Publications by authors named "Xuan Wang"

1,381 Publications

  • Page 1 of 1

DNA-encoded CH functionality via photoredox-mediated hydrogen atom transformation catalysis.

Bioorg Med Chem 2021 May 28;42:116234. Epub 2021 May 28.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address:

We described a mode of catalytic activation that accomplished the α-alkylation of N-Boc saturated heterocycles with DNA-linked acrylamide via photoredox-mediated hydrogen atom transfer (HAT) catalysis. This C(sp3)-C(sp3) bond formation reaction tolerated five-, six- and seven-membered cyclic substrates, substantially streamline synthetic efforts to functionalize the α-position of heterocycles with native CH functional handle. This photoredox catalyzed CH functionalization proceeded in mild DNA-compatible condition, and suited for the construction of DNA-encoded libraries.
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http://dx.doi.org/10.1016/j.bmc.2021.116234DOI Listing
May 2021

Quercetin prevents isoprenaline-induced myocardial fibrosis by promoting autophagy via regulating miR-223-3p/FOXO3.

Cell Cycle 2021 Jun 7:1-17. Epub 2021 Jun 7.

Department of Ophthalmology, Eye Hospital of China Academy of Chinese Medical Sciences, Shijingshan District, Beijing, China.

Atrial fibrillation (AF) is the common arrhythmias. Myocardial fibrosis (MF) is closely related to atrial remodeling and leads to AF. MF is the main cause of cardiovascular diseases and a pathological basis of AF. Thus, the underlying mechanism in MF and AF development should be fully elucidated for AF therapeutic innovation. Autophagy is a highly conserved lysosomal degradation pathway, and the relationship between autophagy and MF has been previously shown. Moreover, research reported that quercetin (Que) could ameliorate MF. The current study aimed to explore the mechanism of Que in MF. The results in this study showed that in clinical AF patients and in aged rats, miR-223-3p was high-expressed, while FOXO3 and autophagy pathway related proteins, such as ATG7, p62/SQSTM1 and the ratio of LC3B-II/LC3B-I were significantly inhibited. In and in studies, we found that Que can effectively inhibit the expression of miR-223-3p in AF model cells and rats myocardial tissues, and meanwhile enhance the expression of FOXO3 and activate the autophagy pathway, and significantly inhibit myocardial fibrosis, and improve myocardial remodeling in atrial fibrillation. All in all, in this study, we found that Que prevents isoprenaline-induced MF by increasing autophagy via regulating miR-223-3p/FOXO3.
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http://dx.doi.org/10.1080/15384101.2021.1932029DOI Listing
June 2021

A Prognostic Ferroptosis-Related lncRNAs Signature Associated With Immune Landscape and Radiotherapy Response in Glioma.

Front Cell Dev Biol 2021 19;9:675555. Epub 2021 May 19.

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are implicated in the regulation of tumor cell ferroptosis. However, the prognostic value of ferroptosis-related lncRNAs has never been comprehensively explored in glioma. In this study, the transcriptomic data and clinical information of glioma patients were downloaded from TCGA, CGGA and Rembrandt databases. We identified 24 prognostic ferroptosis-related lncRNAs, 15 of which (SNAI3-AS1, GDNF-AS1, WDFY3-AS2, CPB2-AS1, WAC-AS1, SLC25A21-AS1, ARHGEF26-AS1, LINC00641, LINC00844, MIR155HG, MIR22HG, PVT1, SNHG18, PAXIP1-AS2, and SBF2-AS1) were used to construct a ferroptosis-related lncRNAs signature (FRLS) according to the least absolute shrinkage and selection operator (LASSO) regression. The validity of this FRLS was verified in training (TCGA) and validation (CGGA and Rembrandt) cohorts, respectively. The Kaplan-Meier curves revealed a significant distinction of overall survival (OS) between the high- and low-risk groups. The receiver operating characteristic (ROC) curves exhibited robust prognostic capacity of this FRLS. A nomogram with improved accuracy for predicting OS was established based on independent prognostic factors (FRLS, age, and WHO grade). Besides, patients in the high-risk group had higher immune, stroma, and ESTIMATE scores, lower tumor purity, higher infiltration of immunosuppressive cells, and higher expression of immune checkpoints. Patients in the low-risk group benefited significantly from radiotherapy, while no survival benefit of radiotherapy was observed for those in the high-risk group. In conclusion, we identified the prognostic ferroptosis-related lncRNAs in glioma, and constructed a prognostic signature which was associated with the immune landscape of glioma microenvironment and radiotherapy response.
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http://dx.doi.org/10.3389/fcell.2021.675555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170051PMC
May 2021

Risk Models for Advanced Melanoma Patients Under Anti-PD-1 Monotherapy- Analyses of Pooled Data From Two Clinical Trials.

Front Oncol 2021 20;11:639085. Epub 2021 May 20.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma, Peking University Cancer Hospital and Institute, Beijing, China.

