Publications by authors named "Dandan Zhao"

203 Publications

Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect.

Cardiovasc Res 2021 May 6. Epub 2021 May 6.

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou, 215000, China.

Aims: Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD.

Methods And Results: Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modeling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time.

Conclusions: In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.
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http://dx.doi.org/10.1093/cvr/cvab154DOI Listing
May 2021

A Security Scheme Based on Intranal-Adding Links for Integrated Industrial Cyber-Physical Systems.

Sensors (Basel) 2021 Apr 15;21(8). Epub 2021 Apr 15.

College of Mathematics and Computer Science, Zhejiang Normal University, Jinhua 321004, China.

With the advent of the Internet of Everything era, the Industrial Internet is increasingly showing mutual integration and development. Its core framework, the industrial CPS (Cyber-Physical Systems), has received more and more attention and in-depth research in recent years. These complex industrial CPS systems are usually composed of multiple interdependent sub-networks (such as physical networks and control networks, etc.). Minor faults or failure behaviors between sub-networks may cause serious cascading failure effects of the entire system. In this paper, we will propose a security scheme based on intranal-adding links in the face of the integrated and converged industrial CPS system environment. Firstly, by calculating the size of the largest connected component in the entire system, we can compare and analyze industrial CPS systems' security performance under random attacks. Secondly, we compare and analyze the risk of cascading failure between integrated industrial CPS systems under different intranal-adding link strategies. Finally, the simulation results verify the system security strategy's effectiveness under different strategies and show a relatively better exchange strategy to enhance the system's security. In addition, this paper's research work can help us design how to further optimize the interdependent industrial CPS system's topology to cope with the integrated and converged industrial CPS system environment.
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http://dx.doi.org/10.3390/s21082794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071418PMC
April 2021

A novel nonsense variant in MT-CO3 causes MELAS syndrome.

Neuromuscul Disord 2021 Mar 3. Epub 2021 Mar 3.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 West Wenhua Road Jinan, Jinan, Shandong 250012 China; Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong 266035 China; Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong 266035 China; Brain Science Research Institute, Shandong University, Jinan, Shandong 250000, China. Electronic address:

Both mitochondrial and nuclear gene mutations can cause cytochrome c oxidase (COX, complex Ⅳ) dysfunction, leading to mitochondrial diseases. Although numerous diseases caused by defects of the COX subunits or COX assembly factors have been documented, clinical cases directly related to mitochondrial cytochrome c oxidase subunit 3 gene (MT-CO3) mutations are relatively rare. Here, we report a 47-year-old female patient presented with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Muscle pathology revealed ragged-red fibres and remarkable COX-deficient muscle fibres. Muscle mitochondrial DNA sequencing analysis identified a novel MT-CO3 variant (m.9553G>A) that changed a highly conserved amino acid to a stop codon (p.Trp116*). This variant was heteroplasmic in multiple tissues, where the mutation load was 13% in oral epithelial cells, 89% in muscle samples, and not detectable in the peripheral blood lymphocytes. Single muscle fiber PCR analysis showed clear segregation of the mutation load with COX deficient fibres. Western blot analysis of the muscle samples revealed a significant decrease in the levels of COX1, COX2, COX3, COX4 and UQCRC2. COX respiration activity was remarkably reduced (58.84%) relative to the controls according to spectrophotometric assays. Taken together, our results indicated that this m.9553G>A variant may be responsible for the MELAS symdrome in the proband by affecting the stability and function of COX. The study expands the clinical and molecular spectrum of COX3-specific mitochondrial diseases.
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http://dx.doi.org/10.1016/j.nmd.2021.02.020DOI Listing
March 2021

Phase Tailoring of Ruddlesden-Popper Perovskite at Fixed Large Spacer Cation Ratio.

Small 2021 Apr 4:e2100560. Epub 2021 Apr 4.

Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Avenida da Universidade, Taipa, Macao, 999078, China.

Ruddlesden-Popper (RP) metal halide perovskites are considered as promising optoelectronic materials due to their good environmental stability and desirable optoelectronic properties. However, the phase composition and ordering in the deposited film, with a fixed ratio of large organic spacer cation in the precursor solution, are hard to be further tailored for specific optoelectronic applications. Herein, it is shown that even with a fixed spacer cation ratio, the phase composition and ordering can still be largely regulated by utilizing different crystallization kinetics of various cations with the inorganic octahedral lead halide. By using two different short cations to compete with the large spacer cation, the phase composition can be continuously tailored from thin multiple quantum wells (MQWs) dominated to 3D perovskite dominated. The phase ordering can be reversed from small n phases' prior to large n phases' prior near the substrate. Finally, with the same amount of large spacer cation protection, the perovskite can be tailored for both high-performance electroluminescence and photovoltaics with favorable energetic landscape for the corresponding desired first-order excitonic recombination and second-order free electron-hole recombination, respectively. This exploration substantially contributes to the understanding of precise phase engineering in RP perovskite and may provide a new insight into the design of multiple functional devices.
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http://dx.doi.org/10.1002/smll.202100560DOI Listing
April 2021

Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway.

Open Life Sci 2020 9;15(1):284-295. Epub 2020 Jun 9.

Department of Hematology, Ji'ning No. 1 People's Hospital, Ji'ning, Shandong, China.

Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway and , deepening our understanding of the TUG1 function in MM.
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http://dx.doi.org/10.1515/biol-2020-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874539PMC
June 2020

Catalpol Protects Against High Glucose-Induced Bone Loss by Regulating Osteoblast Function.

