Publications by authors named "Xing Yang"

425 Publications

A review of the application of machine learning in molecular imaging.

Ann Transl Med 2021 May;9(9):825

Peking University First Hospital, Beijing, China.

Molecular imaging (MI) is a science that uses imaging methods to reflect the changes of molecular level in living state and conduct qualitative and quantitative studies on its biological behaviors in imaging. Optical molecular imaging (OMI) and nuclear medical imaging are two key research fields of MI. OMI technology refers to the optical information generated by the imaging target (such as tumors) due to drug intervention and other reasons. By collecting the optical information, researchers can track the motion trajectory of the imaging target at the molecular level. Owing to its high specificity and sensitivity, OMI has been widely used in preclinical research and clinical surgery. Nuclear medical imaging mainly detects ionizing radiation emitted by radioactive substances. It can provide molecular information for early diagnosis, effective treatment and basic research of diseases, which has become one of the frontiers and hot topics in the field of medicine in the world today. Both OMI and nuclear medical imaging technology require a lot of data processing and analysis. In recent years, artificial intelligence technology, especially neural network-based machine learning (ML) technology, has been widely used in MI because of its powerful data processing capability. It provides a feasible strategy to deal with large and complex data for the requirement of MI. In this review, we will focus on the applications of ML methods in OMI and nuclear medical imaging.
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http://dx.doi.org/10.21037/atm-20-5877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246214PMC
May 2021

Synthesis of KUE-siRNA conjugates for prostate cancer cell-targeted gene silencing.

Chembiochem 2021 Jul 14. Epub 2021 Jul 14.

Peking University First Hospital, Department of Nuclear Medicine, 8 Xishiku Dajie, 100034, Beijing, CHINA.

The delivery of siRNAs to selectively target cells posed a great challenge in RNAi-based cancer therapy. The lack of suitable cell-targeting methods seriously restricted the advance in delivering siRNAs to extrahepatic tissues. Based on prostate-specific membrane antigen (PSMA)-targeting ligands, we here synthesized a series of KUE-siRNA conjugates and verified their effective cell uptake and gene silencing properties in prostate cancers. The results indicated that the KUE-siRNA conjugates could selectively enter PSMA + LNCaP cells, eventually down-regulating the STAT3 expression. Based on post-synthesis modification and receptor mediated endocytosis, this strategy of constructing ligand-siRNA conjugates might provide a general method of siRNA delivery for cell-targeted gene silencing.
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http://dx.doi.org/10.1002/cbic.202100243DOI Listing
July 2021

Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs.

Chem Sci 2021 Jul 17;12(25):8778-8783. Epub 2021 May 17.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University Huaxi District Guiyang 550025 China

4,5-Dihydropyridazinones bearing an aryl substituent at the C6-position are important motifs in drug molecules. Herein, we developed an efficient protocol to access aryl-dihydropyridazinone molecules carbene-catalyzed asymmetric annulation between dinucleophilic arylidene hydrazones and bromoenals. Key steps in this reaction include polarity-inversion of aryl aldehyde-derived hydrazones followed by chemo-selective reaction with enal-derived α,β-unsaturated acyl azolium intermediates. The aryl-dihydropyridazinone products accessed by our protocol can be readily transformed into drugs and bioactive molecules.
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http://dx.doi.org/10.1039/d1sc01891dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246082PMC
July 2021

Early changes to the extracellular space in the hippocampus under simulated microgravity conditions.

Sci China Life Sci 2021 Jun 24. Epub 2021 Jun 24.

Department of Radiology, Peking University Third Hospital, Beijing, 100191, China.

The smooth transportation of substances through the brain extracellular space (ECS) is crucial to maintaining brain function; however, the way this occurs under simulated microgravity remains unclear. In this study, tracer-based magnetic resonance imaging (MRI) and D-mapping techniques were used to image the drainage of brain interstitial fluid (ISF) from the ECS of the hippocampus in a tail-suspended hindlimb-unloading rat model at day 3 (HU-3) and 7 (HU-7). The results indicated that drainage of the ISF was accelerated in the HU-3 group but slowed markedly in the HU-7 group. The tortuosity of the ECS decreased in the HU-3 group but increased in the HU-7 group, while the volume fraction of the ECS increased in both groups. The diffusion rate within the ECS increased in the HU-3 group and decreased in the HU-7 group. The alterations to ISF drainage and diffusion in the ECS were recoverable in the HU-3 group, but neither parameter was restored in the HU-7 group. Our findings suggest that early changes to the hippocampal ECS and ISF drainage under simulated microgravity can be detected by tracer-based MRI, providing a new perspective for studying microgravity-induced nano-scale structure abnormities and developing neuroprotective approaches involving the brain ECS.
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http://dx.doi.org/10.1007/s11427-021-1932-3DOI Listing
June 2021

Soil acidification enhances the mobilization of phosphorus under anoxic conditions in an agricultural soil: Investigating the potential for loss of phosphorus to water and the associated environmental risk.

Sci Total Environ 2021 Jun 19;793:148531. Epub 2021 Jun 19.

