Publications by authors named "Jiyan Liu"

116 Publications

Medium- and Short-Chain Chlorinated Paraffins in Mature Maize Plants and Corresponding Agricultural Soils.

Environ Sci Technol 2021 04 23;55(8):4669-4678. Epub 2021 Mar 23.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

For the most complex artificial chlorinated environmental contaminants, much less is known for medium-chain CPs than short-chain CPs. In this research, the spatial distributions of MCCPs and SCCPs in farmland soil and maize leaves near a CP production facility were found marginally influenced by seasonal winds. The levels of ∑MCCPs and ∑SCCPs were in the ranges of <1.51-188 and 5.41-381 ng/g dw for soils; and 77.6-52930 and 119-61999 ng/g dw for maize leaf, respectively. Bioaccumulation and tissue distributions of the CPs within maize plants were specifically analyzed. Most of the CPs were contained in the tissues directly exposed to airborne CPs. Though the estimated risk of CPs to humans through ingestion of kernels appears to be minimal, the edible safety of MCCPs in maize plants for cattle was nearly in the designated range of adverse effects. To our knowledge, this is the first report on bioaccumulation of CPs in mature maize plants, especially in the parts eaten by humans and domestic animals. It provides a baseline reference to the edible risks of CPs in agricultural food plants and alerts us to the problematic environmental behavior of MCCPs, a probable future replacement for SCCPs commercially.
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http://dx.doi.org/10.1021/acs.est.0c05111DOI Listing
April 2021

Compartmentalization and Excretion of 2,4,6-Tribromophenol Sulfation and Glycosylation Conjugates in Rice Plants.

Environ Sci Technol 2021 03 5;55(5):2980-2990. Epub 2021 Feb 5.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P. R. China.

The most environmentally abundant bromophenol congener, 2,4,6-tribromophenol (2,4,6-TBP, 6.06 μmol/L), was exposed to rice for 5 d both in vivo (intact seedling) and in vitro (suspension cell) to systematically characterize the fate of its sulfation and glycosylation conjugates in rice. The 2,4,6-TBP was rapidly transformed to produce 6 [rice cells (3 h)] and 8 [rice seedlings (24 h)] sulfated and glycosylated conjugates. The predominant sulfation conjugate (TP, 93.0-96.7%) and glycosylation conjugate (TP, 77.1-90.2%) were excreted into the hydroponic solution after their formation in rice roots. However, the sulfation and glycosylation conjugates presented different translocation and compartmentalization behaviors during the subsequent Phase III metabolism. Specifically, the sulfated conjugate could be vertically transported into the leaf sheath and leaf, while the glycosylation conjugates were sequestered in cell vacuoles and walls, which resulted in exclusive compartmentalization within the rice roots. These results showed the micromechanisms of the different compartmentalization behaviors of 2,4,6-TBP conjugates in Phase III metabolism. Glycosylation and sulfation of the phenolic hydroxyl groups orchestrated by plant excretion and Phase III metabolism may reduce the accumulation of 2,4,6-TBP and its conjugates in rice plants.
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http://dx.doi.org/10.1021/acs.est.0c07184DOI Listing
March 2021

Integrated Molecular Characterization of Fumarate Hydratase-deficient Renal Cell Carcinoma.

Clin Cancer Res 2021 Mar 7;27(6):1734-1743. Epub 2021 Jan 7.

Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.

Purpose: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC.

Experimental Design: Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded.

Results: We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade-based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; = 0.03).

Conclusions: These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3788DOI Listing
March 2021

Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer.

Int Immunopharmacol 2021 Feb 23;91:107296. Epub 2020 Dec 23.

Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: Thyroid function abnormality (TFA) is a common immune-related adverse event (irAEs), but the association between it and the efficacy of programmed cell death protein 1 (PD-1) inhibitor in advanced non-small cell lung cancer (NSCLC) is finitely understood.

Materials And Methods: We conducted a single center, retrospective study of advanced NSCLC patients who were treated with PD-1 inhibitors between 10 October 2016 and 1 April 2020. TFA was characterized as new onset subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism. Frequency of development of TFA-irAEs, and its relationship with overall survival (OS) and progression free survival (PFS) were evaluated.

Results: In our study, 191 patients were treated with PD-1 inhibitors. Among them, forty patients (20.9%) developed TFA, of whom 10 (5.2%) presented with subclinical hypothyroidism, 15 (7.9%) with overt hypothyroidism, 6 (3.1%) with subclinical hyperthyroidism and 9 (4.7%) with overt hyperthyroidism. Survival analysis showed that the OS (16.8 months vs. 11.1 months, p < 0.001) and PFS (10.4 months vs. 5.5 months, p < 0.001) were significantly longer in patients with TFA-irAEs than in those without TFA-irAEs. In subgroup analysis of hypothyroidism and hyperthyroidism groups, similar trends were also obtained for both OS and PFS. After adjusting for potential confounding variables, patients with TFA-irAEs had a lower mortality risk (HR 0.334, 95%CI 0.196-0.571) than those without TFA-irAEs.

Conclusions: TFA-irAEs is associated with enhanced PD-1 inhibitor efficacy in advanced NSCLC patients and it may be a biomarker for antitumor immune response.
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http://dx.doi.org/10.1016/j.intimp.2020.107296DOI Listing
February 2021

The thermal/pH-sensitive drug delivery system encapsulated by PAA based on hollow hybrid nanospheres with two silicon source.

J Biomater Sci Polym Ed 2021 Apr 28;32(6):695-713. Epub 2020 Dec 28.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China.

