Publications by authors named "Junjie Jiang"

51 Publications

Comment on: "Phase II study of S-1 and oxaliplatin as neoadjuvant chemotherapy for locally advanced adenocarcinoma of the gastric or esophagogastric junction: KSCC1601. Gastric cancer, 2021 Aug 11" by Iwatsuki et al.

Gastric Cancer 2021 Sep 13. Epub 2021 Sep 13.

Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1007/s10120-021-01247-9DOI Listing
September 2021

Wavelength-Tunable L-Band High Repetition Rate Erbium-Doped Fiber Laser Based on Dissipative Four-Wave Mixing.

Sensors (Basel) 2021 Sep 6;21(17). Epub 2021 Sep 6.

Key Laboratory of Specialty Fiber Optics and Optical Access Networks, Joint International Research Laboratory of Specialty Fiber Optics and Advanced Communication, Shanghai Institute for Advanced Communication and Data Science, Shanghai University, Shanghai 200444, China.

A wavelength-tunable high repetition rate (HRR) erbium-doped fiber laser in L-band based on dissipative four-wave mixing (DFWM) mechanism is demonstrated. The cavity can generate a single-soliton train and bound-soliton train with a fixed repetition rate of ~126 GHz, which is determined by the free spectral range of the intra-cavity Lyot filter. A wide wavelength-tuning operation can also be obtained by rotating the polarization controllers. The wavelength-tuning ranges of the HRR single-soliton state and HRR bound-soliton state are ~38.3 nm and ~22.6 nm, respectively. This laser provides useful references for the area of a wavelength-tunable fiber laser with high repetition rate. The laser may also find useful applications in high-speed communication, sensing, etc.
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http://dx.doi.org/10.3390/s21175975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434646PMC
September 2021

Robust and Multifunctional Porous Polyetheretherketone Fiber Fabricated via a Microextrusion CO Foaming.

Macromol Rapid Commun 2021 Sep 7:e2100463. Epub 2021 Sep 7.

School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510275, P. R. China.

Fabrication of multifunctional porous fibers with excellent mechanical properties has attracted abundant attention in the fields of personal thermal management textiles and smart wearable devices. However, the high cost and harsh preparation environment of the traditional solution-solvent phase separation method for making porous fibers aggravates the problems of resource consumption and environmental pollution. Herein, a microextrusion process that combines environmentally friendly CO physical foaming with fused deposition modeling technology is proposed, via the dual features of high gas uptake and restricted cell growth, to implement the continuous production of porous polyetheretherketone (PEEK) fibers with a production efficiency of 10.5 cm s . The porous PEEK fiber exhibits excellent stretchability (234.8% strain) and good high-temperature thermal insulation property. The open-cell structure on the surface is favorable for the adsorption to achieve superhydrophobicity (154.4°) and high-efficiency photocatalytic degradation of rhodamine B (90.4%). Moreover, the parameterized controllability of the cell structure is beneficial to widening the multifunctional window. In short, the first porous PEEK physical foaming fiber, which opens up a new avenue for the application expansion, especially in the medical field, is realized.
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http://dx.doi.org/10.1002/marc.202100463DOI Listing
September 2021

Letter to the editor: new response evaluation criteria using early morphological change in imatinib treatment for patients with gastrointestinal stromal tumor.

Gastric Cancer 2021 Sep 5. Epub 2021 Sep 5.

Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1007/s10120-021-01246-wDOI Listing
September 2021

Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211033063

Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, China.

Aims: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC.

Methods: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly.

Results: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues.

Conclusions: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.
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http://dx.doi.org/10.1177/15330338211033063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411621PMC
August 2021

Comment on: "Association between triglyceride-glucose index and gastric carcinogenesis: a health checkup cohort study. Gastric cancer, 2021 Aug 5" by Kim et al.

Gastric Cancer 2021 Aug 23. Epub 2021 Aug 23.

Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1007/s10120-021-01232-2DOI Listing
August 2021

Characterization of Long Non-coding RNA Associated Proteins by RNA-Immunoprecipitation.

Methods Mol Biol 2021 ;2372:19-26

Center for Research on Reproduction & Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

With the advances in sequencing technology and transcriptome analysis, it is estimated that up to 75% of the human genome is transcribed into RNAs. This finding prompted intensive investigations on the biological functions of non-coding RNAs and led to very exciting discoveries of microRNAs as important players in disease pathogenesis and therapeutic applications. Research on long non-coding RNAs (lncRNAs) is in its infancy, yet a broad spectrum of biological regulations has been attributed to lncRNAs. RNA-immunoprecipitation (RNA-IP) is a technique of detecting the association of individual proteins with specific RNA molecules in vivo. It can be used to investigate lncRNA-protein interaction and identify lncRNAs that bind to a protein of interest. Here we describe the protocol of this assay with detailed materials and methods.
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http://dx.doi.org/10.1007/978-1-0716-1697-0_3DOI Listing
January 2021

CircRNA circFOXK2 facilitates oncogenesis in breast cancer via IGF2BP3/miR-370 axis.

