Publications by authors named "Ying Li"

6,286 Publications

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Super Stretchable and Compressible Hydrogels Inspired by Hook-and-Loop Fasteners.

Langmuir 2021 Jun 15. Epub 2021 Jun 15.

Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, Connecticut 06269, United States.

Inspired by hook-and-loop fasteners, we designed a hydrogel network containing α-zirconium phosphate (ZrP) two-dimensional nanosheets with a high density of surface hydroxyl groups serving as nanopatches with numerous "hooks," while polymer chains with plentiful amine functional groups serve as "loops." Our multiscale molecular simulations confirm that both the high density of hydroxyl groups on nanosheets and the large number of amine functional groups on polymer chains are essential to achieve reversible interactions at the molecular scale, functioning as nano hook-and-loop fasteners to dissipate energy. As a result, the synthesized hydrogel possesses superior stretchability (>2100% strain), resilience to compression (>90% strain), and durability. Remarkably, the hydrogel can sustain >5000 cycles of compression with torsion in a solution mimicking synovial fluid, thus promising for potential biomedical applications such as artificial articular cartilage. This hook-and-loop model can be adopted and generalized to design a wide range of multifunctional materials with exceptional mechanical properties.
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http://dx.doi.org/10.1021/acs.langmuir.1c00924DOI Listing
June 2021

Evaluation of liver tissue extraction protocol for untargeted metabolomics analysis by ultra-high performance liquid chromatography/tandem mass spectrometry.

J Sep Sci 2021 Jun 15. Epub 2021 Jun 15.

National Key Discipline Laboratory, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, P. R. China.

The aim of untargeted metabolomics study is to obtain a global metabolome coverage from biological samples. Therefore, a comprehensive and systematic protocol for tissue metabolite extraction is highly desirable. In this study, we evaluated a comprehensive liver pretreatment strategy based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to obtain more metabolites using four different protocols. These protocols included (A) methanol protein precipitation, (B) two-step extraction of dichloromethane-methanol followed by methanol-water, (C) two-step extraction of methyl tert-butyl ether-methanol followed by methanol-water, and (D) two-step extraction of isopropanol-methanol followed by methanol-water. Our results showed that protocol D was superior to the others due to more extracted features, annotated metabolites and better reproducibility. And then, the stability and extraction sequence of protocol D were evaluated. The results showed that extraction with isopropanol-methanol followed by methanol-water was the optimum preparation sequence, which offered higher extraction efficiency, satisfactory repeatability and acceptable stability. Furthermore, the optimal protocol was successfully applied by liver samples of rats after high-fat intervention. In summary, our protocol enabled a comprehensive and systematic evaluation of liver pretreatment to obtain more medium-polar and nonpolar metabolites and was suitable for high-throughput metabolomics analysis. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100051DOI Listing
June 2021

Long-term copper exposure promotes apoptosis and autophagy by inducing oxidative stress in pig testis.

Environ Sci Pollut Res Int 2021 Jun 15. Epub 2021 Jun 15.

College of Veterinary, South China Agricultural University, Guangzhou, 510642, China.

Copper (Cu) is a heavy metal which is being used widely in the industry and agriculture. However, the overuse of Cu makes it a common environmental pollutant. In order to investigate the testicular toxicity of Cu, the pigs were divided into three groups and were given Cu at 10 (control), 125, and 250 mg/kg body weight, respectively. The feeding period was 80 days. Serum hormone results showed that Cu exposure decreased the concentrations of follicular stimulating hormone (FSH) and luteinizing hormone (LH) and increased the concentration of thyroxine (T4). Meanwhile, Cu exposure upregulated the expression of Cu transporter mRNA (Slc31a1, ATP7A, and ATP7B) in the testis, leading to increase in testicular Cu and led to spermatogenesis disorder. The Cu exposure led to an increased expression of antioxidant-related mRNA (Gpx4, TRX, HO-1, SOD1, SOD2, SOD3, CAT), along with increase in the MDA concentration in the testis. In LG group, the ROS in the testis was significantly increased. Furthermore, the apoptotic-related mRNA (Caspase3, Caspase8, Caspase9, Bax, Cytc, Bak1, APAF1, p53) and protein (Active Caspase3) and the autophagy-related mRNA (Beclin1, ATG5, LC3, and LC3B) expression increased after Cu exposure. The mitochondrial membrane potential in the testicular tissue decreased, while the number of apoptotic cells increased, as a result of oxidative stress. Overall, our study indicated that the Cu exposure promotes testicular apoptosis and autophagy by mediating oxidative stress, which is considered as the key mechanism causing testicular degeneration as well as dysfunction.
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http://dx.doi.org/10.1007/s11356-021-14853-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203493PMC
June 2021

Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer.

Carbohydr Polym 2021 Sep 21;268:118237. Epub 2021 May 21.

Department of Medical Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510091, China. Electronic address:

The application of traditional chemotherapy drugs for lung cancer has obvious limitations, such as toxic side effects, uncontrolled drug-release, poor bioavailability, and drug-resistance. Thus, to address the limitations of free drugs and improve treatment effects, we developed novel T7 peptide-modified nanoparticles (T7-CMCS-BAPE, CBT) based on carboxymethyl chitosan (CMCS), which is capable of targeted binding to the transferrin receptor (TfR) expressed on lung cancer cells and precisely regulating drug-release according to the pH value and reactive oxygen species (ROS) level. The results showed that the drug-loading content of docetaxel (DTX) and curcumin (CUR) was approximately 7.82% and 6.48%, respectively. Good biosafety was obtained even when the concentration was as high as 500 μg/mL. More importantly, the T7-CMCS-BAPE-DTX/CUR (CBT-DC) complexes exhibited better in vitro and in vivo anti-tumor effects than DTX monotherapy and other nanocarriers loaded with DTX and CUR alone. Furthermore, we determined that CBT-DC can ameliorate the immunosuppressive micro-environment to promote the inhibition of tumor growth. Collectively, the current findings help lay the foundation for combinatorial lung cancer treatment.
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http://dx.doi.org/10.1016/j.carbpol.2021.118237DOI Listing
September 2021

Electric signals counterbalanced posterior vs anterior PTEN signaling in directed migration of Dictyostelium.

