Publications by authors named "Xiaoyi Chen"

162 Publications

Unity and diversity of neural representation in executive functions.

J Exp Psychol Gen 2021 Mar 25. Epub 2021 Mar 25.

Key Laboratory of Cognition and Personality of Ministry of Education.

Although the unity and diversity model of executive functions (EFs) has been replicated, there are some studies questioning the validity of the EFs construct. This debate can be partially resolved by directly combining the brain activity pattern in different executive control processes. Previous univariate activation studies have suggested that the neural substrates of different EFs (e.g., updating, inhibiting, and shifting) involve common and distinct brain regions. However, the underlying multivariate neural representation of EFs in terms of unity and diversity is still elusive. Here, we employed the n-back task, stop signal task, and category switching task to investigate the characteristic of the neural representation in the three EF domains. At the global level, multivoxel pattern analysis revealed that a three-way classifier built with global activation pattern successfully distinguished the three EF tasks. At the local level, although most overlapping activations exhibit lower neural representational similarity, the inferior frontal junction showed similar neural representation across the three EFs, which was further confirmed by searchlight analysis that additionally revealed other similar representational regions were located in the presupplementary motor area extend to dorsal midcingulate cortex. In addition, using machine learning-based predictive framework, the resting-state functional networks built with the representational regions of EFs predicted intellectual abilities to some extent in a large independent sample. These findings suggest that different EFs are characterized by dissociable global neural representation but also share similar local neural representation, which contributes to understanding the neural correlates of the unity and diversity of EFs from an integrated framework. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/xge0001047DOI Listing
March 2021

[Phenotypic and genetic analysis of a case with hypohidrotic ectodermal dysplasia due to Xq13.1 microdeletion].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Mar;38(3):219-223

Department of Neurology, Children's Hospital Affiliated to Zhengzhou University, Henan Provincial Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450018, China.

Objective: To investigate the clinical phenotype and genetic characteristics of a patient with hypohidrotic ectodermal dysplasia (HED) due to partial deletion of EDA gene.

Methods: The child has presented with HED complicated with epilepsy. Family trio whole exome sequencing (Trio-WES), copy number variation sequencing (CNV-seq), and karyotype analysis were carried out to explore the underlying genetic etiology.

Results: The proband, a 7-year-and-8-month-old boy, presented with thin curly hair, thin and sparse eyebrow, xerosis cutis, susceptibility to hyperthermia from childhood, hypohidrosis, sharp/sparse/absent teeth, saddle nose, prominent forehead, auricle adulation and seizure. He was found to have a normal chromosomal karyotype, and no abnormality was found by Trio-WES. Genome-wide CNV-seq revealed a 341.90 kb deletion at Xq13.1q13.1 (chrX: 68 796 566-69 138 468). As verified by PCR-electrophoresis, the deletion has removed part of the EDA gene. The deletion was derived from his mother with normal hair, mild xerosis cutis, and sparse, decidulated and nail-like teeth. The mother was detected with a heterozygous 242.10 kb deletion at Xq13.1q13.1 (chrX: 68 836 154-69 078 250).

Conclusion: Both the proband and his mother have carried a Xq13.1 microdeletion involving part of the EDA gene. The clinical phenotypes of the mother and the proband were consistent with the clinical characteristics of X-linked recessive HED, for which partial deletion of the EDA gene is probably accountable.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200515-00347DOI Listing
March 2021

Concerns Discussed on Chinese and French Social Media during the COVID-19 Lockdown: Comparative Infodemiology Study based on Topic Modeling.

JMIR Form Res 2021 Mar 15. Epub 2021 Mar 15.

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, 15 Rue de l'école de médecine, Paris, FR.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, numerous countries, including China and France, have implemented lockdown measures that have been shown to be effective in controlling the epidemic. However, little is known about the impact of these measures on the population as expressed on social media from different cultural contexts.

Objective: To assess and compare the evolution of the topics discussed on Chinese and French social media during the COVID-19 lockdown.

Methods: We extracted posts containing "COVID-19"- or "lockdown"-related keywords in the most commonly used micro-blogging social media platforms, i.e., Weibo (China) and Twitter (France), from one week before to the lifting of the lockdown. A topic model was applied independently for three periods: pre-lockdown, early lockdown and mid-to-late lockdown, to assess the evolution of the topics discussed on Chinese and French social media.

Results: 6 395, 23 422 and 141 643 Chinese Weibo messages, and 34 327, 119 919, and 282 965 French tweets were extracted in the pre-lockdown, early lockdown and mid-to-late lockdown periods in China and France, respectively. Four categories of topics were discussed in a continuously evolving way in all three periods: epidemic news and everyday life, scientific information, public measures and solidarity & encouragement. The most represented category over all periods in both countries was epidemic news and everyday life. Scientific information was far more discussed on Weibo than in French tweets. Misinformation circulated through social media in both countries; however, it was more concerned with the virus and epidemic in China, whereas it was more concerned with the lockdown measures in France. Regarding public measures, more criticisms were identified in French tweets than on Weibo. Advantages and data privacy concerns regarding tracing apps were also addressed in French tweets. All these differences were explained by the different use of social media, the different timeline of the epidemic and the different cultural context in these two countries.

Conclusions: This study is the first to compare the social media content in Eastern and Western countries during the unprecedented COVID-19 lockdown. Using general COVID-19-related social media data, our results describe common and different public reactions, behaviors and concerns in China and France, covering even the fine topics identified in prior studies focusing on specific interests. We believe our study can help characterize country-specific public needs and appropriately address them during an outbreak.

