Publications by authors named "Yao Chao"

85 Publications

Tanshinone IIA enhances susceptibility of non-small cell lung cancer cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5.

J Leukoc Biol 2021 Apr 28. Epub 2021 Apr 28.

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Natural killer (NK) cells have a great potential in cancer immunotherapy. However, their therapeutic efficacy is clinically limited owing to cancer cell immune escape. Therefore, it is urgently necessary to develop novel method to improve the antitumor immunity of NK cells. In the present study, it was found that the natural product tanshinone IIA (TIIA) enhanced NK cell-mediated killing of non-small cell lung cancer (NSCLC) cells. TIIA in combination with adoptive transfer of NK cells synergistically suppressed the tumor growth of NSCLC cells in an immune-incompetent mouse model. Furthermore, TIIA significantly inhibited the tumor growth of Lewis lung cancer (LLC) in an immune-competent syngeneic mouse model, and such inhibitory effect was reversed by the depletion of NK cells. Moreover, TIIA increased expressions of ULBP1 and DR5 in NSCLC cells, and inhibition of DR5 and ULBP1 reduced the enhancement of NK cell-mediated lysis by TIIA. Besides, TIIA increased the levels of p-PERK, ATF4 and CHOP. Knockdown of ATF4 completely reversed the up-regulation of ULBP1 and DR5 by TIIA in all detected NSCLC cells, while knockdown of CHOP only partly reduced these enhanced expressions in small parts of NSCLC cells. These results demonstrated that TIIA could increase the susceptibility of NSCLC cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5, suggesting that TIIA had a promising potential in cancer immunotherapy, especially in NK cell-based cancer immunotherapy.
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http://dx.doi.org/10.1002/JLB.5MA1120-776RRDOI Listing
April 2021

Binaphthyl-prolinol chiral ligands: design and their application in enantioselective arylation of aromatic aldehydes.

Org Biomol Chem 2021 Apr;19(16):3644-3655

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China. and CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, People's Republic of China.

Binaphthyl-prolinol ligands were designed and applied in enantioselective arylation of aromatic aldehydes and sequential arylation-lactonization of methyl 2-formylbenzoate. Under optimized conditions, the reactions provided the desired diarylmethanols and 3-aryl phthalides in up to 96% yields with up to 99% ee and up to 89% yields with up to 99% ee, respectively. In particular, essentially optically pure 3-aryl phthalides (over 99% ee) were obtained in large quantities through recrystallization.
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http://dx.doi.org/10.1039/d1ob00289aDOI Listing
April 2021

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Mediators Inflamm 2021 1;2021:8856326. Epub 2021 Apr 1.

School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.
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http://dx.doi.org/10.1155/2021/8856326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035014PMC
April 2021

[Clinical Characteristics and Survival Analysis of Patients with IgD Multiple Myeloma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):547-552

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Objective: To explore the clinical features, prognosis and survival of patients with IgD multiple myeloma (MM).

Methods: The clinical data of 20 patients with IgD MM was analyzed retrospectively. The prognostic factors and survival analysis was carried out. We summarized their clinical characteristics. The survival analysis was carried out by Kaplan-Meier method, and the prognostic factor were analyzed by using log-rank test for single factor analysis of observation index. Variables of P<0.15 in single factor analysis were enrolled in multifactor cox regression analysis.

Results: IgD MM patients accounted for 4.3% of all MM patients in the same period, among which 80% were male, the median age of patients was 57.5(35-77) years old, 90% of the patients belongs to λ light chain type. At the time of diagnosis, 18 patients (90%) were in DS-Ⅲ stages, while 10 patients were in ISS-Ⅲ stage. The first clinical manifestations were fatigue, bone pain, kidney function impairment, anemia (Hb<100 g/L) in 14 cases (70%), 12 cases (60%) with osteolytic bone destruction≥3, combined with renal impairment in 8 cases (40%), and elevated blood calcium in 11 cases (51.4%). In only 5 patients the ratio of albumin to globntin was inverted, hypoalbuminemia accounted for 40%, and globulin increase accounted for only 15%. FISH results showed that the positive rate of 1q21 amplification (50%) was the highest, and it was easy to occur at the same time as other cytogenetic abnormalities. Extramedullary infiltration occurred in 4 cases (20%). The analysis of prognostic factors showed that only the increase of lactate dehydrogenase (LDH) level was an independent poor prognostic factor for IgD MM patients. Extramedullary infiltration and various cytogenetic abnormalities were found in 2 IgD MM patients with primary drug resistance, suggesting that extramedullary infiltration and various cytogenetic abnormalities may be prognostic factors, but the difference was not statistically significant, Which maybe related to the small sample size. All 20 patients were treated with bortezomib-containing regimen, of which 19 patients were evaluated, 17 patients (89.4%) showed effective, including CR+VGPR (52.6%), PR (31.5%), MR (5.3%), 2 patients primary drug resistance. The median PFS and OS was 9.5 and 10.5 months, respectively.

Conclusion: IgD MM is a rare and invasive disease. Increased LDH is an independent prognostic factor. Bortizomib-containing regimen can improve the prognosis of IgD MM patients.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.038DOI Listing
April 2021

Core-shell ZIF-8@MIL-68(In) derived ZnO nanoparticles-embedded InO hollow tubular with oxygen vacancy for photocatalytic degradation of antibiotic pollutant.

J Hazard Mater 2021 Feb 17;414:125395. Epub 2021 Feb 17.

Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, PR China; School of Environmental & Safety Engineering, Changzhou University, Changzhou 213164, PR China. Electronic address:

Developing a novel core-multishelled metal oxide hollow tube with rich oxygen vacancy is highly attractive in photocatalytic degradation of antibiotic pollutant. Herein, ZnO@InO core-shell hollow microtubes were synthesized via one-step calcination of ZIF-8@MIL-68(In) formed by an in-situ self-assembly. TEM images demonstrate that 0D ZnO quantum dots (QDs) shell with 0.2 µm were well coated on the surface of 1D InO hollow tube as the core with 1.2 µm. The synthesized heterostructure indicates the enhanced photocatalytic performance in tetracycline (TC) degradation compared with single ZIF-derived ZnO and MIL-68(In)-derived InO under simulated solar irradiation. Besides, organic pollutants including malachite green (MG), methylene blue (MB) and rhodamine B (RhB) are further used to evaluate the photocatalytic activity of ZnO@InO, and the effect of weight ratios between ZnO and InO on degradation efficiency is also studies. The ZnO@InO heterojunction can provide higher specific surface area, expose more active sites, possess appropriate number of oxygen vacancies, enhance light absorption and further effectively boost the transfer and separation of photoinduced charge carriers. In addition, the proposed photocatalytic mechanism and degradation pathway are discussed in detail based on active species trapping test, electron spin resonance (ESR) and LCMS.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125395DOI Listing
February 2021

Pain Relief Dependent on IL-17-CD4 T Cell-β-Endorphin Axis in Rat Model of Brachial Plexus Root Avulsion After Electroacupuncture Therapy.

Front Neurosci 2020 9;14:596780. Epub 2021 Feb 9.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background And Purpose: Neuropathic pain is the typical symptom of brachial plexus root avulsion (BPRA), and no effective therapy is currently available. Electroacupuncture (EA), as a complementary and alternative therapy, plays a critical role in the management of pain-associated diseases. In the present study, we aimed to reveal the peripheral immunological mechanism of EA in relieving the pain of BPRA through the IL-17-CD4 T lymphocyte-β-endorphin axis.

Methods: After receiving repeated EA treatment, the pain of BPRA in rats along with the expressions of a range of neurotransmitters, the contents of inflammatory cytokines, and the population of lymphocytes associated were investigated. CD4 T lymphocytes were either isolated or depleted with anti-CD4 monoclonal antibody. The titers of IL-17A, interferon-γ (IFN-γ), and β-endorphin were examined. The markers of T lymphocytes, myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), macrophages, and natural killer (NK) cells were assessed. The activation of the nuclear transcription factor κB (NF-κB) signaling pathway was tested.

Results: The pain of BPRA was significantly relieved, and the amount of CD4 T lymphocytes was increased after EA treatment. The release of β-endorphin was up-regulated with the up-regulation of IL-17A in CD4 T lymphocytes. The titer of IL-17A was enhanced, leading to an activated NF-κB signaling pathway. The release of β-endorphin and the analgesic effect were almost completely abolished when CD4 T lymphocytes were depleted.

Conclusion: We, for the first time, showed that the neuropathic pain caused by BPRA was effectively relieved by EA treatment via IL-17-CD4 T lymphocyte-β-endorphin mediated peripheral analgesic effect, providing scientific support for EA clinical application.
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http://dx.doi.org/10.3389/fnins.2020.596780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901907PMC
February 2021

[Clinical Characteristic, Prognosis and Treatment Outcome of Elderly Multiple Myeloma Patients with Impaired Renal Function].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Feb;29(1):145-151

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Objective: To explore the risk factors, prognosis and curative effect of elderly patients with MM renal damage.

Methods: 118 patients with primary elderly MM treated in our hospital from January 2011 to December 2018, were enrolled analyzed retrospectively. The clinical characteristics and prognosis of renal function impairment group (RI group) and normal renal function group (non-RI group) were compared. The difference of renal efficacy and survival benefit between the patients treated with bortezomib, thalidomide (combination group) and chemotherapy regimen containing only one of them (single drug group) in RI group was compared.

Results: Univariate analysis showed that DS stage, pulmonary infection, uric acid, β microglobulin and leukocyte in RI group were higher than those in non-RI group, but hemoglobin was lower than that in non-RI group (P<0.05). Multivariate logistic regression analysis showed that β microglobulin was the independent risk factor for renal damage in elderly patients with MM. Kaplan-Meier method showed that the OS and PFS in RI group were significantly lower than those in non-RI group (P<0.05). The renal efficacy in the combined treatment group was significantly better than that of the single drug group (P<0.05), and it could bring benefit to the PFS of the elderly patients with MM renal damage (P<0.05).

Conclusion: The prognosis of elderly MM patients with impaired renal function is poor. The prognosis of these patients can be improved by selecting chemotherapy regimen containing bortezomib and thalidomide at the same time, and monitoring, controlling all kinds of risk factors actively.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.01.023DOI Listing
February 2021

[Clinical Analysis of 46 Cases of Multiple Myeloma with Extramedullary Disease].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Feb;29(1):115-121

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China,E-mail:

Objective: To investigate the effect of clinical baseline data on prognosis in patients with multiple myeloma (MM) complicated by extramedullary disease (EMD).

