Publications by authors named "Yunpeng Liu"

391 Publications

Complete Pathologic Response of Multiple Liver Metastases and Clinical Complete Response of Rectal Cancer in a Patient with Ataxia-Telangiectasia Mutated Gene Mutations After XELOXIRI Plus Bevacizumab: A Case Report.

Onco Targets Ther 2021 15;14:4201-4209. Epub 2021 Jul 15.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People's Republic of China.

Background: Doublet or triplet chemotherapy plus or minus targeted drugs can achieve a high objective response rate (ORR) and are currently considered to be the backbone of conventional therapy for liver metastatic colorectal cancer (mCRC). However, current biomarkers (such as UGT1A1 and DPYD) are limited to the prediction of toxicity and there are no effective biomarkers to predict chemotherapy response. Therefore, personalized cancer chemotherapy underpinned by genomic alterations in mCRC has received increasing attention.

Case Presentation: We present a case of a 28-year-old female rectal cancer patient with multiple liver metastases (clinical risk score, CRS = 5 points). The patient underwent XELOXIRI plus bevacizumab regimen that consisted of irinotecan (150 mg/m2), oxaliplatin (100 mg/m2) on day 1, capecitabine (1700 mg/m2 per day from day 2 to 15), bevacizumab (7.5 mg/kg) on day 1 (on the second cycle), given every three weeks for eight cycles. After multi-disciplinary team (MDT) discussion, the patient underwent right hemihepatectomy, partial liver resection of segment IV and cholecystectomy. Surprisingly, the patient achieved a complete pathologic response (pCR) of the hepatic metastasis and clinical complete response (cCR) of the primary rectal lesion. A paired tumor molecular profile revealed somatic mutations in ataxia-telangiectasia mutated (ATM) genes that may explain why the patient achieved such a dramatic tumor response. Treatment was discontinued after eight cycles of a single oral dose of capecitabine and the patient started a follow-up program of physical and radiological examinations. To monitor the signs of recurrence, we also obtained blood samples to analyze circulating tumor DNA (ctDNA). To date, the patient has remained disease-free.

Conclusion: The XELOXIRI-bevacizumab regimen is a feasible and effective regimen for patients with mCRC. Mutations in the ATM genes may characterize a subset of patients with a better prognosis who are more sensitive to chemotherapy plus biological agents.
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http://dx.doi.org/10.2147/OTT.S320477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289441PMC
July 2021

N-Methyladenosine RNA Demethylase FTO Promotes Gastric Cancer Metastasis by Down-Regulating the m6A Methylation of ITGB1.

Front Oncol 2021 1;11:681280. Epub 2021 Jul 1.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

Abnormal RNA m6A methylation is known to lead to the occurrence and progression of multiple cancers including gastric cancer (GC). However, the integrative effects of all m6A methylation regulators on GC prognosis are unclear. Our research aimed to globally analyze the prognosis values of all 33 m6A RNA methylation regulators in GC by univariate and multivariate Cox regression analyses. Among all 33 m6A RNA methylation regulators, fat mass and obesity-associated protein (FTO), an m6A demethylase, was identified as a key prognostic risk factor on overall survival (OS) of GC patients. It was found that FTO could promote GC cell migration and invasion abilities, and we predicted that ITGB1 was a demethylated target of FTO. Knockdown (KD) of FTO significantly down-regulated ITGB1 expression at both mRNA and protein levels and augmented ITGB1 mRNA m6A modification level. Moreover, overexpression (OE) of ITGB1 could partially reverse FTO-KD-inhibited migration and invasion of GC cells. Our study found that FTO was an independent risk factor for overall survival (OS) of GC patients and FTO could promote GC metastasis by upregulating the expression of Integrin β1(ITGB1) decreasing its m6A level. These results indicated that FTO can be a potent GC biomarker for prognosis prediction as well as a potential target in GC treatment.
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http://dx.doi.org/10.3389/fonc.2021.681280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282183PMC
July 2021

Identification of Prognostic Signature and Gliclazide as Candidate Drugs in Lung Adenocarcinoma.

Front Oncol 2021 24;11:665276. Epub 2021 Jun 24.

Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.

Background: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, with high incidence and mortality. To improve the curative effect and prolong the survival of patients, it is necessary to find new biomarkers to accurately predict the prognosis of patients and explore new strategy to treat high-risk LUAD.

Methods: A comprehensive genome-wide profiling analysis was conducted using a retrospective pool of LUAD patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE18842, GSE19188, GSE40791 and GSE50081 and The Cancer Genome Atlas (TCGA). Differential gene analysis and Cox proportional hazard model were used to identify differentially expressed genes with survival significance as candidate prognostic genes. The Kaplan-Meier with log-rank test was used to assess survival difference. A risk score model was developed and validated using TCGA-LUAD and GSE50081. Additionally, The Connectivity Map (CMAP) was used to predict drugs for the treatment of LUAD. The anti-cancer effect and mechanism of its candidate drugs were studied in LUAD cell lines.