Aging (Albany NY) 2021 07 30;13(14):18978-18992. Epub 2021 Jul 30.

Department of General Surgery, Qingxian People's Hospital, Qingxian, Hebei Province, China.

Metastasis is the leading cause of breast cancer (BC)-related deaths. Circular RNAs (circRNAs) have emerged as essential regulators for cancer progression and metastasis. Therefore, the objective of this study was to investigate the role of circRNAs in BC metastasis and related mechanism. In this study, we established the BC cell line with high or low potential of metastasis. RNA sequencing, migration and invasion assay, Fluorescence hybridization, luciferase report assay, circRNA pulldown, and transmission electron microscopy were performed to elucidate the molecular mechanism. The results showed that circRNA circFOXK2 was significantly increased in BC cells with high metastatic ability, and the upregulation of circFOXK2 was correlated with poor clinicopathological characteristics. Functional experiments demonstrated that overexpression of circFOXK2 promoted migration and invasion of BC cells. Also. circFOXK2 could act with IGF2BP3, an RNA-binding protein, and miR-370 to synergistically promote BC metastasis. Moreover, miR-370 could be transferred through exosomes to enhance the metastatic ability of recipient cells. In conclusion, circFOXK2 functions as a key regulator in BC metastasis, and the role of circFOXK2 on BC metastasis is tightly associated with the involvement of IGF2BP3 and miR-370. CircFOXK2 might serve as a potential biomarker for the diagnosis and treatment of BC.
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http://dx.doi.org/10.18632/aging.203347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351678PMC
July 2021

Intrinsic ORR Activity Enhancement of Pt Atomic Sites by Engineering the d-Band Center via Local Coordination Tuning.

Angew Chem Int Ed Engl 2021 Jul 26. Epub 2021 Jul 26.

School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.

A considerable amount of platinum (Pt) is required to ensure an adequate rate for the oxygen reduction reaction (ORR) in fuel cells and metal-air batteries. Thus, the implementation of atomic Pt catalysts holds promise for minimizing the Pt content. In this contribution, atomic Pt sites with nitrogen (N) and phosphorus (P) co-coordination on a carbon matrix (PtNPC) are conceptually predicted and experimentally developed to alter the d-band center of Pt, thereby promoting the intrinsic ORR activity. PtNPC with a record-low Pt content (≈0.026 wt %) consequently shows a benchmark-comparable activity for ORR with an onset of 1.0 V and half-wave potential of 0.85 V . It also features a high stability in 15 000-cycle tests and a superior turnover frequency of 6.80 s at 0.9 V . Damjanovic kinetics analysis reveals a tuned ORR kinetics of PtNPC from a mixed 2/4-electron to a predominately 4-electron route. It is discovered that coordinated P species significantly shifts d-band center of Pt atoms, accounting for the exceptional performance of PtNPC.
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http://dx.doi.org/10.1002/anie.202107790DOI Listing
July 2021

Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets.

Nat Commun 2021 06 24;12(1):3946. Epub 2021 Jun 24.

Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer. However, little is known about the genomic features of this disease. We perform whole-exome sequencing analysis of AFPGC, and identify 34 significantly mutated genes. Somatic copy number alterations analysis reveals several significant focal amplifications (e.g. 19q12, 17q12) and focal deletions (e.g. 1p36.11, 9p21.3), and some of these negatively affect the patient prognosis. Comparative analyses reveal that AFPGC has distinct genomic features from gastric cancer of The Cancer Genome Atlas as well as four molecular subtypes. Several frequently altered genes with potential as therapeutic targets are identified in AFPGC. Further analysis reveals that AFPGC with amplification of CCNE1 at 19q12 and/or ERBB2 at 17q12 show poorer survival and more aggressive. Subsequently, based on our established patient-derived xenograft models for AFPGC, translational research is performed and the therapeutic value of targeting CCNE1 and ERBB2 is validated. In this work, we provide an understanding of genomic characteristics of AFPGC and propose a platform to explore and validate the genome-guided personalized treatment for this disease.
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http://dx.doi.org/10.1038/s41467-021-24170-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225795PMC
June 2021

A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics.

Gastric Cancer 2021 Jun 6. Epub 2021 Jun 6.

Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Background: Gastric cancer (GC) is one of the leading causes of cancer deaths with high heterogeneity. There is currently a paucity of clinically applicable molecular classification system to guide precise medicine.