Methods: The clinical data of 46 MM patients with EMD were retrospectively analyzed. The clinical data and survival prognosis of MM patients in primary EMD group and recurrent EMD group were analyzed. The classified baseline data were expressed by the number of cases (percentage), the χ test was used to compare the two classification data groups. The OS and PFS curves were drawn by multiplication positive limit method (Kaplan-Meier). Log-rank test was used for the univariate analysis of prognosis, and COX proportional risk regression model was used for the multiple factors of prognosis.

Results: β microglobulin≥2.7 g/L, lactic dehydrogenase≥250 U/L, serum calcium≥2.75 mmol/L, plasma cells in bone marrow≥60% were the poor prognostic factors for PFS. Serum calcium≥2.75 mmol/L and the plasma cells in bone marrow≥60% were the poor prognostic factors for OS. Multivariate regression analysis enroling the statistically significant factors in univariate analysis baseline date in factors in showed that plasma cell level≥60% in bone marrow was independent poor prognostic factors for PFS, and serum calcium≥2.75 mmol/L was an independent poor prognostic factor for OS. The IgG type is the most common type of MM complicated by EMD. The remission depth of primary EMD group≥VGPR was lower than that of recurrent EMD group, and there was significant difference between the two groups (P<0.05), and the median OS time of patients with primary EMD group was shorter than that of patients with recurrent EMD group, the difference was statistically significant (P<0.05). The 3-year survival rates of primary EMD group and recurrent EMD group were 10.0% and 34%, respectively, there was no significant difference between the two groups (P>0.05). The 5-year survival rate was 0 and 20%, respectively, there was significant difference between the two groups (P<0.05).

Conclusion: The remission depth of primary EMD group≥VGPR is lower than that of recurrent EMD group,and the OS time of patients in primary EMD group is shorter than that in recurrent EMD group. Bortezomib-based chemotherapy could not improve the prognosis of patients with primary EMD and recurrent EMD, and the prognosis of patients with primary EMD is even worse.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.01.019DOI Listing
February 2021

Grain-sized moxibustion promotes NK cell antitumour immunity by inhibiting adrenergic signalling in non-small cell lung cancer.

J Cell Mol Med 2021 Mar 27;25(6):2900-2908. Epub 2021 Jan 27.

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Lung cancer is the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer diagnoses. As an ancient therapy, moxibustion has been used to treat cancer-related symptoms in clinical practice. However, its antitumour effect on NSCLC remains largely unexplored. In the present study, a Lewis lung cancer (LLC) xenograft tumour model was established, and grain-sized moxibustion (gMoxi) was performed at the acupoint of Zusanli (ST36). Flow cytometry and RNA sequencing (RNA-Seq) were used to access the immune cell phenotype, cytotoxicity and gene expression. PK136, propranolol and epinephrine were used for natural killer (NK) cell depletion, β-adrenoceptor blockade and activation, respectively. Results showed that gMoxi significantly inhibited LLC tumour growth. Moreover, gMoxi significantly increased the proportion, infiltration and activation of NK cells, whereas it did not affect CD4 and CD8 T cells. NK cell depletion reversed gMoxi-mediated tumour regression. LLC tumour RNA-Seq indicated that these effects might be related to the inhibition of adrenergic signalling. Surely, β-blocker propranolol clearly inhibited LLC tumour growth and promoted NK cells, and gMoxi no longer increased tumour regression and promoted NK cells after propranolol treatment. Epinephrine could inhibit NK cell activity, and gMoxi significantly inhibited tumour growth and promoted NK cells after epinephrine treatment. These results demonstrated that gMoxi could promote NK cell antitumour immunity by inhibiting adrenergic signalling, suggesting that gMoxi could be used as a promising therapeutic regimen for the treatment of NSCLC, and it had a great potential in NK cell-based cancer immunotherapy.
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http://dx.doi.org/10.1111/jcmm.16320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957214PMC
March 2021

SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.

Nat Commun 2021 01 8;12(1):135. Epub 2021 Jan 8.

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200001, China.

Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter. NF-kB binds the disease protective allele in a sequence-specific manner, increasing expression of this immunoregulatory microRNA. Finally, CRISPR activation-based modulation of this enhancer in the PBMCs of SLE patients attenuates type I interferon pathway activation by increasing miR-146a expression. Our work provides a strategy to define non-coding RNA functional regulatory elements using disease-associated variants and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.
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http://dx.doi.org/10.1038/s41467-020-20460-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794586PMC
January 2021

Targeting CD155 by rediocide-A overcomes tumour immuno-resistance to natural killer cells.

Pharm Biol 2021 Dec;59(1):47-53

Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.

Context: Therapeutic benefits of immunotherapy are restricted by cancer immune-resistance mechanisms. Rediocide-A (Red-A), a natural product extracted from Traditional Chinese Medicine, is a promising agent to battle against cancer which acts as an immune checkpoint inhibitor.

Objective: To investigate the effect of Red-A on NK-cell tumouricidal activity.

Materials And Methods: NK cells were co-cultured with A549 or H1299 cells and treated with 10 or 100 nM Red-A for 24 h. Cells treated with 0.1% dimethyl sulphoxide (DMSO) was employed as vehicle control. NK cell-mediated cytotoxicity was detected by biophotonic cytotoxicity and impedance assay. Degranulation, granzyme B, NK cell-tumour cell conjugates and ligands profiling were detected by flow cytometry. Interferon-γ (IFN- γ) production was assessed by enzyme-linked immunosorbent assay (ELISA).

