Publications by authors named "Peilin Chen"

135 Publications

In Vitro 3D Mechanical Stimulation to Tendon-Derived Stem Cells by Bioreactor.

Methods Mol Biol 2021 Sep 10. Epub 2021 Sep 10.

Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, WA, Australia.

Bioreactors can offer an advanced platform to provide conditions that mimic the native microenvironment, which can also provide stretching environment for mechanobiology research. Tendon-derived stem cells (TDSCs) are a type of mechanosensitive and multipotent cells, which behave differently in diverse mechanical stretching environments. We have proved the in vitro three-dimensional (3D) mechanical stimulation could closely mimic the stretching environment in vivo. Thus, here we describe applying a customized bioreactor to provide 3D force for mechanical stimulation on TDSC in vitro.
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http://dx.doi.org/10.1007/7651_2021_432DOI Listing
September 2021

Structural characterization and in vitro fermentation by rat intestinal microbiota of a polysaccharide from Porphyra haitanensis.

Food Res Int 2021 09 19;147:110546. Epub 2021 Jun 19.

Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China. Electronic address:

A sulfated polysaccharide (PHP1) produced by the marine red alga Porphyra haitanensis was structurally characterized, and its effect on rat fecal microbiota fermentations and short chain fatty acids production were investigated. PHP1 was mainly composed of galactose and the main linkage types were identified as → 3)G4Sβ(1 → 3)G(1 → 6)G4Sα(1 → 4)LA(1 → 6)G4Sα(1→. The surface morphology of dried PHP1 films appears to be related to its chemical structure. PHP1 promoted the growth of both propionic acid-producing bacteria and propionic acid production, as well as influencing the composition and abundance of beneficial microbiota species in rats, which may be related to its high level of sulfation. The molecular weight of PHP1 decreased significantly after fermentation, which may result from hydrolysis of the galactan (with α- and β-linkages between galactose residues) by α- or β-galactosidase secreted by the microbiota. These results provided new insights into the structure-activity relationships between P. haitanensis polysaccharide and its regulation of microbiota in vivo.
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http://dx.doi.org/10.1016/j.foodres.2021.110546DOI Listing
September 2021

Compressed Domain Deep Video Super-Resolution.

IEEE Trans Image Process 2021 12;30:7156-7169. Epub 2021 Aug 12.

Real-world video processing algorithms are often faced with the great challenges of processing the compressed videos instead of pristine videos. Despite the tremendous successes achieved in deep-learning based video super-resolution (SR), much less work has been dedicated to the SR of compressed videos. Herein, we propose a novel approach for compressed domain deep video SR by jointly leveraging the coding priors and deep priors. By exploiting the diverse and ready-made spatial and temporal coding priors (e.g., partition maps and motion vectors) extracted directly from the video bitstream in an effortless way, the video SR in the compressed domain allows us to accurately reconstruct the high resolution video with high flexibility and substantially economized computational complexity. More specifically, to incorporate the spatial coding prior, the Guided Spatial Feature Transform (GSFT) layer is proposed to modulate features of the prior with the guidance of the video information, making the prior features more fine-grained and content-adaptive. To incorporate the temporal coding prior, a guided soft alignment scheme is designed to generate local attention off-sets to compensate for decoded motion vectors. Our soft alignment scheme combines the merits of explicit and implicit motion modeling methods, rendering the alignment of features more effective for SR in terms of the computational complexity and robustness to inaccurate motion fields. Furthermore, to fully make use of the deep priors, the multi-scale fused features are generated from a scale-wise convolution reconstruction network for final SR video reconstruction. To promote the compressed domain video SR research, we build an extensive Compressed Videos with Coding Prior (CVCP) dataset, including compressed videos of diverse content and various coding priors extracted from the bitstream. Extensive experimental results show the effectiveness of coding priors in compressed domain video SR.
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http://dx.doi.org/10.1109/TIP.2021.3101826DOI Listing
August 2021

Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells.

Theranostics 2021 11;11(16):7640-7657. Epub 2021 Jun 11.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China.

: Since primary prostate cancer (PCa) can advance to the life-threatening metastatic PCa, exploring the molecular mechanisms underlying PCa metastasis is crucial for developing the novel targeted preventive strategies for decreasing the mortality of PCa. RNA N-methyladenosine (mA) is an emerging regulatory mechanism for gene expression and its specific roles in PCa progression remains elusive. Western blotting, quantitative real-time PCR and immunohistochemical analyses were used to detect target gene expression in PCa cells and prostate tissues from patients. RNA immunoprecipitation was conducted to analyze the specific binding of mRNA to the target protein. Migration and invasion assays were used to assess the migratory capacities of cancer cells. The correlation between target gene expression and survival rate of PCa patients was analyzed based the TCGA database. We found that total RNA N-methyladenosine (mA) modification levels were markedly upregulated in human PCa tissues due to increased expression of methyltransferase like 3 (METTL3). Further studies revealed that the migratory and invasive capacities of PCa cells were markedly suppressed upon METTL3 knockdown. Mechanistically, METTL3 mediates mA modification of USP4 mRNA at A2696, and mA reader protein YTHDF2 binds to and induces degradation of mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells. Our findings highlight the role of METTL3 in modulating invasion and metastasis of PCa cells, providing insight into promising therapeutic strategies for hindering PCa progressing to deadly metastases.
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http://dx.doi.org/10.7150/thno.61178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315076PMC
August 2021

Granulocyte-Macrophage Colony Stimulating Factor in Single Blastocyst Conditioned Medium as a Biomarker for Predicting Implantation Outcome of Embryo.

Front Immunol 2021 30;12:679839. Epub 2021 Jun 30.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.

Background: It is highly desirable to develop new strategies based on secretomics to more accurately selection of embryos with the highest developmental potential for transfer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to promote embryo development and pregnancy establishment. However, the predictive value of GM-CSF in single blastocyst selection remains unclear. This study is to determine the concentration of GM-CSF in human single-blastocyst conditioned medium (SBCM) and to evaluate its association with embryo quality and pregnancy outcome.

