Research Progress----Shanghai Advanced Research Institute,Chinese Academy of Sciences

Researchers Develop Integrative Treatment of Tumor-related Bone Defects

Malignant bone tumors have caused great obstacles and serious illnesses for tumor recurrence and difficulty in reconstructing and repairing large defeats after tumorectomy due to the poor prognosis for metastatic relapse or recurrence for patients with the axial disease. In a study published in Chemical Engineering Journal, a research team from the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences (CAS) reported a novel therapeutic treatment of anti-tumor/bone repair by combination of MoS2 nanosheets with 3D printed bioactive borosilicate glass scaffolds.

　　Malignant bone tumors have caused great obstacles and serious illnesses for tumor recurrence and difficulty in reconstructing and repairing large defeats after tumorectomy due to the poor prognosis for metastatic relapse or recurrence for patients with the axial disease.
　　In a study published in Chemical Engineering Journal, a research team led by Prof. LI Jiusheng from the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences (CAS), collaborated with Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shenzhen University, etc. reported a novel therapeutic treatment of anti-tumor/bone repair by combination of MoS2 nanosheets with 3D printed bioactive borosilicate glass scaffolds.
　　Based on the proof of concept of “integrative treatment”, scientists reported for the first time on the concept of “integrative treatment” on local combating tumor and bone tissue repairing by integrating anti-tumor/bone repair functions together by fixing MoS2 on the surface of materials. The material’s properties, bioactive ability, photothermal stability and capability, osteogenesis and the anti-tumor ability of BGM composite scaffolds in vitro and vivo were later evaluated and investigated in this study.
　　The MoS2-integrated composite BG (BGM) scaffolds can rapidly and effectively elevate temperature, and they exhibited excellent photothermal stability. Notably, the BGM scaffolds can effectively reduce the viability of osteosarcoma cells (MNNG/HOS) in vitro as well as inhibit the tumor growth in nude mice. Furthermore, the prepared BGM scaffolds can stimulate the proliferation and differentiation of rat bone mesenchymal stem cells (rBMSCs), upregulate the expression of osteogenesis-related genes in vitro and promote in vivo bone repair in critical-sized rat calvarial defects.
　　Therefore, the “integrative treatment” BGM scaffolds have great potential to be applied in the treatment of anti-tumor and bone repair, offering ideas for the manufacture of new materials in the tissue engineering field.
　　Schematic diagram for investigation on the integrative treatment of anti-tumor/bone repairing with 3D printing BGM scaffolds (Image by SARI)
　　The study was supported by the National Natural Science Foundation, China (Grant Nos. 51802326) and Youth innovation promotion association of Chinese Academy of Sciences (Grant No. 2020292).
　　Contact: Wang Hui
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: wanghui01@sari.ac.cn

2020-07-17 more+

New Light-based Method Proposed for C(sp3)–H Functionalizations of Light Hydrocarbons

Intrinsic inertness of gaseous hydrocarbons requires harsh reaction conditions to enable C(sp3)–H bond cleavage, resulting in low-yielding and unselective transformation to high-value added chemicals. Motivated by such a challenge, a team collaborated by researchers from Eindhoven University of Technology, ShanghaiTech University and Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences reported a general and mild strategy to directly activate alkanes using decatungstate photocatalysis in flow.

　　Intrinsic inertness of gaseous hydrocarbons (e.g., ethane and methane) requires harsh reaction conditions to enable C(sp3)–H bond cleavage, resulting in low-yielding and unselective transformation to high-value added chemicals. Therefore, direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community.
　　Motivated by such a challenge, a team collaborated by researchers from Eindhoven University of Technology, ShanghaiTech University and Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences reported a general and mild strategy to directly activate alkanes using decatungstate photocatalysis in flow. The study was published in the latest issue of Science on July 3.
　　The newly developed method aims to irradiate the molecules with light in the presence of a suitable catalyst, thereby immediately converting low-weight hydrocarbons into more complex molecules at room temperature and low pressure. To achieve that, researchers had to address the following challenges: first, the cleavage of very strong aliphatic C–H bonds with a bond dissociation energy (BDE) between 96.5 and 105 kcal mol-1 (Figure 1B) and second, appropriate technologies to bring the alkanes and catalyst into close proximity with a suitable catalyst and reaction partner.
　　Given the photoexcited decatungstateanion (W10O324-) has enabled a number of synthetically useful C(sp3)–H functionalizations, scientists reasoned that the use of flow technology is indispensable to facilitate the gas-liquid decatungstate-mediated processes. Through investigation to optimize reaction conditions and transformation scope, scientists solved these two problems by exciting the alkanes with UV light (about 365 nm) in the presence of a suitable catalyst tetrabutylammonium decatungstate (TBADT) in flow.
　　This new method paves the way for the inexpensive production of some medicines, in view of the low cost of catalysts to activate the gaseous alkanes and simplification of reactions. Further research is needed to apply intensified reactors to increase production capacity.
　　Fig. 1 Decatungstate enables the direct C(sp3)–H activation of light hydrocarbons. (Image adapted from Science)
　　Contact: SUN Yuhan
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: sunyh@sari.ac.cn

2020-07-10 more+

NOW OPEN: The expression plasmids for all 29 proteins encoded by the COVID-19 virus are available for request

Now, expression plasmids for all these 29 proteins are available to global scientists through a Protein Bank Program (PBP) launched by the National Facility for Protein Science in Shanghai (NFPS).