The best response and survival outcomes between advanced melanoma patients treated with the anti-PD-1 monotherapy vary greatly, rendering a risk model in need to optimally stratify patients based on their likelihood to benefit from the said treatment. We performed an analysis of 89 advanced melanoma patients treated with the anti-PD-1 monotherapy from two prospective clinical trials at the Peking University Cancer Hospital from April 2016 to May 2018. Clinicodemographical characteristics, baseline and early-on-treatment (median 0.6 months after anti-PD-1 monotherapy initiation) routine laboratory variables, including complete blood count and general chemistry, and best response/survival data were extracted and analyzed in both univariate and multivariate logistic and Cox proportional hazard models. After three rounds of screening, risk factors associated with a poorer PFS included a high pre-treatment neutrophil, derived neutrophil-lymphocyte ratio (dNLR), low pre-treatment hemoglobin, and low early-on-/pre-treatment fold change of eosinophil; those with a poorer OS included a high pre-treatment neutrophil, eosinophil, PLT, early-on/pre-treatment fold change of LDH and neutrophil; and those with a poorer best response included a high pre-treatment NLR and early-on-/pre-treatment LDH fold change. Risk models (scale: low, median-low, median high, and high risk) were established based on these risk factors as dichotomous variables and M stage (with vs. without distant metastasis) for PFS (HR 1.976, 95% CI, 1.507-2.592, < 0.001), OS (HR 2.348, 95% CI, 1.688-3.266), and non-responder (OR 3.586, 95% CI, 1.668-7.713, = 0.001), respectively. For patients with low, median-low, median-high, and high risks of developing disease progression (PD), six-month PFS rates were 64.3% (95% CI, 43.5-95.0%), 37.5% (95% CI, 22.4-62.9%), 9.1% (95% CI, 3.1-26.7%), and 0%, respectively. For patients with OS risks of low, median-low, median-high, and high, OS rates at 12 months were 82.5% (95% CI, 63.1-100%), 76.6% (95% CI, 58.4-100%), 42.1% (95% CI, 26.3-67.3%), and 23.9% (95% CI, 11.1-51.3%), respectively. For patients with risks of low, median-low, median-high, and high of being a non-responder, objective response rates were 50.0% (95% CI, 15.7-84.3%), 27.8% (95% CI, 9.7-53.5%), 10.3% (95% CI, 2.9-24.2%), and 0%, respectively. A risk scoring model based on the clinicodemographical characteristics and easily obtainable routinely tested laboratory biomarkers may facilitate the best response and survival outcome prediction and personalized therapeutic decision making for the anti-PD-1 monotherapy treated advanced melanoma patients in Asia.
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http://dx.doi.org/10.3389/fonc.2021.639085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174451PMC
May 2021

CDK5 Knockdown inhibits proliferation and induces apoptosis and Cell Cycle Arrest in Human Glioblastoma.

J Cancer 2021 10;12(13):3958-3966. Epub 2021 May 10.

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Gliomas are the most common malignant brain neoplasms with high recurrence and lethality rates. Recently, studies have reported that cyclin-dependent kinase 5 (CDK5) is involved in tumorigenesis. Herein, we applied bioinformatics analysis to determine the clinical value of CDK5 in patients with glioma and examined the effects of CDK5 on glioblastoma cell proliferation, apoptosis, and cell cycle . Gene expression profiles containing clinical data of low-grade glioma (LGG) and glioblastoma cohorts were obtained from The Cancer Genome Atlas database and analyzed to determine the association between CDK5 expression and glioma clinicopathological characteristics. Kaplan-Meier survival analysis was performed for prognosis analysis. Gene set enrichment analysis (GSEA) was used to identify the biological pathways involved in differential CDK5 expression. experiments were performed to explore the effects of CDK5 on glioma cell functions. CDK5 expression was substantially higher in glioblastoma than in LGG. GSEA showed that some metabolism-related pathways were associated with the high CDK5 expression phenotype. experiments showed that CDK5 knockdown impaired cell proliferation and colony formation ability, and induced apoptosis and cell cycle arrest. CDK5 may act as a potential biomarker of glioma progression and a valid target for glioma therapy.
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http://dx.doi.org/10.7150/jca.53981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176241PMC
May 2021

Interrelationships Between Oxidative Stress, Cytokines, and Psychotic Symptoms and Executive Functions in Patients With Chronic Schizophrenia.

Psychosom Med 2021 Jun;83(5):485-491

From the Department of Psychiatry, Shenzhen Kangning Hospital (Wu); Shenzhen Mental Health Center (Wu). Shenzhen, Guangdong; Yantai Automobile Engineering Professional College (Yu), Yantai; Department of Psychiatry (Wang, Guan), Hebei Province Rong-Jun Hospital, Baoding; Psychiatry Research Center, Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School (Xiu); and CAS Key Laboratory of Mental Health, Institute of Psychology (Zhang), Chinese Academy of Sciences, Beijing, China.

Objective: Accumulating evidence has demonstrated that the pathophysiology of schizophrenia is involved in various abnormalities in oxidative stress markers and cytokines closely related to synaptic plasticity. However, the interactive effects among key cytokines, oxidative stress, and executive dysfunction and symptoms of schizophrenia have not been investigated yet.

Methods: A total of 189 patients with chronic schizophrenia and 60 controls were recruited in the current study. Tumor necrosis factor α (TNF-α), interleukin (IL)-8, IL-6, and IL-2 levels; catalase, glutathione peroxidase, and superoxide dismutase (SOD) activities; and malondialdehyde (MDA) levels were determined in patients and controls. Executive function was evaluated by the Wisconsin card sorting tests, the verbal fluency tests, and the Stroop word-color test. Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale.

Results: Relative to the controls, the patients had lower activities of SOD and glutathione peroxidase and levels of TNF-α, but higher levels of MDA, IL-8, IL-6, and IL-2 (all p values < .05). A significant negative relationship between SOD activity and IL-8 levels was found only in patients (β = -0.44, p = .008). Furthermore, we found that an interactive effect of low TNF-α level and high MDA level was associated with negative symptoms (β = -0.02, p = .01). Moreover, the interactive effects of IL-8 and MDA or IL-8 and SOD were correlated with executive function only in patients (β = 0.23, p = .02; β = 0.09, p = .03).

