Publications by authors named "Shu Guo"

139 Publications

Current Status of MicroRNAs that Target the Wnt Signaling Pathway in Regulation of Osteogenesis and Bone Metabolism: A Review.

Med Sci Monit 2021 Apr 8;27:e929510. Epub 2021 Apr 8.

Department of Plastic Surgery, The First Hopital of China Medical University, Shenyang, Liaoning, China (mainland).

The directional differentiation of bone mesenchymal stem cells (BMSCs) is regulated by a variety of transcription factors and intracellular signaling pathways. In the past, it was thought that the directional differentiation of BMSCs was related to transforming growth factors, such as bone morphogenetic protein (BMP) and MAPK pathway. However, in recent years, some scholars have pointed out that the Wnt signaling pathway, which is a necessary complex network of protein interactions for biological growth and development, takes a significant role in this process and plays a major part in regulating the development of osteoblasts by exerting signal transduction into cells. Also, they have proved the Wnt protein therapeutic truly have positive effects on the viability and osteogenic capacity of bone graft. Recent studies have shown that microRNAs (miRNAs) play an important regulatory role in this process. MiRNAs such as miRNA-218, miRNA-335, miRNA-29, microRNA-30 and other miRNAs exert negative or positive effects on some crucial molecules in the Wnt/ß-catenin pathway, which in turn affect bone metabolism and osteopathy. Thus, miRNAs have been suggested as therapeutic targets for some metabolic bone diseases. This article aims to provide an update on the current status of microRNAs that target the Wnt signaling pathway in the regulation of osteogenesis and bone metabolism and includes a discussion of future areas of research, which can be a theoretical basis for bone metabolism-related diseases.
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http://dx.doi.org/10.12659/MSM.929510DOI Listing
April 2021

PolG Inhibits Gastric Cancer Glycolysis and Viability by Suppressing PKM2 Phosphorylation.

Cancer Manag Res 2021 16;13:1559-1570. Epub 2021 Feb 16.

Department of Plastic Surgery, China Medical University the First Hospital, Shenyang, 110001, Liaoning Province, People's Republic of China.

Purpose: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related death. There is a critical need for the development of novel therapies in GC. DNA polymerase gamma (PolG) has been implicated in mitochondrial homeostasis and affects the development of numerous types of cancer, however, its effects on GC and molecular mechanisms remain to be fully determined. The aim of the present research was to clarify the effects of PolG on GC and its possible molecular mechanism of action.

Methods: The GSE62254 dataset was used to predict the effect of PolG on prognostic value in GC patients. Lentivirus-mediated transduction was used to silence PolG expression. Western blot analysis evinced the silencing effect. Co-immunoprecipitation (Co-IP) analysis was performed to explore the potential molecular mechanism of action. Analysis of the glycolysis process in GC cells was also undertaken. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Cell migration was detected using the Transwell device. Animal experiments were used to measure in vivo xenograft tumor growth.

Results: GC patients with low PolG expression have worse overall survival (OS) and progression-free survival (PFS). PolG binds to PKM2 and affects the activation of Tyr105-site phosphorylation, thus interfering with the glycolysis of GC cells. In vitro tumor formation experiments in mice also confirmed that PolG silencing of GC has a stronger proliferation ability. PolG can suppress GC cell growth both in vivo and in vitro.

Conclusion: Our study reveals a potential molecular mechanism between PolG and the energy metabolic process of GC tumor cells for the first time, suggesting PolG as an independent novel potential therapeutic target for tumor therapy, and providing new ideas for clinical GC treatment.
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http://dx.doi.org/10.2147/CMAR.S292306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896732PMC
February 2021

Applications of 3D printed bone tissue engineering scaffolds in the stem cell field.

Regen Ther 2021 Mar 5;16:63-72. Epub 2021 Feb 5.

Department of Plastic Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, Liaoning, People's Republic of China.

Due to traffic accidents, injuries, burns, congenital malformations and other reasons, a large number of patients with tissue or organ defects need urgent treatment every year. The shortage of donors, graft rejection and other problems cause a deficient supply for organ and tissue replacement, repair and regeneration of patients, so regenerative medicine came into being. Stem cell therapy plays an important role in the field of regenerative medicine, but it is difficult to fill large tissue defects by injection alone. The scientists combine three-dimensional (3D) printed bone tissue engineering scaffolds with stem cells to achieve the desired effect. These scaffolds can mimic the extracellular matrix (ECM), bone and cartilage, and eventually form functional tissues or organs by providing structural support and promoting attachment, proliferation and differentiation. This paper mainly discussed the applications of 3D printed bone tissue engineering scaffolds in stem cell regenerative medicine. The application examples of different 3D printing technologies and different raw materials are introduced and compared. Then we discuss the superiority of 3D printing technology over traditional methods, put forward some problems and limitations, and look forward to the future.
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http://dx.doi.org/10.1016/j.reth.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868584PMC
March 2021

Emergency Department Experience in the Multi-dimensional Prevention and Control of Pneumonic Plague in Beijing.

Biomed Environ Sci 2020 Dec;33(12):948-952

Department of Emergency, Beijing Chao-Yang Hospital, Affiliated to Capital Medical University, Beijing 100020, China.

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http://dx.doi.org/10.3967/bes2020.131DOI Listing
December 2020

The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways.

Stem Cell Res Ther 2021 Jan 18;12(1):64. Epub 2021 Jan 18.

Department of Plastic Surgery, The First Hospital of China Medical University, NO 155 Nanjing street Heping Strict, Shenyang, 110001, Liaoning Province, China.