Clinicaltrial:
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http://dx.doi.org/10.2196/23593DOI Listing
March 2021

3D printing of chemical-empowered tendon stem/progenitor cells for functional tissue repair.

Biomaterials 2021 Feb 15;271:120722. Epub 2021 Feb 15.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China; China Orthopaedic Regenerative Medicine (CORMed), Hangzhou, China. Electronic address:

Tendon injuries are the leading cause of chronic debilitation to patients. Tendon stem/progenitor cells (TSPCs) are potential seed cells for tendon tissue engineering and regeneration, but TSPCs are prone to lose their distinct phenotype in vitro and specific differentiation into the tenocyte lineage is challenging. Utilizing small molecules in an ex vivo culture system may be a promising solution and can significantly improve the therapeutic applications of these cells. Here, by using an image-based, high-throughput screening platform on small molecule libraries, this study established an effective stepwise culture strategy for TSPCs application. The study formulated a cocktail of small molecules which effected proliferation, tenogenesis initiation and maturation phases, and significantly upregulated expression of various tendon-related genes and proteins in TSPCs, which were demonstrated by high-throughput PCR, ScxGFP reporter assay and immunocytochemistry. Furthermore, by combining small molecule-based culture system with 3D printing technology, we embedded living, chemical-empowered TSPCs within a biocompatible hydrogel to engineer tendon grafts, and verified their enhanced ability in promoting functional tendon repair and regeneration both in vivo and in situ. The stepwise culture system for TSPCs and construction of engineered tendon grafts can not only serve as a platform for further studies of underlying molecular mechanisms of tenogenic differentiation, but also provide a new strategy for tissue engineering and development of novel therapeutics for clinical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120722DOI Listing
February 2021

siRNA-mediated Eppin testicular silencing causes changes in sperm motility and calcium currents in mice.

Reprod Biol 2021 Feb 16;21(2):100485. Epub 2021 Feb 16.

Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Suzhou, China. Electronic address:

Epididymal protease inhibitor (EPPIN) is differentially expressed in the reproductive tissues (such as testicles, outlet tubes, epididymis, vas deferens, and seminal vesicles). Its critical role in sperm function and male reproduction has shed light on EPPIN as a candidate target for male contraceptive vaccines. In this study, we endeavored to further reveal the mechanism through which EPPIN exerts its function. We created a mouse model of reduced Eppin expression by microinjecting small interfering RNA targeting Eppin expression into seminiferous tubules of mice. This mouse model was then used to explore the effects of low Eppin expression on sperm function, which was assessed by Computer Assisted Semen Analysis and patch clamp recording of T-type Ca current in spermatogenic cells. We found that the sperm motility significantly declined when Eppin was downregulated. Further investigation demonstrated that Eppin downregulation significantly affected T-type Ca currents and messenger RNA expression of three subtypes of T-type Ca channels in spermatogenic cells. These findings indicate that low Eppin gene expression induces decreased T-type Ca currents and mRNA expression, which in turn results in the reduced sperm motility.
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http://dx.doi.org/10.1016/j.repbio.2021.100485DOI Listing
February 2021

A versatile chitosan nanogel capable of generating AgNPs in-situ and long-acting slow-release of Ag for highly efficient antibacterial.

Carbohydr Polym 2021 Apr 16;257:117636. Epub 2021 Jan 16.

College of Materials Science and Engineering, Nanjing Tech University, Nanjing, 211816, PR China. Electronic address:

Development of multifunctional antibacterial agent with long-lasting antibacterial activity and biofilm ablation performance is significant for the effective treatment of bacterial infections. Here, by utilizing the electrostatic interaction between sulfonated chitosan (SCS) and Ag and chitosan (CS), and the sodium borohydride reduction method, a versatile antibacterial agent (AgNPs@CS/SCS) capable of generating silver nanoparticles (AgNPs) in-situ and long-acting slow-release Ag was developed. AgNPs@CS/SCS has a good physiological stability and can long-acting slow-release of Ag due to the pH-dependent Ag release behavior of AgNPs. Noteworthy, AgNPs@CS/SCS can exert both excellent short- and long-term antibacterial and biofilm ablation activity. Importantly, it also exhibits superior antibacterial activity in the treatment of implant infections, accompanied by good biocompatibility. Together, this study suggest that AgNPs@CS/CSC is indeed a versatile antibacterial agent, and is expected to provide an effective treatment modality for implant infections in the clinic settings.
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http://dx.doi.org/10.1016/j.carbpol.2021.117636DOI Listing
April 2021

Population-based outcome of muscle-invasive bladder cancer following radical cystectomy: who can benefit from adjuvant chemotherapy?

Transl Androl Urol 2021 Jan;10(1):356-373

Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: The benefit of adjuvant chemotherapy remains controversial in muscle-invasive bladder cancer (MIBC) after radical cystectomy. The present study's primary objective was to construct a predictive tool for the reasonable application of adjuvant chemotherapy.

Methods: All of the patients analyzed in the present study were recruited from the Surveillance Epidemiology and End Results program between 2004 and 2015. Propensity score matching (PSM) was used to reduce inherent selection bias. Cox proportional hazards models were applied to identify the independent prognostic factors of overall survival (OS) and cancer-specific survival (CSS), which were further used to construct prognostic nomogram and risk stratification systems to predict survival outcomes. The prognostic nomogram's performance was assessed by concordance index (C-index), receiver-operating characteristic (ROC) and calibration curves. Decision curve analysis (DCA) was performed to evaluate the clinical net benefit of the prognostic nomogram.

