Publications by authors named "Shuoguo Li"

12 Publications

  • Page 1 of 1

Reprint of "Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation".

Prog Biophys Mol Biol 2021 Mar 26;160:5-15. Epub 2021 Feb 26.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
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http://dx.doi.org/10.1016/j.pbiomolbio.2021.02.001DOI Listing
March 2021

Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation.

Prog Biophys Mol Biol 2020 10 3;156:3-13. Epub 2020 Aug 3.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
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http://dx.doi.org/10.1016/j.pbiomolbio.2020.07.009DOI Listing
October 2020

Furin-mediated intracellular self-assembly of olsalazine nanoparticles for enhanced magnetic resonance imaging and tumour therapy.

Nat Mater 2019 12 21;18(12):1376-1383. Epub 2019 Oct 21.

The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Among the strategies used for enhancement of tumour retention of imaging agents or anticancer drugs is the rational design of probes that undergo a tumour-specific enzymatic reaction preventing them from being pumped out of the cell. Here, the anticancer agent olsalazine (Olsa) was conjugated to the cell-penetrating peptide RVRR. Taking advantage of a biologically compatible condensation reaction, single Olsa-RVRR molecules were self-assembled into large intracellular nanoparticles by the tumour-associated enzyme furin. Both Olsa-RVRR and Olsa nanoparticles were readily detected with chemical exchange saturation transfer magnetic resonance imaging by virtue of exchangeable Olsa hydroxyl protons. In vivo studies using HCT116 and LoVo murine xenografts showed that the OlsaCEST signal and anti-tumour therapeutic effect were 6.5- and 5.2-fold increased, respectively, compared to Olsa without RVRR, with an excellent 'theranostic correlation' (R = 0.97) between the imaging signal and therapeutic response (normalized tumour size). This furin-targeted, magnetic resonance imaging-detectable platform has potential for imaging tumour aggressiveness, drug accumulation and therapeutic response.
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http://dx.doi.org/10.1038/s41563-019-0503-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872935PMC
December 2019

Chemoradiation versus oesophagectomy for locally advanced oesophageal cancer in Chinese patients: study protocol for a randomised controlled trial.

Trials 2019 Apr 11;20(1):206. Epub 2019 Apr 11.

The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, 24 Jinghua Road, Luoyang, 471003, China.

Background: Surgery is the gold standard treatment for local advanced disease, while definitive concurrent chemoradiotherapy (DCRT) is recommended for those who are medically unable to tolerate major surgery or medically fit patients who decline surgery. The primary aim of this trial is to compare the outcomes in Chinese patients with oesophageal squamous cell cancer with locally advanced resectable disease who have received either surgery or DCRT.

Methods/design: One hundred ninety-six patients with T1bN + M0 or T2-4aN0-2 M0 oesophageal squamous cell cancer will be randomised to the DCRT group or the surgery group. In the DCRT group, patients will be given intensity-modulated radiation therapy (IMRT) with 50 Gy/25 fractions and basic chemotherapy with 5-fluorouracil regimens. In the surgery group, patients will receive neoadjuvant chemoradiotherapy (NCRT) and standard oesophagectomy. Five years of follow-up will be scheduled for patients. The primary endpoints are 2-year/5-year overall survival; the secondary endpoints are 2-year/5-year progression-free survival, treatment-related adverse events and the patients' quality of life. The main evaluation methods include oesophagoscopy, endoscopic ultrasonography and biopsy, oesophageal barium meal, computed tomography, positron emission tomography-computed tomography, blood tests and questionnaires.

Discussion: The preponderant oesophageal cancer pathology type is dramatically different in western Caucasian and Asian oesophageal cancer patients: Caucasian patients present with 80% adenocarcinomas, and Asians patients present with 95% squamous cell carcinomas. This phenomenon needs more in-depth studies to elucidate the differences in these populations. Based on the results of this study, we will show whether DCRT will benefit patients more than oesophagectomy. This study will contribute more evidence to the management of oesophageal squamous cell cancer.