The synthesis of drug delivery systems based on hollow mesoporous silica nanoparticles (MSNs) is still a major challenge. In this work, the hollow hybrid MSNs were successfully prepared by cetyltrimethylammonium bromide-directed sol-gel process and one-step hydrothermal treatment process. The hollow hybrid MSNs had hybrid ethane-bridged frameworks with the uniform particle size (250 nm) and mesoporous pore diameter (3.7 nm). The polyacrylic acid (PAA) encapsulated drug delivery system based on hollow hybrid MSNs was prepared by using silanization, surface modification, doxorubicin hydrochloride (DOX) loading, and PAA coating. Drug encapsulation and release behavior at different temperatures and pH were studied by using DOX as a model guest molecule. The results displayed that the modified hollow ethane-bridged MSNs possessed good biocompatibility and excellent thermal/pH-dual-sensitive drug release property. This novel thermal/pH-sensitive drug delivery system based on hollow ethane-bridged MSNs has the advantages of feasible synthesis, no cytotoxicity, and good drug loading capacity, which may have potential applications in the anticancer therapy.
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http://dx.doi.org/10.1080/09205063.2020.1861734DOI Listing
April 2021

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma.

Clin Cancer Res 2021 Jan 27;27(1):43-51. Epub 2020 Oct 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.

Purpose: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2 locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies.

Patients And Methods: This was a phase II, open-label, multicenter, single-arm study of patients with HER2 (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety.

Results: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%-66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6-8.9) and 13.9 months (95% CI, 9.1-NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred.

Conclusions: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2 locally advanced or mUC who had failed at least one line of systemic chemotherapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2488DOI Listing
January 2021

Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma.

Cancer Sci 2021 Jan 6;112(1):305-313. Epub 2020 Nov 6.

Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China.

Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. This single-arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD-L1-positive urothelial carcinoma who progressed during/following platinum-containing therapy and had no prior PD-(L)1 inhibitor treatment. Patients were considered PD-L1 positive if ≥ 25% of tumor/immune cells expressed PD-L1 when using the VENTANA™ PD-L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow-up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy-evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression-free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment-related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3-4 treatment-related adverse events and occurred in ≥ 5% of patients. Three investigator-assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD-L1-positive urothelial carcinoma and had a manageable safety profile.
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http://dx.doi.org/10.1111/cas.14681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780053PMC
January 2021

Synthesis of a novel aluminium salt of nitrogen-containing alkylphosphinate with high char formation to flame retard acrylonitrile-butadiene-styrene.

R Soc Open Sci 2020 Sep 9;7(9):200800. Epub 2020 Sep 9.

Key Laboratory of Optoelectronic Chemical Materials and Devices (Ministry of Education), Flexible Display Materials and Technology Co-innovation Center of Hubei Province, Jianghan University, Wuhan 430056, People's Republic of China.

A novel nitrogen-containing alkylphosphinate salt-aluminium β-(p-nitrobenzamide) ethyl methyl phosphinate (AlNP) was synthesized and used to flame retard acrylonitrile-butadiene-styrene copolymer (ABS). The Fourier transform infrared spectrometry, H, C and P nuclear magnetic resonance and X-ray fluorescent spectroscopy (XRF) were applied to characterize the structure and composition of products. The flame retardancy performance, thermal properties and mechanical strength of the ABS/AlNP with respect to AlNP loading were investigated. AlNP was stable before 330°C and decomposed very slowly with residues high up to 56.1% at 700°C. Adding 25-30 wt% of AlNP alone can make ABS to pass V0 rating in the vertical burning tests (UL 94). The results according to the micro combustion calorimeter, thermogravimetric analysis showed that AlNP can depress the heating release and retard the thermal degradation of the ABS. Scanning electron microscopy observation of the residues from LOI test indicated that AlNP formed the condensed and tough residues layer during combustion; XRF analysis showed that the residues contained phosphorus and aluminium element and nitrogen element was not detected. The compact phosphorus/aluminium-rich substance acted as a barrier to enhance flame-retardant properties of the ABS.
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http://dx.doi.org/10.1098/rsos.200800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540785PMC
September 2020

A novel germline EGFR variant p.R831H causes predisposition to familial CDK12-mutant prostate cancer with tandem duplicator phenotype.

Oncogene 2020 10 25;39(44):6871-6878. Epub 2020 Sep 25.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

5-10% of total prostate cancer (PCa) cases are hereditary. Particularly, immune checkpoint inhibitor-sensitive tandem duplicator phenotype (TDP) accounts for 6.9% of PCa cases, whereas genetic susceptibility genes remain completely unknown. We identified a Chinese family with two PCa patients, in which the PCa phenotype co-segregated with a rare germline variant EGFR. Patient-derived conditionally reprogrammed cells (CRC) exhibited increased EGFR and AKT phosphorylation, and a sensitivity to EGFR antagonist Afatinib in migration assays, suggesting the EGFR allele was constitutively active. Both EGFR-mutant tumours contained biallelic CDK12 inactivation, together with prominent tandem duplication across the genome. These somatic mutations could be detected in urine before surgery. Analysis of public databases showed a significant correlation between the mutation status of EGFR and CDK12. Taken together, our genetic and functional analyses identified a previously undescribed link between EGFR and PCa.
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http://dx.doi.org/10.1038/s41388-020-01476-9DOI Listing
October 2020

Metabolism of SCCPs and MCCPs in Suspension Rice Cells Based on Paired Mass Distance (PMD) Analysis.

