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Studies of radiation interaction with tumor cells often take apoptosis as the desired results. However, mitotic catastrophe and senescence are also promoted by clinically relevant doses of radiation. Furthermore, p53 is a well-known transcription factor that is closely associated with radiosensitivity and radiation-induced cell death. Therefore, we aimed to investigate the involvement of radiosensitivity, cell death modalities and p53 status in response to carbon-ion radiation (CIR) here. Isogenic human colorectal cancer cell lines HCT116 (p53+/+ and p53−/−) were irradiated with high-LET carbon ions. Cell survival was determined by the standard colony-forming assay. 53BP1 foci were visualized to identify the repair kinetics of DNA double-strand breaks (DSBs). Cellular senescence was measured by SA-β-Gal and Ki67 staining. Mitotic catastrophe was determined with DAPI staining. Comparable radiosensitivities of p53+/+ and p53−/− HCT116 colorectal cells induced by CIR were demonstrated, as well as persistent 53BP1 foci indicated DNA repair deficiency in both cell lines. Different degree of premature senescence in isogenic HCT116 colorectal cancer cells suggested that CIR-induced premature senescence was more dependent on p21 but not p53. Sustained upregulation of p21 played multifunctional roles in senescence enhancement and apoptosis inhibition in p53+/+ cells. p21 inhibition further increased radiosensitivity of p53+/+ cells. Complex cell death modalities rather than single cell death were induced in both p53+/+ and p53−/− cells after 5 Gy CIR. Mitotic catastrophe was predominant in p53−/− cells due to inefficient activation of Chk1 and Chk2 phosphorylation in combination with p53 null. Senescence was the major cell death mechanism in p53+/+ cells via p21-dependent pathway. Taken together, p21-mediated premature senescence might be used by tumor cells to escape from CIR-induced cytotoxicity, at least for a time.

Pengcheng Zhang,1– 4 Boyi Yu,1,2 Xiaodong Jin,1,2 Ting Zhao,1 Fei Ye,1,2 Xiongxiong Liu,1,2 Ping Li,1,2 Xiaogang Zheng,1 Weiqiang Chen,1,2 Qiang Li1,2 1Institute of Modern Physics, Chinese Academy of Sciences; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, 730000, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 3The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China; 4Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of ChinaCorrespondence: Weiqiang Chen; Qiang LiInstitute of Modern Physics, Chinese Academy of Sciences; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, 730000, People’s Republic of ChinaEmail chenwq7315@impcas.ac.cn; liqiang@impcas.ac.cnPurpose: Gold nanoparticles (AuNPs) are widely studied as radiosensitizers, but their radiosensitization in carbon ion radiotherapy is unsatisfactory. There is a lack of in vivo data on the radiosensitization of AuNPs under carbon ion irradiation. This study focused on the radiosensitization effect of AuNPs in the mouse melanoma cell line B16-F10 in vitro and in vivo.Materials and Methods: 11-mercaptoundecanoic acid (11-MUA)-coated gold (Au) nanoparticles (mAuNPs) formulations were prepared and characterized. To verify the radiosensitization effect of mAuNPs, hydroxyl radicals were generated in aqueous solution, and the detection of intracellular reactive oxygen species (ROS) and clone survival were carried out in vitro. The tumor growth rate (TGR) and survival of mice were analyzed to verify the radiosensitization effect of mAuNPs in vivo. The apoptosis of tumor cells was detected, and the expression of key proteins in the apoptosis pathway was verified by immunohistochemistry.Results: The intracellular ROS level in B16-F10 cells was enhanced by mAuNPs under carbon ion irradiation. The sensitization rate of mAuNPs was 1.22 with a 10% cell survival rate. Compared with irradiation alone, the inhibitory effect of mAuNPs combined with carbon ion irradiation on tumor growth was 1.94-fold higher, the survival time of mice was prolonged by 1.75-fold, and the number of apoptotic cells was increased by 1.43-fold. The ratio of key proteins Bax and Bcl2 in the apoptosis pathway was up-regulated, and the expression of caspase-3, a key executor of the apoptosis pathway, was up-regulated.Conclusion: In in vivo and in vitro experiments, mAuNPs showed radiosensitivity to carbon ion irradiation. The sensitization effect of mAuNPs on mice tumor may be achieved by activating the mitochondrial apoptosis pathway and increasing tumor tissue apoptosis. To our best knowledge, the present study is the first in vivo evidence for radiosensitization of mAuNPs in tumor-bearing mice exposed to carbon ion irradiation.Keywords: gold nanoparticles, radiosentization, carbon ion irradiation, tumor-bearing mice, apoptosis

Abstract Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC. Graphical Abstract

China is one of the largest producers, consumers, and emitters of cadmium (Cd). This study applies the methods of material flow analysis and inventory analysis to investigate the flows and stocks of Cd in the industry-environment system in mainland China from 1990 to 2015. Special attention is paid to the identification of emissions and corresponding sources. It was found that: (1) more than 63% of Cd input in mainland China comprised unintentional processes that were driven by domestic mining and refining of nonferrous ores, which exceeded the input driven by intentional processes; (2) China became a net importer of Cd in 2000 because of the increasing import of nonferrous ores, which then led to Cd accumulation in domestic solid wastes; (3) Cd resources were mainly consumed in Ni–Cd batteries and plastics, and the in-use stock of Ni–Cd batteries reached a peak in 2008; (4) Cd emissions started to rise in 1990 and remained steady after 2013 due to the relatively stable production of nonferrous ores. The tendency of Cd emissions, use of Cd resources, and development of Cd-relevant industries were also discussed. The results indicated that the utilization of traditional products and the production of new energy materials may become the most important application of Cd resources in China.