Results: A total of 6,384 patients with or without adjuvant chemotherapy were included after PSM. Several independent predictors for OS and CSS were identified and further applied to establish a nomogram for 3-, 5- and 10-year, respectively. The nomogram showed favorable discriminative ability for the prediction of OS and CSS, with a C-index of 0.709 [95% confidence interval (CI): 0.699-0.719] for OS and 0.728 (95% CI: 0.718-0.738) for CSS. ROC and calibration curves showed satisfactory consistency. The DCA revealed high clinical positive net benefits of the prognostic nomogram. The different risk stratification systems showed that adjuvant chemotherapy resulted in better OS (P<0.001) and CSS (P<0.001) than without adjuvant chemotherapy for high-risk patients; while the OS (P=0.350) and CSS (P=0.260) for low-risk patients were comparable.

Conclusions: We have constructed a predictive model and different risk stratifications for selecting a population that could benefit from postoperative adjuvant chemotherapy. Adjuvant chemotherapy was found to be beneficial for high-risk patients, while low-risk patients should be carefully monitored.
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http://dx.doi.org/10.21037/tau-20-960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844522PMC
January 2021

Adaptive responses to gene targeting in hematopoietic stem cells reveal a proliferative mechanism evasive to mTOR inhibition.

Proc Natl Acad Sci U S A 2021 Jan 21;118(1). Epub 2020 Dec 21.

Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229;

The mechanistic target of rapamycin (mTOR) is a central regulator of cell growth and an attractive anticancer target that integrates diverse signals to control cell proliferation. Previous studies using mTOR inhibitors have shown that mTOR targeting suppresses gene expression and cell proliferation. To date, however, mTOR-targeted therapies in cancer have seen limited efficacy, and one key issue is related to the development of evasive resistance. In this manuscript, through the use of a gene targeting mouse model, we have found that inducible deletion of in hematopoietic stem cells (HSCs) results in a loss of quiescence and increased proliferation. Adaptive to the loss, HSCs increase chromatin accessibility and activate global gene expression, contrary to the effects of short-term inhibition by mTOR inhibitors. Mechanistically, such genomic changes are due to a rewiring and adaptive activation of the ERK/MNK/eIF4E signaling pathway that enhances the protein translation of RNA polymerase II, which in turn leads to increased gene expression, allowing the HSCs to thrive despite the loss of a functional mTOR pathway. This adaptive mechanism can also be utilized by leukemia cells undergoing long-term mTOR inhibitor treatment to confer resistance to mTOR drug targeting. The resistance can be counteracted by MNK, CDK9, or c-Myc inhibition. These results provide insights into the physiological role of mTOR in mammalian stem cell regulation and implicate a mechanism of evasive resistance in the context of mTOR targeting.
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http://dx.doi.org/10.1073/pnas.2020102118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817152PMC
January 2021

Oligosaccharides from Polygonatum Cyrtonema Hua: Structural characterization and treatment of LPS-induced peritonitis in mice.

Carbohydr Polym 2021 Mar 10;255:117392. Epub 2020 Nov 10.

State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China; Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China. Electronic address:

Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) for the first time. Structure characterized using FT-IR, MALDI-TOF-MS, NMR, AFM, and TEM, indicated that PFOS was graminan-type fructan with a degree of polymerization ranging from 5 to 10. A murine model of lipopolysaccharide (LPS)-induced peritonitis was used to evaluate the in vivo anti-inflammatory and lung protective efficacy of PFOS. The result shown that pretreatment with PFOS (1.0 mg/mL) in peritonitis-induced mice could significantly inhibit the level of pro-inflammatory cytokines (TNF-α, IL-1β) in serum (P < 0.001), increase mice survival rate from 12.5 % to 54 % (P < 0.05), and alleviated lung injury through ameliorating the damage of the pulmonary cellular architecture and reducing inflammatory monocyte accumulation in lung tissue. This effect of oligosaccharides could explain the traditional usage of P. cyrtonema as a tonic medicine for respiratory problems and it could be used as a potential natural ingredient with anti-inflammatory activity.
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http://dx.doi.org/10.1016/j.carbpol.2020.117392DOI Listing
March 2021

Magnetic-Field-Assisted Cellular Osteogenic Differentiation on Magnetic Zinc Ferrite Coatings via MEK/ERK Signaling Pathways.

ACS Biomater Sci Eng 2020 12 9;6(12):6864-6873. Epub 2020 Nov 9.

The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Combining an external stimulus and stimuli-responsive biomaterials can regulate cellular behaviors. In this paper, a magneto-responsive zinc ferrite (ZnFeO) coating was designed to gain insight into the preosteoblasts behaviors and osteogenic differentiation mechanism under a static magnetic field (SMF). ZnFeO coatings with distinct magnetization (low, medium, and high magnetizations) were prepared by being annealed at different temperatures. Cellular biology experiments indicated that all ZnFeO coatings with the assistance of SMF could promote the early proliferation (3 days) and osteogenic differentiation of MC3T3-E1 cells. Among different ZnFeO samples, low and medium magnetization of ZnFeO showed a higher osteogenesis-related gene expression (Runx2, Col-I, OCN) than that of high magnetization ZnFeO under SMF, while cellular adhesion and proliferation cultured on different ZnFeO samples presented insignificant differences. Molecular biology tests showed that the combination of ferromagnetic ZnFeO and SMF could significantly improve the expression level of α2β1 integrin and p-ERK. However, the addition of the inhibitor U0126 sharply reduced the expression level of p-ERK, which indicated that α2β1 integrin-mediated MEK/ERK signaling pathways play a key role in SMF-assisted cellular osteogenic differentiation over ZnFeO coatings. This work provides an attractive strategy to enhance cellular osteogenic differentiation in a remote-control way, which exhibited enormous potential in the field of bone tissue repair and regeneration.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01087DOI Listing
December 2020

Polarization behavior of bone marrow-derived macrophages on charged P(VDF-TrFE) coatings.