Front Pharmacol 2021 10;12:626621. Epub 2021 Mar 10.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

The overall objective of this study was to investigate the effects of catalpol on bone remodeling of diabetic osteoporosis by regulating osteoblast differentiation and migration. Using a murine model of diabetic osteoporosis, to detect the protective effects of catalpol on bone loss, architectural deterioration of trabecular bone and bone metabolism biomarkers were tested. A model of MC3T3-E1 cells was established by treatment with high glucose; the regulatory role of catalpol in the differentiation and migration was tested by Western blot, ALP staining, and Alizarin Red staining. Catalpol treatment markedly ameliorated trabecular bone deterioration by reducing degenerative changes of the trabecular structure by improving the bone formation marker levels of ALP, osteopontin, type I collagen, and osteocalcin, as well as the level of OPG/RANKL. Catalpol enhanced cell motility and scattering following gap formation of MC3T3-E1 cells. The results indicated that catalpol exhibits a protective effect against diabetic osteoporosis by regulating the differentiation and migration of osteoblast.
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http://dx.doi.org/10.3389/fphar.2021.626621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987667PMC
March 2021

Strategies to improve the adsorption properties of graphene-based adsorbent towards heavy metal ions and their compound pollutants: A review.

J Hazard Mater 2021 Mar 19;415:125690. Epub 2021 Mar 19.

School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.

Heavy metal-containing wastewater can be treated by adsorption technology to obtain ultra-low concentration or high-quality treated effluent. Due to the constraints of the specific surface area, surface electrical structure and spatial effect of conventional adsorbents, it is often difficult to obtain adsorbents within high adsorption capacity. Graphene has characteristics of large specific surface area, small particle size, and high adsorption efficiency. It is considered as one of the research hotspots in recent years. However, despite graphene's unique properties, graphene-based adsorbents still have some drawbacks, i.e. graphene nanosheets are easier to be stacked with each other via π-π stacking and van der Waals interactions, which affect the site exposure, impede the rapid mass transport and limit its adsorption performance. Special strategy is needed to overcome its drawbacks. This work summarizes recent literatures on utilization of three strategies-surface functionalization regulation, morphology and structure control and material composite, to improve the adsorption properties of graphene-based adsorbent towards heavy metal removal. A brief summary, perspective on strategies to improving adsorption properties of graphene-based materials for heavy metal adsorption are also presented. Certainly, this review will be useful for designing and manufacturing of graphene-based nanomaterials for water treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125690DOI Listing
March 2021

Quantifying economic-social-environmental trade-offs and synergies of water-supply constraints: An application to the capital region of China.

Water Res 2021 May 27;195:116986. Epub 2021 Feb 27.

Water & Development Research Group, Department of Built Environment, Aalto University, PO Box 15200, 00076 Espoo, Finland.

Sustainable water management is one of the sustainable development goals (SDGs) and is characterized by a high level of interdependencies with other SDGs from regional to global scales. Many water assessment studies are restricted to silo thinking, mostly focusing on water-related consequences, while lacking a quantification of trade-offs and synergies of economic, social, and environmental dimensions. To fill this knowledge gap, we propose a "nexus" approach that integrates a water supply constrained multi-regional input-output (mixed MRIO) model, scenario analysis, and multi-criteria decision analysis (MCDA) to quantify the trade-offs and synergies at the sectoral level for the capital region of China, i.e. the Beijing-Tianjin-Hebei urban agglomeration. A total of 120 industrial transition scenarios including nine major industries with high water-intensities and water consumption under current development pathways were developed to facilitate the trade-off and synergy analysis between economic loss, social goals (here, the number of jobs) and environmental protection (with grey water footprint representing water pollution) triggered by water conservation measures. Our simulation results show that an imposition of a tolerable water constraint (a necessary water consumption reduction for regional water stress level to move from severe to moderate) in the region would result in an average economic loss of 68.4 (± 16.0) billion Yuan (1 yuan ≈ 0.158 USD$ in 2012), or 1.3 % of regional GDP, a loss of 1.94 (± 0.18) million jobs (i.e. 3.5 % of the work force) and a reduction of 1.27 (± 0.40) billion m or about 2.2% of the regional grey water footprint. A tolerable water rationing in water-intensive sectors such as Agriculture, Food and tobacco processing, Electricity and heating power production and Chemicals would result in the lowest economic and job losses and the largest environmental benefits. Based on MCDA, we selected the 10 best scenarios with regard to their economic, social and environmental performances as references for guiding future water management and suggested industrial transition policies. This integrated approach could be a powerful policy support tool for 1) assessing trade-offs and synergies among multiple criteria and across multiple region-sectors under resource constraints; 2) quantifying the short-term supply-chain effects of different containment measures, and 3) facilitating more insightful evaluation of SDGs at the regional level so as to determine priorities for local governments and practitioners to achieve SDGs.
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http://dx.doi.org/10.1016/j.watres.2021.116986DOI Listing
May 2021

Erratum: LncRNA PFL contributes to cardiac fibrosis by acting as a competing endogenous RNA of let-7d: Erratum.

Theranostics 2021 9;11(8):3961-3962. Epub 2021 Feb 9.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.

[This corrects the article DOI: 10.7150/thno.20846.].
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http://dx.doi.org/10.7150/thno.58328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914346PMC
February 2021

Mechanochemical control of epidermal stem cell divisions by B-plexins.

Nat Commun 2021 02 26;12(1):1308. Epub 2021 Feb 26.

Institute of Pharmacology, University of Marburg, Marburg, Germany.

The precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. However, the molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of the transcriptional coactivator YAP, hyperproliferation, and tissue overgrowth. Mechanistically, we show that B-plexins mediate mechanoresponses to crowding through stabilization of adhesive cell junctions and lowering of cortical stiffness. Finally, we provide evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our data define a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease.
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http://dx.doi.org/10.1038/s41467-021-21513-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910479PMC
February 2021

Ginsenoside Rb1, salvianolic acid B and their combination modulate gut microbiota and improve glucolipid metabolism in high-fat diet induced obese mice.