Trial Registration: ClinicalTrials.gov, NCT02972372 . Registered on 26 November 2016.
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http://dx.doi.org/10.1186/s13063-019-3316-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458742PMC
April 2019

Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination.

Nat Mater 2018 02 4;17(2):187-194. Epub 2018 Jan 4.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.

A major challenge in vaccine formulations is the stimulation of both the humoral and cellular immune response for well-defined antigens with high efficacy and safety. Adjuvant research has focused on developing particulate carriers to model the sizes, shapes and compositions of microbes or diseased cells, but not antigen fluidity and pliability. Here, we develop Pickering emulsions-that is, particle-stabilized emulsions that retain the force-dependent deformability and lateral mobility of presented antigens while displaying high biosafety and antigen-loading capabilities. Compared with solid particles and conventional surfactant-stabilized emulsions, the optimized Pickering emulsions enhance the recruitment, antigen uptake and activation of antigen-presenting cells, potently stimulating both humoral and cellular adaptive responses, and thus increasing the survival of mice upon lethal challenge. The pliability and lateral mobility of antigen-loaded Pickering emulsions may provide a facile, effective, safe and broadly applicable strategy to enhance adaptive immunity against infections and diseases.
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http://dx.doi.org/10.1038/nmat5057DOI Listing
February 2018

High-vacuum optical platform for cryo-CLEM (HOPE): A new solution for non-integrated multiscale correlative light and electron microscopy.

J Struct Biol 2018 01 4;201(1):63-75. Epub 2017 Nov 4.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, CAS, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Cryo-correlative light and electron microscopy (cryo-CLEM) offers a unique way to analyze the high-resolution structural information of cryo-vitrified specimen by cryo-electron microscopy (cryo-EM) with the guide of the search for unique events by cryo-fluorescence microscopy (cryo-FM). To achieve cryo-FM, a trade-off must be made between the temperature and performance of objective lens. The temperature of specimen should be kept below devitrification while the distance between the objective lens and specimen should be short enough for high resolution imaging. Although special objective lens was designed in many current cryo-FM approaches, the unavoided frosting and ice contamination are still affecting the efficiency of cryo-CLEM. In addition, the correlation accuracy between cryo-FM and cryo-EM would be reduced during the current specimen transfer procedure. Here, we report an improved cryo-CLEM technique (high-vacuum optical platform for cryo-CLEM, HOPE) based on a high-vacuum optical stage and a commercial cryo-EM holder. The HOPE stage comprises of a special adapter to suit the cryo-EM holder and a high-vacuum chamber with an anti-contamination system. It provides a clean and enduring environment for cryo specimen, while the normal dry objective lens in room temperature can be used via the optical windows. The 'touch-free' specimen transfer via cryo-EM holder allows least specimen deformation and thus maximizes the correlation accuracy between cryo-FM and cryo-EM. Besides, we developed a software to perform semi-automatic cryo-EM acquisition of the target region localized by cryo-FM. Our work provides a new solution for cryo-CLEM and can be adapted for different commercial fluorescence microscope and electron microscope.
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http://dx.doi.org/10.1016/j.jsb.2017.11.002DOI Listing
January 2018

Using integrated correlative cryo-light and electron microscopy to directly observe syntaphilin-immobilized neuronal mitochondria .

Biophys Rep 2017 21;3(1):8-16. Epub 2017 Mar 21.

National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.

Correlative cryo-fluorescence and cryo-electron microscopy (cryo-CLEM) system has been fast becoming a powerful technique with the advantage to allow the fluorescent labeling and direct visualization of the close-to-physiologic ultrastructure in cells at the same time, offering unique insights into the ultrastructure with specific cellular function. There have been various engineered ways to achieve cryo-CLEM including the commercial FEI iCorr system that integrates fluorescence microscope into the column of transmission electron microscope. In this study, we applied the approach of the cryo-CLEM-based iCorr to image the syntaphilin-immobilized neuronal mitochondria to test the performance of the FEI iCorr system and determine its correlation accuracy. Our study revealed the various morphologies of syntaphilin-immobilized neuronal mitochondria that interact with microtubules and suggested that the cryo-CLEM procedure by the FEI iCorr system is suitable with a half micron-meter correlation accuracy to study the cellular organelles that have a discrete distribution and large size, mitochondrion, Golgi complex, lysosome, .
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http://dx.doi.org/10.1007/s41048-017-0035-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515996PMC
March 2017

Inhibition of glycogen synthase kinase 3 beta (GSK3β) suppresses the progression of esophageal squamous cell carcinoma by modifying STAT3 activity.