Conclusions: Our findings suggest that the interrelationships between oxidative stress markers and cytokines occur in schizophrenia patients, which may be the basis of their pathological mechanisms underlying clinical symptoms and cognitive dysfunction.
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http://dx.doi.org/10.1097/PSY.0000000000000931DOI Listing
June 2021

Long noncoding RNA ANRIL knockdown attenuates neuroinflammation following ischemic stroke via suppressing the expression of NF-κB in vitro and in vivo.

Neurol Res 2021 Jun 3:1-11. Epub 2021 Jun 3.

College of Pharmacology, the Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, China.

Objective: Increasing evidence suggests that long-noncoding RNAs can exert neuroprotective effects in cerebral ischemia-reperfusion injury. Levels of the long noncoding RNA ANRIL (ANRIL) are reportedly altered in ischemic stroke (IS) patients, but its role in IS requires further clarification. This study was designed to explore the mechanistic function of ANRIL in IS.

Methods: , HT22 cells was treated with an oxygen-glucose deprivation/reperfusion (OGD/R). , brain ischemia/reperfusion was induced by 60-minute transient middle cerebral artery occlusion/reperfusion (MCAO/R) IS model in C57/BL6 mice. Additionally, cells were transfected with si-ANRIL, pcDNA3.1-ANRIL, pcDNA3.1-NF-κB, or appropriate negative controls, and si-ANRIL and pcDNA3.1-NF-κB were administered into the lateral ventricles in MCAO/R model mice. Cell viability and apoptosis were detected via MTT and flow cytometry assays. mRNA and protein expression of NF-κB were detected via qRT-PCR and Western blotting. IL-1β, IL-6, TNF-a, and iNOS levels were detected via ELISA. In addition, infarcted area and neuronal injury were evaluated via TTC, Nissl, and immunofluorescent staining.

Results: We found that ANRIL knockdown increased cell viability and reduced apoptosis . Additionally, we found that ANRIL knockdown decreased p-P65, P65, IL-1β, IL-6, TNF-a, and iNOS levels, whereas these effects were reversed by NF-κB overexpression both and .

Conclusion: our results suggest that ANRIL knockdown attenuates neuroinflammation by suppressing the expression of NF-κB both and vivo model of IS, sugguesting that ANRIL might be a potentially viable therapeutictarget to diminish neuroinflammation in IS patients.
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http://dx.doi.org/10.1080/01616412.2021.1934317DOI Listing
June 2021

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant the Nrf2 Pathway.

Front Physiol 2021 12;12:615974. Epub 2021 May 12.

Department of Pain Management, The Affiliated Hospital of Qingdao University, Qingdao, China.

Methane (CH) exerted protective effects against lung ischemia-reperfusion (I/R) injury, but the mechanism remains unclear, especially the role of pulmonary surfactant. Therefore, this study aimed to explore the effects of CH inhalation on pulmonary surfactant in rat lung I/R injury and to elucidate the mechanism. Rats were randomly divided into three groups ( = 6): the sham, I/R control, and I/R CH groups. In the sham group, only thoracotomy was performed on the rats. In the I/R control and I/R CH groups, the rats underwent left hilum occlusion for 90 min, followed by reperfusion for 180 min and ventilation with O or 2.5% CH, respectively. Compared with those of the sham group, the levels of large surfactant aggregates (LAs) in pulmonary surfactant, lung compliance, oxygenation decreased, the small surfactant aggregates (SAs), inflammatory response, oxidative stress injury, and cell apoptosis increased in the control group ( < 0.05). Compared to the control treatment, CH increased LA (0.42 ± 0.06 vs. 0.31 ± 0.09 mg/kg), oxygenation (201 ± 11 vs. 151 ± 14 mmHg), and lung compliance (16.8 ± 1.0 vs. 11.5 ± 1.3 ml/kg), as well as total antioxidant capacity and Nrf2 protein expression and decreased the inflammatory response and number of apoptotic cells ( < 0.05). In conclusion, CH inhalation decreased oxidative stress injury, inflammatory response, and cell apoptosis, and improved lung function through Nrf2-mediated pulmonary surfactant regulation in rat lung I/R injury.
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http://dx.doi.org/10.3389/fphys.2021.615974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149795PMC
May 2021

A new Leuconostoc citreum strain discovered in the traditional sweet potato sour liquid fermentation as a novel bioflocculant for highly efficient starch production.

Food Res Int 2021 Jun 22;144:110327. Epub 2021 Mar 22.

College of Food Science and Nutritional Engineering, China Agricultural University, National Engineering Research Center for Fruit & Vegetable Processing, Key Laboratory of Fruit & Vegetable Processing, Ministry of Agriculture and Agricultural Affairs, Beijing Key Laboratory for Food Non-thermal Processing, Beijing 100083, China. Electronic address:

Sour liquid fermentation is commonly used in the sedimentation process of traditional starch production, where bacteria play a critical role in starch flocculation. In this study, the dynamic changes of bacterial compositions during sweet potato sour liquid (SPSL) fermentation were profiled using the single-molecule real-time (SMRT) sequencing, unveiling that Leuconostoc citreum, Leuconostoc pseudomesenteroides, Lactococcus lactis, and Lactobacillus plantarum were the dominant microorganisms in the process, and Leuconostoc citreum exhibited a strong positive correlation with starch flocculation rate (FR). In total, 75 lactic acid bacterial (LAB) strains were isolated from the SPSL, but only 7 of them caused starch flocculation. For the first time, Leuconostoc citreum strains were reported with excellent starch-flocculating abilities (up to 55.56% FR in 20 min), which might be attributed to their ability to connect starch granules through the cell surface to form large aggregation. This study provides a comprehensive understanding of the bacterial dynamics in SPSL fermentation at the species level. A starch flocculation yield of 93.63% was achieved within 1 h by using the newly discovered Leuconostoc citreum SJ-57. The time required for total starch sedimentation was reduced from 10 h to 4 h, compared with the traditional process. These results suggest that this novel bioflocculant is more suitable for modernizing the traditional SPSL fermentation process and achieving rapid and highly efficient starch sedimentation.
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http://dx.doi.org/10.1016/j.foodres.2021.110327DOI Listing
June 2021

Mitocytosis, a migrasome-mediated mitochondrial quality-control process.