PeerJ 2021 3;9:e10598. Epub 2021 Feb 3.

College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Background: To observe the effect of ginsenoside Rb1, salvianolic acid B and their combination on glucolipid metabolism and structural changes of gut microbiota.

Methods: Eight-week-old C57BL/6J mice were fed 45% high-fat diet to induce obesity. The obese mice were randomly divided into four groups, Con group as model control, ginsenoside Rb1 (Rb1) group, salvianolic acid B (SalB) group and ginsenoside Rb1+ salvianolic acid B (Rb1SalB) group. Mice in Rb1, SalB and Rb1SalB group were treated by gavage with ginsenoside Rb1, salvianolic acid B and the combination of the two ingredients, respectively. While mice in Con group were given the same amount of sterile water. The intervention lasted 8 weeks. Body weight and fasting blood glucose were measured every 2 weeks. Oral glucose tolerance test was conducted on the 4th and 8th week of drug intervention. At the end of the experiment, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol and non-esterified fatty acid content as well as glycated hemoglobin were measured and feces were collected for 16S rDNA sequencing.

Results: Both ginsenoside Rb1 and Rb1SalB combination decreased body weight significantly ( < 0.05). Ginsenoside Rb1, salvianolic acid B and their combination alleviated fasting blood glucose, glycated hemoglobin and blood lipid profiles effectively ( < 0.05, compared with the corresponding indicators in Con group). Oral glucose tolerance test results at the 8th week showed that glucose tolerance was significantly improved in all three treatment groups. Ginsenoside Rb1, salvianolic acid B and their combination reduced the overall diversity of gut microbiota in feces and changed the microbial composition of the obese mice. LDA effect size (LefSe) analysis revealed the key indicator taxa corresponding to the treatment.

Conclusion: Ginsenoside Rb1, salvianolic acid B and their combination could lower blood glucose and lipid level, and improve glucose tolerance of obese mice. The above effect may be at least partially through modulation of gut microbial composition.
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http://dx.doi.org/10.7717/peerj.10598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866888PMC
February 2021

Cytoplasmic DROSHA and non-canonical mechanisms of MiR-155 biogenesis in FLT3-ITD acute myeloid leukemia.

Leukemia 2021 Feb 15. Epub 2021 Feb 15.

Gehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, CA, USA.

We report here on a novel pro-leukemogenic role of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) that interferes with microRNAs (miRNAs) biogenesis in acute myeloid leukemia (AML) blasts. We showed that FLT3-ITD interferes with the canonical biogenesis of intron-hosted miRNAs such as miR-126, by phosphorylating SPRED1 protein and inhibiting the "gatekeeper" Exportin 5 (XPO5)/RAN-GTP complex that regulates the nucleus-to-cytoplasm transport of pre-miRNAs for completion of maturation into mature miRNAs. Of note, despite the blockage of "canonical" miRNA biogenesis, miR-155 remains upregulated in FLT3-ITD+ AML blasts, suggesting activation of alternative mechanisms of miRNA biogenesis that circumvent the XPO5/RAN-GTP blockage. MiR-155, a BIC-155 long noncoding (lnc) RNA-hosted oncogenic miRNA, has previously been implicated in FLT3-ITD+ AML blast hyperproliferation. We showed that FLT3-ITD upregulates miR-155 by inhibiting DDX3X, a protein implicated in the splicing of lncRNAs, via p-AKT. Inhibition of DDX3X increases unspliced BIC-155 that is then shuttled by NXF1 from the nucleus to the cytoplasm, where it is processed into mature miR-155 by cytoplasmic DROSHA, thereby bypassing the XPO5/RAN-GTP blockage via "non-canonical" mechanisms of miRNA biogenesis.
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http://dx.doi.org/10.1038/s41375-021-01166-9DOI Listing
February 2021

Effects of coarse and fine bubble aeration on performances of membrane filtration and denitrification in moving bed membrane bioreactors.

Sci Total Environ 2021 Jun 2;772:145513. Epub 2021 Feb 2.

School of Environmental and Municipal Engineering, Qingdao University of Technology, 11 Fushun Road, Qingdao 266033, PR China. Electronic address:

In this study, two lab-scale Moving Bed Membrane Bioreactors (MBMBR) were setup and operated in parallel to study the effect of coarse and fine bubble aeration on the performances of membrane filtration and denitrification treating domestic wastewater. The bacterial populations in the two MBMBRs were further analyzed to investigate the mechanisms involved in the different denitrification performances. The results showed that coarse bubble aeration could effectively mitigate membrane fouling by decreasing the formation of cake layer, although smaller sizes of bio-flocs were induced. In addition, coarse bubble aeration could also maintain dissolved oxygen (DO) at a relatively lower level without compromising the moving of bio-carriers, which achieved 10% higher total nitrogen removal rate due to anoxic zone created at inner layers of biofilms on bio-carriers. Accumulation of denitrifier (Thiobacillus denitrificans) on the bio-carriers was found under the coarse bubble aeration system, which can explain its superior denitrification performance.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145513DOI Listing
June 2021

BaZiBuShen alleviates altered testicular morphology and spermatogenesis and modulates Sirt6/P53 and Sirt6/NF-κB pathways in aging mice induced by D-galactose and NaNO.

J Ethnopharmacol 2021 May 26;271:113810. Epub 2021 Jan 26.