Background: Human adipose-derived stem cells (hADSCs) are stem cells with the potential to differentiate in multiple directions. miR-204-5p is expressed at low levels during the osteogenic differentiation of hADSCs, and its specific regulatory mechanism remains unclear. Here, we aimed to explore the function and possible molecular mechanism of miR-204-5p in the osteogenic differentiation of hADSCs.

Methods: The expression patterns of miR-204-5p, Runx2, alkaline phosphatase (ALP), osteocalcin (OCN), forkhead box C1 (FOXC1) and growth differentiation factor 7 (GDF7) in hADSCs during osteogenesis were detected by qRT-PCR. Then, ALP and alizarin red staining (ARS) were used to detect osteoblast activities and mineral deposition. Western blotting was conducted to confirm the protein levels. The regulatory relationship among miR-204-5p, FOXC1 and GDF7 was verified by dual-luciferase activity and chromatin immunoprecipitation (ChIP) assays.

Results: miR-204-5p expression was downregulated in hADSC osteogenesis, and overexpression of miR-204-5p suppressed osteogenic differentiation. Furthermore, the levels of FOXC1 and GDF7 were decreased in the miR-204-5p mimics group, which indicates that miR-204-5p overexpression suppresses the expression of FOXC1 and GDF7 by binding to their 3'-untranslated regions (UTRs). Overexpression of FOXC1 or GDF7 improved the inhibition of osteogenic differentiation of hADSCs induced by the miR-204-5p mimics. Moreover, FOXC1 was found to bind to the promoter of miR-204-5p and GDF7, promote the deacetylation of miR-204-5p and reduce the expression of miR-204-5p, thus promoting the expression of GDF7 during osteogenic differentiation. GDF7 induced hADSC osteogenesis differentiation by activating the AKT and P38 signalling pathways.

Conclusions: Our results demonstrated that the miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of hADSCs via the AKT and p38 signalling pathways. This study further revealed the regulatory mechanism of hADSC differentiation from the perspective of miRNA regulation.
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http://dx.doi.org/10.1186/s13287-020-02117-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814734PMC
January 2021

Osteogenically-induced exosomes stimulate osteogenesis of human adipose-derived stem cells.

Cell Tissue Bank 2021 Mar 20;22(1):77-91. Epub 2020 Nov 20.

Department of Plastic surgery, The First affiliated Hospital of China Medical University, No 155 Nanjing North Street, Shenyang, 110002, China.

Exosomes exhibit great therapeutic potential in bone tissue engineering. The study aimed to investigate whether the exosomes derived from human adipose-derived stem cells (hADSCs-Exos) during different time-span of osteogenic differentiation could promote osteogenesis. The appropriate concentrations of hADSCs-Exos to enhance the proliferation, migration and osteogenesis of hADSCs-Exos were also examined. PKH67 labelled hADSCs-Exos was used to detect the internalization ability of hADSCs. The osteogenic differentiation abilities of hADSCs after treatment with hADSCs-Exos was evaluated by Alizarin red staining (ARS). The proliferation and migration of hADSCs was examined by cell counting kit-8 and wound healing assay, respectively. The expression of exosomal surface markers and osteoblast-related protein of hADSCs was assessed by Western blot. PKH67-labelled exosomes were internalized by hADSCs after 4 h incubation. ARS showed that the amount of mineralized nodules in Exo group was significantly higher than that in Exo group. hADSCs-Exos could promote the proliferation and migration capacity of hADSCs. Western blot analysis showed that after hADSCs-Exos treatment, ALP and RUNX2 were significantly enhanced. Specially, the Exo group of 15 μg/mL significantly upregulated the expression of RUNX2 than the other exosomes treated groups. Our findings suggest that exosomes secreted by hADSCs during osteogenic induction for 1-14 days could be efficiently internalized by hADSCs and could induce osteogenic differentiation of hADSCs. Moreover, administration of Exo at 15 μg/mL promoted the proliferation and migration of hADSCs. In conclusion, our research confirmed that comprised of hADSCs-Exos and hADSCs may provide a new therapeutic paradigm for bone tissue engineering.
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http://dx.doi.org/10.1007/s10561-020-09867-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864848PMC
March 2021

Preparation and antioxidant activities of polysaccharides obtained from abalone viscera by combination of enzymolysis and multiple separation methods.

J Food Sci 2020 Dec 14;85(12):4260-4270. Epub 2020 Nov 14.

College of Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, China.

Abalone viscera were byproducts of the abalone processing and usually discarded as wastes. In this study, we tried to obtain functional polysaccharides from abalone viscera by a combination of enzymatic hydrolysis, membrane separation, anion exchange chromatography, and gel filtration techniques. Abalone viscera underwent successive hydrolyzation with alcalase and flavourzyme. Each enzymolysis was followed by deproteinization via membrane separation. The final yield of crude abalone viscera polysaccharide (CAVP) was 19.72%; the polysaccharide content of CAVP was 51.75%. Furthermore, three fractions of polysaccharides (AVP1, AVP2, and AVP3) were isolated from the CAVP by anion exchange chromatography and gel filtration. The molecular weights of each AVP were 14.99 kDa, 58.48 kDa, and 39.63 kDa, with a carbohydrate content of 62.75, 23.09, and 44.67%, respectively. These AVPs showed excellent antioxidant activities in vitro. Our results provide a scientific basis for the further utilization of polysaccharides from abalone viscera. PRACTICAL APPLICATION: This study demonstrated an eco-friendly approach for industrial production of high purity animal-derived polysaccharides without any environmental pollution caused by the viscera waste of abalone and promoting the comprehensive utilization of abalone resources.
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http://dx.doi.org/10.1111/1750-3841.15520DOI Listing
December 2020

Exosomal PD-L1: New Insights Into Tumor Immune Escape Mechanisms and Therapeutic Strategies.