Cell 2021 May;184(11):2896-2910.e13

State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

Damaged mitochondria need to be cleared to maintain the quality of the mitochondrial pool. Here, we report mitocytosis, a migrasome-mediated mitochondrial quality-control process. We found that, upon exposure to mild mitochondrial stresses, damaged mitochondria are transported into migrasomes and subsequently disposed of from migrating cells. Mechanistically, mitocytosis requires positioning of damaged mitochondria at the cell periphery, which occurs because damaged mitochondria avoid binding to inward motor proteins. Functionally, mitocytosis plays an important role in maintaining mitochondrial quality. Enhanced mitocytosis protects cells from mitochondrial stressor-induced loss of mitochondrial membrane potential (MMP) and mitochondrial respiration; conversely, blocking mitocytosis causes loss of MMP and mitochondrial respiration under normal conditions. Physiologically, we demonstrate that mitocytosis is required for maintaining MMP and viability in neutrophils in vivo. We propose that mitocytosis is an important mitochondrial quality-control process in migrating cells, which couples mitochondrial homeostasis with cell migration.
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http://dx.doi.org/10.1016/j.cell.2021.04.027DOI Listing
May 2021

NUMB suppression by miR-9-5P enhances CD44 prostate cancer stem cell growth and metastasis.

Sci Rep 2021 May 27;11(1):11210. Epub 2021 May 27.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Experimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44 PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44 PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.
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http://dx.doi.org/10.1038/s41598-021-90700-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160147PMC
May 2021

Differential microbial assemblages associated with shikonin-producing Borage species in two distinct soil types.

Sci Rep 2021 May 24;11(1):10788. Epub 2021 May 24.

State Key Laboratory of Pharmaceutical Biotechnology, Institute for Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China.

Shikonin and its derivatives are the main components of traditional Chinese medicine, Zicao. The pharmacological potential of shikonin and its derivatives have been extensively studied. Yet, less is known about the microbial assemblages associated with shikonin producing Borage plants. We studied microbial profiles of two Borage species, Echium plantagineum (EP) and Lithospermum erythrorhizon (LE), to identify the dynamics of microbial colonization pattern within three rhizo-compatments and two distinct soil types. Results of α and β-diversity via PacBio sequencing revealed significantly higher microbial richness and diversity in the natural soil along with a decreasing microbial gradient across rhizosphere to endosphere. Our results displayed genotype and soil type-dependent fine-tuning of microbial profiles. The host plant was found to exert effects on the physical and chemical properties of soil, resulting in reproducibly different micro-biota. Analysis of differentially abundant microbial OTUs displayed Planctomycetes and Bacteroidetes to be specifically enriched in EP and LE rhizosphere while endosphere was mostly prevailed by Cyanobacteria. Network analysis to unfold co-existing microbial species displayed different types of positive and negative interactions within different communities. The data provided here will help to identify microbes associated with different rhizo-compartments of potential host plants. In the future, this might be helpful for manipulating the keystone microbes for ecosystem functioning.
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http://dx.doi.org/10.1038/s41598-021-90251-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144371PMC
May 2021

Reverse-Phase Protein Array: Technology, Application, Data Processing, and Integration.

J Biomol Tech 2021 Apr;32(1):15-29

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.

Reverse-phase protein array (RPPA) is a high-throughput antibody-based targeted proteomics platform that can quantify hundreds of proteins in thousands of samples derived from tissue or cell lysates, serum, plasma, or other body fluids. Protein samples are robotically arrayed as microspots on nitrocellulose-coated glass slides. Each slide is probed with a specific antibody that can detect levels of total protein expression or post-translational modifications, such as phosphorylation as a measure of protein activity. Here we describe workflow protocols and software tools that we have developed and optimized for RPPA in a core facility setting that includes sample preparation, microarray mapping and printing of protein samples, antibody labeling, slide scanning, image analysis, data normalization and quality control, data reporting, statistical analysis, and management of data. Our RPPA platform currently analyzes ∼240 validated antibodies that primarily detect proteins in signaling pathways and cellular processes that are important in cancer biology. This is a robust technology that has proven to be of value for both validation and discovery proteomic research and integration with other omics data sets.
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http://dx.doi.org/10.7171/jbt.21-3202-001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121080PMC
April 2021

Molecular insights into the complex mechanics of plant epidermal cell walls.

Science 2021 05;372(6543):706-711

Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.