Results: We identified a 5-gene signature (KIF20A, KLF4, KRT6A, LIFR and RGS13). Risk Score (RS) based on 5-gene signature was significantly associated with overall survival (OS). Nomogram combining RS with clinical pathology parameters could potently predict the prognosis of patients with LUAD. Moreover, gliclazide was identified as a candidate drug for the treatment of high-RS LUAD. Finally, gliclazide was shown to induce cell cycle arrest and apoptosis in LUAD cells possibly by targeting CCNB1, CCNB2, CDK1 and AURKA.

Conclusion: This study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.
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http://dx.doi.org/10.3389/fonc.2021.665276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264429PMC
June 2021

Insight into the ion exchange in the adsorptive removal of fluoride by doped polypyrrole from water.

Environ Sci Pollut Res Int 2021 Jul 10. Epub 2021 Jul 10.

Department of Environmental Science and Engineering, State Key Laboratory of Multiphase Flow in Power Engineering, School of Energy and Power Engineering, Xi'an Jiaotong University, Xi'an, 710049, China.

In this study, the polypyrrole (PPy) samples doped with Cl (PPy-Cl), SO (PPy-SO4) and SO+Cl (PPy-SO4+Cl) were synthesized by chemical polymerization for the adsorptive removal of fluoride ion from water. The structure and morphology of the as-prepared PPy samples were characterized by FT-IR, BET, SEM, XPS, and zeta potential. The adsorption experiments revealed that the PPy-Cl exhibited faster kinetics and higher adsorption capacity (13.98 mg/g), more than 4 times that of PPy-SO4 (3.08 mg/g) and PPy-SO4+Cl (3.17 mg/g). The kinetics of the adsorption followed the pseudo-second-order model and the adsorption isotherm data fitted well to the Langmuir model. FT-IR, EDX, and XPS tests for PPy samples before and after fluoride adsorption demonstrated that anion exchange between F and Cl or SO4 was the prior mechanism for fluoride ion removal from water. Cl was more favorable than SO in the ion exchange with F. Meanwhile, the Cl or SO exchanged with F was mainly bound to the active nitrogen that accounts for 6% of the total nitrogen in PPy molecular matrix. Further study of zeta potential and pH influence experiment demonstrated the electrostatic interaction is auxiliary interaction for the fluoride removal by doped PPy samples.
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http://dx.doi.org/10.1007/s11356-021-15027-6DOI Listing
July 2021

Chemotaxis of Beneficial Rhizobacteria to Root Exudates: The First Step towards Root-Microbe Rhizosphere Interactions.

Int J Mol Sci 2021 Jun 22;22(13). Epub 2021 Jun 22.

Jiangsu Provincial Key Lab for Organic Solid Waste Utilization, National Engineering Research Center for Organic-Based Fertilizers, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, Nanjing Agricultural University, Nanjing 210095, China.

Chemotaxis, the ability of motile bacteria to direct their movement in gradients of attractants and repellents, plays an important role during the rhizosphere colonization by rhizobacteria. The rhizosphere is a unique niche for plant-microbe interactions. Root exudates are highly complex mixtures of chemoeffectors composed of hundreds of different compounds. Chemotaxis towards root exudates initiates rhizobacteria recruitment and the establishment of bacteria-root interactions. Over the last years, important progress has been made in the identification of root exudate components that play key roles in the colonization process, as well as in the identification of the cognate chemoreceptors. In the first part of this review, we summarized the roles of representative chemoeffectors that induce chemotaxis in typical rhizobacteria and discussed the structure and function of rhizobacterial chemoreceptors. In the second part we reviewed findings on how rhizobacterial chemotaxis and other root-microbe interactions promote the establishment of beneficial rhizobacteria-plant interactions leading to plant growth promotion and protection of plant health. In the last part we identified the existing gaps in the knowledge and discussed future research efforts that are necessary to close them.
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http://dx.doi.org/10.3390/ijms22136655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269324PMC
June 2021

Effect of Ferulic Acid-Grafted-Chitosan Coating on the Quality of Pork during Refrigerated Storage.

Foods 2021 Jun 14;10(6). Epub 2021 Jun 14.

College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, China.

Pork is perishable due to oxidation and microbial spoilage. Edible coating based on biopolymers and phenolic compounds is an effective way to preserve the quality of pork. In this study, ferulic acid-grafted-CS (ferulic acid-g-CS) with strong antioxidant and antimicrobial activities was synthesized through a carbodiimide-mediated coupling reaction. The obtained ferulic acid-g-CS was used as an edible coating material for fresh pork. The effect of ferulic acid-g-CS coating on the quality of pork during storage was investigated at 4 °C for 8 days. As compared to the uncoated pork, pork coated with CS and ferulic acid-g-CS showed lower total viable counts, total volatile basic nitrogen values, pH values, thiobarbituric acid reactive substances, and drip losses. Besides, pork coated with CS and ferulic acid-g-CS presented more compact microstructures than the uncoated pork at the eighth day. Sensory evaluation assay showed pork coated with CS and ferulic acid-g-CS had better color, odor, and over acceptance in comparison with the uncoated pork. Ferulic acid-g-CS coating, due to its relatively higher antioxidant and antimicrobial activities compared to CS coating, had a better performance in refrigerated pork preservation. Ferulic acid-g-CS coating effectively extended the shelf life of refrigerated pork to 7 days. This study revealed ferulic acid-g-CS coating was a promising technology for refrigerated pork preservation.
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http://dx.doi.org/10.3390/foods10061374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231958PMC
June 2021

Mutations of key driver genes in gastric cancer metastasis risk: a systematic review and meta-analysis.