Methods: A total of 70 Chinese patients with GC were included in this study and whole-exome sequencing was performed. Unsupervised clustering was undertaken to identify genomic subgroups, based on mutational signature, copy number variation, neoantigen, clonality, and essential genomic alterations. Subgroups were characterized by clinicopathological factors, molecular features, and prognosis.

Results: We identified 32 significantly mutated genes (SMGs), including TP53, ARID1A, PIK3CA, CDH1, and RHOA. Of these, PREX2, PIEZO1, and FSIP2 have not been previously reported in GC. Using a novel genome-based classification method that integrated multidimensional genomic features, we categorized GC into four subtypes with distinct clinical phenotypes and prognosis. Subtype 1, which was predominantly Lauren intestinal type, harbored recurrent TP53 mutation and ERBB2 amplification, high tumor mutation burden (TMB)/tumor neoantigen burden (TNB), and intratumoral heterogeneity, with a liver metastasis tendency. Subtype 2 tended to occur at an elder age, accompanying with frequent TP53 and SYNE1 mutations, high TMB/TNB, and was associated with poor prognosis. Subtype 3 and subtype 4 included patients with mainly diffuse/mixed type tumors, high frequency of peritoneal metastasis, and genomical stability, whereas subtype 4 was associated with a favorable prognosis.

Conclusions: By integrating multidimensional genomic characteristics, we proposed a novel genomic classification system of GC associated with clinical phenotypes and provided a new insight to facilitate genome-guided risk stratification and disease management.
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http://dx.doi.org/10.1007/s10120-021-01201-9DOI Listing
June 2021

Effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats.

Braz J Med Biol Res 2021 31;54(9):e10842. Epub 2021 May 31.

Department of Hand Surgery, Yantaishan Hospital, Yantai, China.

Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.
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http://dx.doi.org/10.1590/1414-431X2020e10842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186374PMC
June 2021

FSTL1 promotes growth and metastasis in gastric cancer by activating AKT related pathway and predicts poor survival.

Am J Cancer Res 2021 1;11(3):712-728. Epub 2021 Mar 1.

The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, P. R. China.

Accumulating evidence on the role of Follistatin-like protein 1 (FSTL1) in tumorigenesis and cancer progression is conflicting. Nevertheless, the underlying mechanisms by which FSTL1 contributes to gastric cancer (GC) remain unknown. This study shows that FSTL1 was frequently upregulated in primary GC tissues and significantly correlated with infiltrating depth, lymph node metastasis, unfavorable tumor stage and poor prognosis of GC. Down or up-regulation of FSTL1 inhibited or increased, respectively, the proliferation by reducing apoptosis, clonogenicity, migration and invasion of GC cells . Moreover, the higher expression of FSTL1 promoted subcutaneous xenograft tumor growth and lung/liver tumor metastasis . Furthermore, we demonstrate that FSTL1 is involved in regulation of the AKT signaling through analyzing databases and experimental results. Mechanistic studies showed that FSTL1 promoted proliferation, migration and invasion in GC, at least partially, by activating AKT via regulating TLR4/CD14. In all, this study highlights the role of the FSTL1-TLR4/CD14-AKT axis, which provided novel insights into the mechanism of growth and metastasis in GC for the first time.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994156PMC
March 2021

Constructing Atomic Heterometallic Sites in Ultrathin Nickel-Incorporated Cobalt Phosphide Nanosheets via a Boron-Assisted Strategy for Highly Efficient Water Splitting.

Nano Lett 2021 Jan 5;21(1):823-832. Epub 2021 Jan 5.

Center for Clean Energy Technology, School of Mathematical and Physical Science, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia.

Identification of active sites for highly efficient catalysts at the atomic scale for water splitting is still a great challenge. Herein, we fabricate ultrathin nickel-incorporated cobalt phosphide porous nanosheets (Ni-CoP) featuring an atomic heterometallic site (NiCoP) via a boron-assisted method. The presence of boron induces a release-and-oxidation mechanism, resulting in the gradual exfoliation of hydroxide nanosheets. After a subsequent phosphorization process, the resultant Ni-CoP nanosheets are implanted with unsaturated atomic heterometallic NiCoP sites (with Co vacancies) for alkaline hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The optimized Ni-CoP exhibits a low overpotential of 88 and 290 mV at 10 mA cm for alkaline HER and OER, respectively. This can be attributed to reduced free energy barriers, owing to the direct influence of center Ni atoms to the adjacent Co/P atoms in NiCoP sites. These provide fundamental insights on the correlation between atomic structures and catalytic activity.
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http://dx.doi.org/10.1021/acs.nanolett.0c04569DOI Listing
January 2021

Prevalence of and Risk Factors for Community-Based Osteoporosis and Associated Fractures in Beijing: Study Protocol for a Cross-Sectional and Prospective Study.