Plants have evolved complex nanofibril-based cell walls to meet diverse biological and physical constraints. How strength and extensibility emerge from the nanoscale-to-mesoscale organization of growing cell walls has long been unresolved. We sought to clarify the mechanical roles of cellulose and matrix polysaccharides by developing a coarse-grained model based on polymer physics that recapitulates aspects of assembly and tensile mechanics of epidermal cell walls. Simple noncovalent binding interactions in the model generate bundled cellulose networks resembling that of primary cell walls and possessing stress-dependent elasticity, stiffening, and plasticity beyond a yield threshold. Plasticity originates from fibril-fibril sliding in aligned cellulose networks. This physical model provides quantitative insight into fundamental questions of plant mechanobiology and reveals design principles of biomaterials that combine stiffness with yielding and extensibility.
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http://dx.doi.org/10.1126/science.abf2824DOI Listing
May 2021

Progress on biosynthesis and function of the natural products of Zi Cao as a traditional Chinese medicinal herb.

Yi Chuan 2021 May;43(5):459-472

State Key Laboratory of Pharmaceutical Biotechnology, Institute for Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing 210023, China.

Zi Cao is an important traditional medicinal plant resource in China. Shikonin and its derivatives, as the purple-red naphthoquinones among natural products of its roots, are commonly used clinically in the treatment of sores and skin inflammations. Over the past few decades, due to their highly effective multiple biological activities, pharmacological effects, good clinical efficacy and high utilization value, shikonin and its derivatives have attracted increasing attention of domestic and foreign researchers. For this reason, the wild plant germplasm resources have been suffering a grievous exploitation, leading to a serious threat to the habitat. With the development of the biosynthesis, molecular metabolism and biotechnology, as well as the continuous innovation of research methods on the biological activities and pharmacological effects of plant natural products, significant progress has been made in the research on the biosynthetic pathways and related regulatory genes of shikonin. The pharmacological action and its mechanism of shikonin have also been deeply elucidated, which greatly promoted the basic research and clinical application development of shikonin. In this review, we briefly introduce and analyze the classification of Zi Cao, structure and composition of natural shikonin and its biosynthesis pathway, functional genes related to the regulation of shikonin biosynthesis, and biological activities and pharmacological functions of shikonin. Finally, we address possible prospective for the trend on the future research and development of natural shikonin and its derivatives, hoping to provide a useful reference for the deep mining and development of medicinal natural products from important Chinese medicinal materials, and to promote the modern development of traditional Chinese medicine.
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http://dx.doi.org/10.16288/j.yczz.20-341DOI Listing
May 2021

Divergent On-DNA Transformations from DNA-Linked Piperidones.

J Org Chem 2021 May 7. Epub 2021 May 7.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, P. R. China.

A group of highly efficient and divergent transformations for constructing multiple DNA-linked chemotypes based on a piperidone core were successfully developed. We reported the first procedure for the synthesis of a DNA-conjugated piperidine intermediate under basic conditions. Subsequently, this substructure was subjected to additional reactions to generate several privileged scaffolds, including 4-aminopiperidine, fused [1,2,4]triazolo[1,5-]pyrimidine, and a quinoline derivative. These transformations paved the way for constructing focused scaffold-based DNA-encoded libraries with druglike properties.
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http://dx.doi.org/10.1021/acs.joc.1c00670DOI Listing
May 2021

Circular RNAs and Hepatocellular Carcinoma: New Epigenetic Players With Diagnostic and Prognostic Roles.

Front Oncol 2021 20;11:653717. Epub 2021 Apr 20.

Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Department of Collaborative Innovation Center for Biomedicine, Shanghai, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Due to the lack of potent diagnosis and prognosis biomarkers and effective therapeutic targets, the overall prognosis of survival is poor in HCC patients. Circular RNAs (circRNAs) are a class of novel endogenous non-coding RNAs with covalently closed loop structures and implicated in diverse physiological processes and pathological diseases. Recent studies have demonstrated the involvement of circRNAs in HCC diagnosis, prognosis, development, and drug resistance, suggesting that circRNAs may be a class of novel targets for improving HCC diagnosis, prognosis, and treatments. In fact, some artificial circRNAs have been engineered and showed their therapeutic potential in treating HCV infection and gastric cancer. In this review, we introduce the potential of circRNAs as biomarkers for HCC diagnosis and prognosis, as therapeutic targets for HCC treatments and discuss the challenges in circRNA research and chances of circRNA application.
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http://dx.doi.org/10.3389/fonc.2021.653717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093866PMC
April 2021

SARS-CoV-2 transmission and control in a hospital setting: an individual-based modelling study.

R Soc Open Sci 2021 Mar 22;8(3):201895. Epub 2021 Mar 22.

Department of Mathematics, Applied Mathematics, and Statistics, Case Western Reserve University, Cleveland, OH 44106, USA.

Development of strategies for mitigating the severity of COVID-19 is now a top public health priority. We sought to assess strategies for mitigating the COVID-19 outbreak in a hospital setting via the use of non-pharmaceutical interventions. We developed an individual-based model for COVID-19 transmission in a hospital setting. We calibrated the model using data of a COVID-19 outbreak in a hospital unit in Wuhan. The calibrated model was used to simulate different intervention scenarios and estimate the impact of different interventions on outbreak size and workday loss. The use of high-efficacy facial masks was shown to be able to reduce infection cases and workday loss by 80% (90% credible interval (CrI): 73.1-85.7%) and 87% (CrI: 80.0-92.5%), respectively. The use of social distancing alone, through reduced contacts between healthcare workers, had a marginal impact on the outbreak. Our results also indicated that a quarantine policy should be coupled with other interventions to achieve its effect. The effectiveness of all these interventions was shown to increase with their early implementation. Our analysis shows that a COVID-19 outbreak in a hospital's non-COVID-19 unit can be controlled or mitigated by the use of existing non-pharmaceutical measures.
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http://dx.doi.org/10.1098/rsos.201895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074975PMC
March 2021

Tumor-treating fields (TTFields)-based cocktail therapy: a novel blueprint for glioblastoma treatment.