Biomater Sci 2021 Feb;9(3):874-881

School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Zhejiang University, Hangzhou 310027, China.

The immune response of bone implants is closely related to the interaction between macrophages and biomaterial surfaces. In this work, the polarization behavior of mouse bone marrow-derived macrophages (BMDMs), including their morphology and expression of phenotypic markers, genes and cytokines, on charged surfaces with different potential intensities was systematically explored. We found that the charged surface could effectively promote BMDM polarization, and a higher potential intensity was conducive to the upregulation of the polarization of BMDMs into the M2 phenotype. Based on the analysis of the signaling pathways involved in integrins (αMβ2 and α5β1) and the potassium ion channel (Kv1.3), a possible underlying mechanism revealed that the integrin originated signaling pathways could more dominantly regulate macrophage polarization to the M2 phenotype. The present work therefore demonstrates that the surface charge, as a physicochemical property of material surfaces, could effectively regulate macrophage polarizations, which may provide an immunoregulation view for the surface design of biomaterials.
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http://dx.doi.org/10.1039/d0bm01604gDOI Listing
February 2021

Zwitterionic Hydrogel-Impregnated Membranes with Polyamide Skin Achieving Superior Water/Salt Separation Properties.

ACS Appl Mater Interfaces 2020 Oct 16;12(43):49192-49199. Epub 2020 Oct 16.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

Support-free nonporous membranes have emerged as a new material platform for osmotic pressure-driven processes due to its insusceptibility to internal concentration polarization (ICP). Herein, we demonstrate high-performance membranes of zwitterionic hydrogels impregnated in porous membranes with a skin layer of highly cross-linked polyamides on both sides prepared by gel-liquid interfacial polymerization (GLIP). Such a configuration eliminates the pores and thus ICP, while the thin polyamide layer provides high salt rejection but negligible resistance to the water transport compared with the hydrogels. The polyamide skin layers are characterized using scanning electron microscopy and atomic force microscopy. The effect of the hydrogel compositions and polyamide formation conditions on the water/salt separation properties is thoroughly investigated. Example membranes show water permeance and salt rejection comparable to state-of-the-art commercial forward osmosis membranes and essentially no ICP.
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http://dx.doi.org/10.1021/acsami.0c13363DOI Listing
October 2020

Grafting Activated Graphene Oxide Nanosheets onto Ultrafiltration Membranes Using Polydopamine to Enhance Antifouling Properties.

ACS Appl Mater Interfaces 2020 Oct 8;12(42):48179-48187. Epub 2020 Oct 8.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

Graphene oxide (GO) nanosheets are negatively charged and exhibit excellent antifouling properties. However, their hydrophilicity makes it challenging for their grafting onto membrane surfaces to improve antifouling properties for long-term underwater operation. Herein, we demonstrate a versatile approach to covalently graft GO onto ultrafiltration membrane surfaces in aqueous solutions at ≈22 °C. The membrane surface is first primed using dopamine and then reacted with activated GO (aGO) containing amine-reactive esters. The aGO grafting improves the membrane surface hydrophilicity without decreasing water permeance. When the membranes are challenged with 1.0 g/L sodium alginate in a constant-flux crossflow system, the aGO grafting increases the critical flux by 20% and reduces the fouling rate by 63% compared with the pristine membrane. The modified membranes demonstrate stability for 48 h operation and interval cleanings using NaOH solutions.
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http://dx.doi.org/10.1021/acsami.0c14210DOI Listing
October 2020

Association of plasma chromium with metabolic syndrome among Chinese adults: a case-control study.

Nutr J 2020 09 23;19(1):107. Epub 2020 Sep 23.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Backgroud: Chromium has been suggested playing a role in alleviating diabetes, insulin resistance and lipid anomalies, but the effect on metabolic syndrome (MetS) in humans remains controversial.

Methods: We conducted a matched case-control study in a Chinese population, involving 2141 MetS cases and 2141 healthy controls, which were 1:1 matched by age (±2 years) and sex. Plasma chromium was measured by inductively coupled plasma mass spectrometry.

Results: Plasma chromium levels were lower in MetS group than in control group (mean: 4.36 μg/L and 4.66 μg/L, respectively, P < 0.001), and progressively decreased with the number of MetS components (P for trend < 0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence intervals) for MetS across increasing quartiles of plasma chromium levels were 1 (reference), 0.84 (0.67-1.05), 0.76 (0.61-0.95), and 0.62 (0.49-0.78), respectively (P for trend < 0.001). For the components of MetS (high waist circumference, high triglycerides and high blood glucose), the odds ratios (95% confidence intervals) of the highest quartiles were 0.77 (0.61-0.95), 0.67 (0.55-0.80), and 0.53 (0.44-0.64), respectively (P for trend < 0.05).

Conclusions: Our results indicated that plasma chromium levels were inversely associated with MetS in Chinese adults. The association may be explained by the relations between plasma chromium levels and high waist circumference, and the triglycerides and blood glucose levels.
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http://dx.doi.org/10.1186/s12937-020-00625-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513538PMC
September 2020

Impact of phosphorus fertilizer level on the yield and metabolome of goji fruit.

