Publications by authors named "Hong An"

170 Publications

Genomic insights into the origin, domestication and diversification of Brassica juncea.

Nat Genet 2021 Sep 6;53(9):1392-1402. Epub 2021 Sep 6.

College of Agronomy, Hunan Agricultural University, Changsha, China.

Despite early domestication around 3000 BC, the evolutionary history of the ancient allotetraploid species Brassica juncea (L.) Czern & Coss remains uncertain. Here, we report a chromosome-scale de novo assembly of a yellow-seeded B. juncea genome by integrating long-read and short-read sequencing, optical mapping and Hi-C technologies. Nuclear and organelle phylogenies of 480 accessions worldwide supported that B. juncea is most likely a single origin in West Asia, 8,000-14,000 years ago, via natural interspecific hybridization. Subsequently, new crop types evolved through spontaneous gene mutations and introgressions along three independent routes of eastward expansion. Selective sweeps, genome-wide trait associations and tissue-specific RNA-sequencing analysis shed light on the domestication history of flowering time and seed weight, and on human selection for morphological diversification in this versatile species. Our data provide a comprehensive insight into the origin and domestication and a foundation for genomics-based breeding of B. juncea.
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http://dx.doi.org/10.1038/s41588-021-00922-yDOI Listing
September 2021

Ultrastable High-Connected Chromium Metal-Organic Frameworks.

J Am Chem Soc 2021 Sep 31;143(36):14470-14474. Epub 2021 Aug 31.

Department of Chemistry, University of California, Riverside, California 92521, United States.

State-of-the-art MOFs are generally known for chemical stability at one end of the pH scale (i.e., pH < 0 or pH > 14). Herein, we report new Cr-MOFs capable of withstanding extreme pH conditions across approximately 16 pH units from pH < 0 to pH > 14, likely the largest observed pH range for MOFs. The integration of multiple stability-enhancing factors including nonlabile Cr, mixed Cr-N and Cr-O cross-links, and the highest possible connectivity by CrO trimers enables extraordinary chemical stability confirmed by both PXRD and gas adsorption. Notably, the base stability is much higher than literature Cr-MOFs, thereby revitalizing Cr-MOF's viability in the pursuit for the most chemically stable MOFs. Among known cationic MOFs, the chemical stability of these new Cr-MOFs is unmatchable, to our knowledge. These Cr-MOFs can be developed into multiseries of isoreticular MOFs with a rich potential for functionalization, pore size, and pore geometry engineering and applications.
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http://dx.doi.org/10.1021/jacs.1c07277DOI Listing
September 2021

Comparison of Pharmacokinetics and Tissue Distribution Characteristics of Three Diterpenoid Esters in Crude and Prepared Semen Euphorbiae.

Evid Based Complement Alternat Med 2021 16;2021:7402120. Epub 2021 Aug 16.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

Background: Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP) have a long history of medicinal use. SEP is the processed product of SE; both ancient and modern studies have shown that SEP has a lower toxicity compared to SE. To clarify the influence of processing on the pharmacological properties of SE and SEP, a study was carried out to compare the pharmacokinetics and distribution characteristics of three active compounds after oral administration of SE and SEP extracts.

Methods: A UPLC-MS/MS method was established to simultaneously determine the contents of Euphorbia factors L, L, and L in rat plasma and mouse tissues after an oral administration of crude and processed SE with approximately the same dosage. Plasma and heart, liver, spleen, lung, kidney, and colon tissue samples were treated with ethyl acetate and separated by gradient elution on a C18 column with a mobile phase of 0.1% formic acid and methanol.

Results: The established method had good selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery. The area under the concentration time curve, time to maximum concentration, maximum concentration, half-life of elimination, and mean retention time of plasma samples in SEP-treated group decreased, and the clearance in SEP-treated group increased. Moreover, the active component concentrations in colon, liver, and kidney tissues were more followed by those in the heart, lungs, and spleen.

Conclusion: These results indicate that the processing could influence the pharmacokinetics and tissue distribution of Euphorbia factors L, L, and L after oral administration of crude and processed SE. The data obtained may lay a foundation for the clinical use of SE and for further study on the processing mechanism of SE.
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http://dx.doi.org/10.1155/2021/7402120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384516PMC
August 2021

Development and Characterization of a Novel Peptide-Drug Conjugate with DM1 for Treatment of FGFR2-Positive Tumors.

Biomedicines 2021 Jul 21;9(8). Epub 2021 Jul 21.

Department of Cell Biology, Institute of Biomedicine, Jinan University, Guangzhou 510000, China.

A maytansin derivative, DM1, is a promising therapeutic compound for treating tumors, but is also a highly poisonous substance with various side effects. For clinical expansion, we tried to develop novel peptide-drug conjugates (PDCs) with DM1. In the study, a one-bead one-compound (OBOC) platform was used to screen and identify a novel, highly stable, non-natural amino acid peptide targeting the tyrosine receptor FGFR2. Then, the identified peptide, named LLC2B, was conjugated with the cytotoxin DM1. Our results show that LLC2B has high affinity for the FGFR2 protein according to an isothermal titration calorimetry (ITC) test. LLC2B-Cy5.5 binding to FGFR2-positive cancer cells was confirmed by fluorescent microscopic imaging and flow cytometry in vitro. Using xenografted nude mouse models established with breast cancer MCF-7 cells and esophageal squamous cell carcinoma KYSE180 cells, respectively, LLC2B-Cy5.5 was observed to specifically target tumor tissues 24 h after tail vein injection. Incubation assays, both in aqueous solution at room temperature and in human plasma at 37 °C, suggested that LLC2B has high stability and strong anti-proteolytic ability. Then, we used two different linkers, one of molecular disulfide bonds and another of a maleimide group, to couple LLC2B to the toxin DM1. The novel peptide-drug conjugates (PDCs) inhibited tumor growth and significantly increased the maximum tolerated dose of DM1 in xenografted mice. In brief, our results suggest that LLC2B-DM1 can be developed into a potential PDC for tumor treatment in the future.
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http://dx.doi.org/10.3390/biomedicines9080849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389697PMC
July 2021

Angiogenic Microspheres for the Treatment of a Thin Endometrium.