Am J Cancer Res 2021 15;11(4):1069-1086. Epub 2021 Apr 15.

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, China.

Glioblastoma is one of the most common malignant tumors in the central nervous system. Due to the high plasticity, heterogeneity and complexity of the tumor microenvironment, these tumors are resistant to almost all therapeutic strategies when they reach an advanced stage. Along with being a unique and effective way to kill cancer cells, tumor-treating fields (TTFields) has emerged as a breakthrough among glioblastoma therapies since the advent of temozolomide (TMZ), and the combination of these treatments has gradually been promoted and applied in the clinic. The combination of TTFields with other therapies is particularly suitable for this type of "cold" tumors and has attracted a large amount of attention from clinicians and researchers in the era of cancer cocktail therapy. Here, we introduced the current treatment regimen for glioblastoma, highlighting the unique advantages of TTFields in the treatment of glioblastoma. Then, we summarized current glioblastoma clinical trials that combine TTFields and other therapies. In addition, the main and potential mechanisms of TTFields were introduced to further understand the rationale for each combination therapy. Finally, we focused on the most advanced technologies applied in glioblastoma research and treatment and the prospect of their combination with TTFields. This review provides a unique overview of glioblastoma treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085847PMC
April 2021

Design of ultrasonic standing wave levitation support for three-dimensional printed filaments.

J Acoust Soc Am 2021 Apr;149(4):2848

School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 029, China.

Fused deposition modeling (FDM) three-dimensional (3D) printing is the process of forming a part by depositing molten thermoplastic materials layer by layer. Support structures need to be added below the overhangs or bridges in 3D printing. This paper proposes an idea for support-free FDM printing by studying the method of filament levitation. In this paper, an ultrasonic phased array device is designed, and different slender objects with length much longer than the sound wavelength are levitated in the air by multiple standing wave points. Experiments show that slender objects can be stably held at the sound pressure nodes in the standing wave field. After adding the ultrasonic field in FDM printing, the maximum deformation of single filament due to gravity on the bridge structure decreases from 5 to 2 mm. This proves that it is feasible for an ultrasonic phased array system to play an important role in the field of support-free FDM printing.
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http://dx.doi.org/10.1121/10.0003922DOI Listing
April 2021

Homocysteine restrains hippocampal neurogenesis in focal ischemic rat brain by inhibiting DNA methylation.

Neurochem Int 2021 Jul 1;147:105065. Epub 2021 May 1.

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, 300070, China. Electronic address:

Ischemic stroke represents a major cause of mortality worldwide. An elevated level of homocysteine (Hcy) is recognized as a powerful risk factor of ischemic stroke. We previously reported that Hcy induces cytotoxicity and proliferation inhibition in neural stem cells (NSCs) derived from the neonatal rat hippocampus in vitro. However, the toxic potential of Hcy on NSCs and its underlying mechanisms are not entirely clear in ischemic brain. Since DNA methylation is critical for establishing the diverse cell fates in the central nervous system, we hypothesized that negative effect of Hcy (an intermediate in the one-carbon metabolism) on neurogenesis might be link to DNA methylation in ischemic stroke. In our study, the rats in Hcy intervention group were intraperitoneally injected with 2% Hcy solution (5 mL/kg/d) for 7 consecutive days before MCAO surgery until they were sacrificed. Our study indicated that Hcy inhibited NSCs self-renewal capacity, which was exhibited by lowering the number of DCX/BrdU and NeuN/BrdU in ischemic brain hippocampus. A reduction in the activity of the DNA methyltransferases (DNMTs), total methylation level and the number of 5mC/NeuN and DCX/5mC cells was observed in Hcy-treated ischemic brains. Additionally, Hcy also induced an increase in S-adenosylhomocysteine (SAH), and a decrease in the ratio of S-adenosylmethionine (SAM) to SAH. These results suggest that the alterations in DNA methylation may be an important mechanism by which Hcy inhibits neurogenesis after stroke. Hcy-induced DNA hypomethylation may be mainly caused by a reduction in the DNMT activity which is regulated by the concentrations of SAM and SAH. Maintaining normal DNA methylation by lowering Hcy level may possess therapeutic potential for promoting neurological recovery and reconstruction after stroke.
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http://dx.doi.org/10.1016/j.neuint.2021.105065DOI Listing
July 2021

Short-Term Inhalation of Ultrafine Zinc Particles Could Alleviate Cardiac Dysfunctions in Rats of Myocardial Infarction.

Front Bioeng Biotechnol 2021 14;9:646533. Epub 2021 Apr 14.

Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

It is not clear for inhalation of ultrafine metal particles in air pollution to impair human health. In the study, we aimed to investigate whether short-term (4 weeks) inhalation of ultrafine zinc particles could deteriorate the cardiac and hemodynamic functions in rats of myocardial infarction (MI). MI was induced in Wistar rats through coronary artery ligation surgery and given an inhalation of ultrafine zinc particles for 4 weeks (post-MI 4 weeks, 4 days per week, and 4 h per day). Cardiac strain and strain rate were quantified by the speckle tracking echocardiography. The pressure and flow wave were recorded in the carotid artery and analyzed by using the Womersley model. Myocardial infarction resulted in the LV wall thinning, LV cavity dilation, remarkable decrease of ejection fraction, dp/dt Max, -dp/dt Min, myocardial strain and strain rates, and increased LV end-diastolic pressure, as well as impaired hemodynamic environment. The short-term inhalation of ultrafine zinc particles significantly alleviated cardiac and hemodynamic dysfunctions, which could protect from the MI-induced myocardial and hemodynamic impairments albeit it is unknown for the long-term inhalation.
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http://dx.doi.org/10.3389/fbioe.2021.646533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081065PMC
April 2021

A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia.