Results: Red-A increased NK cell-mediated lysis of A549 cells by 3.58-fold (21.86% vs. 78.27%) and H1299 cells by 1.26-fold (59.18% vs. 74.78%), compared to vehicle control. Granzyme B level was increased by 48.01% (A549 cells) and 53.26% (H1299 cells) after 100 nM Red-A treatment. INF-γ level was increased by 3.23-fold (A549 cells) and 6.77-fold (H1299 cells) after 100 nM Red-A treatment. Red-A treatment down-regulated the expression level of CD155 by 14.41% and 11.66% in A549 cells and H1299 cells, respectively, leading to the blockade of tumour immuno-resistance to NK cells.

Conclusions: Red-A overcomes immuno-resistance of NSCLCs to NK cells by down-regulating CD155 expression, which shows the possibility of developing checkpoint inhibitors targeting TIGIT/CD155 signalling to overcome immuno-resistance of cancer cells.
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http://dx.doi.org/10.1080/13880209.2020.1865410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801066PMC
December 2021

Development of a Predictive Immune-Related Gene Signature Associated With Hepatocellular Carcinoma Patient Prognosis.

Cancer Control 2020 Jan-Dec;27(1):1073274820977114

Department of Hepatobiliary Surgery, BengBu Medical College, BengBu, China.

Background: Hepatocellular carcinoma (HCC) remains the third leader cancer-associated cause of death globally, but the etiological basis for this complex disease remains poorly clarified. The present study was thus conceptualized to define a prognostic immune-related gene (IRG) signature capable of predicting immunotherapy responsiveness and overall survival (OS) in patients with HCC.

Methods: Five differentially expressed IRG associated with HCC were established the immune-related risk model through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Patients were separated at random into training and testing cohorts, after which the association between the identified IRG signature and OS was evaluated using the "survival" R package. In addition, maftools was leveraged to assess mutational data, with tumor mutation burden (TMB) scores being calculated as follows: (total mutations/total bases) × 10. Immune-related risk term abundance was quantified via "ssGSEA" algorithm using the "gsva" R package.

Results: HCC patients were successfully stratified into low-risk and high-risk groups based upon a signature composed of 5 differentially expressed IRGs, with overall survival being significantly different between these 2 groups in training cohort, testing cohort and overall patient cohort ( = 1.745e-06, = 1.888e-02, = 4.281e-07). No association was observed between TMB and this IRG risk score in the overall patient cohort ( = 0.461). Notably, 19 out of 29 immune-related risk terms differed substantially in the overall patient dataset. These risk terms mainly included checkpoints, human leukocyte antigens, natural killer cells, dendritic cells, and major histocompatibility complex class I.

Conclusion: In summary, an immune-related prognostic gene signature was successfully developed and used to predict survival outcomes and immune system status in patients with HCC. This signature has the potential to help guide immunotherapeutic treatment planning for patients affected by this deadly cancer.
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http://dx.doi.org/10.1177/1073274820977114DOI Listing
December 2020

Correction to: Sophoridine induces apoptosis and S phase arrest via ROS-dependent JNK and ERK activation in human pancreatic cancer cells.

J Exp Clin Cancer Res 2020 Nov 26;39(1):263. Epub 2020 Nov 26.

School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s13046-020-01764-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690084PMC
November 2020

Binaphthyl-based chiral ligands: design, synthesis and evaluation of their performance in enantioselective addition of diethylzinc to aromatic aldehydes.

Org Biomol Chem 2020 Dec 25;18(47):9712-9725. Epub 2020 Nov 25.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, People's Republic of China.

The design strategy and the performance of binaphthyl-based chiral ligands were evaluated with computation and enantioselective addition of diethylzinc to aromatic aldehydes. Under optimized conditions, enantioselective addition of diethylzinc to aromatic aldehydes provided the desired optically active secondary alcohols in high isolated yields (up to 91%) and excellent enantiomeric excesses (up to 98% ee).
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http://dx.doi.org/10.1039/d0ob02127jDOI Listing
December 2020

Accessing Highly Oriented Two-Dimensional Perovskite Films via Solvent-Vapor Annealing for Efficient and Stable Solar Cells.

Nano Lett 2020 Dec 9;20(12):8880-8889. Epub 2020 Nov 9.

Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.

Accessing vertical orientation of two-dimensional (2D) perovskite films is key to achieving high-performance solar cells with these materials. Herein, we report on solvent-vapor annealing (SVA) as a general postdeposition strategy to induce strong vertical orientation across broad classes of 2D perovskite films. We do not observe any local compositional drifts that would result in impure phases during SVA. Instead, our experiments point to solvent vapor plasticizing 2D perovskite films and facilitating their surface-induced reorientation and concomitant grain growth, which enhance out-of-plane charge transport. Solar cells with SVA 2D perovskites exhibit superior efficiency and stability compared to their untreated analogs. With a certified efficiency of (18.00 ± 0.30) %, our SVA (BDA)(CsFA)PbI solar cell boasts the highest efficiency among all solar cells with 2D perovskites ( ≤ 5) reported so far.
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http://dx.doi.org/10.1021/acs.nanolett.0c03914DOI Listing
December 2020

Long non-coding RNA expression profiles in neutrophils revealed potential biomarker for prediction of renal involvement in SLE patients.

Rheumatology (Oxford) 2021 Apr;60(4):1734-1746

Department of Rheumatology, Renji Hospital, Shanghai Institute of Rheumatology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: The long non-coding RNA plays an important role in inflammation and autoimmune diseases. The aim of this study is to screen and identify abnormally expressed lncRNAs in peripheral blood neutrophils of SLE patients as novel biomarkers and to explore the relationship between lncRNAs levels and clinical features, disease activity and organ damage.