University of Wuppertal, School of Architecture and Civil Engineering, Institute of Foundation Engineering, Water- and Waste-Management, Laboratory of Soil- and Groundwater-Management, Pauluskirchstraße 7, 42285 Wuppertal, Germany; Department of Environment, Energy and Geoinformatics, Sejong University, Seoul 05006, Republic of Korea. Electronic address:

Soil redox potential (E) and pH are key parameters regulating the solubility and fate of phosphorus (P). However, the impact of soil acidification on the redox-induced mobilization and speciation of P in soils under a wide range of E values has not been extensively studied. Here, we investigated the mobilization and speciation of P in an acidified agricultural soil at two different pH values (e.g., highly acidic soil; pH = 5.6 and slightly acidic soil; pH = 6.1) compared to the un-acidified soil (control soil; pH = 7.3) under a wide range of E condition (+459 to -281 mV). The impacts of E/pH-dependent changes of Fe-Mn oxides, and dissolved organic (DOC) and inorganic (DIC) carbon on P mobilization and speciation were also investigated using geochemical and spectroscopic (X-ray absorption near edge structure) techniques. The concentrations of dissolved P under anoxic conditions increased up to 69.3% in the highly acidic soil compared with the control soil. The decrease of the Fe-P fraction, the decrease of Ferrihydrite-P speciation, and the strong linear correlation between the dissolved P and Fe (R > 0.85) supports the finding that enhanced P mobilization under anoxic conditions may be attributed to Fe reduction in the highly acidic soil. The concentration of dissolved Fe and P remained low until pH dropped below 6.35 for P and 6.28 for Fe, while a liner increase was found in dissolved Mn accompanying a general trend of pH decrease. This result suggests that the dissolution of reducible Mn under acidic soil conditions was an important factor for enhancing mobilization of dissolved P under anoxic conditions. This trend was due to the low amount of Mn, indirectly speeding up Fe reduction. These results can help to develop management practices to effectively mitigate P export and protect water resources from diffuse P pollution.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148531DOI Listing
June 2021

Molecular PET/CT Profiling of ACE2 Expression In Vivo: Implications for Infection and Outcome from SARS-CoV-2.

Adv Sci (Weinh) 2021 Jun 26:e2100965. Epub 2021 Jun 26.

Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research Evaluation of Radiopharmaceuticals (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, 100142, China.

Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID-19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin-converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first-in-human translational ACE2 imaging of healthy volunteers and a SARS-CoV-2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID-19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS-CoV-2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS-CoV-2 entry receptor, to noninvasively monitor organs impacted by the COVID-19.
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http://dx.doi.org/10.1002/advs.202100965DOI Listing
June 2021

Tip estimation approach for concentric tube robots using 2D ultrasound images and kinematic model.

Med Biol Eng Comput 2021 Jun 22. Epub 2021 Jun 22.

Department of Electronic and Electrical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.

Concentric tube robot (CTR) is an efficient approach for minimally invasive surgery (MIS) and diagnosis due to its small size and high dexterity. To manipulate the robot accurately and safely inside the human body, tip position and shape information need to be well measured. In this paper, we propose a tip estimation method based on 2D ultrasound images with the help of the forward kinematic model of CTR. The forward kinematic model can help to provide a fast ultrasound scanning path and narrow the region of interest in ultrasound images. For each tube, only three scan positions are needed by combining the kinematic model prediction as prior knowledge. After that, the curve fitting method is used for its shape reconstruction, while its tip position can be estimated based on the constraints of its structure and length.7 This method provides the advantage that only three scan positions are needed for estimating the tip of each telescoping section. Moreover, no structure modification is needed on the robot, which makes it an appropriate approach for existing flexible surgical robots. Experimental results verified the feasibility of the proposed method and the tip estimation error is 0.59 mm. Graphical abstract In this paper, we propose a tip estimation method based on 2D Ultrasound images with the help of the forward kinematic model of CTR. The forward kinematic model can help to provide a fast Ultrasound scanning path and narrow the region of interest in Ultrasound images. For each tube, only three scan positions are needed by combining the kinematic model prediction as prior knowledge. After that, the curve fitting method is used for its shape reconstruction, while its tip position can be estimated based on the constraints of its structure and length.
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http://dx.doi.org/10.1007/s11517-021-02369-zDOI Listing
June 2021

A norbisabolane and an arabitol benzoate from Talaromyces marneffei, an endophytic fungus of Epilobium angustifolium.

Fitoterapia 2021 Jun 1;153:104948. Epub 2021 Jun 1.

School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050,PR China; The Provincial Education Key Laboratory of Screening, Evaluation and Advanced Processing of Traditional Chinese Medicine and Tibetan Medicine, School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, PR China.

A norbisabolane and an arabitol benzoate, Talaromarnine A (1), Talaromarnine B (2), together with eight known compounds were obtained from cultures of Talaromyces marneffei, an endophytic fungus of Epilobium angustifolium. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra, and their absolute configuration was determined by single-crystal X-ray diffraction and molecular computation. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but no compounds exhibited significant activities.
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http://dx.doi.org/10.1016/j.fitote.2021.104948DOI Listing
June 2021

Simplified Method of Microcontact Force Measurement by Using Micropressure Sensor.

Micromachines (Basel) 2021 May 4;12(5). Epub 2021 May 4.

The State Key Laboratory of Precision Measurement Technology and Instrumentation, Department of Precision Instrument, Tsinghua University, Beijing 100084, China.