Cell Biosci 2021 Jun 14;11(1):111. Epub 2021 Jun 14.

Department of Dermatology, School of Medicine, University of California, Davis, CA, 95618, USA.

Background: Cells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K and PTEN jointly play counterbalancing roles in this event via a bilateral regulation of PIP3 signaling. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive.

Methods: Dictyostelium cells with different genetic backgrounds were treated with direct current electric signals to investigate the genetic regulation of electrotaxis.

Results: We demonstrated that electric signals promoted PTEN phosphatase activity and asymmetrical translocation to the posterior plasma membrane of the electrotaxing cells. Electric stimulation produced a similar but delayed rear redistribution of myosin II, immediately before electrotaxis started. Actin polymerization is required for the asymmetric membrane translocation of PTEN and myosin. PTEN signaling is also responsible for the asymmetric anterior redistribution of PIP3/F-actin, and a biased redistribution of pseudopod protrusion in the forwarding direction of electrotaxing cells.

Conclusions: PTEN controls electrotaxis by coordinately regulating asymmetric redistribution of myosin to the posterior, and PIP3/F-actin to the anterior region of the directed migration cells.
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http://dx.doi.org/10.1186/s13578-021-00580-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201722PMC
June 2021

Enantioselective aerobic oxidative cross-dehydrogenative coupling of glycine derivatives with ketones and aldehydes cooperative photoredox catalysis and organocatalysis.

Chem Sci 2020 Apr 18;11(18):4741-4746. Epub 2020 Apr 18.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University 222 Tianshui South Road Lanzhou 730000 P. R. China

The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective aerobic oxidative cross-dehydrogenative coupling between glycine derivatives and simple ketones or aldehydes, which provides an efficient approach for the rapid synthesis of enantiopure unnatural α-alkyl α-amino acid derivatives in good yield with excellent diastereo- (up to >99 : 1) and enantioselectivities (up to 97% ee). This process includes the direct photoinduced oxidation of glycine derivatives to an imine intermediate, followed by the asymmetric Mannich-type reaction with an enamine intermediate generated from a ketone or aldehyde and a chiral secondary amine organocatalyst. This mild method allows the direct formation of a C-C bond with simultaneous installation of two new stereocenters without wasteful removal of functional groups.
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http://dx.doi.org/10.1039/d0sc00683aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159221PMC
April 2020

Dual-Emission Ratiometric Fluorescent Probe Based on Lanthanide-Functionalized Carbon Quantum Dots for White Light Emission and Chemical Sensing.

ACS Omega 2021 Jun 27;6(22):14629-14638. Epub 2021 May 27.

School of Materials Science & Engineering, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China.

Herein, we develop a novel method to synthesize lanthanide-functionalized carbon quantum dots via free-radical copolymerization using the methyl methacrylate (MMA) monomer as a functional monomer and introducing a lanthanide complex to obtain the dual-emission fluorescent composite material FCQDs-Ln(TFA) (Ln = Eu, Tb; TFA: trifluoroacetylacetone). The obtained composites were fully characterized, and their structures were investigated by Fourier transform infrared spectroscopy (FTIR), H NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Subsequently, a series of white-light-emitting polymer composite films FCQDs- (Eu:Tb)(TFA)/poly(methyl methacrylate) (PMMA) were designed and synthesized by adjusting the ratio of Eu(TFA)/Tb(TFA) under different wavelengths. More significantly, FCQDs-Tb(TFA) was selected as a sensitive probe for sensing metal cations due to excellent photoluminescence properties, revealing a unique capability of FCQDs-Tb(TFA) of detecting Fe(III) cations with high efficiency and selectivity. Furthermore, the sensing experiment results indicated that FCQDs-Tb(TFA) is ideal as a fluorescent nanoprobe for Fe ion detection, and the lowest detection limit for Fe is 0.158 μM, which is superior to many other previous related research studies. This pioneering work provides a new idea and method for constructing a dual-emission ratio sensor based on carbon quantum dots and also extends the potential application in the biological and environmental fields.
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http://dx.doi.org/10.1021/acsomega.1c01745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190926PMC
June 2021

Simultaneously boosting the conjugation, brightness and solubility of organic fluorophores by using AIEgens.

Chem Sci 2020 Jul 27;11(32):8438-8447. Epub 2020 Jul 27.

Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration and Reconstruction, Institute for Advanced Study, Department of Chemical and Biological Engineering, Institute of Molecular Functional Materials, The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong China

Organic near-infrared (NIR) emitters hold great promise for biomedical applications. Yet, most organic NIR fluorophores face the limitations of short emission wavelengths, low brightness, unsatisfactory processability, and the aggregation-caused quenching effect. Therefore, development of effective molecular design strategies to improve these important properties at the same time is a highly pursued topic, but very challenging. Herein, aggregation-induced emission luminogens (AIEgens) are employed as substituents to simultaneously extend the conjugation length, boost the fluorescence quantum yield, and increase the solubility of organic NIR fluorophores, being favourable for biological applications. A series of donor-acceptor type compounds with different substituent groups (, hydrogen, phenyl, and tetraphenylethene (TPE)) are synthesized and investigated. Compared to the other two analogs, with TPE substituents exhibits the reddest fluorescence, highest brightness, and best solubility. Both the conjugated structure and twisted conformation of TPE groups endow the resulting compounds with improved fluorescence properties and processability for biomedical applications. The and applications reveal that the NIR nanoparticles function as a potent probe for tumour imaging. This study would provide new insights into the development of efficient building blocks for improving the performance of organic NIR emitters.
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http://dx.doi.org/10.1039/d0sc03423aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163428PMC
July 2020

Blood Vessel Segmentation of Fundus Retinal Images Based on Improved Frangi and Mathematical Morphology.

