Publications by authors named "Jing Geng"

141 Publications

Gender and the Subjective Well-Being of Older Widows and Widowers.

Int J Aging Hum Dev 2022 Apr 25:914150221092990. Epub 2022 Apr 25.

Department of Sociology, 1757Virginia Tech, Blacksburg, VA, USA.

Previous research on older adults who are widowed often focuses on the immediate subjective impacts of spousal loss, and how gender might influence this. Our interest here is on the factors that influence subjective well-being after a period of at least two years' post-bereavement, and how this might differ for men and women. We draw on theoretical considerations from previous research on gender and on widowhood and use two different measures-life satisfaction and happiness-to assess possible differences in this subjective outcome. We used data from the 2014 Health and Retirement Study on 692 widowed adults aged 65 and over (578 females and 114 males) and employed regression and postestimation analyses to examine whether and how gender influences their subjective well-being. Our findings show that gender did not affect overall levels of subjective well-being, regardless of measure. However, gender did influence the predictors, such as total household income, total wealth, and social support from children and friends, for life satisfaction and happiness somewhat differently. Our study highlights the importance of examining gender differences among older widows and widowers and also underlines the importance of introducing different measures of subjective well-being that might yield different yet valuable findings.
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http://dx.doi.org/10.1177/00914150221092990DOI Listing
April 2022

Comparison of the accuracy (trueness and precision) of virtual dentofacial patients digitized by three different methods based on 3D facial and dental images.

J Prosthet Dent 2022 Mar 31. Epub 2022 Mar 31.

Professor, Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases &National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, Beijing, PR China. Electronic address:

Statement Of Problem: The accuracy of virtual dentofacial patients has been explored, but the accuracy of virtual patients established by using a straightforward and reliable method and the accuracy of different virtual patients are unclear.

Purpose: The purpose of this clinical study was to compare the accuracy of virtual dentofacial patients digitized by using registered-block impression, exposed anterior teeth, and cone beam computed tomography (CBCT) reconstruction methods based on 3-dimensional (3D) facial and dental images.

Material And Methods: From the 15 selected participants who needed CBCT scanning, 3 kinds of virtual dentofacial patients were established by using 3 registration methods based on digital dental casts: 3D facial images, CBCT data, and registered-block impression. Compared with actual measurement, 25 linear distances of all virtual dentofacial patients were selected and measured by using a software program, and 3 separate measurements were calculated by the same person. The 1-way analysis of variance (ANOVA) was used to compare the deviations among 3 kinds of virtual dentofacial patients (trueness) and the deviations within groups (precision). The 1-sample t test was used to compare the difference between the deviation and the ideal error of 0.00 (α=.05).

Results: Compared with the actual measurement, the trueness of the average deviations for registered-block impression (1.02 ±1.24 mm) was better than that of exposed anterior teeth (2.35 ±1.71 mm) and CBCT reconstruction (2.86 ±1.61 mm). The precision of the average deviations for registered-block impression (1.29 ±1.43 mm) was better than that of exposed anterior teeth (2.00 ±1.72 mm) and CBCT reconstruction (2.12 ±1.94 mm). Significant differences in trueness and precision were found among the 3 groups of virtual dentofacial patients (P<.01). Significant differences among the deviations of all linear distances and the ideal error of 0.00 were observed for all groups of virtual dentofacial patients (P<.05).

Conclusions: The accuracy of registered-block impression was better than that of the exposed anterior teeth and CBCT reconstruction. The accuracy of exposed anterior teeth was lower than that of the other methods but could satisfy the requirements of clinical diagnostics and scientific methods. The accuracy of CBCT reconstruction was poor and could only be used for special situations that permitted low accuracy.
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http://dx.doi.org/10.1016/j.prosdent.2022.01.035DOI Listing
March 2022

Dihydromyricetin Alleviates Pulmonary Fibrosis by Regulating Abnormal Fibroblasts Through the STAT3/p-STAT3/GLUT1 Signaling Pathway.

Front Pharmacol 2022 14;13:834604. Epub 2022 Mar 14.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with a poor prognosis. Although dihydromyricetin (DHM), extracted from vine tea and other Ampelopsis species, has been proven to have anti-inflammatory and antioxidant functions, the effects of DHM on IPF remain unclear. The effects of DHM on the differentiation, migration, proliferation, and respiratory functions of primary mouse lung fibroblasts (PMLFs) and primary human lung fibroblasts (PHLFs) were detected by western blotting, the Transwell assay, EdU staining, and the Mito Stress test. Then, the impacts of DHM on bleomycin (BLM)-induced pulmonary fibrosis were evaluated by pathological staining, western blotting, and coimmunofluorescence staining. The signaling pathway influenced by DHM was also investigated. DHM could regulate the differentiation of fibroblasts to myofibroblasts and suppress the abnormal migration, proliferation, and respiratory functions of myofibroblasts induced by TGF-1 or myofibroblasts from IPF patients. DHM could also alleviate pulmonary fibrosis induced by BLM. All these effects were achieved by regulating the STAT3/p-STAT3/GLUT1 signaling pathway. DHM could regulate the abnormal functions of myofibroblasts induced by TGF-1 and myofibroblasts from IPF patients and alleviate pulmonary fibrosis induced by BLM; thus, DHM might be a candidate medicinal treatment for IPF.
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http://dx.doi.org/10.3389/fphar.2022.834604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964100PMC
March 2022

Nicotinamide riboside promotes Mfn2-mediated mitochondrial fusion in diabetic hearts through the SIRT1-PGC1α-PPARα pathway.