Expert Rev Mol Diagn 2021 Jul 1:1-10. Epub 2021 Jul 1.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

: Associations between gene mutations and metastasis in gastric cancer (GC) remain contradictory, resulting in the inaccurate estimation of the magnitude of the risk associated with specific genotypes.: In this study, we first screened out four key driver genes (TP53, PIK3CA, APC and ARID1A) by jointly analyzing the mutation levels and searching the literature for genes associated with GC metastasis. We then performed a meta-analysis to demonstrate the relationship between these key driver gene mutations and GC metastasis, including lymphatic and distance metastasis.: We found out four key driver genes (TP53, PIK3CA, APC and ARID1A), associated with risk of GC metastasis. The results showed that TP53 (OR 1.39, 95% CI 1.12-1.72) and APC mutations (OR 0.58, 95% CI 0.38-0.89) were associated with lymph node metastasis and distant metastasis in GC. And TP53 mutations (OR 1.65, 95% CI 1.25-2.18) were significantly related to GC metastasis in the Asian population. APC mutations (OR 0.54, 95% CI 0.29-1.00) were also related to GC metastasis in the European and American populations. There was no significant association with GC metastasis in PIK3CA or ARID1A mutations.Mutations of TP53 and APC play important roles in lymph node metastasis and distant metastasis of GC and may be potential important biomarkers of progression and therapeutic targets. These observations should be further prospectively verified.
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http://dx.doi.org/10.1080/14737159.2021.1946394DOI Listing
July 2021

Salimicrobium humidisoli sp. nov., Isolated from Saline-Alkaline Soil.

Curr Microbiol 2021 Aug 28;78(8):3292-3298. Epub 2021 Jun 28.

Key Laboratory of Microbial Resources Collection and Preservation, Ministry of Agriculture, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, P.R. China.

A Gram-staining-positive, aerobic, non-endospore-forming, coccus-shaped, non-flagellated, and non-motile bacterium, designated WN024, was isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China. Cells of strain WN024 were catalase- and oxidase-positive. The isolate was able to grow between 20 and 45 °C (optimal at 33-37 °C), pH 6.5-11.0 (optimal 7.5-8.0), and in the presence of 5.0-25.0% NaCl (optimal at 10.0-15.0%, w/v). The isolate could be affiliated to the genus Salimicrobium and the highest 16S rRNA gene sequence similarity of strain WN024 to its closest relative Salimicrobium salexigens DSM 22782 was 97.9%. The size of the genome was 2,622,223 bp in size with a G + C content of 47.1%. The sole respiratory quinone of strain WN024 was MK-7, the predominant fatty acids were iso-C, anteiso-C and anteiso-C. The major polar lipids were phosphatidylglycerol (PG), glycolipid (GL), phospholipid (PL) and diphosphatidylglycerol (DPG). The cell-wall diamino acid was meso-diaminopimelic acid. The DNA-DNA hybridization values between strain WN024 and the closest relative S. salexigens DSM 22782 was 47.3 ± 2.3%. The highest average nucleotide identity (ANI) value was 92.3% to S. salexigens DSM 22782 (GenBank Accession No. GCA_900156705.1). Therefore, we propose a novel species in the genus Salimicrobium to accommodate this novel isolate, named Salimicrobium humidisoli sp. nov. The type strain is WN024 (= ACCC 19979 = KCTC 33897).
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http://dx.doi.org/10.1007/s00284-021-02551-4DOI Listing
August 2021

Loss of vagal integrity disrupts immune components of the microbiota-gut-brain axis and inhibits the effect of Lactobacillus rhamnosus on behavior and the corticosterone stress response.

Neuropharmacology 2021 Jun 24;195:108682. Epub 2021 Jun 24.

McMaster Brain-Body Institute, The Research Institute of St. Joseph's Hamilton, Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, Canada. Electronic address:

The vagus nerve is one of the major signalling components between the gut microbiota and brain. However, the exact relationship between gut-brain signaling along the vagus and the effects of gut microbes on brain function and behaviour is unclear. In particular, the relationship between the vagus nerve and immune signaling, that also appears to play a critical role in microbiota-gut-brain communication, has not been delineated. The aim of the present study was to determine the effect of subdiaphragmatic vagotomy on peripheral and central immune changes associated with the anxiolytic actions of L.rhamnosus. Male mice underwent vagotomy or sham surgery, followed by administration of L.rhamnosus for 14 days. L.rhamnosus administration following sham surgery resulted in reduced anxiety-like behaviour, and an attenuation of the hypothalamic-pituitary-adrenal axis (HPA axis), as indicated by reduced plasma corticosterone after acute restraint stress. These effects were associated with an increase in splenic T regulatory cells and a decrease in activated microglia in the hippocampus. The anxiolytic effects, HPA modulation and increase in T regulatory cells were prevented by vagotomy, whereas vagotomy alone led to a significant increase in activated microglia in the hippocampus that was not altered with L.rhamnosus treatment. Thus, both microbe induced and constitutive vagal signaling influences critical immune components of the microbiota-gut-brain axis. These findings suggest that, rather than acting as a direct neural link to the central nervous system, the role of the vagus nerve in gut-microbe to brain signalling is as an integral component of a bi-directional neuroimmunoendocrine pathway.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108682DOI Listing
June 2021

Global distribution and evolutionary transitions of angiosperm sexual systems.