Environ Sci Technol 2020 08 13;54(16):9990-9999. Epub 2020 Jul 13.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) are mixtures of complex chemical compounds with intensive usage. They are frequently detected in various environmental samples. However, the interaction between CPs and plants, especially the biotransformation behaviors of CPs within plants, is poorly understood. In this study, 1,2,5,6,9,10-hexachlorodecane (CP-4, a typical standard of individual SCCP congeners) and 52%-MCCP (a commercial mixture standard of MCCPs with 52% chlorine content by mass) were selected as representative chemicals to explore the metabolic behaviors of SCCPs and MCCPs using suspension rice cell culture exposure systems. Both 79.53% and 40.70% of CP-4 and 52%-MCCP were metabolized by suspension rice cells, respectively. A complementary suspected screening strategy based on the pair mass distances (PMD) analysis algorithm was used to study the metabolism of CPs mediated by the plant cells. Forty and 25 metabolic products for CP-4 and 52%-MCCP, respectively, were identified, including (multi-) hydroxylation, dechlorination, -HCl- elimination metabolites, (hydroxylation-) sulfation, and glycosylation conjugates. Here, we propose a comprehensive metabolic molecular network and provide insight on degradation pathways of SCCPs and MCCPs in plants for the first time, aiding in further understanding of the transformation behaviors of CPs.
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http://dx.doi.org/10.1021/acs.est.0c01830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703871PMC
August 2020

Uptake, phytovolatilization, and interconversion of 2,4-dibromophenol and 2,4-dibromoanisole in rice plants.

Environ Int 2020 09 25;142:105888. Epub 2020 Jun 25.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.

The structural analogs, 2,4-dibromophenol (2,4-DBP) and 2,4-dibromoanisole (2,4-DBA), have both natural and artificial sources and are frequently detected in environmental matrices. Their environmental fates, especially volatilization, including both direct volatilization from cultivation solution and phytovolatilization through rice plants were evaluated using hydroponic exposure experiments. Results showed that 2,4-DBA displayed stronger volatilization tendency and more bioaccumulation in aboveground rice tissues. Total volatilized 2,4-DBA accounted for 4.74% of its initial mass and was 3.43 times greater than 2,4-DBP. Phytovolatilization of 2,4-DBA and 2,4-DBP contributed to 6.78% and 41.7% of their total volatilization, enhancing the emission of these two contaminants from hydroponic solution into atmosphere. In this study, the interconversion processes between 2,4-DBP and 2,4-DBA were first characterized in rice plants. The demethylation ratio of 2,4-DBA was 12.0%, 32.0 times higher than methylation of 2,4-DBP. Formation of corresponding metabolites through methylation and demethylation processes also contributed to the volatilization of 2,4-DBP and 2,4-DBA from hydroponic solution into the air phase. Methylation and demethylation processes increased phytovolatilization by 12.1% and 36.9% for 2,4-DBP and 2,4-DBA. Results indicate that phytovolatilization and interconversion processes in rice plants serve as important pathways for the global cycles of bromophenols and bromoanisoles.
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http://dx.doi.org/10.1016/j.envint.2020.105888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670850PMC
September 2020

Super-resolution observation of lysosomal dynamics with fluorescent gold nanoparticles.

Theranostics 2020 15;10(13):6072-6081. Epub 2020 May 15.

Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

Because lysosomes play critical roles in multiple cellular functions and are associated with many diseases, studying them at the subcellular level could elucidate their functionality and support the discovery of therapeutic drugs for treating those diseases. The commonly used dyes for super-resolution imaging of lysosomes are the commercial molecular LysoTrackers. But the tolerance to changes in the lysosomal microenvironment and to lysosomal membrane permeabilization (LMP) and the photostability of the LysoTrackers are worrisome. The purpose of our study was to evaluate the feasibility of performing a fluorescent gold nanoprobe for super-resolution observation of lysosomal dynamics in living cells and compare it to the commercial LysoTrackers. : The nanoprobe contained three parts: a bio-inert gold core, a biocompatible polyethylene glycol spacer, and a fluorophore cyanine 5. Structured illumination microscopy (SIM) was employed to capture the fluorescence of in cells. The tolerance assays to changes in the lysosomal microenvironment and to LMP, the photobleaching assay, and the long-term lysosomes labelling assay of were compared with commercial LysoTrackers. The super-resolution observation of lysosomal dynamics with was performed. : can light up lysosomes specifically under SIM. Compared with commercial lysosomal molecular probes, exhibited stronger tolerance in lysosomes during various treatments, and changes in the lysosomal microenvironment and LMP did not cause to lose track of their targets. demonstrated an excellent anti-photobleaching ability, and a long-term labelling assay revealed that they could label lysosomes more than 3 d. Biological events of lysosomes such as the kiss-and-run process, fusion, fission, and mitophagy were recorded with the fluorescent under SIM. : The nanoprobe was successfully used as a lysosomal probe for the super-resolution observation in living cells and found to overcome the limitations of commercial LysoTrackers. Our results thus confirm that nanoparticles can be useful tools for subcellular super-resolution imaging and highlight new avenues for using nanoparticles in biology.
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http://dx.doi.org/10.7150/thno.42134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254985PMC
May 2020

Anlotinib for Patients With Metastatic Renal Cell Carcinoma Previously Treated With One Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor: A Phase 2 Trial.

Front Oncol 2020 7;10:664. Epub 2020 May 7.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Sequential therapy with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) is effective in some patients with metastatic renal cell carcinoma (mRCC) progressed from or were intolerant to a prior TKIs. Anlotinib is a multi-kinase inhibitor targeting VEGFR1/2/3, PDGFR and FGFR, which has demonstrated efficacy and safety in first-line treatment of mRCC. This study assessed the potential of anloitnib as second-line treatment for patients with mRCC after prior one VEGFR-TKI. This is a single-arm, open-label, phase 2 study. Patients progressed after or were intolerant to sorafenib or sunitinib were enrolled. Anlotinib was administrated orally 12 mg once daily for 14 days every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), safety and quality of life (QoL). Forty three patients were enrolled and 42 received anlotinib, of whom 32 progressed after and 10 were intolerant to sorafenib or sunitinib. Median PFS were 14.0 months (95% CI 8.3-20.3) and 8.5 months (95% CI 5.6-16.6) for overall population and patients progressed after a previous VEGFR-TKI, respectively. Median OS was 21.4 months (95% CI 16.0-34.5), confirmed ORR and DCR were 16.7 and 83.3% in overall population. The most common adverse events included diarrhea (47.6%), hypertension (45.2%), hand and foot syndrome (42.9%), and fatigue (40.5%). Grade 3 hematological adverse events occurred in four cases, while no grade 4 hematological adverse events was observed. Anlotinib showed promising efficacy as well as favorable safety as second-line treatment for patients with mRCC. www.ClinicalTrials.gov, identifier: NCT02072044.
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http://dx.doi.org/10.3389/fonc.2020.00664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221023PMC
May 2020

Metallic Fingerprints of Carbon: Label-Free Tracking and Imaging of Graphene in Plants.