Free Radic Biol Med 2022 04 19;183:75-88. Epub 2022 Mar 19.

Department of Cardiology, Tangdu Hospital, Airforce Medical University, Xi'an, 710038, China. Electronic address:

Myocardial dysfunction is associated with an imbalance in mitochondrial fusion/fission dynamics in patients with diabetes. However, effective strategies to regulate mitochondrial dynamics in the diabetic heart are still lacking. Nicotinamide riboside (NR) supplementation ameliorated mitochondrial dysfunction and oxidative stress in both cardiovascular and aging-related diseases. This study investigated whether NR protects against diabetes-induced cardiac dysfunction by regulating mitochondrial fusion/fission and further explored the underlying mechanisms. Here, we showed an evident decrease in NAD (nicotinamide adenine dinucleotide) levels and mitochondrial fragmentation in the hearts of leptin receptor-deficient diabetic (db/db) mouse models. NR supplementation significantly increased NAD content in the diabetic hearts and promoted mitochondrial fusion by elevating Mfn2 level. Furthermore, NR-induced mitochondrial fusion suppressed mitochondrial HO and O• production and reduced cardiomyocyte apoptosis in both db/db mice hearts and neonatal primary cardiomyocytes. Mechanistically, chromatin immunoprecipitation (ChIP) and luciferase reporter assay analyses revealed that PGC1α and PPARα interdependently regulated Mfn2 transcription by binding to its promoter region. NR treatment elevated NAD levels and activated SIRT1, resulting in the deacetylation of PGC1α and promoting the transcription of Mfn2. These findings suggested the promotion of mitochondrial fusion via oral supplementation of NR as a potential strategy for delaying cardiac complications in patients with diabetes.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.03.012DOI Listing
April 2022

Single-Cell Transcriptomics Reveals Peripheral Immune Responses in Anti-Synthetase Syndrome-Associated Interstitial Lung Disease.

Front Immunol 2022 17;13:804034. Epub 2022 Feb 17.

Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing, China.

Objective: Interstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition.

Methods: We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq.

Results: We used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among NK cells, monocytes, T cells, and B cells. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher in patients than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs, evaluated by the expression patterns of chemokine receptors.

Conclusions: The scRNA-seq data analyses reveal that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, and involvement of differentiation signaling pathways of CD4 T cells. The flow cytometry analyses show that the proportions of Th17 cells and Th2 cells are increased and the proportion of Th1 cells is decreased in patients with ASS-ILD. These findings may provide foundations of novel therapeutic targets for patients with this condition.
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http://dx.doi.org/10.3389/fimmu.2022.804034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891123PMC
May 2022

Fatty Acid Metabolism and Idiopathic Pulmonary Fibrosis.

Front Physiol 2021 14;12:794629. Epub 2022 Jan 14.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Fatty acid metabolism, including the synthesis, uptake, oxidation, and derivation of fatty acids, plays several important roles at cellular and organ levels. Recent studies have identified characteristic changes in fatty acid metabolism in idiopathic pulmonary fibrosis (IPF) lungs, which implicates its dysregulation in the pathogenesis of this disorder. Here, we review the evidence for how fatty acid metabolism contributes to the development of pulmonary fibrosis, focusing on the profibrotic processes associated with specific types of lung cells, including epithelial cells, macrophages, and fibroblasts. We also summarize the potential therapeutics that target this metabolic pathway in treating IPF.
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http://dx.doi.org/10.3389/fphys.2021.794629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795701PMC
January 2022

Krebs von den Lungen-6 levels in untreated idiopathic pulmonary fibrosis.

Clin Respir J 2022 Mar 26;16(3):234-243. Epub 2022 Jan 26.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Beijing, China.

Background: Serum Krebs von den Lungen-6 (KL-6) has been reported to be elevated in patients with idiopathic pulmonary fibrosis (IPF).

Objective: The aim of this study was to evaluate the diagnostic value of KL-6 and whether the expression value of KL-6 could indicate the severity of the disease in IPF patients. To address this question, it is necessary to see whether the patients' physical characteristics and other clinical conditions could affect the baseline KL-6 level.

Design: We conducted a study of 100 patients who were diagnosed with IPF. Lung function, computed tomography (CT), and serological lab tests data were analyzed.