Ecol Lett 2021 Jun 14. Epub 2021 Jun 14.

Institute of Ecology and Key Laboratory for Earth Surface Processes of the Ministry of Education, College of Urban and Environmental Sciences, Peking University, Beijing, China.

Angiosperm sexual systems are fundamental to the evolution and distribution of plant diversity, yet spatiotemporal patterns in angiosperm sexual systems and their drivers remain poorly known. Using data on sexual systems and distributions of 68453 angiosperm species, we present the first global maps of sexual system frequencies and evaluate sexual system evolution during the Cenozoic. Frequencies of dioecy and monoecy increase with latitude, while hermaphrodites are more frequent in warm and arid regions. Transitions to dioecy from other states were higher than to hermaphroditism, but transitions away from dioecy increased since the Cenozoic, suggesting that dioecy is not an evolutionary end point. Transitions between hermaphroditism and dioecy increased, while transitions to monoecy decreased with paleo-temperature when paleo-temperature >0℃. Our study demonstrates the biogeography of angiosperm sexual systems from a macroecological perspective, and enhances our understanding of plant diversity patterns and their response to climate change.
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http://dx.doi.org/10.1111/ele.13815DOI Listing
June 2021

Comparative Analysis and in vitro Experiments of Signatures and Prognostic Value of Immune Checkpoint Genes in Colorectal Cancer.

Onco Targets Ther 2021 31;14:3517-3534. Epub 2021 May 31.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.

Purpose: Immune checkpoints, as pivotal regulators of immune escape in cancer, can motivate the emergence of immune checkpoint inhibitors (ICIs). The aim of this study is to identify the expression of the immune checkpoint genes (ICGs) in colorectal cancer (CRC) and to relate their individual as well as combined expression to prognosis and therapeutic effectiveness in CRC.

Methods: RNA expression of 47 ICGs and clinical information of CRC patients were collected from two public databases to elucidate the expression levels and prognostic values of these ICGs in CRC. Then, the Shapiro-Wilk normality test was used to determine the normality of variables. Overall survival (OS) rates of each subset were found by Kaplan-Meier method, and the statistical significance was determined by the Log rank test ( < 0.05).

Results: The expression of 13 and 9 ICGs was significantly associated with CRC prognosis in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. A series of ICGs was found to be significantly associated with TMB, neoantigens and MMR in CRC indicating that the combination of immunotherapy treatment biomarkers and ICGs may achieve accurate prognostic stratification of CRC, and potentially identify CRC cases that might respond to checkpoint inhibitors (CPIs). The subsets of high or low PD1/PD-L1/IDO1 expression stratified by CD48 were accurately associated with prognosis in CRC. In addition, in vitro experiments confirmed that VTCN1(B7-H4)-KD increases anti-PD-L1-mediated NK cell cytotoxicity on CRC tumor cells.

Conclusion: Although the expression of a single immune-checkpoint molecule does not predict the efficacy of immunotherapy in CRC, our findings infer that subsets defined by ICGs are associated with prognosis and imply the possibility that VTCN1 and CD48 serve as new immunotherapeutic targets.
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http://dx.doi.org/10.2147/OTT.S304297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180296PMC
May 2021

Integrin α5 promotes migration and invasion through the FAK/STAT3/AKT signaling pathway in icotinib-resistant non-small cell lung cancer cells.

Oncol Lett 2021 Jul 24;22(1):556. Epub 2021 May 24.

Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Patients with non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (TKIs) ultimately develop drug resistance and metastasis. Therefore, there is a need to identify the underlying mechanisms of resistance to EGFR-TKIs. In the present study, colony formation and MTT assays were performed to investigate cell viability following treatment with icotinib. Gene Expression Omnibus datasets were used to identify genes associated with resistance. Wound healing and Transwell assays were used to detect cell migration and invasion with icotinib treatment and integrin α5-knockdown. The expression levels of integrin α5 and downstream genes were detected using western blotting. Stable icotinib-resistant (IcoR) cell lines (827/IcoR and PC9/IcoR) were established that showed enhanced malignant properties compared with parental cells (HCC827 and PC9). Furthermore, the resistant cell lines were resistant to icotinib in terms of proliferation, migration and invasion. The enrichment of function and signaling pathways analysis showed that integrin α5-upregulation was associated with the development of icotinib resistance. The knockdown of integrin α5 attenuated the migration and invasion capability of the resistant cells. Moreover, a combination of icotinib and integrin α5 siRNA significantly inhibited migration and partly restored icotinib sensitivity in IcoR cells. The expression levels of phosphorylated (p)-focal adhesion kinase (FAK), p-STAT3 and p-AKT decreased after knockdown of integrin α5, suggesting that FAK/STAT3/AKT signaling had a notable effect on the resistant cells. The present study revealed that the integrin α5/FAK/STAT3/AKT signaling pathway promoted icotinib resistance and malignancy in IcoR NSCLC cells. This signaling pathway may provide promising targets against acquired resistance to EGFR-TKI in patients with NSCLC.
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http://dx.doi.org/10.3892/ol.2021.12817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161469PMC
July 2021

Impact of 2D-3D Heterointerface on Remote Epitaxial Interaction through Graphene.