Methods: RNA-seq technology was used to screen differentially expressed lncRNAs in neutrophils from SLE patients and healthy donors. Based on the results of screening, candidate lncRNA levels in neutrophils of 88 SLE patients, 35 other connective disease controls, and 78 healthy controls were qualified by real-time quantitative polymerase chain reaction.

Results: LncRNA expression profiling revealed 360 up-regulated lncRNAs and 224 down-regulated lncRNAs in neutrophils of SLE patients when compared with healthy controls. qPCR assay validated that the expression of Lnc-FOSB-1:1 was significantly decreased in neutrophils of SLE patients when compared with other CTD patients or healthy controls. It correlated negatively with SLE Disease Activity Index 2000 (SLEDAI-2K) score (r = -0.541, P < 0.001) and IFN scores (r = -0.337, P = 0.001). More importantly, decreased Lnc-FOSB-1:1 expression was associated with lupus nephritis. Lower baseline Lnc-FOSB-1:1 level was associated with higher risk of future renal involvement (within an average of 2.6 years) in patients without renal disease at baseline (P = 0.019).

Conclusion: LncRNA expression profile in neutrophils of SLE patients revealed differentially expressed lncRNAs. Validation study on Lnc-FOSB-1:1 suggest that it is a potential biomarker for prediction of near future renal involvement.
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http://dx.doi.org/10.1093/rheumatology/keaa575DOI Listing
April 2021

Rosthorin A inhibits non-small cell lung cancer cell growth and metastasis through repressing epithelial-mesenchymal transition via downregulating Slug.

Anticancer Drugs 2020 11;31(10):997-1003

Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University.

Lung cancer always ranks first in the number of cancer deaths every year, accounting for 18.4% of total cancer deaths in 2018. Metastasis is the main cause of death in lung cancer patients. The identification of bioactive components of traditional Chinese medicine is very important for the development of novel reagents against non-small cell lung cancer (NSCLC). Rosthorin A has originated from Rabdosia rosthornii (Diels) Hara which excerpts from 'Chinese materia medica', and is known to have 'clear heat phlegm' properties in the folk. Little is known about the biological functions and mechanisms of Rosthorin A in cancer cells at present. The role of EMT in metastasis of a tumor cell is self-evident. Slug is an important EMT inducer, which is related to the development of lung cancer. Cell growth, clone assay, cell migration, cell invasion, and protein expression, and NSCLC transplanted tumor growth were performed in A549, H1299, and H1975 cells. Rosthorin A significantly inhibited the growth of NSCLC cells, it could prolong the survival of nude mice. Rosthorin A inhibited the migration and invasion of A549, H1299, and H1975 cells. Rosthorin A up-regulated E-cadherin expression level and down-regulated the expression of β-catenin, N-cadherin, vimentin, Slug, and Twist. Rosthorin A could promote the expression of E-cadherin and inhibit the development of EMT by downregulating Slug, to inhibit the development and metastasis of NSCLC cells. In summary, Rosthorin A could be used as a promising candidate for the treatment of NSCLC patients with recurrence and metastasis.
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http://dx.doi.org/10.1097/CAD.0000000000000973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566306PMC
November 2020

Thevebioside, the active ingredient of traditional Chinese medicine, promotes ubiquitin-mediated SRC-3 degradation to induce NSCLC cells apoptosis.

Cancer Lett 2020 11 20;493:167-177. Epub 2020 Aug 20.

School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address:

Non-small cell lung cancer (NSCLC) accounts for more than 85% of lung cancer with high incidence and mortality. Accumulating studies have shown that traditional Chinese medicine (TCM) and its active ingredients have good anti-tumor activity. However, the anti-tumor effect of Thevebioside (THB), an active ingredient from TCM, is still unknown in NSCLC. In this study, to our best knowledge, it was the first time to report the underlying mechanism of its tumor-suppressive activity in NSCLC based on our previous high-throughput screening data. We further demonstrated that THB effectively inhibited the proliferation of NSCLC cells (A549 and H460) by inducing cellular apoptosis rather than cell cycle arrest. Notably, it was demonstrated that SRC-3 was significantly down-regulated after THB treatment dependent on ubiquitin-proteasome-mediated degradation, which subsequently inhibited the IGF-1R-PI3K-AKT signaling pathway and promoted apoptosis via both in vivo and in vitro experiments. Collectively, THB exerted inhibitory effect on tumor growth of NSCLC through inhibiting SRC-3 mediated IGF-1R-PI3K-AKT signaling by ubiquitination to induce cellular apoptosis with minimal toxicity no matter in vitro or vivo.
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http://dx.doi.org/10.1016/j.canlet.2020.08.011DOI Listing
November 2020

Clay-activated carbon adsorbent obtained by activation of spent bleaching earth and its application for removing Pb(II) ion.

Environ Sci Pollut Res Int 2021 Jan 20;28(1):711-723. Epub 2020 Aug 20.

School of Petrochemical Engineering, Changzhou University, Changzhou, 213164, People's Republic of China.