Front Med (Lausanne) 2020 9;7:544697. Epub 2020 Dec 9.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Osteoporosis (OP) patients are usually asymptomatic until osteoporotic fractures occur, which makes early diagnosis and prevention difficult, and the associated fractures secondary to OP could be preventable with appropriate management. Therefore, early identification and relevant evidence-based management of OP could guide the prevention of subsequent fractures. This study will investigate the prevalence of OP and the incidence of osteoporotic fractures in Beijing community residents to further explore the related risk factors and put forward suggestions for people aged 45-80 years old. Over 2 years, this study will conduct an OP screening and a prospective follow-up in the Beijing community to investigate the incidence of osteoporotic fractures. The study will undertake bone mineral density detection, collect biological samples, and record information via questionnaires. The study aims to investigate the potential risk factors for osteoporosis and explore syndromes from traditional Chinese medicine that are associated with this condition based on large samples from the Beijing community. Data on the incidence of osteoporotic fractures among community dwellers in Beijing over the two-years will be available on the Chinese clinical trial registry: ChiCTR-SOC-17013090.
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http://dx.doi.org/10.3389/fmed.2020.544697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757753PMC
December 2020

First-Line Contact Aspiration vs Stent Retriever for Proximal Occlusion in Acute Ischemic Stroke: A Systemic Review and Meta-Analysis.

J Stroke Cerebrovasc Dis 2020 Dec 27;29(12):105374. Epub 2020 Oct 27.

952 hospital of the Chinese people's liberation army ground force, Neurology department, Geermu, Qinghai Province, 816000, China. Electronic address:

Introduction: The aim of this systematic review and meta-analysis was to compare the performance of first-line contact aspiration (ASP) and stent retriever (SR) in acute ischemic stroke caused by proximal large vessel occlusion.

Methods: Cochrane databases, MEDLINE and EMBASE were systematically searched for literatures reporting outcomes on thrombectomy with both first-line aspiration and first-line stent retriever in proximal occlusion.

Results: Thirteen studies with a total of 1614 patients were included. No differences were identified between the SR and ASP groups in terms of final reperfusion rate (modified thrombolysis in cerebral infarction 2b/3) (OR: 1.54, 95% CI: 0.88-2.70), complete recanalization rate (modified thrombolysis in cerebral infarction 3) (OR: 1.78, 95% CI: 0.58-5.44), and favorable outcomes (modified Rankin scale ≤2) (OR: 1.02, 95% CI: 0.79-1.32). With regard to adverse events, emboli to new territories (OR: 0.81, 95% CI: 0.31-2.14), intracranial hemorrhage (OR: 0.71, 95% CI: 0.40-1.28), 90-days mortality (OR: 1.02, 95% CI: 0.71-1.47) were similar between groups, while symptomatic intracerebral hemorrhage (OR: 0.43 95% CI: 0.21-0.86) was less seen in ASP. Subgroup analysis indicated that ASP was comparable to stent retriever with local aspiration (SRLA) (OR: 1.25 95% CI: 0.25-6.22) and superior to stent retriever alone (OR: 1.85 95% CI: 1.22-2.81). Moreover, in posterior circulation, contact aspiration achieved a significantly higher reperfusion (OR: 1.97 95% CI: 1.03-3.76) compared to stent retriever, and needed relatively less rescue therapies (21.5% vs 29.6%, p < 0.05).

Conclusion: Our study suggested that contact aspiration might be advantageous over stent retriever alone and more suitable in posterior circulation. While ASP and SRLA thrombectomy were equally effective in achieving good clinical outcomes. However, further studies are needed to confirm these results.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105374DOI Listing
December 2020

Poly(ether imide)/Epoxy Foam Composites with a Microcellular Structure and Ultralow Density: Bead Foam Fabrication, Compression Molding, Mechanical Properties, Thermal Stability, and Flame-Retardant Properties.

ACS Omega 2020 Oct 29;5(40):25784-25797. Epub 2020 Sep 29.

School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, Guangdong Province, China.