ACS Nano 2021 Jun 3;15(6):10587-10596. Epub 2021 Jun 3.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Remote epitaxy has drawn attention as it offers epitaxy of functional materials that can be released from the substrates with atomic precision, thus enabling production and heterointegration of flexible, transferrable, and stackable freestanding single-crystalline membranes. In addition, the remote interaction of atoms and adatoms through two-dimensional (2D) materials in remote epitaxy allows investigation and utilization of electrical/chemical/physical coupling of bulk (3D) materials 2D materials (3D-2D-3D coupling). Here, we unveil the respective roles and impacts of the substrate material, graphene, substrate-graphene interface, and epitaxial material for electrostatic coupling of these materials, which governs cohesive ordering and can lead to single-crystal epitaxy in the overlying film. We show that simply coating a graphene layer on wafers does not guarantee successful implementation of remote epitaxy, since atomically precise control of the graphene-coated interface is required, and provides key considerations for maximizing the remote electrostatic interaction between the substrate and adatoms. This was enabled by exploring various material systems and processing conditions, and we demonstrate that the rules of remote epitaxy vary significantly depending on the ionicity of material systems as well as the graphene-substrate interface and the epitaxy environment. The general rule of thumb discovered here enables expanding 3D material libraries that can be stacked in freestanding form.
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http://dx.doi.org/10.1021/acsnano.1c03296DOI Listing
June 2021

Immune Landscape of Gastric Carcinoma Tumor Microenvironment Identifies a Peritoneal Relapse Relevant Immune Signature.

Front Immunol 2021 13;12:651033. Epub 2021 May 13.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

Background: Gastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC.

Methods: In this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated single-sample gene set enrichment (ssGSEA) analysis algorithm. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to select the valuable immune cells and construct the final model for the prediction of PR. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to check the accuracy of PRIs. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the molecular pathways associated with PRIs.

Results: A peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively.

Conclusion: Overall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.
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http://dx.doi.org/10.3389/fimmu.2021.651033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155484PMC
May 2021

Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial.

J Thorac Oncol 2021 May 23. Epub 2021 May 23.

Peking Union Medical College Hospital, Department of Pulmonary Medicine, Beijing, People's Republic of China.

Introduction: Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC).

Methods: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points.

Results: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]).

Conclusions: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
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http://dx.doi.org/10.1016/j.jtho.2021.05.005DOI Listing
May 2021

Significantly improving the thermostability of a hyperthermophilic GH10 family xylanase XynAF1 by semi-rational design.

Appl Microbiol Biotechnol 2021 Jun 20;105(11):4561-4576. Epub 2021 May 20.

Key Laboratory of Microbial Resources Collection and Preservation, Ministry of Agriculture, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, 100081, People's Republic of China.

Xylanases have a broad range of applications in industrial biotechnologies, which require the enzymes to resist the high-temperature environments. The majority of xylanases have maximum activity at moderate temperatures, which limited their potential applications in industries. In this study, a thermophilic GH10 family xylanase XynAF1 from the high-temperature composting strain Aspergillus fumigatus Z5 was characterized and engineered to further improve its thermostability. XynAF1 has the optimal reaction temperature of 90 °C. The crystal structure of XynAF1 was obtained by X-ray diffraction after heterologous expression, purification, and crystallization. The high-resolution X-ray crystallographic structure of the protein-product complex was obtained by soaking the apo-state crystal with xylotetraose. Structure analysis indicated that XynAF1 has a rigid skeleton, which helps to maintain the hyperthermophilic characteristic. The homologous structure analysis and the catalytic center mutant construction of XynAF1 indicated the conserved catalytic center contributed to the high optimum catalytic temperature. The amino acids in the surface of xylanase XynAF1 which might influence the enzyme thermostability were identified by the structure analysis. Combining the rational design with the saturation mutation at the high B-value regions, the integrative mutant XynAF1-AC with a 6-fold increase of thermostability was finally obtained. This study efficiently improved the thermostability of a GH10 family xylanase by semi-rational design, which provided a new biocatalyst for high-temperature biotechnological applications. KEY POINTS: • Obtained the crystal structure of GH10 family hyperthermophilic xylanase XynAF1. • Shed light on the understanding of the GH10 family xylanase thermophilic mechanism. • Constructed a 6-fold increased thermostability recombinant xylanase.
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http://dx.doi.org/10.1007/s00253-021-11340-9DOI Listing
June 2021

Zoom lens with high zoom ratio design based on Gaussian bracket and particle swarm optimization.