Front Cell Dev Biol 2020 15;8:569219. Epub 2020 Oct 15.

Cancer Therapy Research Institute, The First Affiliated Hospital of China Medical University, Shenyang, China.

As a classical immune checkpoint molecule, PD-L1 on the surface of tumor cells plays a pivotal role in tumor immunosuppression, primarily by inhibiting the antitumor activities of T cells by binding to its receptor PD-1. PD-1/PD-L1 inhibitors have demonstrated unprecedented promise in treating various human cancers with impressive efficacy. However, a significant portion of cancer patients remains less responsive. Therefore, a better understanding of PD-L1-mediated immune escape is imperative. PD-L1 can be expressed on the surface of tumor cells, but it is also found to exist in extracellular forms, such as on exosomes. Recent studies have revealed the importance of exosomal PD-L1 (ExoPD-L1). As an alternative to membrane-bound PD-L1, ExoPD-L1 produced by tumor cells also plays an important regulatory role in the antitumor immune response. We review the recent remarkable findings on the biological functions of ExoPD-L1, including the inhibition of lymphocyte activities, migration to PD-L1-negative tumor cells and immune cells, induction of both local and systemic immunosuppression, and promotion of tumor growth. We also discuss the potential implications of ExoPD-L1 as a predictor for disease progression and treatment response, sensitive methods for detection of circulating ExoPD-L1, and the novel therapeutic strategies combining the inhibition of exosome biogenesis with PD-L1 blockade in the clinic.
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http://dx.doi.org/10.3389/fcell.2020.569219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593554PMC
October 2020

Novel mutation of the TJP2 gene in a Chinese child with progressive cholestatic liver disease coexistent with hearing impairment.

Hepatobiliary Pancreat Dis Int 2020 Oct 27. Epub 2020 Oct 27.

Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

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http://dx.doi.org/10.1016/j.hbpd.2020.10.004DOI Listing
October 2020

How Does Chronic Intermittent Hypoxia Influence Upper Airway Stability in Rats?

Nat Sci Sleep 2020 15;12:749-758. Epub 2020 Oct 15.

Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, People's Republic of China.

Background: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway collapse during sleep. The contraction of upper airway dilator muscles plays a crucial role in maintaining UA patency. Chronic intermittent hypoxia (CIH) is the most important pathophysiological process of OSA. Exposure to CIH induced not only the damage of dilator muscles but also the plasticity of the muscles. This study aimed to dynamically assess the influence of CIH on the upper airway.

Methods: The experiments were performed on 44 rats. They were randomly divided into a normoxia (NO) group (n=22) and CIH group (n=22). In each group (n=6, respectively), EMG, transcranial magnetic stimulation (TMS) response, and critical pressure (Pcrit) value were recorded on day 0 (the day before exposure), and the 7th, 14th, 21st, and 28th day of air/CIH exposure. For each group, 16 rats were used for transmission electron microscopy observations on day 0, and the 7th, 14th and 28th day of air/CIH exposure (n=4 for every time point).

Results: Compared to the NO group at the same point, the CIH group showed a damaged ultrastructure of genioglossus, increased activity of genioglossus corticomotor area, and increased Pcrit of the upper airway from the 7th to the 28th day of CIH. Increased EMG activity occurred at the 14th day of CIH and lasted for 2 weeks.

Conclusion: The elevated genioglossus corticomotor excitability in response to the CIH could not counterbalance the damage effect of CIH on upper airway dilator muscles, which ultimately increased the collapsibility of the upper airway.
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http://dx.doi.org/10.2147/NSS.S249948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573330PMC
October 2020

Endoscopic retrograde cholangiopancreatography in the treatment of pancreaticopleural fistula in children.

World J Gastroenterol 2020 Oct;26(37):5718-5730

China National Clinical Research Center of Respiratory Diseases, Department of Respiratory, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Background: Pancreaticopleural fistula (PPF) is a rare disease, especially in children. Conservative treatment and surgery are traditional therapies, but surgery is invasive. The emergence of endoscopic retrograde cholangiopancreatography (ERCP) has provided a new noninvasive treatment for PPF and may become the first choice for children with PPF.

Aim: To explore the treatment response to ERCP for PPF in children.

Methods: Seven children with PPF were hospitalized in the Gastroenterology Department of Beijing Children's Hospital from December 2007 to May 2019. Data on these seven patients' clinical characteristics, diagnosis, treatments, and outcomes were analyzed, and their treatment responses following surgery and ERCP were compared. The correlation between the length of hospital stay and conservative treatment was analyzed. Peer-reviewed articles written in English and Chinese published from January 2009 to December 2019 were obtained from various open data sources and reviewed.

Results: The seven patients comprised three boys and four girls with a mean age of 6.57 ± 3.26 years. The main symptoms were chest tightness and pain ( = 4), intermittent fever ( = 3), dyspnea ( = 3), and abdominal pain ( = 1), and all patients had bloody pleural effusion. All seven patients were diagnosed with PPF by magnetic resonance cholangiopancreatography, and all were initially treated conservatively for a mean of 34.67 ± 22.03 d with a poor response. Among five patients who underwent ERCP, one required surgery because of intubation failure; thus, the success rate of ERCP was 80%. Two patients were successfully treated with surgery (100%). The postoperative hospital stay of the two patients treated by surgery was 20 and 30 d, respectively (mean of 25 d), and that of the four patients treated by ERCP ranged from 12 to 30 d (mean of 19.25 ± 8.85 d). The recovery time after ERCP was short [time to oral feeding, 4-6 d (mean, 5.33 ± 1.15 d); duration of closed thoracic drainage, 2-22 d (mean, 13.3 d)]. Analysis of previous cases of PPF published worldwide during the past decade showed that the treatment success rate of ERCP is not lower than that of surgery. There was no significant difference in the postoperative hospital stay between surgery (16 ± 10.95 d) and ERCP (18.7 ± 6.88 d, > 0.05). A positive linear correlation was found between the overall hospital stay and ERCP intervention time ( = 0.9992).