Sci Rep 2020 09 4;10(1):14656. Epub 2020 Sep 4.

College of Horticulture, Northwest A & F University, Yangling, 712000, Shan Xi, China.

Goji (Lycium barbarum L.) is a highly medicinal value tree species. The yield and nutritional contents of goji fruit are significant affected by fertilizer level. In this study, we analyzed the yield and nutritional contents change of goji fruit, which planted in pot (vermiculite:perlite, 1:2, v:v) in growth chamber under P0 (32.5 g/per tree), P1 (65 g/per tree), and P2 (97.5 g/per tree). Meanwhile, we utilized an integrated Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) to analysis of the response of the metabolome in goji fruit to phosphorus level. The results show that the yield of goji fruits had strongly negative correlation with phosphorus level, especially in the third harvest time. The amino acids, flavonoids, polysaccharides, and betaine contents of goji fruits in the first harvest time had obvious correlated with the level of phosphorus level. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the impact of different phosphorus fertilizer levels on each group mainly involved the biosynthesis of flavonoids. The results provide new insights into the theoretical basis of the relationship between the nutritional contents of goji fruits and phosphorus fertilizer level.
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http://dx.doi.org/10.1038/s41598-020-71492-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474080PMC
September 2020

Interference with circBC048201 inhibits the proliferation, migration, and invasion of bladder cancer cells through the miR-1184/ITGA3 axis.

Mol Cell Biochem 2020 Nov 12;474(1-2):83-94. Epub 2020 Aug 12.

Department of Urology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, 310003, Zhejiang, China.

The abnormal expression of circular RNA (circRNA) is bound up with the progress of various human cancers. This study aimed to reveal the potential role and mechanism of circBC048201 in the proliferation, migration, and invasion of bladder cancer cells. Quantitative real-time PCR was performed to detect the expression of circBC048201. Cell Counting Kit-8, colony formation, and transwell migration and invasion assays were used to confirm the in vitro functions of circBC048201. Western blot, RNA pull-down, and dual-luciferase reporter gene experiments were performed to study the potential mechanism. circBC048201 was abnormally highly expressed in bladder cancer tissues and cells, and the interference with circBC048201 inhibited bladder cancer cell proliferation, migration, and invasion. From the potential mechanism analysis, our data suggested that circBC048201 and miR-1184, miR-1184 and ITGA3 could bind to each other, and the interference with circBC048201 repressed bladder cancer cell proliferation, migration, and invasion through the miR-1184/ITGA3 axis. In summary, our results showed that circBC048201 was abnormally highly expressed in bladder cancer tissues and cells, and the interference with circBC048201 inhibited the proliferation, migration, and invasion of bladder cancer cells through the miR-1184/ITGA3 axis.
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http://dx.doi.org/10.1007/s11010-020-03835-2DOI Listing
November 2020

COVID-19-Associated Coagulopathy: An Exacerbated Immunothrombosis Response.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620943293

Department of Hematology and Oncology, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.

Since the onset of the global pandemic in early 2020, coronavirus disease 2019 (COVID-19) has posed a multitude of challenges to health care systems worldwide. In order to combat these challenges and devise appropriate therapeutic strategies, it becomes of paramount importance to elucidate the pathophysiology of this illness. Coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is characterized by a dysregulated immune system and hypercoagulability. COVID-associated coagulopathy (CAC) was recognized based on profound d-dimer elevations and evidence of microthrombi and macrothrombi, both in venous and arterial systems. The underlying mechanisms associated with CAC have been suggested, but not clearly defined. The model of immunothrombosis illustrates the elaborate crosstalk between the innate immune system and coagulation. The rendering of a procoagulant state in COVID-19 involves the interplay of many innate immune pathways. The SARS-CoV2 virus can directly infect immune and endothelial cells, leading to endothelial injury and dysregulation of the immune system. Activated leukocytes potentiate a procoagulant state via release of intravascular tissue factor, platelet activation, NETosis, and inhibition of anticoagulant mechanisms. Additional pathways of specific relevance in CAC include cytokine release and complement activation. All these mechanisms have recently been reported in COVID-19. Immunothrombosis provides a comprehensive perspective of the several synergistic pathways pertinent to the pathogenesis of CAC.
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http://dx.doi.org/10.1177/1076029620943293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401047PMC
August 2020

Urinary exfoliated tumor single-cell metabolomics technology for establishing a drug resistance monitoring system for bladder cancer with intravesical chemotherapy.

Med Hypotheses 2020 Oct 13;143:110100. Epub 2020 Jul 13.

Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China. Electronic address:

Bladder cancer is one of the most common urogenital malignant with a rising incidence rate all over the world. Non-muscle invasive bladder cancer (NMIBC) has the characteristics of high recurrence rate and easy progression after receiving transurethral tumor resection combined with intravesical chemotherapy. The intrinsic or/and acquired drug resistance is mainly causing this poor outcome. The continuing advances in metabolomics and single-cell mass spectrometry have been considered as the key to promoting clinical precision medicine. Urinary exfoliated tumor cells (UETCs) carry the first-hand biological information on the genesis and progression of primary bladder cancer. Therefore, we hypothesized that the establishment of a drug resistance monitoring system for bladder cancer with intravesical chemotherapy based on UETCs single-cell metabolomics technology has a broad application prospect.
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http://dx.doi.org/10.1016/j.mehy.2020.110100DOI Listing
October 2020

Enhancing osteogenic differentiation of BMSCs on high magnetoelectric response films.