Microcontact force measurement is widely applied in micro/nano manufacturing, medicine and microelectromechanical systems. Most microcontact force measurements are performed by using mass comparators, nano-indenter and precision electronic balance, and weighing sensors. However, these instruments have a complex structure and high cost. Nevertheless, the rapid development of microsensor technology provides a new, simple and low-cost approach for microcontact force measurement. In this study, we present a method of microcontact force measurement by using micropressure sensors and study the relationship amongst the microcontact force, output voltage and contact position of the sensor. We use a microcapacitance pressure sensor as an example, then we perform a simulation calculation and construct a microcontact force experiment system to verify the simulation results. The experimental and simulation results are consistent. In addition, an equation that describes the relationship amongst the microcontact force, output voltage and contact position of the sensor is obtained. Based on this simple and low-cost method, we build a micro-manipulation system, which indicates that the micropressure sensors can be used to measure microcontact force in various applications easily and cost-effectively. Furthermore, it is considerably relevant to research and application in this field.
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http://dx.doi.org/10.3390/mi12050515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147840PMC
May 2021

Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-κB signaling pathway.

Bioorg Chem 2021 Aug 27;113:104978. Epub 2021 May 27.

Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China. Electronic address:

Osteoarthritis (OA) is a chronic disease featured by joint hyperplasia, deterioration of articular cartilage, and progressive degeneration. Abnormal expression of microRNAs (miRNAs) has been found to be implicated in the pathological process of OA. In this study, the role of miR-361-5p transferred by exosomes derived from human bone mesenchymal stem cells (hBMSCs) in OA was investigated. The expression of Asp-Glu-Ala-Asp-box polypeptide 20 (DDX20) and miR-361-5p in interleukin-1β (IL-1β)-treated chondrocytes was determined by reverse transcription quantitative polymerase chain reaction. DDX20 was knocked down by transfection of short hairpin RNA targeting DDX20, and the effects of DDX20 downregulation on IL-1β-induced damage of chondrocytes were detected. The interaction between DDX20 and miR-361-5p was tested by luciferase report assay. hBMSCs-derived exosomes loaded with miR-361-5p were co-incubated with chondrocytes followed by detection of cell viability, proliferation and inflammatory response. An OA rat model was established to further explore the role of miR-361-5p in vivo. Western blot, luciferase reporter and immunofluorescence staining assays were used to evaluate the activation of the nuclear factor kappa-B (NF-κB) signaling pathway. We found that DDX20 was upregulated, while miR-361-5p was underexpressed in IL-1β-treated chondrocytes. Downregulation of DDX20 inhibits levels of matrix metalloproteinases (MMPs) and suppresses inflammation induced by IL-1β. Mechanistically, miR-361-5p was verified to directly target DDX20. In addition, hBMSC-derived exosomes-transferred miR-361-5p alleviates chondrocyte damage and inhibits the NF-κB signaling pathway via targeting DDX20. Inhibition of NF-κB signaling reverses the effect of overexpressed DDX20 on IL-1β-induced chondrocyte damage. Moreover, exosomal miR-361-5p alleviates OA damage in vivo. Overall, hBMSC-derived exosomal miR-361-5p alleviates OA damage by targeting DDX20 and inactivating the NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.bioorg.2021.104978DOI Listing
August 2021

18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in atrial fibrillation: a pilot prospective study.

Eur Heart J Cardiovasc Imaging 2021 May 29. Epub 2021 May 29.

Department of Nuclear Medicine, Beijing Chaoyang Hospital, Capital Medical University, 8th Gongtinanlu Rd, Chaoyang District, Beijing 100020, China.

Aims: This prospective study explored relevant factors and clinical significance of atrial 18F-fluorodeoxyglucose (FDG) uptake in patients with atrial fibrillation (AF).

Methods And Results: One hundred AF patients underwent baseline FDG imaging prior to radiofrequency catheter ablation (RFCA). Of those, 30 subjects underwent additional FDG imaging at 3 months post-RFCA. Voltage mapping of the left atrium was analysed as a voltage score. Patients who received RFCA were followed for 26 months (17-31 months) to assess recurrence. At baseline FDG imaging, 74% of patients with persistent AF (PsAF) and 24% of patients with paroxysmal AF showed increased atrial FDG uptake. The prevalence was higher in the right atrium (49%) than in the left atrium (15%, P < 0.001) or left atrial appendage (21%, P < 0.001). Multivariate analysis demonstrated that PsAF and elevated B-type natriuretic peptide (BNP) were related to enhanced right atrial (RA) activity, and increased epicardial adipose tissue (EAT) activity was predictive of left atrial (LA) activity. LA activity was inversely associated with voltage score, while increased FDG uptake in the right atrium was predictive of successful AF termination by RFCA. Atrial FDG activities decreased significantly post-RFCA, but none of the FDG parameters were predictive of AF recurrence.

Conclusions: Enhanced RA activity was associated with elevated BNP level, whereas LA activity was related to the increased activity of EAT and inversely correlated with LA fibrosis. Increased RA activity was predictive of successful AF termination by RFCA in PsAF patients.
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http://dx.doi.org/10.1093/ehjci/jeab088DOI Listing
May 2021

Visualizing Tumors in Real Time: A Highly Sensitive PSMA Probe for NIR-II Imaging and Intraoperative Tumor Resection.