It is challenging to prepare ultralow-density microcellular foams based on high-performance polymers due to their low gas solubility and rigid polymer matrix. In this study, by applying microcellular foaming technology using CO/acetone as the blowing agent, ultralow-density poly(ether imide) (PEI) bead foams with an expansion ratio of 30-56 times and cell density of 10-10 cells/cm were fabricated, resulting from the enhanced plasticization effect of the mixed fluid. The slow diffusivity of acetone at room temperature ensured the saturated PEI beads to foam after desorption for more than 6 days, which potentially reduces the transportation cost of PEI bead foams significantly. A novel compression molding process was developed to prepare the molded PEI bead foams (MPEIs) using epoxy as a coating agent. The good infiltration character of epoxy on bead foams endowed the MPEIs with excellent mechanical properties, together with an ultralow density of 80-200 kg/m, long-term dimensional stability at 160 °C, and excellent flame-retardant properties of V0 rating. These features made the MPEIs very promising for many advanced applications.
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http://dx.doi.org/10.1021/acsomega.0c03072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557248PMC
October 2020

Identification of and as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis.

Front Oncol 2020 11;10:1765. Epub 2020 Sep 11.

Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Gastric cancer (GC) is the fifth most frequently diagnosed malignancy, and the third leading cause of tumor-related mortalities worldwide. Due to a high heterogeneity in GC, its treatment and prognosis are challenging, necessitating urgent identification of novel prognostic predictors for GC patients. We downloaded RNA sequence data, from the Cancer Genome Atlas and microarray data from Gene Expression Omnibus database, then identified common differentially-expressed genes (DEGs) between GC and normal gastric tissues across four datasets. We then used a combination of protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) to identify key genes with prognostic value in GC. Thereafter, we used quantitative real time polymerase chain reaction (qRT-PCR) to validate expression of the identified key genes in the Zhejiang University (ZJU) cohort. Finally, we evaluated the relationships between gene expression and immune factors, including immune cells and biomarkers of immunotherapy. Among 426 common DEGs screened, 333 and 93 were upregulated and downregulated, respectively. PPI network and WGCNA successfully identified the top 30 hub genes, among which , and were common. Furthermore, and were negatively associated with prognosis of GC patients, implying that they were key GC predictors. Interestingly, and were positively correlated with predictive biomarkers for GC immunotherapy, including PD-L1 expression, CD8 T cells infiltration, and EBV status. and were identified as two novel key genes with prognostic value in GC by network analysis.
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http://dx.doi.org/10.3389/fonc.2020.01765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516284PMC
September 2020

Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma.

Cancer Med 2020 11 24;9(22):8498-8518. Epub 2020 Sep 24.

Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Several biomarkers such as tumor mutation burden (TMB), neoantigen load (NAL), programmed cell-death receptor 1 ligand (PD-L1) expression, and lactate dehydrogenase (LDH) have been developed for predicting response to immune checkpoint inhibitors (ICIs) in melanoma. However, some limitations including the undefined cut-off value, poor uniformity of test platform, and weak reliability of prediction have restricted the broad application in clinical practice. In order to identify a clinically actionable biomarker and explore an effective strategy for prediction, we developed a genetic mutation model named as immunotherapy score (ITS) for predicting response to ICIs therapy in melanoma, based on whole-exome sequencing data from previous studies. We observed that patients with high ITS had better durable clinical benefit and survival outcomes than patients with low ITS in three independent cohorts, as well as in the meta-cohort. Notably, the prediction capability of ITS was more robust than that of TMB. Remarkably, ITS was not only an independent predictor of ICIs therapy, but also combined with TMB or LDH to better predict response to ICIs than any single biomarker. Moreover, patients with high ITS harbored the immunotherapy-sensitive characteristics including high TMB and NAL, ultraviolet light damage, impaired DNA damage repair pathway, arrested cell cycle signaling, and frequent mutations in NF1 and SERPINB3/4. Overall, these findings deserve prospective investigation in the future and may help guide clinical decisions on ICIs therapy for patients with melanoma.
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http://dx.doi.org/10.1002/cam4.3481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666739PMC
November 2020

Publisher's Note: "Predicting phase and sensing phase coherence in chaotic systems with machine learning" [Chaos 30, 083114 (2020)].

Chaos 2020 08;30(8):089901

School of Electrical, Computer and Energy Engineering, Arizona State University, Tempe, Arizona 85287, USA.

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http://dx.doi.org/10.1063/5.0025053DOI Listing
August 2020

Predicting phase and sensing phase coherence in chaotic systems with machine learning.

Chaos 2020 Aug;30(8):083114

School of Electrical, Computer and Energy Engineering, Arizona State University, Tempe, Arizona 85287, USA.