BE/C-A750-1/1 is prepared by carbonizing SBE and then activating with KOH. BE/C-A750-1/1 has good adsorption capacity for Pb(II), and the adsorption capacity for Pb(II) is 206.65 mg/g. The harmful effects of coexisting cations are listed in ascending order: K < Na < Mg. Adsorption and desorption studies show that the adsorption capacity of BE/C-A750-1/1 for Pb(II) after adsorption and desorption 3 times is 183.62 mg/g. The adsorption mechanism mainly includes electrostatic attraction, ion exchange, physical adsorption, and chemical complexation. This suggests that activated BE/C may be a promising candidate for removing Pb(II) from industrial wastewater. Clay/carbon nanocomposites were prepared by carbonizing and activating the spent bleaching earth served as adsorbents for the efficient removal of Pb(II) from wastewater.
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http://dx.doi.org/10.1007/s11356-020-10473-0DOI Listing
January 2021

The MicroRNA Represses Th17 Cell Pathogenicity by Targeting PTEN-Regulated Pathways.

Immunohorizons 2020 06 9;4(6):308-318. Epub 2020 Jun 9.

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China;

Multiple sclerosis is a chronic autoimmune disease driven by pathogenic Th17 cells. In this study, we dissected the role of - in pathogenic Th17 cells by autoantigen-specific disease models. We first showed that was upregulated in peripheral lymphoid organs and spinal cords of mice developed autoimmune encephalomyelitis. Although - was upregulated in multiple Th cell subsets, it was dispensable for Th cell differentiation in vitro. Whereas mice exhibited milder symptoms of disease in an active experimental autoimmune encephalomyelitis model, adoptive transfer of 2D2 Th17 cells into naive recipient mice promoted higher disease incidence and severity compared with mice transferred with control 2D2 Th17 cells. Global transcriptional analysis of deficient pathogenic Th17 cells revealed upregulated genes in phosphatase and tensin homologue (PTEN)-mediated pathways, and was further identified as one of its potential targets. Therefore, we identified that Th17 cell-intrinsic could protect mice from autoimmunity by targeting PTEN-regulated pathways.
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http://dx.doi.org/10.4049/immunohorizons.2000008DOI Listing
June 2020

Inhibition of Glycolysis in Pathogenic T17 Cells through Targeting a -c-Rel Pathway Prevents Autoimmunity.

J Immunol 2020 06 15;204(12):3160-3170. Epub 2020 May 15.

Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China;

It is well known that some pathogenic cells have enhanced glycolysis; the regulatory network leading to increased glycolysis are not well characterized. In this study, we show that CNS-infiltrated pathogenic T17 cells from diseased mice specifically upregulate glycolytic pathway genes compared with homeostatic intestinal T17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro-derived pathogenic T17 cells are highly glycolytic compared with nonpathogenic T17 cells. Chromatin landscape analyses demonstrate T17 cells in vivo that show distinct chromatin states, and pathogenic T17 cells show enhanced chromatin accessibility at glycolytic genes with NF-κB binding sites. Mechanistic studies reveal that targets the E3 ubiquitin ligase -c-Rel pathway to promote glucose metabolism of pathogenic T17 cells. Therapeutic targeting c-Rel-mediated glycolysis in pathogenic T17 cells represses autoimmune diseases. These findings extend our understanding of the regulation T17 cell glycolysis in vivo and provide insights for future therapeutic intervention to T17 cell-mediated autoimmune diseases.
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http://dx.doi.org/10.4049/jimmunol.2000060DOI Listing
June 2020

A high-throughput assay for screening natural products that boost NK cell-mediated killing of cancer cells.

Pharm Biol 2020 Dec;58(1):357-366

Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Natural killer (NK) cells can eliminate malignant cells and play a vital role in immunosurveillance. Administration of natural compounds represents a promising approach for antitumor immunotherapy, which may enhance the NK cell activity via multiple mechanisms. Establishing approaches to evaluate the effect of select natural products on NK cell-mediated cytotoxicity. We selected a natural product library containing 2880 pure compounds, which was provided by the National Centre for Drug Screening of China. 0.1% DMSO was employed as a negative control, and 100 U/mL human recombinant IL-2 was employed as a positive control. To evaluate the % of tumour cells which were killed by NK cells, expanded NK cells were co-cultured with tumour cells and then treated with natural products at the concentration of 10 μM. After 24-h co-incubation, luminescent signal was detected and percent lysis was calculated. We report on the results of a three-round high-throughput screening effort that identified 20-deoxyingenol 3-angelate (DI3A) and its analogue ingenol 3-angelate (I3A) as immuno enhancers which boosts NK cell-mediated killing of non-small cell lung cancer cells (NSCLCs). Biophotonic cytotoxicity assay and calcein release assay were used as two well-established NK cell cytotoxicity detection assays to validate the immuno-enhancing effects of DI3A and I3A, which was achieved by increasing degranulation and interferon-gamma secretion of NK cells. Our newly established ATP-based method was a valuable and information-rich screening tool to investigate the biological effects of natural products on both NK cells and tumour cells.
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http://dx.doi.org/10.1080/13880209.2020.1748661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241510PMC
December 2020

Trifluoromethyl Group-Modified Non-Fullerene Acceptor toward Improved Power Conversion Efficiency over 13% in Polymer Solar Cells.

ACS Appl Mater Interfaces 2020 Mar 28;12(10):11543-11550. Epub 2020 Feb 28.

School of Advanced Materials, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

Herein, we report a new molecule structure modification strategy for non-fullerene small-molecule electron acceptors (NFAs) for solar cells through trifluoromethylation of end-capping groups. The synthesized trifluoromethylated acceptor ITCF3 exhibits narrower band gap, stronger light absorption, lower molecular energy levels, and better electron transport property compared to the reference NFA without the trifluoromethyl group (ITIC). Bulk heterojunction solar cells based on ITCF3 combined with the PM6 polymer donor exhibit a significantly improved power conversion efficiency of 13.3% compared with the ITIC-based device (8.4%). This work reveals great potential of trifluoromethylation in the design of efficient photovoltaic acceptor materials.
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http://dx.doi.org/10.1021/acsami.9b20544DOI Listing
March 2020

A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications.