Appl Opt 2021 Apr;60(11):3217-3223

In this paper, we use Gaussian brackets and a particle swarm optimization (PSO) algorithm to design a 20× four-group zoom lens with a focus tunable lens and two moving groups. This method uses Gaussian brackets to derive the paraxial design equations of the zoom lens and determine the lens parameters. In the optimization stage, we define an objective function as a performance indicator to optimize its first-order design and implement the PSO algorithm in MATLAB to find its global optimal first-order design. The optimized 20× zoom lens has a focal length of 4.5-90 mm and a total length of 145 mm. This method solves the difficulty of solving the initial structure of the zoom. Compared with traditional trial and error, the calculation speed is faster, the accuracy is higher, and it does not rely on the initial value. The results show that this method is suitable for the first-order design of complex optical systems.
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http://dx.doi.org/10.1364/AO.418970DOI Listing
April 2021

Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Gastroenterol Hepatol 2021 Jul 8;6(7):559-568. Epub 2021 May 8.

Department of Intervention, Fujian Cancer Hospital, Fuzhou, China.

Background: Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma.

Methods: AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860.

Findings: Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators.

Interpretation: Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile.

Funding: Jiangsu Hengrui Medicine.
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http://dx.doi.org/10.1016/S2468-1253(21)00109-6DOI Listing
July 2021

Graphene Buffer Layer on SiC as a Release Layer for High-Quality Freestanding Semiconductor Membranes.

Nano Lett 2021 05 26;21(9):4013-4020. Epub 2021 Apr 26.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Free-standing crystalline membranes are highly desirable owing to recent developments in heterogeneous integration of dissimilar materials. Van der Waals (vdW) epitaxy enables the release of crystalline membranes from their substrates. However, suppressed nucleation density due to low surface energy has been a challenge for crystallization; reactive materials synthesis environments can induce detrimental damage to vdW surfaces, often leading to failures in membrane release. This work demonstrates a novel platform based on graphitized SiC for fabricating high-quality free-standing membranes. After mechanically removing epitaxial graphene on a graphitized SiC wafer, the quasi-two-dimensional graphene buffer layer (GBL) surface remains intact for epitaxial growth. The reduced vdW gap between the epilayer and substrate enhances epitaxial interaction, promoting remote epitaxy. Significantly improved nucleation and convergent quality of GaN are achieved on the GBL, resulting in the best quality GaN ever grown on two-dimensional materials. The GBL surface exhibits excellent resistance to harsh growth environments, enabling substrate reuse by repeated growth and exfoliation.
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http://dx.doi.org/10.1021/acs.nanolett.1c00673DOI Listing
May 2021

Vagotomy and insights into the microbiota-gut-brain axis.

Neurosci Res 2021 Jul 19;168:20-27. Epub 2021 Apr 19.

McMaster Brain-Body Institute, The Research Institute of St. Joseph's Hamilton, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address:

The Microbiota-gut-brain axis describes the bidirectional communication between central nervous system and microorganisms in the gastrointestinal tract. Increasing evidence has suggests that the vagus nerve, a major neural connection between the gut and brain, plays a key role in facilitating signaling along the microbiota-gut-brain axis. Much of this evidence has come from studies employing surgical subdiaphragmatic vagotomy. Here we provide a review of the use of vagotomy as a tool to explore the role of the vagus nerve in gut to brain signaling and the knowledge this approach has provided. We also examine how, more recently, vagotomy has contributed to the understanding of the vagus nerve as a bridge for multi-systemic communication; linking microbiota, immune and central nervous systems. Finally, we address limitations to surgical vagotomy and identify such limitations may be mitigated in future studies.
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http://dx.doi.org/10.1016/j.neures.2021.04.001DOI Listing
July 2021

Bacillus velezensis tolerance to the induced oxidative stress in root colonization contributed by the two-component regulatory system sensor ResE.

Plant Cell Environ 2021 Apr 17. Epub 2021 Apr 17.

Jiangsu Provincial Key Lab for Organic Solid Waste Utilization, National Engineering Research Center for Organic-based Fertilizers, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, Nanjing Agricultural University, Nanjing, China.

Efficient root colonization of plant growth-promoting rhizobacteria is critical for their plant-beneficial functions. However, the strategy to overcome plant immunity during root colonization is not well understood. In particular, how Bacillus strains cope with plant-derived reactive oxygen species (ROS), which function as the first barrier of plant defence, is not clear. In the present study, we found that the homolog of flg22 in Bacillus velezensis SQR9 (flg22 ) has 78.95% identity to the typical flg22 (flg22 ) and induces a significant oxidative burst in cucumber and Arabidopsis. In contrast to pathogenic or beneficial Pseudomonas, live B. velezensis SQR9 also induced an oxidative burst in cucumber. We further found that B. velezensis SQR9 tolerated higher H O levels than Pst DC3000, the pathogen that harbours the typical flg22, and that it possesses the ability to suppress the flg22-induced oxidative burst, indicating that B. velezensis SQR9 may exploit a more efficient ROS tolerance system than DC3000. Further experimentation with mutagenesis of bacteria and Arabidopsis showed that the two-component regulatory system, ResDE, in B. velezensis SQR9 is involved in tolerance to plant-derived oxidative stress, thus contributing to root colonization. This study supports a further investigation of the interaction between beneficial rhizobacteria and plant immunity.
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http://dx.doi.org/10.1111/pce.14068DOI Listing
April 2021

Correction to: LncRNA APCDD1L-AS1 induces icotinib resistance by inhibition of EGFR autophagic degradation via the miR-1322/miR-1972/ miR-324-3p-SIRT5 axis in lung adenocarcinoma.

