Publications by authors named "Weiqing Liu"

95 Publications

Hyperglycemia accelerates inflammaging in the gingival epithelium through inflammasomes activation.

J Periodontal Res 2021 Mar 2. Epub 2021 Mar 2.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background And Objective: Diabetes accelerates inflammaging in various tissue with an increase in senescent cell burden and senescence-associated secretory phenotype (SASP) secretion, which is a significant cause of tissue dysfunction and contributes to the diabetic complications. Recently, inflammasomes are thought to contribute to inflammaging. Here, utilizing diabetic models in vivo and in vitro, we investigated the potential association between hyperglycemia-induced inflammaging and gingival tissue dysfunction and the mechanism underlying inflammasome-associated inflammaging.

Materials And Methods: Gingival epithelium and serum were collected from control and diabetic patients and mice. The expression of p16, p21, and inflammasomes in the gingival epithelium, SASP factors in serum, and the molecular factors associated with gingival epithelial barrier function were assessed. Human oral keratinocyte (HOK) was stimulated with normal and high glucose, and pre-treated with Z-YVAD-FMK (Caspase-1 inhibitor) prior to evaluating cellular senescence, SASP secretion, and inflammasome activation.

Results: In vivo, hyperglycemia significantly elevated the local burden of senescent cells in the gingival epithelium and SASP factors in the serum and simultaneously reduced the expression levels of Claudin-1, E-cadherin, and Connexin 43 in the gingival epithelium. Interestingly, the inflammasomes were activated in the gingival epithelium. In vitro, high glucose-induced the inflammaging in HOK, and blocking inflammasome activation through inhibiting Caspase-1 and glucose-induced inflammaging.

Conclusions: Hyperglycemia accelerated inflammaging in the gingival epithelium through inflammasomes activation, which is potentially affiliated with a decline in the gingival epithelial barrier function in diabetes. Inflammasomes-related inflammaging may be the crucial mechanism underlying diabetic periodontitis and represents significant opportunities for advancing prevention and treatment options.
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http://dx.doi.org/10.1111/jre.12863DOI Listing
March 2021

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

JAMA Psychiatry 2021 Mar;78(3):320-330

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood.

Objective: To explore the genetic basis of BD in the Han Chinese population.

Design, Setting, And Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020.

Main Outcomes And Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association.

Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956).

Conclusions And Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.3738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711567PMC
March 2021

A kinetic/thermodynamic study of transparent co-adsorbents and colored dye molecules in visible light based on microgravimetric quartz-crystal microbalance on porous TiO films for dye-sensitized solar cells.

Phys Chem Chem Phys 2020 Dec;22(46):26828-26837

Jiangxi Engineering Laboratory for Optoelectronics Testing Technology, Nanchang Hangkong University, Nanchang 330063, P. R. China.

In this study, a quartz crystal microbalance (QCM) in situ method is used to study the kinetic and thermodynamic processes of the adsorption of ruthenium-based dyes (N719, N3, N749), and the co-adsorbent chenodeoxycholic acid (CDCA) on the TiO2 film surface. The results of the kinetic studies show that the adsorption rate of N749 is slightly higher than the other two dyes, and the adsorption rate of CDCA is more sensitive to temperature change. The adsorption mechanism of the dye and CDCA on the surface of TiO2 can be reasonably inferred based on the result of the activation energy. The isotherm adsorption model studies show that the ratio of the number of surface molecules (296 K) is n(N719) : n(N3) : n(N749) : n(CDCA) = 0.69 : 1.48 : 0.50 : 1. The Keq value of CDCA is about two orders of magnitude smaller than that of all the dye molecules, which indicates that the adsorption strength of CDCA is much weaker than that of the dye molecules. Thermodynamic studies show that the adsorption reaction is an endothermic reaction. The ΔS is ΔS(N3 = 143.11 J mol-1) > ΔS(N719 = 112.72 J mol-1) > ΔS(N749 = 109.43 J mol-1) > ΔS(CDCA = 96.14 J mol-1). The Gibbs free energy ΔG is negative, and indicates that the adsorption reaction of the four molecules on the surface of the TiO2 film is spontaneous. The results of this paper show that the tedious and lengthy experimental process of the traditional method can be simplified by QCM. In addition, the development of this study provides a certain theoretical and experimental basis for future studies on the interaction mechanism between dyes and co-adsorbents.
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http://dx.doi.org/10.1039/d0cp05403hDOI Listing
December 2020

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations.

Nat Commun 2020 11 5;11(1):5596. Epub 2020 Nov 5.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases.
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http://dx.doi.org/10.1038/s41467-020-19360-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645772PMC
November 2020

[Corrigendum] FNDC3B promotes epithelial-mesenchymal transition in tongue squamous cell carcinoma cells in a hypoxic microenvironment.

Oncol Rep 2020 Aug 25. Epub 2020 Aug 25.

Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

During the preparation of the above article, the authors inadvertently selected an incorrect pair of data panels for Fig. 5B. Essentially, in the published version of Fig. 5B, the images were presented incorrectly for the NC migration and KD#3 migration and invasion data panels associated with the TSCCA cell Transwell assay experiments. Furthermore, in Fig. 7A, the GAPDH control bands were erroneously selected for the figure. Figs. 5 and 7 as they should have appeared in the Journal are shown opposite, incorporating the correct data for Figs. 5B and 7A. These errors did not affect either the results or the conclusions of this work. The authors all agree to this Corrigendum, and thank the Editor of Oncology Reports for allowing them to have the opportunity to present their corrected data. Furthermore, the authors apologize to the readership for any inconvenience these errors may have caused. [the original article was published in Oncology Reports 39: 1853‑1859, 2018; DOI: 10.3892/or.2018.6231].
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http://dx.doi.org/10.3892/or.2020.7744DOI Listing
August 2020

Experimental investigation on the long-term behaviour of prefabricated timber-concrete composite beams with steel plate connections.

Constr Build Mater 2021 Jan 1;266:120892. Epub 2020 Oct 1.

College of Civil Engineering, Nanjing Tech University, Nanjing 211816, PR China.

This paper presents the results of long-term experiments performed on three timber-concrete composite (TCC) beams. An innovative fabricated steel plate connection system, which consists of screws and steel plates embedded in concrete slabs, was adopted in the TCC beam specimens. The adopted shear connection can provide dry-type connection for TCC beams. Steel plates were embedded in concrete slabs while the concrete slab was constructed in factories. The timber beam and concrete slab can be assembled together using screws at the construction site. In this experimental programme, the beam specimens were subjected to constant loading for 613 days in indoor uncontrolled environments. The influence of long-term loading levels and the number of shear connections on the long-term performance of TCC beams was investigated and discussed. The mid-span deflection, timber strain, and interface relative slip at the positions of both connections and beam-ends were recorded throughout the long-term tests. It was found the long-term deflection of the TCC beam increased by approximately 60% while the long-term loads were doubled. Under the influence of the variable temperature and humidity, the TCC specimens with 8 shear connections showed slighter fluctuations compared with the TCC beam with 6 shear connections. In the 613-day observation period, the maximum deflection increment recorded was 6.56 mm for the specimen with eight shear connections and 20% loading level. A rheological model consisting of two Kelvin bodies was employed to fit the curves of creep coefficients. The final deflections predicted of all specimens at the end of 50-year service life were 2.1~2.7 times the initial deflections caused by the applied loads. All beam specimens showed relative small increments in mid-span deflection, strain and relative slip over time without any degradations, demonstrating the excellent long-term performance of TCC beams using the innovative steel plate connection system, which is also easily fabricated.
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http://dx.doi.org/10.1016/j.conbuildmat.2020.120892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527798PMC
January 2021

Endogenous GDF11 regulates odontogenic differentiation of dental pulp stem cells.

J Cell Mol Med 2020 10 26;24(19):11457-11464. Epub 2020 Aug 26.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Dental stem cell-based tooth regeneration is the futuristic treatment for missing teeth. Growth differentiation factor 11 (GDF11), a novel member of the TGF-beta superfamily, has been reported to play a critical role in regulating stem cell differentiation. However, the role of endogenous GDF11 during dental stem cell differentiation remains unknown. Here, we have shown that GDF11 was highly expressed in dental pulp tissues in both mouse and human. Knockdown of endogenous GDF11 in human dental pulp stem cells (hDPSCs) led to comparable proliferation and migration but attenuated odontogenic differentiation as evidenced by alkaline phosphatase and Alizarin Red S staining. In addition, transcriptional levels of odontogenic-related genes were significantly down-regulated according to real-time polymerase chain reaction. Mechanistically, we performed RNA sequencing analysis and found that silencing of endogenous GDF11 compromised the process of ossification and osteoblast differentiation, especially down-regulated transcription expression of Wnt pathway-specific genes. Immunofluorescence staining also showed diminished β-catenin expression and nuclei accumulation after knockdown of endogenous GDF11 in hDPSCs. In summary, our results suggested that endogenous GDF11 positively regulate odontogenic differentiation of hDPSCs through canonical Wnt/β-catenin signalling pathway.
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http://dx.doi.org/10.1111/jcmm.15754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576269PMC
October 2020

A Support Vector Machine Model Predicting the Risk of Duodenal Cancer in Patients with Familial Adenomatous Polyposis at the Transcript Levels.

Biomed Res Int 2020 16;2020:5807295. Epub 2020 Jun 16.

Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Objective: Familial adenomatous polyposis (FAP) is one major type of inherited duodenal cancer. The estimate of duodenal cancer risk in patients with FAP is critical for selecting the optimal treatment strategy.

Methods: Microarray datasets related with FAP were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified by FAP vs. normal samples and FAP and duodenal cancer vs. normal samples. Furthermore, functional enrichment analyses of these differentially expressed genes were performed. A support vector machine (SVM) was performed to train and validate cancer risk prediction model.

Results: A total of 196 differentially expressed genes were identified between FAP compared with normal samples. 177 similarly expressed genes were identified both in FAP and duodenal cancer, which were mainly enriched in pathways in cancer and metabolic-related pathway, indicating that these genes in patients with FAP could contribute to duodenal cancer. Among them, Cyclin D1, SDF-1, AXIN, and TCF were significantly upregulated in FAP tissues using qRT-PCR. Based on the 177 genes, an SVM model was constructed for prediction of the risk of cancer in patients with FAP. After validation, the model can accurately distinguish FAP patients with high risk from those with low risk for duodenal cancer.