Anal Chem 2020 01 8;92(2):1948-1955. Epub 2020 Jan 8.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences , Chinese Academy of Sciences , Beijing 100085 , China.

Detection and quantification of carbon nanomaterials are extremely challenging, especially under the background interference of carbon. Here, we propose a new label-free method to quantify, track, and in situ image graphene and graphene oxide (GO) in plants based on their inherent metallic impurities as fingerprints. We show the ubiquity and high stability of inherent metallic fingerprints of graphene and GO obtained from different exposure routes under the natural environments, which enables the materials to be easily quantified and in situ imaged by high-sensitivity (laser ablation) inductively coupled plasma mass spectrometry. The method was applied to investigate the uptake and spatial distribution of graphene and GO in soybean plants. The plants were cultivated in graphene or GO solutions for 7 days, and the indicative elements (Ni or Mn) in different parts of plants were monitored and imaged. We found that graphene and GO showed different distribution patterns in plants (the highest uptake percentages in root up to 14.4% for graphene and 47.8% for GO), and high concentration of material exposure might cause excessive accumulation of materials in roots which blocked their further transport to the other parts of plants. The present method is more straightforward, accessible, and economical than normally used isotopic or metal-labeling methods. It also avoids the uncertainties or alterations of properties caused by the labeling process and thus has great promise in analysis and risk assessment of carbon nanomaterials.
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http://dx.doi.org/10.1021/acs.analchem.9b04262DOI Listing
January 2020

Transformation of 1,1,1,3,8,10,10,10-octachlorodecane in air phase increased by phytogenic volatile organic compounds of pumpkin seedlings.

Sci Total Environ 2020 Feb 21;704:135455. Epub 2019 Nov 21.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.

Short chain chlorinated paraffins (SCCPs) are widely distributed persistent organic pollutants (POPs). Airborne chlorodecanes were hypothesized to be transformed by reactive phytogenic volatile organic compounds (PVOCs) in our previous work. To test this hypothesis, PVOCs of pumpkin (Cucurbita maxima x C. moschata) were collected and reacted with 1,1,1,3,8,10,10,10-octachlorodecane in the air phase of a sealed glass bottle under illumination for 10 days (reaction system I, simulating atmospheric reaction conditions with PVOCs). The reaction control group (reaction system II) was set at the same conditions but only had chlorodecane (without PVOCs) inside the bottle. Transformation of SCCPs in the air phase of reaction control group was unexpectedly found. Results showed that 1,1,1,3,8,10,10,10-octachlorodecane was transformed to a great extent to CCl, CCl, and CCl in the air phase after 10-d illumination in both with and without the presence of PVOCs, which is explained by carbon chain decomposition, dechlorination and chlorine rearrangement products of the parent SCCP. Those transformation processes were increased to some extent by the PVOCs from pumpkin seedlings. This study provides the first experimental data on atmospheric transformation of SCCPs and also the first evidence that plant emissions (PVOCs) can increase the transformation of SCCPs in air under light and experimental conditions. It provides new insight into the potential transformation and fate of CPs in the environment.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029796PMC
February 2020

A facile method in removal of PVP ligands from silver nanowires for high performance and reusable SERS substrate.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 2;228:117733. Epub 2019 Nov 2.

Instrumental Analysis and Research Center, Sun Yat-sen University, Guangzhou, 510275, China.

Silver nanowires (i.e., AgNWs) can act as effective surface-enhanced Raman spectroscopy (i.e., SERS) substrates to detect small molecules. However, a lot of prepared AgNWs were often wrapped by polyvinylpyrrolidone (i.e., PVP) thin film to form an insulating layer to produce ill-defined AgNWs-PVP-AgNWs interface, limiting the plasmonic coupling among the stacked AgNWs. Herein, we reported a facile method in removal of PVP ligands from AgNWs for high performance and reusable SERS substrate. Sodium borohydride (NaBH) was used to completely remove the PVP ligands from the surface of AgNWs and produce a clean AgNWs-AgNWs interface that effectively enhances the localized surface plasmon resonance (i.e., LSPR) was produced, greatly improving the SERS activity of the AgNWs thin film. The SERS detection of rhodamine 6G (i.e., R6G) used with PVP AgNWs and without PVP AgNWs is 1.0 × 10 and 1.0 × 10 M, and the average enhancement factor (EF) is about 0.86 × 10 and 9.35 × 10, respectively. Moreover, the recyclable behavior of the AgNWs with several analyte molecules is much more interesting than that of the PVP@AgNWs. The SERS detection of AgNWs for R6G, the 3-mercaptopropionic acid (i.e., 3-MPA) and melamine with good recyclability in nanomolar and millimolar concentration can be easily detected.
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http://dx.doi.org/10.1016/j.saa.2019.117733DOI Listing
March 2020

Abiotic Methylation of Tetrabromobisphenol A (TBBPA) with the Occurrence of Methyl Iodide in Aqueous Environments.

Environ Sci Technol Lett 2019 Sep 5;6(9):558-564. Epub 2019 Aug 5.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.

Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant in the world. Its biotic methylation products, tetrabromobisphenol A mono- and dimethyl ether (TBBPA MME and TBBPA DME, respectively), are frequently detected in the environment, but the importance of abiotic methylation reactions of TBBPA in the environment is not known. In this study, the methylation of TBBPA mediated by methyl iodide (CHI), a ubiquitous compound in aqueous environments, was investigated in simulated waters in the laboratory. It was found that abiotic methylation occurred under both light and dark conditions and was strongly affected by the pH, temperature, and natural organic matter concentration of the water. Abiotic methylation was further verified in natural river water, and the yield of TBBPA MME mediated abiotically by CHI was much greater than that of biotic methylation. According to our calculations and by comparison of the activation energies () for the abiotic methylation of TBBPA and the other four typical phenolic contaminants and/or metabolites (bisphenol A, triclosan, 5-OH-BDE-47, and 4'-OH-CB-61) mediated by CHI, those phenolic compounds all show great methylation potentials. The results indicate a new abiotic pathway for generating TBBPA MME and TBBPA DME from TBBPA, and they also confirm the potentials for abiotic methylation of other phenolic contaminants in aqueous environments.
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http://dx.doi.org/10.1021/acs.estlett.9b00445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643859PMC
September 2019

Occurrences of perfluoroalkyl and polyfluoroalkyl substances in tree bark: Interspecies variability related to chain length.

Sci Total Environ 2019 Nov 27;689:1388-1395. Epub 2019 Jun 27.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.

Occurrences of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in tree bark from four species were investigated. Species-dependent congener distribution patterns were firstly reported for perfluorocarboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs). The majority of PFSAs and PFCAs in Chinese red pine bark were C5-C7 PFSAs and perfluorohexanoic acid (PFHxA, containing six carbon atoms, C6), whereas perfluorobutanesulfonic acid (PFBS, C4) and longer chain congeners (PFCAs: C ≥ 7; PFSAs: C ≥ 8) took a larger proportion in the fissured bark from Canadian poplar, Chinese scholartree and weeping willow. The species-dependent congener profiles depended on the structures and chemical compositions of tree bark, as well as the translocation of PFASs within plants. Different tree bark characteristics caused different retention abilities for particle-bound and gaseous PFASs. Particle-bound PFASs retained in the rougher structures of fissured bark led to preferential retention of long chain congeners (the major fraction in the particle phase), while lipid-rich Chinese red pine bark retained more gaseous PFASs (mainly short chain congeners). Besides, the abundance of short chain PFASs in red pine bark was consistent with the chain length-dependent translocation behaviors of PFASs in various plants, suggesting that translocation of PFASs within plants to tree bark may be invovled.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.454DOI Listing
November 2019

Depth-Resolved Enhanced Spectral-Domain OCT Imaging of Live Mammalian Embryos Using Gold Nanoparticles as Contrast Agent.

Small 2019 08 15;15(35):e1902346. Epub 2019 Jul 15.

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.

High-resolution and real-time visualization of the morphological changes during embryonic development are critical for studying congenital anomalies. Optical coherence tomography (OCT) has been used to investigate the process of embryogenesis. However, the structural visibility of the embryo is decreased with the depth due to signal roll-off and high light scattering. To overcome these obstacles, in this study, combined is a spectral-domain OCT (SD-OCT) with gold nanorods (GNRs) for 2D/3D imaging of live mouse embryos. Inductively coupled plasma mass spectrometry is used to confirm that GNRs can be effectively delivered to the embryos during ex vivo culture. OCT signal, image contrast, and penetration depth are all enhanced on the embryos with GNRs. These results show that after GNR treatment, more accurate spatial localization and better contrasting of the borders among organs can be observed on E9.5 and E10.5 mouse embryos. Furthermore, the strong optical absorbance of GNRs results in much clearer 3D images of the embryos, which can be used for calculating the heart areas and volumes of E9.5 and E10.5 embryos. These findings provide a promising strategy for monitoring organ development and detecting congenital structural abnormalities in mice.
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http://dx.doi.org/10.1002/smll.201902346DOI Listing
August 2019

AKR1C3 expression in primary lesion rebiopsy at the time of metastatic castration-resistant prostate cancer is strongly associated with poor efficacy of abiraterone as a first-line therapy.

Prostate 2019 09 11;79(13):1553-1562. Epub 2019 Jul 11.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Background: Previous studies had demonstrated that aldo-keto reductase family 1 member C3 (AKR1C3), a crucial enzyme in the steroidogenic pathway, played an important role in abiraterone (ABI)-resistance in metastatic castration-resistant prostate cancer (mCRPC) by increasing intratumoral androgen synthesis. However, its value in predicting treatment response in patients with mCRPC is unknown.

Method And Materials: Data of 163 patients with metastatic prostate cancer between 2016 and 2018 were retrospectively analyzed. All patients received androgen deprivation therapy plus bicalutamide after initial diagnosis. After mCRPC, either ABI or docetaxel (DOC) treatment was used. No patient had the experience of therapy to the primary tumor. AKR1C3 protein was detected by immunohistochemical staining from rebiopsy (re-Bx) of primary prostate lesions at mCRPC. Kaplan-Meier curves and Cox regression were used to analyze the association between AKR1C3 and treatment outcomes.