Results: The tests showed that there is a significant elevation of KL-6 in IPF patients compared with other interstitial lung disease (ILD) and healthy controls. It was noted that serum KL-6 is a stable biomarker not affected by lung infection and smoking, though IPF patients with antinuclear antibody (ANA) showed higher KL-6 levels. KL-6, in conjunction with poor pulmonary function and higher radiological fibrosis scores, indicates the severity of the disease but not poor survival.

Conclusions: It is identified that serum KL-6 is a useful noninvasive biomarker to help improve the certainty of IPF diagnosis from other interstitial lung disease and assist evaluation of disease severity and prognosis.
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http://dx.doi.org/10.1111/crj.13475DOI Listing
March 2022

Heat shock transcription factor (Hsf) gene family in common bean (Phaseolus vulgaris): genome-wide identification, phylogeny, evolutionary expansion and expression analyses at the sprout stage under abiotic stress.

BMC Plant Biol 2022 Jan 14;22(1):33. Epub 2022 Jan 14.

College of Agriculture, Heilongjiang BaYi Agricultural University, Daqing, 163319, Heilongjaing, China.

Background: Common bean (Phaseolus vulgaris) is an essential crop with high economic value. The growth of this plant is sensitive to environmental stress. Heat shock factor (Hsf) is a family of antiretroviral transcription factors that regulate plant defense system against biotic and abiotic stress. To date, few studies have identified and bio-analyzed Hsfs in common bean.

Results: In this study, 30 Hsf transcription factors (PvHsf1-30) were identified from the PFAM database. The PvHsf1-30 belonged to 14 subfamilies with similar motifs, gene structure and cis-acting elements. The Hsf members in Arabidopsis, rice (Oryza sativa), maize (Zea mays) and common bean were classified into 14 subfamilies. Collinearity analysis showed that PvHsfs played a role in the regulation of responses to abiotic stress. The expression of PvHsfs varied across different tissues. Moreover, quantitative real-time PCR (qRT-PCR) revealed that most PvHsfs were differentially expressed under cold, heat, salt and heavy metal stress, indicating that PvHsfs might play different functions depending on the type of abiotic stress.

Conclusions: In this study, we identified 30 Hsf transcription factors and determined their location, motifs, gene structure, cis-elements, collinearity and expression patterns. It was found that PvHsfs regulates responses to abiotic stress in common bean. Thus, this study provides a basis for further analysis of the function of PvHsfs in the regulation of abiotic stress in common bean.
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http://dx.doi.org/10.1186/s12870-021-03417-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759166PMC
January 2022

Glycogen accumulation and phase separation drives liver tumor initiation.

Cell 2021 10 21;184(22):5559-5576.e19. Epub 2021 Oct 21.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:

Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.
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http://dx.doi.org/10.1016/j.cell.2021.10.001DOI Listing
October 2021

[Occurrence, Distribution, and Ecological Risk Assessment of Pharmaceutical and Personal Care Products in the Aquatic Environment of Sanya City, China].

Huan Jing Ke Xue 2021 Oct;42(10):4717-4726

ZHAI Ming-guo Academician Workstation, University of Sanya, Sanya 572000, China.

The occurrence, distribution, and risk of 11 typical pharmaceutical and personal care products(PPCPs) were investigated in the major rivers and bay areas of Sanya City. The results showed that the significant seasonal variations in eleven PPCPs in major rivers of the city were affected by intense tourism alongside reduced annual runoff. In winter, all 11 PPCPs had 100% detection frequencies, of which CFI had the highest concentration at 1449.10 ng·L. The highest concentration of MTP was 427.06 ng·L and highest concentration of RTM was 311.59 ng·L. In summer, all 11 PPCPs were again detected, with a lowest detection rate of 87.5%, of which CFI, MTP, RTM, ETM, and OFL were predominant. All 11 PPCPs were also detected in the surface seawater of the main bay areas, with detection frequencies of 85.7%, 57.1%, and 71.4% for SMX, MTP, and CFI respectively; the other eight PPCPs had 100% detection frequencies. CFI had the highest concentration at 220.78 ng·L. An ecological risk assessment of the 11 PPCPs showed that the risk quotients(RQ) of STZ at Yuechuan Bridge and RTM at Fenghuang Road were higher than 1 in winter, posing a high risk to the aquatic ecology. This was mainly attributed to the discharge of water from nearby hospitals and sewage treatment plants. In summer, the RQ of STZ at Sanya Bridge and RTM at Hongsha Wharf was between 0.1 and 1, which indicates a medium level of risk to the aquatic environment in Sanya City.
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http://dx.doi.org/10.13227/j.hjkx.202102031DOI Listing
October 2021

The Expression Patterns and Roles of Lysyl Oxidases in Aortic Dissection.

Front Cardiovasc Med 2021 7;8:692856. Epub 2021 Jul 7.

Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Lysyl oxidases (LOXs), including LOX, LOXL1, LOXL2, LOXL3, and LOXL4, catalyze the formation of a cross-link between elastin (ELN) and collagen. Multiple LOX mutations have been shown to be associated with the occurrence of aortic dissection (AD) in humans, and LOX-knockout mice died during the perinatal period due to aortic aneurysm and rupture. However, the expression levels and roles of other LOX members in AD remain unknown. A total of 33 aorta samples of AD and 15 normal aorta were collected for LOXs mRNA and protein levels detection. We also analyzed the datasets of AD in GEO database through bioinformatics methods. LOXL2 and LOXL3 were knocked down in primary cultured human aortic smooth muscle cells (HASMCs) via lentivirus. Here, we show that the protein levels of LOXL2 and LOXL3 are upregulated, while LOXL4 is downregulated in AD subjects compared with non-AD subjects, but comparable protein levels of LOX and LOXL1 are detected. Knockdown of LOXL2 suppressed MMP2 expression, the phosphorylation of AKT (p-AKT) and S6 (p-S6), but increased the mono-, di-, tri-methylation of H3K4 (H3K4me1/2/3), H3K9me3, and p-P38 levels in HASMCs. These results indicate that LOXL2 is involved in regulation of the extracellular matrix (ECM) in HASMCs. In contrast, LOXL3 knockdown inhibited PCNA and cyclin D1, suppressing HASMC proliferation. Our results suggest that in addition to LOX, LOXL2 and LOXL3 are involved in the pathological process of AD by regulating ECM and the proliferation of HASMCs, respectively. Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion. Thus, differential regulation of LOXs might be a novel strategy to prevent or treat AD.
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http://dx.doi.org/10.3389/fcvm.2021.692856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292648PMC
July 2021

TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection.

Nat Commun 2021 06 10;12(1):3519. Epub 2021 Jun 10.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

TLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response.
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http://dx.doi.org/10.1038/s41467-021-23683-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192512PMC
June 2021

Delayed KCNQ1/KCNE1 assembly on the cell surface helps I fulfil its function as a repolarization reserve in the heart.

J Physiol 2021 07 1;599(13):3337-3361. Epub 2021 Jun 1.

Department of Physiology & Biophysics, Virginia Commonwealth University, Richmond, VA, USA.

Key Points: In adult ventricular myocytes, the slow delayed rectifier (I ) channels are distributed on the surface sarcolemma, not t-tubules. In adult ventricular myocytes, KCNQ1 and KCNE1 have distinct cell surface and cytoplasmic pools. KCNQ1 and KCNE1 traffic from the endoplasmic reticulum to the plasma membrane by separate routes, and assemble into I channels on the cell surface. Liquid chromatography/tandem mass spectrometry applied to affinity-purified KCNQ1 and KCNE1 interacting proteins reveals novel interactors involved in protein trafficking and assembly. Microtubule plus-end binding protein 1 (EB1) binds KCNQ1 preferentially in its dimer form, and promotes KCNQ1 to reach the cell surface. An LQT1-associated mutation, Y111C, reduces KCNQ1 binding to EB1 dimer.

Abstract: Slow delayed rectifier (I ) channels consist of KCNQ1 and KCNE1. I functions as a 'repolarization reserve' in the heart by providing extra current for ventricular action potential shortening during β-adrenergic stimulation. There has been much debate about how KCNQ1 and KCNE1 traffic in cells, where they associate to form I channels, and the distribution pattern of I channels relative to β-adrenergic signalling complex. We used experimental strategies not previously applied to KCNQ1, KCNE1 or I , to provide new insights into these issues. 'Retention-using-selected-hook' experiments showed that newly translated KCNE1 constitutively trafficked through the conventional secretory path to the cell surface. KCNQ1 largely stayed in the endoplasmic reticulum, although dynamic KCNQ1 vesicles were observed in the submembrane region. Disulphide-bonded KCNQ1/KCNE1 constructs reported preferential association after they had reached cell surface. An in situ proximity ligation assay detected I channels in surface sarcolemma but not t-tubules of ventricular myocytes, similar to the reported location of adenylate cyclase 9/yotiao. Fluorescent protein-tagged KCNQ1 and KCNE1, in conjunction with antibodies targeting their extracellular epitopes, detected distinct cell surface and cytoplasmic pools of both proteins in myocytes. We conclude that, in cardiomyocytes, KCNQ1 and KCNE1 traffic by different routes to surface sarcolemma where they assemble into I channels. This mode of delayed channel assembly helps I fulfil its function of repolarization reserve. Proteomic experiments revealed a novel KCNQ1 interactor, microtubule plus-end binding protein 1 (EB1). EB1 dimer (active form) bound KCNQ1 and increased its surface level. An LQT1 mutation, Y111C, reduced KCNQ1 binding to EB1 dimer.
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http://dx.doi.org/10.1113/JP281773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411300PMC
July 2021

An oxygen-coordinated molybdenum single atom catalyst for efficient electrosynthesis of ammonia.