Department of Chinese Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China. Electronic address:

Ethnopharmacological Relevance: Sperm infertility and testicular atrophy are symptoms associated with aging. BaZiBuShen formula (BZBS), a patented Chinese herbal prescription composed of Semen Cuscutae, Fructus Lycii, Epimedii Folium, Fructus Schisandrae Sphenantherae, Fructus Cnidii, Fructus Rosae Laevigatae, Semen Allii Tuberosi., Radix Morindae Officinalis, Herba Cistanches, Fructus Rubi, Radix Rehmanniae Recens, Radix Cyathulae, Radix Ginseng, Cervi Cornu Pantotrichum, Hippocampus, and Fuctus Toosendan, has been used as a kidney-tonifying and anti-aging drug as well as for the treatment of impotence and male infertility in traditional Chinese medicine.

Aim Of The Study: We aimed at investigating whether BZBS preserves sperm and testes morphology in aging mice, and to explore the underlying mechanisms.

Materials And Methods: BZBS was orally administered to aging mice induced by D-galactose (D-gal) and NaNO for 65 days. Sperm quality and testes pathophysiological alterations were examined by a Semen Analysis System, hematoxylin-eosin staining, transmission electron microscopy, and mitochondrial complex IV activity. In addition, serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OH-dG), reduced glutathione (GSH), oxidized glutathione disulfide (GSSG), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expressions of P450 aromatase (CYP19), sirtuin 6 (Sirt6), P53, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB)-p65, and phospho-NF-κB-p65 (NF-κB-pp65) in the testes were examined by western blot and/or immunohistochemical staining.

Results: Sustained exposure to D-gal/NaNO caused a deterioration of sperm quality and testes morphology in this rapid aging mouse model. BZBS treatment curtailed these alterations. These beneficial effects were associated with increased serum levels of TAC, GSH/GSSG, T, E, and FSH, and decreased levels of MDA, TNF-α, and 8-OH-dG. BZBS treatment also downregulated the expressions of P53, iNOS, and NF-κB-pp65, as well as upregulated the expressions of Sirt6 and CYP19 in aging testes.

Conclusions: BZBS preserves testicular morphology and spermatogenesis possibly via inhibition of oxidative stress and the modulation of the Sirt6/P53 and Sirt6/NF-κB signaling pathways. The results shed light on the beneficial effect of BZBS on sperm quality and fertility in aging males.
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http://dx.doi.org/10.1016/j.jep.2021.113810DOI Listing
May 2021

The inhibitive effects of proteasome inhibitor MG-132 on pterygium fibroblasts in vitro and the potential key regulators involved.

Life Sci 2021 Apr 20;270:119088. Epub 2021 Jan 20.

Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:

This study aimed to determine whether MG-132 as a proteasome inhibitor can effectively hinder pterygium progression, and to screen out potential regulators involved in MG-132 mediated process. Human pterygium fibroblasts (HPFs) were derived from pterygium tissues from 5 patients. Cell proliferation was examined by MTT, cell cycle and apoptosis were detected by flow cytometry. The overgrowth pterygium tissues were characterized by H&E staining and IHC compared with normal tissues. Differential mRNA expression with MG-132 treatment was determined by RNA sequencing and analyzed by GO and KEGG pathways. The expression levels of Nrf2, MCPIP1, CDKN1B and XBP1, four genes closely associated with pterygium, were detected by RT-qPCR and western blotting. MG-132 dose-dependently inhibited the growth of HPFs, induced G2/M phase arrest of cell cycle at a certain dose, and also caused cell apoptosis, with the levels of cleaved caspase3, cleaved PARP, Bax and p21 increased. Ki-67 and Bcl-2 were highly expressed while Bax was decreased in pterygium tissues. Total 7199 differentially expressed genes (DEGs) were identified, including HSPA family most significantly increased, and AL590428.1, AL122125.1 and lincRNAs such as FGF14-AS2 decreased. The up-regulated DEGs were mainly enriched in RNA degradation pathway, while down-regulated DEGs were related to the regulation of cell cycle. The expressions of Nrf2 and MCPIP1 were significantly increased, while XBP1 and CDKN1B were decreased. In conclusion, MG-132 inhibited the proliferation and induced apoptosis of HPFs in vitro with 7199 DEGs participated in, which may provide a useful reference for the exploitation of MG-132 in treating pterygium.
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http://dx.doi.org/10.1016/j.lfs.2021.119088DOI Listing
April 2021

MicroRNA-520c-3p suppresses vascular endothelium dysfunction by targeting RELA and regulating the AKT and NF-κB signaling pathways.

J Physiol Biochem 2021 Feb 7;77(1):47-61. Epub 2021 Jan 7.

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

Endothelial injury, which can cause endothelial inflammation and dysfunction, is an important mechanism for the development of atherosclerotic plaque. This study aims to investigate the functional role of miR-520c-3p in vascular endothelium during inflammatory diseases such as atherosclerosis. Quantitative real-time PCR was used to detect miR-520c-3p expression in in human umbilical vein endothelial cells (HUVECs) after treatment with platelet-derived growth factor (PDGF). Furthermore, the effects of miR-520c-3p overexpression and silencing on cell proliferation, adhesion, and apoptosis were assessed. Bioinformatics analysis and Biotin-labeled miRNA pull-down assay were used to confirm the targets of miR-520-3p. Then, the effects of miR-520c-3p on AKT and NF-κB signaling pathways were detected by western blot. Herein, we observed that the expression level of miR-520c-3p was downregulated in HUVECs under PDGF stimulation. Overexpression of miR-520c-3p not only decreased cell adhesion but also promoted proliferation and inhibited apoptosis to protect the viability of endothelial cells. It was confirmed that RELA is the target of miR-520c-3p. MiR-520c-3p inhibited the protein phosphorylation of AKT and RELA, and si-RELA reversed the promotion of AKT and RELA protein phosphorylation by anti-miR-520c-3p. In summary, our study suggested that miRNA-520c-3p targeting RELA through AKT and NF-κB signaling pathways regulated the proliferation, apoptosis, and adhesion of vascular endothelial cells. We conclude that miR-520c-3p may play an important role in the suppression of endothelial injury, which could serve as a biomarker and therapeutic target for atherosclerosis.
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http://dx.doi.org/10.1007/s13105-020-00779-5DOI Listing
February 2021

Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor.