Methods: The patients with ≤38 years of age receiving the first cycle of assisted reproductive therapy were included in this study. The patients who had <4 top-quality embryos formed by the fertilized two pronuclear zygotes on day 3 were excluded. A total of 126 SBCM samples (SBCMs) were included, of which blastocysts from 77 SBCMs were later transferred in subsequent frozen-thawed embryo transfer. The concentrations of GM-CSF were detected by single-molecule array (SIMOA) and analyzed for their possible association with embryo quality and pregnancy outcomes. The top-quality embryo (TQ), positive HCG (HP), clinical pregnancy (CP), and ongoing pregnancy (OP) rates were determined and compared between groups divided based on GM-CSF concentrations.

Results: The detection rate of GM-CSF was found to be 50% in all SBCMs. There were significant differences in TQ rate, HP rate, CP rate and OP rate among high concentration group, medium concentration group and low concentration group. Both GM-CSF alone or GM-CSF combined with the morphological score (MS) had a greater AUC of ROC curve than that of MS alone to predict the pregnancy outcome, and GM-CSF combined with MS had the highest AUC.

Conclusions: The concentration of GM-CSF in SBCM was detected at fg/ml levels, which was associated with embryo quality and pregnancy outcome. Collectively, GM-CSF may be used as a biomarker for prediction of pregnancy outcome and selection of embryos with high developmental potential for transfer in assisted reproductive technology (ART).
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http://dx.doi.org/10.3389/fimmu.2021.679839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278135PMC
October 2021

Reduction of mechanical loading in tendons induces heterotopic ossification and activation of the β-catenin signaling pathway.

J Orthop Translat 2021 Jul 18;29:42-50. Epub 2021 May 18.

Division of Orthopaedic Surgery, Department of Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Background: Tendons are the force transferring tissue that enable joint movement. Excessive mechanical loading is commonly considered as a primary factor causing tendinopathy, however, an increasing body of evidence supports the hypothesis that overloading creates microdamage of collagen fibers resulting in a localized decreased loading on the cell population within the damaged site. Heterotopic ossification is a complication of late stage tendinopathy, which can significantly affect the mechanical properties and homeostasis of the tendon. Here, we the examine the effect of mechanical underloading on tendon ossification and investigate its underlying molecular mechanism.

Method: Rabbit Achilles tendons were dissected and cultured in an underloading environment (3% cyclic tensile stain,0.25 ​Hz, 8 ​h/day) for either 10, 15 or 20 days. Using isolated tendon-derived stem cells (TDSCs) 3D constructs were generated, cultured and subjected to an underloading environment for 6 days. Histological assessments were performed to evaluate the structure of the 3D constructs; qPCR and immunohistochemistry were employed to study TDSC differentiation and the β-catenin signal pathway was investigated by Western blotting. Mechanical testing was used to determine ability of the tendon to withstand force generation.

Result: Tendons cultured for extended times in an environment of underloading showed progressive heterotopic ossification and a reduction in biomechanical strength. qPCR revealed that 3D TDSCs constructs cultured in an underloading environment exhibited increased expression of several osteogenic genes: these include RUNX2, ALP and osteocalcin in comparison to tenogenic differentiation markers (scleraxis and tenomodulin). Immunohistochemical analysis further confirmed high osteocalcin production in 3D TDSCs constructs subject to underloading. Western blotting of TDSC constructs revealed that β-catenin accumulation and translocation were associated with an increase in phosphorylation at Ser552 and decrease phosphorylation at Ser33.

Conclusion: These findings unveil a potential mechanism for heterotopic ossification in tendinopathy due to the underloading of TDSCs at the damage sites, and also that β-catenin could be a potential target for treating heterotopic ossification in tendons.

The Translational Potential: Tendon heterotopic ossification detrimentally affect quality of life especially for those who has atheletic career. This study reveals the possible mechanism of heterotpic ossification in tendon related to mechanical loading. This study provided the possible to develop a mechanical stimulation protocol for preventive and therapeutic purpose for tendon heterotopic ossification.
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http://dx.doi.org/10.1016/j.jot.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142054PMC
July 2021

Dual-scale categorization based deep learning to evaluate programmed cell death ligand 1 expression in non-small cell lung cancer.

Medicine (Baltimore) 2021 May;100(20):e25994

Oncology Department, Changhai Hospital of Shanghai, Shanghai, China.

Abstract: In precision oncology, immune check point blockade therapy has quickly emerged as novel strategy by its efficacy, where programmed death ligand 1 (PD-L1) expression is used as a clinically validated predictive biomarker of response for the therapy. Automating pathological image analysis and accelerating pathology evaluation is becoming an unmet need. Artificial Intelligence and deep learning tools in digital pathology have been studied in order to evaluate PD-L1 expression in PD-L1 immunohistochemistry image. We proposed a Dual-scale Categorization (DSC)-based deep learning method that employed 2 VGG16 neural networks, 1 network for 1 scale, to critically evaluate PD-L1 expression. The DSC-based deep learning method was tested in a cohort of 110 patients diagnosed as non-small cell lung cancer. This method showed a concordance of 88% with pathologist, which was higher than concordance of 83% of 1-scale categorization-based method. Our results show that the DSCbased method can empower the deep learning application in digital pathology and facilitate computer-aided diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000025994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137090PMC
May 2021

Application of X-ray diffraction and energy dispersive spectroscopy in the isolation of sulfated polysaccharide from Porphyra haitanensis and its antioxidant capacity under in vitro digestion.

J Sci Food Agric 2021 Dec 27;101(15):6452-6462. Epub 2021 May 27.

Engineering Research Center of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, China.

Background: The separation and purification of Porphyra haitanensis polysaccharide (PHP), and the determination of changes in molecular weight (Mw) and antioxidant capacity after in vitro digestion, were undertaken.

Results: Analysis of two polysaccharide fractions (PHP0.5-1-UF and PHP1.0-1-UF) by various techniques showed that they were very pure sulfated polysaccharides without pigment or protein. PHP0.5-1-UF was filamentous or 'tape-like' sheets, whereas PHP1.0-1-UF had some filaments and large numbers of rounded aggregates. The Mw of PHP, PHP0.5-1-UF and PHP1.0-1-UF was 2.06 × 10 (±2.02%), 6.68 × 10 (±3.17%), and 1.14 × 10 (±3.44%) (g mol ), respectively. After in vitro digestion, the Mw of PHP, PHP0.5-1-UF, and PHP1.0-1-UF decreased. Their antioxidant capacities were markedly higher than before digestion, especially PHP0.5-1-UF and its digestion products, which might be related to the reductions in Mw.

