The most common clinical manifestations include movement disorders, cognitive impairment, and neuropsychiatric signs that gradually emerge in middle-aged patients. To broaden the PFBC mutation spectrum, we examined nine members of a family with PFBC and two sporadic cases from clinical departments, and sequenced all PFBC-causative genes in the index case. Two novel frameshift mutations in [NM_001257180.2; c.806delC, p.(Pro269Glnfs49) and c.1154delG, p.(Ser385Ilefs70)] and one novel splice donor site mutation (NM_002608.4, c.456+1G>C, r.436_456del) in were identified in the patient cohort. c.806delC co-segregated with brain calcification and led to haploinsufficiency among the affected family members. The c.456+1G>C mutation in resulted in aberrant mRNA splicing, thereby forming mature transcripts containing an in-frame 21 base pair (bp) deletion, which might create a stably truncated protein [p.(Val146_Gln152del)] and exert a dominant negative effect on wild-type PDGFB. All three mutations were located in highly conserved regions among multiple species and predicted to be pathogenic, as evaluated by at least eight common genetic variation scoring systems. This study identified three novel mutations in and , which broadened and enriched the PFBC mutation spectrum.
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http://dx.doi.org/10.3389/fgene.2021.643452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138311PMC
May 2021

Electrostatic Interaction Between NS1 and Negatively Charged Lipids Contributes to Flavivirus Replication Organelles Formation.

Front Microbiol 2021 6;12:641059. Epub 2021 May 6.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.

Flavivirus replication occurs in membranous replication compartments, also known as replication organelles (ROs) derived from the host ER membrane. Our previous study showed that the non-structural (NS) protein 1 (NS1) is the essential factor for RO creation by hydrophobic insertion into the ER membrane. Here, we found that the association of NS1 with the membrane can be facilitated by the electrostatic interaction between NS1 and negatively charged lipids. NS1 binds to a series of negatively charged lipids, including PI4P, and a positively charged residue, R31, located on the membrane-binding face of NS1, plays important roles in this interaction. The NS1 R31E mutation significantly impairs NS1 association with negatively charged membrane and its ER remodeling ability in the cells. To interfere with the electrostatic interaction between NS1 and negatively charged lipids, intracellular phosphatidylinositol phosphates (PIPs) level was downregulated by the overexpression of Sac1 or treatment with PI3K and PI4K inhibitors to attenuate flavivirus replication. Our findings emphasize the importance of electrostatic interaction between NS1 and negatively charged lipids in flavivirus RO formation.
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http://dx.doi.org/10.3389/fmicb.2021.641059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138564PMC
May 2021

Novel Cryo-EM structures of the D1 dopamine receptor unlock its therapeutic potential.

Signal Transduct Target Ther 2021 May 22;6(1):205. Epub 2021 May 22.

Computational Chemistry and Molecular Biophysics Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.

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http://dx.doi.org/10.1038/s41392-021-00630-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141052PMC
May 2021

In situ loading MnO onto 3D Aramid nanofiber aerogel as High-Performance lead adsorbent.

J Colloid Interface Sci 2021 May 12;600:403-411. Epub 2021 May 12.

State Key Laboratory of Separation Membranes and Membrane Processes/National Center for International Joint Research on Separation Membranes, Tiangong University, Tianjin 300387, PR China; School of Textile Science and Engineering, Tiangong University, Tianjin 300387, PR China. Electronic address:

Fabricating a high-performance adsorbent as a desirable candidate for removing Pb from aqueous water remains a challenge. Aramid nanofibers (ANFs) are promising building blocks that have realized multifunctional applications due to their intrinsic mechanical and chemical stability. Herein, an in situ loading strategy for preparing nanofiber composite aerogel was proposed by assembling ANFs into a 3D aerogel and applying it as host media for the in situ polymerization of pyrrole followed by facile redox reaction between the polypyrrole (PPy) and MnO to load manganese dioxide (MnO). The idea was to fully exploit the structural advantages of ultra-low bulk density, large specific surface area, and high porosity of ANFs, and the possible chemical adsorption characteristics of MnO on the basis of ion exchange reaction. The adsorption capacity of 3D ANF/MnO composite aerogel was as large as 554.36 mg/g for Pb. The adsorption mechanism based on an exchange reaction between Pb and protons on the surface of MnO was also investigated. The desorption results showed that the adsorption performance could remain up to 90% after five times of usage. In conclusion, this research provides promising insights into the preparation of high-performance lead adsorbent for water treatment.
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http://dx.doi.org/10.1016/j.jcis.2021.05.048DOI Listing
May 2021

A novel selective mitochondrial-targeted curcumin analog with remarkable cytotoxicity in glioma cells.

Eur J Med Chem 2021 Oct 12;221:113528. Epub 2021 May 12.

Department of Surgery, Children's Hospital of Soochow University, Suzhou, 215021, PR China. Electronic address:

Naturally occurring polyphenol curcumin (4) or demethoxycurcumin (5) and their synthetic derivatives display promising anticancer activities. However, their further development is limited by low bioavailability and poor selectivity. Thus, a mitochondria-targeted compound 14 (DMC-TPP) was prepared in the present study by conjugating a triphenylphosphine moiety to the phenolic hydroxyl group of demethoxycurcumin to enhance its bioavailability and treatment efficacy. The in vitro biological experiments of DMC-TPP showed that it not only displayed higher cytotoxicity as compared with its parent compound 5, but also exhibited superior mitochondria accumulation ability. Glioma cells were more sensitive to DMC-TPP, which inhibited the proliferation of U251 cells with an IC of 0.42 μM. The mechanism studies showed that DMC-TPP triggers mitochondria-dependent apoptosis, caused by caspase activation, production of reactive oxygen species (ROS) and decrease of mitochondrial membrane potential (MMP). In addition, DMC-TPP efficiently inhibited cellular thioredoxin reductase, which contributed to its cytotoxicity. Significantly, DMC-TPP delayed tumor progression in a mouse xenograft model of human glioma cancer. Taken together, the potent in vitro and in vivo antitumor activity of DMC-TPP warrant further comprehensive evaluation as a novel anti-glioma agent.
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http://dx.doi.org/10.1016/j.ejmech.2021.113528DOI Listing
October 2021