Biomark Res 2021 Apr 14;9(1):25. Epub 2021 Apr 14.

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, No.155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China.

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http://dx.doi.org/10.1186/s40364-021-00279-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048049PMC
April 2021

Distinct prognostic values of programmed death-ligand 1 and programmed cell death protein 1 in lung adenocarcinoma and squamous cell carcinoma patients.

Ann Transl Med 2021 Mar;9(5):397

Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.

Background: Although immunotherapy has demonstrated similar clinical activities in the treatment of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), several studies have shown programmed death-ligand 1 (PD-L1) to have different predictive roles in ADC and SCC. This study was conducted to compare the different functions of PD-L1/programmed cell death protein 1 (PD-1) pathway in these malignancies.

Methods: A multi-dimensional analysis based on public databases and 2 independent cohorts including 262 patients with lung cancer was performed. Immunohistochemistry (IHC) and fluorescence-based multiplexed staining were used to detect the immune factors.

Results: PD-L1 was observed to have different expressions and regulatory mechanisms between SCC and ADC. PD-L1 was significantly increased from the messenger RNA (mRNA) to protein levels in the SCC group compared with the ADC group. Also, PD-L1 on tumor cells (TCs) was positively correlated with CD8 tumor lymphocyte infiltrates in ADC, but not in SCC. More importantly, PD-L1 was considered to be an independent predictor of overall survival (OS) for ADC patients. In contrast, in SCC patients, PD-1 tumor-infiltrating lymphocytes (TILs) were considered a poor prognostic predictor.

Conclusions: These findings showed that PD-L1 in ADC and PD-1 TILs in SCC respectively indicates T-cell function, which plays a crucial role in determining prognosis. The distinct functions of the biomarkers between ADC and SCC might provide potential avenues for guiding anti-PD-1/PD-L1 immunotherapy.
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http://dx.doi.org/10.21037/atm-20-968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033326PMC
March 2021

Tricycloquinazoline-Based 2D Conductive Metal-Organic Frameworks as Promising Electrocatalysts for CO Reduction.

Angew Chem Int Ed Engl 2021 Jun 6;60(26):14473-14479. Epub 2021 May 6.

Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Science, Tianjin University, Tianjin, 300072, China.

2D conductive metal-organic frameworks (2D c-MOFs) are promising candidates for efficient electrocatalysts for the CO reduction reaction (CO RR). A nitrogen-rich tricycloquinazoline (TQ) based multitopic catechol ligand was used to coordinate with transition-metal ions (Cu and Ni ), which formed 2D graphene-like porous sheets: M (HHTQ) (M=Cu, Ni; HHTQ=2,3,7,8,12,13-Hexahydroxytricycloquinazoline). M (HHTQ) can be regarded as a single-atom catalyst where Cu or Ni centers are uniformly distributed in the hexagonal lattices. Cu (HHTQ) exhibited superior catalytic activity towards CO RR in which CH OH is the sole product. The Faradic efficiency of CH OH reached up to 53.6 % at a small over-potential of -0.4 V. Cu (HHTQ) exhibited larger CO adsorption energies and higher activities over the isostructural Ni (HHTQ) and the reported archetypical Cu (HHTP) . There is a strong dependence of both metal centers and the N-rich ligands on the electrocatalytic performance.
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http://dx.doi.org/10.1002/anie.202103398DOI Listing
June 2021

Chitosan Films Functionalized with Different Hydroxycinnamic Acids: Preparation, Characterization and Application for Pork Preservation.

Foods 2021 Mar 5;10(3). Epub 2021 Mar 5.

College of Food Science and Engineering, Yangzhou University, Yangzhou 225127, China.

Hydroxycinnamic acids are one category of bioactive phenolic acids that are widely distributed in plants. In this study, chitosan (CS) was functionalized with three kinds of hydroxycinnamic acids (-coumaric acid, caffeic acid and ferulic acid) through the carbodiimide-mediated grafting method. The obtained hydroxycinnamic-acid-grafted CSs (hydroxycinnamic acid-g-CSs) were further fabricated into food packaging films through solvent casting. For the first time, the functionalities of the different hydroxycinnamic acid-g-CS films were compared. Results showed the grafting ratio of -coumaric acid-g-CS, caffeic acid-g-CS and ferulic acid-g-CS was 73.68, 129.42 and 91.75 mg/g, respectively. Instrumental analyses confirmed hydroxycinnamic acids conjugated with CS through amide and ester bonds. The functionalization of CS film with hydroxycinnamic acids produced a more compact microstructure and higher UV light barrier ability, mechanical strength, water vapor barrier ability, thermal stability and antioxidant and antimicrobial activities. Among the different hydroxycinnamic acid-g-CS films, caffeic acid-g-CS film presented the strongest barrier, mechanical, antioxidant and antimicrobial properties. Moreover, caffeic acid-g-CS film packaging effectively extended the shelf life of pork to 10 days at 4 °C. Our results suggest caffeic acid-g-CS film can be used in the active food packaging field.
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http://dx.doi.org/10.3390/foods10030536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000987PMC
March 2021

Interferon regulatory factor 6 correlates with the progression of non-small cell lung cancer and can be regulated by miR-320.