Conclusion: These findings provide a greater understanding of the separation and purification of sulfated polysaccharides and the influence of digestion on biological activity. They also contribute to the practical application of sulfated polysaccharides in functional foods. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11316DOI Listing
December 2021

Immune cell shuttle for precise delivery of nanotherapeutics for heart disease and cancer.

Sci Adv 2021 Apr 23;7(17). Epub 2021 Apr 23.

Ph.D. Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan.

The delivery of therapeutics through the circulatory system is one of the least arduous and less invasive interventions; however, this approach is hampered by low vascular density or permeability. In this study, by exploiting the ability of monocytes to actively penetrate into diseased sites, we designed aptamer-based lipid nanovectors that actively bind onto the surface of monocytes and are released upon reaching the diseased sites. Our method was thoroughly assessed through treating two of the top causes of death in the world, cardiac ischemia-reperfusion injury and pancreatic ductal adenocarcinoma with or without liver metastasis, and showed a significant increase in survival and healing with no toxicity to the liver and kidneys in either case, indicating the success and ubiquity of our platform. We believe that this system provides a new therapeutic method, which can potentially be adapted to treat a myriad of diseases that involve monocyte recruitment in their pathophysiology.
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http://dx.doi.org/10.1126/sciadv.abf2400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064633PMC
April 2021

Revealing the Phagosomal pH Regulation and Inflammation of Macrophages after Endocytosing Polyurethane Nanoparticles by A Ratiometric pH Nanosensor.

Adv Biol (Weinh) 2021 01 30;5(1):e2000200. Epub 2020 Dec 30.

Institute of Polymer Science and Engineering, National Taiwan University, Taipei, 10617, Taiwan (R.O.C.).

The effect of the intracellular pH of macrophages after taking up biodegradable polymer nanoparticles (NPs) on immunomodulating functions has not been explored so far. Previous studies have demonstrated that biodegradable polyurethane (PU) NPs exhibit immunosuppressive activity. Yet, the intracellular mechanism is not clearly understood. In this study, a uniquely designed pH nanosensor is employed for tracking the intracellular pH value of macrophages to reveal the intracellular journey of PU NPs and to clarify the intracellular pH effect on the corresponding inflammatory response. First, fluorescent mesoporous silica nanoparticles (FRMSNs) is used to detect the pH change in macrophages after endo/phagocytosis of PU NPs. Second, PU is coated on the external surface of FRMSNs to examine the intracellular trafficking process of PU in the macrophages. The results show that the majority of PU-coated FRMSNs remain to stay at the cytosol-early endosome/phagosome regions. The intracellular pH value and other supporting results show that the immune response of PU NPs may be correlated to their internalization journey. The retardation in the degradation process of the PU NPs may intervene with the lysosome activity and repress the immunostimulatory effect, which contributes to the low immune response of PU NPs.
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http://dx.doi.org/10.1002/adbi.202000200DOI Listing
January 2021

A novel biocompatible polymeric blend for applications requiring high toughness and tailored degradation rate.

J Mater Chem B 2021 03 4;9(10):2532-2546. Epub 2021 Mar 4.

Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and the UWA Centre for Medical Research, The University of Western Australia, Perth, Australia.

Finding the right balance in mechanical properties and degradation rate of biodegradable materials for biomedical applications is challenging, not only at the time of implantation but also during biodegradation. For instance, high elongation at break and toughness with a mid-term degradation rate are required for tendon scaffold or suture application, which cannot be found in each alpha polyester individually. Here, we hypothesise that blending semi-crystalline poly(p-dioxanone) (PDO) and poly(lactide-co-caprolactone) (LCL) in a specific composition will enhance the toughness while also enabling tailored degradation times. Hence, blends of PDO and LCL (PDO/LCL) were prepared in varying concentrations and formed into films by solvent casting. We thoroughly characterised the chemical, thermal, morphological, and mechanical properties of the new blends before and during hydrolytic degradation. Cellular performance was determined by seeding mouse fibroblasts onto the samples and culturing for 72 hours, before using proliferation assays and confocal imaging. We found that an increase in LCL content causes a decrease in hydrolytic degradation rate, as indicated by induced crystallinity, surface and bulk erosions, and tensile properties. Interestingly, the noncytotoxic blend containing 30% PDO and 70% LCL (PDO3LCL7) resulted in small PDO droplets uniformly dispersed within the LCL matrix and demonstrated a tailored degradation rate and toughening behaviour with a notable strain-hardening effect reaching 320% elongation at break; over 3 times the elongation of neat LCL. In summary, this work highlights the potential of PDO3LCL7 as a biomaterial for biomedical applications like tendon tissue engineering or high-performance absorbable sutures.
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http://dx.doi.org/10.1039/d0tb02971hDOI Listing
March 2021

Natural population re-sequencing detects the genetic basis of local adaptation to low temperature in a woody plant.

Plant Mol Biol 2021 Apr 2;105(6):585-599. Epub 2021 Mar 2.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing, 100093, China.

Key Message: Total of 14 SNPs associated with overwintering-related traits and 75 selective regions were detected. Important candidate genes were identified and a possible network of cold-stress responses in woody plants was proposed. Local adaptation to low temperature is essential for woody plants to against changeable climate and safely survive the winter. To uncover the specific molecular mechanism of low temperature adaptation in woody plants, we sequenced 134 core individuals selected from 494 paper mulberry (Broussonetia papyrifera), which naturally distributed in different climate zones and latitudes. The population structure analysis, PCA analysis and neighbor-joining tree analysis indicated that the individuals were classified into three clusters, which showed forceful geographic distribution patterns because of the adaptation to local climate. Using two overwintering phenotypic data collected at high latitudes of 40°N and one bioclimatic variable, genome-phenotype and genome-environment associations, and genome-wide scans were performed. We detected 75 selective regions which possibly undergone temperature selection and identified 14 trait-associated SNPs that corresponded to 16 candidate genes (including LRR-RLK, PP2A, BCS1, etc.). Meanwhile, low temperature adaptation was also supported by other three trait-associated SNPs which exhibiting significant differences in overwintering traits between alleles within three geographic groups. To sum up, a possible network of cold signal perception and responses in woody plants were proposed, including important genes that have been confirmed in previous studies while others could be key potential candidates of woody plants. Overall, our results highlighted the specific and complex molecular mechanism of low temperature adaptation and overwintering of woody plants.
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http://dx.doi.org/10.1007/s11103-020-01111-xDOI Listing
April 2021

Intramuscular injection of Botox causes tendon atrophy by induction of senescence of tendon-derived stem cells.