ACS Biomater Sci Eng 2021 Aug 20. Epub 2021 Aug 20.

Key Laboratory of System Bio-medicine of Jiangxi Province, Jiujiang University, Jiujiang, Jiangxi 332000, P. R. China.

The poor vascular development of an endometrium is the key cause of a thin endometrium due to the vascular endothelial growth factor (VEGF) decreasing in the glandular epithelium. Hence, inducing angiogenesis is an effective strategy for thin endometrium treatment in clinic. Herein, we developed a novel angiogenic hydrogel microsphere based on methacrylated hyaluronic acid (HAMA) loaded with VEGF for the treatment of a thin endometrium by a microfluidic electrospray technique. The generated HAMA microspheres with uniform size, porous structure, and satisfactory biocompatibility increased the drug-loading ability and controlled the drug-release rate by adjusting the hydrogel concentration. Besides, the HAMA microspheres loaded with VEGF showed satisfactory biocompatibility and promoted blood vessel formation in vitro. More importantly, the combination of HA and VEGF promoted new blood vessels and endometrial regeneration of a thin endometrium in vivo. Therefore, the combination of HA and VEGF would be conducive to the development of a drug-delivery microsphere with excellent biocompatibility and therapeutic effect for thin endometrium treatment and other biomedical applications.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00615DOI Listing
August 2021

Hemophagocytic lymphohistiocytosis associated with parvovirus B19-induced aplastic crisis in a hereditary spherocytosis patient: A case report and literature review.

Pediatr Hematol Oncol 2021 Aug 9:1-8. Epub 2021 Aug 9.

Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation. It occurs because of severe inflammation due to uncontrolled proliferation of activated lymphocytes and histiocytes, characterized by the production of excessive levels of cytokines. Virus-associated HLH is a well-known entity, and parvovirus B19 is one of the common causes. Parvovirus B19 can also affect blood cell lineages. Therefore, HLH may be accompanied by several diseases such as cytopenia, aplastic anemia, and myelodysplastic syndrome. Herein, we report the case of a patient with hereditary spherocytosis who was diagnosed with parvovirus B19-induced HLH and aplastic crisis. A 7-year-old girl presented to our hospital with fever, pleural effusion, pancytopenia, hepatosplenomegaly, and hypotension. A bone marrow biopsy was performed under the suspicion of HLH, which revealed hemophagocytes. The diagnostic criteria for HLH were met, and prompt chemoimmunotherapy was initiated considering the clinically unstable situation. Her health improved rapidly after initiating treatment. Further study revealed that she had hereditary spherocytosis, and parvovirus B19 had caused aplastic crisis and HLH. The patient's clinical progress was excellent, and chemoimmunotherapy was reduced and discontinued at an early stage. This case shows that aplastic crisis and HLH can coexist with parvovirus B19 infection in patients with hereditary spherocytosis. Although the prognosis was good in this case of HLH caused by parvovirus B19, early detection and active treatment are essential.
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http://dx.doi.org/10.1080/08880018.2021.1949082DOI Listing
August 2021

Open-Label, Multicenter Phase II Study of Combination Therapy of Imatinib Mesylate and Mycophenolate Mofetil in Pediatric Patients with Steroid-Refractory Sclerotic/Fibrotic Type Chronic Graft-versus-Host Disease.

Transplant Cell Ther 2021 Jul 24. Epub 2021 Jul 24.

Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, Republic of Korea; Wide River Institute of Immunology, Seoul National University, Gangwon, Republic of Korea. Electronic address:

Steroid-refractory chronic graft-versus-host disease (cGVHD) is associated with high morbidity. To date, there is no standard therapy for patients who fail to respond to steroids. In this nonrandomized, open-label, single-arm, multicenter prospective phase II study, we evaluated the efficacy and safety of imatinib mesylate and mycophenolate mofetil (MMF) to treat sclerotic/fibrotic type cGVHD. The primary endpoint was the overall response rate (ORR) to imatinib mesylate plus MMF in 1 year, and the secondary endpoints included safety, quality of life, discontinuation of steroids, and overall survival (OS) rate. A total of 13 patients were enrolled, with a median age of 10.4 years (range, 5.0 to 20.1 years). All patients received a myeloablative conditioning regimen. Specifically, 6 of these patients had previously experienced acute GVHD. The most frequently affected organs were the eyes, lungs, skin, and liver. There were 2 premature deaths. One patient died of pulmonary infection and progression of cGVHD, and the other patient died from neuroblastoma progression and septic shock. The ORR was 76.9% (10 of 13 patients), and the median steroid dose was decreased from 1.0 mg/kg/day to 0.21 mg/kg/day. One-year OS was 84.6% (n = 13), and common adverse events included elevated liver enzyme and serum creatinine levels and fever. Although our sample size was limited, treatment of cGVHD with imatinib mesylate plus MMF shows promising results with acceptable toxicity.
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http://dx.doi.org/10.1016/j.jtct.2021.07.019DOI Listing
July 2021

Long non-coding RNA colorectal neoplasia differentially expressed correlates negatively with miR-33a and miR-495 and positively with inflammatory cytokines in asthmatic children.