Conclusion: ERCP is recommended as the first-choice treatment for PPF in children. ERCP should be performed as early as possible if conditions permit.
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http://dx.doi.org/10.3748/wjg.v26.i37.5718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545396PMC
October 2020

Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs.

Neuron 2020 11 5;108(4):784-796.e3. Epub 2020 Oct 5.

Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, College of Medicine, Genetics Institute, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, Norman Fixel Institute for Neurological Disease, University of Florida, Gainesville, FL 32610, USA. Electronic address:

Mordes et al. (2020) did not detect the survival or motor phenotypes in C9orf72 BAC transgenic mice originally described by Liu et al. (2016). We discuss methodological differences between the Mordes and Liu studies, several additional studies in which survival and motor phenotypes were found, and possible environmental and genetic effects. First, Nguyen et al. (2020) showed robust ALS/FTD phenotypes in C9-BAC versus non-transgenic (NT) mice and that α-GA treatment improved survival, behavior, and neurodegeneration. The groups of Gelbard and Saxena also show decreased survival of C9-BAC versus NT mice and neuropathological and behavioral deficits similar to those shown by Liu et al. (2016). Although FVB/N mice can have seizures, increases in seizure severity and death of C9 and NT animals, which may mask C9 disease phenotypes, have been observed in recent C9-500 FVB/NJ-bred cohorts. In summary, we provide an update on phenotypes seen in FVB C9-BAC mice and additional details to successfully use this model. This Matters Arising Response paper addresses the Mordes et al. (2020) Matters Arising paper, published concurrently in Neuron.
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http://dx.doi.org/10.1016/j.neuron.2020.09.009DOI Listing
November 2020

Distribution and risk factor analysis for -associated diarrhea among hospitalized children over one year of age.

Pediatr Investig 2020 Mar 28;4(1):37-42. Epub 2019 Oct 28.

Department of Gastroenterology Beijing Children' s Hospital Faculty of Digestive Diseases Capital Medical University National Clinical Research Center f or Digestive Diseases Beijing 100045 China.

Importance: associated diarrhea (CDAD) is a severe type of antibiotic-associated diarrhea (AAD). However, the risk factors for CDAD in children with AAD have not yet been clarified.

Objective: To investigate the distribution and risk factors for CDAD among hospitalized children in Beijing Children's Hospital.

Methods: Stool samples from 197 children with AAD were tested for the pathogenic genes ( and ) using polymerase chain reaction between January 2011 and January 2014. Children who tested positive for or were included in the CDAD group, and those remaining comprised the non-CDAD group.

Results: The rate of CDAD among the 197 children with AAD was 42.6% (84/197). The age distribution was 1-15.6 years, among which the majority of children (54.8%, 46/84) were aged 1-4 years. Differences in the CDAD-positive rates among AAD children belonging to different age groups were not statistically significant. Univariate analysis revealed that the duration of antibiotic therapy, the length of hospitalization prior to diarrhea, and gastrointestinal tract operations were significant risk factors ( 0.05). Children with CDAD underwent more antibiotic therapy and had longer periods of hospitalization prior to diarrhea onset than children in the non-CDAD group. Using multivariate regression analysis, hospitalization for ≥ 10 days prior to diarrhea was found to be an independent risk factor for CDAD.

Interpretation: This study revealed that the length of hospitalization (≥ 10 days) prior to diarrhea was an independent risk factor for CDAD in children with AAD.
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http://dx.doi.org/10.1002/ped4.12155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331383PMC
March 2020

Immunosuppressive Property of MSCs Mediated by Cell Surface Receptors.

Front Immunol 2020 28;11:1076. Epub 2020 Jul 28.

Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China.

In the past decade, mesenchymal stem cells (MSCs) tend to exhibit inherent tropism for refractory inflammatory diseases and engineered MSCs have appeared on the market as therapeutic agents. Recently, engineered MSCs target to cell surface molecules on immune cells has been a new strategy to improve MSC applications. In this review, we discuss the roles of multiple receptors (ICAM-1, Gal-9, PD-L1, TIGIT, CD200, and CXCR4) in the process of MSCs' immunosuppressive properties. Furthermore, we discuss the principles and strategies for developing receptor-regulated MSCs and their mechanisms of action and the challenges of using MSCs as immunosuppressive therapies.
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http://dx.doi.org/10.3389/fimmu.2020.01076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399134PMC
March 2021

Synthesis, structure, and magnetism of BCC KIrO.

Dalton Trans 2020 Sep;49(34):12018-12024

Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.