Stem Cell Res Ther 2021 01 7;12(1):38. Epub 2021 Jan 7.

Center for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Australia.

Background: Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but the mechanism of action is poorly understood.

Hypothesis: We hypothesised that the reduction of patellar-tendon mechanical-loading following intra-muscular injection of Botox results in tendon atrophy that is at least in part mediated by the induction of senescence of tendon-derived stem cells (TDSCs).

Study Design: Controlled laboratory study METHODS: A total of 36 mice were randomly divided into 2 groups (18 Botox-injected and 18 vehicle-only control). Mice were injected into the right vastus lateralis of quadriceps muscles either with Botox (to induce mechanical stress deprivation of the patellar tendon) or with normal saline as a control. At 2 weeks post-injection, animals were euthanized prior to tissues being harvested for either evaluation of tendon morphology or in vitro studies. TDSCs were isolated by cell-sorting prior to determination of viability, differentiation capacity or the presence of senescence markers, as well as assessing their response to mechanical loading in a bioreactor. Finally, to examine the mechanism of tendon atrophy in vitro, the PTEN/AKT-mediated cell senescence pathway was evaluated in TDSCs from both groups.

Results: Two weeks after Botox injection, patellar tendons displayed several atrophic features including tissue volume reduction, collagen fibre misalignment and increased degradation. A colony formation assay revealed a significantly reduced number of colony forming units of TDSCs in the Botox-injected group compared to controls. Multipotent differentiation capacities of TDSCs were also diminished after Botox injection. To examine if mechanically deprived TDSC are capable of forming tendon tissue, we used an isolated bioreactor system to culture tendon constructs using TDSC. These results showed that TDSCs from the Botox-treated group failed to restore tenogenic differentiation after appropriate mechanical loading. Examination of the signalling pathway revealed that injection of Botox into quadriceps muscles causes PTEN/AKT-mediated cell senescence of TDSCs.

Conclusion: Intramuscular injection of Botox interferes with tendon homeostasis by inducing tendon atrophy and senescence of TDSCs. Botox injection may have long-term adverse consequences for the treatment of tendinopathy.

Clinical Relevance: Intramuscular Botox injection for tendinopathy or tendon injury could result in adverse effects in human tendons and evaluation of its long-term efficacy is warranted.
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http://dx.doi.org/10.1186/s13287-020-02084-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791643PMC
January 2021

5D superresolution imaging for a live cell nucleus.

Curr Opin Genet Dev 2021 04 28;67:77-83. Epub 2020 Dec 28.

Brain Research Center, National Tsing Hua University, Hsinchu, 30013, Taiwan; Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan. Electronic address:

With a spatial resolution breaking the diffraction limit of light, superresolution imaging allows the visualization of detailed structures of organelles such as mitochondria, cytoskeleton, nucleus, and so on. With multi-dimensional imaging (x, y, z, t, λ), namely, multi-color 3D live imaging enables us fully understand the function of the cell. It is necessary to analyze structural changes or molecular interactions across a large volume in 3D with different labelled targets. To achieve this goal, scientists recently have expanded the original 2D superresolution microscopic tools into 3D imaging techniques. In this review, we will discuss recent development in superresolution microscopy for live imaging with minimal phototoxicity. We will focus our discussion on the cell nucleus where the genetic materials are stored and processed. Machine learning algorism will be introduced to improve the axial resolution of superresolution imaging.
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http://dx.doi.org/10.1016/j.gde.2020.11.005DOI Listing
April 2021

Evaluation of Nanoparticle Penetration in the Tumor Spheroid Using Two-Photon Microscopy.

Biomedicines 2020 Dec 24;9(1). Epub 2020 Dec 24.

Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan.

Mesoporous silica nanoparticles (MSNs) have emerged as a prominent nanomedicine platform, especially for tumor-related nanocarrier systems. However, there is increasing concern about the ability of nanoparticles (NPs) to penetrate solid tumors, resulting in compromised antitumor efficacy. Because the physicochemical properties of NPs play a significant role in their penetration and accumulation in solid tumors, it is essential to systematically study their relationship in a model system. Here, we report a multihierarchical assessment of the accumulation and penetration of fluorescence-labeled MSNs with nine different physicochemical properties in tumor spheroids using two-photon microscopy. Our results indicated that individual physicochemical parameters separately could not define the MSNs' ability to accumulate in a deeper tumor region; their features are entangled. We observed that the MSNs' stability determined their success in reaching the hypoxia region. Moreover, the change in the MSNs' penetration behavior postprotein crowning was associated with both the original properties of NPs and proteins on their surfaces.
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http://dx.doi.org/10.3390/biomedicines9010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824314PMC
December 2020

Comparative transcriptome study of switchgrass ( L.) homologous autopolyploid and its parental amphidiploid responding to consistent drought stress.

Biotechnol Biofuels 2020 15;13:170. Epub 2020 Oct 15.

Department of Grassland Science, Animal Science and Technology College, Sichuan Agricultural University, Chengdu, 611130 China.

Background: Newly formed polyploids may experience short-term adaptative changes in their genome that may enhance the resistance of plants to stress. Considering the increasingly serious effects of drought on biofuel plants, whole genome duplication (WGD) may be an efficient way to proceed with drought resistant breeding. However, the molecular mechanism of drought response before/after WGD remains largely unclear.