J Immunother Cancer 2021 Jan;9(1)

Oncology Discovery, Bristol-Myers Squibb Co, Princeton, New Jersey, USA

Background: Hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) has been demonstrated as a negative intracellular immune checkpoint in mediating antitumor immunity in studies with HPK1 knockout and kinase dead mice. Pharmacological inhibition of HPK1 is desirable to investigate the role of HPK1 in human immune cells with therapeutic implications. However, a significant challenge remains to identify a small molecule inhibitor of HPK1 with sufficient potency, selectivity, and other drug-like properties suitable for proof-of-concept studies. In this report, we identified a novel, potent, and selective HPK1 small molecule kinase inhibitor, compound K (CompK). A series of studies were conducted to investigate the mechanism of action of CompK, aiming to understand its potential application in cancer immunotherapy.

Methods: Human primary T cells and dendritic cells (DCs) were investigated with CompK treatment under conditions relevant to tumor microenvironment (TME). Syngeneic tumor models were used to assess the in vivo pharmacology of CompK followed by human tumor interrogation ex vivo.

Results: CompK treatment demonstrated markedly enhanced human T-cell immune responses under immunosuppressive conditions relevant to the TME and an increased avidity of the T-cell receptor (TCR) to recognize viral and tumor-associated antigens (TAAs) in significant synergy with anti-PD1. Animal model studies, including 1956 sarcoma and MC38 syngeneic models, revealed improved immune responses and superb antitumor efficacy in combination of CompK with anti-PD-1. An elevated immune response induced by CompK was observed with fresh tumor samples from multiple patients with colorectal carcinoma, suggesting a mechanistic translation from mouse model to human disease.

Conclusion: CompK treatment significantly improved human T-cell functions, with enhanced TCR avidity to recognize TAAs and tumor cytolytic activity by CD8+ T cells. Additional benefits include DC maturation and priming facilitation in tumor draining lymph node. CompK represents a novel pharmacological agent to address cancer treatment resistance.
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http://dx.doi.org/10.1136/jitc-2020-001402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789447PMC
January 2021

Phospholipase D- and phosphatidic acid-mediated phospholipid metabolism and signaling modulate symbiotic interaction and nodulation in soybean (Glycine max).

Plant J 2021 Apr 27;106(1):142-158. Epub 2021 Feb 27.

State Key Laboratory of Tea Plant Biology and Utilization, College of Tea and Food Science and Technology, Anhui Agricultural University, Hefei, 230036, China.

Symbiotic rhizobium-legume interactions, such as root hair curling, rhizobial invasion, infection thread expansion, cell division and proliferation of nitrogen-fixing bacteroids, and nodule formation, involve extensive membrane synthesis, lipid remodeling and cytoskeleton dynamics. However, little is known about these membrane-cytoskeleton interfaces and related genes. Here, we report the roles of a major root phospholipase D (PLD), PLDα1, and its enzymatic product, phosphatidic acid (PA), in rhizobium-root interaction and nodulation. PLDα1 was activated and the PA content transiently increased in roots after rhizobial infection. Levels of PLDα1 transcript and PA, as well as actin and tubulin cytoskeleton-related gene expression, changed markedly during root-rhizobium interactions and nodule development. Pre-treatment of the roots of soybean seedlings with n-butanol suppressed the generation of PLD-derived PA, the expression of early nodulation genes and nodule numbers. Overexpression or knockdown of GmPLDα1 resulted in changes in PA levels, glycerolipid profiles, nodule numbers, actin cytoskeleton dynamics, early nodulation gene expression and hormone levels upon rhizobial infection compared with GUS roots. The transcript levels of cytoskeleton-related genes, such as GmACTIN, GmTUBULIN, actin capping protein 1 (GmCP1) and microtubule-associating protein (GmMAP1), were modified in GmPLDα1-altered hairy roots compared with those of GUS roots. Phosphatidic acid physically bound to GmCP1 and GmMAP1, which could be related to cytoskeletal changes in rhizobium-infected GmPLDα1 mutant roots. These data suggest that PLDα1 and PA play important roles in soybean-rhizobium interaction and nodulation. The possible underlying mechanisms, including PLDα1- and PA-mediated lipid signaling, membrane remodeling, cytoskeleton dynamics and related hormone signaling, are discussed herein.
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http://dx.doi.org/10.1111/tpj.15152DOI Listing
April 2021

Cerebrotendinous xanthomatosis with peripheral neuropathy: a clinical and neurophysiological study in Chinese population.

Ann Transl Med 2020 Nov;8(21):1372

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.

Background: Cerebrotendinous xanthomatosis (CTX) is an inborn disorder of bile acid metabolism caused by deficiency of sterol 27-hydroxylase () gene. CTX-related peripheral neuropathy has rarely been discussed in Chinese population. Here, we reported 6 CTX cases and performed a literature review focused on CTX with neuropathy to summarize its clinical and neurophysiological features.

Methods: All clinical data of 6 CTX cases were collected, and 21 reported Chinese CTX patients (including this study) were reviewed and summarized.