Mater Sci Eng C Mater Biol Appl 2020 Aug 17;113:110970. Epub 2020 Apr 17.

School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Zhejiang University, Hangzhou 310027, China. Electronic address:

High performance of biomaterial surfaces provides a sound basis to mediate cellular growth behavior. In this work, we attempted to incorporate both positive and negative magnetostriction particles of CoFeO (CFO) and TbDyFe alloy (TD) into piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for forming high magnetoelectric effect films, on which osteogenic differentiation could be dynamically mediated by a magnetic-field-induced surface potential (φ).The negatively poled film with TD/CFO volume ratio of 1:4 (1T4C) showed a highest magnetoelectric effect with φ of -171 mV at 2800 Oe. Compared with CFO/P(VDF-TrFE) and TD/P(VDF-TrFE) films, the φ increased about 213% and 173%, respectively. This could result from that P(VDF-TrFE) dipole domains receive a larger off-axial stress caused by the distribution characteristic of CFO and TD in P(VDF-TrFE), consequently to facilitate P(VDF-TrFE) dipole domain rearrangement. When MSCs were cultured on 1T4C film for 7 or 14 days, the magnetic actuation was setup to begin at the 4th or 8th day after the culture. The 7-day osteogenic differentiation was hardly affected for magnetic actuation at 4th day, moreover, the 14-day differentiation was significantly enhanced for magnetic actuation at 8th day. The enhancement appears just at a relatively late period of the cell growth, probably because the cells need a steady change in cell membrane potential to disassociate pairs of β-catenin and E-cadherin and activate osteogenic-related signaling pathway. This work could provide an alternative way to promote performance for magnetoelectric materials, and get insight into understanding of interactions of surface potential with cells.
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http://dx.doi.org/10.1016/j.msec.2020.110970DOI Listing
August 2020

Grafting polysiloxane onto ultrafiltration membranes to optimize surface energy and mitigate fouling.

Soft Matter 2020 Jun 26;16(21):5044-5053. Epub 2020 May 26.

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.

Conventional approaches to mitigate fouling of membrane surfaces impart hydrophilicity to the membrane surface, which increases the water of hydration and fluidity near the surface. By contrast, we demonstrate here that tuning the membrane surface energy close to that of the dispersive component of water surface tension (21.8 mN m) can also improve the antifouling properties of the membrane. Specifically, ultrafiltration (UF) membranes were first modified using polydopamine (PDA) followed by grafting of amine-terminated polysiloxane (PSi-NH). For example, with 2 g L PSi-NH coating solution, the obtained coating layer contains 53% by mass fraction PSi-NH and exhibits a total surface energy of 21 mN m, decreasing the adsorption of bovine serum albumin by 44% compared to the unmodified membrane. When challenged with 1 g L sodium alginate in a constant-flux crossflow system, the PSi-NH-grafted membrane exhibits a 70% lower fouling rate than the pristine membrane at a water flux of 110 L (m h) and good stability when cleaned with NaOH solutions.
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http://dx.doi.org/10.1039/d0sm00551gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679028PMC
June 2020

Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer.

J Immunother Cancer 2020 05;8(1)

Laboratory of Integrative Immunology and cancerology, INSERM, University of Paris, Cordeliers Research centre, Immunomonitoring Platform, Laboratory of Immunology, AP-HP (Assistance Publique-Hôpitaux de Paris) Hôpital Européen Georges Pompidou, Paris, France

Background: New and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction.

Methods: Immunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538).

Results: Optical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II-III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes.

Conclusion: IS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.
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http://dx.doi.org/10.1136/jitc-2019-000272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253006PMC
May 2020

Cx43 and AKAP95 regulate G1/S conversion by competitively binding to cyclin E1/E2 in lung cancer cells.

Thorac Cancer 2020 06 27;11(6):1594-1602. Epub 2020 Apr 27.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.

Background: This study aimed to overexpress or silence connexin 43 (Cx43) and A-kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes.

Methods: The study mainly used Western blot analysis and Co-immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1-S phase was explored with qualitative and quantitative analysis.

Results: The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion.

Conclusions: This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS-2B cells were treated with PDGF-BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration.
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http://dx.doi.org/10.1111/1759-7714.13435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262948PMC
June 2020

Ultra-efficient Antibacterial System Based on Photodynamic Therapy and CO Gas Therapy for Synergistic Antibacterial and Ablation Biofilms.

ACS Appl Mater Interfaces 2020 May 5;12(20):22479-22491. Epub 2020 May 5.

College of Materials Science and Engineering, Nanjing Tech University, 30 Puzhu Road, 211816 Nanjing, P. R. China.

In recent years, with the emergence of various kinds of drug-resistant bacteria, existing antibiotics have become inefficient in killing these bacteria, and the formation of biofilms has further weakened the therapeutic effect. More problematically, the massive use and abuse of antibiotics have caused severe side effects. Thus, the development of ultra-efficient and safe antibacterial systems is urgently needed. Herein, a photodynamic therapy (PDT)-driven CO-controlled delivery system (Ce6&CO@FADP) is developed for synergistic antibacterial and ablation biofilms. Ce6&CO@FADP is constructed using a fluorinated amphiphilic dendritic peptide (FADP) and physically loaded with Ce6 and CORM-401. After efficiently entering the bacteria, Ce6&CO@FADP can rapidly release CO intracellularly by the massive consumption of the HO generated during the PDT process, without affecting the generation of singlet oxygen (O). As such, the combination of CO and O exerts notable synergistic antibacterial and biofilm ablation effects both in vitro and in vivo (including subcutaneous bacterial infection and biofilm catheter models) experiments. More importantly, all biosafety assessments suggest the good biocompatibility of Ce6&CO@FADP. Together, these results reveal that Ce6&CO@FADP is an efficient and safe antibacterial system, which has essential application prospects for the treatment of bacterial infections and ablation of biofilms in vivo.
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http://dx.doi.org/10.1021/acsami.0c01967DOI Listing
May 2020

Plasma miR-1273g-3p acts as a potential biomarker for early Breast Ductal Cancer diagnosis.