Result: We found that autoploid switchgrass ( L.) 8X Alamo had higher drought tolerance than its parent amphidiploid 4X Alamo using physiological tests. RNA and microRNA sequencing at different time points during drought were then conducted on 8X Alamo and 4X Alamo switchgrass. The specific differentially expressed transcripts (DETs) that related to drought stress (DS) in 8X Alamo were enriched in ribonucleoside and ribonucleotide binding, while the drought-related DETs in 4X Alamo were enriched in structural molecule activity. Ploidy-related DETs were primarily associated with signal transduction mechanisms. Weighted gene co-expression network analysis (WGCNA) detected three significant DS-related modules, and their DETs were primarily enriched in biosynthesis process and photosynthesis. A total of 26 differentially expressed microRNAs (DEmiRs) were detected, and among them, sbi-microRNA 399b was only expressed in 8X Alamo. The targets of microRNAs that were responded to polyploidization and drought stress all contained cytochrome P450 and superoxide dismutase genes.

Conclusions: This study explored the drought response of 8X and 4X Alamo switchgrass on both physiological and transcriptional levels, and provided experimental and sequencing data basis for a short-term adaptability study and drought-resistant biofuel plant breeding.
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http://dx.doi.org/10.1186/s13068-020-01810-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559793PMC
October 2020

Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis.

J Clin Invest 2021 01;131(1)

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.
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http://dx.doi.org/10.1172/JCI130740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773376PMC
January 2021

A visualized clinical model predicting good quality blastocyst development in the first IVF/ICSI cycle.

Reprod Biomed Online 2020 Nov 23;41(5):807-817. Epub 2020 Jul 23.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen Guangdong 518045, People's Republic of China. Electronic address:

Research Question: Is it possible to establish a visualized clinical model predicting good quality blastocyst (GQB) formation for patients in their first IVF/intracytoplasmic sperm injection (ICSI) cycle?

Design: A total of 4783 patients in their first IVF/ICSI cycle between January 2015 and December 2019 were retrospectively included and randomly divided into the training set (n = 3826) and the testing set (n = 957) in an 8:2 ratio. The least absolute shrinkage and selection operator (LASSO) regression was adopted to select the most critical predictors for GQB formation to construct a visualized nomogram model based on the data of patients in the training set. Receiver operating characteristic and calibration curves were used to evaluate the predictive accuracy and discriminative ability. The performance of the model was also validated on independent data from patients treated in the testing set.

Results: Maternal age, maternal serum anti-Müllerian hormone (MsAMH) concentration and the number of oocytes retrieved were highlighted as critical predictors of GQB development and were incorporated into the nomogram model. Based on the area under the curve (AUC) values, the predictive ability for ≥1, ≥3 and ≥5 GQB were 0.831, 0.734 and 0.748, respectively. The calibration curve also showed high concordance between the observed and predicted results. The AUC for predicting ≥1, ≥3 and ≥5 GQB in the testing set were 0.805, 0.695 and 0.707, respectively, which were similar to those for the training set.

Conclusions: The visualized nomogram model provides great predictive value for GQB development in patients in their first IVF/ICSI cycle and can be used to improve clinical counselling.
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http://dx.doi.org/10.1016/j.rbmo.2020.07.018DOI Listing
November 2020

Applying a Three-dimensional Uniaxial Mechanical Stimulation Bioreactor System to Induce Tenogenic Differentiation of Tendon-Derived Stem Cells.

J Vis Exp 2020 08 1(162). Epub 2020 Aug 1.

Centre of Orthopaedic Translational Research, Medical School, University of Western Australia;

Tendinopathy is a common chronic tendon disease relating to inflammation and degeneration in an orthopaedic area. With high morbidity, limited self-repairing capacity and, most importantly, no definitive treatments, tendinopathy still influences patients' life quality negatively. Tendon-derived stem cells (TDSCs), as primary precursor cells of tendon cells, play an essential role in both the development of tendinopathy, and functional and structural restoration after tendinopathy. Thus, a method that can in vitro mimic the in vivo differentiation of TDSCs into tendon cells would be useful. Here, the present protocol describes a method based on a three-dimensional (3D) uniaxial stretching system to stimulate the TDSCs to differentiate into tendon-like tissues. There are seven stages of the present protocol: isolation of mice TDSCs, culture and expansion of mice TDSCs, preparation of stimulation culture medium for cell sheet formation, cell sheet formation by culturing in stimulation medium, preparation of 3D tendon stem cell construct, assembly of the uniaxial-stretching mechanical stimulation complex, and evaluation of the mechanical stimulated in vitro tendon-like tissue. The effectiveness was demonstrated by histology. The entire procedure takes less than 3 weeks. To promote extracellular matrix deposition, 4.4 mg/mL ascorbic acid was used in the stimulation culture medium. A separated chamber with a linear motor provides accurate mechanical loading and is portable and easily adjusted, which is applied for the bioreactor. The loading regime in the present protocol was 6% strain, 0.25 Hz, 8 h, followed by 16 h rest for 6 days. This protocol could mimic cell differentiation in the tendon, which is helpful for the investigation of the pathological process of tendinopathy. Moreover, the tendon-like tissue is potentially used to promote tendon healing in tendon injury as an engineered autologous graft. To sum up, the present protocol is simple, economic, reproducible and valid.
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http://dx.doi.org/10.3791/61278DOI Listing
August 2020

Perinatal and neonatal outcomes of pregnancies after early rescue intracytoplasmic sperm injection in women with primary infertility compared with conventional intracytoplasmic sperm injection: a retrospective 6-year study.

BMC Pregnancy Childbirth 2020 Aug 12;20(1):460. Epub 2020 Aug 12.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Guangdong, 518045, Shenzhen, People's Republic of China.

Background: Early rescue intracytoplasmic sperm injection (ICSI) has been used in clinic as appropriate currently. While the outcomes of children born after this method were not well assessed. The purpose of this study was to evaluate the effect of early rescue ICSI on women with primary infertility.

Methods: Fresh embryo transfer cycles after rescue (n = 214) and conventional (n = 546) ICSI were retrospectively evaluated from women with primary infertility who underwent their first assisted reproductive technology cycles at our center in 2012-2017. The conventional ICSI group was subdivided into ICSI-1 (semen suitable for in vitro fertilization, IVF) and ICSI-2 (poor semen quality) to minimize bias from differences in semen quality. Pregnancy, delivery and neonatal outcomes were compared between groups.