Clin Respir J 2021 Jul 20. Epub 2021 Jul 20.

Second Department of Pediatrics, Xingtai People's Hospital, Xingtai, China.

Objectives: It is reported that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) targets microRNA (miR)-33a, miR-181a and miR-495 to regulate inflammation process, while few studies report their clinical application for paediatric asthma management. Therefore, this study aimed to explore the interaction of lncRNA CRNDE with miR-33a, miR-181a and miR-495, as well as their correlation with inflammation, exacerbation risk and severity in paediatric patients with asthma.

Methods: Asthmatic exacerbation children (N = 65), asthmatic controlled children (N = 65) and controls (N = 65) were recruited. LncRNA CRNDE, miR-33a, miR-181a and miR-495 expressions in peripheral blood mononuclear cells were detected by RT-qPCR. Besides, serum inflammatory cytokines (including TNF-α, IL-1β, IL-6 and IL-17) were determined by enzyme-linked immunosorbent assay (ELISA).

Results: LncRNA CRNDE, miR-33a and miR-495 expressions were different, while miR-181a expression was similar among asthmatic exacerbation children, asthmatic controlled children and controls. Moreover, lncRNA CRNDE negatively correlated with miR-33a and miR-495 in asthmatic exacerbation children and asthmatic controlled children, but not in controls. Further analyses showed that lncRNA CRNDE positively correlated with TNF-α, IL-1β, IL-17 and exacerbation severity, while it negatively correlated with FEV /FVC in asthmatic exacerbation children. Meanwhile, miR-33a, miR-181a and miR-495 all negatively correlated with some individual inflammatory cytokines, while only miR-33a negatively correlated with exacerbation severity in asthmatic exacerbation children.

Conclusion: LncRNA CRNDE correlates negatively with miR-33a and miR-495 and positively with inflammatory cytokines in asthmatic children.
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http://dx.doi.org/10.1111/crj.13424DOI Listing
July 2021

Pore-Space Partition and Optimization for Propane-Selective High-Performance Propane/Propylene Separation.

ACS Appl Mater Interfaces 2021 Jul 8. Epub 2021 Jul 8.

Department of Chemistry, University of California, Riverside, California 92521, United States.

The development of effective propane (CH)-selective adsorbents for the purification of propylene (CH) from CH/CH mixture is a promising alternative to replace the energy-intensive cryogenic distillation. However, few materials possess the dual desirable features of propane selectivity and high uptake capacity. Here, we report a family of pore-space-partitioned crystalline porous materials (CPM) with remarkable CH uptake capacity (up to 10.9 mmol/g) and the highly desirable yet uncommon CH selectivity (up to 1.54 at 0.1 bar and 1.44 at 1 bar). The selectivity-capacity synergy endows them with record-performing CH/CH separation potential (i.e., CH recovered from the mixture). Moreover, these CPMs exhibit outstanding properties including high stability, low regeneration energy, and multimodular chemical and geometrical tunability within the same isoreticular framework. The high CH/CH separation performance was further confirmed by the breakthrough experiments.
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http://dx.doi.org/10.1021/acsami.1c10391DOI Listing
July 2021

The Evolutionary History of Wild, Domesticated, and Feral Brassica Oleracea (Brassicaceae).

Mol Biol Evol 2021 Jun 22. Epub 2021 Jun 22.

Division of Biological Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, U.S.A.

Understanding the evolutionary history of crops, including identifying wild relatives, helps to provide insight for conservation and crop breeding efforts. Cultivated Brassica oleracea has intrigued researchers for centuries due to its wide diversity in forms, which include cabbage, broccoli, cauliflower, kale, kohlrabi, and Brussels sprouts. Yet, the evolutionary history of this species remains understudied. With such different vegetables produced from a single species, B. oleracea is a model organism for understanding the power of artificial selection. Persistent challenges in the study of B. oleracea include conflicting hypotheses regarding domestication and the identity of the closest living wild relative. Using newly generated RNA-seq data for a diversity panel of 224 accessions, which represents 14 different B. oleracea crop types and nine potential wild progenitor species, we integrate phylogenetic and population genetic techniques with ecological niche modeling, archaeological, and literary evidence to examine relationships among cultivars and wild relatives to clarify the origin of this horticulturally important species. Our analyses point to the Aegean endemic B. cretica as the closest living relative of cultivated B. oleracea, supporting an origin of cultivation in the Eastern Mediterranean region. Additionally, we identify several feral lineages, suggesting that cultivated plants of this species can revert to a wild-like state with relative ease. By expanding our understanding of the evolutionary history in B. oleracea, these results contribute to a growing body of knowledge on crop domestication that will facilitate continued breeding efforts including adaptation to changing environmental conditions.
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http://dx.doi.org/10.1093/molbev/msab183DOI Listing
June 2021

Perivascular cell-derived extracellular vesicles stimulate colorectal cancer revascularization after withdrawal of antiangiogenic drugs.