Chem Commun (Camb) 2021 Jun;57(44):5410-5413

Key Laboratory of Materials Physics, Centre for Environmental and Energy Nanomaterials, Anhui Key Laboratory of Nanomaterials and Nanotechnology, CAS Center for Excellence in Nanoscience, Institute of Solid State Physics, HFIPS, Chinese Academy of Sciences, Hefei 230031, China.

Electrochemical nitrogen (N2) reduction has been regarded as a promising strategy for artificial ammonia (NH3) production under ambient conditions. Herein, we report the fabrication of molybdenum (Mo) single atoms anchored on activated carbon (Mo-SAs/AC) for the electrochemical N2 reduction to NH3. The surface-rich oxygen functional groups of activated carbon can effectively capture the Mo precursor, and concurrently act as the coordination sites to anchor Mo single atoms by forming Mo-Ox bonds. As a result, the Mo-SAs/AC as an electrocatalyst shows high activity toward the N2 reduction reaction (NRR), affording an NH3 yield rate of 2.55 ± 0.31 mg h-1 mgMo-1 and a faradaic efficiency (FE) of 57.54 ± 6.98% at -0.40 V (vs. RHE) in 0.1 M Na2SO4 electrolyte with good stability and durability. The constructed Mo-Ox sites are responsible for high NRR activity of Mo-SAs/AC.
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http://dx.doi.org/10.1039/d1cc01455bDOI Listing
June 2021

Rectal-vaginal pressure gradient in patients with pelvic organ prolapse and symptomatic rectocele.

BMC Womens Health 2021 04 20;21(1):165. Epub 2021 Apr 20.

Department of Obstetrics and Gyencology, Peking University People's Hospital, No. 11 of Xizhimen south Street, Xicheng District, Beijing, 100048, China.

Objective: The aim of this study is to examine the relationship between rectal-vaginal pressure and symptomatic rectocele in patients with pelvic organ prolapse (POP).

Method: Patients with posterior vaginal prolapse staged III or IV in accordance with the POP Quantitation classification method who were scheduled for pelvic floor reconstructive surgery in the years 2016-2019 were included in the study. Rectocele was diagnosed using translabial ultrasound, and obstructed defecation (OD) was diagnosed in accordance with the Roma IV diagnostic criteria. Both rectal and vaginal pressure were measured using peritron manometers at maximum Vasalva. To ensure stability, the test was performed three times with each patient.

Results: A total of 217 patients were enrolled in this study. True rectocele was diagnosed in 68 patients at a main rectal ampulla depth of 19 mm. Furthermore, 36 patients were diagnosed with OD. Symptomatic rectocele was significantly associated with older age (p < 0.01), a higher OD symptom score (p < 0.001), and a lower grade of apical prolapse (p < 0.001). The rectal-vaginal pressure gradient was higher in patients with symptomatic rectocele (37.4 ± 11.7 cm HO) compared with patients with asymptomatic rectocele (16.9 ± 8.4 cm HO, p < 0.001), and patients without rectocele (17.1 ± 9.2 cm HO, p < 0.001).

Conclusion: The rectal-vaginal pressure gradient was found to be a risk factor for symptomatic rectocele in patients with POP. A rectal-vaginal pressure gradient of > 27.5 cm HO was suggested as the cut-off point of the elevated pressure gradient.
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http://dx.doi.org/10.1186/s12905-021-01304-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056717PMC
April 2021

Structured re-training to reduce peritonitis in a pediatric peritoneal dialysis program: a quality improvement intervention.

Pediatr Nephrol 2021 10 2;36(10):3191-3200. Epub 2021 Apr 2.

Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, NUHS Tower Block Level 12, 1E Kent Ridge Road, Singapore, 119228, Singapore.

Background: Decline in skills and knowledge among patients and/or caregivers contributes to peritoneal-dialysis (PD)-related peritonitis. Re-training is important, but no guidelines exist. We describe the implementation of a structured re-training program to decrease peritonitis rates.

Methods: This is a prospective quality improvement study involving pediatric patients on long-term home automated PD at National University Hospital, Singapore, between 2012 and 2018. With increasing peritonitis rates, systematic root cause analysis was performed, and based on the contributory factors identified, a structured re-training program was implemented from 2015. This was conducted in 5 cycles, each consisting of 4 modules (hand hygiene, exit site care, peritonitis, and PD troubleshooting).

Results: Peritonitis rates were analyzed in 2 phases: Phase 1 (2012-2014) when no re-training was performed and Phase 2 (2016-2018) after re-training was instituted. Fifty-nine patients were included. Of these, 45 patients were in Phase 1, 32 in Phase 2, and 18 in both phases. Peritonitis rates decreased from 0.37 ± 0.67 episodes per patient-year in Phase 1 to 0.13 ± 0.32 episodes per patient-year in Phase 2. After adjusting for age at kidney failure onset, PD vintage, years of nursing experience, and the average patient-to-nurse ratio over the study period for each patient, the adjusted peritonitis rates decreased by 0.38 episodes per patient-year (95% CI, 0.09 to 0.67, p = 0.011) from Phase 1 to Phase 2.