Comput Math Methods Med 2021 26;2021:4761517. Epub 2021 May 26.

College of Communication and Information Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.

An improved blood vessel segmentation algorithm on the basis of traditional Frangi filtering and the mathematical morphological method was proposed to solve the low accuracy of automatic blood vessel segmentation of fundus retinal images and high complexity of algorithms. First, a global enhanced image was generated by using the contrast-limited adaptive histogram equalization algorithm of the retinal image. An improved Frangi Hessian model was constructed by introducing the scale equivalence factor and eigenvector direction angle of the Hessian matrix into the traditional Frangi filtering algorithm to enhance blood vessels of the global enhanced image. Next, noise interferences surrounding small blood vessels were eliminated through the improved mathematical morphological method. Then, blood vessels were segmented using the Otsu threshold method. The improved algorithm was tested by the public DRIVE and STARE data sets. According to the test results, the average segmentation accuracy, sensitivity, and specificity of retinal images in DRIVE and STARE are 95.54%, 69.42%, and 98.02% and 94.92%, 70.19%, and 97.71%, respectively. The improved algorithm achieved high average segmentation accuracy and low complexity while promising segmentation sensitivity. This improved algorithm can segment retinal vessels more accurately than other algorithms.
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http://dx.doi.org/10.1155/2021/4761517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172282PMC
May 2021

Nitric Oxide Is Associated With Heterosis of Salinity Tolerance in L.

Front Plant Sci 2021 28;12:649888. Epub 2021 May 28.

College of Life Sciences, Laboratory Center of Life Sciences, Nanjing Agricultural University, Nanjing, China.

Heterosis is most frequently manifested as the superior performance of a hybrid than either of the parents, especially under stress conditions. Nitric oxide (NO) is a well-known gaseous signaling molecule that acts as a functional component during plant growth, development, and defense responses. In this study, the L. hybrid (F1, NJ4375 × MB1942) showed significant heterosis under salt stress, during both germination and post-germination periods. These phenotypes in the hybrid were in parallel with the better performance in redox homeostasis, including alleviation of reactive oxygen species accumulation and lipid peroxidation, and ion homeostasis, evaluated as a lower Na/K ratio in the leaves than parental lines. Meanwhile, stimulation of endogenous NO was more pronounced in hybrid plants, compared with parental lines, which might be mediated by nitrate reductase. Proteomic and biochemical analyses further revealed that protein abundance related to several metabolic processes, including chlorophyll biosynthesis, proline metabolism, and tricarboxylic acid cycle metabolism pathway, was greatly suppressed by salt stress in the two parental lines than in the hybrid. The above responses in hybrid plants were intensified by a NO-releasing compound, but abolished by a NO scavenger, both of which were matched with the changes in chlorophyll and proline contents. It was deduced that the above metabolic processes might play important roles in heterosis upon salt stress. Taken together, we proposed that heterosis derived from F1 hybridization in salt stress tolerance might be mediated by NO-dependent activation of defense responses and metabolic processes.
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http://dx.doi.org/10.3389/fpls.2021.649888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194068PMC
May 2021

Immunosuppressive PLGA TGF-β1 Microparticles Induce Polyclonal and Antigen-Specific Regulatory T Cells for Local Immunomodulation of Allogeneic Islet Transplants.

Front Immunol 2021 27;12:653088. Epub 2021 May 27.

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States.

Allogeneic islet transplantation is a promising cell-based therapy for Type 1 Diabetes (T1D). The long-term efficacy of this approach, however, is impaired by allorejection. Current clinical practice relies on long-term systemic immunosuppression, leading to severe adverse events. To avoid these detrimental effects, poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) were engineered for the localized and controlled release of immunomodulatory TGF-β1. The co-incubation of TGF-β1 releasing PLGA MPs with naïve CD4 T cells resulted in the efficient generation of both polyclonal and antigen-specific induced regulatory T cells (iTregs) with robust immunosuppressive function. The co-transplantation of TGF-β1 releasing PLGA MPs and Balb/c mouse islets within the extrahepatic epididymal fat pad (EFP) of diabetic C57BL/6J mice resulted in the prompt engraftment of the allogenic implants, supporting the compatibility of PLGA MPs and local TGF-β1 release. The presence of the TGF-β1-PLGA MPs, however, did not confer significant graft protection when compared to untreated controls, despite measurement of preserved insulin expression, reduced intra-islet CD3 cells invasion, and elevated CD3Foxp3 T cells at the peri-transplantation site in long-term functioning grafts. Examination of the broader impacts of TGF-β1/PLGA MPs on the host immune system implicated a localized nature of the immunomodulation with no observed systemic impacts. In summary, this approach establishes the feasibility of a local and modular microparticle delivery system for the immunomodulation of an extrahepatic implant site. This approach can be easily adapted to deliver larger doses or other agents, as well as multi-drug approaches, within the local graft microenvironment to prevent transplant rejection.
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http://dx.doi.org/10.3389/fimmu.2021.653088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190479PMC
May 2021

Metabolic alterations mediated by STAT3 promotes drug persistence in CML.

Leukemia 2021 Jun 12. Epub 2021 Jun 12.

Department of Medicine, Division of Hematology/Oncology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.

