Publications by authors named "Xuan Yang"

372 Publications

A pH/ultrasonic dual-response step-targeting enterosoluble granule for combined sonodynamic-chemotherapy guided gastrointestinal tract imaging in orthotopic colorectal cancer.

Nanoscale 2021 Feb;13(7):4278-4294

Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P. R. China. and Key Laboratory of Biomedical Photonics (HUST), Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P. R. China.

Colorectal cancer is one of the malignant tumors with high morbidity and lethality. Its efficient diagnosis and treatment has important significance. In this study, the orthotopic cancer model mouse, which could perfectly simulate clinical inflammatory colorectal cancer, was constructed by chemical induction. Based on this model, a new pH/ultrasonic dual-response, step-targeting and precisely controlled-release enteric-coated granule was designed for the combined sonodynamic (SDT)-chemotherapy. The enteric-coated granule was fabricated by enwrapping carboxymethyl chitosan (CMC) on folic acid-modified phospholipid (SLB-FA) encapsulating mesoporous silicon-coated gold nanoparticles loaded with chlorin (Ce6) and doxorubicin hydrochloride (DOX), titled as Au@mSiO2/Ce6/DOX/SLB-FA@CMC (GMCDS-FA@CMC). The diameter of the Au@mSiO2/Ce6/DOX/SLB-FA (GMCDS-FA) nanoprobe was 61.21 nm and that of the GMCDS-FA@CMC enteric-coated granule was 1.1 μm. MTT results showed that the cell survival rate was still as high as 76.55 ± 1.27% when the concentration of GMCDS-FA was up to 200 μg mL-1, which can indicate the low cytotoxicity of the nanoprobe. According to CT imaging, the enteric-coated granule had the highest concentration in the colorectum of the orthotopic cancer mouse after 7-9 h with oral administration, and was nearly metabolized out of the body after 24 h. The in vitro and in vivo experiments showed that the targeting enteric-coated granule had the best effect of treatment and desired prognosis after combined SDT-chemotherapy.
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http://dx.doi.org/10.1039/d0nr08100kDOI Listing
February 2021

Adult trkB signaling in parvalbumin interneurons is essential to prefrontal network dynamics.

J Neurosci 2021 Feb 15. Epub 2021 Feb 15.

Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden

Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of gamma oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/Tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP - abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.BDNF/trkB signaling promotes the maturation of inhibitory PV interneurons - neurons central to local cortical dynamics, gamma rhythms, and cognition. Here, we used a novel viral approach for reduced BDNF/trkB signaling in PV interneurons in the mPFC to establish the role of BDNF/trkB signaling in adult prefrontal network activities. Reduced BDNF/trkB signaling caused pronounced morphological alterations, reduced PV inhibition, and deficient prefrontal network dynamics. The altered network activity appeared to manifest across stimuli and brain states and was associated with aberrant LFP activities and increased aggression. The results demonstrate that adult BDNF/trkB signaling is essential to PV inhibition and prefrontal circuit function and directly links BDNF/trkB signaling to network integrity in the adult brain.
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http://dx.doi.org/10.1523/JNEUROSCI.1848-20.2021DOI Listing
February 2021

Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice.

Nat Commun 2021 02 15;12(1):1026. Epub 2021 Feb 15.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Proprioceptive neurons (PNs) are essential for the proper execution of all our movements by providing muscle sensory feedback to the central motor network. Here, using deep single cell RNAseq of adult PNs coupled with virus and genetic tracings, we molecularly identify three main types of PNs (Ia, Ib and II) and find that they segregate into eight distinct subgroups. Our data unveil a highly sophisticated organization of PNs into discrete sensory input channels with distinct spatial distribution, innervation patterns and molecular profiles. Altogether, these features contribute to finely regulate proprioception during complex motor behavior. Moreover, while Ib- and II-PN subtypes are specified around birth, Ia-PN subtypes diversify later in life along with increased motor activity. We also show Ia-PNs plasticity following exercise training, suggesting Ia-PNs are important players in adaptive proprioceptive function in adult mice.
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http://dx.doi.org/10.1038/s41467-021-21173-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884389PMC
February 2021

Phytoplankton responses to solar UVR and its combination with nutrient enrichment in a plateau oligotrophic Lake Fuxian: a mesocosm experiment.

Environ Sci Pollut Res Int 2021 Feb 12. Epub 2021 Feb 12.

Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Sciences, Yunnan University, Kunming, 650500, China.

Multiple stressors associated with global change are influencing the phytoplankton taxonomic composition and biomass in plateau lakes, such as higher levels of ultraviolet radiation (UVR, 280-400 nm) and the risk of eutrophication. Although the restrictive effects of high UVR on phytoplankton are generally recognized, the effects will be impacted by the UVR levels of seasonal changes and the nutrient status. In this study, in situ phytoplankton productivity was measured seasonally under full solar radiation and only visible light (photosynthetically active radiation, PAR) conditions in the plateau oligotrophic Lake Fuxian, Southwest China. To determine the single effects of UVR and nutrient enrichment and their combined impact on phytoplankton communities, a mesocosm experiment (1 month) was conducted outdoors during late summer (rainy season). The interactive experiment was designed with two radiation treatments (UVR + PAR and PAR) and four nutrient treatments (raw water, nitrogen addition, phosphorus addition, nitrogen and phosphorus addition). Our results suggested that the response of phytoplankton to UVR depended largely on nutrient availability, which was embodied in the no significant responses of phytoplankton productivity and total biomass to UVR in the oligotrophic raw water from Lake Fuxian, but the positive responses of total biomass to UVR in the nutrient enrichment treatment. Furthermore, the response of phytoplankton to UVR was also taxa dependent. Chlorophytes and dinoflagellates showed positive response to UVR, whereas chrysophytes were quite sensitive to UVR; diatoms had no significant response to UVR under all nutrient conditions, while the response of cyanobacteria to UVR was highly dependent on nutrient status. This study highlights that the increase in nutrient concentrations in oligotrophic lake not only directly promotes the growth of phytoplankton but also combines with low UVR during summer to benefit the growth of eutrophic taxa based on the non-negative effect of UVR on total phytoplankton biomass and the positive effect on eutrophic taxa.
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http://dx.doi.org/10.1007/s11356-021-12705-3DOI Listing
February 2021

Triptycene End-Capped Indigo Derivatives - Turning Insoluble Pigments to Soluble Dyes.