Results: AKR1C3 was positive in 58 of 163 (35.6%) cases. AKR1C3 was associated with significantly shorter median prostate-specific antigen progression-free survival (mPSA-PFS, 5.6 mo vs 10.7 mo; P < .001), median radiographic progression-free survival (mrPFS, 11.1 mo vs 18.0 mo; P = .018), and numerically shorter median overall survival (mOS, 20.4 mo vs 26.4 mo; P = .157). Notably, AKR1C3-positive patients treated with ABI, but not DOC, had shorter mPSA-PFS and mrPFS compared with AKR1C3-negative men, (mPSA-PFS, 5.7 mo vs. 11.2 mo; P < .001; mrPFS, 12.4 mo vs 23.3 mo; P = .048). However, AKR1C3 expression had no correlation to PSA response or OS. Multivariate Cox regression indicated that AKR1C3 was independently accompanied with rapid PSA progression (hazard ratio [HR], 3.64; 95% confidence interval [CI], 2.10-6.31; P < 0.001) and radiological progression (HR, 2.08; 95% CI, 1.05-4.11; P = .036) in the ABI-treated subgroup.

Conclusion: This study demonstrated that AKR1C3 detection in tissues from prostate re-Bx at mCRPC was associated with early resistance to ABI but not DOC. These results will help to make optimal personalized treatment decisions for patients with mCRPC, facilitate physicians predicting the effectiveness of ABI.
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http://dx.doi.org/10.1002/pros.23875DOI Listing
September 2019

Glycosylation of Tetrabromobisphenol A in Pumpkin.

Environ Sci Technol 2019 Aug 8;53(15):8805-8812. Epub 2019 Jul 8.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences , Chinese Academy of Sciences , P.O. Box 2871, Beijing , 100085 , China.

Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardant (BFR), and it bioaccumulates throughout the food chains. Its fate in the first trophic level, plants, is of special interest. In this study, a four-day hydroponic exposure of TBBPA at a concentration of 1 μmol L to pumpkin seedlings was conducted. A nontarget screening method for hydrophilic bromine-containing metabolites was modified, based on both typical isotope patterns of bromine and mass defect, and used to process mass spectra data. A total of 20 glycosylation and malonyl glycosylation metabolites were found for TBBPA in the pumpkin plants. Representative glycosyl TBBPA reference standards were synthesized to evaluate the contribution of this glycosylation process. Approximately 86% of parent TBBPA was metabolized to form those 20 glycosyl TBBPAs, showing that glycosylation was the most dominant metabolism pathway for TBBPA in pumpkin at the tested exposure concentration.
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http://dx.doi.org/10.1021/acs.est.9b02122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931399PMC
August 2019

Multiple Metabolic Pathways of 2,4,6-Tribromophenol in Rice Plants.

Environ Sci Technol 2019 07 19;53(13):7473-7482. Epub 2019 Jun 19.

State Key Laboratory of Environmental Chemistry and Ecotoxicology , Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085 , China.

Bromophenols occur naturally and are used globally as man-made additives in various industrial products. They are decomposition products of many emerging organic pollutants, such as tetrabromobisphenol A, polybrominated dibenzo- p-dioxin (PBDD), polybrominated diphenyl ethers (PBDE), and others. To characterize their biotransformation pathways, bromophenol congener 2,4,6-tribromophenol, being used most frequently in the synthesis of brominated flame retardants and having the greatest environmental abundance, was selected to hydroponically expose rice plants. After exposure for 5 days, 99.2% of 2,4,6-tribromophenol was metabolized by rice. Because of the lack of relative reference standards, an effective screening strategy was used to screen for potential metabolites that were further qualitatively identified by gas and liquid chromatography combined with high-resolution mass spectrometry. Forty transformation products were confirmed or tentatively identified at different confidence levels, including 9 phase I and 31 phase II metabolites. A large number of metabolites (39) were found in rice root, and 10 of them could be translocated and detected in rice stems or leaves. Many transformation pathways were proposed, including debromination, hydroxylation, methylation, coupling reactions, sulfation, and glycosylation. It was remarkable that a total of seven hydrophobic, persistent, and toxic OH-PBDEs and PBDD/Fs were found, indicating the biotic dimeric reactions of 2,4,6-tribromophenol that occurred in the rice plants. These results improve our understanding of the transformation and environmental fates of bromophenols, and they indicate new potential sources for OH-PBDEs and PBDD/Fs in the environment, especially in food chains.
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http://dx.doi.org/10.1021/acs.est.9b01514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931395PMC
July 2019

Carbon Chain Decomposition of Short Chain Chlorinated Paraffins Mediated by Pumpkin and Soybean Seedlings.

Environ Sci Technol 2019 06 3;53(12):6765-6772. Epub 2019 Jun 3.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences , Chinese Academy of Sciences , P.O. Box 2871, Beijing 100085 , China.

Short chain chlorinated paraffins (SCCPs) are a group of complex emerging persistent organic pollutants. In this study, the uptake, translocation, and transformation of four constitutionally defined SCCP isomers were studied using whole pumpkin ( Cucurbita maxima × C. moschata) and soybean ( Glycine max L. Merrill) seedlings via hydroponic exposure. Results showed that the daughter SCCPs were CCl and CCl. The metabolic transformation of all tested isomers included dechlorination and chlorine rearrangement. In addition, carbon chain decomposition products were found for isomers with trichlorinated carbon atoms (CCl-groups) in both pumpkin and soybean seedlings. This study provides the first evidence of carbon chain decomposition of SCCPs in whole plants, and it suggests new metabolism pathways of SCCPs in the environment. The influence of carbon chain length and degree of chlorination of SCCPs on their fate and behavior within different plant species were also investigated. Bioaccumulation of SCCPs in pumpkin and soybean increased with increasing carbon chain length and degree of chlorination. In comparison, soybean translocated and degraded parent SCCPs faster and to a greater extent than pumpkin, but pumpkin accumulated parent SCCPs to a greater extent than soybean. After 10 days exposure, less than 4% of the initial mass of exposed chemicals remained in solution of exposure groups. The parent chemicals accumulated in roots ranging from 23.6% to 59.9% for pumpkin and 1.98% to 54.5% for soybean and in stems ranging from 0.7% to 3.81% for pumpkin and 0.50% to 2.54% for soybean. These results give new perspectives on the transport, transformation, and fate of SCCPs in the environment.
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http://dx.doi.org/10.1021/acs.est.9b01215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931393PMC
June 2019

Anlotinib Versus Sunitinib as First-Line Treatment for Metastatic Renal Cell Carcinoma: A Randomized Phase II Clinical Trial.