Leukemic stem cells (LSCs) can acquire non-mutational resistance following drug treatment leading to therapeutic failure and relapse. However, oncogene-independent mechanisms of drug persistence in LSCs are incompletely understood, which is the primary focus of this study. We integrated proteomics, transcriptomics, and metabolomics to determine the contribution of STAT3 in promoting metabolic changes in tyrosine kinase inhibitor (TKI) persistent chronic myeloid leukemia (CML) cells. Proteomic and transcriptional differences in TKI persistent CML cells revealed BCR-ABL-independent STAT3 activation in these cells. While knockout of STAT3 inhibited the CML cells from developing drug-persistence, inhibition of STAT3 using a small molecule inhibitor sensitized the persistent CML cells to TKI treatment. Interestingly, given the role of phosphorylated STAT3 as a transcription factor, it localized uniquely to genes regulating metabolic pathways in the TKI-persistent CML stem and progenitor cells. Subsequently, we observed that STAT3 dysregulated mitochondrial metabolism forcing the TKI-persistent CML cells to depend on glycolysis, unlike TKI-sensitive CML cells, which are more reliant on oxidative phosphorylation. Finally, targeting pyruvate kinase M2, a rate-limiting glycolytic enzyme, specifically eradicated the TKI-persistent CML cells. By exploring the role of STAT3 in altering metabolism, we provide critical insight into identifying potential therapeutic targets for eliminating TKI-persistent LSCs.
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http://dx.doi.org/10.1038/s41375-021-01315-0DOI Listing
June 2021

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omics.

Genomics Proteomics Bioinformatics 2021 Jun 9. Epub 2021 Jun 9.

BGI-Shenzhen, Shenzhen 518083, China.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, and cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancy, delivery histories, cesarean section, and breast-feeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breast-feeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiome, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.
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http://dx.doi.org/10.1016/j.gpb.2021.01.005DOI Listing
June 2021

Reactive oxygen species-responsive nanoplatforms for nucleic acid-based gene therapy of cancer and inflammatory diseases.

Biomed Mater 2021 Jun 11. Epub 2021 Jun 11.

China Pharmaceutical University, State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 210009, P. R. China, Nanjing, Jiangsu, 210009, CHINA.

Nucleic acid-based gene therapy has recently made important progress toward clinical implementation, and holds tremendous promise for the treatment of some life-threatening diseases, such as cancer and inflammation. However, the on-demand delivery of nucleic acid therapeutics in target cells remains highly challenging. The development of delivery systems responsive to specific pathological cues of diseases is expected to offer promising alternatives for overcoming this problem. Among them, the reactive oxygen species (ROS)-responsive delivery systems, which in response to elevated ROS in cancer cells or activated inflammatory cells, can deliver nucleic acid therapeutics on-demand via ROS-induced structural and assembly behavior changes, constitute a promising approach for cancer and anti-inflammation therapies. In this short review, we briefly introduce the ROS-responsive chemical structures, ROS-induced release mechanisms and some representative examples to highlight the current progress in constructing ROS-responsive delivery systems. We aim to provide new insights into the rational design of on-demand gene delivery vectors.
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http://dx.doi.org/10.1088/1748-605X/ac0a8fDOI Listing
June 2021

Novel small molecule inhibitors of the transcription factor ETS-1 and their antitumor activity against hepatocellular carcinoma.

Eur J Pharmacol 2021 Jun 8;906:174214. Epub 2021 Jun 8.

Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150040, China. Electronic address:

The transcription factor ETS-1 (E26 transformation specific sequence 1) is the key regulator for malignant tumor cell proliferation and invasion by mediating the transcription of the invasion/migration related factors, e.g. MMPs (matrix metalloproteinases). This work aims to identify the novel small molecule inhibitors of ETS-1 using a small molecule compound library and to study the inhibitors' antitumor activity against hepatocellular carcinoma (HCC). The luciferase reporter is used to examine the inhibition and activation of ETS-1's transcription factor activity in HCC cells, including a highly invasive HCC cell line, MHCC97-H, and five lines of patient-derived cells. The inhibition of the proliferation of HCC cells is examined using the MTT assay, while the invasion of HCC cells is examined using the transwell assay. The anti-tumor activity of the selected compound on HCC cells is also examined in a subcutaneous tumor model or intrahepatic tumor model in nude mice. The results show that for the first time, four compounds, EI1~EI-4, can inhibit the transcription factor activation of ETS-1 and the proliferation or invasion of HCC cells. Among the four compounds, EI-4 has the best activation. The results from this paper contribute to expanding our understanding of ETS-1 and provide alternative, the safer and more effective, HCC molecular therapy strategies.
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http://dx.doi.org/10.1016/j.ejphar.2021.174214DOI Listing
June 2021

A "double-locked" probe for the detection of hydrogen sulfide in a viscous system.

Chem Commun (Camb) 2021 Jun 11. Epub 2021 Jun 11.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.

A novel "double-locked" probe, DCO-H2S-V, was prepared for detecting hydrogen sulfide in a highly viscous system. Experiments demonstrated that only when H2S and a high viscosity environment coexist in a cell, can the probe be activated effectively and emit fluorescence. This has been successfully used for detecting the changes in viscosity and H2S in a Parkinson's disease model, PC-12 cells treated with glutamate.
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http://dx.doi.org/10.1039/d1cc01819aDOI Listing
June 2021

Chronic dantrolene treatment attenuates cardiac dysfunction and reduces atrial fibrillation inducibility in a rat myocardial infarction heart failure model.

Heart Rhythm O2 2020 Jun 15;1(2):126-135. Epub 2020 Jun 15.

Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York.

Background: Cardiac ryanodine receptor 2 (RyR2) dysfunction and elevated diastolic Ca leak have been linked to arrhythmogenesis not only in inherited arrhythmia syndromes but also in acquired forms of heart disease including heart failure (HF) and atrial fibrillation (AF). Thus, stabilizing RyR2 may exert therapeutic effects in these conditions.

Objective: The purpose of this study was to investigate the effects of stabilizing RyR2 with chronic dantrolene treatment on HF development and AF inducibility in a myocardial infarction (MI)-induced HF model in rats.

Methods: MI was induced in adult Sprague-Dawley rats by ligation of the left anterior descending coronary artery. Two weeks after MI surgery, rats with large MI (≥40%) were randomly assigned to MI-vehicle (n = 14) or MI-dantrolene (10 mg/kg/d; n = 13) groups. Sham-surgery rats (n = 7) served as controls.