Conclusion: Despite an improvement in staffing ratio, peritonitis rates only improved significantly after intensive structured re-training was instituted.
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http://dx.doi.org/10.1007/s00467-021-05039-2DOI Listing
October 2021

Systemic immune-inflammation index predicts prognosis in patients with different EGFR-mutant lung adenocarcinoma.

Medicine (Baltimore) 2021 Feb;100(6):e24640

Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi.

Abstract: Lung cancer is the most common type of cancer worldwide with a high mortality rate. The specific tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR) have made enormous strides in non-small-cell lung cancer (NSCLC) treatment. The novel systemic immune-inflammation index (SII), a parameter that integrates lymphocytes, neutrophils, and platelets, has been found to play the vital role of a marker for predicting survival and recrudescence in various tumors.We retrospectively examined 102 patients with different EGFR-mutant lung adenocarcinomas. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. Cut-off points were identified using the receiver operating characteristic curves with the maximum log-rank values. The Cox proportional hazards regression, expressed as p value, hazards regression, and 95% confidence interval, was conducted to assess the prognostic values of variables in overall survival (OS)/ progression-free survival (PFS).Lower SII was associated with prolonged survival in patients with different EGFR mutant lung adenocarcinomas in both variable and multivariable analyses.SII before treatment was a powerful indicator for the PFS and OS of patients who received the first-generation EGFR-TKI.
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http://dx.doi.org/10.1097/MD.0000000000024640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886494PMC
February 2021

Long non-coding RNA nuclear paraspeckle assembly transcript 1 promotes activation of T helper 2 cells via inhibiting STAT6 ubiquitination.

Hum Cell 2021 May 7;34(3):800-807. Epub 2021 Feb 7.

The Rhinology Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China.

T helper (Th) 2 cell-medicated immune response participates in various immune diseases, including systemic lupus erythematosus (SLE). Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be associated with T helper 2 (Th2) cell activation. Here, we demonstrated the molecular mechanism of NEAT1 in regulating Th2 cell activation. We found that NEAT1 was located in nucleus. NEAT1 overexpression promoted the levels of Th2-related cytokines IL-4, IL-5 and IL-13 in CD4 T cells. Moreover, NEAT1 up-regulation reduced Th1-related cytokine INF-γ production and enhanced the levels of Th17-related cytokines IL-17 in CD4 T cells. STAT6 deficiency reduced the levels of IL-4, IL-5, IL-13 and IL-17 enhanced the levels of INF-γ in CD4 T cells, which was rescued by NEAT1 overexpression. Moreover, NEAT1 promoted STAT6 protein expression, whereas NEAT1 had no effect on the expression of STAT6 mRNA. Furthermore, NEAT1 interacted with STAT6, inhibited the ubiquitination of STAT6 in CD4 T cells. In conclusion, our work has confirmed that NEAT1 promotes STAT6 expression by inhibiting STAT6 ubiquitination, thereby promoting Th2 cell activation. Thus, our work may highlight novel insights into the molecular mechanism of NEAT1 in regulating Th2 cell activation.
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http://dx.doi.org/10.1007/s13577-021-00496-1DOI Listing
May 2021

Emission and ecological risk of pharmaceuticals and personal care products affected by tourism in Sanya City, China.

Environ Geochem Health 2021 Aug 27;43(8):3083-3097. Epub 2021 Jan 27.

Key Laboratory of the Ministry of Education for Coastal Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Fujian, 361102, China.

In recent years, concern around the impact of pharmaceuticals and personal care products (PPCPs) on the environment has grown. In order to investigate the influence of tourists on emissions and ecological risk of PPCPs, the concentrations of thirty PPCPs were measured in influent and effluent from the four largest wastewater treatment plants, as well as surface river water at six sites in a famous tourist city (Sanya City, China). Substantial increasing trends on PPCPs levels were observed from low to high tourist season (ng/L to µg/L, or µg/L to mg/L). Caffeine (CAF) was dominant with concentrations as high as 185 µg/L. Emission load per capita was estimated to explore the contribution of different populations. Tourist migrant population might be a dominant contributor, as they were mostly elderly people who took long-term medication. The predicted no-effect concentration was derived using the species sensitivity distribution method to calculate the ecological risk quotient (RQ) of the dominant PPCPs. Additionally, RQs of seven dominant PPCPs in rivers were > 1, indicating high chronic ecological risk for freshwater ecosystems. The results of this study will assist in raising the awareness and improving management of emerging pollutants in less industrialized regions.
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http://dx.doi.org/10.1007/s10653-021-00828-yDOI Listing
August 2021

Protein kinase D participates in cardiomyocyte hypertrophy by regulating extracellular signal-regulated and myocyte enhancer factor 2D.

Rev Port Cardiol (Engl Ed) 2021 Mar 14;40(3):191-200. Epub 2020 Dec 14.

Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, PR China. Electronic address:

Objective: Cardiomyocyte hypertrophy is an important feature of hypertension. However, its molecular underpinnings, especially the signaling cascades, remain unclear. Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II).

Methods: Neonatal rat cardiomyocytes from 2- to 3-day-old Sprague-Dawley rats were prepared and Western blot, real-time quantitative PCR and immunofluorescence staining were used to assess the activation and translocation of pathway signaling molecules. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression and [3H]-leucine (Leu) incorporation were measured to determine cell hypertrophy.

Results: Elevated levels of phosphorylated PKD (p-PKD) and ERK5 (p-ERK5) were observed in cardiomyocytes stimulated with Ang II, while silencing protein kinase C epsilon (PKCɛ) resulted in significantly lower levels of p-PKD. Furthermore, Ang II-induced ERK5 activated translocation was mediated by the PKD pathway. Consequently, inhibiting PKCɛ, PKD and ERK5 by siRNA significantly attenuated Ang II-induced MEF2D activation, ANP and BNP mRNA expression, and [3H]-Leu incorporation.

Conclusions: Our studies are the first to show that the PKCɛ/PKD/ERK5/MEF2D pathway plays an important role in the cardiomyocyte hypertrophy response to Ang II.
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http://dx.doi.org/10.1016/j.repc.2020.08.008DOI Listing
March 2021

Global and Local Tensor Factorization for Multi-criteria Recommender System.

Patterns (N Y) 2020 May 8;1(2):100023. Epub 2020 May 8.

Institute for Infocomm Research, 1 Fusionopolis Way, Singapore 138632, Singapore.

In multi-criteria recommender systems, matrix factorization characterizes users and items via latent factor vectors inferred from user-item rating patterns. However, two-dimensional matrix factorization models may not be able to cope with the recommendation problem that involves additional criterion-specific rating data. This study introduces a tensor factorization method to handle three-dimensional user-item-criterion rating data. Moreover, we observe that using single global tensor factorization alone may not be sufficient to characterize diverse preferences among different groups of users, and a combined global and local tensor factorization method (GLTF) for multi-criteria recommendation is thus proposed. One key benefit of the GLTF is that it can leverage global user-item-criterion rating patterns while also exploiting local user-subset specific rating behaviors to jointly infer the latent factor representations for users, items, and specific item criteria. Experimental results, which used real-life data available to the public, demonstrated that the GLTF is superior to well-established baseline methods.
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http://dx.doi.org/10.1016/j.patter.2020.100023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660452PMC
May 2020

Idiopathic Pulmonary Fibrosis Registry China study (PORTRAY): protocol for a prospective, multicentre registry study.

BMJ Open 2020 11 11;10(11):e036809. Epub 2020 Nov 11.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Capital Medical University, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterised by a fibrotic histological pattern found in usual interstitial pneumonia. Its causes, pathogenesis, clinical phenotype and molecular mechanisms are poorly defined. Large-scale, multicentre studies are warranted to better understand IPF as a disease in China, its associated risk factors, clinical characteristics, diagnosis, disease progression and treatment.

Methods And Analysis: The Idiopathic Pulmonary Fibrosis Registry China Study (PORTRAY) is a prospective, multicentre registry study of patients with IPF in China. Eight hundred patients will be enrolled over a 36-month period and followed for at least 3 years to generate a comprehensive database on baseline characteristics and various follow-up parameters including patient-reported outcomes. Biological specimens will also be collected from patients to develop a library of blood, bronchoalveolar lavage fluid and lung biopsy samples, to support future research. As of 15 December 2019, 204 patients from 19 large medical centres with relatively high IPF diagnosis and treatment rates had been enrolled. Patient characteristics will be presented using descriptive statistics. The Kaplan-Meier method will be used for survival analyses. Repeated measures will be used to compare longitudinal changes in lung function, imaging and laboratory tests. Results following analysis have been projected to be available by July 2025.

Ethics And Dissemination: The study protocol was reviewed and approved by the Institutional Review Board from all the study sites currently recruiting patients. Study results will be published in peer-reviewed journals.

Trial Registration Number: NCT03666234.
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http://dx.doi.org/10.1136/bmjopen-2020-036809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661367PMC
November 2020

Correction: Rapamycin increases CCN2 expression of lung fibroblasts via phosphoinositide 3-kinase.

Lab Invest 2021 Jan;101(1):136-137

Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1038/s41374-020-00501-5DOI Listing
January 2021

Targeting FSTL1 for Multiple Fibrotic and Systemic Autoimmune Diseases.