J Pharm Pharmacol 2021 Mar;73(5):682-691

Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China.

Objectives: The expression of interferon regulatory factor 6 (IRF6) has been reported in several cancer types, but its roles underlying the progression of lung cancer have not been detailedly investigated.

Methods: The pairs of lung cancer tissues and para-carcinoma tissues and The Cancer Genome Atlas database were collected to detect IRF6 expression. Cell counting kit-8, transwell and terminal-deoxynucleoitidyl transferase-mediated nick end labelling assays were used to evaluate cell proliferation, migration and apoptosis.

Key Findings: A significant up-regulation of IRF6 in both lung adenocarcinoma and lung squamous cell carcinoma tissues compared with normal non-tumor tissues. Subsequently, Immunostaining also revealed that canceration of lung tissues predisposed to evoke IRF6 expression. In vitro experiments revealed the antitumour effects, including growth and migration inhibition, of IRF6 siRNA transfection. Considering miR-320 as an endogenous inhibitor to IRF6, miR-320 mimics transfection led to the inhibition of proliferation and migration of lung cancer cells. However, overexpressed IRF6 neutralized the antineoplastic activities of miR-320 in lung cancer cells.

Conclusions: The miR-320/IRF6 signalling axis was implicated in pulmonary canceration. miR-320 as an endogenous inhibitor of IRF6 provided a novel therapeutic strategy for the treatment of lung cancer.
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http://dx.doi.org/10.1093/jpp/rgab009DOI Listing
March 2021

Experimental evaluation of an OFDM-PWM-based X-ray communication system.

Opt Express 2021 Feb;29(3):3596-3608

We experimentally demonstrate an improved orthogonal frequency division multiplexing (OFDM) into the pulse width modulation (PWM) scheme for the X-ray communication (XCOM). The scheme is insensitive to the nonlinearity of the grid-controlled X-ray tube with switching 'on' and 'off' between two points. The dependence of this system's bit-error-rate (BER) performances on the data rates and the working parameters including the anode voltage and filament current of the grid-controlled X-ray tube are studied. The OFDM-PWM scheme reaches the data rate of 360 kbps at a BER of the forward error correction threshold of 3.8 × 10 over a 5 cm air channel. In addition, an experiment aided by density-based spatial clustering of applications with noise nonlinear compensation is carried out, and the results demonstrate the improvements in Q-factor by 0.62 dB.
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http://dx.doi.org/10.1364/OE.415291DOI Listing
February 2021

Bioinformatics-Based Identification of HDAC Inhibitors as Potential Drugs to Target EGFR Wild-Type Non-Small-Cell Lung Cancer.

Front Oncol 2021 8;11:620154. Epub 2021 Mar 8.

Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, Shenyang, China.

Patients with EGFR-mutant non-small-cell lung cancer (NSCLC) greatly benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) while the prognosis of patients who lack EGFR-sensitive mutations (EGFR wild type, EGFR-WT) remains poor due to a lack of effective therapeutic strategies. There is an urgent need to explore the key genes that affect the prognosis and develop potentially effective drugs in EGFR-WT NSCLC patients. In this study, we clustered functional modules related to the survival traits of EGFR-WT patients using weighted gene co-expression network analysis (WGCNA). We used these data to establish a two-gene prognostic signature based on the expression of CYP11B1 and DNALI1 by combining the least absolute shrinkage and selection operator (LASSO) algorithms and Cox proportional hazards regression analysis. Following the calculation of risk score (RS) based on the two-gene signature, patients with high RSs showed a worse prognosis. We further explored targeted drugs that could be effective in patients with a high RS by the connectivity map (CMap). Surprisingly, multiple HDAC inhibitors (HDACis) such as trichostatin A (TSA) and vorinostat (SAHA) that may have efficacy were identified. Also, we proved that HDACis could inhibit the proliferation and metastasis of NSCLC cells . Taken together, our study identified prognostic biomarkers for patients with EGFR-WT NSCLC and confirmed a novel potential role for HDACis in the clinical management of EGFR-WT patients.
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http://dx.doi.org/10.3389/fonc.2021.620154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982742PMC
March 2021

SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice.

Animal Model Exp Med 2021 03 6;4(1):2-15. Epub 2021 Mar 6.

Key Laboratory of Human Disease Comparative Medicine National Health Commission of China (NHC) Institute of Laboratory Animal Science Peking Union Medicine College Chinese Academy of Medical Sciences Beijing China.

Background: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are top two chronic comorbidities that increase the severity and mortality of COVID-19. However, how SARS-CoV-2 alters the progression of chronic diseases remain unclear.

Methods: We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice. SARS-CoV-2's impacts on pathogenesis of chronic diseases were studied through histopathological, virologic and molecular biology analysis.

Results: Pre-existing CVDs resulted in viral invasion, ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection. Viral infection increased fasting blood glucose and reduced insulin response in DM model. Bone mineral density decreased shortly after infection, which associated with impaired PI3K/AKT/mTOR signaling.

Conclusion: We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases. Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection, which further aggravated the pre-existing diseases. This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.
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http://dx.doi.org/10.1002/ame2.12155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954823PMC
March 2021
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