2020-06-22 more+

Efficient Indium Oxide Catalysts Designed for CO2 Hydrogenation to Methanol

Catalytic hydrogenation of carbon dioxide is a green and sustainable means of synthesizing commodity chemicals such as methanol.Recent studies revealed the potential for a family of metal oxides to catalyze this reaction. However, further optimizing their catalytic performance for industrial applications remained a great challenge.A team at the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences reported a successful case of theory-guided rational design of indium oxide (In2O3) catalysts for CO2 hydrogenation to methanol with high activity and selectivity.

　　Catalytic hydrogenation of carbon dioxide (CO2) is a green and sustainable means of synthesizing commodity chemicals such as methanol. This conversion process is key to realizing the “methanol economy” or creating “liquid sunshine,” both aspects of the circular economy. Recent studies revealed the potential for a family of metal oxides to catalyze this reaction. However, further optimizing their catalytic performance for industrial applications remained a great challenge, mostly due to the difficulties related to the rational design and controlled synthesis of these catalysts.
　　Motivated by such a challenge, a team jointly led by Profs. SUN Yuhan, GAO Peng, and LI Shenggang at the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences, reported a successful case of theory-guided rational design of indium oxide (In2O3) catalysts for CO2 hydrogenation to methanol with high activity and selectivity. The new findings were published in the latest issue of Science Advances on June 17.
　　To rationally design In2O3-based nanocatalysts with favorable methanol synthesis performance, researchers carried out extensive density functional theory (DFT) calculations to establish the catalytic mechanism of the In2O3 catalyst during CO2 hydrogenation to methanol and carbon dioxide by identifying preferred pathways. The computational modeling identified the rarely studied {104} facet of hexagonal In2O3 as the most favorable for methanol synthesis.
　　On the basis of this theoretical prediction, several experimental methods were then employed to synthesize In2O3 catalysts in different phases with distinct morphologies.
　　Interestingly, one of the four In2O3 catalysts synthesized in this way was confirmed to mainly expose the theoretically identified {104} facets. This catalyst also exhibited the best performance in terms of both activity and selectivity, confirming the DFT prediction. The methanol synthesis reaction catalyzed by this catalyst is favorable even at the very high temperature of 360 °C.
　　The space-time yield of methanol reached 10.9 mmol/g/hour at this temperature, which surpassed all previously known catalysts for this reaction, including previously reported In2O3-based catalysts and well-known Cu-based catalysts.
　　The In2O3 catalyst discovered in this research is promising as a way to directly convert CO2 into methanol for industrial applications. In addition, the discovery of this In2O3 catalyst will promote the further development of oxide/zeolite bifunctional catalysts for direct CO2 hydrogenation to various C2+ hydrocarbons (lower olefins, gasoline, aromatics and so on) via the methanol intermediate. Just as importantly, this discovery also highlights the pivotal role of computational science in helping to design industrially relevant catalysts.
　　 Schematic illustration of the most favorable CO2 hydrogenation pathways on different cubic (c–In2O3) and hexagonal indium oxide (c–In2O3) surfaces (Figures adapted from Science Advances)
　　
　　 Structural characterization and catalytic performance of various In2O3 catalyst materials for CO2 hydrogenation (Figures adapted from Science Advances)
　　

2020-06-18 more+

SSRF Helps on the COVID-19 Structure Determination to Understand the Infection Mechanism and Drugs R&D

To meet the urgent needs of determining the protein structure, Shanghai Synchrotron Radiation Facility (SSRF) has opened a green channel to fully support the research teams carrying out studies related to COVID-19. At the end of January, SSRF promptly rebooted the accelerator that was shut down for maintenance. Three protein crystallography beamlines reopened: BL17U1, BL18U1 and BL19U1, which also played a significant role in the studies of the previous epidemic like H1N1, H7N9, MERS, Zika, and Ebola.