Results: There was a higher rate of polyspermy and a lower rate of top-quality embryos (TQE) on day 3 for oocytes subject to rescue ICSI compared with conventional ICSI. This reduced the total number of TQE and the number of TQE transferred in the rescue ICSI group. There was no significant difference between groups in clinical pregnancy, ongoing pregnancy, early miscarriage and live birth. For pregnant women, gestational age, route of delivery, risk of preterm birth and gestational diabetes mellitus were also comparable. Neonatal outcomes including sex ratio, birth weight, neonatal intensive care unit admission and birth defects were also similar after rescue and conventional ICSI. Moreover, no differences were observed with the different ICSI subgroups.

Conclusions: For women with primary infertility who have a high risk of IVF fertilization failure (FF), rescue ICSI provides a safe and efficient alternative to minimize FF after initial IVF, but results in fewer TQE on day 3.
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http://dx.doi.org/10.1186/s12884-020-03155-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425156PMC
August 2020

Simultaneous Single-Particle Tracking and Dynamic pH Sensing Reveal Lysosome-Targetable Mesoporous Silica Nanoparticle Pathways.

ACS Appl Mater Interfaces 2020 Sep 9;12(38):42472-42484. Epub 2020 Sep 9.

Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.

Nanoparticle (NP)-based targeted drug delivery is intended to transport therapeutically active molecules to specific cells and particular intracellular compartments. However, there is limited knowledge regarding the complete route of NPs in this targeting scenario. In this study, simultaneously performing motion and dynamic pH sensing using single-particle tracking (SPT) leads to an alternative method of gaining insights into the mesoporous silica nanoparticle's (MSN) journey in targeting lysosome. Two different pH-sensitive dyes and a reference dye are incorporated into mesoporous silica nanoparticles (MSNs) co-condensation to broaden the measurable pH range (pH 4-7.5) of the nanoprobe. The phosphonate, amine, and lysosomal sorting peptides (YQRLGC) are conjugated onto the MSN's surface to study intracellular nano-biointeractions of two oppositely charged and lysosome-targetable MSNs. The brightness and stability of these MSNs allow their movement and dynamic pH evolution during their journey to be simultaneously monitored in real time. Importantly, a multidimensional analysis of MSN's movement and local pH has revealed new model intracellular dynamic states and distributions of MSNs, previously inaccessible when using single parameters alone. A key result is that YQRLGC-conjugated MSNs took an alternative route to target lysosomes apart from the traditional one, which sped up to 4 h and enhanced their targeting efficiency (up to 32%). The findings enrich our understanding of the intracellular journey of MSNs. This study offers complementary information on correlating the surface design with the full pathway of nanoparticles to achieve targeted delivery of therapeutic payload.
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http://dx.doi.org/10.1021/acsami.0c07917DOI Listing
September 2020

Cooperation between and Its Symbiotic Fungal Community To Improve Local Adaptation of the Host.

Appl Environ Microbiol 2020 09 1;86(18). Epub 2020 Sep 1.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, China

The genetic basis of plant local adaptation has been extensively studied, yet the interplay between local adaptation, plant genetic divergence, and the microbial community remains unclear. Our study used the restriction-site associated DNA sequencing (RAD-seq) approach to explore genetic divergence in and used internal transcribed spacers (ITS) to characterize fungal community. RAD-seq results show that individuals could be divided into three genotypes; this genotyping result was consistent with the classification of climate type at the sample site. Most of the 101 highly differentiated genes were related to stress resistance and the microbiome. Moreover, β-diversity results indicated that genetic divergence had a significant effect on fungal community across all compartments (0.01). At genus and operational taxonomic unit (OTU) level, , , OTU81578 (), and OTU1665209 () were found to be the major OTUs that contribute to differences in fungal community. The properties of cooccurrence networks vary greatly among three genotypes. The results of redundancy analysis (RDA) indicated that -associated fungal community was significantly related to its local adaptability. Our findings suggest that genetic divergence of is closely related to local adaptation, with significant effects on the associated fungal community, which in turn would enhance host local adaptability. This improves present understanding about the coevolution of microbial communities and the host plant. The coevolution of plants with the associated fungal community and its effect on plant adaptability are not clear, especially for native trees. This study focuses on the genetic basis of local adaptation in plants and the effect of genetic divergence of on the associated fungal community. We identified genes related to the microbiome that are important for local adaptation of the host. Our results show that genetic divergence in significantly affects the fungal community, which has a close connection with local adaptation. This helps us to understand the relationship between local adaptation, genetic divergence, and associated fungal communities. This study highlights the effect of plant genetic divergence on associated fungal community for native trees and establishes a close connection between this effect and local adaptability in the host. In addition, these observations lay a foundation for the research of coevolution of plants and their symbiotic microbiome through genome-wide association study (GWAS).
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http://dx.doi.org/10.1128/AEM.00464-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480386PMC
September 2020

Comparative secretome profile analysis of cultured immortalized human endometrial stromal cells supplemented with implanted versus nonimplanted blastocyst-conditioned medium: A preliminary analysis.

J Obstet Gynaecol Res 2020 Sep 8;46(9):1809-1818. Epub 2020 Jul 8.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.

Aim: Human endometrial stromal cells (HESCs) were previously shown to be capable of discriminating embryos with different qualities. Here we aimed to compare the specific response of the HESC secretome to implanted blastocyst-conditioned medium (BCM) versus nonimplanted medium and identify cytokine candidates useful for the assessment of blastocyst implantation.

Methods: Cleavage embryos were individually cultured in one microdrop of medium for blastocyst formation. The BCM was collected after fresh blastocyst transfer on day 5 and used to supplement HESC culture medium. A high-throughput antibody array covering 440 cytokines was used to detect the secretory proteins of HESCs supplemented with implanted or nonimplanted BCM.

Results: A total of 22 differentially expressed proteins were found out of 440 cytokines in the supernatant of HESCs supplemented with BCM from the implanted group compared to the nonimplanted group, including seven upregulated and 15 downregulated proteins. Gene Ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in cell chemotaxis and motility, and ERK1/2 cascade regulation. Kyoto Encyclopedia of Genes and Genomes analysis suggested that the mitogen-activated protein kinase and phosphatidylinositol 3 kinase/Akt pathways were mainly involved.