KIrO3 in the body-centered cubic variant of the KSbO3-type structure is reported. Black cube-shaped single crystals, obtained from the solid-state reaction in a half-closed silver capsule in a sealed quartz tube, were used for the structural characterization by single-crystal X-ray diffraction. The material, space group Im3[combining macron] (no. 204), exhibits a disordered K array and a three-dimensional (3D) IrO6-based tunnel-like framework. Temperature-dependent magnetization and heat capacity measurements suggest a paramagnetic state for KIrO3, with significant contribution of temperature independent paramagnetism and without any sign of long-range magnetic ordering (down to 1.8 K). The 3D motif of this material, based on the 5d Ir5+ ion, is of interest for investigating unconventional magnetism.
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http://dx.doi.org/10.1039/d0dt01836hDOI Listing
September 2020

Exosomal miR-130a-3p regulates osteogenic differentiation of Human Adipose-Derived stem cells through mediating SIRT7/Wnt/β-catenin axis.

Cell Prolif 2020 Oct 17;53(10):e12890. Epub 2020 Aug 17.

Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China.

Objectives: It is of profound significance for clinical bone regeneration to clarify the specific molecular mechanism from which we found that osteogenic differentiation of adipose-derived stem cells (ADSCs) will be probably promoted by exosomes.

Materials And Methods: By means of lentiviral transfection, miR-130a-3p overexpression and knockdown ADSCs were constructed. Alizarin Red S was used to detect the calcium deposits, and qPCR was used to detect osteogenesis-related genes, to verify the effect of miR-130a-3p on the osteogenic differentiation of ADSCs. CCK-8 was used to detect the effect of miR-130a-3p on the proliferation of ADSCs. The target binding between miR-130a-3p and SIRT7 was verified by dual-luciferase reporter gene assay. Furthermore, the role of Wnt signalling pathway in the regulation of ADSCs osteogenesis and differentiation by miR-130a-3p was further verified by detecting osteogenic-related genes and proteins and alkaline phosphatase activity.

Results: (a) Overexpression of miR-130a-3p can enhance the osteogenic differentiation of ADSCs while reducing protein and mRNA levels of SIRT7, a target of miR-130a-3p. (b) Our study further found that overexpression of miR-130a-3p leads to down-regulation of SIRT7 expression with up-regulation of Wnt signalling pathway-associated protein. (c) Overexpression of miR-130a-3p inhibited proliferation of ADSCs, while knockdown promoted it.

Conclusions: The obtained findings indicate that exosomal miR-130a-3p can promote osteogenic differentiation of ADSCs partly by mediating SIRT7/Wnt/β-catenin axis, which will hence promote the application of exosomal microRNA in the field of bone regeneration.
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http://dx.doi.org/10.1111/cpr.12890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574877PMC
October 2020

Metformin inhibits RAN translation through PKR pathway and mitigates disease in ALS/FTD mice.

Proc Natl Acad Sci U S A 2020 08 20;117(31):18591-18599. Epub 2020 Jul 20.

Center for NeuroGenetics, College of Medicine, University of Florida, Gainesville, FL 32610;

Repeat associated non-AUG (RAN) translation is found in a growing number of microsatellite expansion diseases, but the mechanisms remain unclear. We show that RAN translation is highly regulated by the double-stranded RNA-dependent protein kinase (PKR). In cells, structured CAG, CCUG, CAGG, and GC expansion RNAs activate PKR, which leads to increased levels of multiple RAN proteins. Blocking PKR using PKR-K296R, the TAR RNA binding protein or PKR-KO cells, reduces RAN protein levels. p-PKR is elevated in ALS/FTD human and mouse brains, and inhibiting PKR in BAC transgenic mice using AAV-PKR-K296R or the Food and Drug Administration (FDA)-approved drug metformin, decreases RAN proteins, and improves behavior and pathology. In summary, targeting PKR, including by use of metformin, is a promising therapeutic approach for ALS/FTD and other expansion diseases.
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http://dx.doi.org/10.1073/pnas.2005748117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414156PMC
August 2020

The Effects of Timing of Postoperative Radiotherapy on Hypertrophic Scar in a Rabbit Model.

Med Sci Monit 2020 07 17;26:e921263. Epub 2020 Jul 17.

Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).

BACKGROUND Hypertrophic scar is associated with excessive proliferation of fibroblasts, the accumulation of collagen fibers, and angiogenesis associated with chronic inflammation. Scar resection, combined with radiotherapy, is widely used in clinical practice, but timing remains controversial. This study aimed to investigate the association between the timing of postoperative radiotherapy and the effects on hypertrophic scar in a rabbit model. MATERIAL AND METHODS Forty New Zealand white rabbits, 8-12 months old, weighing 1.8-2.3 kg were used in the model of hypertrophic scar and underwent surgical resection with or without postoperative radiotherapy. The study groups included: Group 1, the non-resection group; Group 2, the resection and non-radiotherapy group; Group 3, the immediate postoperative radiotherapy group; Group 4, the 12-hour postoperative radiotherapy group; Group 5, the 24-hour postoperative radiotherapy group; Group 6, the 48-hour postoperative radiotherapy group; Group 7, the 72-hour postoperative radiotherapy group; and Group 8, the 120-hour postoperative radiotherapy group. The rabbit ear skin was observed after treatment, and the hypertrophic scar index (HI), fibroblast numerical area density (NA), and collagen fiber area density (AA) were determined. RESULTS The HI, NA, and AA were significantly lower after 48 hours of postoperative radiotherapy (P<0.05), with the effects occurring mainly within 24 hours. There was no difference in HI, NA, and AA between the radiotherapy and non-radiotherapy groups within 24 hours after surgery. CONCLUSIONS In a rabbit model of hypertrophic scar, surgical resection combined with radiotherapy resulted in an optimal effect within 24 hours after surgery.
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http://dx.doi.org/10.12659/MSM.921263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382302PMC
July 2020

Understanding the Instability of the Halide Perovskite CsPbI through Temperature-Dependent Structural Analysis.