Mol Carcinog 2017 10 4;56(10):2301-2316. Epub 2017 Jul 4.

Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky.

Although GSK3β has been reported to have contrasting effects on the progression of different tumors, it's possible functions in esophageal squamous cell carcinoma (ESCC) and the related molecular mechanisms remain unknown. Here, we investigated the expression, function, and molecular mechanism of GSK3β in the development of ESCC in vitro and in vivo. Though the expression of total GSK3β was significantly increased, the phosphorylated (inactivated) form of GSK3β (Ser9) was concurrently decreased in the cancerous tissues of patients with ESCC compared with controls, suggesting that GSK3β activity was enhanced in cancerous tissues. Further pathological data analysis revealed that higher GSK3β expression was associated with poorer differentiation, higher metastasis rates, and worse prognosis of ESCC. These results were confirmed in different ESCC cell lines using a pharmacological inhibitor and specific siRNA to block GSK3β. Using a cancer phospho-antibody array, we found that STAT3 is a target of GSK3β. GSK3 inhibition reduced STAT3 phosphorylation, and overexpression of constitutively active GSK3β had the opposite effect. Moreover, STAT3 inhibition mimicked the effects of GSK3β inhibition on ESCC cell migration and viability, while overexpression of a plasmid encoding mutant STAT3 (Y705F) abrogated these effects, and these results were further substantiated by clinicopathological data. In addition, a GSK3 inhibitor (LiCl) and/or STAT3 inhibitor (WP-1066) efficiently suppressed the growth of ESCC cells in a xenograft tumor model. Altogether, these results reveal that higher GSK3β expression promotes ESCC progression through STAT3 in vitro and in vivo, and GSK3β-STAT3 signaling could be a potential therapeutic target for ESCC treatment.
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http://dx.doi.org/10.1002/mc.22685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583014PMC
October 2017

Expression of serum- and glucocorticoid-regulated kinase 1 and its association with clinicopathological factors and the survival of patients with adenocarcinoma of the esophagogastric junction.

Oncol Lett 2017 May 27;13(5):3572-3578. Epub 2017 Mar 27.

Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan 455000, P.R. China.

While the aberrant expression and the controversial results of serum- and glucocorticoid-regulated kinase (SGK1) have been reported in a number of malignancies, the expression of SGK1 and its possible association with the progression of adenocarcinoma in the esophagogastric junction (AEG) remain to be elucidated. To the best of our knowledge, the expression and localization of SGK1 was examined for the first time in the present study in cancerous and adjacent tissue from 60 patients with AEG, and compared with 20 healthy mucosa control tissue samples. Furthermore, the association between SGK1 expression and the clinicopathological characteristics, and prognosis of patients with AEG was statistically analyzed. The expression level of SGK1 was identified to be significantly higher (P<0.0001) in the cancerous AEG tissue samples (65%) compared with that of the adjacent tissue (31.7%) and healthy control (10%) samples. Enhanced SGK1 was primarily localized in the cytoplasm and the expression level of SGK1 was associated with the differentiation (P=0.045) and lymph node metastasis (P=0.006) of AEG. Notably, increased expression of SGK1 was demonstrated to be significantly correlated with poor overall survival (P=0.027). The results of the present study revealed the expression profile of SGK1 in AEG and demonstrated that SGK1 expression in cancerous tissue is an indicator for the progression of AEG. Thus, SGK1 may be a potential molecular marker for the diagnosis, interference therapy and prognosis of AEG.
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http://dx.doi.org/10.3892/ol.2017.5927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431499PMC
May 2017

Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer.

Infect Agent Cancer 2016 19;11. Epub 2016 Jan 19.

Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003 China ; Department of Oncology, Henan University of Science and Technology, 24 Jinghua Road, Jianxi Qu, Luoyang, 471500 Henan China.

Background: Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, we examined the presence of P. gingivalis in esophageal mucosa, and the relationship between P. gingivalis infection and the diagnosis and prognosis of ESCC.

Methods: The presence of P. gingivalis in the esophageal tissues from ESCC patients and normal controls was examined by immunohistochemistry using antibodies targeting whole bacteria and its unique secreted protease, the gingipain Kgp. qRT-PCR was used as a confirmatory approach to detect P. gingivalis 16S rDNA. Clinicopathologic characteristics were collected to analyze the relationship between P. gingivalis infection and development of ESCC.

Results: P. gingivalis was detected immunohistochemically in 61 % of cancerous tissues, 12 % of adjacent tissues and was undetected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis 16S rDNA was also observed. Moreover, statistic correlations showed P. gingivalis infection was positively associated with multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.

Conclusion: These findings demonstrate for the first time that P. gingivalis infects the epithelium of the esophagus of ESCC patients, establish an association between infection with P. gingivalis and the progression of ESCC, and suggest P. gingivalis infection could be a biomarker for this disease. More importantly, these data, if confirmed, indicate that eradication of a common oral pathogen could potentially contribute to a reduction in the overall ESCC burden.
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http://dx.doi.org/10.1186/s13027-016-0049-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717526PMC
January 2016

MicroRNA-645, up-regulated in human adencarcinoma of gastric esophageal junction, inhibits apoptosis by targeting tumor suppressor IFIT2.

BMC Cancer 2014 Aug 29;14:633. Epub 2014 Aug 29.

Oncology Department of the First Affiliated Hospital of Henan, University of Science and Technology, No, 24 Jinghua Road, Luoyang, Henan, China.

Background: An increasing body of evidence indicates that miRNAs have a critical role in carcinogenesis and cancer progression; however, the role of miRNAs in the tumorigenesis of adencarcinoma of gastric esophageal junction (AGEJ) remains largely unclear.

Methods: The SGC7901 and BGC-823 gastric cancer cell lines were used. The expressions of miR-645 and IFIT2 (Interferon-induced protein with tetratricopeptide repeats 2) were examined by qRT-PCR, The expressions of IFIT2 was examined by western blotting and immunohistochemistry assay. The cell apoptosis was determined by FACS. MiR-645 inhibitor, mimics and plasmid-IFIT2 transfections were performed to study the loss- and gain-function. Caspase-3/7 activity was examined by caspase-3/7 assay.

Results: In the present study, we have reported an increased expression of miR-645 in AGEJ clinical specimens compared with paired non-cancerous tissues. We also observed a significant miR-645 up-regulation in two gastric cancer (GC) cell lines, SGC7901 and BGC-823, which were used as cell models because there was no available AGEJ cell lines established to date. We found that inhibition of miR-645 could sensitize dramatically SGC7901 and BGC-823 cells to both serum starvation- and chemotherapeutic drug-induced apoptosis by up-regulating IFIT2, a mediator of apoptosis via a mitochondrial pathway, with a potential binding site for miR-645 in its mRNA's 3'UTR. Further investigation exhibited that IFIT2 expression decreases in SGC7901 and BGC-823 cells and AGEJ tissues. IFIT2 ectopic expression leads to promotion of cell apoptosis, indicating that IFIT2 may function as a suppressor in the development of AGEJ. Furthermore, inhibition of miR-645 induces up-regulation of IFIT2 and increased caspase-3/7 activity compared with control groups.

Conclusions: Our data suggest that miR-645 functions as an oncogene in human AGEJ by, at least partially through, targeting IFIT2.
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http://dx.doi.org/10.1186/1471-2407-14-633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161885PMC
August 2014

Are ATPase6 polymorphisms associated with osteosarcoma?

Exp Mol Pathol 2014 Jun 12;96(3):446-7. Epub 2014 Feb 12.

Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan, China.

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http://dx.doi.org/10.1016/j.yexmp.2014.01.004DOI Listing
June 2014