J Med Chem 2021 06 28;64(11):7735-7745. Epub 2021 May 28.

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Owing to the complex anatomical structure, precise resection of a tumor while maintaining adjacent tissue is a challenge in radical prostatectomy for prostate cancer (PCa). Optical imaging in near-infrared window II (NIR-II) is a promising technology for intraoperative guidance, whereas there is no available probe for PCa yet. In this article, a novel probe () bearing two prostate-specific membrane antigen (PSMA) binding motifs was developed, displaying excellent optical properties (λ = 1092 nm) and ultrahigh affinity ( = 80 pM) toward PSMA. The tumor was visualized with high resolution (tissue-to-normal tissue ratio = 7.62 ± 1.05) and clear margin by NIR-II imaging using in a mouse model. During the tumor resection, residual tumors missed by visible inspection were detected by the real-time imaging. Overall, displayed excellent performance in delineating the tumor margin and detecting residual tumors, demonstrating promising potential for precise PCa tumor resection in clinical practice.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00444DOI Listing
June 2021

GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling.

Cancer Lett 2021 Aug 21;514:90-102. Epub 2021 May 21.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan, 650203, China. Electronic address:

Effective treatment regimens for triple-negative breast cancer (TNBC) are relatively scarce due to a lack of specific therapeutic targets. Epidermal growth factor receptor (EGFR) signaling is highly active in TNBC and is associated with poor prognosis. Most EGFR antagonists, which significantly improve outcome in lung and colon cancer, have shown limited clinical effects in breast cancer. However, limiting EGFR expression in TNBC is a potential strategy for improving the clinical efficacy of EGFR antagonists. Here, we found that the gamma-aminobutyric acid type A receptor π subunit (GABRP), as a membrane protein enriched in TNBC stem cells, interacted with EGFR and significantly sustained its expression, resulting in stemness maintenance and chemotherapy resistance. Silencing GABRP induced down-regulation of EGFR signaling, which hindered cell stemness and enhanced sensitivity to chemotherapies, including paclitaxel, doxorubicin, and cisplatin. We also identified that retigabine, an FDA-approved drug for adjunctive treatment of seizures, increased the sensitivity of EGFR to gefitinib in gefitinib-resistant cells. Our findings show that GABRP can sustain the stemness of TNBC via modulating EGFR expression, suggesting that GABRP may be a potential therapeutic target that can address EGFR inhibitor resistance in TNBC.
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http://dx.doi.org/10.1016/j.canlet.2021.04.028DOI Listing
August 2021

Immobilization of cadmium and lead using phosphorus-rich animal-derived and iron-modified plant-derived biochars under dynamic redox conditions in a paddy soil.

Environ Int 2021 May 12;156:106628. Epub 2021 May 12.

University of Wuppertal, School of Architecture and Civil Engineering, Institute of Foundation Engineering, Water- and Waste-Management, Laboratory of Soil- and Groundwater-Management, Pauluskirchstraße 7, 42285 Wuppertal, Germany; University of Sejong, Department of Environment, Energy and Geoinformatics, Guangjin-Gu, Seoul 05006, Republic of Korea. Electronic address:

Functionalized biochar has gained extensive interests as a sustainable amendment for an effective remediation of paddy soils contaminated with heavy metals (HMs). We examined the efficiency of pig carcass-derived biochar (P-rich biochar, total P = 8.3%) and pristine (raw biochar, total Fe = 0.76%) and Fe-modified (Fe-rich biochar, total Fe = 5.5%) green waste-derived biochars for the immobilization of cadmium (Cd) and lead (Pb) in a paddy soil under pre-defined redox conditions (Eh, from -400 to +300 mV). Average concentrations (μg L) of dissolved Cd increased under reducing conditions up to 10.9 in the control soil, and decreased under oxidizing conditions to below the detection limit (LDL = 2.7) in the raw and Fe-rich biochar treated soils. Application of the raw biochar decreased the concentrations of dissolved Cd by 43-59% under Eh ≤ -100 mV, compared to the non-treated control, which was more effective than the Fe-rich biochar (31-59%) and the P-rich biochar (8-19%). The immobilization of Cd under low Eh might be due to its precipitation with sulfide (S), whereas its immobilization under high Eh might be due to the associated increase of pH. Concentrations (μg L) of Pb ranged from 29.4 to 198.2 under reducing conditions, and decreased to LDL (12.5) under oxidizing conditions. The P-rich biochar was more effective in immobilizing Pb than the raw and Fe-rich biochars, particularly under Eh ≤ 0 mV (55-82%), which might be due to the retention of Pb by phosphates. The raw and Fe-rich biochars immobilized Pb under low Eh (≤ -300 mV), but both biochars, particularly the Fe-rich biochar mobilized Pb under Eh higher than -200 mV, especially at +100 mV, due to the decrease of pH at this point (pH = 6.0 to 6.5). These results improved our understanding of using P-rich and Fe-rich functionalized biochars for the immobilization of Cd and Pb in a paddy soil under stepwise redox changes. The amendment of P-rich pig carcass-derived biochar to paddy soils could be a promising approach for mitigating the risk of Pb for human health and the environment. The raw and Fe-rich green waste-derived biochars can be used for immobilizing Cd and mitigating its risk in paddy soils under both reducing and oxidizing conditions.
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http://dx.doi.org/10.1016/j.envint.2021.106628DOI Listing
May 2021

The outcomes in STEMI patients with high thrombus burden treated by deferred versus immediate stent implantation in primary percutaneous coronary intervention: a prospective cohort study.