Results: Compared to the MI-vehicle group, 4-week dantrolene treatment significantly improved cardiac function, with increased left ventricular (LV) fractional shortening (19.48% ± 3.61% vs 15.43% ± 2.65%; <.01), and decreased LV end-diastolic pressure (12.58 ± 8.52 mm Hg vs 21.91 ± 7.25 mm Hg; <.01), left atrial diameter (4.97 ± 0.75 mm vs 6.09 ± 1.53 mm; <.05), and fibrosis content (6.42% ± 0.78% vs 9.76% ± 2.25%; <.001). Dantrolene significantly decreased AF inducibility (69% in MI-vehicle vs 23% in MI-dantrolene; <.05). Dantrolene treatment was associated with reduced RyR2 phosphorylation and favorably altered gene expression involving ion channels, sympathetic signaling, oxidative stress, and inflammatory markers.

Conclusion: Chronic dantrolene treatment attenuated LV dysfunction and reduced AF inducibility, which was associated with decreased RyR2 phosphorylation and normalization of many adverse changes in gene expression. Thus, stabilizing RyR2 with chronic dantrolene treatment is a promising novel strategy for decreasing AF in HF.
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http://dx.doi.org/10.1016/j.hroo.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183840PMC
June 2020

Novel beta-blocker pretreatment prevents alcohol-induced atrial fibrillation in a rat model.

Heart Rhythm O2 2020 Jun 15;1(2):120-125. Epub 2020 Jun 15.

Department of Clinical Specialties, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York.

Background: A case report published in 2019 described a patient who presented with difficult-to-manage atrial fibrillation (AF) that consistently was associated with alcohol consumption. After the patient did not respond to drug therapy, a novel beta-blocker (BB) pretreatment regimen initiated immediately before alcohol consumption successfully prevented AF occurrence.

Objective: The purpose of this study was to test the hypothesis that a novel prophylactic BB therapy given before alcohol consumption could prevent AF in a rat model.

Methods: An alcohol-induced AF model was developed in adult Sprague-Dawley rats of both sexes by administering alcohol (2 g/kg intraperitoneal [IP]) once every other day for a total of 4 times. Three groups were enrolled: alcohol (EtOH; n = 10); alcohol plus BB (metoprolol 50 mg/kg IP) pretreatment (EtOH+BB; n = 10); and control (n = 9). Cardiac function (assessed by echocardiography and left ventricular hemodynamics) and atrial electrophysiology and AF inducibility tests were performed 24 hours after the last injection.

Results: All but 1 rat completed the study. Alcohol exposure did not significantly impact cardiac function and the atrial effective refractory period. However, alcohol exposure significantly increased AF inducibility [median (first and third quartile [Q1-Q3]) 0% (0%-0%) in control vs 60% (25%-100%) in the EtOH group;  <.05] and AF duration [0 second (0-0 second) in control vs 0.81 second (0.24-3.67 seconds) in the EtOH group; <.05]. Compared to the EtOH group, the EtOH+BB group had significantly reduced AF inducibility [0% (0%-22.5%); <.05] and duration [0 second (0-0.2 second); <.05].

Conclusion: Metoprolol pretreatment before alcohol administration significantly decreased AF induction in rats. These findings suggest that BB pretreatment is a promising prophylaxis regimen for alcohol-induced AF.
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http://dx.doi.org/10.1016/j.hroo.2020.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183851PMC
June 2020

rs641738 Is Not Associated With the Risk of Hepatocellular Carcinoma or Persistent Hepatitis B Infection.

Front Oncol 2021 25;11:639438. Epub 2021 May 25.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: A hot genetic variant, rs641738 within the and , was recently reported to be associated with several liver diseases. However, the results remain controversial. Therefore, this study aimed to explore the role of rs641738 in the risk of hepatocellular carcinoma (HCC) and persistent hepatitis B virus (HBV) infection.

Methods: We first conducted a case-control study that included 779 HCC cases and 1412 cancer-free controls. Controls consisted of 678 persistent HBV carriers and 734 spontaneously recovered subjects. The gene variant rs641738 was genotyped using the MassARRAY platform. The results were analyzed in five genetic models using multivariate logistic regression analyses. Next, we performed a systematic review and meta-analysis to further explore the role of this variant in HCC risk.

Results: The results suggested no association between rs641738 and HCC risk in most genetic models (all > 0.05). Although a marginally significant association was observed in TT . CC ( = 0.037) and the recessive models ( = 0.044). The meta-analysis of 2135 HCC cases and 4388 controls supported that this variant was not related to HCC risk, even in the TT . CC and recessive models. We also determined that this variant did not influence persistent HBV infection.

Conclusion: Our work highlights that rs641738 is not associated with the risk of HCC or persistent HBV infection. This study provides some clues to identify the "truth" of potential disease-related genetic factors in the post-genome era.
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http://dx.doi.org/10.3389/fonc.2021.639438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185222PMC
May 2021

MicroRNA‑142‑3p suppresses cell proliferation, invasion and epithelial‑to‑mesenchymal transition via RAC1‑ERK1/2 signaling in colorectal cancer.

Mol Med Rep 2021 Aug 10;24(2). Epub 2021 Jun 10.

Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China.