European J Org Chem 2021 Jan 3;2021(1):72-76. Epub 2020 Nov 3.

Organisch-Chemisches Institut Ruprecht-Karls-Universität Heidelberg Im Neuenheimer Feld 270 69120 Heidelberg Germany.

The synthesis of a highly soluble triptycene end-capped indigo and its bay annulated derivative is reported. Both compounds have been studied by absorption and emission spectroscopy cyclic voltammetry, as well as theoretical calculations and compared to the parent indigo and bay annulated indigo. Besides a large improvement of solubility in organic solvents by the factor of approx. 70(!) the compounds also show a pronounced tendency to form crystals. Both properties, making these compounds promising electron acceptors for organic electronics.
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http://dx.doi.org/10.1002/ejoc.202001362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821156PMC
January 2021

The density of endometrial glandular openings: a novel variable to predict the live birth rate in patients with intrauterine adhesions following hysteroscopic adhesiolysis.

Hum Reprod 2021 Jan 22. Epub 2021 Jan 22.

Department of Gynecology, Third Xiangya Hospital of Central South University, Changsha, 410013, China.

Study Question: Can the density of endometrial glandular openings (DEGO) be a reliable and simple new variable in the prediction of live birth after hysteroscopic adhesiolysis?

Summary Answer: The DEGO grade at follow-up hysteroscopy outperforms American Fertility Society (AFS) score in predicting the live birth rate after hysteroscopic adhesiolysis for patients with intrauterine adhesions (IUAs).

What Is Known Already: Several methods, such as endometrial thickness and AFS score, have been proposed for predicting the live birth rate in patients with IUAs who undergo hysteroscopic adhesiolysis.

Study Design, Size, Duration: A test cohort of 457 patients with IUAs who underwent hysteroscopic adhesiolysis and had satisfactory follow-up hysteroscopy videos were retrospectively enrolled between January 2016 and January 2017. A validation cohort comprising 285 IUA patients was prospectively enrolled from March 2018 to August 2018.

Participants/materials, Setting, Methods: An automated counting software tested the follow-up hysteroscopy videos to calculate the DEGO grade of all the 742 patients with IUAs after hysteroscopic adhesiolysis. The AFS score for each patient was also calculated at the same follow-up hysteroscopy. Logistic regression analysis was performed to develop prediction models to predict the live birth rate following hysteroscopic adhesiolysis. The performance of each of these prediction models was compared by calculating the AUC.

Main Results And The Role Of Chance: In the test cohort (n = 457), 231 patients had a live birth, but 226 patients failed. In the validation cohort (n = 285), 117 patients had a live birth, while 168 patients did not. The logistic regression analysis revealed that both the DEGO grade and AFS score at follow-up hysteroscopy were closely correlated with the live birth rate in patients with IUAs (P = 0). The AUCs of AFS score and DEGO grade in the test cohort were 0.7112 and 0.8498, respectively (P < 0.0001). The AUCs of AFS score and DEGO grade in the prospective external validation cohort were 0.6937 and 0.8248, respectively (P < 0.0001).

Limitations, Reasons For Caution: Further well-designed prospective clinical studies with a multicentric larger sample size should be needed to confirm the feasibility and efficacy of DEGO.

Wider Implications Of The Findings: The DEGO grade is an accurate predictor factor of live birth rate in patients with IUAs following hysteroscopic adhesiolysis and can represent in the future an important and promising tool for assessing obstetric outcomes in IUAs.

Study Funding/competing Interest(s): This study is supported by National Key Research and Development Program of China (Grant No. 2018YFC1004800), Natural Science Foundation of China (Grant No. 81671492), Natural Science Foundation of Hunan (Grant No. 2020JJ5859). B.G. is supported by Chinese Scholarship Council (File number. 201806370178). The authors have no conflicts of interest to declare.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa377DOI Listing
January 2021

L-Histidinium Chiral Ionic Liquid Functionalized β-Cyclodextrin as Chiral Selector in Capillary Electrophoresis.

J Chromatogr Sci 2021 Jan 22. Epub 2021 Jan 22.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, P. R. China.

Nowadays, ionic liquids (ILs) functionalized cyclodextrins (CDs) have drawn increasing attention in chiral separation. Herein, a novel β-CD derivative functionalized by L-histidinium IL, mono-6-deoxy-6-L-histidinium-β-cyclodextrin chloride (L-HMCDCl), was synthesized for the first time and utilized for enantioseparation of nefopam and chlorphenamine in capillary electrophoresis. The L-HMCDCl exhibited superior enantioselectivity compared with native β-CD. The effect of some key parameters such as chiral selector concentration, buffer pH and applied voltage on the enantioseparation was investigated in detail. In the interest of the chiral discrimination mechanism and the enhanced enantioselectivity of L-HMCDCl, molecular modeling with AutoDock was employed to study the interaction, which was in good agreement with experimental results.
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http://dx.doi.org/10.1093/chromsci/bmaa115DOI Listing
January 2021

Online informatics resources to facilitate cancer target and chemical probe discovery.

RSC Med Chem 2020 Jun 9;11(6):611-624. Epub 2020 Apr 9.

Department of Pharmacology and Chemical Biology , Emory University School of Medicine , Emory University , 1510 Clifton Road , Atlanta , GA 30322 , USA . Email: ; ; Tel: +1 404 727 6343.