Adv Mater 2020 Aug 7;32(32):e2001069. Epub 2020 Jul 7.

Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA.

Despite the tremendous interest in halide perovskite solar cells, the structural reasons that cause the all-inorganic perovskite CsPbI to be unstable at room temperature remain mysterious, especially since many tolerance-factor-based approaches predict CsPbI should be stable as a perovskite. Here single-crystal X-ray diffraction and X-ray pair distribution function (PDF) measurements characterize bulk perovskite CsPbI from 100 to 295 K to elucidate its thermodynamic instability. While Cs occupies a single site from 100 to 150 K, it splits between two sites from 175 to 295 K with the second site having a lower effective coordination number, which, along with other structural parameters, suggests that Cs rattles in its coordination polyhedron. PDF measurements reveal that on the length scale of the unit cell, the PbI octahedra concurrently become greatly distorted, with one of the IPbI angles approaching 82° compared to the ideal 90°. The rattling of Cs, low number of CsI contacts, and high degree of octahedral distortion cause the instability of perovskite-phase CsPbI These results reveal the limitations of tolerance factors in predicting perovskite stability and provide detailed structural information that suggests methods to engineer stable CsPbI -based solar cells.
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http://dx.doi.org/10.1002/adma.202001069DOI Listing
August 2020

Distribution of Microbiota in Fine Particulate Matter Particles in Guangzhou, China.

Biomed Environ Sci 2020 May;33(5):306-314

Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China;Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, Guangdong, China;The Key Laboratory for Virology of Guangzhou, College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong, China.

Objective: High PM concentration is the main feature of increasing haze in developing states, but information on its microbial composition remains very limited. This study aimed to determine the composition of microbiota in PM in Guangzhou, a city located in the tropics in China.

Methods: In Guangzhou, from March 5 to 10 , 2016, PM was collected in middle volume air samplers for 23 h daily. The 16S rDNA V4 region of the PM sample extracted DNA was investigated using high-throughput sequence.

Results: Among the Guangzhou samples, , , , , and were the dominant microbiota accounting for more than 90% of the total microbiota, and was the dominant gram-negative bacteria, accounting for 21.30%-23.57%. We examined the difference in bacterial distribution of PM between Beijing and Guangzhou at the genus level; was found in both studies, but was only detected in Guangzhou.

Conclusion: In conclusion, the diversity and specificity of microbial components in Guangzhou PM were studied, which may provide a basis for future pathogenicity research in the tropics.
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http://dx.doi.org/10.3967/bes2020.042DOI Listing
May 2020

Exploring the impact of environmental regulations on happiness: new evidence from China.

Environ Sci Pollut Res Int 2020 Jun 25;27(16):19484-19501. Epub 2020 Mar 25.

School of Management, China University of Mining and Technology, Xuzhou, 221116, China.

Lower happiness caused by environmental pollution has attracted widespread attention, but existing studies have ignored the impact of environmental governance on happiness, and hardly a research has discussed whether environmental regulations will affect happiness. To make up for the above shortfall, based on the micro data come from Chinese General Social Survey (CGSS) in 2015 and the macro data of 28 provinces in China from 2013 to 2015, this study distinguishes three types of environmental regulations which are economical environmental regulation (EER), legal environmental regulation (LER) and supervised environmental regulation (SER), and the econometrical analysis of the linear relationship or potential nonlinear relationship between them and happiness is carried by ordinary least square (OLS) and ordered probit (Oprobit). Considering the time lag of policy implementation, this paper further tests the lagging effects. The results show that EER significantly improves happiness in the long run after implementation, and LER has no significant effect on happiness in the current year and the following year, while the significant nonlinear relationship appear after 2 years, whereas SER has a negative effect on happiness in the year and 2 years later. Therefore, in addition to continuing to increase government investment in environmental administration with adequate budgets, local governments should strengthen the environmental legal system and administrative accountability. And the most important of all, the government should create more avenues for public participation and pay enough attention to the supervision of the public. Finally, this research has great theoretical and realistic significance for the government to control environmental pollution.
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http://dx.doi.org/10.1007/s11356-020-08508-7DOI Listing
June 2020

Central Sleep Apnea Alters Neuronal Excitability and Increases the Randomness in Sleep-Wake Transitions.

IEEE Trans Biomed Eng 2020 11 9;67(11):3185-3194. Epub 2020 Mar 9.

Objective: While most studies on Central Sleep Apnea (CSA) have focused on breathing and metabolic disorders, the neuronal dysfunction that causes CSA remains largely unknown. Here, we investigate the underlying neuronal mechanism of CSA by studying the sleep-wake dynamics as derived from hypnograms.

Methods: We analyze sleep data of seven groups of subjects: healthy adults (n = 48), adults with obstructive sleep apnea (OSA) (n = 29), adults with CSA (n = 25), healthy children (n = 40), children with OSA (n = 18), children with CSA (n = 73) and CSA children treated with CPAP (n = 10). We calculate sleep-wake parameters based on the probability distributions of wake-bout durations and sleep-bout durations. We compare these parameters with results obtained from a neuronal model that simulates the interplay between sleep- and wake-promoting neurons.

Results: We find that sleep arousals of CSA patients show a characteristic time scale (i.e., exponential distribution) in contrast to the scale-invariant (i.e., power-law) distribution that has been reported for arousals in healthy sleep. Furthermore, we show that this change in arousal statistics is caused by triggering more arousals of similar durations, which through our model can be related to a higher excitability threshold in sleep-promoting neurons in CSA patients.