Oncologist 2019 08 22;24(8):e702-e708. Epub 2019 Mar 22.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China

Background: Anlotinib is a tyrosine kinase inhibitor inhibiting angiogenesis. This multicenter, randomized phase II trial aimed to investigate the efficacy and safety of anlotinib in comparison with sunitinib as first-line treatment for patients with metastatic renal cell carcinoma (mRCC).

Materials And Methods: Patients with mRCC from 13 clinical centers were randomly assigned in a 2:1 ratio to receive anlotinib ( = 90) or sunitinib ( = 43). Anlotinib was given orally at a dose of 12 mg once daily (2 weeks on/1 week off), and sunitinib was given orally at 50 mg once daily (4 weeks on/2 weeks off). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

Results: The median PFS was similar with anlotinib and sunitinib (17.5 vs. 16.6 months, > .05). The median OS (30.9 vs. 30.5 months, > .05), ORR (30.3% vs. 27.9%), and 6-week DCR (97.8% vs. 93.0%) were similar in the two groups. Adverse events (AEs) of grade 3 or 4 were significantly less frequent with anlotinib than with sunitinib (28.9% vs. 55.8%, < .01), especially in terms of thrombocytopenia and neutropenia. AEs occurring at a lower frequency with anlotinib were hand-foot syndrome, eyelid edema, hair depigmentation, skin yellowing, neutropenia, thrombocytopenia, and anemia. The incidence of serious AEs was lower with anlotinib than with sunitinib.

Conclusion: The clinical efficacy of anlotinib was similar to that of sunitinib as the first-line treatment for mRCC, but with a more favorable safety profile.

Implications For Practice: This study evaluated the efficacy and safety of anlotinib for the first-line treatment of metastatic renal cell carcinoma. Anlotinib, which was developed independently in China, is a new tyrosine kinase inhibitor inhibiting multiple kinases involved in angiogenesis and tumor proliferation. Results indicated that the efficacy of anlotinib is comparable to and the safety is better than that of sunitinib.
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http://dx.doi.org/10.1634/theoncologist.2018-0839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693716PMC
August 2019

Synergy of Single-ion Conductive and Thermo-responsive Copolymer Hydrogels Achieving Anti-Arrhenius Ionic Conductivity.

Chem Asian J 2019 May 28;14(9):1404-1408. Epub 2019 Mar 28.

State key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China.

Artificial intelligence sensations have aroused scientific interest from electronic conductors to bio-inspired ionic conductors. The conductivity of electrons decreases with increasing temperature, while the ionic conductivity agrees with an Arrhenius equation or a modified Vogel-Tammann-Fulcher (VTF) equation. Herein, thermo-responsive poly(N-isopropyl amide) (PNIPAm) and single-ion-conducting poly(2-acrylamido-2-methyl-1-propanesulfonic lithium salt) (PAMPSLi) were copolymerized via a facile radical polymerization to demonstrate a very intriguing anti-Arrhenius ionic conductivity behaviour during thermally induced volume-phase transition. These smart hydrogels presented very promising scaffolds for architecting flexible, wearable or advanced functional ionic devices.
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http://dx.doi.org/10.1002/asia.201900051DOI Listing
May 2019

Tumor calcification as a prognostic factor in cetuximab plus chemotherapy-treated patients with metastatic colorectal cancer.

Anticancer Drugs 2019 02;30(2):195-200

Department of Medical Oncology, Cancer Center.

This study aimed to explore the correlation between survival and tumor calcification in patients with metastatic colorectal cancer who received cetuximab combined with chemotherapy. The study was a single-center retrospective analysis that enrolled 111 patients who had received therapy between April 2011 and October 2016. Tumor calcification and treatment efficacy were evaluated independently by radiologists on the basis of computed tomography scans. Clinical characteristics and follow-up data were collected from electronic medical records. Correlations between tumor calcification and clinical characteristics, tumor response rate, and patient survival were analyzed. Among the 111 enrolled patients, 27 had tumor calcification [27/111 (24.3%)]. The median progression-free survival was significantly longer for patients with tumor calcification than for those without calcification (9.3 vs. 6.2 months, P=0.022). Patients with tumor calcification also had a higher objective response rate (55.6 vs. 31%, P=0.021) and better overall survival (21.9 vs. 16.5 months, P=0.084). The correlation between calcification features and prognosis showed that patients with an increasing number of calcifications after treatment had a significantly longer median overall survival (22.9 vs. 9.1 months, P=0.033). Simultaneously, new liver metastases and multiple calcifications also showed a trend toward better overall survival. There were also no significant correlations between clinical characteristics (sex, age, gene mutation, primary tumor location, pathological type, blood test result) and survival (Supplementary Table 1, Supplemental digital content 1, http://links.lww.com/ACD/A280). Tumor calcification is associated with a better treatment outcome and is a potential prognostic marker.
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http://dx.doi.org/10.1097/CAD.0000000000000726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365256PMC
February 2019

Hybridization of graphene oxide into nanogels to acquire higher photothermal effects for therapeutic delivery.

Nanotechnology 2019 Mar 17;30(11):115701. Epub 2018 Dec 17.

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, People's Republic of China.