Conclusion: This study proposed a cancer risk prediction model based on an SVM at the transcript levels.
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http://dx.doi.org/10.1155/2020/5807295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315318PMC
April 2021

Experimental Investigation on the Fire Resistance of Glued-In Rod Timber Joints with Heat Resistant Modified Epoxy Resin.

Materials (Basel) 2020 Jun 16;13(12). Epub 2020 Jun 16.

School of Civil Engineering, Suzhou University of Science and Technology, Suzhou 215011, China.

This paper presents an experimental evaluation of the fire resistance of glued-in rod timber joints using epoxy resin, with and without modification. A heat-resistant modified resin was designed by adding inorganic additives into the epoxy resin, aiming to improve the heat resistance. Joints that were made using the modified epoxy resin at room temperature showed a bearing capacity comparable to those with commercial epoxy resin. Twenty-one joint specimens with the modified epoxy resin and six with a commercial epoxy resin were tested in a fire furnace to evaluate the fire resistance. The main failure mode was the pull-out of the rod, which is typical in fire tests of this type of joints. As to the effects of the test parameters, this study considered the effects of adhesive types, sectional sizes, stress levels, and fireproof coatings. The test results showed that the fire resistance period of a joint can be evidently improved by modifying the resin and using the fireproof coating, as the improvements reached 73% and 35%, respectively, compared with the joint specimens with commercial epoxy resin. It was also found that, for all specimens, the fire resistance period decreased with an increase in the stress level and increased with an increase in the sectional sizes.
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http://dx.doi.org/10.3390/ma13122731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345967PMC
June 2020

Effect and Molecular Mechanisms of Collateral Vessel Growth Mediated by Activation of Transient Receptor Potential Vanilloid Type 1.

J Vasc Res 2020 11;57(4):185-194. Epub 2020 Jun 11.

Department of Anatomy & Histology & Embryology, Kunming Medical University, Kunming, China,

Information on the function of transient receptor potential vanilloid 1 (TRPV1) in arteriogenesis is limited. We aimed to verify whether TRPV1 is involved in collateral vessel growth in rat hind limbs and elucidate the possible subcellular action mechanisms. Adult Sprague Dawley rats were chosen to establish the hind limb ischemic model and treatment with capsaicin. Angiographies were performed, and tissue was isolated for immunohistochemistry. In vitro, rat aortic endothelial cells (RAECs) were treated with capsaicin and antagonist capsazepine. The RAEC proliferation was determined, and the protein and mRNA levels of Ca2+-dependent transcription factors were assessed. In vivo, the collateral vessels exhibited positive outward remodeling characterized by enhanced inflammatory cell/macrophage accumulation in the adventitia and activated cell proliferation in all layers of the vascular wall and elevated endothelial NO synthetase expression in the rats with hind limb ligation. In RAECs, TRPV1 activation-induced Ca2+-dependent transcriptional factors, nuclear factor of activated T cells 1, calsenilin and myocyte enhancer factor 2C increase, and augmented RAEC proliferation could be a subcellular mechanism for TRPV1 in endothelial cells and ultimately contribute to collateral vessel growth. TRPV1, a novel candidate, positively regulates arteriogenesis, meriting further studies to unravel the potential therapeutic target leading to improved collateral vessel growth for treating ischemic diseases.
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http://dx.doi.org/10.1159/000506516DOI Listing
September 2020

Author Correction: Chronic Kidney Disease Impairs Bone Defect Healing in Rats.

Sci Rep 2020 Jun 8;10(1):9482. Epub 2020 Jun 8.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-65651-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280222PMC
June 2020

In-vivo histocompatibility and osteogenic potential of biodegradable PLDLA composites containing silica-based bioactive glass fiber.

J Biomater Appl 2020 07 31;35(1):59-71. Epub 2020 Mar 31.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The purpose of this two-year study was to evaluate the histocompatibility and osteogenic properties of a composite material consisting of poly(l--d,l lactide) (PLDLA) and silica-based bioactive glass fibers in vivo. PLDLA and PLDLA/silica-based bioactive glass fibers pins were implanted into the erector spinae muscles and femurs of beagles. Muscle and bone tissue samples were harvested 6, 12, 16, 26, 52, 78, and 104 weeks after implantation. Histology analysis was used to assess the histocompatibility, angiogenesis, and bone-implant contact. Micro-computed tomography was used to evaluate bone formation around the pins. Immunohistochemistry and western blotting revealed the expression level of the osteogenesis-related proteins. Addition of bioactive glass was demonstrated to possess better histocompatibility and reduce the inflammatory reactions in vivo. Moreover, PLDLA/silica-based bioactive glass fibers pins were demonstrated to promote angiogenesis and increase osteogenesis-related proteins expression, and thus played a positive role in osteogenesis and osseointegration after implantation. Our findings indicated that a composite of PLDLA and silica-based bioactive glass fiber is a promising biodegradable material for clinical use.
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http://dx.doi.org/10.1177/0885328220911598DOI Listing
July 2020

Ubiquitin-Specific Protease 34 Inhibits Osteoclast Differentiation by Regulating NF-κB Signaling.