J Extracell Vesicles 2021 May 21;10(7):e12096. Epub 2021 May 21.

College of Pharmacy Jinan University Guangzhou China.

Antiangiogenic tyrosine kinase inhibitors (AA-TKIs) have become a promising therapeutic strategy for colorectal cancer (CRC). In clinical practice, a significant proportion of cancer patients temporarily discontinue AA-TKI treatment due to recurrent toxicities, economic burden or acquired resistance. However, AA-TKI therapy withdrawal-induced tumour revascularization frequently occurs, hampering the clinical application of AA-TKIs. Here, this study demonstrates that tumour perivascular cells mediate tumour revascularization after withdrawal of AA-TKI therapy. Pharmacological inhibition and genetic ablation of perivascular cells largely attenuate the rebound effect of CRC vascularization in the AA-TKI cessation experimental settings. Mechanistically, tumour perivascular cell-derived extracellular vehicles (TPC-EVs) contain Gas6 that instigates the recruitment of endothelial progenitor cells (EPCs) for tumour revascularization via activating the Axl pathway. Gas6 silence and an Axl inhibitor markedly inhibit tumour revascularization by impairing EPC recruitment. Consequently, combination therapy of regorafenib with the Axl inhibitor improves overall survival in mice metastatic CRC model by inhibiting tumour growth. Together, these data shed new mechanistic insights into perivascular cells in off-AA-TKI-induced tumour revascularization and indicate that blocking the Axl signalling may provide an attractive anticancer approach for sustaining long-lasting angiostatic effects to improve the therapeutic outcomes of antiangiogenic drugs in CRC.
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http://dx.doi.org/10.1002/jev2.12096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138700PMC
May 2021

Brassica rapa Domestication: Untangling Wild and Feral Forms and Convergence of Crop Morphotypes.

Mol Biol Evol 2021 07;38(8):3358-3372

Department of Botany, University of Wisconsin-Madison, Madison, WI, USA.

The study of domestication contributes to our knowledge of evolution and crop genetic resources. Human selection has shaped wild Brassica rapa into diverse turnip, leafy, and oilseed crops. Despite its worldwide economic importance and potential as a model for understanding diversification under domestication, insights into the number of domestication events and initial crop(s) domesticated in B. rapa have been limited due to a lack of clarity about the wild or feral status of conspecific noncrop relatives. To address this gap and reconstruct the domestication history of B. rapa, we analyzed 68,468 genotyping-by-sequencing-derived single nucleotide polymorphisms for 416 samples in the largest diversity panel of domesticated and weedy B. rapa to date. To further understand the center of origin, we modeled the potential range of wild B. rapa during the mid-Holocene. Our analyses of genetic diversity across B. rapa morphotypes suggest that noncrop samples from the Caucasus, Siberia, and Italy may be truly wild, whereas those occurring in the Americas and much of Europe are feral. Clustering, tree-based analyses, and parameterized demographic inference further indicate that turnips were likely the first crop type domesticated, from which leafy types in East Asia and Europe were selected from distinct lineages. These findings clarify the domestication history and nature of wild crop genetic resources for B. rapa, which provides the first step toward investigating cases of possible parallel selection, the domestication and feralization syndrome, and novel germplasm for Brassica crop improvement.
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http://dx.doi.org/10.1093/molbev/msab108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321528PMC
July 2021

The contributions from the progenitor genomes of the mesopolyploid Brassiceae are evolutionarily distinct but functionally compatible.

Genome Res 2021 May 16;31(5):799-810. Epub 2021 Apr 16.

Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27695, USA.

The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of , a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein-protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a "mix and match" model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.
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http://dx.doi.org/10.1101/gr.270033.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092008PMC
May 2021

A Novel Method to Identify the Differences Between Two Single Cell Groups at Single Gene, Gene Pair, and Gene Module Levels.

Front Genet 2021 15;12:648898. Epub 2021 Mar 15.

Medical Clinical Laboratory, The Second People's Hospital of Lianyungang, Lianyungang, China.

Single-cell sequencing technology can not only view the heterogeneity of cells from a molecular perspective, but also discover new cell types. Although there are many effective methods on dropout imputation, cell clustering, and lineage reconstruction based on single cell RNA sequencing (RNA-seq) data, there is no systemic pipeline on how to compare two single cell clusters at the molecular level. In the study, we present a novel pipeline on comparing two single cell clusters, including calling differential gene expression, coexpression network modules, and so on. The pipeline could reveal mechanisms behind the biological difference between cell clusters and cell types, and identify cell type specific molecular mechanisms. We applied the pipeline to two famous single-cell databases, Usoskin from mouse brain and Xin from human pancreas, which contained 622 and 1,600 cells, respectively, both of which were composed of four types of cells. As a result, we identified many significant differential genes, differential gene coexpression and network modules among the cell clusters, which confirmed that different cell clusters might perform different functions.
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http://dx.doi.org/10.3389/fgene.2021.648898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005607PMC
March 2021

Selective Crystallization of Rare-Earth Ions into Cationic Metal-Organic Frameworks for Rare-Earth Separation.

Angew Chem Int Ed Engl 2021 May 8;60(20):11148-11152. Epub 2021 Apr 8.

Department of Chemistry and Biochemistry, California State University Long Beach, Long Beach, CA, 90840, USA.