The advances in cancer genomics, chemical biology, high-throughput screening technologies, and synthetic medicinal chemistry have tremendously expanded the biological space of cancer targets and chemical space of bioactive small molecules to interrogate oncogenic signaling. To explore and leverage these exponentially growing cancer-associated data, a great number of computational tools, databases, and algorithms have been developed. This review summarizes recent cancer-related web resources that allow researchers working at the interface of chemical, biological, and cancer genomics fields to integrate clinical and genomics data for specific actionable targets and selective chemical compounds to facilitate cancer therapeutic discovery.
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http://dx.doi.org/10.1039/d0md00012dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429978PMC
June 2020

Benzo-Fused Perylene Oligomers with up to 13 Linearly Annulated Rings.

Angew Chem Int Ed Engl 2021 Jan 18. Epub 2021 Jan 18.

Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120, Heidelberg, Germany.

The longer acenes with more than six linearly fused six-membered rings are still fascinating chemists and physicists because of their unique photophysical properties and their high potential for organic electronics applications. Unfortunately, with increasing size (seven and more rings) these compounds rapidly lose chemical stability. Besides kinetic and chemical stabilization approaches introducing either bulky or electron-withdrawing groups or both, such systems also have been stabilized by peri-annulation. Although strictly spoken, these peri-annulated compounds are no longer real acenes, they have fascinating properties as well. Herein, we describe the first synthesis of a new series of peri-annulated acenes with up to 13 linearly fused rings, which is unprecedented till date. Furthermore, this new series contains perylene units connected through benzene rings along their [b,k]edges, responsible for unique absorption and emission properties.
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http://dx.doi.org/10.1002/anie.202017062DOI Listing
January 2021

Hierarchical macro-microporous WPU-ECM scaffolds combined with Microfracture Promote Articular Cartilage Regeneration in Rabbits.

Bioact Mater 2021 Jul 22;6(7):1932-1944. Epub 2020 Dec 22.

Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro-microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro-microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.
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http://dx.doi.org/10.1016/j.bioactmat.2020.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772526PMC
July 2021

Linking phytosterols and oxyphytosterols from food to brain health: origins, effects, and underlying mechanisms.

Crit Rev Food Sci Nutr 2021 Jan 5:1-18. Epub 2021 Jan 5.

College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou, China.

Phytosterols and their oxidation products, namely oxyphytosterols, are natural compounds present in plant foods. With increased intake of phytosterol-enriched functional food products, the exposure of both phytosterols and oxyphytosterols is rising. Over the past ten years, researches have been focused on their absorption and metabolism in human body, as well as their biological effects. More importantly, recent studies showed that phytosterols and oxyphytosterols can traverse the blood-brain barrier and accumulate in the brain. As brain health problems resulting from ageing being more serious, attenuating central nervous system (CNS) disorders with active compounds in food are becoming a hot topic. Phytosterols and oxyphytosterols have been shown to implicated in cognition altering and the pathologies of several CNS disorders, including Alzheimer's disease and multiple sclerosis. We will overview these findings with a focus on the contents of phytosterols and oxyphytosterols in food and their dietary intake, as well as their origins in the brain, and illustrate molecular pathways through which they affect brain health, in terms of inflammation, cholesterol homeostasis, oxidative stress, and mitochondria function. The existing scientific gaps of phytosterols and oxyphytosterols to brain health in knowledge are also discussed, highlighting research directions in the future.
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http://dx.doi.org/10.1080/10408398.2020.1867819DOI Listing
January 2021

Hypomorph Mutation-Directed Small-Molecule Protein-Protein Interaction Inducers to Restore Mutant SMAD4-Suppressed TGF-β Signaling.

Cell Chem Biol 2020 Dec 4. Epub 2020 Dec 4.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Hematology and Medical Oncology and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. Electronic address:

Tumor suppressor genes represent a major class of oncogenic drivers. However, direct targeting of loss-of-function tumor suppressors remains challenging. To address this gap, we explored a variant-directed chemical biology approach to reverse the lost function of tumor suppressors using SMAD4 as an example. SMAD4, a central mediator of the TGF-β pathway, is recurrently mutated in many tumors. Here, we report the development of a TR-FRET technology that recapitulated the dynamic differential interaction of SMAD4 and SMAD4 with SMAD3 and identified Ro-31-8220, a bisindolylmaleimide derivative, as a SMAD4/SMAD3 interaction inducer. Ro-31-8220 reactivated the dormant SMAD4-mediated transcriptional activity and restored TGF-β-induced tumor suppression activity in SMAD4 mutant cancer cells. Thus, demonstration of Ro-31-8220 as a SMAD4/SMAD3 interaction inducer illustrates a general strategy to reverse the lost function of tumor suppressors with hypomorph mutations and supports a systematic approach to develop small-molecule protein-protein interaction (PPI) molecular glues for biological insights and therapeutic discovery.
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http://dx.doi.org/10.1016/j.chembiol.2020.11.010DOI Listing
December 2020

An association study between MiR-146a and INSR gene polymorphisms and hypertensive disorders of pregnancy in Northeastern Han Chinese population.

Placenta 2021 Jan 5;104:94-101. Epub 2020 Dec 5.

Department of Ultrasound, Shenzhen University General Hospital, NO.1098, Xueyuan Avenue, Nanshan District, Shenzhen, 518055, Guangdong, China. Electronic address:

Introduction: Hypertensive disorders of pregnancy(HDP) is a complex and challenging group of pregnancy complications that is one of the leading causes of maternal and fetal death worldwide. Recent studies have shown that the single nucleotide polymorphism(SNP) may play a role in the pathogenesis of HDP. This study aimed to investigate the association of MiR-146a rs2910164 and insulin receptor(INSR) rs2059806 SNPs with HDP and their associated complications in the Han population of Northeast China.

Methods: A total of 240 HDP patients and 380 healthy controls were selected for genotype determination. For the most special and high incidence of HDP, we also studied the SNPs in association with pre-eclampsia(PE) patients. In addition, HDP complicated with gestational diabetes mellitus(GDM) patients was further analyzed to identify the association between SNPs and HDP-related complications. Multivariate logical regression analysis combined with 10, 000 permutation test corrections was used to analyze the association of MiR-146a and INSR SNPs with HDP.