　　Since the outbreak of novel coronavirus 2019 (COVID-19), the number of confirmed cases has reached 1,016,000 worldwide and the global death has exceeded 53,000. This highly infectious disease is caused by the virus SARS-CoV-2. COVID-19 poses a great threat to human activities and keeps the world in suspense. A comprehensive knowledge of this novel virus will help fight against COVID-19. Several important proteins play a crucial role in the process of the virus infection. Structural information of these proteins will be helpful for the understanding of the infectious mechanism and offer a basis for the drug development. Macromolecular X-Ray Crystallographys using synchrotron radiation facility is an efficient technique to determine the 3-D structures of protein.
　　
　　To meet the urgent needs of determining the protein structure, Shanghai Synchrotron Radiation Facility (SSRF) has opened a green channel to fully support the research teams carrying out studies related to COVID-19. At the end of January, SSRF promptly rebooted the accelerator that was shut down for maintenance. Three protein crystallography beamlines reopened: BL17U1, BL18U1 and BL19U1, which also played a significant role in the studies of the previous epidemic like H1N1, H7N9, MERS, Zika, and Ebola.
　　
　　Since January 2020, SSRF has assisted research teams by arranging enough beam shifts (Jan. 12, Feb. 2-3, Feb. 11, Feb. 17, and Feb. 23) to carry out their studies on protein structure related to COVID-19 and selection of candidate active substances, including Zihe Rao team for the viral main protease (Mpro or also 3CLpro), Jianxun Qi and Xinquan Wang teams for the spike protein, and other teams for the drug screening.
　　
　　1. On January 12, 2020, the research team led by Zihe Rao and Haitao Yang at Shanghai Tech University collected the diffraction data of COVID-19 coronavirus 3CL hydrolase (Mpro) and took the lead in determining its high-resolution crystal structure. Related link:
　　https://www.rcsb.org/news?year=2020&article=5e39e03fa5007a04a313edc3
　　The crystal structure of COVID-19 Main protease in complex with an inhibitor N3 (PDB entry 6LU7)
　　
　　2. On February 11, 2020, the research team led by Jianxun Qi at Institute of Microbiology, CAS, collected the diffraction data of COVID-19 RBD-ACE2 and shared its 2.5 ANG crystal structure to the whole community. An article titled with “structural and functional basis of SARS-CoV2 entry by using human ACE2” was published on Cell.
　　DOI: 10.1016/j.cell.2020.03.045
　　Structure of novel coronavirus spike receptor-binding domain complexed with its receptor ACE2 (PDB entry 6LZG)
　　
　　3. On February 17, 2020, the research team led by Xinquan Wang and Linqi Zhang at Tsinghua University collected the diffraction data of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, then determined and shared its crystal structure. The article was published on Natural on March 30, 2020:
　　https://www.nature.com/articles/s41586-020-2180-5
　　Crystal structure of COVID-19 spike receptor-binding domain bound with ACE2
　　(PDB entry 6M0J))
　　
　　4. Moreover, beamtime was also allocated to the relevant drug screening. There are six research teams working on drug development at SSRF during this rapid access program simultaneously. Dozens of potential active substances are screened.
　　 SSRF will be available to all users very soon and also continue to give higher priority to drug development against COVID-19.

2020-04-07 more+

Researchers Reveal a Dynamic Mechanism for Ni–Au Bimetallic Nanoparticles during CO2 Hydrogenation

The high catalytic performance of core–shell nanoparticles (NP) is usually attributed to the syngergy of distinct geometric and electronic structures. Although the general assumption is that core–shell NPs maintain their configuration under working conditions, it remains unclear whether they maintain their structure throughout a reaction.Scientists recently reported a different working mechanism and demonstrated that the core–shell structure may not exist under a specific set of conditions, which overturns the conventional understanding.

　　The high catalytic performance of core–shell nanoparticles (NP) is usually attributed to the syngergy of distinct geometric and electronic structures. Although the general assumption is that core–shell NPs maintain their configuration under working conditions, it remains unclear whether they maintain their structure throughout a reaction.
　　Scientists recently reported a different working mechanism and demonstrated that the core–shell structure may not exist under a specific set of conditions, which overturns the conventional understanding.
　　
　　The results appear in a study conducted by a team from the Shanghai Advanced Research Institute (SARI) of the Chinese Academy of Sciences (CAS) along with other collaborators in the latest issue of Nature Catalysis entitled “Reversible loss of core–shell structure for Ni–Au bimetallic nanoparticles during CO2 hydrogenation.”
　　
　　The scientists use environmental transmission electron microscopy (ETEM) to directly visualize the dynamic process at atomic level, coupled with multiple state-of-the-art in situ techniques, including synchrotron X-ray absorption spectroscopy, infrared spectroscopy and theoretical simulations, to precisely analyze the imaging conditions of over 3,000 high-resolution transmission electron microscopy (TEM) images.
　　
　　By tracing the real-time changes of the surface atomic structure during the entire reaction process, the result exhibits a highly selective CO production in CO2 hydrogenation, features an intact ultrathin Au shell over the Ni core before and after the reaction. However, the catalytic performance could not be attributed to the Au shell surface, but rather to the formation of a transient reconstructed alloy surface, promoted by CO adsorption during the reaction.
　　
　　Density functional theory (DFT) calculations also confirmed that it is the kinetically alloyed surface, rather than the ultrathin Au shell surface, that is catalytically active during the highly selective reverse water gas shift reaction.
　　
　　The discovery of such a reversible transformation urges us to reconsider the reaction mechanism beyond the stationary model, and may have important implications not only for core–shell nanoparticles, but also for other well-defined nanocatalysts.
　　Dynamic Mechanism for Ni–Au Bimetallic Nanoparticles during CO2 Hydrogenation (Image by SARI)
　　In situ observation and theoretical interpretation of the structural transition of NiAu NPs during the reaction (Figures adapted from Nature Catalysis)
　　Contact: GAO Yi
　　Shanghai Advanced Research Institute, Chinese Academy of Sciences
　　Email: gaoyi@zjlab.org.cn
　　

2020-04-01 more+