Recent interest in exploiting machine learning for model-free prediction of chaotic systems focused on the time evolution of the dynamical variables of the system as a whole, which include both amplitude and phase. In particular, in the framework based on reservoir computing, the prediction horizon as determined by the largest Lyapunov exponent is often short, typically about five or six Lyapunov times that contain approximately equal number of oscillation cycles of the system. There are situations in the real world where the phase information is important, such as the ups and downs of species populations in ecology, the polarity of a voltage variable in an electronic circuit, and the concentration of certain chemical above or below the average. Using classic chaotic oscillators and a chaotic food-web system from ecology as examples, we demonstrate that reservoir computing can be exploited for long-term prediction of the phase of chaotic oscillators. The typical prediction horizon can be orders of magnitude longer than that with predicting the entire variable, for which we provide a physical understanding. We also demonstrate that a properly designed reservoir computing machine can reliably sense phase synchronization between a pair of coupled chaotic oscillators with implications to the design of the parallel reservoir scheme for predicting large chaotic systems.
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http://dx.doi.org/10.1063/5.0006304DOI Listing
August 2020

Methods for the Study of Long Noncoding RNA in Cancer Cell Signaling.

Methods Mol Biol 2021 ;2174:89-118

Center for Reproduction and Women's Health, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

With the advances in sequencing technology and transcriptome analysis, it is estimated that up to 75% of the human genome is transcribed into RNAs. This finding prompted intensive investigations on the biological functions of noncoding RNAs and led to very exciting discoveries of microRNAs as important players in disease pathogenesis and therapeutic applications. Research on long noncoding RNAs (lncRNAs) is in its infancy, yet a broad spectrum of biological regulations has been attributed to lncRNAs. Here, we provide a collection of detailed experimental protocols for lncRNA studies, including lncRNA immunoprecipitation, lncRNA pull-down, lncRNA northern blot analysis, lncRNA in situ hybridization, and lncRNA knockdown. We hope that the information included in this chapter can speed up research on lncRNAs biology and eventually lead to the development of clinical applications with lncRNA as novel prognostic markers and therapeutic targets.
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http://dx.doi.org/10.1007/978-1-0716-0759-6_7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587466PMC
April 2021

Systematic Characterization of Recurrent Genomic Alterations in Cyclin-Dependent Kinases Reveals Potential Therapeutic Strategies for Cancer Treatment.

Cell Rep 2020 07;32(2):107884

Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Recurrent copy-number alterations, mutations, and transcript fusions of the genes encoding CDKs/cyclins are characterized in >10,000 tumors. Genomic alterations of CDKs/cyclins are dominantly driven by copy number aberrations. In contrast to cell-cycle-related CDKs/cyclins, which are globally amplified, transcriptional CDKs/cyclins recurrently lose copy numbers across cancers. Although mutations and transcript fusions are relatively rare events, CDK12 exhibits recurrent mutations in multiple cancers. Among the transcriptional CDKs, CDK7 and CDK12 show the most significant copy number loss and mutation, respectively. Their genomic alterations are correlated with increased sensitivities to DNA-damaging drugs. Inhibition of CDK7 preferentially represses the expression of genes in the DNA-damage-repair pathways and impairs the activity of homologous recombination. Low-dose CDK7 inhibitor treatment sensitizes cancer cells to PARP inhibitor-induced DNA damage and cell death. Our analysis provides genomic information for identification and prioritization of drug targets for CDKs and reveals rationales for treatment strategies.
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http://dx.doi.org/10.1016/j.celrep.2020.107884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391471PMC
July 2020

Noise-enabled species recovery in the aftermath of a tipping point.

Phys Rev E 2020 Jan;101(1-1):012206

School of Electrical, Computer and Energy Engineering, Arizona State University, Tempe, Arizona 85287, USA.

The beneficial role of noise in promoting species coexistence and preventing extinction has been recognized in theoretical ecology, but previous studies were mostly concerned with low-dimensional systems. We investigate the interplay between noise and nonlinear dynamics in real-world complex mutualistic networks with a focus on species recovery in the aftermath of a tipping point. Particularly, as a critical parameter such as the mutualistic interaction strength passes through a tipping point, the system collapses and approaches an extinction state through a dramatic reduction in the species populations to near-zero values. We demonstrate the striking effect of noise: when the direction of parameter change is reversed through the tipping point, noise enables species recovery which otherwise would not be possible. We uncover an algebraic scaling law between the noise amplitude and the parameter distance from the tipping point to the recovery point and provide a physical understanding through analyzing the nonlinear dynamics based on an effective, reduced-dimension model. Noise, in the form of small population fluctuations, can thus play a positive role in protecting high-dimensional, complex ecological networks.
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http://dx.doi.org/10.1103/PhysRevE.101.012206DOI Listing
January 2020

Integrative comparison of the genomic and transcriptomic landscape between prostate cancer patients of predominantly African or European genetic ancestry.

PLoS Genet 2020 02 14;16(2):e1008641. Epub 2020 Feb 14.

Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10-03), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10-02), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10-03). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10-48). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10-125). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.
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http://dx.doi.org/10.1371/journal.pgen.1008641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046294PMC
February 2020

Dietary Supplementation with Phytase and Protease Improves Growth Performance, Serum Metabolism Status, and Intestinal Digestive Enzyme Activities in Meat Ducks.