Although the special architecture of two-dimensional (2D) nanomaterials endows them with unique properties, their poor colloidal stability remains a main bottleneck to fully exploit their applications in the biomedical field. Herein, this study aims to develop a simple and effective approach to in situ incorporate 2D graphene oxide (GO) nanoplatelets into a thermosensitive matrix to acquire hybrid nanogels with good stability and photothermal effect. In order to improve its stability, GO firstly underwent silanization to its surface with double bonds, followed by intercalation with N-isopropylacrylamide (NIPAM) in the presence of a disulfide-containing crosslinker via an emulsion method. Radical polymerization was then initiated to accelerate direct GO exfoliation in PNIPAM nanogels by forming covalent bonds between them. The well-dispersed GO nanopletlets in the nanogels not only displayed an enhanced photothermal effect, but also improved the encapsulation efficiency of an anticancer drug. The hybrid nanogels accelerate drug release under conditions mimicking the acidic/reducible solid tumor and intracellular microenvironments, most importantly, it can be further enhanced via remote photothermal treatment. The multifunctional nanogels potentiate their synergistic anticancer bioactivity as an ideal nanoplatform for cancer treatment.
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http://dx.doi.org/10.1088/1361-6528/aaf8e4DOI Listing
March 2019

Sorption and transport of aluminum dialkyl phosphinate flame retardants and their hydrolysates in soils.

Environ Pollut 2019 Mar 1;246:1-10. Epub 2018 Dec 1.

State Key Laboratory of Environmental and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Aluminum dialkyl phosphinates (ADPs) are a class of promising phosphorus-containing flame retardants, but their environmental fate is not well understood. Sorption and transport behaviors of ADPs, and their hydrolysates dialkyl phosphinic acids (DPAs) were studied by batch and column experiments. ADPs are less mobile in soil columns with more than half (>52.6%) of ADPs retained in the soil and residues in the topmost 2-cm layer account for more than 57% of total residues. Dissolution and dispersion of fine grain ADPs were responsible for the transport of ADPs. Sorption DPAs (logK) was significantly related to the lipophilicity of DPAs (logD) (p < 0.05). Soil pH and clay content were the dominant factors governing the sorption and transport of DPAs in soils, indicating the importance of electrostatic interactions. The retardation factors (R) of DPAs derived from leaching experiments were pH-dependent with larger R values in the acidic soil (pH = 4.0) where anionic and neutral species of DPAs coexisted. Both physical and chemical non-equilibrium convection-dispersion equations (CDE) yield appropriate modeling for DPAs transport. In most cases, R values estimated from column tests differed from those derived from the batch experiments, which might be attributed to non-equilibrium sorption processes in dynamic conditions.
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http://dx.doi.org/10.1016/j.envpol.2018.11.105DOI Listing
March 2019

Expression and epigenetic regulatory mechanism of BNIP3 in clear cell renal cell carcinoma.

Int J Oncol 2019 Jan 24;54(1):348-360. Epub 2018 Oct 24.

Department of Urology, Institute of Urology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

The majority of clear cell renal cell carcinomas (ccRCCs) are caused by an accumulation of hypoxia‑inducible factor (HIF) and the overexpression of downstream genes in response to the von Hippel‑Lindau (VHL) gene becoming inactivated. In the present study, our hypothesis was that BNIP3, a gene positioned downstream of HIF, would be expressed at a higher level in ccRCC; however, instead, lower levels of BNIP3 expression were identified in RCC tumor tissues compared with adjacent non‑tumor tissues. These changes were associated with lower levels of VHL, and higher levels of HIF and vascular endothelial growth factor. BNIP3 was also undetectable in three investigated RCC cell lines (786‑O, ACHN, A498) and GRC‑1‑1 cells. Methylation of the BNIP3 promoter was not detected, and neither did treatment with a methylation inhibitor cause cell proliferation. However, treatment with a histone deacetylation inhibitor, trichostatin A (TSA), inhibited cultured RCC cell proliferation, promoted apoptosis and restored BNIP3 expression. Furthermore, histone deacetylation of the BNIP3 promoter was identified in ACHN and 786‑O cells, and the acetylation status was restored following TSA treatment. Taken together, the results of the present study suggest that histone deacetylation, but not methylation, is most likely to cause BNIP3 inactivation in RCC. The data also indicated that restoration of BNIP3 expression by a histone deacetylation inhibitor led to growth inhibition and apoptotic promotion in RCC.
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http://dx.doi.org/10.3892/ijo.2018.4603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254932PMC
January 2019

Comparison of phytochemical profiles and antiproliferative activities of different proanthocyanidins fractions from Choerospondias axillaris fruit peels.

Food Res Int 2018 11 5;113:298-308. Epub 2018 Jul 5.

Jiangxi Qiyunshan Food Co., Ltd, Ganzhou 341000, Jiangxi, PR China.

Epidemiological studies had indicated that the incidence of colorectal cancer is inversely correlated to the consumption of proanthocyanidins (PAs). In this study, five PAs fractions isolated from Choerospondias axillaris fruit peels with different mean degree of polymerization (mDP) were characterized and their antiproliferative effects on Caco-2 cells were investigated. MALDI-TOF-MS results indicated that PAs fractions were composed of procyanidins with DP up to 13-mers. All PAs fractions induced dose and time-dependent reductions of Caco-2 cell viability. The IC values of PAs fractions with increasing mDP were 240 ± 16.0, 143 ± 9.53, 87.0 ± 3.55, 44.3 ± 4.89, and 42.8 ± 2.20 μg/mL after 24 h incubation, respectively. The observed reduction in Caco-2 cell viability was due to apoptosis via the activation of caspase-9, caspase-3, caspase-8 and the elevation of intracellular ROS generation. Moreover, the extent of the reduction in cell viability after exposure to PAs fractions was positively correlated with their mDP and galloylation. These results indicate that Choerospondias axillaris peel is a potential source of natural chemopreventive agents for the treatment of colorectal cancer.
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http://dx.doi.org/10.1016/j.foodres.2018.07.006DOI Listing
November 2018