Conclusions: We propose a neuronal mechanism to shed light on CSA pathophysiology and a method to discriminate between CSA and OSA. We show that higher neuronal excitability thresholds can lead to complex reorganization of sleep-wake dynamics.

Significance: The derived sleep parameters enable a more specific evaluation of CSA severity and can be used for CSA diagnosis and monitor CSA treatment.
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http://dx.doi.org/10.1109/TBME.2020.2979287DOI Listing
November 2020

Fe doped NiP nanosheet arrays with rich P vacancies via phase transformation for efficient overall water splitting.

Nanoscale 2020 Mar 5;12(10):6204-6210. Epub 2020 Mar 5.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China.

Proper vacancy engineering is considered as a promising strategy to improve intrinsic activity, but it is challenging to construct rich vacancies by a simple strategy. Herein, Fe doped NiP nanosheet arrays with rich P vacancies are developed via a facile phase transformation strategy. Based on systematic investigations, we have demonstrated that an optimized surface electronic structure, abundant active sites and improved charge transport capability can be effectively achieved by vacancy engineering. Consequently, Fe doped NiP with rich vacancies show remarkable catalytic performances with 94.5 mV for the hydrogen evolution reaction (HER) and 217.3 mV for the oxygen evolution reaction (OER) at 10 mA cm, respectively, as well as good durability. When directly employed as working electrodes, the as-obtained Fe doped NiP with rich vacancies can attain 10 mA cm at a low voltage of 1.59 V. This work demonstrates a feasible strategy for rationally fabricating electrocatalysts with rich vacancies via a simple phase transformation.
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http://dx.doi.org/10.1039/c9nr10240jDOI Listing
March 2020

KIrO and KIrO, Low-Dimensional Iridates with Infinite IrO Chains.

J Am Chem Soc 2020 Mar 4;142(11):5389-5395. Epub 2020 Mar 4.

Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.

A previously unreported 1D iridate, KIrO, has been grown by a flux method in O-rich environment, and its crystal structure was determined via single crystal structural analysis. It exhibits straight chains of face-sharing [IrO] octahedra, which are arranged along the crystallographic axis, separated by nonmagnetic K ions. No magnetic transitions are observed during measured range, and the material is electrically insulating. Potentially interesting electronic behavior for KIrO is supported by electronic structure calculations. A structurally related material, KIrO, which displays similar fundamental geometric units but in a different spatial arrangement-zigzag chains-based on edge and face sharing [IrO] octahedra, is also reported. Both materials are of interest for probing the properties of a 1D system with strong spin-orbit coupling.
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http://dx.doi.org/10.1021/jacs.0c00849DOI Listing
March 2020

Differential circular RNA expression profiling during osteogenic differentiation in human adipose-derived stem cells.

Epigenomics 2020 02 13;12(4):289-302. Epub 2020 Feb 13.

Department of Stem Cells & Regenerative Medicine, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, Liaoning 110013, PR China.

Circular RNAs (circRNAs) are essential for stem cell differentiation. This study aimed to investigate their exact mechanism of action in human adipose-derived stem cell (hADSC) osteogenesis. Isolated hADSCs were cultured in growth medium or osteogenic medium, then total RNA was extracted for circRNA microarray, hierarchical cluster, gene ontology, regulating pathway and circRNA-miRNA-mRNA network analyses. A total of 171 circRNAs were upregulated and 119 were downregulated in induced groups compared with those in noninduced groups. Eight circRNAs, 40 miRNAs and 342 mRNAs were selected to construct a competing circRNA-miRNA-mRNA network. These findings may provide novel insight into altered and specific circRNAs that might function as competing endogenous RNAs in hADSCs during osteogenic differentiation.
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http://dx.doi.org/10.2217/epi-2019-0218DOI Listing
February 2020

Do driving restrictions improve air quality: Take Beijing-Tianjin for example?

Sci Total Environ 2020 Apr 7;712:136408. Epub 2020 Jan 7.

School of Management, China University of Mining and Technology, Xuzhou 221116, China. Electronic address:

To manage air quality, Tianjin introduced driving restriction (DR) in 2014 and new driving restriction (NDR) in 2018. Ever since February 22th, 2018, private cars that belong to Beijing have been treated equally as local cars of Tianjin. However, existing studies rarely compare the effects of driving restrictions in different cities. In this paper, using the regression discontinuity design (RDD) model and urban air quality monitoring data from Beijing and Tianjin during the period 2014 to 2018, we explore whether driving restriction policies can improve air quality in Beijing and Tianjin. The main results are as follows. (1) Our results of regression discontinuity design revealed that the DR had no obvious improvement in the air quality in Tianjin. Furthermore, the effect of the DR decreases along with its implementation. (2) The implementation of the DR in Tianjin had slight improvement in air quality in Beijing, which mainly reduced emissions from cars. In other words, the DR brought about weak externality. (3) We found that the effect of NDR on the air pollution was limited in both Tianjin and Beijing. To sum up, we compared the NDR with DR and found out that the DR was more effective in the short run, while the NDR could work well in the long term.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136408DOI Listing
April 2020

Antibody Therapy Targeting RAN Proteins Rescues C9 ALS/FTD Phenotypes in C9orf72 Mouse Model.

Neuron 2020 02 9;105(4):645-662.e11. Epub 2019 Dec 9.