Results: Clinical manifestations of 6 CTX cases showed great heterogeneity. Cognitive decline, spastic paraplegia, cerebellar ataxia and advanced bulbar palsy were common neurological disorders, often accompanied by non-neurological signs like xanthomas, cataract, diarrhea and pes cavus. Dentate nuclei hyperintensity with or without hyposignal is a valuable MRI hallmark. Pooling our patients and literature review together, peripheral neuropathy was predominant sensorimotor demyelinating type in Chinese population, with an evident length dependent pattern and increased vulnerability in motor nerves. Demyelinating and axonal degeneration tend to exist in severe neuropathy. Three novel mutations including c.1055C>A; c.432T>G; c.472T>G were identified in CYP27A1 and predicted to be pathogenic. Oral CDCA therapy could ameliorate some of the existing symptoms and provide clinical stability, but it could not cease disease progression completely.

Conclusions: Our study broadens the phenotype and mutation spectrum of CTX. Patients with cognitive decline, spastic tetraparesis, cerebellar ataxia and bulbar palsy, should be highly suspicious of CTX even no xanthomas disclosed. Peripheral neuropathy was predominant sensorimotor demyelinating type in Chinese population, with mixed axonal and demyelinating type in severe cases. Three novel likely pathogenic mutations including c.1055C>A; c.432T>G; c.472T>G were identified in CYP27A1.
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http://dx.doi.org/10.21037/atm-20-2746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723652PMC
November 2020

Effects of rotavirus NSP4 protein on the immune response and protection of the S-VP8* nanoparticle rotavirus vaccine.

Vaccine 2021 01 11;39(2):263-271. Epub 2020 Dec 11.

Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Rotavirus causes severe diarrhea and dehydration in young children. Even with the implementation of the current live vaccines, rotavirus infections still cause significant mortality and morbidity, indicating a need for new rotavirus vaccines with improved efficacy. To this end, we have developed an S-VP8*/S-VP8* nanoparticle rotavirus vaccine candidate that will be delivered parenterally with Alum adjuvant. In this study, as parts of our further development of this nanoparticle vaccine, we evaluated 1) roles of rotavirus nonstructural protein 4 (NSP4) that is the rotavirus enterotoxin, a possible vaccine target, and an immune stimulator, and 2) effects of CpG adjuvant that is a toll-like receptor 9 (TLR9) ligand and agonist on the immune response and protection of our S-VP8*/S-VP8* nanoparticle vaccine. The resulted vaccine candidates were examined for their IgG responses in mice. In addition, the resulted mouse sera were assessed for i) blocking titers against interactions of rotavirus VP8* proteins with their glycan ligands, ii) neutralization titers against rotavirus replication in cell culture, and iii) passive protection against rotavirus challenge with diarrhea in suckling mice. Our data showed that the Alum adjuvant appeared to work better with the S-VP8*/S-VP8* nanoparticles than the CpG adjuvant, while an addition of the NSP4 antigen to the S-VP8*/S-VP8* vaccine may not help to further increase the immune response and protection of the resulted vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822095PMC
January 2021

The efficacy and safety of Yuxingcao eye drops in the treatment of COVID-19 conjunctivitis: A protocol for a systematic review.

Medicine (Baltimore) 2020 Dec;99(49):e23093

School of Eye.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is no specific cure for this disease, and the clinical management mainly depends on supportive treatment. This disease may affect SARS-CoV-2 conjunctivitis. Yuxingcao eye drops is used in treating COVID-19 conjunctivitis in China.

Methods: A comprehensive literature search will be conducted. Two methodological trained researchers will read the title, abstract, and full texts and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analyses for outcomes related to COVID-19 conjunctivitis. The heterogeneity of data will be investigated by Cochrane X and I tests. Then publication bias assessment will be conducted by funnel plot analysis and Egger test.

Results: The results of our research will be published in a peer-reviewed journal.

Conclusion: Our study aims to systematically present the clinical evidence of Yuxingcao eye drops in treating COVID-19 conjunctivitis, which will be of significant meaning for further research and clinical practice.

Prospero Registration Number: PROSPERO CRD42020209059.
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http://dx.doi.org/10.1097/MD.0000000000023093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717853PMC
December 2020

A mitochondrial myopathy-associated tRNA 7453G>A mutation alters tRNA metabolism and mitochondrial function.

Mitochondrion 2021 03 3;57:1-8. Epub 2020 Dec 3.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong 266035 China; Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Background: Mitochondrial disorders are a group of heterogeneous diseases characterized by biochemical disturbances in oxidative phosphorylation (OXPHOS). Mutations in mitochondrial transfer RNA (mt-tRNA) genes are the most frequently in mitochondrial disease. However, few studies have detailed the molecular mechanisms behind these mutations.

Methods: We performed clinical evaluation, genetic analysis, muscle histochemistry, and molecular and biochemical investigations in muscle tissue and proband-derived cybrid cell lines.

Results: We found a mitochondrial tRNA mutation (m.7453G>A) in a 15-year-old patient with severe mitochondrial myopathy. We demonstrated that this mutation caused impairment of mitochondrial translation, respiratory deficiency, overproduction of reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP), which ultimately led to severe mitochondrial myopathy.

Conclusion: Our findings offer valuable new insights into the tRNA m.7453G>A mutation for both the pathogenic mechanism and functional consequences.
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http://dx.doi.org/10.1016/j.mito.2020.11.015DOI Listing
March 2021

Genome-wide analysis and metabolic profiling unveil the role of peroxidase CsGPX3 in theaflavin production in black tea processing.

Food Res Int 2020 11 17;137:109677. Epub 2020 Sep 17.