Results: After adjusting for relevant factors, MiR-146a rs2910164 or INSR rs2059806 SNPs were not significantly different between HDP or PE patients and healthy controls(P>0.05). Meanwhile, MiR146a rs2910164 and INSR rs2059806 SNPs were not significantly different between HDP complicated with GDM and control group.

Discussion: Our data indicates that MiR-146a rs2910164 and INSR rs2059806 SNPs may not be significantly related with HDP in the Han population of Northeast China living in Heilongjiang Province.
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http://dx.doi.org/10.1016/j.placenta.2020.11.011DOI Listing
January 2021

Identifying a Potential Key Gene, TIMP1, Associated with Liver Metastases of Uveal Melanoma by Weight Gene Co-Expression Network Analysis.

Onco Targets Ther 2020 19;13:11923-11934. Epub 2020 Nov 19.

Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People's Republic of China.

Purpose: Uveal melanoma (UM) is a primary intraocular tumor in adults, with a high percentage of metastases to the liver. Identifying potential key genes may provide information for early detection and prognosis of UM metastasis.

Patients And Methods: Differentially expressed genes (DEGs) were identified using the GSE22138 dataset. Weighted gene co-expression network analysis was used to construct co-expression modules. Functional enrichment analysis was performed for DEGs and genes of key modules. Hub genes were screened by co-expression network and protein-protein interaction network (PPI), and validated by survival analysis in The Cancer Genome Atlas database. Gene set enrichment analysis (GSEA) was used to explore the potential metastasis mechanism of UM. Transient transfection was used to investigate the effect of TIMP1 on the proliferation, migration, and invasion of UM cells.

Results: In total, 552 DEGs were identified between primary and metastatic UM and mainly enriched in extracellular matrix, cellular senescence and focal adhesion pathway. A weighted gene co‑expression network was built to identify key gene modules associated with UM metastasis (n=36). The turquoise module is positively correlated with metastasis and genes in this module were mainly enriched in peptidyl-tyrosine autophosphorylation and regulation of organ growth. The hub gene was screened out by co-expression network and PPI analysis. High expression of TIMP1 was related to p53 pathway by GSEA and short overall survival time. Experimental results indicated that overexpression of TIMP1 inhibited the proliferation and migration, while it had no significant effect on invasion of UM cells.

Conclusion: Our study indicates that might be associated with metastasis in UM, which might have important significance for identifying patients with high risk of metastasis and predicting the prognosis of UM.
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http://dx.doi.org/10.2147/OTT.S280435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682792PMC
November 2020

Reciprocal REGγ-mTORC1 regulation promotes glycolytic metabolism in hepatocellular carcinoma.

Oncogene 2021 Jan 23;40(3):677-692. Epub 2020 Nov 23.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

Despite significant progression in the study of hepatocellular carcinoma (HCC), the role of the proteasome in regulating cross talk between mTOR signaling and glycolysis in liver cancer progression is not fully understood. Here, we demonstrate that deficiency of REGγ, a proteasome activator, in mice significantly attenuates DEN-induced liver tumor formation. Ablation of REGγ increases the stability of PP2Ac (protein phosphatase 2 catalytic subunit) in vitro and in vivo, which dephosphorylates PRAS40 (AKT1 substrate 1) and stabilizes the interaction between PRAS40 and Raptor to inactive mTORC1-mediated hyper-glycolytic metabolism. In the DEN-induced animal model and clinical hepato-carcinoma samples, high levels of REGγ in HCC tumor regions contribute to reduced expression of PP2Ac, leading to accumulation of phosphorylated PRAS40 and mTORC1-mediated activation of HIF1α. Interestingly, mTORC1 enhances REGγ activity in HCC, forming a positive feedback regulatory loop. In conclusion, our study identifies REGγ-PP2Ac-PRAS40 axis as a new layer in regulating mTORC1 activity and downstream glycolytic alterations during HCC development, highlighting the REGγ-proteasome as a potential target for personalized HCC therapy.
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http://dx.doi.org/10.1038/s41388-020-01558-8DOI Listing
January 2021

A convenient approach for antibacterial polypeptoids featuring sulfonium and oligo(ethylene glycol) subunits.

Biomater Sci 2020 Dec;8(24):6969-6977

Key Laboratory of Biobased Polymer Materials, College of Polymer Science and Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China.

Bioinspired polypeptoids show great potential in many applications. Here, we report a convenient approach to synthesize a novel type of polypeptoid containing both sulfonium and oligo(ethylene glycol) (OEG) moieties by ring-opening polymerization (ROP) and a post-modification strategy. Three types of epoxides with (OEG)n (n = 1-3) groups are involved to offer various functionalities. The obtained polypeptoid sulfonium salts show positive ζ potential, irrespective of the solution pH and the degree of polymerization (DP). We demonstrate that the polypeptoids exhibit excellent antibacterial activity against Staphylococcus aureus (S. aureus) with MIC (minimal inhibitory concentration) in the range of 3.9-7.8 μg mL-1. In addition, the polypeptoids have a low hemolysis property and good in vitro biocompatibility. Remarkably, the as-prepared polypeptoids show rapid and potent antibacterial activity within 5 min. These features suggest that the obtained polypeptoids offer great potential for antimicrobial agents.
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http://dx.doi.org/10.1039/d0bm01384fDOI Listing
December 2020

[Impacts of Nitrogen Application on Ammonia Volatilization During Maize Season in Northern China].

Huan Jing Ke Xue 2020 Nov;41(11):5176-5184

Beijing Key Laboratory of Prevention, Control and Restoration of Farmland and Soil Pollution, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China.