Background and purpose Radiotherapy is the most important therapeutic measure against glioblastoma multiforme (GBM), which is regarded as the most common and highly lethal type of brain cancer. Nevertheless, most relapses originate in the close vicinity of the irradiated target volume. Genistein is a natural product that can suppress the invasive potential of cancer cells. In this study, DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-proficient and -deficient GBM cells were selected for in vitro and in vivo studies to investigate the inhibiting effects of genistein on radiation-induced invasion and migration and the corresponding mechanism. Materials and methods GBM cell lines with or without genistein pre-treatment were irradiated with X-rays. Cell survival was determined using colony formation assay and the rate of cellular proliferation was analyzed with a real-time cell electronic sensing system. For in vitro study, invasion and migration abilities were evaluated via wound-healing and transwell assays, while protein expression was determined with western blotting. Genistein interaction with DNA-PKcs was estimated with pull-down, recombinant and binding assays. For in vivo study, cells were stereotactically injected into NOD-SCID mice to establish tumors. Hematoxylin and eosin and immunohistochemistry were used to assess the invasive potential of GBM. Results X-ray irradiation enhanced the migration and invasion of DNA-PKcs-positive but not DNA-PKcs-negative GBM cells. It also activated the DNA-PKcs/Akt2/Rac1 signaling pathway, which contributed to GBM malignant progression by aggravating GBM cell invasive potential. The study successfully demonstrated that genistein can specifically bind to DNA-PKcs and block the DNA-PKcs/Akt2/Rac1 pathway, thereby effectively inhibiting radiation-induced invasion and migration of GBM cells in vitro and in vivo. The present study emphasized that radiation-induced invasive potential is initiated by DNA-PKcs, which is a well-known double strand breaks (DSB) repair protein, and determined the exact site for genistein binding to DNA-PKcs. Conclusion DNA-PKcs is not only a potential target for cancer therapy, but also a reliable biomarker for predicting radiation-induced invasion and migration of GBM cells. Thus, genistein might serve as a novel therapeutic strategy for treating GBM.

Endoplasmic reticulum (ER) stress is a conserved cellular process for cells to clear unfolded or misfolded proteins and maintain cell homeostasis under stress conditions. Autophagy may act as a pro-survival strategy to cope with multiple stress conditions in tumor progression and distant metastasis. Although many studies have demonstrated that there is a close correlation between radiation-induced ER stress and autophagy, the molecular mechanisms currently remain unclear. In the present study, we performed an in vivo study concerning the effect of autophagy induced by ER stress on the radiosensitivity of mouse sarcoma using X-rays. Our results documented that X-rays could induce ER stress in sarcoma and then autophagy was activated by unfolded protein response (UPR) through the IRE1-JNK-pBcl2-Beclin1 signaling axis. The induction of autophagy caused a decline in cell apoptosis while inhibiting the autophagy resulted in increased apoptosis and inhibition of tumor progression. Combined treatment of X-ray exposure and chloroquine increased ER stress-related apoptosis and enhanced the radiosensitivity of mouse sarcoma that was not sensitive to X-ray irradiation alone. Thus, our study indicates that inhibition of ER stress-induced autophagy might be a novel strategy to improve the efficacy of radiotherapy against radioresistant sarcoma.

Bisphenol A (BPA), a synthetic organic chemical, is creating a new category of ecological and human health challenges due to unintended leakage. Effectively managing the use and leakage of BPA can benefit from an understanding of the anthropogenic BPA cycles (i.e., the size of BPA flows and stocks). In this work, we provide a dynamic analysis of the anthropogenic BPA cycles in China for 2000-2014. We find that China's BPA consumption has increased 10-fold since 2000, to ∼3 million tonnes/year. With the increasing consumption, China's in-use BPA stock has increased 500-fold to 14.0 million tonnes (i.e., 10.2 kg BPA/capita). It is unclear whether a saturation point has been reached, but in 2004-2014, China's in-use BPA stock has been increasing by 0.8 kg BPA/capita annually. Electronic products are the biggest contributor, responsible for roughly one-third of China's in-use BPA stock. Optical media (DVD/VCD/CDs) is the largest contributor to China's current End-of-Life (EoL) BPA flow, totaling 0.9 million tonnes/year. However, the EoL BPA flow due to e-waste will increase quickly, and will soon become the largest EoL BPA flow. The changing quantities and sources of EoL BPA flows may require a shift in the macroscopic BPA management strategies.

Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.

Background Mounting evidence suggests that circular RNAs (circRNAs) are closely related to the regulation of gene expression during tumour development. However, the role of circRNAs in modulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells has not been explored. Methods Transcriptome sequencing was used to explore the expression profiles of circRNAs in NSCLC. The expression level of circRNAs was changed by inducing instantaneous knockdown or overexpression. Changes in proliferation and radiosensitivity of NSCLC cells were investigated using CCK-8, EDU, and clonal survivals. Results By analysing the circRNA expression profile of NSCLC cells, we found that circRNA ZNF208 (circZNF208) was significantly upregulated in a radioresistant NSCLC cell line (A549-R11), which was acquired from the parental NSCLC cell line A549. Knockout experiments indicated that circZNF208 enhanced the radiosensitivity of A549 and A549-R11 cells to X-rays. Mechanistically, circZNF208 upregulated SNCA expression by acting as a sponge of miR-7-5p and subsequently promoted the resistance of NSCLC cells to low linear energy transfer (LET) X-rays. However, this effect was not observed in NSCLC cells exposed to high-LET carbon ions. Conclusions Knockdown of circZNF208 altered the radiosensitivity of patients with NSCLC to X-rays but did not significantly change the sensitivity to carbon ions. Therefore, circZNF208 might serve as a potential biomarker and therapeutic target for NSCLC treatment with radiotherapy of different modalities.

Altered microRNA expression has been found to be a common feature of several cancers, including lung carcinomas. However, the possible roles of miR-768-3p in the pathological changes of lung carcinomas are still unknown. The aim of the present study was to investigate the expression and possible effects of miR-768-3p in human non-small cell lung carcinomas (NSCLC). Eighty-three NSCLC patients attending the clinic of Kunming Hospital were invited to participate in the study. Their tumor samples were obtained for qRT-PCR analysis. Human NSCLC cell lines, A549 and HCC4006, were employed and transfected with either miR-768-3p mimics or miR-768-3p antagomir. Following transfection, the in vitro and in vivo proliferation, apoptosis fractions, migration and invasion of NSCLC cells were evaluated. The data revealed that: i) upregulated miR-768-3p in tumors were associated with the clinicopathological features of NSCLC patients; ii) inhibiting miR-768-3p function by miR-768-3p antagomir induced distinctly apoptosis and Fas/FasL expressional alteration of NSCLC cells; iii) miR-768-3p antagomir transduction also decreased the viability, migration and invasion, as well as MMP-2 and MMP-9 activities in A549 and HCC4006 cells; and iv) miR-768-3p antagomir transfection also inhibited the growth and proliferation of NSCLC xenografts in nude mice. The present results suggested that abnormal elevated miR-768-3p in NSCLC tumors and cell lines played important roles in NSCLC carcinogenic progression, and the targeting of miR-768-3p might be a potential therapeutic strategy for the treatment of NSCLC.