An Acad Bras Cienc 2020 22;92(1):e20181203. Epub 2020 Apr 22.

School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, People's Republic of China.

Circulating miRNAs presenting in plasma in a stable manner have been demonstrated their potential role as a promising biomarkers in many human diseases, such as Alzheimer's disease, melanoma and ovarian carcinoma. However, few circulating miRNAs could be used for breast ductal cancer diagnosis. Here, we identified miR-1273g-3p as a biomarker for detecting breast ductal cancer. We detected miR-1273g-3p levels in the plasma of 39 sporadic breast ductal cancer patients and 40 healthy donors by Stem-loop Quantitative Real-time PCR (qRT-PCR). The results showed the plasma miR-1273g-3p level were significantly up-regulated in breast ductal cancer patients compared with healthy donors (p=0.0139). Receiver operating characteristic (ROC) curve also revealed the significantly diagnostic ability of miR-1273g-3p in patients (p=0.0414). In addition, the plasma level of miR-1273g-3p was closely related to IIIB-IIIC TNM stage. We also confirmed the higher expression level of miR-1273g-3p in breast cancer cell lines MCF-7 (4.872±0.537) than normal breast cells (Hs 578Bst). Taken together, miR-1273g-3p could represent as a potential biomarker for early breast ductal cancer diagnosis.
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http://dx.doi.org/10.1590/0001-3765202020181203DOI Listing
April 2020

Diagnosis support systems for rare diseases: a scoping review.

Orphanet J Rare Dis 2020 04 16;15(1):94. Epub 2020 Apr 16.

Centre de Recherche des Cordeliers, INSERM, Université de Paris, Sorbonne Université, F-75006, Paris, France.

Introduction: Rare diseases affect approximately 350 million people worldwide. Delayed diagnosis is frequent due to lack of knowledge of most clinicians and a small number of expert centers. Consequently, computerized diagnosis support systems have been developed to address these issues, with many relying on rare disease expertise and taking advantage of the increasing volume of generated and accessible health-related data. Our objective is to perform a review of all initiatives aiming to support the diagnosis of rare diseases.

Methods: A scoping review was conducted based on methods proposed by Arksey and O'Malley. A charting form for relevant study analysis was developed and used to categorize data.

Results: Sixty-eight studies were retained at the end of the charting process. Diagnosis targets varied from 1 rare disease to all rare diseases. Material used for diagnosis support consisted mostly of phenotype concepts, images or fluids. Fifty-seven percent of the studies used expert knowledge. Two-thirds of the studies relied on machine learning algorithms, and one-third used simple similarities. Manual algorithms were encountered as well. Most of the studies presented satisfying performance of evaluation by comparison with references or with external validation. Fourteen studies provided online tools, most of which aimed to support the diagnosis of all rare diseases by considering queries based on phenotype concepts.

Conclusion: Numerous solutions relying on different materials and use of various methodologies are emerging with satisfying preliminary results. However, the variability of approaches and evaluation processes complicates the comparison of results. Efforts should be made to adequately validate these tools and guarantee reproducibility and explicability.
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http://dx.doi.org/10.1186/s13023-020-01374-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164220PMC
April 2020

Host-Enhanced Phenyl-Perfluorophenyl Polar-π Interactions.

J Am Chem Soc 2020 04 13;142(16):7356-7361. Epub 2020 Apr 13.

Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

Phenyl-perfluorophenyl polar-π interactions have been revisited for the design and fabrication of functional supramolecular systems. The relatively weak associative interactions (Δ ≈ -1.0 kcal/mol) have limited their use in aqueous self-assembly to date. Herein, we propose a strategy to strengthen phenyl-perfluorophenyl polar-π interactions by encapsulation within a synthetic host, thus increasing the binding affinity to Δ= -15.5 kcal/mol upon formation of heteroternary complexes through social self-sorting. These heteroternary complexes were used as dynamic, yet strong, cross-linkers in the fabrication of supramolecular gels, which exhibited excellent viscoelasticity, stretchability, self-recovery, self-healing, and energy dissipation. This work unveils a general approach to exploit host-enhanced polar-π interactions in the design of robust aqueous supramolecular systems.
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http://dx.doi.org/10.1021/jacs.0c02275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181256PMC
April 2020

A novel Z-scheme porous g-CN nanosheet/AgPO photocatalyst decorated with N-doped CDs for high efficiency removal of antibiotics.

Dalton Trans 2020 Apr;49(16):5205-5218

College of Chemical Engineering, Huaqiao University, Xiamen, 361021, China.