J Bone Miner Res 2020 08 8;35(8):1597-1608. Epub 2020 Apr 8.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The ubiquitination and deubiquitination enzymes ensure the stability and proper function of most cellular proteins. Disturbance of either enzyme compromises tissue homeostasis. We recently have identified that the ubiquitin-specific protease 34 (USP34) contributes to bone formation by promoting osteogenic differentiation of mesenchymal stem cells. However, its role in bone resorption, which couples bone formation, remains unknown. Here we show that knockdown of Usp34 promotes osteoclast differentiation of RAW264.7 cells. Conditional knockout of Usp34 in bone marrow-derived macrophages (BMMs) or in osteoclasts leads to elevated osteoclast function and low bone mass. Mechanically, we identify that USP34 restrains NF-κB signaling by deubiquitinating and stabilizing the NF-κB inhibitor alpha (IκBα). Overexpression of IκBα represses osteoclastic hyperfunction of Usp34-deficient RAW264.7 cells. Collectively, our results show that USP34 inhibits osteoclastogenesis by regulating NF-κB signaling. © 2020 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.4015DOI Listing
August 2020

Mechanical and degradative properties of PLDLA biodegradable pins with bioactive glass fibers in a beagle model.

Biomed Mater 2020 03 27;15(3):035010. Epub 2020 Mar 27.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.

The present study aimed to evaluate the mechanical and degradative properties of poly(L-co-D,L-lactic acid)/silicate bioactive glass fibers (PLDLA/SGFs) composite pins in vivo. Both PLDLA and PLDLA/SGFs pins were inserted into the erector spinae muscles and femurs of beagle dogs and were harvested 6, 12, 16, 26, 52, 78, and 104 weeks after insertion. Bone formation around the pins was evaluated by micro-computed tomography. Mechanical properties were measured by the shear strength test. Thermogravimetric analysis, differential scanning calorimetry, and gel permeation chromatography were used to assess the degradation of these materials. The surface and cross-sectional morphology of both pins were observed using a scanning electron microscope. The experimental data demonstrated that PLDLA/SGFs pins can support new bone formation due to the influence of bioactive glass fibers. PLDLA/SGFs composite pins had higher initial shear strength and were relatively stable for at least 26 weeks. The addition of bioactive glass fibers accelerated the degradation rate of the composite pins. Thus, PLDLA/SGFs composite pins have promising potential for bone fixation applications.
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http://dx.doi.org/10.1088/1748-605X/ab772dDOI Listing
March 2020

An in situ exchange mechanism for dye molecules and cations at the nano-semiconductor film/electrolyte interface.

Phys Chem Chem Phys 2020 Feb;22(7):3784-3788

School of International Education, Nanchang Hangkong University, Nanchang 330063, P. R. China.

This communication uses electrochemical quartz crystal microbalance (EQCM) in combination with the potentiostatic method to study the in situ exchange mechanism for dye molecules and cations on the nano-film surface under a constant potential. The relationship between dye molecule desorption mass and charge was analyzed. A theoretical model was established to obtain the important parameters of cation exchange number and apparent valence electron number during dye desorption, and the microscopic desorption mechanism of the dye is further revealed.
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http://dx.doi.org/10.1039/c9cp06288bDOI Listing
February 2020

Growth differentiation factor 11 impairs titanium implant healing in the femur and leads to mandibular bone loss.

J Periodontol 2020 09 14;91(9):1203-1212. Epub 2020 Feb 14.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Background: Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor-β superfamily, has recently been suggested as an anti-aging factor that declines with age in the bloodstream, and restoration of the youthful level by administration of its recombinant protein could reverse age-related dysfunctions. However, its effects on titanium implant osseointegration and mandibular bone during aging remain unknown.

Methods: Two-month-old and 18-month-old C57BL male mice were given daily intraperitoneal injections of recombinant GDF11 (rGDF11) or vehicle for 6 weeks. Experimental titanium implants were inserted into femurs on the fourth week. Inhibition of GDF11 function was achieved by GDF11 antibody. Implant-bearing femurs were subjected to histomorphometric analysis and biomechanical evaluation. Mandibles were scanned with micro-CT and decalcified for histological measurements.

Results: In both young adult and aged mice, supraphysiologic GDF11 leads to a significantly decreased bone-to-implant contact ratio (BIC) and peri-implant bone volume/total volume (BV/TV) at the histologic level and reduced resistance at the biomechanical level, indicating weakened implant fixation. Moreover, rGDF11 administration resulted in less trabecular bone volume and thinner cortical thickness in the mandible, which was further compromised in the old animals. In contrast, inhibition of GDF11 improved peri-implant bone healing in old mice.

Conclusions: Rather than functioning as a rejuvenating factor, exogenous GDF11 negatively affects not only titanium implant healing but also mandibular bone in both young and old mice. In contrast, neutralization of endogenous GDF11 has positive effects on implant fixation in aged mice.
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http://dx.doi.org/10.1002/JPER.19-0247DOI Listing
September 2020

Identification of 12 cancer types through genome deep learning.