Aberrant expression of microRNAs (miRNAs/miRs) is associated with the initiation and progression of colorectal cancer (CRC), but how they regulate colorectal tumorigenesis is still unknown. The present study was designed to investigate the expression profile of miRNAs in human CRC tissues, and to reveal the molecular mechanism of miRNA‑142‑3p in suppressing colon cancer cell proliferation. The expression of miRNA was examined using an Exiqon miRNA array. Bioinformatics was used to predict the target genes of differentially expressed miRNAs and to analyze their biological function in CRC. The effect of miR‑142‑3p in colon cancer cells was evaluated using cell proliferation, colony formation and Transwell assays. Dual‑luciferase reporter gene assays were performed to investigate the association between miR‑142‑3p and Rac family small GTPase 1 (RAC1). The effect of miR‑142‑3p regulation on colon cancer proliferation was assessed through western blotting and quantitative polymerase chain reaction analysis. Compared with their expression in adjacent non‑cancer mucosal tissues, 76 miRNAs were upregulated and 102 miRNAs were downregulated in CRC. One of the most significantly and differentially regulated miRNAs was miR‑142‑3p, which was downregulated in 81.0% (51/63) of primary CRC tissues. After transfection of miR‑142‑3p mimics into colon cancer cells, proliferation and colony formation were decreased, and migration and invasion were markedly suppressed. was a possible target of miR‑142‑3p, which was confirmed by dual‑luciferase reporter assay. Transfection of miR‑142‑3p mimics decreased the levels of RAC1 and suppressed epithelial‑to‑mesenchymal transition in colon cancer cells. The phosphorylation of extraceullar signal‑regulated kinase (ERK) was decreased significantly by the inhibition of RAC1 or transfection of miR‑142‑3p mimics in colon cancer cells. In conclusion, aberrant miRNAs are implicated in CRC. Decreased expression of miR‑142‑3p may be associated with CRC tumorigenesis via Rac1‑ERK signaling.
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http://dx.doi.org/10.3892/mmr.2021.12207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201444PMC
August 2021

Multiplexed patterning of hybrid lipid membrane and protein arrays for cell signaling study.

Lab Chip 2021 Jun 10. Epub 2021 Jun 10.

Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan. and Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taiwan.

The supported lipid bilayer (SLB) is a powerful tool for studying dynamic cell-environment interactions and has been widely used for biosensing applications. Using a reusable microfluidic chip, we present here a strategy to fabricate highly multiplexed SLB and protein arrays for cell signaling research. This approach allows for the rapid patterning of hundreds of highly reproducible and size-tunable SLB arrays with distinct lipid composition and mobility. Using fluorescence microscopy and fluorescence correlation spectroscopy, the lipid mobility is found to play a central role for patterning this membrane assay. Adding protein rings as diffusion barriers extends the accessible mobility range and maintains long-term stability of the hybrid array. Subsequent protein functionalizations on the SLB could be conducted using standard conjugation methods. The utility of the hybrid array for cell signaling experiments is demonstrated by studying the immune NF-κB signaling, whose activity is triggered by the binding of the membrane receptor, toll-like-receptor 4 (TLR 4), to its ligand, lipopolysaccharide (LPS), that is functionalized on the SLB. The patterned array allows cells to adhere and spread on areas without LPS before migrating to interact with membrane-bound LPS to initiate NF-κB activation. Overall, the strategy offers an efficient route to rapidly generate easily controllable and multiplexed molecular arrays that can serve as versatile platforms for biosensing and cell signaling research.
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http://dx.doi.org/10.1039/d1lc00178gDOI Listing
June 2021

Integrated Analysis of Long Noncoding RNA Expression Profiles in Acute-on-Chronic Liver Failure.

Biomed Res Int 2021 18;2021:5387856. Epub 2021 May 18.

Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.

People infected with chronic hepatitis B virus (HBV) might progress to acute-on-chronic liver failure (ACLF) with a high fatality rate. Long noncoding RNAs (lncRNAs) are involved in human diseases, but it is unknown whether lncRNAs are involved in the progression of chronic HBV infection to ACLF. Hence, this study is aimed at systemically identifying and characterizing the landscape and the molecular mechanism of lncRNAs in the pathogenesis of chronic HBV infection progress to ACLF. RNA sequencing (RNA-Seq) of peripheral blood samples from 5 ACLF and 5 HBV infection patients was performed. We detected 9733 lncRNAs, including 406 annotated lncRNAs and 9327 novel lncRNAs. A total of 407 lncRNAs were found to be significantly dysregulated in the patients with ACLF as compared with those in the chronic HBV infection patients. The flanking protein-coding genes of differentially expressed lncRNAs were enriched with pathways that might contribute to the pathogenesis of ACLF, such as the WNT signaling pathway. Furthermore, 9 selected differentially expressed lncRNAs validated by the qRT-PCR, showing that the expression patterns of these 9 lncRNAs were consistent with the RNA-Seq data. Four selected differentially expressed lncRNAs were also validated in another patient cohort comprising 80 patients with ACLF and 65 patients with chronic HBV infection. Aberrant lncRNAs might be used to develop novel diagnostic biomarkers or drug targets for ACLF.
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http://dx.doi.org/10.1155/2021/5387856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158414PMC
May 2021

The chronotype conjecture in the association between dietary carbohydrate intake and high-sensitivity C-reactive protein (hs-CRP): a cross-sectional study from NHANES 2015 data.

Sleep Sci 2021 Jan-Mar;14(1):3-10

Harbin Medical University, Department of Nutrition and Food Hygiene, School of Public Health - Harbin - Heilongjiang - China.

Substantial evidence suggests that the timing of macronutrient intake affects cardiovascular health. The present study aims to assess the association between the dietary carbohydrate intake (DCI) and the high-sensitivity C-reactive protein (hs-CRP) combined with the implication of the chronotype. Thus, we explored the most recently released National Health and Nutrition Examination Survey (NHANES) data. We analysed data from 5,616 participants of the NHANES in 2015. We selected participants with available data for the DCI, sleep and wake-up time, and the hs-CRP. Chronotypes were categorized according to the sleep times. Binary logistic regression analysis was performed to predict participants with low or high levels of hs-CRP based on the DCI and chronotypes. Moderation analysis was used to investigate the effect of the chronotypes on the DCI-hs-CRP's association. A higher DCI was significantly associated with the higher hs-CRP levels (odds ratio (OR) = 1.36, 95% confidence interval (CI) = [0.9-1.8]). Moderate evening (ME) chronotypes had higher risk for high hs-CRP level (OR = 1.15, 95% CI = [1.22-1.23]) compared to the intermediate and the morning chronotypes. The chronotype significantly moderated the hs-CRP given the DCI (moderation coefficient, α2=0.05, 95% CI = [0.01-0.08]). The chronotype diminished the hs-CRP predicted by the DCI. The findings of the study underscore the significance of assessing the protective effect of individuals' chronotype concerning cardiovascular health.
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http://dx.doi.org/10.5935/1984-0063.20200047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157775PMC
June 2021

Copper induces mitochondria-mediated apoptosis via AMPK-mTOR pathway in hypothalamus of Pigs.