Animals (Basel) 2020 Feb 8;10(2). Epub 2020 Feb 8.

Institute of Livestock and Poultry, Tongwei Co., Ltd., Chengdu 610041, China.

Two experiments were conducted to investigate the effects of dietary supplementation with protease and phytase on growth performance, serum physiochemical parameters, and activities of digestive enzymes in jejunal digesta of meat ducks. Experiment 1 was carried out to determine the effects of different protease or phytase on growth performance, serum physiochemical parameter, and activities of digestive enzymes in jejunal digesta of meat ducks to select the optimal phytase or protease. According to the hatching age and initial weight, a total of 5040 Cherry Valley ducks (15 days of age) were randomly assigned into six treatments. Treatments included a basal control diet (CON) and 5 basal diets supplemented with different enzyme preparations, which were phytase preparation A (PA, 160 g/t), phytase preparation B (PB, 800 g/t), protease preparation A (PTA, 80 g/t), protease preparation B (PTB, 300 g/t) and protease preparation C (PTC, 200 g/t). The enzyme activities were as follows: Phytase A and B as well as protease A, B, and C were 50,000, 10,000, 250,000, 50,000, and 60,000 U/g, respectively. Each treatment had 7 replicates with 120 meat ducks per replicate. Experiment 1 lasted for 28 days. The results showed that: compared with the CON group, the PA group significantly decreased contents of serum phosphorus and calcium (p < 0.05), and the PTA, PTB, and PTC groups had higher activities of trypsin in jejunal digesta (p < 0.05), and the activity of jejunal chymotrypsin in PTA group was greater (p < 0.05). Experiment 2 was carried out to determine the effects of dietary supplementation with protease and phytase in low-energy and low-protein diet on growth performance, serum physiochemical parameters, and activities of digestive enzymes in jejunal digesta of meat ducks. According to the hatching age and initial weight, a total of 5760 Cherry Valley ducks (15 days of age) were randomly assigned into four treatments on the basis of a trial of 2 × 2 factorial design. Treatments included a basal control diet (PC), basal diet supplemented with enzymes (PCE), low-energy and low-protein diet (LEP), and low-energy and low-protein diet supplemented with enzymes (LEPE), the nutrient levels of energy and CP of basal diet were 2747.2 cal·ME/kg and 16.80%, respectively, and the nutrient levels of energy and CP of low-energy and low-protein diet decreased 45.90 kcal·ME/kg and 0.52% on the basis of basal diet, respectively. According to the results of experiment 1, phytase A and protease A were determined as the optimal enzyme combination of Experiment 2, and additional dosage of which were identical with Experiment 1. Each treatment had 6 replicates with 240 meat ducks per replicate. Experiment 2 lasted for 28 days. The results showed that: compared with PC and LEP groups, PCE and LEPE groups had higher final weight and average daily gain (ADG) (p < 0.05), higher activities of trypsin and chymotrypsin in jejunal digesta (p < 0.05), lower contents of serum calcium and phosphorus as well as higher levels of high-density lipoprotein in the serum (p < 0.05). In conclusion, dietary supplementation with phytase and protease in different energy and protein diets could increase digestive enzymes in jejunal digesta, effect serum physiochemical parameters, improve metabolic status, and increase the growth performance of meat ducks. Meanwhile, with the dietary supplementation with phytase and protease in the lower energy and protein diet, the growth performance could reach to the degree of the higher energy and increased protein diet, but without the addition of phytase and protease.
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http://dx.doi.org/10.3390/ani10020268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070931PMC
February 2020

Quantitative ultrashort echo time magnetization transfer (UTE-MT) for diagnosis of early cartilage degeneration: comparison with UTE-T2* and T2 mapping.

Quant Imaging Med Surg 2020 Jan;10(1):171-183

Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Background: To investigate the feasibility of using quantitative ultrashort echo time magnetization transfer (UTE-MT) technique in diagnosing early cartilage degeneration and to compare the technique's diagnostic efficacy with UTE-T2* mapping and T2 mapping.