Classical proteomics approaches involve enzymatic hydrolysis of proteins (either separated by polyacrylamide gels or in solution) followed by peptide identification using LC-MS/MS analysis. This method requires normally more than sixteen hours to complete. In the case of clinical analysis, it is of the utmost importance to provide fast and reproducible analysis with minimal manual sample handling. Herein we report the method development for online protein digestion on immobilized monolithic enzymatic reactors (IMER) to accelerate protein digestion, reduce manual sample handling, and provide reproducibility to the digestion process in clinical laboratory. An integrated online digestion and separation method using monolithic immobilized enzymatic reactor was developed and applied to digestion and separation of in-vitro-fertilization media. This article is protected by copyright. All rights reserved

During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption. Therefore, a pseudo-MMP (PMMP) was formed via maintenance of exogenous positive charges. Proton backflow was severely impaired, leading to a decrease in ATP production and an increase in AMP production. Excess AMP activates AMP kinase, which inhibits the MTOR (mechanistic target of rapamycin) pathway and induces macroautophagy/autophagy. Therefore, we conclude that MitoQ increases PMMP via proton displacement with exogenous positive charges. In addition, PMMP triggered autophagy in hepatocellular carcinoma HepG2 cells via modification of mitochondrial bioenergetics pathways.

Arsenic is a trace element and a global contaminant. There are currently large uncertainties associated with our understanding and quantification of the arsenic cycles in the global environment. This study proposes a research framework where the major anthropogenic processes affecting anthropogenic arsenic cycles (AACs) are identified. A characteristic of this framework is that it divides AACs into two parts: one related to intentional uses, and the other driven by unintentional uses. Several significant features of AACs are summarized as follows: (1) existing studies reveal that AACs at Earth's surface is at the same order of magnitudes as its natural cycles; (2) arsenic mostly enters modern anthroposphere as a companion element of nonferrous metal ores or fossil fuels, and currently there is abundant arsenic reserves relative to the limited intentional use of arsenic; (3) China owns the majority of arsenic reserves and is the biggest producer of arsenic for the present day, while U.S. was the biggest user of arsenic in the whole 20th century; (4) there were several waves of rise and fall of intentional arsenic use in the 20th century of U.S., with the rises driven by various applications of arsenic in agriculture and industry (such as glass making in the 1900s, agricultural applications in the 1920s, and wood preservatives in the 1970s), and the falls mainly resulting from the regulations in response to its toxicity; (5) the majority of intentional arsenic uses are in the form of chemical compounds rather than single substance, and almost all intentional uses of arsenic not only are unrecyclable but also result in emissions that may last years or decades after being used.

Background Radiotherapy (RT) is considered an important therapeutic strategy in the fight against colorectal cancer (CRC). However, the existence of some radioresistance factors becomes the main challenge for the RT. Recently, non-coding RNAs (ncRNAs) have shown an important role in modulating cancer cell responses to ionizing radiation (IR). It is therefore of great significance to elucidate the exact mechanisms of ncRNAs in IR-mediated responses to CRC. Methods Microarrays were used to identify specific miRNAs that may be altered in response to IR. Bioinformatics, luciferase reporter analyses were used to explore the targets of miR-6778-5p. CircRNA CBL.11 was identified to bind with miR-6778-5p by bioinformatic analysis, AGO2 immunoprecipitation and biotinylated RNA pull-down assay. Functional experiments, including CCK-8 assay, cell colony formation assay and EdU incorporation were conducted to investigate the biological roles of miR-6778-5p and circular RNA CBL.11. Results MiR-6778-5p was suppressed in CRC cells after irradiation. Results of functional experiments indicated that miR-6778-5p promoted the proliferation of CRC cells. Luciferase reporter analyses showed that YWHAE was a target of miR-6778-5p, which mediated the function of miR-6778-5p in the proliferation of CRC cells via the p53 pathway. Furthermore, we have noticed that after carbon ion irradiation, circRNA CBL.11 was increased in CRC cells and could function as a competing endogenous RNA (ceRNA) to regulate YWHAE expression by sponging miR-6778-5p, resulting in regulation the proliferation of CRC cells. Conclusion CircRNA CBL.11 may play an important role in improving the efficacy of carbon ion RT against CRC. Electronic supplementary material The online version of this article (10.1186/s12885-019-6017-2) contains supplementary material, which is available to authorized users.

Although radiotherapy, especially carbon-ion radiotherapy, is an effective treatment modality against non-small-cell lung cancer (NSCLC), studies using radiation combined with sensitizer for improving the efficacy of radiotherapy are still needed. In this work, we aimed to investigate in NSCLC A549 and H1299 cell lines the effects of different linear energy transfer (LET) radiations combined with diverse sensitizing compounds. Cells pretreated with the CHK1/CHK2 inhibitor AZD7762, Honokiol or Tunicamycin were irradiated with low-LET X-rays and high-LET carbon ions. Cell survival was assessed using the clonogenic cell survival assay. Cell cycle distribution and apoptosis were measured with flow cytometry, and DNA double strand break (DSB) and repair were detected using γ-H2AX immunofluorescence staining. Our results revealed that AZD7762, Honokiol and Tunicamycin demonstrated low cytotoxicity to NSCLC cells and a pronounced radiosensitizing effect on NSCLC cells exposed to carbon ions than X-rays. Unrepaired DNA DSB damages, the abrogation of G2/M arrest induced by irradiation, and finally apoptotic cell death were the main causes of the radiosensitizing effect. Thus, our data suggest that high-LET carbon ion combined with these compounds may be a potentially effective therapeutic strategy for locally advanced NSCLC.

The exploration of biocompatible materials with circularly polarized luminescence (CPL) activity is becoming an attractive topic due to the great potential application in biosensing and bioimaging. Here, we describe a strategy to fabricate new CPL-active biomaterials using achiral carbazole-based biscyanine fluorophores coassembled with chiral deoxyribonucleic acid (DNA) molecules. This cyanine molecule has been shown to behave as a DNA detecting probe, featuring strong fluorescent emission induced by restriction of intramolecular rotation (RIR). When the achiral cyanine molecules are bound to the minor groove of DNA via electrostatic attraction in aqueous solution, the chirality of the DNA molecules can be transferred to the confined RIR cyanine dyes, triggering a remarkable circularly polarized luminescent emission. The chirality of the CPL signal can be regulated by the structures of the DNA templates. Stimuli-responsive CPL activates were observed from DNA-cyanine complexes. We further verified this strategy on different DNA-based nanomaterials, including DNA origami nanostructure. Our design presents a new avenue to fabricate compatible CPL materials.