Ecotoxicol Environ Saf 2021 Sep 5;220:112395. Epub 2021 Jun 5.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, PR China. Electronic address:

Copper (Cu), one of the heavy metals, is far beyond the carrying capacity of the environment with Cu mining, industrial wastewater discharging and the use of Cu-containing pesticides. Intaking excess Cu can cause toxic effects on liver, kidney, heart, but few studies report Cu toxicity on brain tissue. It is noteworthy that most toxicity tests are based on rodent models, but large mammals chosen as animal models has no reported. To explore the relationship of the Cu toxicity and mitochondria-mediated apoptosis on hypothalamus in pigs, the content of Cu, histomorphology, mitochondrial related indicators, apoptosis, and AMPK-mTOR signaling pathway were detected. Results showed that Cu could accumulate in hypothalamus and lead to mitochondrial dysfunction, evidenced by the decrease of ATP production, activities of respiratory chain complex I-IV, and mitochondrial respiratory function in Cu-treated groups. Additionally, the genes and proteins expression of Bax, Caspase-3, Cytc in treatment group were higher than control group. Furthermore, the protein level of p-AMPK was enhanced significantly and p-mTOR was declined, which manifested that AMPK-mTOR signaling pathway was activated in Cu-treated groups. In conclusion, this study illuminated that the accumulation of Cu could cause mitochondrial dysfunction, induce mitochondria-mediated apoptosis and activate AMPK-mTOR pathway in hypothalamus.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112395DOI Listing
September 2021

Guanosine and uridine alleviate airway inflammation via inhibition of the MAPK and NF-κB signals in OVA-induced asthmatic mice.

Pulm Pharmacol Ther 2021 Jun 5;69:102049. Epub 2021 Jun 5.

Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, PR China. Electronic address:

Asthma is one of the most common respiratory diseases. Lack of response or poor adherence to corticosteroids demands the development of new drug candidates for asthma. Endogenous nucleosides could be potential options since uridine has been reported to have an anti-inflammatory effect in asthma model. However, its molecular pathways and whether other nucleosides have similar therapeutic effects remain untouched. Thus, we herein report our investigation into the anti-inflammatory effects of guanosine and uridine, and the related inner signaling pathways in asthma model. Present study shows that administration of guanosine or uridine can reduce lung inflammation in OVA-challenged mice. Total cell counts in BALF, cytokines such as IL-4, IL-6, IL-13, OVA-specific IgE and mRNA level of Cxcl1, Cxlc3, IL-17 and Muc5ac were decreased in asthmatic mice after treatment. Besides, the production of IL-6 in LPS/IFN-γ induced THP-1 cells was also decreased by both nucleosides. In vivo and in vitro expressions of key molecules in the MAPK and NF-κB pathways were reduced after the treatment of both compounds. These findings suggest that guanosine has a similar potential therapeutic value in asthma as uridine and they exert anti-inflammatory effects through suppression of the MAPK and NF-κB pathways.
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http://dx.doi.org/10.1016/j.pupt.2021.102049DOI Listing
June 2021

Renal protective effects and mechanisms of the angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Life Sci 2021 Jun 5;280:119692. Epub 2021 Jun 5.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address:

Aims: This study investigated the renal protective effects and mechanisms of angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Materials And Methods: Mice were divided into abdominal aortic ligation alone, or treatment with LCZ696 or valsartan, whilst those undergoing sham surgery served as controls. Rat proximal renal tubular epithelial cells from the NRK-52E line were treated with control solution, LCZ696 or valsartan, in the presence or absence of Ang II for 24 h.

Key Findings: Compared to controls, abdominal aortic ligation significantly increased plasma NT-proBNP and urine neutrophil gelatinase-associated lipocalin (NGAL), which were associated with reduced renal length and velocity time integral on ultrasonography. Histology revealed wrinkling of the glomerular capillary wall and sclerosis of the glomerulus, dilatation of the Bowman's capsule, accompanied by diffuse renal tubular atrophy and fibrosis, accompanied by lower kidney index and higher percentage area of fibrosis. Increases in NGAL and decreased ANP protein and mRNA expression levels were observed. These abnormalities were significantly prevented by LCZ696 and to a lesser extent by valsartan. Cellular experiments demonstrated a central role of Ang II/transforming growth factor-β1/Smad2/3/connective tissue growth factor-dependent signaling leading to type IV collagen deposition. This upregulation was reversed by LCZ696 in a greater extent than valsartan treatment alone, accompanied by a significant improvement in NGAL.

Significance: LCZ696 can reduce kidney injury to a level beyond valsartan therapy alone in mice with cardiorenal syndrome, which can be speculated by effects on epithelial-mesenchymal transition and fibrosis through downregulating the TGF-β1/Smad2/3/CTGF/Collagen IV pathway.
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http://dx.doi.org/10.1016/j.lfs.2021.119692DOI Listing
June 2021

A bamboo leaf-specific aquaporin gene PePIP2;7 is involved in abiotic stress response.

Plant Cell Rep 2021 Jun 7. Epub 2021 Jun 7.

Key Laboratory of National Forestry and Grassland Administration/Beijing for Bamboo & Rattan Science and Technology, Institute of Gene Science and Industrialization for Bamboo and Rattan Resources, International Centre for Bamboo and Rattan, Beijing, 100102, China.