Sci Rep 2019 11 21;9(1):17256. Epub 2019 Nov 21.

China National GeneBank, BGI-Shenzhen, Shenzhen, 518116, China.

Cancer is a major cause of death worldwide, and an early diagnosis is required for a favorable prognosis. Histological examination is the gold standard for cancer identification; however, large amount of inter-observer variability exists in histological diagnosis. Numerous studies have shown cancer genesis is accompanied by an accumulation of harmful mutations, potentiating the identification of cancer based on genomic information. We have proposed a method, GDL (genome deep learning), to study the relationship between genomic variations and traits based on deep neural networks. We analyzed 6,083 samples' WES (Whole Exon Sequencing) mutations files from 12 cancer types obtained from the TCGA (The Cancer Genome Atlas) and 1,991 healthy samples' WES data from the 1000 Genomes project. We constructed 12 specific models to distinguish between certain type of cancer and healthy tissues, a total-specific model that can identify healthy and cancer tissues, and a mixture model to distinguish between all 12 types of cancer based on GDL. We demonstrate that the accuracy of specific, mixture and total specific model are 97.47%, 70.08% and 94.70% for cancer identification. We developed an efficient method for the identification of cancer based on genomic information that offers a new direction for disease diagnosis.
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http://dx.doi.org/10.1038/s41598-019-53989-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872744PMC
November 2019

[Design of Paravertebral Muscle Monitoring System Based on Surface Electromyography].

Zhongguo Yi Liao Qi Xie Za Zhi 2019 Sep;43(5):318-321

School of Nanjing University of Aeronautics and Astronautics, Nanjing, 210016.

In order to diagnose and evaluate the human spinal lesions through the paravertebral muscles, a paravertebral muscle monitoring system based on surface EMG signals was designed. The system used surface mount electrodes to obtain the surface myoelectric signal (sEMG) of paravertebral muscle. The signal was filtered and amplified by the conditioning circuit. The signal was collected by the microcontroller NRF52832 and was sent to the mobile APP. After the signal was preprocessed by the wavelet threshold denoising algorithm in APP, the time and frequency characteristics of the sEMG signal reflecting the functional state of the muscle were extracted. The calculated characteristic parameters was displayed in real time in the application interface. The experimental results show that the system meets the design requirements in analog signal acquisition, digital processing of signals and calculation of characteristic parameters. The system has certain application value.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2019.05.002DOI Listing
September 2019

Coexistence of oscillation and quenching states: Effect of low-pass active filtering in coupled oscillators.

Chaos 2019 Jul;29(7):073110

Potsdam Institute for Climate Impact Research, Telegraphenberg, D-14415 Potsdam, Germany.

Effects of a low-pass active filter (LPAF) on the transition processes from oscillation quenching to asymmetrical oscillation are explored for diffusively coupled oscillators. The low-pass filter part and the active part of LPAF exhibit different effects on the dynamics of these coupled oscillators. With the amplifying active part only, LPAF keeps the coupled oscillators staying in a nontrivial amplitude death (NTAD) and oscillation state. However, the additional filter is beneficial to induce a transition from a symmetrical oscillation death to an asymmetrical oscillation death and then to an asymmetrical oscillation state which is oscillating with different amplitudes for two oscillators. Asymmetrical oscillation state is coexisting with a synchronous oscillation state for properly presented parameters. With the attenuating active part only, LPAF keeps the coupled oscillators in rich oscillation quenching states such as amplitude death (AD), symmetrical oscillation death (OD), and NTAD. The additional filter tends to enlarge the AD domains but to shrink the symmetrical OD domains by increasing the areas of the coexistence of the oscillation state and the symmetrical OD state. The stronger filter effects enlarge the basin of the symmetrical OD state which is coexisting with the synchronous oscillation state. Moreover, the effects of the filter are general in globally coupled oscillators. Our results are important for understanding and controlling the multistability of coupled systems.
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http://dx.doi.org/10.1063/1.5093919DOI Listing
July 2019

Immunomodulation of human CD19CD25 regulatory B cells via Th17/Foxp3 regulatory T cells and Th1/Th2 cytokines.

Hum Immunol 2019 Oct 28;80(10):863-870. Epub 2019 Jun 28.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, PR China. Electronic address:

Regulatory B (Breg) cells are a special subset of immunoregulatory cells with unique phenotypes and functions. In this study, human CD19CD25 Breg cells were purified from human peripheral blood. Based on the coculture system of Breg cells and CD4 T cells in vitro, Breg cells were found to promote the increase in regulatory T (Treg) cells while decreasing the number of Th17 cells. Breg cells regulate Treg cells through two processes: cell-cell contact and cytokines. TGF-βsRII, a blocker of transforming growth factor-β (TGF-β), can attenuate the effects of Treg elevation, suggesting that TGF-β is the main cytokine, while Breg cells rather than interleukin-10 (IL-10) regulate the differentiation of Treg cells. However, Th17 cells were mainly regulated by cytokines, without an obvious regulatory effect on cell-cell contacts. Breg cells may regulate Th17 cells by a pathway independent of TGF-β and IL-6. The coculture of Breg cells and CD4 T cells led to changes in the cytokine spectrum, which included significant increases in IL-4, IL-6 and IL-10 but not obvious changes in IL-2, IFN-γ and TNF. The inhibitory effect of Breg cells was weakened by blocking cell-cell contacts in cultures separated with the Transwell chamber because IL-10 decreased while IL-6 increased when compared with cocultured Breg and CD4 T cells. When the IL-10 inhibitor IL-10sRα was added, IL-6 and TNF levels significantly increased, while treatment with the TGF-β inhibitor TGF-βsRII did not result in similar changes, suggesting that IL-10 is an important molecule to inhibit the proinflammatory factors IL-6 and TNF in this culture system.
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http://dx.doi.org/10.1016/j.humimm.2019.05.011DOI Listing
October 2019

Interactome Analyses implicated CAMK2A in the genetic predisposition and pharmacological mechanism of Bipolar Disorder.

J Psychiatr Res 2019 08 25;115:165-175. Epub 2019 May 25.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China; (m)CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. Electronic address:

Bipolar disorder (BPD) is a severe mental illness characterized by fluctuations in mood states, behaviors and energy levels. Growing evidence suggests that genes associated with specific illnesses tend to interact together and encode a tight protein-protein interaction (PPI) network, providing valuable information for understanding their pathogenesis. To gain insights into the genetic and physiological foundation of BPD, we conduct the physical PPI analysis of 184 BPD risk genes distilled from genome-wide association studies and exome sequencing studies. We have identified several hub genes (CAMK2A, HSP90AA1 and PLCG1) among those risk genes, and observed significant enrichment of the BPD risk genes in certain pathways such as calcium signaling, oxytocin signaling and circadian entrainment. Furthermore, while none of the 184 genetic risk genes are "well established" BPD drug targets, our PPI analysis showed that αCaMKII (encoded by CAMK2A) had direct physical PPIs with targets (HRH1, SCN5A and CACNA1E) of clinically used anti-manic BPD drugs, such as carbamazepine. We thus speculated that αCaMKII might be involved in the cellular pharmacological actions of those drugs. Using cultured rat primary cortical neurons, we found that carbamazepine treatment induced phosphorylation of αCaMKII in dose-dependent manners. Intriguingly, previous study showed that CAMK2A heterozygous knockout (CAMK2A) mice exhibited infradian oscillation of locomotor activities that can be rescued by carbamazepine. Our data, in combination with previous studies, provide convergent evidence for the involvement of CAMK2A in the risk of BPD.
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http://dx.doi.org/10.1016/j.jpsychires.2019.05.024DOI Listing
August 2019

Growth differentiation factor 11 inhibits adipogenic differentiation by activating TGF-beta/Smad signalling pathway.

Cell Prolif 2019 Jul 30;52(4):e12631. Epub 2019 Apr 30.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objectives: Growth differentiation factor 11 (GDF11), an emerging secreted member of the TGF-beta superfamily, plays essential roles in development, physiology and multiple diseases; however, its role during adipogenic differentiation and the underlying mechanisms remains poorly understood.

Materials And Methods: Bone marrow-derived human mesenchymal stem cells (hMSCs) and 3T3-L1 pre-adipocytes were induced with adipogenic culture medium supplementing with different concentrations of recombinant GDF11 (rGDF11 0, 10, 50, 100 ng mL ). Oil Red O staining, qRT-PCR analysis, Western blot analysis and immunofluorescence staining were performed to assay adipogenesis.

Results: For both hMSCs and 3T3-L1 pre-adipocytes, the presence of rGDF11 leads to a dose-dependent reduction of intracellular lipid droplet accumulation and suppressed adipogenic-related gene expression. Mechanically, GDF11 inhibits adipogenesis by activating Smad2/3-dependent TGF-beta signalling pathway, and these inhibitory effects could be restored by SB-431542, a pharmacological TGF-beta type I receptor inhibitor.

Conclusions: Taken together, our data indicates that GDF11 inhibits adipogenic differentiation in both hMSCs and 3T3-L1 pre-adipocytes by activating Smad2/3-dependent TGF-beta signalling pathway.
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http://dx.doi.org/10.1111/cpr.12631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668979PMC
July 2019

Compressive Behavior of Composite Concrete Columns with Encased FRP Confined Concrete Cores.

Sensors (Basel) 2019 Apr 15;19(8). Epub 2019 Apr 15.

College of Civil Engineering, Nanjing Tech University, Nanjing 211816, China.