Feifei Li,1,2,* Zihou Li,2,3,* Xiaodong Jin,1 Yan Liu,1 Pengcheng Zhang,1,2 Ping Li,1 Zheyu Shen,3 Aiguo Wu,3 Weiqiang Chen,1 Qiang Li1 1Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; 2University of Chinese Academy of Sciences, Beijing 100049, China; 3Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China *These authors contributed equally to this work Background: Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radiosensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation.Method and materials: GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation.Results: GONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation.Conclusion: This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation. Keywords: gadolinium oxide nanocrystal, radiosensitization, cytostatic autophagy, apoptosis, oxidative stress

Wind energy is key to addressing the global climate challenge, but its development is subject to potential constraints of finite primary materials. Prior studies on material demand forecasting of wind power development are often limited to a few materials and with low technological resolution, thus hindering a comprehensive understanding of the impact of microengineering parameters on the resource implications of wind energy. In this study, we developed a component-by-component and stock-driven prospective material flow analysis model and used bottom-up data on engineering parameters and wind power capacities to characterize the materials demand and secondary supply potentials of wind energy development in Denmark, a pioneering and leading country in wind power. We also explicitly addressed the uncertainties in the prospective modeling by the means of statistical estimation and sensitivity analysis methods. Our results reveal increasing challenges of materials provision and end-of-life (EoL) management in Denmark's ambitious transition toward 100% renewable energy in the next decades. Harnessing potential secondary resource supply from EoL and extending lifetime could curtail the primary material demand, but they could not fully alleviate the material supply risk. Such a model framework that considers bottom-up engineering parameters with increased precision could be applied to other emerging technologies and help reveal synergies and trade-offs of relevant resource, energy, and climate strategies in the future renewable energy and climate transition.

The radio-protective effects of the oxazolone derivative chemical compound 4-(4-methoxy-3-methoxyphenyl-methyl)-2-phenyl- 5(4H)-oxazolone (GANRA-5) against different types of radiation including X-rays, carbon ion beams, microwaves and ultraviolet light (UV) were studied. Cell proliferation/cytotoxicity assay and colony-forming assay were conducted to evaluate the toxicity of GANRA-5. To test its influence on the induction of double-stranded break (DSB) formation and genomic instability, γH2AX focus-forming assay as well as cytokinesis-block micronucleus assay was utilized. Our results indicate that GANRA-5 exhibits low toxicity, while providing high radio-protective effects for MRC-5 cells against different types of radiation. We also found that GANRA-5 acts as a free radical scavenger. Our animal studies provided evidence that GANRA-5 significantly increases the survival rate of mice after X-ray irradiation. Analyses of hemogram, visceral index and detection of superoxide dismutase (SOD) and malondialdehyde (MDA) in the viscera indicate both low toxicity of GANRA-5, combined with its ability to shield radiation risk. In conclusion, our results suggest that GANRA-5 has the potential to be used as a safe and efficient radio-protectant.

Xi Liu,1–4 Yan Liu,1–4 Pengcheng Zhang,1–4 Xiaodong Jin,1–3 Xiaogang Zheng,1–4 Fei Ye,1–4 Weiqiang Chen,1–3 Qiang Li1–3 1Institute of Modern Physics, 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 4School of Life Science, University of Chinese Academy of Sciences, Beijing, People’s Republic of China Abstract: Reductive drug-functionalized gold nanoparticles (AuNPs) have been proposed to enhance the damage of X-rays to cells through improving hydroxyl radical production by secondary electrons. In this work, polyethylene glycol-capped AuNPs were conjugated with tirapazamine (TPZ) moiety, and then thioctyl TPZ (TPZs)-modified AuNPs (TPZs-AuNPs) were synthesized. The TPZs-AuNPs were characterized by transmission electron microscopy, ultraviolet-visible spectra, dynamic light scattering, and inductively coupled plasma mass spectrometry to have a size of 16.6±2.1nm in diameter and a TPZs/AuNPs ratio of ~700:1. In contrast with PEGylated AuNPs, the as-synthesized TPZs-AuNPs exhibited 20% increment in hydroxyl radical production in water at 2.0Gy, and 19% increase in sensitizer enhancement ratio at 10% survival fraction for human hepatoma HepG2 cells under X-ray irradiation. The production of reactive oxygen species in HepG2 cells exposed to X-rays in vitro demonstrated a synergistic radiosensitizing effect of AuNPs and TPZ moiety. Thus, the reductive drug-conjugated TPZs-AuNPs as a kind of AuNP radiosensitizer with low gold loading provide a new strategy for enhancing the efficacy of radiation therapy. Keywords: AuNPs, radiation enhancement, synergistic effect, human hepatoma cells, hydroxyl radical production

We demonstrate low threshold lasing oscillation in a photonic crystal (PhC) laser by using tert-butyl Rhodamine B (t-Bu-RhB) doped gain media. Lactonic t-Bu-RhB is synthesized to improve doping concentration in polymethylmethacrylate (PMMA) films, and then isomerized to the zwitterion form to achieve highly fluorescent gain medium. The t-Bu-RhB doped PMMA film is sandwiched by a pair of polystyrene colloidal crystals to construct a PhC resonating cavity. Single-mode laser oscillation at 592 nm is observed when the PhC resonating cavity is pumped by a Nd:YAG laser. The lasing threshold is 0.12 MW cm(-2) utilizing 6.9 wt% t-Bu-RhB doped PMMA films, which is only 1/60 of that with 3 wt% t-Bu-RhB doped PMMA films. The concentration-dependent lasing action is attributed to different gain factors of the t-Bu-RhB doped PMMA films. Furthermore, a spatially and spectrally coherent laser beam from the PhC resonating cavity is verified by exploring the far-field image and angular dependence of the lasing emission. The approach provides a facile and efficient strategy to reduce the lasing threshold for fabricating low threshold PhC lasers.

Scandium (Sc) is the most expensive rare earth element and is widely considered as one of the most critical materials for various emerging applications such as the third-generation Solid Oxide Fuel Cell (SOFC) battery. The global Sc demand is expected to increase rapidly, while its supply is mainly constrained by limited mineral reserve and environmental burdens associated with its production. There are few Sc deposits distributed in the world, with small reserves and complicated extraction processes. A large amount of Sc is mainly concentrated in tailings and has not been extracted in large quantities. Besides, detailed assessments on the potential environmental impacts of rare earths production, and Sc in particular, are very rare. This study aims to fill this gap to assess the environmental impacts of the production of Sc2O3, where the technical processes are modelled based on a recent project of Sc recovery from rare earths tailings in Bayan Obo mine. The environmental impacts of 5 major processes and 22 sub-processes involved in the beneficiation stage and the smelting stage have been evaluated with the synergies of various inventory data. It is found that the beneficiation stage accounts for 88% of the overall impact, around 56% of which is contributed by the secondary separation process. Among the ten assessed categories, Human toxicity non-cancer (HTNC) and Global Warming Air (GWA) are the top two significant impacts caused by Sc2O3 production. Through comparative analysis with published results, it’s found that the environmental impact of Sc2O3 production from the tailings of Bayan Obo mine are much lower than those of direct production from the mixed rare earths ores. Our hotspot analysis identifies that the consumption of steam in Fe separation (II) and oxalic acid in oxalic acid precipitation are the major contributors to the total environmental impacts of Sc2O3 production. Thus, strategies to reduce their use and improve environmental performance in their production are highly encouraged. This study can provide a basis for sustainable raw material sourcing for the clean development of the third-generation SOFC battery.