State Key Laboratory of Tea Plant Biology and Utilization, College of Tea and Food Science and Technology, Anhui Agricultural University, Hefei 230036, China. Electronic address:

Plucked tea leaves can be processed into black tea (Camellia sinensis), which is rich in health-promoting molecules, including flavonoid antioxidants. During black tea processing, theaflavins (TFs) and thearubigins (TRs) are generated via the successive oxidation of catechins by endogenous polyphenol oxidase (PPO)- or peroxidase (POD)-mediated reactions. This process must be well controlled to achieve the proper TF/TR ratio, which is an important quality parameter of the tea beverage. However, little is known about the POD/PPO catalyzed TF formation process at the molecular genetic level. Here, we identified and characterized the POD genes responsible for TF production in tea. Genome-wide analysis of POD/PPO family genes, metabolite profiling, and expression analysis of PPO/POD genes in tea leaves enabled us to select several PPO/POD genes potentially involved in TF production. Differential gene expression in plant tissues and enzyme activity in several tea varieties traditionally used for processing of various beverage types indicate that black tea processing primarily depends on PPO/POD activity. Among these POD/PPO genes, the POD CsGPX3 is involved in the generation of TFs during black tea processing. The capacity of PPO/POD-catalysed TF production is potentially used for controlling catechin oxidation during black tea processing and could be used to create molecular markers for breeding of tea plant varieties suitable for the production of high-quality black tea beverages.
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http://dx.doi.org/10.1016/j.foodres.2020.109677DOI Listing
November 2020

Security Evaluation under Different Exchange Strategies Based on Heterogeneous CPS Model in Interdependent Sensor Networks.

Sensors (Basel) 2020 Oct 28;20(21). Epub 2020 Oct 28.

College of Mathematics and Computer Science, Zhejiang Normal University, Jinhua 321004, China.

In the real Internet of Everything scenario, many large-scale information systems can be converted into interdependent sensor networks, such as smart grids, smart medical systems, and industrial Internet systems. These complex systems usually have multiple interdependent sensor networks. Small faults or failure behaviors between networks may cause serious cascading failure effects of the entire system. Therefore, in this paper, we will focus on the security of interdependent sensor networks. Firstly, by calculating the size of the largest functional component in the entire network, the impact of random attacks on the security of interdependent sensor networks is analyzed. Secondly, it compares and analyzes the impact of cascading failures between interdependent sensor networks under different switching edge strategies. Finally, the simulation results verify the effect of the security of the system under different strategies, and give a better exchange strategy to enhance the security of the system. In addition, the research work in this article can help design how to further optimize the topology of interdependent sensor networks by reducing the impact of cascading failures.
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http://dx.doi.org/10.3390/s20216123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662949PMC
October 2020

Salvianolic acid B prevents body weight gain and regulates gut microbiota and LPS/TLR4 signaling pathway in high-fat diet-induced obese mice.

Food Funct 2020 Oct;11(10):8743-8756

The Scientific Research Centre, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.

Salvianolic acid B (Sal B) exhibits anti-obesity activity, yet the underlying mechanism linking this effect to metabolic endotoxemia remains unexplored. For this purpose, high-fat diet-induced obese mice were orally administered with Sal B for 10 weeks. Hematoxylin/eosin staining, transmission electron microscopy, and immunohistochemical staining were used to evaluate histopathological alterations in the white adipose tissue (WAT) and/or jejunums. The expression levels of genes related to fat and cholesterol synthesis in the WAT were determined by qPCR. The composition of fecal microbiota was profiled by 16S rRNA gene pyrosequencing. Western blotting was employed to evaluate the relative protein expressions involved in lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway in the WAT. Treatment of obese mice with Sal B improves insulin sensitivity, attenuates body weight gain and alleviates serum levels of LPS and tumor necrosis factor alpha, which is associated with an improvement in intestinal epithelial integrity and probiotic composition as well as a reduction in Gram-negative Proteobacteria and Deferribacteres. In addition, Sal B downregulates the expressions of TLR4 and myeloid differential factor-88, as well as the phosphorylation levels of Jun N-terminal kinase, nuclear factor-kappa B p65, and an insulin receptor substrate in the WAT. In summary, Sal B may attenuate body weight gain and insulin resistance through the regulation of gut microbiota abundances and LPS/TLR4 signaling pathway in obese mice, suggesting Sal B could be a promising drug candidate for protection against obesity.
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http://dx.doi.org/10.1039/d0fo01116aDOI Listing
October 2020

Retinoic acid promotes metabolic maturation of human Embryonic Stem Cell-derived Cardiomyocytes.

Theranostics 2020 1;10(21):9686-9701. Epub 2020 Aug 1.

Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Suzhou 215000, China.

Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development. However, the effects of RA on cardiomyocyte differentiation efficiency and maturation are still unknown. RA was added at different time intervals to identify the best treatment windows for cardiomyocyte differentiation and maturation. The efficiency of cardiomyocyte differentiation was detected by quantitative real-time PCR and flow cytometry. Cardiomyocytes maturation was detected by immunofluorescence staining, metabolic assays and patch clamp to verify structural, metabolic and electrophysiological maturation, respectively. RNA sequencing was used for splicing analysis. We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of , and on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number. RNA sequencing revealed RA promoted RNA isoform switch to the maturation-related form. Meanwhile, RA promoted electrophysiological maturation and calcium handling of hESC-CMs. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. Our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.
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http://dx.doi.org/10.7150/thno.44146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449904PMC
August 2020

Electrospun nanofibrous membrane of fish collagen/polycaprolactone for cartilage regeneration.

Am J Transl Res 2020 15;12(7):3754-3766. Epub 2020 Jul 15.

Department of Breast Surgery, Hainan General Hospital, Hainan Medical University Hainan, P. R. China.