Center for NeuroGenetics, Department of Molecular Genetics and Microbiology, Genetics Institute, McKnight Brain Institute, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL 32610, USA. Electronic address:

The intronic C9orf72 G4C2 expansion, the most common genetic cause of ALS and FTD, produces sense- and antisense-expansion RNAs and six dipeptide repeat-associated, non-ATG (RAN) proteins, but their roles in disease are unclear. We generated high-affinity human antibodies targeting GA or GP RAN proteins. These antibodies cross the blood-brain barrier and co-localize with intracellular RAN aggregates in C9-ALS/FTD BAC mice. In cells, α-GA interacts with TRIM21, and α-GA treatment reduced GA levels, increased GA turnover, and decreased RAN toxicity and co-aggregation of proteasome and autophagy proteins to GA aggregates. In C9-BAC mice, α-GA reduced GA as well as GP and GR proteins, improved behavioral deficits, decreased neuroinflammation and neurodegeneration, and increased survival. Glycosylation of the Fc region of α-GA is important for cell entry and efficacy. These data demonstrate that RAN proteins drive C9-ALS/FTD in C9-BAC transgenic mice and establish a novel therapeutic approach for C9orf72 ALS/FTD and other RAN-protein diseases.
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http://dx.doi.org/10.1016/j.neuron.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391607PMC
February 2020

Improving intraoperative storage conditions for autologous bone grafts: An experimental investigation in mice.

J Tissue Eng Regen Med 2019 12 6;13(12):2169-2180. Epub 2019 Nov 6.

Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA.

Autologous bone grafts constitute the second most transplanted tissue in medicine today. The viability, and consequently the osteogenic capacity, of an autograft is directly impacted by the interval between harvest and transplantation, but how the temperature and the solution in which the graft is held intraoperatively affect viability is not clear. Using a syngeneic mouse model and in vivo bone-forming assays, these variables were tested for their effects on programmed cell death, osteoprogenitor cell proliferation, and the ability of the autograft to ultimately produce new bone in an ectopic site. Based on these results, the intraoperative treatment with a WNT protein therapeutic was tested for its effects on the viability and osteogenic capacity of an autograft. Viability, programmed cell death, mitotic activity, osteogenic protein expression, and bone-forming capacity were assessed. Experimental results demonstrated that the osteogenic capacity of an autograft is significantly improved by intraoperative storage in L-WNT3A at physiological temperature.
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http://dx.doi.org/10.1002/term.2970DOI Listing
December 2019

Adipose-derived stem cell-conditioned medium protects fibroblasts at different senescent degrees from UVB irradiation damages.

Mol Cell Biochem 2020 Jan 10;463(1-2):67-78. Epub 2019 Oct 10.

Educational Department, Liaoning Cancer Hospital, Shenyang, 110001, Liaoning, People's Republic of China.

Adipose-derived stem cells (ADSCs) and their derivatives have aroused intense interest in fields of dermatological and aesthetic medicine. As a major component detected in ADSCs secretome, platelet-derived growth factor AA (PDGF-AA) has been reported mediating extracellular matrix deposition and remodeling, thus might contribute to its anti-aging effect. On the basis of establishing an experimental model that simulate actual skin aging by exposing HDFs to both intrinsic and extrinsic aging factors, we pretreated human dermal fibroblasts (HDFs) with ADSC-conditioned medium (ADSC-CM) before being irradiated, aiming at exploring preventive effects of ADSCs secretome against aging damages. 48 h after irradiation, we detected cellular proliferation; β-galactosidase stain; mRNA expressions of MMP-1, MMP-9, and TIMP-1; and protein expressions of collagen I, collagen III, and elastin. Moreover, we detected related protein expression of PI3K/Akt signal pathway, which can be activated by PDGF-AA and was newly found to promote extracellular matrix protein synthesis. Concentration of PDGF-AA in the prepared ADSC-CM decreased over time and maintained excellent bioactivity at low temperature until the 11th week. ADSC-CM pretreatment can slightly or significantly improve cellular proliferative activity and reduce cellular senescence in irradiated HDFs. Besides, ADSC-CM pretreatment increased collagen I, collagen III, elastin, and TIMP-1 expressions but decreased MMP-1 and MMP-9 expressions both in irradiated and nonirradiated HDFs. ADSC-CM pretreatment significantly increased pAkt protein expression, and ECM protein expression greatly decreased in case of LY294002 application. The results were similar in three generations of HDFs, yet varied with different degrees. Generally, ADSC-CM we prepared demonstrates a certain degree of positive role in preventing HDFs from intrinsic and extrinsic aging damages and that PDGF-AA may contribute to making it become effective with some other components in ADSC-CM.
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http://dx.doi.org/10.1007/s11010-019-03630-8DOI Listing
January 2020

Efficient green upconversion luminescence in highly crystallized ultratransparent nano-glass ceramics containing isotropic KYF nanocrystals.

Opt Lett 2019 Oct;44(19):4674-4677

Yb/Er co-doped nano-glass ceramics (GCs) containing isotropic KYF nanocrystals (NCs) are obtained from a simple ternary oxyfluoride glass by controlled crystallization. The nano-GCs thus obtained, albeit having very large crystallinity of ∼35%, are ultratransparent in the whole visible-light wavelength region of 300-700 nm. Remarkably enhanced green upconversion luminescence (UCL) of Er (by 55 times) is observed in the nano-GCs as compared to the precursor glass. Absolute quantum efficiency of the green UCL reaches as high as 0.41±0.02% in the GCs under 10  W/cm power density. The UCL efficiency is comparable to that of the famous ZBLAN: Yb/Er glass and GCs containing β-NaYF:Yb/Er NCs, and nearly twice as large as that of GCs containing KYF:Yb/Er NCs under the same excitation conditions.
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http://dx.doi.org/10.1364/OL.44.004674DOI Listing
October 2019