Tungsten is deemed a critical raw material by many nations, given its irreplaceable use in industrial and military applications. In particular, much concern has been drawn to China's high share in global tungsten supply. While various studies have focused on the criticality of tungsten, few have specifically explored how tungsten is produced, consumed, and traded. In this paper, the dynamic material flow analysis is applied to quantify China's annual tungsten cycle from 1949 – 2017. It is estimated that total tungsten mined from ores in China over the past 68-year period is ~2500 kilo-tons (kt). Among those, ~750 kt of tungsten has been exported to other countries, and around 970 kt tungsten is domestically consumed. It is noted ≈1720 kt has been lost from mining, production, and end-of-life stage, and merely ~130 kt has been recycled as end-of-life scrap. Our material flow analysis further refined China's tungsten dominance. Although China currently dominates the global production of tungsten, this dominance will not extend too far into the future given China's limited share of world tungsten reserves and its declining ore quality. Our trade flow analysis reveals that China imported ~35 kt of high value-added downstream tungsten products from outside manufacturers, whose mineral resource was originally imported from China. At present, China by itself is experiencing overcapacity issues in the primary production, which discourages the recycling of at end-of-life (EoL) stage and makes the EoL recycling rate only 10%. It is noted that the percentage of Chinese tungsten for domestic consumption has been increasing in the past few years. This highlights the need for systematic measures from stakeholders along the tungsten cycle to promote sustainable practices for efficient tungsten production, use, and recycling in China. Meanwhile, the results also suggest the importance of monitoring the criticality of tungsten and other critical minerals from a dynamic and material cycle perspective.

Given copper mineral is becoming rarer and harder to obtain, China needs to find alternative sources to meet its future demand. Copper in-use stocks are potential reservoirs accessible for urban mining. Thus, detailed analyses of domestic copper in-use stocks and flows are required, especially for a high-resolution mapping of the spatio-temporal distribution of copper stocks and flows in China. This paper firstly constructs the China’s provincial copper in-use stocks (CPCS) database by compiling around 74 types of copper-containing products in 31 provinces from 1978 to 2016, and estimates copper in-use stocks, demand, and scrap generation in each province. Results indicate that (1) the total copper in-use stocks in China is about 90 MMT (million metric tons) in 2016, which is around four times as much as China’s copper ore reserves; (2) Per-capita copper in-use stocks increased from 14 kg in 1978 to 75 kg in 2016 with large regional disparity across the whole country, and is still below the western nations’ level; (3) Total copper scrap generation increased rapidly from 0.003 MMT in 1979 to 1.50 MMT in 2016, mainly in the eastern coastal region, indicating that the time window for copper urban mining is opening in the region. This study can help clarify the location, amount, and category of copper in-use stocks available for future urban mining, and tailor more regional-specific resource and waste management policies for sustainable copper management in China.

Although mitochondria are known to play an important role in radiation-induced cellular damage, the mechanisms by which ionizing radiation modulates mitochondrial dynamics are largely unknown. In this study, human cervical carcinoma cell line HeLa was used to demonstrate the different modes of mitochondrial network in response to different quality radiations such as low linear energy transfer (LET) X-rays and high-LET carbon ions. Mitochondria fragmented into punctate and clustered ones upon carbon ion irradiation in a dose- and LET-dependent manner, which was associated with apoptotic cell death. In contrast, low-dose X-ray irradiation promoted mitochondrial fusion while mitochondrial fission was detected until the radiation dose was more than 1 Gy. This fission was driven by ERK1/2-mediated phosphorylation of Drp1 on Serine 616. Inhibition of mitochondrial fragmentation suppressed the radiation-induced apoptosis and thus enhanced the resistance of cells to carbon ions and high-dose X-rays, but not for cells irradiated with X-rays at the low dose. Our results suggest that radiations of different qualities cause diverse changes of mitochondrial dynamics in cancer cells, which play an important role in determining the cell fate.

Enantioenriched α-exo-methylene γ-butyrolactones have been obtained via a two-step sequence consisting of a highly enantioselective chromium-catalyzed carbonyl 2-(alkoxycarbonyl)allylation and lactonization. A variety of functional groups are compatible under the mild reaction conditions. The synthetic utility of this methodology was demonstrated by two short derivatization transformations and the enantioselective synthesis of (+)-methylenolactocin.

An efficient direct carboxylation of a series of benzyl chlorides with CO2 catalyzed by Pd(OAc)2/dicyclohexyl (2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (SPhos) was developed to afford the corresponding phenylacetic acids in combination with Mn powder as a reducing reagent and MgCl2 as an indispensable additive. The reaction proceeded smoothly under 1 atm CO2. The application of Mn powder instead of a sensitive reducing reagent represents an operationally simple access to phenylacetic acids. Notably, MgCl2 is able to stabilize the (SPhos)2PdII(Bn)(Cl)(η1-CO2)(MgCl2) adduct and thus facilitates CO2 insertion into the PdII−C bond, which is supported by a DFT study.

The chemical conversion of CO2 at atmospheric pressure and room temperature remains a great challenge. The triphenylphosphine complex of silver(I) carbonate was proved to be a robust bifunctional catalyst for the carboxylative cyclization of propargylic alcohols and CO2 at ambient conditions leading to the formation of α-methylene cyclic carbonates in excellent yields. The unprecedented performance of [(PPh3)2Ag]2CO3 is presumably attributed to the simultaneous activation of CO2 and propargylic alcohol. Moreover, the highly compatible basicity of the catalytic species allows propargylic alcohol to react with CO2 leading to key silver alkylcarbonate intermediates: the bulkier [(Ph3P)2Ag(I)](+) effectively activates the carbon-carbon triple bond and enhances O-nucleophilicity of the alkylcarbonic anion, thereby greatly promoting the intramolecular nucleophilic cyclization. Notably, this catalytic protocol also worked well for the reaction of propargylic alcohols, secondary amines, and CO2 (at atmospheric pressure) to afford β-oxopropylcarbamates.