Ammonia volatilization is one of the major paths of nitrogen (N) loss and may exert a substantial impact on air quality. This study aims to explore the effects of nitrogen (N) fertilizer types, fertilization rate, and application timing and gas collection method on NH volatilization during the maize season in Northern China. This study collected the publications on the NH volatilization from maize farming which were conducted in Northern China from 1980 to 2018, and undertook a systematic analysis. The study found that with the increase of N rate, the total and net NH volatilization at the basal and topdressing fertilization stages increased at exponential and power function, respectively. When the ratio of basal/topdressing N rate was 1/1, the total and net NH volatilization during the topdressing stage (58.4% of the whole season emission) was significantly higher than that in the basal fertilization stage (41.6%) (<0.05). The priming effect first showed a negative effect and then gradually turned into a positive effect with the increase of N rate. Due to the positive priming effect, the net NH volatilization, without considering the priming effect, was overestimated under the conventional N application (>297 kg·hm). There is a significant difference between the NH volatilization measured by the venting method and the sponge absorption method, and the data from the venting method are more stable (<0.01). Compared with conventional urea, slow-release urea may reduce NH volatilization by 20% to 50%. Control fertilizer N rate at the topdressing stage is more efficient in reducing the NH volatilization from maize production in Northern China, and the venting method is more suitable for the quantification of NH volatilization than the sponge absorption method under a high rate of fertilizer N.
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http://dx.doi.org/10.13227/j.hjkx.202002113DOI Listing
November 2020

A Facile Synthesis of Novel Amorphous TiO Nanorods Decorated rGO Hybrid Composites with Wide Band Microwave Absorption.

Nanomaterials (Basel) 2020 Oct 27;10(11). Epub 2020 Oct 27.

School of Physics, Dalian University of Technology, Dalian 116024, China.

Amorphous structures may play important roles in achieving highly efficient microwave absorption performance due to the polarization losses induced by the disorders, vacancies and other functional groups existed in them. Herein, a kind of amorphous TiO/rGO composite (a-TiO/rGO) was successfully fabricated via a facile one-step solvothermal method. The complex permittivity of the composites can be regulated by adjusting the addition of precursor solution. The minimum reflection loss of a-TiO/rGO composites reached -42.8 dB at 8.72 GHz with a thickness of 3.25 mm, and the widest efficient absorption bandwidth (EAB) was up to 6.2 GHz (11.8 to 18 GHz) with a thickness of only 2.15 mm, which achieved the full absorption in Ku band (12 to 18 GHz). Furthermore, the EAB was achieved ranging from 3.97 to 18 GHz by adjusting the thickness of the absorber, covering 87.7% of the whole radar frequency band. It is considered that the well-matched impedance, various polarization processes, capacitor-like structure and conductive networks all contributed to the excellent microwave absorption of a-TiO/rGO. This study provides reference on constructing amorphous structures for future microwave absorber researches and the as-prepared a-TiO/rGO composites also have great potential owing to its facile synthesis and highly efficient microwave absorption.
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http://dx.doi.org/10.3390/nano10112141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692450PMC
October 2020

Interaction kinetics of peptide lipids-mediated gene delivery.

J Nanobiotechnology 2020 Oct 17;18(1):144. Epub 2020 Oct 17.

Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Sciences, Dalian Minzu University, Dalian, 116600, China.

Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency.

Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (- 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the "proton sponge effect" of the lipid.

Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.
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http://dx.doi.org/10.1186/s12951-020-00707-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568367PMC
October 2020

Construction of Microunits by Adipose-Derived Mesenchymal Stem Cells Laden with Porous Microcryogels for Repairing an Acute Achilles Tendon Rupture in a Rat Model.

Int J Nanomedicine 2020 29;15:7155-7171. Epub 2020 Sep 29.

Department of Orthopedic Surgery, Key Laboratory of Musculoskeletal Trauma &war Injuries PLA, Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing 100853, People's Republic of China.

Objective: Tissue engineering approaches seem to be an attractive therapy for tendon rupture. Novel injectable porous gelatin microcryogels (GMs) can promote cell attachment and proliferation, thus facilitating the repair potential for target tissue regeneration. The research objectives of this study were to assess the efficacy of tissue-like microunits constructed by multiple GMs laden with adipose-derived mesenchymal stem cells (ASCs) in accelerated tendon regeneration in a rat model.

Methods: Through a series of experiments, such as isolation and identification of ASCs, scanning electron microscopy, mercury intrusion porosimetry (MIP), laser scanning confocal microscopy and the CCK-8 test, the biocompatibility of GMs was evaluated. In an in vivo study, 64 rat right transected Achilles tendons were randomly divided into four groups: the ASCs+GMs group (microunits aggregated by multiple ASC-laden GMs injected into the gap), the ASCs group ( injected into the gap), the GMs group (GMs injected into the gap) and the blank defect group (non-treated). At 2 and 4 weeks postoperatively, the healing tissue was harvested to evaluate the gross observation and scoring, biomechanical testing, histological staining and quantitative scoring. Gait analysis was performed over time. The 64 rats were randomly assigned into 4 groups: (1) micro-unit group (ASCs+GMs) containing ASC (10)-loaded 120 GMs in 60 μL DMEM; (2) cell control group (ASCs) containing 10 ASCs in 60 μL DMEM; (3) GM control group (GMs) containing 120 blank GMs in 60 μL DMEM; (4) blank defect group (Defect) containing 60 μL DMEM, which were injected into the defect sites. All animals were sacrificed at 2 and 4 weeks postsurgery (Table 1).

Results: In an in vitro study, GMs (from 126 μm to 348 μm) showed good porosities and a three-dimensional void structure with a good interpore connectivity of the micropores and exhibited excellent biocompatibility with ASCs. As the culture time elapsed, the extracellular matrix (ECM) secreted by ASCs encased the GMs, bound multiple microspheres together, and then formed active tendon tissue-engineering microunits. In animal experiments, the ASCs+GMs group and the ASCs group showed stimulatory effects on Achilles tendon healing. Moreover, the ASCs+GMs group was the best at improving the macroscopic appearance, histological morphology, Achilles functional index (AFI), and biomechanical properties of repair tissue without causing adverse immune reactions.