A composite concrete column with encased fiber reinforced polymer (FRP) confined concrete cores (EFCCC) is proposed in this paper. The cross-sectional form of the EFCCC column is composed of several orderly arranged FRP confined concrete cores (FCCCs) surrounding a filled core concrete. This novel composite column has several advantages, such as higher compressive capacity, stronger FRP confinement, and ductile response. The compressive experiment is employed to investigate the compressive behavior of the EFCCC column with deferent parameters, such as outside concrete and stirrups. Test results show that the main failure mode of the EFCCC column with and without an outside concrete or stirrups is tensile fracture of the glass fiber reinforced polymer (GFRP) tubes. Compared to a reinforced concrete (RC) column, the strength and ductility of the EFCCC column was obviously improved by 20% and 500%, respectively. A finite element model (FEM) based on the Drucker-Prager (D-P) was developed that can accurately predict the axial compression behavior of the composite column with FRP confined concrete core. The predicted results obtained by using this FEM have excellent agreement with the experimental results.
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http://dx.doi.org/10.3390/s19081792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515226PMC
April 2019

Axial Compression Behaviours of Pultruded GFRP⁻Wood Composite Columns.

Sensors (Basel) 2019 Feb 13;19(4). Epub 2019 Feb 13.

College of Civil Engineering, Nanjing Tech University, Nanjing 211816, China.

An innovative pultruded fiber reinforced polymer (FRP)⁻wood composite (PFWC) column with a lightweight southern pine wood core confined by outer FRP sheets was manufactured using an improved pultrusion process. Axial compression tests with both ends pinned as boundary conditions were employed to investigate the mechanical performance of such PFWC columns under concentric load. Through experimental investigations, the effects of the slenderness ratio on the failure modes and the axial load bearing capacities of the PFWC columns were evaluated. The failure modes showed that the specimens with a slenderness ratio less than 43.2 failed through compressive failure at junctions on FRP sheets, while those with slenderness ratios larger than 57.6 showed global buckling. Strain responses on specimens with different slenderness ratios are consistent with the observed failure modes. Finite element analysis was carried out to validate the experimental results, and satisfactory agreement was found between the failure modes and load⁻displacement curves. An empirical equation was developed with a new factor taking 0.65 into account to predict the load bearing capacities of the PFWC columns, and good agreement was found.
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http://dx.doi.org/10.3390/s19040755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412685PMC
February 2019

Coronary sinus reducer for the treatment of refractory angina.

Int J Cardiol 2019 02;277:27

Department of Cardiovascular Medicine, The Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan 412000, China.. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2018.09.072DOI Listing
February 2019

Recombinant growth differentiation factor 11 impairs fracture healing through inhibiting chondrocyte differentiation.

Ann N Y Acad Sci 2019 03 21;1440(1):54-66. Epub 2018 Dec 21.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Growth differentiation factor 11 (GDF11), a secreted member of the transforming growth factor-β (TGF-β) superfamily, has been reported to have the capacity to reverse age-related pathologic changes and regulate organ regeneration after injury; however, the role of GDF11 in fracture healing and bone repair is still unclear. Here, we established a fracture model in 12-week-old male mice to observe two healing states: the cartilaginous callus and bony callus formation phases. Our results showed that recombinant GDF11 (rGDF11) injection inhibits cartilaginous callus maturation and hard callus formation, thereby impairing fracture healing in vivo. In vitro, rGDF11 administration inhibited chondrocyte differentiation and maturation by phosphorylating SMAD2/3 protein and inhibiting RUNX2 expression. Notably, inhibition of TGF-β activity by a SMAD-specific inhibitor attenuated GDF11 effects. Thus, our study demonstrates that, rather than acting as a rejuvenating agent, rGDF11 impairs fracture healing by inhibiting chondrocyte differentiation and maturation.
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http://dx.doi.org/10.1111/nyas.13994DOI Listing
March 2019

Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population.

Transl Psychiatry 2018 12 7;8(1):270. Epub 2018 Dec 7.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.

Genetic analyses of psychiatric illnesses, such as bipolar disorder (BPD), have revealed essential information regarding the underlying pathological mechanisms. While such studies in populations of European ancestry have achieved prominent success, understanding the genetic risk factors of these illnesses (especially BPD) in Chinese population remains an urgent task. Given the lack of genome-wide association study (GWAS) of BPD in Chinese population from Mainland China, replicating the previously reported GWAS hits in distinct populations will provide valuable information for future GWAS analysis in Han Chinese. In the present study, we have recruited 1146 BPD cases and 1956 controls from Mainland China for genetic analyses, as well as 65 Han Chinese brain amygdala tissues for mRNA expression analyses. Using this clinical sample, one of the largest Han Chinese BPD samples till now, we have conducted replication analyses of 21 single nucleotide polymorphisms (SNPs) extracted from previous GWAS of distinct populations. Among the 21 tested SNPs, 16 showed the same direction of allelic effects in our samples compared with previous studies; 6 SNPs achieved nominal significance (p < 0.05) at one-tailed test, and 2 additional SNPs showed marginal significance (p < 0.10). Aside from replicating previously reported BPD risk SNPs, we herein also report several intriguing findings: (1) the SNP rs174576 was associated with BPD in our Chinese sample and in the overall global meta-analysis, and was significantly correlated with FADS1 mRNA in diverse public RNA-seq datasets as well as our in house collected Chinese amygdala samples; (2) two (partially) independent SNPs in MAD1L1 were both significantly associated with BPD in our Chinese sample, which was also supported by haplotype analysis; (3) a rare SNP rs78089757 in 10q26.13 region was a genome-wide significant variant for BPD in East Asians, and this SNP was near monomorphic in Europeans. In sum, these results confirmed several significant BPD risk genes. We hope this Chinese BPD case-control sample and the current brain amygdala tissues (with continuous increasing sample size in the near future) will provide helpful resources in elucidating the genetic and molecular basis of BPD in this major world population.
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http://dx.doi.org/10.1038/s41398-018-0337-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286364PMC
December 2018

The Neuropeptide Secretoneurin Exerts a Direct Effect on Arteriogenesis In Vivo and In Vitro.