Conclusion: HESCs specifically responded to BCM from different quality blastocysts, a finding that can be used to develop a novel approach for blastocyst quality assessment.
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http://dx.doi.org/10.1111/jog.14359DOI Listing
September 2020

A method for the detection of hCG β in spent embryo culture medium based on multicolor fluorescence detection from microfluidic droplets.

Biomicrofluidics 2020 Mar 7;14(2):024107. Epub 2020 Apr 7.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, Guangdong, People's Republic of China.

The evaluation of embryo quality via human chorionic gonadotropin beta (hCG β) and other proteins secreted by embryos in a spent embryo culture medium (SECM) receives a close review in the field of assisted reproduction. However, accurate and quantitative detection of these trace proteins is still a challenge. In this study, a highly sensitive protein detection method using microfluidic droplets and multicolor fluorescence detection was developed and used to detect hCG β secreted by embryos in SECM. β-Galactosidase (β-Gal) was used to label hCG β and can catalyze the conversion of nonfluorescent substrate fluorescein di-β-d-galactopyranoside to produce fluorescein to amplify the signal strength. Compared with previous studies, the proposed method requires only a simple microfluidic chip and can eliminate false-positive signals generated by free β-Gal through simultaneous detection of fluorescence, which can ensure the accuracy of the results. The lower detection limit of hCG β was 0.1 pg/ml. Using the developed method, hCG β in SECM was successfully detected; the hCG β secreted by top-quality blastocysts was significantly higher than that of non-top-quality blastocysts and embryos that do not develop into blastocysts. The proposed method can be used to detect secretory proteins from embryos in SECM and has application value in the screening of other biomarkers.
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http://dx.doi.org/10.1063/1.5141490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156014PMC
March 2020

Detection of IL-6, IL-10, and TNF-α level in human single-blastocyst conditioned medium using ultrasensitive Single Molecule Array platform and its relationship with embryo quality and implantation: a pilot study.

J Assist Reprod Genet 2020 Jul 15;37(7):1695-1702. Epub 2020 May 15.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, 518045, Guangdong, People's Republic of China.

Purpose: The purpose was to investigate the association between embryonic development or implantation and the content of interleukin-6 and 10 (IL-6, IL-10) and tumor necrosis factor-α (TNF-α) in single-blastocyst conditioned medium (SBCM).

Methods: Thirty-eight SBCM samples (SBCMs) were collected from blastocysts with different morphological scores. IL-6, IL-10, and TNF-α concentration in 38 SBCMs was detected by Single Molecule Array and compared according to the blastocyst quality: top-quality (TQ) and non-top quality (NTQ), or blastulation time: day 5 (D5) and day 6 (D6). In another experiment, 61 SBCMs were collected from TQ blastocyst transplanted on D5, and IL-6 concentration in SBCM was compared based on whether embryos are implanted or not (implanted and non-implanted).

Results: In the first experiment, IL-6, IL-10, and TNF-α concentration was not significantly different between the TQ-SBCM and NTQ-SBCM. The D6-SBCM had a higher IL-6 concentration compared with the D5-SBCM, while IL-10 and TNF-α concentration was not significantly different between the D5-SBCM and D6-SBCM. The IL-6 concentration in D5-NTQ or D6-TQ SBCM was higher than that in D5-TQ or D6-NTQ SBCM (P < 0.05), respectively. Furthermore, the spearman analysis demonstrated that IL-6 concentration in SBCM was negatively correlated with the blastocyst quality on D5 and positively correlated with the blastocyst quality on D6. In the second experiment, no significant difference in IL-6 concentration was found between SBCM from implanted and non-implanted blastocyst.

Conclusion: IL-6 concentration in SBCM was associated with embryo quality depending on the blastulation time, although it might not be associated with the blastocyst implantation.
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http://dx.doi.org/10.1007/s10815-020-01805-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376610PMC
July 2020

Horizontal fissuring at the osteochondral interface: a novel and unique pathological feature in patients with obesity-related osteoarthritis.

Ann Rheum Dis 2020 06 8;79(6):811-818. Epub 2020 Apr 8.

Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia

Objectives: Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA.

Methods: We analysed the correlation between BMI and the age at which patients undergo total knee replacement (TKR) in 41 023 patients from the Australian Orthopaedic Association National Joint Replacement Registry. We then investigated the effect of BMI on pathological changes of the tibia plateau of knee joint in a representative subset of the registry.

Results: 57.58% of patients in Australia who had TKR were obese. Patients with overweight, obese class I & II or obese class III received a TKR 1.89, 4.48 and 8.08 years earlier than patients with normal weight, respectively. Microscopic examination revealed that horizontal fissuring at the osteochondral interface was the major pathological feature of obesity-related OA. The frequency of horizontal fissure was strongly associated with increased BMI in the predominant compartment. An increase in one unit of BMI (1 kg/m) increased the odds of horizontal fissures by 14.7%. 84.4% of the horizontal fissures were attributable to obesity. Reduced cartilage degradation and alteration of subchondral bone microstructure were also associated with increased BMI.

Conclusions: The key pathological feature in OA patients with obesity is horizontal fissuring at the osteochondral unit interface. Obesity is strongly associated with a younger age of first TKR, which may be a result of horizontal fissures.
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http://dx.doi.org/10.1136/annrheumdis-2020-216942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286031PMC
June 2020

Catcher in the rel: Nanoparticles-antibody conjugate as NF-κB nuclear translocation blocker.

Biomaterials 2020 07 30;246:119997. Epub 2020 Mar 30.