Conclusion: Porous GMs were conducive to promoting cell proliferation and facilitating ECM secretion. The ASCs-GMs matrices showed an obvious therapeutic efficiency for Achilles tendon rupture in rats.
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http://dx.doi.org/10.2147/IJN.S238399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535144PMC
November 2020

Hierarchical Microstructure of Laser Powder Bed Fusion Produced Face-Centered-Cubic-Structured Equiatomic CrFeNiMn Multicomponent Alloy.

Materials (Basel) 2020 Oct 11;13(20). Epub 2020 Oct 11.

Department of Chemistry and Materials Science, Aalto University School of Chemical Engineering, P.O. Box 16100, FI-00076 Espoo, Finland.

A cobalt-free equiatomic CrFeNiMn multicomponent alloy was fabricated from gas-atomized powder using laser powder bed fusion (L-PBF), also known as selective laser melting (SLM). The as-built specimens had a single face-centered cubic (FCC) structure, relative density of 98%, and hardness up to 248 HV for both the scanning speeds applied. In this work, we report the hierarchical microstructural features observed in the as-built specimens. These are comprised of melt pools, grains, cell structures including dendritic cells, elongated cells, equiaxed cells (~500 nm), and sub-cells (150-300 nm). The cell and sub-cell walls are composed of a notably high density of dislocations. In addition, segregation of Mn and Ni was detected at the cell walls, but only occasionally at the sub-cell walls. SLM exhibits the capability to produce FCC-structured equiatomic CrFeNiMn multicomponent alloy with the refined and hierarchical microstructure.
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http://dx.doi.org/10.3390/ma13204498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601856PMC
October 2020

Homotype-Targeted Biogenic Nanoparticles to Kill Multidrug-Resistant Cancer Cells.

Pharmaceutics 2020 Oct 9;12(10). Epub 2020 Oct 9.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

"Off-targeting" and receptor density expressed at the target sites always compromise the efficacy of the nanoparticle-based drug delivery systems. In this study, we isolated different cell membranes and constructed cell membrane-cloaked biogenic nanoparticles for co-delivery of antitumor paclitaxel (PTX) and multidrug resistance (MDR)-modulator disulfiram (DSF). Consequently, MDR cancer cell membrane (A549/T)-coated hybrid nanoparticles (A549/T CM-HNPs) selectively recognized the source cells and increased the uptake by ninefold via the homotypic binding mechanism. Moreover, the A549/T CM-HNPs sensitized MDR cells to PTX by suppressing P-glycoprotein (P-gp) activity by 3.2-fold and induced effective apoptosis (70%) in homologous A549/T cells. Cell-membrane coating based on the "homotypic binding" is promising in terms of promoting the accumulation of chemotherapeutics in MDR cells and killing them.
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http://dx.doi.org/10.3390/pharmaceutics12100950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600481PMC
October 2020

Influencing factors for peripheral and posterior lesions in mild non-proliferative diabetic retinopathy-the Kailuan Eye Study.

Int J Ophthalmol 2020 18;13(9):1467-1476. Epub 2020 Sep 18.

Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.

Aim: To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy (NPDR) in the Kailuan area of Tangshan, Hebei Province, China.

Methods: In this non-interventional, retrospective study, 683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study. Based on the undilated ultra-wide field (200°; UWF) images and partial dilated digital fundus images, the diabetic retinopathy (DR) of the surveyed population was graded. Interobserver agreement was estimated by using Cohen's Kappa statistics. The main outcome indicators included gender, age, weight, height, body mass index, blood pressure, circumferences of neck, waist and hip, current smoking, levels of fasting plasma glucose (FPG), hypersensitive C-reactive protein, creatinine, and cholesterol, . According to different lesions' locations of patients with mild NPDR, logistic regression models were used to estimate the odds ratios (ORs) and their 95%CIs of each risk factor.

Results: The study group of 683 patients included 570 males and 113 females. The mean age of the patients was 62.18±9.41y. Compared with dilated fundus examinations, there was fair agreement with the level of DR identified on UWF images in 63.91% of eyes (=0.369, 95%CI, 0.00-0.00). Detected by UWF images, there were 98 patients with mild NPDR having peripheral retinal lesions, 35 patients with mild NPDR having posterior lesions, 44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area, and 336 patients with non obvious DR. Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance (OR, 1.124; 95%CI, 1.044-1.211), and with posterior lesions were FPG (OR, 1.052; 95%CI, 1.007-1.099).

Conclusion: UWF is an effectiveness means of DR screening. Moreover, it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR. The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found. And the influencing factors in mild NPDR are differing by different lesions' locations.
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http://dx.doi.org/10.18240/ijo.2020.09.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459214PMC
September 2020

Antibacterial self-assembled nanodrugs composed of berberine derivatives and rhamnolipids against Helicobacter pylori.

J Control Release 2020 Dec 15;328:575-586. Epub 2020 Sep 15.

Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China. Electronic address:

The prevalence of infections with Helicobacter pylori (H. pylori) has progressively increased worldwide, which demonstrated to be closely correlated to its biofilm formation. H. pylori biofilms protect the bacteria by significantly decreasing their sensitivity to antibiotics. Moreover, H. pylori colonizes on the gastrointestinal tract epithelium which is covered by mucus layer, acting as another barrier to prevent antibacterial agents from reaching the colonization sites. Herein, we prepared four types of versatile self-assembled nanodrugs (BD/RHL NDs) containing lipophilic alkyl berberine derivatives (BDs) and rhamnolipids (RHL) to overcome the dual obstructions of both mucus layer and biofilms. Molecular dynamics simulations estimated that the driving forces for self-assembly of BD/RHL NDs were electrostatic and hydrophobic interactions. BD/RHL NDs, characterized by appropriate size, negative charge and enhanced hydrophilicity, successfully penetrated through mucus layer without interacting with mucins. In in vitro experiments, BD/RHL NDs exhibited substantial ability to eradicate H. pylori biofilms by destroying their extracellular polymeric substances (EPS) and killing planktonic H. pylori. Furthermore, BD/RHL NDs inhibited the adherence of H. pylori on both biotic and abiotic surfaces, therefore cut off the critical step of the biofilm re-formation which was associated with the recrudescence of infections. In an H. pylori-infected mice model, C10-BD/RHL NDs group showed 40 folds less remnant H. pylori and greater mucosal protection compared with the conventional clinical triple therapy. In conclusion, BD/RHL NDs could penetrate through mucus layer and effectively eradicate H. pylori biofilms in vitro and in vivo, providing a novel strategy for clinical treatment of biofilm-related infections.
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http://dx.doi.org/10.1016/j.jconrel.2020.09.025DOI Listing
December 2020

Self-Densification of Highly Mesoporous Wood Structure into a Strong and Transparent Film.