Background and purpose Previously, we found genistein could sensitize cancer cells to low linear energy transfer (LET) X-rays via inhibiting DNA-PKcs activities. Especially, high-LET heavy ion produces more DNA double strand breaks (DSBs) than low-LET radiation. Thus, the study was designed to investigate the detailed molecular mechanisms of genistein on sensitizing cancer cells to heavy ions. Materials and methods Human glioblastoma (GBM) cell lines with or without genistein pre-treatment were irradiated with high-LET carbon ions. Cell survival was determined with colony formation assay. DNA DSBs were evaluated by means of detecting γ-H2AX foci and immuno-blotting DSB repair proteins, cell apoptosis was detected using Annexin V and PI staining. The interaction of genistein with DNA-PKcs activation site was estimated by molecular docking in the autodock software. Results Genistein sensitized DNA-PKcs proficient GBM cells to high-LET carbon ions via delaying the clearance of γ-H2AX foci. Genistein was physically bound to DNA-PKcs and functionally inhibited the phosphorylation of DNA-PKcs. Consequently, the non-homologous end joining (NHEJ) repair of DSBs was inhibited and the homologous recombination (HR) repair was delayed by genistein, thereby leading to an increase in apoptosis in DNA-PKcs proficient GBM cells after irradiation. Conclusion Our study demonstrated that genistein holds promise as a radiosensitizer for enhancing the efficacy of carbon ion radiotherapy against DNA-PKcs proficient GBM via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways.

Hypoxia-inducible factor-1α (HIF-1α), a key mediator in tumor metastasis and angiogenesis, is associated with poor patient prognosis and has been recognized as an important cancer drug target. In this work, four novel series of ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were designed, synthesized, and evaluated for anti-tumor activity as HIF-1α inhibitors. The majority of the compounds showed an excellent ability to inhibit the expression of HIF-1α. In particular, 11b inhibited HIF-1α transcriptional activity under hypoxic conditions with IC50=36.9μM. The cytotoxicity of these compounds was also assessed in human colon cancer cell HCT116 cells by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC50>100μmol/L), which was lower than that of ursolic acid (IC50=23.8μmol/L). The mechanism of action of the representative compound 11b was also investigated.

Arsenic (As) is a trace element in the global environment with toxicity to both humans and ecosystem. This study characterizes China's historical anthropogenic arsenic cycles (AACs) from 1990 to 2010. Key findings include the following: (1) the scale of China's AACs grew significantly during the studied period, making China the biggest miner, producer, and user of arsenic today; (2) the majority of arsenic flows into China's anthroposphere are the impurity of domestically mined nonferrous metal ores, which far exceeds domestic intentional demands; (3) China has been a net exporter of arsenic trioxide and arsenic metalloid, thus suffering from the environmental burdens of producing arsenic products for other economies; (4) the growth of arsenic use in China is driven by simultaneous increases in many applications including glass making, wood preservatives, batteries, semiconductors, and alloys, implying the challenge for regulating arsenic uses in multiple applications/industries at the same time; (5) the dissipative arsenic emissions resulting from intentional applications are at the same order of magnitude as atmospheric emissions from coal combustion, and their threats to human and ecosystem health can spread widely and last years to decades. Our results demonstrate that the characterization of AACs is indispensable for developing a complete arsenic emission inventory.

Syntheses, crystal structures and magnetic properties of three molecular solids, [2RBzTPP]2[Cu(mnt)2] (mnt2− = maleonitriledithiolate; [2RBzTPP]+ = 1-(2′-R-benzyl)triphenylphosphonium, R = F(1), Cl(2) and Br(3)) are investigated. All three molecular metals crystallize in the triclinic space group P-1. The change of the molecular topology of the counteraction when the o-substituted group in the benzyl ring has changed from F to Cl and Br, results in the difference in the dihedral angles, the stacking mode and the weak interactions of the cations and anions of 1, 2 and 3. The effect of weak intramolecular interactions such as C H⋯X(X = F, Cl, Br), C H⋯S, C H⋯N, C H⋯Cu, C H⋯π hydrogen bonds and the short X⋯X interactions generates a 3D network structure. The magnetic susceptibilities of these molecular metals measured in the temperature range 2.0–300 K show that the overall magnetic behaviors of 1–3 correspond to a paramagnetic system with a very weak ferromagnetic coupling interaction with θ = 0.013 K for 1, 0.019 K for 2 and 0.025 K for 3.

A new ion-paired compound [4NO2BzPy]2[Co(NCS)4] (1) ([4NO2BzPy]+ = 1-(4′-nitrobenzyl)pyridinium, NCS− = isothiocyanate) is synthesized and characterized by elemental analysis, IR and UV-Vis spectra, ESI-MS and single crystal X-ray diffraction. Compound 1 is orthorhombic, space group Pbcn, with a = 13.188(2) A, b = 8.458(1) A, c = 29.281(4) A, V = 3266.2(7) A3, D calc = 1.468 g/cm3, Z = 4, F(000) = 1476, R 1 = 0.0332. The [Co(NCS)4]2− anions form an unusual layer structure by S…N and S…Co interactions, while the [4NO2BzPy]+ cations stack into a 1D column by the p…π stacking interaction in the solid state of 1. A magnetic measurement in the range 2–300 K shows a weak antiferromagnetic exchange with θ = −2.42 K in 1.

Three new molecular metals, [2RBzTPP][Ni(mnt) 2 ] (mnt 2− = maleonitriledithiolate; [2RBzTPP] + = 1-(2′-R-benzyl)triphenylphosphonium, R = F( 1 ), Br( 2 ), NO 2 ( 3 )) have been synthesized and characterized by elemental analyses, IR, UV, single crystal X-ray diffraction and magnetic measurements. The single-crystal structure analysis indicates that 1 crystallizes in the triclinic space group P − 1, while both 2 and 3 crystallizes in the monoclinic space group P 2 1 / n . The Ni(III) ions of 1 , 2 , and 3 form a 1D non-uniform magnetic chain within a [Ni(mnt) 2 ] − anions column through Ni⋯Ni, Ni⋯S or S⋯S interactions. The effect of weak intramolecular interactions such as C H⋯N, C H⋯F, C H⋯Br, C H⋯π or C H⋯O hydrogen bonds in these molecular solids 1 , 2 or 3 generate a 3D network structure. Magnetic measurements have shown that 1 exhibits a characteristic of spin-gap (Δ/ k b = 249.5 K) around 128 K, while 2 and 3 showed a very strong antiferromagnetic coupling feature with J = −875.6 and −820.3 cm −1 when the temperature is lowered.