Ann Transl Med 2021 Apr;9(7):573

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: No-/slow-reflow indicates worse outcomes in ST-elevation myocardial infarction (STEMI) patients with high thrombus burden. We examined whether deferred stenting (DS) strategy reduces no-/slow-reflow or major adverse cardiovascular events (MACEs) in primary percutaneous coronary intervention (pPCI) for patients with acute STEMI and high thrombus burden.

Methods: We performed an open-label, multi-center, prospective cohort study among eligible patients with acute STEMI and high thrombus burden who further received pPCI. All participants received PCI with DS (second procedure performed within 48-72 h) or immediate-stenting (IS) strategy. The primary outcome was the incidence of no-/slow-reflow. We evaluated MACEs and bleeding events during hospitalization and at 30- and 90-day follow-ups.

Results: We recruited 245 patients to this study, including 51 with DS and 194 with IS. Baseline clinical characters were comparable between the 2 strategies. Incidence of no-/slow-reflow defined by thrombolysis in myocardial infarction (TIMI) flow grade was not significantly different between the 2 strategies [DS: 5 (9.8%), IS: 33 (17.0%), P=0.21]. No-/slow-reflow by TIMI myocardial perfusion grade (TMPG) was less prevalent in DS [20 (39.2%) 107 (55.2%), P=0.04]. No significant differences were found in recurrence of myocardial infarction (P=0.56), cardiac death (P=0.37), all-cause mortality (P=0.37), heart failure-induced readmission (P=0.35), or bleeding (P=0.61) between the 2 strategies in-hospital, and at 30- and 90-day follow-up.

Conclusions: In STEMI patients with high thrombus burden who underwent pPCI, DS strategy reduced no-/slow-reflow of microcirculation. However, DS strategy did not reduce incidence of MACEs or bleeding.
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http://dx.doi.org/10.21037/atm-21-1130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105830PMC
April 2021

Risk factors associated with functional dyspepsia in Chinese children: a cross-sectional study.

BMC Gastroenterol 2021 May 12;21(1):218. Epub 2021 May 12.

Department of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Background: There is no study assessing the risk factors associated with functional dyspepsia (FD) in Chinese children based on the Rome IV criteria.

Methods: In this cross-sectional study, we analyzed data from eight representative primary and secondary schools to assess the risk factors associated with FD in Chinese children based on the Rome IV criteria.

Results: A total of 6976 Chinese children were enrolled. The mean age was 14.3 ± 2.5 years, with a range from 7 to 17 years, and 3497 (50.1%) participants were female. FD was prevalent in 209 (3.0%) of the Chinese child population studied. Age (OR = 1.112, P = 0.006), living independent of parents (OR = 1.677, P < 0.001), prolonged school meals (OR = 2.107, P < 0.001), never eat breakfast (OR = 2.192, P = 0.003), often/daily eat cold foods (OR = 2.296, P = 0.002; OR = 2.736, P = 0.011), and often eat pickled foods (OR = 2.390, P = 0.001) were found to be independent risk factors for FD. A nomogram with these risk factors had good discrimination (AUC = 0.727) and calibration (Hosmer-Lemeshow test was 0.851).

Conclusions: Age, living independent of parents, prolonged school meals, never eat breakfast, often/daily eat cold foods and often eat pickled foods were independent risk factors for FD. The nomogram could be used as a quick screening tool to assess FD in Chinese children.
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http://dx.doi.org/10.1186/s12876-021-01800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114539PMC
May 2021

Modulatory Effects of emu-let-7-5p on the Immunological Functions of RAW264.7 Macrophages.

Front Vet Sci 2021 15;8:663497. Epub 2021 Apr 15.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China.

is a zoonotic tapeworm with great medical significance. In -infected mice, parasite-derived let-7-5p (emu-let-7-5p) is present in the sera, but its role remains unclear. Using qPCR, ELISA and flow cytometry, the immunomodulatory effects of emu-let-7-5p were investigated using RAW264.7 macrophages. Compared with the control, emu-let-7-5p significantly downregulated IL-1α ( < 0.05), but anti-inflammatory cytokine genes remained to be stably expressed in the treated macrophages. Moreover, significantly decreased expression of and , key components in the LPS/TLR4 signaling pathway, was also observed in the emu-let-7-5p-transfected cells ( < 0.05). Furthermore, CD40 was upregulated in these transfected cells ( < 0.05), while CD86, CD54 and CD80 remained unchanged compared that in the control. These results demonstrate a property of emu-let-7-5p in regulation of immune functions of macrophages, making it be possibly involved in the pathogen-host interplay during infection.
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http://dx.doi.org/10.3389/fvets.2021.663497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081858PMC
April 2021

Discovery of novel IDO1 inhibitors via structure-based virtual screening and biological assays.

J Comput Aided Mol Des 2021 May 27;35(5):679-694. Epub 2021 Apr 27.