Nat Commun 2021 04 30;12(1):2474. Epub 2021 Apr 30.

Experimental Medicine Program, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded by PTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.
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http://dx.doi.org/10.1038/s41467-021-22625-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087683PMC
April 2021

Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with .

Pathogens 2021 Apr 6;10(4). Epub 2021 Apr 6.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine 1-1, Mukogawa, Nishinomiya 663-8501, Japan.

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma-carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. () is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. was detected in SSA/Ps by fluorescence in situ hybridization using a -targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for . Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of -positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to -negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced expression in Caco2 cells. may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.
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http://dx.doi.org/10.3390/pathogens10040434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067346PMC
April 2021

Effect of Acetylated SEBS/PP for Potential HVAC Cable Insulation.

Materials (Basel) 2021 Apr 7;14(8). Epub 2021 Apr 7.

Key Laboratory of Engineering Dielectrics and Its Application, Ministry of Education, Harbin University of Science and Technology, Harbin 150080, China.

Blending polypropylene (PP) with thermoplastic elastomer SEBS can effectively improve the mechanical toughness of PP, thus leading to the promise of SEBS/PP as the primary insulation material for high voltage alternating current (HVAC) cables. However, the growth of electrical trees during cable operation limits the application of SEBS/PP. In this paper, acetylation reaction is used to construct acetophenone group at the end of the benzene ring on SEBS so that it has the effect of both a toughening agent and a voltage stabilizer. Then PP was melt blended with acetylated SEBS (Ac-SEBS), and the effects of Ac-SEBS on the mechanical properties, electrical tree resistance, alternating current (AC) breakdown strength, and dielectric spectrum of PP were mainly investigated with reference to PP and SEBS/PP. The results showed that Ac-SEBS with 30% content could enhance the mechanical toughness of PP and improve the electrical tree resistance and AC breakdown strength of SEBS/PP. The AC breakdown field strength of Ac-SEBS/PP reached the highest when the acetylation level was 4.6%, which was 9.2% higher than that of SEBS/PP. At this time, Ac-SEBS was also able to absorb high-energy electrons through the keto-enol interchange isomerization reaction, which inhibited the initiation and growth of electric trees and caused the development of electric dendrites in a jungle-like manner. Moreover, the dielectric loss factor of AC-SEBS/PP in power frequency is within the allowable range of industry. Therefore, Ac-SEBS/PP is expected to be applied to HVAC cables, thus further improving the efficiency of HVAC power transmission.
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http://dx.doi.org/10.3390/ma14081811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067628PMC
April 2021

Biomarker evaluation under imperfect nested case-control design.

Stat Med 2021 Apr 29. Epub 2021 Apr 29.

Department of Biostatistics, Harvard University, Boston, Massachusetts, USA.

The nested case-control (NCC) design has been widely adopted as a cost-effective sampling design for biomarker research. Under the NCC design, markers are only measured for the NCC subcohort consisting of all cases and a fraction of the controls selected randomly from the matched risk sets of the cases. Robust methods for evaluating prediction performance of risk models have been derived under the inverse probability weighting framework. The probabilities of samples being included in the NCC cohort can be calculated based on the study design ``a previous study'' or estimated non-parametrically ``a previous study''. Neither strategy works well due to model mis-specification and the curse of dimensionality in practical settings where the sampling does not entirely follow the study design or depends on many factors. In this paper, we propose an alternative strategy to estimate the sampling probabilities based on a varying coefficient model, which attains a balance between robustness and the curse of dimensionality. The complex correlation structure induced by repeated finite risk set sampling makes the standard resampling procedure for variance estimation fail. We propose a perturbation resampling procedure that provides valid interval estimation for the proposed estimators. Simulation studies show that the proposed method performs well in finite samples. We apply the proposed method to the Nurses' Health Study II to develop and evaluate prediction models using clinical biomarkers for cardiovascular risk.
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http://dx.doi.org/10.1002/sim.9012DOI Listing
April 2021

Recurrent infantile digital fibromatosis with HPV infection: a case report.

AME Case Rep 2021 25;5:20. Epub 2021 Apr 25.

Department of Dermatology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

Infantile digital fibromatosis is a rare, benign fibrous tumor among infants usually limited to fingers and toes. Most cases present themselves with round eosinophilic inclusion bodies of different sizes, similar to erythrocyte in the parakarytoplasm. Although infantile digital fibromatosis had been observed with a tendency of spontaneous regression after a rapid phase of growth in some reports, the recurrence rate of early surgical intervention remains high. And the mechanism of recurrence is still unknown. Human papillomavirus (HPV), as a circular icosahedral double-stranded DNA virus, is famous for its remarkable significant correlation with cervical cancer. However, the reports about the possible relationship of recurrent infantile digital fibromatosis and HPV infection are rare and inconsistent. Here, we report a recurrent case of infantile digital fibromatosis after surgical resection. Pathological biopsy of the recurrent site not only identified the diagnosis of infantile digital fibromatosis again, but found the sign of HPV infection. Family history indicated that the patient's grandmother had a history of verruca plana. After complete resection of recurrence, the tumor recurred again and the case is still being followed up. The unique case may serve as a clue to the pathogenesis of the relationship between recurrent infantile digital fibromatosis and HPV infection.
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http://dx.doi.org/10.21037/acr-20-95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060154PMC
April 2021

Multicomponent-assembled nanodiamond hybrids for targeted and imaging guided triple-negative breast cancer therapy a ternary collaborative strategy.