Two hybrid salts, [2ClBzTPP]2[Ni(i-mnt)2] (1) and [4ClBzTPP]2[Ni(i-mnt)2] (2), were obtained in crystalline form by the reaction of disodium iso-maleonitriledithiolate (K2(i-mnt)) with nickel(II) chloride hexahydrate and 1-(2′-chlorobenzyl)triphenyl-phosphonium or 1-(4′-chlorobenzyl)triphenylphospho-nium bromide ([2ClBzTPP]Br/[4ClBzTPP]Br) in methanol. Two salts were characterized by elemental analyses, UV, IR, ESI-MS, molar conductivity, and single-crystal X-ray diffraction. Both salts crystallize in the triclinic space group P-1 and the central Ni(II) ion has a distorted square planar coordination geometry. Lattice stability is provided by weak interactions observed in 1 and 2 such as C-H···S, C-H···Cl, and C-H···Ni hydrogen bonds and π···π or p···π interactions, which results in the forming of a 3D network structure.

Two new complexes of tetra(isothiocyanate)cobalt(II) dianion and meta-substituted benzyl triphenylphosphinium, [3BrBzTPP]2[Co(NCS)4] (1) and [3CNBzTPP]2[Co(NCS)4] (2) ([3BrBzTPP]+ = 1-(3′-bromobenzyltriphenylphosphonium and [3CNBzTPP]+ = 1-(3′-cyanobenzyltriphenylphosphonium), were prepared and characterized by elemental analysis, FT–IR, UV-vis spectra, ESI-MS, and single-crystal X-ray diffraction method. Both 1 and 2 crystallize in monoclinic P2(1)/c, and the Co(II) ion of the [Co(NCS)4]2− anion shows a distorted tetrahedral coordination geometry. The C-H···S hydrogen bonds and p···π interaction found in 1 and 2 consolidate the stacking of the crystal. Magnetic susceptibility measurement in the temperature range 2–300 K shows that 1 and 2 exhibit a weak antiferromagnetic coupling behavior.

Two new molecular metals, [2FBz-2NH2Py][Ni(mnt)2] (1) and [4FBz-2NH2Py][Ni(mnt)2] (2) ([2FBz-2NH2Py]+ = 1-(2′-fluobenzyl)-2-aminopyridinium, [4FBz-2NH2Py]+ = 1-(4′-fluobenzyl)-2-aminopyridinium mnt2− = maleonitriledithiolate), have been prepared and characterized by elemental analyses, IR, MS spectra, single crystal X-ray diffraction. The Ni(III) ions of 1 and 2 form a 1D zigzag non-uniform magnetic chain within a [Ni(mnt)2]− column through Ni⋯Ni, Ni⋯S, Ni⋯C, S⋯C, N⋯C or π⋯π interactions both at 293 and 150 K (the crystal structure of 2 at 293 K has been briefly reported earlier, here the crystal structure at 150 K and magnetic susceptibility are investigated). Upon the temperature is lowered, the non-uniform chain has been compressed with the shortness of Ni⋯Ni distance. Variable temperature magnetic susceptibility measurements agree very well with the 1D non-uniform chain structures, and 1 exhibits a spin-gap transition around 260 K with Δ/kB = 1160.0 K, while 2 shows two spin-gap transitions around 235.7 K (Δ/kB = 867.8 K) and 10.4 K (Δ/kB = 19.1 K), respectively.

Although a series of protein levels from several protein pathways have been shown to differ between white (WA) and brown (BA) adipocytes, proteomic work on this subject with the exception of mitochondrial protein differences is limited. It was, therefore, the aim of the study to compare WA with BA soluble protein levels. Proteins were extracted from WA and BA and the soluble fraction was run on two-dimensional gel electrophoresis. Quantification of spot volume was carried out and protein spots, statistically different between groups (P

Four novel ion-pair complexes, [FClBzTPP]2[Cu(mnt)2](1), [DiClBzTPP]2[Cu(mnt)2](2), [FClBzTPP][Ni(mnt)2](3) and [DiClBzTPP][Ni(mnt)2](4), where [FClBzTPP]+ = 1-(2′-chloro-4′-flurobenzyl)triphenylphosphonium, [DiClBzTPP]+ = 1-(2′, 4′-chlorobenzyl)triphenylphosphonium and mnt2− = maleonitriledithiolate, have been prepared and characterized by elemental analyses, IR, UV, single crystal X-ray diffraction and magnetic measurements. Weak interactions such as F⋯F, Cl⋯Cl, and C–H⋯N, C–H⋯Cl, C–H⋯Cu observed in 1 and 2 consolidate 3D network structure. The Ni(III) ions of 3 and 4 form a 1D linear chain in a column of [Ni(mnt)2]− anions by intermolecular Ni⋯Ni and Ni⋯S or π⋯π weak interactions. The change of 4-substituted group in the benzyl ring from F to Cl atom results in the crystal system, space group, and the stacking and overlapping modes of [Ni(mnt)2]− anions in 3 and 4. Magnetic susceptibility measurements show that 1 and 2 at 20–300 K exhibit weak ferromagnetic coupling with θ = 4.21 K and 1.80 K, whereas while 3 and 4 show antiferromagnetic coupling with J = −36.42 cm−1 and −55.78 cm−1.

Graphical abstract, The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CLpro. 3CLpro plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CLpro inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CLpro. Structure–activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k1 showed most potent inhibitory activity against 3CLpro (IC50 = 1.04 μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.

To investigate the anti-hepatoma mechanism of α-pinene, HepG2 cell was treated with α-pinene and the change of cell cycle was examined by flow cytometry. The expression of miR-221, which was related the regulation of G₂/M phase, was detected by quantitative Real-time PCR. Meanwhile, TargetScan and other online bioinformatics methods were used to analyze and predict the target genes of miR-221, then the expression level of related target genes were detected by quantitative Real-time PCR. The results showed that α-pinene inhibited the proliferation of HepG2 cells in dose-dependent manner. It was also proved that HepG2 cells were arrested at G₂/M phase by α-pinene (P

Tetraphenylethylene (TPE), an archetypal luminogen with aggregation-induced emission (AIE), was grafted to a salt-responsive peptide to yield a yet luminescent hydrogelator. After testing different parameters, we found that only in the presence of salt rather than temperature, pH, and solvent, did the monodisperse hydrogelators self-assemble into a hydrogel network with bright emission turned on. The induced luminescence was a dynamic change and enabled real time monitoring of hydrogel formation. Grating AIE molecules to stimuli-responsive peptides is a promising approach for the development of self-revealing soft materials for biological applications.