For rare-earth separation, selective crystallization into metal-organic frameworks (MOFs) offers new opportunities. Especially important is the development of MOF platforms with high selectivity toward target ions. Here we report a MOF platform (CPM-66) with low-coordination-number environment for rare-earth ions. This platform is highly responsive to the size variation of rare-earth ions and shows exceptional ion-size selectivity during crystallization. CPM-66 family are based on M O trimers (M=6-coordinated Sc, In, Er-Lu) that are rare for lanthanides. We show that the size matching between urea-type solvents and metal ions is crucial for their successful synthesis. We further show that CPM-66 enables a dramatic multi-fold increase in separation efficiency over CPM-29 with 7-coordinated ions. This work provides some insights into methods to prepare low-coordinate MOFs from large ions and such MOFs could serve as high-efficiency platforms for lanthanide separation, as well as other applications.
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http://dx.doi.org/10.1002/anie.202017042DOI Listing
May 2021

Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism.

Gut 2021 Feb 10. Epub 2021 Feb 10.

Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Stockholm, Sweden

Objective: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy.

Design: Two unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33-ST2-CXCL3-CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models.

Results: IL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33-ST2-MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3-CXCR2 signalling. Type III collagen was identified as the CXCL3-CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis.

Conclusions: Our work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.
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http://dx.doi.org/10.1136/gutjnl-2020-322744DOI Listing
February 2021

[Efficiency of diode laser-assisted methods in direct pulp capping of carious teeth].

Shanghai Kou Qiang Yi Xue 2020 Oct;29(5):554-556

Department of VIP, Stomatological Hospital of Xi'an Jiao Tong University. Xi'an 710004, Shaanxi Province, China.

Purpose: To explore the efficiency of diode laser-assisted methods in direct pulp capping of carious teeth.

Methods: A total of 100 carious teeth were randomly divided into experimental group and control group, 50 in each group. Patients in the control group were treated with conventional treatment, while in the experimental group, 808 nm, 1.5 W laser with fiber diameter of 320 μm was used on the exposure site to control hemorrhage, and 1W laser was used to decontaminate the cavity. SPSS 19.0 software package was used for data analysis.

Results: Of 50 patients in the experimental group, three teeth were lost to follow-up, the total effective rate was 89.4%. Of 50 patients in the control group, five teeth were lost to follow-up, the total effective rate was 73.3%. The difference between the two groups was statistically significant (P<0.05).

Conclusions: Laser-assisted procedure in carious exposures is more effective than conventional treatment in pulp-capping therapy, which is worthy of wide application.
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October 2020

Genes derived from ancient polyploidy have higher genetic diversity and are associated with domestication in Brassica rapa.

New Phytol 2021 04;230(1):372-386

Department of Ecology & Evolutionary Biology, University of Arizona, Tucson, AZ, 85721, USA.

Many crops are polyploid or have a polyploid ancestry. Recent phylogenetic analyses have found that polyploidy often preceded the domestication of crop plants. One explanation for this observation is that increased genetic diversity following polyploidy may have been important during the strong artificial selection that occurs during domestication. In order to test the connection between domestication and polyploidy, we identified and examined candidate genes associated with the domestication of the diverse crop varieties of Brassica rapa. Like all 'diploid' flowering plants, B. rapa has a diploidized paleopolyploid genome and experienced many rounds of whole genome duplication (WGD). We analyzed transcriptome data of more than 100 cultivated B. rapa accessions. Using a combination of approaches, we identified > 3000 candidate genes associated with the domestication of four major B. rapa crop varieties. Consistent with our expectation, we found that the candidate genes were significantly enriched with genes derived from the Brassiceae mesohexaploidy. We also observed that paleologs were significantly more diverse than non-paleologs. Our analyses find evidence for that genetic diversity derived from ancient polyploidy played a key role in the domestication of B. rapa and provide support for its importance in the success of modern agriculture.
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http://dx.doi.org/10.1111/nph.17194DOI Listing
April 2021

Outcomes of infants with severe bronchopulmonary dysplasia in the pediatric intensive care unit.

Pediatr Int 2021 May 10;63(5):529-535. Epub 2021 May 10.

Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: Some infants with severe bronchopulmonary dysplasia (sBPD) are referred to higher-level centers for multidisciplinary care, including the pediatric intensive care unit (PICU). However, information regarding these infants is limited in PICUs.

Methods: We investigated the characteristics and outcomes of preterm infants with sBPD referred to the PICU of a tertiary hospital. This retrospective cohort study included 14 preterm infants with sBPD who were transferred to the PICU beyond 40 weeks' postmenstrual age (PMA) because of weaning failure, from January 1, 2014, to September 30, 2018.

Results: The median age at referral was 47.1 weeks (range, 43.6-55.9 weeks), and the median length of stay in the previous neonatal intensive care unit was 154 days (range, 105.8-202.3 days) after birth. After referral the following major comorbidities were found in the patients: large airway malacia, n = 7 (50.0%); significant upper airway obstruction, n = 3 (21.4%); and pulmonary arterial hypertension, n = 8 patients (57.1%). Finally, eight patients (57.1%) were successfully extubated without tracheostomy. Final respiratory support of the patients was determined at a median PMA of 56 weeks (range, 48-63 weeks). Age at referral (P = 0.023) and large airway obstruction (P = 0.028) were significantly related to a decrease in successful extubation.