School of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the first and rate-limiting step in catabolism of tryptophan via the kynurenine pathway, which plays a pivotal role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for many diseases, such as breast cancer, lung cancer, colon cancer, prostate cancer, etc. In this study, docking-based virtual screening and bioassays were conducted to identify novel inhibitors of IDO1. The cellular assay demonstrated that 24 compounds exhibited potent inhibitory activity against IDO1 at micromolar level, including 8 compounds with IC values below 10 μM and the most potent one (compound 1) with IC of 1.18 ± 0.04 μM. Further lead optimization based on similarity searching strategy led to the discovery of compound 28 as an excellent inhibitor with IC of 0.27 ± 0.02 μM. Then, the structure-activity relationship of compounds 1, 2, 8 and 14 analogues is discussed. The interaction modes of two compounds against IDO1 were further explored through a Python Based Metal Center Parameter Builder (MCPB.py) molecular dynamics simulation, binding free energy calculation and electrostatic potential analysis. The novel IDO1 inhibitors of compound 1 and its analogues could be considered as promising scaffold for further development of IDO1 inhibitors.
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http://dx.doi.org/10.1007/s10822-021-00386-6DOI Listing
May 2021

Bach2 regulates autophagy to modulate UVA-induced photoaging in skin fibroblasts.

Free Radic Biol Med 2021 06 18;169:304-316. Epub 2021 Apr 18.

National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology of Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, China. Electronic address:

Senescence is a cellular process that can be initiated by certain stressors such as UVA irradiation. The mechanism by which skin cells protect themselves from the UVA-induced senescence has not been fully investigated. Here, we demonstrate that Bach2 modulates the extent of UVA-induced photoaging through regulation of autophagy in skin fibroblasts. In fact chronic exposure of skin fibroblasts to UVA resulted in a significant decrease in Bach2 expression, both in vitro and in vivo. In addition, knockdown of Bach2 in skin fibroblasts led to an increased expression of cell senescence-related genes, which further enhanced the UVA irradiation-induced photoaging. On the other hand, the overexpression of Bach2 resulted in a decrease in the expression of cell senescence-related genes. We also demonstrate that the knockdown of Bach2 in skin fibroblasts can lead to a decreased expression of autophagy-related genes and vice versa, suggesting that autophagy is involved in Bach2-mediated regulation of senescence in skin fibroblasts. Additionally, inhibition of autophagy with autophagy inhibitor 3-MA suppressed the expression of autophagy-related proteins and promoted cell senescence. Furthermore, knockout of Atg5 or Atg7 in embryonic mouse fibroblasts led to a significant increase in the expression of cell senescence-related genes. Immunoprecipitation assays further demonstrated that Bach2 directly interacts with Beclin-1, Atg3, Atg7, and LC3 in fibroblasts. Taken together, these findings revealed a critical role for Bach2 in suppressing the UVA irradiation-induced cell senescence via autophagy in skin fibroblasts. Bach2 can therefore be a potential target for the therapy of UV-induced photoaging because of its ability to regulate the process of autophagy in the skin.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.003DOI Listing
June 2021

Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke.

Blood 2021 07;138(1):91-103

Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology-Ministry of Education (MOE) Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.

Intracerebral hemorrhage associated with thrombolytic therapy with tissue plasminogen activator (tPA) in acute ischemic stroke continues to present a major clinical problem. Here, we report that infusion of tPA resulted in a significant increase in markers of neutrophil extracellular traps (NETs) in the ischemic cortex and plasma of mice subjected to photothrombotic middle cerebral artery occlusion. Peptidylarginine deiminase 4 (PAD4), a critical enzyme for NET formation, is also significantly upregulated in the ischemic brains of tPA-treated mice. Blood-brain barrier (BBB) disruption after ischemic challenge in an in vitro model of BBB was exacerbated after exposure to NETs. Importantly, disruption of NETs by DNase I or inhibition of NET production by PAD4 deficiency restored tPA-induced loss of BBB integrity and consequently decreased tPA-associated brain hemorrhage after ischemic stroke. Furthermore, either DNase I or PAD4 deficiency reversed tPA-mediated upregulation of the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). Administration of cGAMP after stroke abolished DNase I-mediated downregulation of the STING pathway and type 1 interferon production and blocked the antihemorrhagic effect of DNase I in tPA-treated mice. We also show that tPA-associated brain hemorrhage after ischemic stroke was significantly reduced in cGas-/- mice. Collectively, these findings demonstrate that NETs significantly contribute to tPA-induced BBB breakdown in the ischemic brain and suggest that targeting NETs or cGAS may ameliorate thrombolytic therapy for ischemic stroke by reducing tPA-associated hemorrhage.
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http://dx.doi.org/10.1182/blood.2020008913DOI Listing
July 2021

Quantitative analysis of the relationship of derivatization reagents and detection sensitivity of electrospray ionization-triple quadrupole tandem mass spectrometry: Hydrazines as prototypes.

Anal Chim Acta 2021 May 13;1158:338402. Epub 2021 Mar 13.