Tissue engineering technology provides a promising approach for cartilage repair, and in this strategy, scaffolds play a pivotal role in directing cartilage regeneration. Fish collagen (FC) is currently considered an alternative source of mammalian collagen (MC) for tissue engineering due to its excellent biocompatibility, suitable biodegradability, inert immunogenicity, rich sources, low price and lack of risk for the transmission of zoonosis. Here, we fabricated three types of electrospun nanofibrous membranes composed of FC and polycaprolactone (PCL) with three different FC/PCL ratios (9/1, 7/3, 5/5) and investigated the feasibility of using the membranes with chondrocytes in cartilage regeneration. Our results demonstrated that increases in the FC content were associated with improvements in biodegradability, absorption, and cell adhesion capacity, but weaker mechanical properties. In addition, all three nanofibrous membranes showed satisfactory biocompatibility as evidenced by supporting chondrocyte proliferation and cartilage formation . Furthermore, all three membranes seeded with chondrocytes formed mature cartilage-like tissue after 8 weeks of culture, but satisfactory homogeneous cartilage regeneration was only achieved with the F9P1 group. The current results demonstrated that the electrospun FC/PCL membrane is a promising scaffold for cartilage regeneration and that the F9P1 group might represent a relatively suitable ratio. The research models established in the current study provide detailed information for the regeneration of cartilage and other tissue based on electrospun FC/PCL membranes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407687PMC
July 2020

Distal myopathy due to TCAP variants in four unrelated Chinese patients.

Neurogenetics 2021 03 6;22(1):1-10. Epub 2020 Aug 6.

Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, China.

Distal myopathies are a group of clinically and genetically heterogeneous hereditary muscle disorders characterized by progressive muscular weakness starting in the distal parts of the limbs. The most common subtype of distal myopathy is GNE myopathy, a rare muscle disease with autosomal recessive inheritance. Limb-girdle muscular dystrophy 2G (LGMD2G) is a rare autosomal recessive subtype of LGMDs caused by TCAP variant. Patients with LGMD2G can present with distal myopathy and rimmed vacuoles on muscle pathology. Thus far, the most reported TCAP mutations related to LGMD2G were recessive frameshift or nonsense variants. Here, we described four Chinese patients from unrelated families with LGMD2G due to TCAP mutations. The clinical symptoms of our patients were similar to those previously reported in LGMD2G patients. Three different pathogenic TCAP variants were identified in these patients, including two frameshift variants and one intronic variant. Autophagolysosomes have been observed in one patient by electron microscopy. Our research expands the genetic spectrum of TCAP mutations in China, indicating c.165-166insG is likely the common pathogenic variant. We also provide evidences that autophagy may be involved in the pathophysiology of LGMD2G.
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http://dx.doi.org/10.1007/s10048-020-00623-4DOI Listing
March 2021

Calcium-Loaded Municipal Sludge-Biochar as an Efficient and Stable Catalyst for Biodiesel Production from Vegetable Oil.

ACS Omega 2020 Jul 6;5(28):17471-17478. Epub 2020 Jul 6.

School of Mechanical and Power Engineering, Nanjing Technology University, Nanjing 211816, China.

In this contribution, biochar from municipal sludge was used as a novel matrix for the synthesis of a series of calcium-based heterogeneous catalysts toward biodiesel production. Their catalytic activity was investigated in terms of catalyst loading and calcination temperature during preparation, in addition to the transesterification parameters including the methanol/oil molar ratio, reaction time, and catalyst amount. The highest biodiesel yield up to 93.77% was achieved with the 30Ca/A-SBC-700, and it maintained as high as 84.9% even after 10 cycles of a consecutively alternating catalysis and regeneration process. It was revealed that the porous municipal sludge biochar and autologous SiO were accountable for the superior stability of the present catalyst. This work may provide a new path to value-added valorization of sludge waste and also a renewable and efficient catalyst for biodiesel production at a low cost.
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http://dx.doi.org/10.1021/acsomega.0c01970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377231PMC
July 2020

A novel multi-target tyrosine kinase inhibitor anlotinib combined with irinotecan has in-vitro anti-tumor activity against human small-cell lung cancer.

Anticancer Drugs 2020 11;31(10):1057-1064

Medical Oncology Translational Research Laboratory.

Anlotinib is a multi-target tyrosine kinase inhibitor developed independently in China. Its biological effects remain unclear in small-cell lung cancer (SCLC). The current study aimed to evaluate the effects of anlotinib in combination with irinotecan on H446 and H2227 SCLC cell lines and provide new treatment strategy for SCLC. Cell growth of two cell lines was inhibited by anlotinib, irinotecan and the combination in a dose-dependent manner. After 72 h incubation, the inhibition rate was greater in the combination group than all single drug group. A similar result was found when apoptosis was assessed after 12 h, but not after 6 h of treatment. Compared with single drug, combination drug suppressed the migration and invasion abilities in two cell lines; however, there was no difference between individual anlotinib or irinotecan. The colony formation rate was obviously lower in the combination group. Vascular endothelial growth factor receptor, fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor were expressed in two cell lines after treatment regardless single or combination, but FGFR was expressed more after combination treatment than anlotinib. The expression of phosphorylated (p) ERK was decreased with anlotinib alone or combination treatment and pAKT expression was impaired with combination treatment, but not with anlotinib or irinotecan alone. The biological function of anlotinib and irinotecan may be mediated through the AKT/ERK signaling pathway. Additional investigations on biomarker-guided patient-stratification and elucidating individualized targets in patients anlotinib are urgently needed.
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http://dx.doi.org/10.1097/CAD.0000000000000969DOI Listing
November 2020