Conclusion: Based on a timely and individualized multidisciplinary approach, some of the prolonged ventilator-dependent infants, even those beyond term age, could be successfully extubated.
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http://dx.doi.org/10.1111/ped.14546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252616PMC
May 2021

Treatment outcome and long-term follow-up of central nervous system germ cell tumor using upfront chemotherapy with subsequent photon or proton radiation therapy: a single tertiary center experience of 127 patients.

BMC Cancer 2020 Oct 9;20(1):979. Epub 2020 Oct 9.

Departments of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of brain tumors, which are more common in Asian countries. There have been different therapeutic strategies in treating germinoma and non-germinomatous germ cell tumors (NGGCT), depending on prognosis. Moreover, long-term follow up should be emphasized due to higher late complication rates. Here, we investigated long-term outcomes and complication profiles of 127 CNS GCT patients who received uniform upfront chemotherapy.

Methods: We retrospectively evaluated outcomes of CNS GCT patients treated in Seoul National University Children's Hospital from August 2004 to April 2019. Patients were classified as low risk (LR) or high risk (HR) based on pathologic diagnosis and tumor markers. Most patients received upfront systemic chemotherapy with carboplatin, cyclophosphamide, etoposide, and/or bleomycin, followed by either proton or photon radiation therapy according to patients' choice.

Results: The median age at diagnosis was 11.9 (range, 3.8-25.1) years, and 54.3% of patients were LR. Photon and proton radiation therapy were administered to 73.2 and 25.2% of patients, respectively. In both LR and HR groups, there were no significant differences in survival between photon and proton radiation therapy. The 10-year relapse incidences were 9.3 and 5.6% in the LR and HR groups, respectively. All recurrences, except one, were local relapse. Six secondary malignancies occurred; the 10-year incidences of secondary malignancy were 2.2 and 7.6% in the LR and HR groups, respectively. The 10-year overall survival rates were 98.3 ± 1.7 and 91.8 ± 3.9% in the LR and HR groups, respectively. In a subgroup analysis of HR group, pathologically diagnosed NGGCT patients (n = 20) showed worse 10-year EFS (65.9 ± 11.9%, p < 0.001) and OS (77.9 ± 9.8%, p = 0.024) rates compared to other HR patients who were not pathologically diagnosed or were confirmed as germinoma with elevated tumor markers. All mortalities were related to disease progression or secondary malignancy.

Conclusion: The strategy of treating CNS GCTs with upfront chemotherapy according to risk groups resulted in good clinical outcomes and acceptable relapse incidence. However, further modification in the definition of the HR group is needed to reduce long-term complications.
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http://dx.doi.org/10.1186/s12885-020-07484-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547441PMC
October 2020

Columellar Wound Immediately After Open Rhinoseptoplasty Treated With Application of DuoDERM Extra Thin.

J Craniofac Surg 2021 Jan-Feb 01;32(1):e98-e99

From the Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University College of Medicine, Daejeon, Republic of Korea.

Abstract: Most patients who undergo open rhinoseptoplasty do not develop any wound at the transcolumellar incision site. However, some patients require wound care immediately post-operation. Dressing is difficult to perform in the columellar region because of the location. Here, we report 2 cases of columellar wound as a complication of open rhinoseptoplasty. A patient developed mild wound dehiscence immediately after primary rhinoseptoplasty, whereas another developed partial columellar skin necrosis after the revision operation. We applied DuoDERM Extra Thin dressing (ConvaTec Group, Deeside, UK) for columellar wound and achieved healing. DuoDERM Extra Thin can be a simple and easy dressing material for immediate care of transcolumellar wounds.
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http://dx.doi.org/10.1097/SCS.0000000000006782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769182PMC
June 2021

TRPM8-regulated calcium mobilization plays a critical role in synergistic chemosensitization of Borneol on Doxorubicin.

Theranostics 2020 13;10(22):10154-10170. Epub 2020 Aug 13.

Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.

Lung cancer has a high mortality rate and is resistant to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that facilitates the bioavailability of drugs. In this study, we investigated the effects of NB on chemosensitivity in the A549 human lung adenocarcinoma cell line and to elucidate therapeutic molecular target of NB. The chemosensitivity effects of NB in A549 cells were examined by MTT assay. The mechanism of NB action was evaluated using flow cytometry and Western blotting assays. Surface plasmon resonance (SPR) and LC-MS combined analysis (MS-SPRi) was performed to elucidate the candidate molecular target of NB. The chemosensitizing capacity of NB was assessed in nude mice bearing A549 tumors. NB pretreatment sensitized A549 cells to low doxorubicin (DOX) dosage, leading to a 15.7% to 41.5% increase in apoptosis. This increase was correlated with ERK and AKT inactivation and activation of phospho-p38 MAPK, phospho-JNK, and phosphor-p53. Furthermore, this synergism depends on reactive oxygen species (ROS) generation. MS-SPRi analysis revealed that transient receptor potential melastatin-8 (TRPM8) is the candidate target of NB in potentiating DOX killing potency. Genetically, TRPM8 knock-down significantly suppresses the chemosensitizing effects of NB and inhibits ROS generation through restraining calcium mobilization. Moreover, pretreatment with NB synergistically enhances the anticancer effects of DOX to delay tumor progression . These results suggest that TRPM8 may be a valid therapeutic target in the potential application of NB, and show that NB is a chemosensitizer for lung cancer treatment.
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http://dx.doi.org/10.7150/thno.45861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481425PMC
May 2021

Virtual screening of approved clinic drugs with main protease (3CL) reveals potential inhibitory effects on SARS-CoV-2.