Anat Rec (Hoboken) 2018 11 5;301(11):1917-1927. Epub 2018 Oct 5.

Department of Anatomy, Histology & Embryology, Kunming Medical University, Kunming, Yunnan, China.

It is well known that nerves modulate the development and remodeling of blood vessels by releasing different neuropeptides and neurotransmitters. Secretoneurin (SN), a neuropeptide located in nerve fibers along blood vessels, acts as a pro-angiogenic agent and induces postnatal vasculogenesis. However, little is known about its involvement in arteriogenesis. In the present study, we tested the hypothesis that SN promotes arteriogenesis in a rat model of hind limb ischemia, as such, we evaluated the effect of this neuropeptide on proliferation and the production of adhesion and chemotaxis molecules in vascular smooth muscle cells (VSMCs), the main component that carries the burden of the transformation of a small arteriole into a large collateral vessel. In vivo, SN-immunoreactive nerve fibers were abundantly distributed in the adventitia of the collateral vessel. Moreover, administration of SN induced cell proliferation in the vascular wall and the infiltration of inflammatory cells/macrophages to promote collateral vessel growth. This was shown by an increased density of arterioles/arteries, together with a well-developed network of collateral vessels, and well-preserved skeletal muscles. In vitro, SN exerted proliferative effects on VSMCs and stimulated these cells to express adhesion molecules. In conclusion, our data demonstrate for the first time that SN acts as a mediator of inflammation, contributing to collateral vessel growth, in addition to directly stimulating cell proliferation in the vascular wall to promote collateral vessel growth in a rat model of hind limb ischemia. Anat Rec, 301:1917-1927, 2018. © 2018 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ar.23929DOI Listing
November 2018

Kinetics of in situ desorption of dye molecules on sensitized TiO nanoparticles in a high concentration solution: ion parasitic adsorption process and mass reference.

Phys Chem Chem Phys 2018 Aug;20(32):20856-20862

Jiangxi Engineering Laboratory for Optoelectronics Testing Technology, Nanchang Hangkong University, Nanchang, 330063, P. R. China.

The reverse process of dye molecule adsorption on the surface of nanoparticles, that is, the desorption process, has long been neglected in the field of dye-sensitized solar cells (DSCs). It is crucial to develop an in situ technology that controls the rate of dye desorption. Meanwhile, controlling the coverage of dye-sensitized films is still a major challenge. The work presented in this paper applies a simple and effective method to study the in situ mass change responses on dye-sensitized TiO2 films over different potential ranges. The result shows that dye molecule desorption is accompanied by the adsorption of ions in solution. Due to this parasitic adsorption process, the frequency responses in the electrochemical quartz crystal microbalance (EQCM) test cannot be completely attributable to dye molecule desorption. We established a new model to eliminate the impact of this parasitic adsorption process. The kinetics of in situ desorption of dye molecules on sensitized TiO2 nanoparticles in a high-concentration solution was studied. We found that the in situ desorption of dye could be described by pseudo-first-order kinetics. The results suggest that the dye in situ desorption rate is dependent on the bias voltage, and the coverage of dye on the surface of TiO2 films can be further controlled. In-depth research of the dye desorption process is theoretically significant to study DSC stability, new dye synthesis and complex interface structures.
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http://dx.doi.org/10.1039/c8cp03059fDOI Listing
August 2018

Further Evidence of an Association between rs1064395 and Bipolar Disorder.

Mol Neuropsychiatry 2018 Jun 17;4(1):30-34. Epub 2018 May 17.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China.

Genome-wide association studies suggest that rs1064395 in the neurocan gene () is a potential risk factor for bipolar disorder (BPD), and further replication analyses in larger independent samples are needed. We herein analyzed rs1064395 in a Han Chinese sample of 1,146 BPD cases and 2,031 controls, followed by a meta-analysis of BPD samples from worldwide populations including a total of 15,318 cases and 91,990 controls. The meta-analysis found that rs1064395 showed a genome-wide significant association with BPD ( = 4.92 × 10, OR = 1.126 for the A allele), although it did not reach the significance level in the Han Chinese sample ( = 0.415, OR = 1.070 for the A allele). We also examined the association between the single nucleotide polymorphisms and major depressive disorder (MDD) given the presumed genetic overlap between BPD and MDD, and rs1064395 was also associated with MDD ( = 0.0068, OR = 1.067 for the A allele) in a meta-analysis of 14,543 cases and 14,856 controls. Our data provide further evidence for the involvement of in the genetic susceptibility to BPD and also implicate its broader role in major mood disorders.
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http://dx.doi.org/10.1159/000488590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032033PMC
June 2018