Biomed Pharmacother 2020 May 12;125:109767. Epub 2020 Feb 12.

Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China. Electronic address:

Diabetes mellitus (DM) is a major world health problem and one of the most studied diseases, which are highly prevalent in the whole world, it is frequently associated with severe clinical complications, such as diabetic cardiomyopathy, nephropathy, retinopathy, neuropathy etc. Scientific research is continuously casting about for new monomer molecules from Chinese herbal medicine that could be invoked as candidate drugs for fighting against diabetes and its complications. Resveratrol (RES), a polyphenol phytoalexin, possesses diverse biochemical and physiological actions, including antiplatelet, estrogenic, and anti-inflammatory properties. It is recently gaining scientific interest for RES in controlling blood sugar and fighting against diabetes and its complications properties in various types of diabetic models. These beneficial effects seem to be due to the multiple actions of RES on cellular functions, which make RES become a promising molecule for the treatment of diabetes and diabetic complications. Here, we review the mechanism of action and potential therapeutic use of RES in prevention and mitigation of these diseases in recent ten years to provide a reference for further research and development of RES.
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http://dx.doi.org/10.1016/j.biopha.2019.109767DOI Listing
May 2020

Long non-coding RNAs: How to regulate the metastasis of non-small-cell lung cancer.

J Cell Mol Med 2020 03 12;24(6):3282-3291. Epub 2020 Feb 12.

Center for Traditional Chinese Medicine and Immunology Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Non-small-cell lung cancer (NSCLC) has become the most lethal human cancer because of the high rate of metastasis. Hence, clarifying the molecular mechanism underlying NSCLC metastasis is very important to improve the prognosis of patients with NSCLC. Long non-coding RNAs (LncRNAs) are a class of RNA molecules longer than 200 nucleotides, which can participate in diverse biological processes. About 18% of human LncRNAs were recently found to be associated with tumours. Many studies indicated that aberrant expression of LncRNAs played key roles in the progression and metastasis of NSCLC. According to the function in tumours, LncRNAs can be divided into two classes: oncogenic LncRNAs and tumour-suppressor LncRNAs. In this review, we summarized the main molecular mechanism of LncRNAs regulating NSCLC metastasis, including three aspects: (a) LncRNAs interact with miRNAs as ceRNAs; (b) LncRNAs bind with target proteins; and (c) LncRNAs participate in the transduction of different signal pathways. Then, LncRNAs can exert their function to regulate the metastasis of NSCLC through influencing the progression of epithelial-mesenchymal transition (EMT) and the properties of cancer stem cell (CSC). But, it is necessary to do some further research to demonstrate the LncRNAs particular regulatory mechanism of inhibiting the metastasis of NSCLC and explore new drugs targeting LncRNAs.
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http://dx.doi.org/10.1111/jcmm.15054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131947PMC
March 2020

Full spectrum driven SCR removal of NO over hierarchical CeVO/attapulgite nanocomposite with high resistance to SO and HO.

J Hazard Mater 2020 03 26;386:121977. Epub 2019 Dec 26.

Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA. Electronic address:

Removal of hazardous NO at low temperature via photo-assisted selective catalytic reduction (photo-SCR) strategy is promising, however fully harvesting of solar energy and achieving high SO/HO tolerance still remain a challenge. Herein, the phosphoric acid modified natural attapulgite(P-ATP) was employed as a matrix to immobilize CeVO by microwave hydrothermal method. Results show that P-ATP provides abundant active sites facilitating the in situ grow of CeVO nanorods on its surface which hierarchically construct a dendritic-like photocatalyst. The near-infrared (NIR) light is upconverted to visible and UV light through CeVO which not only broaden the absorption range of solar light, but also build Z-scheme heterostructure with P-ATP enhancing the redox potential of charge carriers. The CeVO/P-ATP nanocomposite can reach as high as 92 % for NO conversion under full-spectrum solar irradiation, while retaining nearly 60 % conversion under NIR light. Moreover, the catalyst exhibits outstanding tolerance with SO and HO due to the presence of Ce species which can prevent NH from being sulfated, while ATP prevent catalyst from being corroded by HO. This work may open up a new window for full-spectrum driven SCR of NO based on cost-effective mineral catalyst.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121977DOI Listing
March 2020

Deep Image-to-Video Adaptation and Fusion Networks for Action Recognition.

IEEE Trans Image Process 2019 Dec 11. Epub 2019 Dec 11.