Methods: Twenty human anterolateral condyle specimens with degeneration were obtained from volunteers undergoing total knee arthroplasty (TKA); they then underwent magnetic resonance (MR) scan on a clinical 3.0T scanner (GE, MR750). Seventy-two regions of interest (ROI) were manually drawn on specimens for UTE-MT, UTE-T2*, and T2 measurement, and the corresponding cartilage-bone regions were further divided into degeneration classifications of normal (n=11, Mankin scores 0-1), mild (n=28, Mankin scores 2-5), moderate (n=21, Mankin scores 6-9), and severe (n=12, Mankin scores 10-14) based on histological measures of degeneration (i.e., Mankin scores) as a reference standard. Differences among groups and correlations between quantitative MR parameters and Mankin scores were assessed using analysis of variance (ANOVA), Tamhane-T2, LSD, Kruskal-Wallis tests, and Spearman's correlation coefficient. The receiver-operating characteristic (ROC) curve was used to compare the diagnostic efficacy of different quantitative MR parameters for the detection of mild cartilage degeneration.

Results: The UTE magnetization transfer ratio (UTE-MTR) in the normal group was significantly different from the mild group (P=0.021), moderate group (P<0.001), and severe group (P<0.001). Significant differences were observed in the T2* values between both the normal group and the moderate group (P<0.032), and between the normal group and the severe group (P<0.001). For T2 values, the only significant difference was observed between the severe group and the normal group (P=0.011). The UTE-MTR, UTE-T2*, and T2 values were all significantly correlated with Mankin scores: UTE-MTR values were strongly (r=-0.678, P<0.001) correlated, UTE-T2* values were markedly correlated (r=-0.501, P<0.001), and T2 values were weakly correlated (r=0.337, P=0.004) correlated with Mankin scores. The diagnostic efficacy of UTE-MTR (AUC =0.828, P=0.002) was better than UTE T2* mapping and T2 mapping (AUC =0.604, P=0.318; AUC =0.644, P=0.165, respectively) for the diagnosis of early cartilage degeneration.

Conclusions: UTE-MTR values were strongly correlated with histological grades of cartilage degeneration, and its diagnostic efficacy was better than both UTE T2* mapping and T2 mapping in detecting early cartilage degeneration. Once the clinical potential of the technique has been confirmed, UTE-MT may provide a promising imaging biomarker with potential application in a more comprehensive diagnosis and monitoring of cartilage degeneration.
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http://dx.doi.org/10.21037/qims.2019.12.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960424PMC
January 2020

LncRNA RP11-361F15.2 promotes osteosarcoma tumorigenesis by inhibiting M2-Like polarization of tumor-associated macrophages of CPEB4.

Cancer Lett 2020 03 2;473:33-49. Epub 2020 Jan 2.

The Institute of Intervention Vessel, Shanghai Tenth People's Hospital, Shanghai, PR China. Electronic address:

Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
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http://dx.doi.org/10.1016/j.canlet.2019.12.041DOI Listing
March 2020

Optimizing biologically inspired transport networks by control.

Phys Rev E 2019 Sep;100(3-1):032309

School of Electrical, Computer and Energy Engineering, Arizona State University, Tempe, Arizona 85287, USA.

Transportation networks with intrinsic flow dynamics governed by the Kirchhoff's current law are ubiquitous in natural and engineering systems. There has been recent work on designing optimal transportation networks based on biological principles with the goal to minimize the total dissipation associated with the flow. Despite being biologically inspired, e.g., adaptive network design based on slime mold Physarum polycephalum, such methods generally lead to suboptimal networks due to the difficulty in finding a global or nearly global optimum of the nonconvex optimization function. Here we articulate a design paradigm that combines engineering control and biological principles to realize optimal transportation networks. In particular, we show how small control signals applied only to a fraction of edges in an adaptive network can lead to solutions that are far more optimal than those based solely on biological principles. We also demonstrate that control signals, if not properly designed, can lead to networks that are less optimal. Incorporating control principle into biology-based optimal network design has broad applications not only in biomedical science and engineering but also in other disciplines such as civil engineering for designing resilient infrastructure systems.
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http://dx.doi.org/10.1103/PhysRevE.100.032309DOI Listing
September 2019

Harnessing tipping points in complex ecological networks.

J R Soc Interface 2019 09 11;16(158):20190345. Epub 2019 Sep 11.

School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ 85287, USA.

Complex and nonlinear ecological networks can exhibit a tipping point at which a transition to a global extinction state occurs. Using real-world mutualistic networks of pollinators and plants as prototypical systems and taking into account biological constraints, we develop an ecologically feasible strategy to manage/control the tipping point by maintaining the abundance of a particular pollinator species at a constant level, which essentially removes the hysteresis associated with a tipping point. If conditions are changing so as to approach a tipping point, the management strategy we describe can prevent sudden drastic changes. Additionally, if the system has already moved past a tipping point, we show that a full recovery can occur for reasonable parameter changes only if there is active management of abundance, again due essentially to removal of the hysteresis. This recovery point in the aftermath of a tipping point can be predicted by a universal, two-dimensional reduced model.
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http://dx.doi.org/10.1098/rsif.2019.0345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769319PMC
September 2019
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