J Biomol Struct Dyn 2020 Sep 10:1-11. Epub 2020 Sep 10.

Institute of Biomedicine & Department of cell Biology, Jinan University, Guangzhou, China.

3CL is the main protease of the novel coronavirus (SARS-CoV-2) responsible for their intracellular duplication. Based on virtual screening technology and molecular dynamics simulation, we found 23 approved clinical drugs such as Viomycin, Capastat, Carfilzomib and Saquinavir, which showed high affinity with the 3CL active sites. These findings showed that there were potential drugs that inhibit SARS-Cov-2's 3CL in the current clinical drug library, and these drugs can be further tested or chemically modified for the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1817786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544985PMC
September 2020

Analysis of hyperbilirubinemia in patients with Kawasaki disease.

Medicine (Baltimore) 2020 Sep;99(36):e21974

Department of Paediatrics, Xingtai People's Hospital, Xingtai, Hebei, China.

The present study attempted to analyze the clinical characteristics and pathogenesis of Kawasaki disease (KD) in children with hyperbilirubinemia.A total of 390 children with KD hospitalized in our hospital from September 2018 to July 2019 were selected and divided into control (270 cases) and hyperbilirubinemia (120 cases) groups based on the total, direct, and indirect bilirubin values after admission. Clinical data of the inflammatory index and fever process of the 2 groups were analyzed and compared.The difference in sex and age between the 2 groups was statistically nonsignificant (P > .05). In the hyperbilirubinemia group, the white blood cell count, C-reactive protein, hemoglobin, platelet count, erythrocyte sedimentation rate, alanine aminotransferase, aspartate aminotransferase, albumin, and routine urine leucocyte; and incidence of coronary artery expansion, heart injury, and unreactive gamma globulin treatment were higher than those in the control group and the differences were statistically significant (P < .05). In the hyperbilirubinemia group, the mean fever duration before admission was shorter than that in the control group, whereas the fever duration after gamma globulin treatment was longer than that in the control group; these differences were statistically significant (P < .05).Hyperbilirubinemia incidence in children with KD was approximately 30.77% (120 cases), of which increased direct bilirubin was observed in 70.83% (85 cases) and increased indirect bilirubin in 29.17% (35 cases). Children with KD combined with hyperbilirubinemia exhibited a strong inflammatory reaction, which may be due to liver damage or biliary block.
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http://dx.doi.org/10.1097/MD.0000000000021974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478457PMC
September 2020

A Strategy for Constructing Pore-Space-Partitioned MOFs with High Uptake Capacity for C Hydrocarbons and CO.

Angew Chem Int Ed Engl 2020 Oct 26;59(43):19027-19030. Epub 2020 Aug 26.

Department of Chemistry, University of California, Riverside, CA, 92521, USA.

Introduction of pore partition agents into hexagonal channels of MIL-88 type (acs topology) endows materials with high tunability in gas sorption. Here, we report a strategy to partition acs framework into pacs (partitioned acs) crystalline porous materials (CPM). This strategy is based on insertion of in situ synthesized 4,4'-dipyridylsulfide (dps) ligands. One third of open metal sites in the acs net are retained in pacs MOFs; two thirds are used for pore-space partition. The Co V-pacs MOFs exhibit near or at record high uptake capacities for C H , C H , C H , and CO among MOFs. The storage capacity of C H is 234 cm  g (298 K) and 330 cm  g (273 K) at 1 atm for CPM-733-dps (the Co V-BDC form, BDC=1,4-benzenedicarboxylate). These high uptake capacities are accomplished with low heat of adsorption, a feature desirable for low-energy-cost adsorbent regeneration. CPM-733-dps is stable and shows no loss of C H adsorption capacity following multiple adsorption-desorption cycles.
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http://dx.doi.org/10.1002/anie.202008696DOI Listing
October 2020

Phylogeny and multiple independent whole-genome duplication events in the Brassicales.

Am J Bot 2020 08 24;107(8):1148-1164. Epub 2020 Aug 24.

Division of Biological Sciences and Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, 65211, USA.

Premise: Whole-genome duplications (WGDs) are prevalent throughout the evolutionary history of plants. For example, dozens of WGDs have been phylogenetically localized across the order Brassicales, specifically, within the family Brassicaceae. A WGD event has also been identified in the Cleomaceae, the sister family to Brassicaceae, yet its placement, as well as that of WGDs in other families in the order, remains unclear.

Methods: Phylo-transcriptomic data were generated and used to infer a nuclear phylogeny for 74 Brassicales taxa. Genome survey sequencing was also performed on 66 of those taxa to infer a chloroplast phylogeny. These phylogenies were used to assess and confirm relationships among the major families of the Brassicales and within Brassicaceae. Multiple WGD inference methods were then used to assess the placement of WGDs on the nuclear phylogeny.

Results: Well-supported chloroplast and nuclear phylogenies for the Brassicales and the putative placement of the Cleomaceae-specific WGD event Th-ɑ are presented. This work also provides evidence for previously hypothesized WGDs, including a well-supported event shared by at least two members of the Resedaceae family, and a possible event within the Capparaceae.