Graduate Institute of Nanomedicine and Medical Engineering, Taipei Medical University, Taipei, 110, Taiwan; Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan. Electronic address:

Transcription factor complex NF-κB (p65/p50) is localized to the cytoplasm by its inhibitor IκBα. Upon activation, the Rel proteins p65/p50 are released from IκBα and transported through nuclear pore to affect many gene expressions. While inhibitions of up or down stream signal pathways are often ineffective due to crosstalks and compensations, direct blocking of the Rel proteins p65/p50 has long been proposed as a potential target for cancer therapy. In this work, a nanoparticle/antibody complex targeting NF-κB is employed to catch the Rel protein p65 in perinuclear region and thus blocking the translocation near the nuclear pore gate. TAT peptide conjugated on mesoporous silica nanoparticles (MSN) help non-endocytosis cell-membrane transducing and converge toward perinuclear region, where the p65 specific antibody performed the targeting and catching against active NF-κB p65 effectively. The size of the p65 bound nanoparticle becomes too big to enter nucleus. Simultaneous treatment of mice with the hybrid MSN and doxorubicin conferred a significant therapeutic effect against 4T1 tumor-bearing mice. The new approach of anti-body therapy targeting on transcription factor with "nucleus focusing" and "size exclusion blocking" effects of the antibody-conjugated nanoparticle is general and may be applicable to modulating other transcription factors.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119997DOI Listing
July 2020

Association between the number of top-quality blastocysts and live births after single blastocyst transfer in the first fresh or vitrified-warmed IVF/ICSI cycle.

Reprod Biomed Online 2020 Apr 18;40(4):530-537. Epub 2020 Jan 18.

Shenzhen Key Laboratory of Reproductive Immunology for Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen Guangdong 518045, People's Republic of China. Electronic address:

Research Question: Is there an association between the total number of top-quality blastocysts (TQB) developed in the first IVF/intracytoplasmic sperm injection cycle (ICSI) and live births after a single blastocyst transfer (SBT)?

Design: Pregnancy outcomes from 1336 infertile women who had undergone their first IVF/ICSI treatment and accepted a first-time embryo transfer with a single fresh or vitrified-warmed blastocyst between January 2016 and August 2018 were assessed retrospectively. The restricted cubic splines method was used to evaluate the association between the number of TQB, and ongoing pregnancies and live births.

Results: A significant non-linear functional form was found between the number of TQB and the ongoing pregnancies and live births (P < 0.05). The odds of an ongoing pregnancy or live birth were similar, at about 11% or higher for each additional TQB up to five TQB (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.01-1.21). After this, pregnancy outcomes nearly plateaued, indicating that the number of TQB was not related to pregnancy when it was greater than five.

Conclusions: The quantity of TQB available for transfer or cryopreservation can provide important predictors for pregnancy and live birth after the first embryo transfer cycle with a single blastocyst. This valuable information may assist with the future application of SBT.
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http://dx.doi.org/10.1016/j.rbmo.2020.01.005DOI Listing
April 2020

The effect of plant compartments on the Broussonetia papyrifera-associated fungal and bacterial communities.

Appl Microbiol Biotechnol 2020 Apr 20;104(8):3627-3641. Epub 2020 Feb 20.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

Plants associate with numerous microbes, but little is known about how microbiome components, especially fungi, adapt to specific plant compartments. The adaptability of microbial function to the plant compartment is also not clear especially for woody species. Here, we characterized the bacterial and fungal communities in root endosphere, stems, and rhizospheres of 33 Broussonetia papyrifera seedlings, based on amplification of 16S and ITS rRNA. Results showed that the α-diversity indexes of the bacterial community were significantly different in different plant compartments and they significantly increased from stem to root endosphere to the rhizosphere, whereas those of the fungal community were similar (p > 0.05). However, the result of constrained PCoA (CPCoA) and analysis of similarity (ANOSIM) showed that both bacterial and fungal compositions were significantly affected by plant compartments (p < 0.01). In detail, the operational taxonomic units (OTUs) distribution of the bacterial community was significantly different, but 249 of 252 fungal OTUs were shared in different plant compartments. Both the bacterial and fungal compositions were significantly influenced by plant compartments, based on the result on phyla, core OTUs, and indicator OTUs level. Further, 40 of 42 enriched KEGG pathways involving the bacteria also differed significantly among plant compartments (p < 0.01). This study provides an understanding of the influence of plant compartments on the microbiome and confirms that the disperse limitation of fungal OTUs across different plant compartments is smaller. This study sheds light on how the microbial community adapts to and thrives in different plant compartments.
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http://dx.doi.org/10.1007/s00253-020-10466-6DOI Listing
April 2020

Carbon Nanotube/Conducting Polymer Hybrid Nanofibers as Novel Organic Bioelectronic Interfaces for Efficient Removal of Protein-Bound Uremic Toxins.

ACS Appl Mater Interfaces 2019 Nov 12;11(47):43843-43856. Epub 2019 Nov 12.

Department of Nephrology , Chang Gung Memorial Hospital , Taoyuan , Taiwan.

Protein-bound uremic toxins (PBUTs) can cause noxious effects in patients suffering from renal failure as a result of inhibiting the transport of proteins and inducing their structural modification. They are difficult to remove through standard hemodialysis (HD) treatment. Herein, we report an organic bioelectronic HD device system for the effective removal of PBUTs through electrically triggered dissociation of protein-toxin complexes. To prepare this system, we employed electrospinning to fabricate electrically conductive quaternary composite nanofiber mats-comprising multiwalled carbon nanotubes (MWCNTs), poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS)-on conventional polyethersulfone (PES) dialysis membranes. These composite nanofiber platforms exhibited (i) long-term water resistance (due to cross-linking among PSS, PEO, and GOPS), (ii) high adhesion strength on the PES membrane (due to GOPS functioning as an adhesion promoter), (iii) enhanced electrical properties [due to the MWCNTs and PEDOT:PSS promoting effective electrical stimulation (ES) operation in devices containing bioelectronic interfaces (BEI)], and (iv) good anticoagulant ability and negligible hemolysis of red blood cells. We employed this organic BEI electronic system as a novel single-membrane HD device to study the removal efficiency of four kinds of uremic toxins [-cresol (PC), indoxyl sulfate, and hippuric acid as PBUTs; creatinine as a non-PBUT] as well as the effects of ES on lowering the protein binding ratio. Our organic BEI devices provided a high rate of removal of PC with low protein loss after 4 h of a simulated dialysis process. It also functioned with low complement activation, low contact activation levels, and lower amounts of platelet adsorption, suggesting great suitability for use in developing next-generation bioelectronic medicines for HD.
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http://dx.doi.org/10.1021/acsami.9b14351DOI Listing
November 2019
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