A number of porous g-C3N4 nanosheet/Ag3PO4/NCDs (PCNNS/AP/NCDs) with little amounts of Ag3PO4 were synthesized via an in situ sedimentation-calcination method. The PCNNS/AP/NCDs photocatalyst exhibited excellent photocatalytic performance for the photocatalytic degradation of tetracycline (TC) under visible light irradiation at a removal rate of 90.5% in 40 min. The study of the reaction kinetics of the as-prepared samples was in accordance with the pseudo-second-order kinetics, with the correlation coefficient (R2) being greater than 0.9776. Meanwhile, the photocatalyst was capable of degrading ciprofloxacin (CIP), and showed good performance even under actual water conditions with natural sunlight irradiation, indicating that the photocatalyst has wide practical applications. In addition, the photocatalytic performance and the XRD and FTIR spectra showed no obvious changes even after four photocatalytic degradation cycles, which revealed the high stability of the PCNNS/AP/NCDs photocatalyst. Furthermore, the possible degradation pathways of TC and the possible Z-scheme mechanism were proposed with ˙O2- and h+ as the main active species contributing to photocatalytic degradation. The results provide a novel insight into the fabrication of Z-scheme PCNNS/AP/NCDs and introduce them as an efficient visible-light-responsive photocatalyst for use in practical applications.
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http://dx.doi.org/10.1039/d0dt00408aDOI Listing
April 2020

SAP97 polymorphisms associated with early onset Parkinson's disease.

Neurosci Lett 2020 05 26;728:134931. Epub 2020 Mar 26.

Maternal and Children's Health Research Institute, Shunde Maternal and Children's Hospital, Guangdong Medical University, Foshan, 528300, China; Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China. Electronic address:

Objective: To investigate the relationship between SAP97 genetic polymorphisms and sporadic Parkinson's disease (PD) in Han Chinese population with the expectation of offering genetic data for the early prevention and treatment of the disease.

Methods: In this study, we genotyped single-nucleotide polymorphisms (SNPs) (rs3915512 and rs9843659) in theSAP97 gene in 317 patients with PD and 317 healthy-matched controls in a Han Chinese population through the improved multiplex ligation detection reaction (imLDR) technique. Then, we analyzed the association of each SNP, alone or in combination, with risk or age of onset of PD.

Results: The SAP97 rs3915512 and rs9843659 polymorphisms were not associated with the risk of PD. However, the minor allele of the rs3915512 and rs9843659 were significantly more common in PD patients with an early age of onset. Additionally, significant differences in the distribution of the onset age of the PD among different genotypes of the rs9843659 polymorphism. The CA haplotype was significantly related to early onset PD.

Conclusions: Our data are the first to suggest that the SAP97 SNPs rs3915512 and rs9843659 and the CA haplotype may be significantly associated with early onset PD in China.
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http://dx.doi.org/10.1016/j.neulet.2020.134931DOI Listing
May 2020

CDCA5 functions as a tumor promoter in bladder cancer by dysregulating mitochondria-mediated apoptosis, cell cycle regulation and PI3k/AKT/mTOR pathway activation.

J Cancer 2020 10;11(9):2408-2420. Epub 2020 Feb 10.

Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.

Bladder cancer (BC) is one of the most prevalent cancers worldwide and has high rates of relapse and progression. Cell division cycle associated 5 (CDCA5), a substrate of the anaphase-promoting complex, was reported to be upregulated in several types of cancer; however, the function of CDCA5 in BC remains unclear. In this study, we observed that BC tissues had higher levels of CDCA5 expression than adjacent normal tissues. We also found that high CDCA5 expression in patients was associated with poor survival rates. An in vitro study showed that knockdown of CDCA5 in T24 and 5637 cells reduced cell proliferation and induced apoptosis in T24 and 5637 cells, while overexpression of CDCA5 in UMUC3 cells caused the opposite effects. In an additional experiment, we found that CDCA5 promoted cell proliferation by upregulating two key cell cycle factors, cell division cycle protein 2 (CDC2) and cyclin B1, and by activating the PI3K/AKT/mTOR pathway. Furthermore, CDCA5 regulate cancer cell apoptosis through the mitochondrial apoptosis pathway. In conclusion, CDCA5 plays a pivotal role in the proliferation of BC cells. A better understanding of CDCA5 may provide new insights into its role as a therapeutic target for BC.
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http://dx.doi.org/10.7150/jca.35372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066009PMC
February 2020

Chronic acrylamide exposure induced glia cell activation, NLRP3 infl-ammasome upregulation and cognitive impairment.

Toxicol Appl Pharmacol 2020 04 5;393:114949. Epub 2020 Mar 5.

Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China. Electronic address:

Acrylamide (ACR), a potential neurotoxin, is present in diet and drinking water. Dietary exposure contributes to cognitive impairment, but relevant mechanism information is limited. Neuroinflammation plays important roles in neurodegenerative disorders. This study aimed to explore whether chronic acrylamide exposure induced neuronal lesions, microglial activation, NLRP3 inflammasome-mediated neuroinflammation and cognitive impairment. For this purpose, 36 Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12/group) and maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. Chronic exposure to ACR caused gait abnormality and cognitive dysfunction, which was associated with neuronal lesions, decrease in synapse associated proteins including synapsin I (SYN1), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), neurogenesis suppression as shown by reduced brain derived neurotrophic factor (BDNF) and doublecortin (DCX) in the hippocampus and frontal cortex. ACR stimulated glial proliferation and microglial activation by increasing GFAP, Iba-1, Iba-1CD68 positive cells. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3, caspase-1 and increased pro-IL-1β and IL-1β. ACR elevated the protein P62 to suppress NLPR3 inflammasome cleavage. Inflammatory cytokines including TNF-α, IL-6 and Cox-2 were also significantly increased after NF-κB pathway activation, which aggravated neuronal lesions and caused memory deficits. This work helped to propose the possible mechanism of chronic exposure of ACR-induced neurotoxicity.
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http://dx.doi.org/10.1016/j.taap.2020.114949DOI Listing
April 2020