Adv Mater 2020 Oct 2;32(42):e2003653. Epub 2020 Sep 2.

Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, AlbaNova University Centre, Stockholm, SE-106 91, Sweden.

In the native wood cell wall, cellulose microfibrils are highly aligned and organized in the secondary cell wall. A new preparation strategy is developed to achieve individualization of cellulose microfibrils within the wood cell wall structure without introducing mechanical disintegration. The resulting mesoporous wood structure has a high specific surface area of 197 m g when prepared by freeze-drying using liquid nitrogen, and 249 m g by supercritical drying. These values are 5 to 7 times higher than conventional delignified wood (36 m g ) dried by supercritical drying. Such highly mesoporous structure with individualized cellulose microfibrils maintaining their natural alignment and organization can be processed into aerogels with high porosity and high compressive strength. In addition, a strong film with a tensile strength of 449.1 ± 21.8 MPa and a Young's modulus of 51.1 ± 5.2 GPa along the fiber direction is obtained simply by air drying owing to the self-densification of cellulose microfibrils driven by the elastocapillary forces upon water evaporation. The self-densified film also shows high optical transmittance (80%) and high optical haze (70%) with interesting biaxial light scattering behavior owing to the natural alignment of cellulose microfibrils.
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http://dx.doi.org/10.1002/adma.202003653DOI Listing
October 2020

High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients.

J Transl Med 2020 09 1;18(1):334. Epub 2020 Sep 1.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Emory University, 1510 Clifton Road, Atlanta, GA, 30322, USA.

Background: African American women experience a twofold higher incidence of triple-negative breast cancer (TNBC) and are 40% more likely to die from breast cancer than women of other ethnicities. However, the molecular bases for the survival disparity in breast cancer remain unclear, and no race-specific therapeutic targets have been proposed. To address this knowledge gap, we performed a systematic analysis of the relationship between gene mRNA expression and clinical outcomes determined for The Cancer Genome Atlas (TCGA) breast cancer patient cohort.

Methods: The systematic differential analysis of mRNA expression integrated with the analysis of clinical outcomes was performed for 1055 samples from the breast invasive carcinoma TCGA PanCancer cohorts. A deep learning fully-convolutional model was used to determine the association between gene expression and tumor features based on breast cancer patient histopathological images.

Results: We found that more than 30% of all protein-coding genes are differentially expressed in White and African American breast cancer patients. We have determined a set of 32 genes whose overexpression in African American patients strongly correlates with decreased survival of African American but not White breast cancer patients. Among those genes, the overexpression of mitogen-activated protein kinase kinase 3 (MKK3) has one of the most dramatic and race-specific negative impacts on the survival of African American patients, specifically with triple-negative breast cancer. We found that MKK3 can promote the TNBC tumorigenesis in African American patients in part by activating of the epithelial-to-mesenchymal transition induced by master regulator MYC.

Conclusions: The poor clinical outcomes in African American women with breast cancer can be associated with the abnormal elevation of individual gene expression. Such genes, including those identified and prioritized in this study, could represent new targets for therapeutic intervention. A strong correlation between MKK3 overexpression, activation of its binding partner and major oncogene MYC, and worsened clinical outcomes suggests the MKK3-MYC protein-protein interaction as a new promising target to reduce racial disparity in breast cancer survival.
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http://dx.doi.org/10.1186/s12967-020-02502-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465409PMC
September 2020

Intuitionistic Fuzzy Hierarchical Multi-Criteria Decision Making for Evaluating Performances of Low-Carbon Tourism Scenic Spots.

Int J Environ Res Public Health 2020 08 28;17(17). Epub 2020 Aug 28.

School of Information, Zhejiang University of Finance & Economics, Hangzhou 310018, China.

Low-carbon tourism is an effective solution to cope with the goal conflict between developing tourist economy and responding to carbon emission reduction and ecological environment protection. Tourism scenic spots are important carriers of tourist activities and play a crucial role in low-carbon tourism. There are multiple factors affecting the low-carbon performance of a tourism scenic spot, and thus the performance evaluation and ranking of low-carbon tourism scenic spots can be framed as a hierarchical multi-criteria decision making (MCDM) problem. This paper develops a novel method to tackle hierarchical MCDM problems, in which the importance preferences of criteria over the decision goal and sub-criteria with respect to the upper-level criterion are provided by linguistic-term-based pairwise comparisons and the assessments of alternatives over each of sub-criteria at the lowest level are furnished by positive interval values. The linguistic-term-based pairwise comparison matrices are converted into intuitionistic fuzzy preference relations and an approach is developed to obtain the global importance weights of the lowest level sub-criteria. A multiplicatively normalized intuitionistic fuzzy decision matrix is established from the interval-value-based assessments of alternatives and a method is proposed to determine the intuitionistic fuzzy value based comprehensive scores of alternatives. A case study is offered to illustrate how to build a performance evaluation index system of low-carbon tourism scenic spots located at Zhejiang Province of China and show the use of the proposed intuitionistic fuzzy hierarchical MCDM method.
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http://dx.doi.org/10.3390/ijerph17176259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503655PMC
August 2020

HER2-positive pure mucinous breast carcinoma: A case report and literature review.