Existing deep learning methods for action recognition in videos require a large number of labeled videos for training, which is labor-intensive and time-consuming. For the same action, the knowledge learned from different media types, e.g., videos and images, may be related and complementary. However, due to the domain shifts and heterogeneous feature representations between videos and images, the performance of classifiers trained on images may be dramatically degraded when directly deployed to videos. In this paper, we propose a novel method, named Deep Image-to-Video Adaptation and Fusion Networks (DIVAFN), to enhance action recognition in videos by transferring knowledge from images using video keyframes as a bridge. The DIVAFN is a unified deep learning model, which integrates domain-invariant representations learning and cross-modal feature fusion into a unified optimization framework. Specifically, we design an efficient cross-modal similarities metric to reduce the modality shift among images, keyframes and videos. Then, we adopt an autoencoder architecture, whose hidden layer is constrained to be the semantic representations of the action class names. In this way, when the autoencoder is adopted to project the learned features from different domains to the same space, more compact, informative and discriminative representations can be obtained. Finally, the concatenation of the learned semantic feature representations from these three autoencoders are used to train the classifier for action recognition in videos. Comprehensive experiments on four real-world datasets show that our method outperforms some state-of-the-art domain adaptation and action recognition methods.
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http://dx.doi.org/10.1109/TIP.2019.2957930DOI Listing
December 2019

The Ancient Chinese Decoction Yu-Ping-Feng Suppresses Orthotopic Lewis Lung Cancer Tumor Growth Through Increasing M1 Macrophage Polarization and CD4 T Cell Cytotoxicity.

Front Pharmacol 2019 8;10:1333. Epub 2019 Nov 8.

Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The tumor microenvironment (TME) has a deep influence on cancer progression and has become into a new target for cancer treatment. In our previous study, we found that Yu-Ping-Feng (YPF), an ancient Chinese herbal decoction, significantly inhibited the Lewis lung cancer (LLC) tumor growth in a subcutaneous xenograft tumor model, and prolonged the survival of tumor-bearing mice. But the regulation of Yu-Ping-Feng on tumor microenvironment is unknown. To access the effect of Yu-Ping-Feng on non-small cell lung cancer, an orthotopic luciferase stably expressed Lewis lung cancer tumor model was established on C57BL/6 mice, and then the survival and the tumor growth were evaluated. To address the tumor microenvironment immune regulation, the percentages of CD4 T cells, CD8 T cells, natural killer cells (NK), regulatory T cells (Treg), macrophages, and myeloid-derived suppressor cells (MDSC) in spleens and tumor tissues, the macrophage polarization and CD4 T cell cytotocixity were analyzed by flow cytometry, biophotonic cell killing activity assay, real-time PCR and western-blot. Yu-Ping-Feng significantly prolonged orthotopic lung tumor-bearing mouse survival, and increased the percentages of CD4 T cell and M1 macrophages and the cytotoxicity of CD4 T cells. Yu-Ping-Feng significantly enhanced macrophage-mediated lysis of LLC in a concentration-dependent manner, and had no effect on CD4 T cell-mediated lysis of LLC, but significantly increased CD4 T cell-mediated lysis after co-incubated with macrophages. In addition, Yu-Ping-Feng induced M1 macrophage polarization through promoting the phosphorylation of STAT1. Yu-Ping-Feng induced M1 macrophages polarization, and then activated CD4 T lymphocytes, resulting in killing of LLC cells. Yu-Ping-Feng was a potent regulator of M1 macrophage polarization and might have a promising application in tumor immunotherapy.
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http://dx.doi.org/10.3389/fphar.2019.01333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857089PMC
November 2019

Direct Z-scheme LaCeMnO catalyst for photothermal degradation of toluene.

Environ Sci Pollut Res Int 2019 Dec 19;26(36):36832-36844. Epub 2019 Nov 19.

School of Petrochemical Engineering, Changzhou University, Changzhou, 213164, People's Republic of China.

A series of Ce-doped LaMnO (LaCeMnO) were prepared and were tested for gaseous toluene oxidation in order to investigate the effect of cerium doping in LaMnO on activity under photothermal conditions. It was found that the activity and CO yield of the catalyst can be effectively increased when x = 0.25. A group of characterization is used to characterize the morphology, composition, and physical properties of the as-prepared catalysts. Results show that the Ce-doped LaMnO can form coexistence of LaCeMnO and CeO, the reaction of CeO/LaCeMnO under photothermal conditions follows the Mars-van Krevelen redox cycle mechanism, and the prepared CeO/LaCeMnO can form a highly efficient Z-scheme heterojunction, which can enhance the electrons transfer speed of the catalyst. Moreover, in the photothermal catalytic degradation, lattice oxygen is the most important active substance, a small amount of cerium doping can increase the lattice oxygen content of perovskite and increase the activity of the reaction.
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http://dx.doi.org/10.1007/s11356-019-06856-7DOI Listing
December 2019

Design and Synthesis of 4-(Heterocyclic Substituted Amino)-1-Pyrazole-3-Carboxamide Derivatives and Their Potent Activity against Acute Myeloid Leukemia (AML).

Int J Mol Sci 2019 Nov 15;20(22). Epub 2019 Nov 15.

School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China.

Fms-like receptor tyrosine kinase 3 (FLT3) has been emerging as an attractive target for the treatment of acute myeloid leukemia (AML). By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1-pyrazole-3-carboxamide derivatives were designed and synthesized. Compound showed strong activity against FLT3 (IC: 0.089 nM) and CDK2/4 (IC: 0.719/0.770 nM), which is more efficient than FN-1501(FLT3, IC: 2.33 nM; CDK2/4, IC: 1.02/0.39 nM). Compound also showed excellent inhibitory activity against a variety of FLT3 mutants (IC < 5 nM), and potent anti-proliferative effect within the nanomolar range on acute myeloid leukemia (MV4-11, IC: 1.22 nM). In addition, compound significantly inhibited the proliferation of most human cell lines of NCI60 (GI < 1 μM for most cell lines). Taken together, these results demonstrated the potential of as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics.
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http://dx.doi.org/10.3390/ijms20225739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887723PMC
November 2019