Biomater Sci 2021 May;9(10):3838-3850

The Faculty of Environment and Life, Beijing University of Technology, No. 100 Pingleyuan, Chaoyang District, Beijing 100124, P.R. China.

Uniting combinational strategies has been confirmed to be a robust choice for high-performance cancer treatment due to their abilities to overcome tumor heterogeneity and complexity. However, the development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. In this study, we integrated multicomponent hyaluronic acid (HA), protamine (PS), nanodiamonds (NDs), curcumin (Cur), and IR780 into a single nanoplatform (denoted as HPNDIC) based on the combination of hydrophobic and electrostatic noncovalent interactions for dual-modal fluorescence/photoacoustic imaging guided ternary collaborative Cur/photothermal/photodynamic combination therapy of triple-negative breast cancer (TNBC). A two-step coordination assembly strategy was utilized to realize this purpose. In the first step, PS was utilized to modify the NDs clusters to form positively charged [email protected] (PND) and the simultaneous encapsulation of the natural small-molecule drug Cur and the photosensitive small-molecule IR780 (PNDIC). Second, HA was adsorbed onto the outer surface of the PNDIC through charge complexation for endowing a tumor-targeting ability (HPNDIC). The resulting HPNDIC had a uniform size, high drug-loading ability, and excellent colloidal stability. It was found that under the near-infrared irradiation condition, IR780 could be triggered to exhibit both PTT/PDT dual-pattern therapy effects, leading to an enhanced therapy efficiency of Cur both in vitro and in vivo with good biocompatibility. Due to the intrinsic imaging property of IR780, the biodistribution and accumulation behavior of HPNDIC in vivo could be monitored by dual-modal fluorescence/photoacoustic imaging. Taken together, our current work demonstrated the assembly of a NDs-based multicomponent theranostic platform for dual-modal fluorescence/photoacoustic imaging guided triple-collaborative Cur/photothermal/photodynamic against TNBC.
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http://dx.doi.org/10.1039/d1bm00283jDOI Listing
May 2021

Correlations between tumor mutation burden and immune infiltrates and their prognostic value in pancreatic cancer by bioinformatic analysis.

Life Sci 2021 Jul 16;277:119505. Epub 2021 Apr 16.

Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address:

Purpose: We aimed to investigate the patterns and prognostic roles of tumor mutation burden and immune microenvironment in pancreatic cancer.

Methods: The somatic mutation data, transcriptome profiles and clinical information were downloaded from the Cancer Genome Atlas database. Gene expression difference, Gene ontology, KEGG, gene set enrichment analyses and "CIBERSORT" algorithm were performed to screen differentially expressed genes, enriched functions or pathways and immune infiltrates differences between high and low TMB groups. Single sample gene set enrichment and unsupervised consensus clustering analyses were used for immunity grouping. Immune cell infiltration and expressions of HLA and checkpoint genes were investigated. Finally, a nomogram model integrating TMB and immune infiltration was established.

Results: A total of 608 differentially expressed genes were identified between high and low TMB groups, KEGG base excision repair and DNA replication pathways were enriched in high TMB group. Infiltration levels of M0 macrophages were higher and dendritic resting cells were lower in high TMB group. The risk model based on TMB-related immune genes, FAM19A2 and SLC22A17 was established and high risk scores indicated poorer prognosis. The expressions of HLA genes and immune checkpoint genes were higher in high immunity group. The nomogram showed remarkable ability for individualized survival estimation with good AUC values (0.794 and 0.800, respectively) for 3- and 5-year survival rates prediction.

Conclusions: The characteristics of tumor mutation burden and immune infiltration in pancreatic cancer provide new insights into the tumor microenvironment, immunotherapies and a novel prognostic nomogram model for pancreatic cancer patients.
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http://dx.doi.org/10.1016/j.lfs.2021.119505DOI Listing
July 2021

miR-671-5p Attenuates Neuroinflammation via Suppressing NF-κB Expression in an Acute Ischemic Stroke Model.

Neurochem Res 2021 Jul 19;46(7):1801-1813. Epub 2021 Apr 19.

College of Pharmacology, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, 400016, China.

This study was designed to investigate the role of miR-671-5p in in vitro and in vivo models of ischemic stroke (IS). Middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 mice as well as oxygen-glucose deprivation and reoxygenation (OGD/R) in a mouse hippocampal HT22 neuron line were used as in vivo and in vitro models of IS injury, respectively. miR-671-5p agomir, miR-671-5p antagomir, pcDNA3.1-NF-κB, and negative controls were transfected into cells using riboFECT CP reagent. miR-671-5p agomir, pcDNA3.1-NF-κB, and negative vectors were administered into MCAO/R mice via intracerebroventricular injection. The results showed that miR-671-5p was significantly downregulated and that miR-671-5p agomir alleviated injury and neuroinflammation induced by ischemic reperfusion. A dual-luciferase reporter assay confirmed that NF-κB is a direct target of miR-671-5p. Reverse experiments showed that miR-671-5p agomir reduced neuroinflammation via suppression of NF-κB expression in both in vitro and in vivo models of IS. Our data suggest that miR-671-5p may be a viable therapeutic target for diminishing neuroinflammation in patients with IS.
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http://dx.doi.org/10.1007/s11064-021-03321-1DOI Listing
July 2021