Medicine (Baltimore) 2020 Aug;99(33):e20996

Department of Mammary Gland, Fudan University Cancer Hospital, Shanghai, China.

Introduction: Pure mucinous carcinoma is a rare type of breast carcinoma, but it usually has a favorable prognosis. Tumors of pure mucinous carcinoma are typically positive for both estrogen receptor (ER) and progesterone receptor (PR), and they do not commonly overexpress human epidermal growth factor receptor 2 (HER2). However, when tumors have HER2 overexpression and are progesterone receptor negative, the prognosis is worse.

Patient Concerns: A 59-year-old female reported a slow growth mass of 3 years, which was radiologically diagnosed as fibroadenoma at another institution. The patient came to our institution for treatment and follow-up. She had no salient past history.

Diagnosis: Excisional biopsy revealed a pure mucinous breast carcinoma that was ER (100%, moderate-strong intensity), PR(-), 5% Ki-67 (+), and HER2(3+) by immunohistochemistry. The HER2 gene was found to be amplified by fluorescence in situ hybridization (FISH). The clinical staging was T2N0M0, with pathological grade I, subtype luminal B.

Interventions: After a modified radical mastectomy, she received four 21-day cycles of intravenous docetaxel (75 mg/m), intravenous cyclophosphamide (600 mg/m), and intravenous trastuzumab (8 mg/kg) (loading dose) on day 1 followed by 6 mg/kg every 3 weeks to complete a full year of treatment. She then received 2.5 mg of letrozole daily for 5 years.

Outcomes: After following up for 2 years, the patient's outcome was survival without recurrence. Cardiac ultrasounds were performed every 3 months and there was no change in the left ventricular ejection fraction (LEVF).

Conclusion: It is essential to correctly diagnose the ER(+), PR(-) HER2(+) subtype in mucinous carcinoma. This type should be treated with chemotherapy and anti-HER2 therapy, as well as aromatase inhibitor endocrine therapy.
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http://dx.doi.org/10.1097/MD.0000000000020996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437824PMC
August 2020

MAP30 protein from Momordica charantia is therapeutic and has synergic activity with cisplatin against ovarian cancer in vivo by altering metabolism and inducing ferroptosis.

Pharmacol Res 2020 11 16;161:105157. Epub 2020 Aug 16.

Department of Obstetrics & Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

Increasing evidence shows that Traditional Chinese Medicine (TCM) has an obvious appeal for cancer treatment, but there is still a lack of scientific investigation of its underlying molecular mechanisms. Bitter melon or bitter gourd (Momordica charantia) is an edible fruit that is commonly consumed, and it is used to cure different diseases in various ancient folk medical practices. We report that a bioactive protein, MAP30, isolated from bitter melon seeds exhibited potent anticancer and anti-chemoresistant effects on ovarian cancer cells. Functional studies revealed that MAP30 inhibited cancer cell migration, cell invasion, and cell proliferation in various ovarian cancer cells but not normal immortalized ovarian epithelial cells. When administered with cisplatin, MAP30 produced a synergistic effect on cisplatin-induced cell cytotoxicity in ovarian cancer cells. When low doses of cisplatin and MAP30 were co-injected intraperitoneally, a remarkable reduction of tumor dissemination and tumor growth was observed in an ovarian cancer ascites mouse model. Notably, blood tests confirmed that MAP30 did not cause any adverse effects on liver and kidney functions in the treated mice. MAP30 activated AMP-activated protein kinase (AMPK) signaling via CaMKKβ and induced cell cycle arrest in the S-phase. MAP30 modulated cell metabolism of ovarian cancer cells via suppression of GLUT-1/-3-mediated glucose uptake, adipogenesis, and lipid droplet formation in tumor development and progression. MAP30 also induced an increase in intracellular Ca ion concentration, which triggered ROS-mediated cancer cell death via apoptosis and ferroptosis. Collectively, these findings suggest that natural MAP30 is a non-toxic supplement that may enhance chemotherapeutic outcomes and benefit ovarian cancer patients with peritoneal metastases.
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http://dx.doi.org/10.1016/j.phrs.2020.105157DOI Listing
November 2020

Preparation and characterization of bear bile-loaded pH sensitive gel eye drops for ocular drug delivery.

Iran J Basic Med Sci 2020 Jul;23(7):922-929

School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.

Objectives: In this study, a stable bear bile-loaded pH sensitive eye drop gel was prepared for sustain delivery and enhanced therapeutic application.

Materials And Methods: Bear bile-loaded ocular gels with different Carbopol/Hydroxypropyl methylcellulose (HPMC) ratios were prepared and their stability was tested in PBS at a series of pH at 40 C. The morphology was observed by SEM examination and rheology was observed by Rheometer equipped with a 60-mm cone-plate at apex angle of 1. Gel erosion and release kinetics of Tauroursodeoxycholic acid (TUDCA) was determined by HPLC. While, the dwelling time was obtained after administering the fluorescent-loaded gel in ocular disease-free New Zealand rabbits. Finally, biocompatibility and toxicity was observed by irritation test and H&E staining of eye-ball tissues, respectively.

Results: The bear bile-loaded ocular gel showed excellent stability at different pH (pH 5.0, 5.5, 6.0, 6.5, 7.0 and 8.0) up to 5 days, and bear bile extract significantly attenuated the gelling ability of the gel. The viscosity of gels formulation was decreased with increase in shear rate (0.01 to 100 s-1), and morphological examination of freeze-dried preparation showed three-dimensional reticular structure at physiological pH. The ocular gel exhibited promising sustained drug release up to 160 min , and showed prolonged retention time up to 3-folds . Finally, the biocompability data confirmed that the formulation did not induce any toxic effects and was completely compatible with eye tissues.

Conclusion: pH sensitive ocular gel provides new research opportunities to efficiently treat eye diseases.
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http://dx.doi.org/10.22038/IJBMS.2020.45386.10562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395188PMC
July 2020