Department of Chemistry, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, PR China. Electronic address:

Chemical derivatization-assisted electrospray ionization-triple quadrupole mass spectrometry (ESI-QqQ-MS) has become an efficient tool for the quantification of low-molecular-weight molecules. Many studies found that the derivatives of the same analytes derivatized by different derivatization reagents with the same reaction group had different detection sensitivity, even under the same conditions of electrospray ionization-mass spectrometry (ESI-MS). This phenomenon was suggested to be caused by the different modifying groups in the derivatization reagents. However, there is still a lack of systematic study on how modifying groups in the derivatization reagents affect the detection sensitivity of their corresponding derivatives of analytes, especially theoretical investigations. In this study, we employed a quantitative structure-activity relationship (QSAR) modeling approach to explore the relationship between modifying group structures and the detection sensitivity of derivatization reagents and their derivatives during ESI-MS detection. A total of 110 derivatization reagents of the hydrazine family and their hexanal derivatives (substituted hydrazones) were selected as the prototypes to construct QSAR models. The established models suggested that several molecular descriptors, related to hydrophobicity, electronegativity, and molecular shape, were related to the detection sensitivity of hexanal derivatives induced by different modifying groups in the derivatization reagents. Besides, we found that the detection sensitivity of compounds detected in selected ion mode (SIM) showed a positive correlation with that obtained in multiple reaction monitoring mode (MRM), and the ionization efficiency was the key factor on the detection sensitivity in both modes.
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http://dx.doi.org/10.1016/j.aca.2021.338402DOI Listing
May 2021

Access to Allene-Containing Molecules via Enantioselective Reactions of Azolium Cumulenolate Intermediates.

Angew Chem Int Ed Engl 2021 06 24;60(27):14817-14823. Epub 2021 May 24.

Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University Huaxi District, Guiyang, 550025, China.

Azolium cumulenolates are a special type of intermediates in N-heterocyclic carbene catalysis. They contain elongated linear structures with three contiguous C=C bonds and sterically unhindered α-carbon atoms. These structural features make it difficult to develop enantioselective reactions for these intermediates. Here we disclose the first carbene-catalyzed highly enantioselective addition reactions of azolium cumulenolates. The reaction starts with alkynals as the precursors for azolium cumulenolate intermediates that undergo enantioselective addition to activated ketones. From the same set of substrates, both allene and spirooxindole products can be obtained with high yields and excellent enantioselectivities. The allene moieties in our optically enriched products carry rich reactivities and can be transformed to diverse molecules. The spirooxindole scaffolds in our products are important structural motifs in natural products and medicines.
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http://dx.doi.org/10.1002/anie.202102177DOI Listing
June 2021

Gas sensing materials roadmap.

J Phys Condens Matter 2021 Jun 11;33(30). Epub 2021 Jun 11.

College of Mechanical Engineering, Yangzhou University, People's Republic of China.

Gas sensor technology is widely utilized in various areas ranging from home security, environment and air pollution, to industrial production. It also hold great promise in non-invasive exhaled breath detection and an essential device in future internet of things. The past decade has witnessed giant advance in both fundamental research and industrial development of gas sensors, yet current efforts are being explored to achieve better selectivity, higher sensitivity and lower power consumption. The sensing layer in gas sensors have attracted dominant attention in the past research. In addition to the conventional metal oxide semiconductors, emerging nanocomposites and graphene-like two-dimensional materials also have drawn considerable research interest. This inspires us to organize this comprehensive 2020 gas sensing materials roadmap to discuss the current status, state-of-the-art progress, and present and future challenges in various materials that is potentially useful for gas sensors.
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http://dx.doi.org/10.1088/1361-648X/abf477DOI Listing
June 2021

An Infrared Touch System for Automatic Behavior Monitoring.

Neurosci Bull 2021 Jun 31;37(6):815-830. Epub 2021 Mar 31.

Shenzhen Key Laboratory of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Key requirements of successful animal behavior research in the laboratory are robustness, objectivity, and high throughput, which apply to both the recording and analysis of behavior. Many automatic methods of monitoring animal behavior meet these requirements. However, they usually depend on high-performing hardware and sophisticated software, which may be expensive. Here, we describe an automatic infrared behavior-monitor (AIBM) system based on an infrared touchscreen frame. Using this, animal positions can be recorded and used for further behavioral analysis by any PC supporting touch events. This system detects animal behavior in real time and gives closed-loop feedback using relatively low computing resources and simple algorithms. The AIBM system automatically records and analyzes multiple types of animal behavior in a highly efficient, unbiased, and low-cost manner.
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http://dx.doi.org/10.1007/s12264-021-00661-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192659PMC
June 2021

A Self-test Prediction Model to Determine the Probability Risk of Non-alcoholic Fatty Liver Disease.

Biomed Environ Sci 2020 Nov;33(11):857-861

School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing 100069, China.

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http://dx.doi.org/10.3967/bes2020.116DOI Listing
November 2020

Comparison of the phase change process in a GST-loaded silicon waveguide and MMI.

Opt Express 2021 Feb;29(3):3503-3514

In the past decades, silicon photonic integrated circuits (PICs) have been considered a promising approach to solve the bandwidth bottleneck in optical communications and interconnections. Despite the rapid advances, large-scale PICs still face a series of technical challenges, such as large footprint, high power consumption, and lack of optical memory, resulting from the active tuning methods used to control the optical waves. These challenges can be partially addressed by combining chalcogenide phase change materials (PCMs) such as GeSbTe (GST) with silicon photonics, especially applicable in reconfigurable optical circuit applications due to the nonvolatile nature of the GST. We systematically investigate the phase change process induced by optical and electrical pulses in GST-loaded silicon waveguide and multimode interferometer. Using optical pulse excitation to amorphize GST has a clear advantage in terms of operation speed and energy efficiency, while electrical pulse excitation is more suitable for large-scale integration because it does not require complex optical routing. This study helps us better understand the phase change process and push forward the further development of the Si-GST hybrid photonic integration platform, bringing in new potential applications.
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http://dx.doi.org/10.1364/OE.413660DOI Listing
February 2021

Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats.