Key Message: PePIP2;7, a leaf-specific aquaporin gene in bamboo, is upregulated under abiotic stresses. Overexpressing PePIP2;7 confers abiotic stresses tolerance in transgenic Arabidopsis plant and yeast. Aquaporins (AQPs) participate in the regulation of water balance in plants. However, the function of AQPs in bamboo remains unclear. Here, PePIP2;7 was identified as a leaf-specific aquaporin gene in moso bamboo based on the expression analysis of transcriptome data and PCR. In situ hybridization further indicated that PePIP2;7 was mainly expressed in mesophyll cells of mature leaves, while in immature leaves it was dominant in blade edge cells followed by mesophyll cells. Interestingly, PePIP2;7 was strongly expressed in the mesophyll cells near bulliform cells of immature leaves, suggesting that PePIP2;7 might function in water transport and contribute to leaf unfolding. The transient expression assay showed that PePIP2;7 was a plasma membrane intrinsic protein. Furthermore, PePIP2;7 was upregulated under abiotic stresses such as high light, drought, and NaCl. Compared with Col-0, transgenic Arabidopsis plants overexpressing PePIP2;7 had better seed germination rate, longer taproot length, higher SOD activity, and lower MDA content under abiotic stresses. Besides, yeasts expressing PePIP2;7 also had higher tolerance to stress compared to the control. Taken together, our results show that PePIP2;7 is leaf-specific and involved in stress response, which provides new insights into aquaporin function in bamboo.
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http://dx.doi.org/10.1007/s00299-021-02673-wDOI Listing
June 2021

Nuclear translocation of the 4-pass transmembrane protein Tspan8.

Cell Res 2021 Jun 7. Epub 2021 Jun 7.

State Key Laboratory of Oncogenes and Related Genes, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1038/s41422-021-00522-9DOI Listing
June 2021

Indications for Lumbar Fusion in the Skeletally Mature Adolescent: How to Address Oblique Takeoff and Limb Length Discrepancy.

J Pediatr Orthop 2021 Jul;41(Suppl 1):S59-S63

Department of Orthopaedic Surgery, Emory University, Children's Healthcare of Atlanta, Atlanta, GA.

Background: Indications for posterior spinal fusion (PSF) with segmental spinal instrumentation (SSI) of a scoliotic deformity in a skeletally mature individual are based on the balance between the anticipated benefit of stopping future curve progression and the potential downside of loss of spinal mobility. The dilemma regarding PSF with SSI in the adolescent population is exacerbated by the patient's participation in athletics requiring flexibility and motion of the spine, the location of the curve, the presence of pelvic obliquity, and the impact of a limb length discrepancy. The purpose of this review is to discuss the potential advantages and disadvantages of PSF with SSI in a hypothetical skeletally mature adolescent with a 45-degree lumbar curve, pelvic obliquity, and limb length discrepancy.

Discussion: Natural history studies of untreated adolescent idiopathic scoliosis (AIS) have shown that slow curve progression throughout adulthood is likely. Adults with untreated AIS may also have more back pain and dissatisfaction with their appearance. Although the clinical and radiographic outcomes of PSF with SSI are excellent, patients should be counseled about the impact of fusing the lumbar spine on back pain, decreased spinal mobility, and potential inability to return to athletics at the same level. Adults who undergo surgery for AIS have greater operative morbidity and number of levels fused compared with adolescents.

Conclusion: These factors should be presented when discussing observation versus PSF with SSI with patients and families. Delaying surgery until formal athletic participation is complete should be considered.
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http://dx.doi.org/10.1097/BPO.0000000000001805DOI Listing
July 2021

CircRAB3B suppresses proliferation, motility, cell cycle progression and promotes the apoptosis of IL-22-induced keratinocytes depending on the regulation of miR-1228-3p/PTEN axis in psoriasis.

Autoimmunity 2021 Jun 7:1-10. Epub 2021 Jun 7.

Department of Dermatology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.

Introduction: Psoriasis is an immune-related chronic skin disease, and interleukin-22 (IL-22) is involved in psoriasis pathogenesis through promoting proliferation and migration abilities of keratinocytes. Here, we analysed the role of circular RNA (circRNA) RAB3B, member RAS oncogene family (circRAB3B) in regulating the phenotypes of IL-22-induced HaCaT cells.

Methods: RT-qPCR was implemented to assess RNA abundance. Western blot assay was adopted to assess protein abundance. Cell proliferation capacity was examined by cell counting kit-8 (CCK8) assay and 5-ethynyl-2'-deoxyuridine (Edu) assay. Cell motility was assessed by transwell assays and wound healing assay. Flow cytometric analysis was utilized to evaluate cell cycle progression and apoptosis. The intermolecular binding relations were tested via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. CircRAB3B expression was reduced in psoriatic cutaneous specimens and IL-22-treated HaCaT cells.

Results: CircRAB3B overexpression hampered the proliferation, motility, and cell cycle progression and elevated the apoptotic rate of IL-22-treated HaCaT cells, and circRAB3B silencing exhibited opposite effects in IL-22-induced HaCaT cells. CircRAB3B acted as microRNA-1228-3p (miR-1228-3p) sponge in HaCaT cells, and miR-1228-3p overexpression largely overturned circRAB3B overexpression-induced effects in HaCaT cells. MiR-1228-3p interacted with phosphatase and tensin homolog (PTEN), and circRAB3B sponged miR-1228-3p to induce PTEN level. MiR-1228-3p accumulation-mediated effects were partly alleviated by PTEN overexpression in HaCaT cells upon IL-22 treatment.

Conclusions: CircRAB3B suppressed psoriasis progression partly through down-regulating miR-1228-3p and up-regulating PTEN.
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http://dx.doi.org/10.1080/08916934.2021.1934825DOI Listing
June 2021