Conclusions: Phylogenetics and the placement of WGDs within highly polyploid lineages continues to be a major challenge. This study adds to the conversation on WGD inference difficulties by demonstrating that sampling is especially important for WGD identification and phylogenetic placement. Given its economic importance and genomic resources, the Brassicales continues to be an ideal group for assessing WGD inference methods.
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http://dx.doi.org/10.1002/ajb2.1514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496422PMC
August 2020

SCF-FBXO24 regulates cell proliferation by mediating ubiquitination and degradation of PRMT6.

Biochem Biophys Res Commun 2020 09 29;530(1):75-81. Epub 2020 Jul 29.

College of Life Science and Technology, Jinan University, Guangzhou, 510630, China; Institute of Biomedicine & National Engineering Research Center of Genetic Medicine, Guangzhou, 510630, China. Electronic address:

The protein arginine methyltransferase 6 (PRMT6) is a coregulator of gene expression by methylation of the histone H3 on arginine 2 (H3R2), H4R3 and H2AR3 [1,2]. PRMT6 is aberrantly expressed in various types of human cancer, and abnormal methylation in cancers caused by overexpression of PRMT6 is considered to correlate with poor recovery prognosis [3,4]. However, mechanisms that regulate PRMT6 protein stability in cells remain largely unknown. Here we identified that an orphan F-box protein, FBXO24, that binds to 270 to 275 amino acid residues of PRMT6 to cause polyubiquitination of lysine at position 369 of PRMT6, which mediates its degradation via the ubiquitin-proteasome pathway. Overexpression of FBXO24 or knockout of PRMT6 was found to inhibit cell proliferation, migration, and invasion in H1299 cells. PRMT6 K369R mutant became resistant to degradation. Overexpression of PRMT6 K369R caused cell cycle progression, resulting in cell proliferation. Thus, our data confirm that FBXO24 regulates cell proliferation by mediating ubiquitin-dependent proteasomal degradation of PRMT6.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.007DOI Listing
September 2020

Sequential and Iterative Auto-Segmentation of High-Risk Clinical Target Volume for Radiotherapy of Nasopharyngeal Carcinoma in Planning CT Images.

Front Oncol 2020 23;10:1134. Epub 2020 Jul 23.

Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Accurate segmentation of tumor targets is critical for maximizing tumor control and minimizing normal tissue toxicity. We proposed a sequential and iterative U-Net (SI-Net) deep learning method to auto-segment the high-risk primary tumor clinical target volume (CTVp1) for treatment planning of nasopharyngeal carcinoma (NPC) radiotherapy. The SI-Net is a variant of the U-Net architecture. The input of SI-Net includes one CT image, the CTVp1 contour on this image, and the next CT image. The output is the predicted CTVp1 contour on the next CT image. We designed the SI-Net, using the left side to learn the volumetric features and the right to localize the contour on the next image. Two prediction directions, one from inferior to superior (forward direction) and the other from superior to inferior (backward direction), were tested. The performance was compared between the SI-Net and the U-Net using Dice similarity coefficient (DSC), Jaccard index (JI), average surface distance (ASD), and Hausdorff distance (HD) metrics. The DSC and JI values from the forward direction SI-Net model were 5 and 6% higher than those from the U-Net model (0.84 ± 0.04 vs. 0.80 ± 0.05 and 0.74 ± 0.05 vs. 0.69 ± 0.05, < 0.001). The smaller ASD and HD values also indicated a better performance (2.8 ± 1.0 vs. 3.3 ± 1.0 mm and 8.7 ± 2.5 vs. 9.7 ± 2.7 mm, < 0.01) for the SI-Net model. For the backward direction SI-Net model, the DSC and JI values were still better than those from the U-Net model ( < 0.01), although there were no significant differences in ASD and HD. The SI-Net model preserved the continuity between adjacent images and thus improved the segmentation accuracy compared with the conventional U-Net model. This model has potential of improving the efficiency and consistence of CTVp1 contouring for NPC patients.
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http://dx.doi.org/10.3389/fonc.2020.01134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390915PMC
July 2020

Artificial Intelligence in Cutaneous Oncology.

Front Med (Lausanne) 2020 10;7:318. Epub 2020 Jul 10.

Department of Biomedical Engineering, Yonsei University, Wonju, South Korea.

Skin cancer, previously known to be a common disease in Western countries, is becoming more common in Asian countries. Skin cancer differs from other carcinomas in that it is visible to our eyes. Although skin biopsy is essential for the diagnosis of skin cancer, decisions regarding whether or not to conduct a biopsy are made by an experienced dermatologist. From this perspective, it is easy to obtain and store photos using a smartphone, and artificial intelligence technologies developed to analyze these photos can represent a useful tool to complement the dermatologist's knowledge. In addition, the universal use of dermoscopy, which allows for non-invasive inspection of the upper dermal level of skin lesions with a usual 10-fold magnification, adds to the image storage and analysis techniques, foreshadowing breakthroughs in skin cancer diagnosis. Current problems include the inaccuracy of the available technology and resulting legal liabilities. This paper presents a comprehensive review of the clinical applications of artificial intelligence and a discussion on how it can be implemented in the field of cutaneous oncology.
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http://dx.doi.org/10.3389/fmed.2020.00318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366843PMC
July 2020

Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors.

Nat Commun 2020 07 24;11(1):3704. Epub 2020 Jul 24.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77, Stockholm, Sweden.

FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2 tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2 pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2 tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2 breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
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http://dx.doi.org/10.1038/s41467-020-17525-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382445PMC
July 2020
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