Front Pharmacol 2021 9;12:616803. Epub 2021 Mar 9.

Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both and , which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.
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http://dx.doi.org/10.3389/fphar.2021.616803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985071PMC
March 2021

Imaging of Fibroblast Activation Protein in Cancer Xenografts Using Novel (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine-Based Small Molecules.

J Med Chem 2021 04 17;64(7):4059-4070. Epub 2021 Mar 17.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, United States.

Fibroblast activation protein (FAP) has become a favored target for imaging and therapy of malignancy. We have synthesized and characterized two new (4-quinolinoyl)-glycyl-2-cyanopyrrolidine-based small molecules for imaging of FAP, and [In], using optical and single-photon computed tomography/CT, respectively. Binding of imaging agents to FAP was assessed in six human cancer cell lines of different cancer types: glioblastoma (U87), melanoma (SKMEL24), prostate (PC3), NSCLC (NCIH2228), colorectal carcinoma (HCT116), and lung squamous cell carcinoma (NCIH226). Mouse xenograft models were developed with FAP-positive U87 and FAP-negative PC3 cells to test pharmacokinetics and binding specificity . and [In] demonstrated nanomolar inhibition of FAP at values of 1.26 and 16.20 nM, respectively. Both were selective for FAP over DPP-IV, a related serine protease. Both enabled imaging of FAP-expressing tumors specifically . [In] showed high uptake at 18.2 percent injected dose per gram in the U87 tumor at 30 min post-administration.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214312PMC
April 2021

Chiral voltammetric sensor for tryptophan enantiomers by using a self-assembled multiwalled carbon nanotubes/polyaniline/sodium alginate composite.

Chirality 2021 05 6;33(5):248-260. Epub 2021 Mar 6.

College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou, China.

Due to the crucial role of amino acids in life sciences and pharmaceutics, identification of optical amino acid molecules is of great significance. In this study, the two materials (CNT and PANI) were combined together to obtain the magnification of electrochemical signal by substrate material (CNT/PANI). Then a self-assembled multiwalled carbon nanotubes/polyaniline/sodium alginate (CNT/PANI/SA) nanocomposite with chiral sites and conductive material was synthesized as the electrochemical sensing interface. Next, a novel electrochemical sensing interface was fabricated via modifying the as-prepared chiral material on a polished glassy carbon electrode (CNT/PANI/SA/GCE) for precisely, efficiently, and rapidly differentiation of tryptophan (Trp) enantiomers. It was observed that CNT/PANI/SA/GCE showed desirable stereoselective recognition effect in the variety of signal strength to peak current (Ip) to the different optical activity of Trp enantiomers. In the case of optimal conditions, the peak current ratio in the solution of l-Trp and d-Trp (I /I ) was observed to be 2.1 at CNT/PANI/SA/GCE by differential pulse voltammogram (DPV). UV-visible spectroscopy further showed that CNT/PANI/SA had a greater binding energy to l-Trp. Also different factors affecting the enantioselectivity of CNT/PANI/SA/GCE, such as the incubation time, pH, and dropcoating volume of CNT/PANI/SA were optimized. Moreover, the proposed CNT/PANI/SA/GCE showed excellent specific stereoselectivity and anti-interference ability. Besides, the proposed chiral sensing platform can be effectively applied in real samples to detect Trp enantiomers sensitively. This work inspires us a new path for the preparation of substrate material with excellent electrical conductivity, as well as extend its application potential in chiral recognition.
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http://dx.doi.org/10.1002/chir.23305DOI Listing
May 2021

Role of the Wnt pathway in the formation, development, and degeneration of intervertebral discs.

Pathol Res Pract 2021 Apr 8;220:153366. Epub 2021 Feb 8.

The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Department of Orthopaedics, Second Hospital of Lanzhou University, Lanzhou, Gansu 730000, China; Key Laboratory of Orthopaedics Disease of Gansu Province, Lanzhou, Gansu 730000, China. Electronic address:

Intervertebral disc degeneration (IVDD) is an age-related degenerative disease that is the main cause of low back pain. It seriously affects the quality of life of patients and places a heavy economic burden on families and society. The Wnt pathway plays an important role in the growth, development, and degeneration of intervertebral discs (IVDs). In the embryonic stage, the Wnt pathway participates in the growth and development of IVD by promoting the transformation of progenitor cells into notochord cells and the extension of the notochord. However, the activation of the Wnt pathway after birth promotes IVD cell senescence, apoptosis, and degradation of the extracellular matrix and induces the production of inflammatory factors, thereby accelerating the IVDD process. This article reviews the relationship between the Wnt pathway and IVD, emphasizing its influence on IVD growth, development, and degeneration. Targeting this pathway may become an effective strategy for the treatment of IVDD.
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http://dx.doi.org/10.1016/j.prp.2021.153366DOI Listing
April 2021