To improve the overall performance of the domestic high-modulus carbon fiber/cyanate composites, a macromolecular coupling agent (SCC) based on the raw material styrene, methyl acrylate and γ-methyl (acryloyl) trimethoxysilane was synthesized. It also studies the effect of coupling agent content on the mechanical properties of composites. The results show that the dosage of macromolecular coupling agent with 3%, the performance of the composite materials has been notable improved, its bend strength and interlaminar shear strength are 1100Mpa and 63.5Mpa, which has been raised 6.0% and 16.1%, respectively. SEM micrographs show that the addition of a coupling agent effectively improve the interface compatibility between the resin and fibers in composite.

Two new ion-pair complexes, based on [Ni(i-mnt)2]2– (i-mnt = isomaleonitriledithiolate) anion, [Bz-4-MePy]2[Ni(i-mnt)2]([Bz-4- MePy]+ = 1-benzyl-4′-methylpyridinium) (1) and [Bz-4-MeQl]2 [Ni(i-mnt)2]([Bz-4-MeQl]+ = 1-benzyl-4′-methylquinolinium) (2), were obtained and characterized. The most obvious structure feature of 1 and 2 is that the [Ni(i-mnt)2]2– anions form a 1D chain through C···N or C···C short interactions between the i-mnt ligands, and the [Bz-4-MeQl]+ cations of 2 form a 2D structure through the π···π stacking interactions between the aromatic rings. The C–H···N and C–H···Ni hydrogen bonds observed in the anions and cations consolidate the stacking of the molecules and give rise to a 3D network structure.

Bis(iso-maleonitriledithiolate)nickel(II) benzylpiperidinium, [BzPid]2[Ni(i-mnt)2] (1) is prepared and characterized by elemental analyses, UV, IR, molar conductivity, and single crystal X-ray diffraction. It is found that 1 crystallizes in the monoclinic space group P21/n with a = 9.551(1) A, b = 16.520(2) A, c = 11.004(1) A, β = 96.60(1)°, V = 1724.6(3) A3, Z = 2. Consolidate the stacking of the molecules The electrostatic interaction between [Ni(i-mnt)2]2− anions and [BzPid]+ cations consolidates the stacking of the molecules.

Three new molecular magnets [DiFBzPid][Ni(mnt)2]·0.5CH3COCH3(1), [DiBrBzPid][Ni(mnt)2](2) and [DiNO2BzPid][Ni(mnt)2](3) have been obtained by self-assembly of the [Ni(mnt)2]− (mnt2− = maleonitriledithiolate) anion and [DiRBzPid]+ ([DiRBzPid]+ = N,N′-diRbenzylpiperidinium; R = F, Br, NO2) cation. The Ni(III) ions of the anions in 1 and 3 form a 1D alternating magnetic chain within a [Ni(mnt)2]− column through Ni⋯S, S⋯S, S⋯N, S⋯C or C⋯N short interactions, while the anions in 2 form a dimer. The cations in three compounds stack into a 1D column in different shapes via p⋯π, F⋯F, Br⋯Br, and O⋯O weak interactions or C H⋯π hydrogen bonds. In addition, the [DiNO2BzPid]+ cations (C) and [Ni(mnt)2]− anions (A) of 3 stack into a 1D alternative column with a A–CC–A–CC–A sequence. The change of the substituent group in the benzyl ring from F(1) to Br(2) and NO2(3) results in the significant differences in the anion–anion, anion–cation and cation–cation stacking modes of 1, 2 and 3. Magnetic susceptibility measurements in the temperature range of 2–300 K show that 1 and 3 show characteristic of spin-gap (Δ/kb = 524.6 K or 1706.6 K), while 2 exhibits a strong antiferromagnetic coupling feature with J/kb = −663.2 K.

Two new ion-pair compounds based on [Ni(tdas)2]2− (tdas = 1,2,5-thiadiazole-3,4-dithiolate) anion with substituted benzyl triphenylphosphium cation, [2ClBzTPP]2[Ni(tdas)2](1) and [4ClBzTPP]2[Ni(tdas)2](2), have been prepared and characterized by UV, IR, ESI-MS, molar conductivity, and single-crystal X-ray diffraction. Single-crystal X-ray diffraction analyses indicate that 1 crystallizes in the triclinic space group P–1, while 2 crystallizes in the monoclinic space group P21/n. Some intramolecular contacts such as C−H···Cl, C−H···S, C−H···N or S···Cl weak interactions observed in 1 and 2 consolidate the crystal packing and generate a 3D network structure.

We have investigated the photoinitiating properties of the photoinitiator 3,6-bis[2-(4-nitrophenyl)-ethynyl]-9-(4-methoxy-benzyl)-carbazole (BNMBC), which has an intramolecular radical quenching group "p-methoxybenzyl," in the substrate lines fabrication of two-photon induced photopolymerization (TPIP). Another photoinitiator 3,6-bis[2-(4-nitrophenyl)-ethynyl]-9-benzyl-carbazole (BNBC) with similar chemical structure but not radical quenching group was studied for comparison. Their photopolymerization properties were studied with resins in which BNBC and BNMBC were used as photoinitiators with a molar ratio of 0.02%, respectively. The linewidth of polymer lines fabricated by TPIP of the photoresist that contained BNMBC could be decreased to 65% of those using BNBC. Besides, we introduced a radical quencher, phenyl methyl ether (PhOCH3), to BNBC and further studied the photopolymerization properties by using BNBC, BNBC/PhOCH3 and BNMBC as photoinitiators with a molar ratio of 0.1%. The results further indicated that BNMBC was effective to confine the radical diffusion in polymerization due to the radical quenching effect of moiety. This intramolecular radical quenching moiety exhibited more effective confining effect of radical diffusion compared to the intermolecular radical quencher PhOCH3. Furthermore, arbitrary complex three-dimensional (3D) microstructure was achieved using the photoresist with photoinitiator BNMBC. The approach could open up broad prospect for improving the resolution in TPIP.

Enantioenriched α-exo-methylene γ-butyrolactones have been obtained via a two-step sequence consisting of a highly enantioselective chromium-catalyzed carbonyl 2-(alkoxycarbonyl)allylation and lactonization. A variety of functional groups are compatible under the mild reaction conditions. The synthetic utility of this methodology was demonstrated by two short derivatization transformations and the enantioselective synthesis of (+)-methylenolactocin.