Mol Ther 2021 01 23;29(1):347-364. Epub 2020 Sep 23.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Tianjin Key Laboratory of Protein Sciences, Nankai University, Tianjin 300071, China. Electronic address:

Follistatin-like 1 (FSTL1) is a matricellular protein that is upregulated during development and disease, including idiopathic pulmonary fibrosis (IPF), keloid, and arthritis. The profibrotic and pro-inflammatory roles of FSTL1 have been intensively studied during the last several years, as well as in this report. We screened and identified epitope-specific monoclonal neutralizing antibodies (nAbs) to functionally block FSTL1. FSTL1 nAbs attenuated bleomycin-induced pulmonary and dermal fibrosis in vivo and transforming growth factor (TGF)-β1-induced dermal fibrosis ex vivo in human skin. In addition, FSTL1 nAbs significantly reduced existing lung fibrosis and skin fibrosis in experimental models. FSTL1 nAbs exerted their potent antifibrotic effects via reduced TGF-β1 responsiveness and subsequent myofibroblast activation and extracellular matrix production. We also observed that FSTL1 nAbs attenuated the severity of collagen-induced arthritis in mice, which was accompanied by reduced inflammatory responses in vitro. Our findings suggest that FSTL1 nAbs are a promising new therapeutic strategy for the treatment of multiple organ fibrosis and systemic autoimmune diseases.
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http://dx.doi.org/10.1016/j.ymthe.2020.09.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791083PMC
January 2021

Direct medical costs of hospitalized patients with idiopathic pulmonary fibrosis in a tertiary hospital in China.

Chin Med J (Engl) 2020 Oct;133(20):2498-2500

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China.

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http://dx.doi.org/10.1097/CM9.0000000000001089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575163PMC
October 2020

Psychometric testing of the Chinese version of Self-Care of Coronary Heart Disease Inventory.

Int J Nurs Pract 2021 Apr 10;27(2):e12885. Epub 2020 Sep 10.

School of Health Sciences, Wuhan University, Wuhan, Hubei, China.

Aim: To psychometrically test the Chinese version of Self-Care of Coronary Heart Disease Inventory.

Background: Self-care is a significant step to impede the progression of coronary heart disease and serves as the primary outcome in self-care interventions. In China, however, no instrument is available to measure self-care in patients with coronary heart disease. To address this gap, we introduce the Self-Care of Coronary Heart Disease Inventory into China.

Design: A cross-sectional design.

Methods: We translated the inventory into Chinese using standardized methods. Then, it was psychometrically tested on a convenience sample of 301 patients with coronary heart disease (October 2017 to May 2018). Construct validity was evaluated via exploratory factor analysis and testing hypotheses. Internal consistency reliability was measured with Cronbach's alpha or composite reliability.

Results: Both self-care maintenance and management subscales showed a two-factor structure, whereas self-care confidence subscale showed a one-dimension structure. All subscales were significantly correlated with associated variables (disease-related knowledge and perceived control). The internal consistency reliability for all three subscales was acceptable.

Conclusion: The Chinese version showed acceptable psychometric properties when applied to the sample group of this study. It is recommended for use in self-care interventions targeting coronary heart disease.
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http://dx.doi.org/10.1111/ijn.12885DOI Listing
April 2021

Possible association of idiopathic pulmonary hemosiderosis with rheumatoid arthritis: A case report.

Exp Ther Med 2020 Sep 25;20(3):2291-2297. Epub 2020 Jun 25.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, P.R. China.

Idiopathic pulmonary hemosiderosis (IPH) is a rare interstitial lung disease, usually occurring in children or young adults. Although several studies reported on the coexistence of IPH and immune system diseases, the association between these conditions has not been well described. The present study reports on the case of a 21-year-old female patient who presented with bilateral lung abnormalities. The patient was admitted due to a 2-year history of progressive exertional dyspnea, as well as arthralgia and joint swelling in the recent 2 months. During the past 15 years, the patient had been diagnosed with anemia and received repeated blood transfusions. Serial chest CT scans indicated an interstitial pattern. On physical examination, the patient had pale skin with a hemoglobin level of 65 g/l and exhibited finger-clubbing. Arterial blood gas analysis revealed hypoxia. Anticyclic-citrullinated protein antibody and rheumatoid factor were highly positive. Pulmonary function tests revealed restrictive ventilation dysfunction and decreased diffusion capacity. Bronchoscopy and biopsy confirmed diffuse alveolar hemorrhage. Following assessment of the etiology, the diagnosis of IPH was made by exclusion. The patient's symptoms and laboratory findings combined also confirmed the diagnosis of rheumatoid arthritis (RA). After receiving corticosteroid treatment, the patient's condition improved, and she was discharged and followed up. Based on this patient and a review of the literature, the present study demonstrated for the first time that IPH may mediate the development of an RA pathology. Therefore, early diagnosis is important for the timely management of IPH, which may also delay or even prevent the development of immune system diseases, e.g. RA, in patients with IPH. Further attention should be paid to determine the association between IPH and immune system diseases in the clinical setting.
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http://dx.doi.org/10.3892/etm.2020.8938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401859PMC
September 2020

[Corrigendum] Kinase inhibitors fail to induce mesenchymal‑epithelial transition in fibroblasts from fibrotic lung tissue.

Int J Mol Med 2020 09 26;46(3):1249. Epub 2020 Jun 26.

Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.

Following the publication of the above article, an interested reader drew to the authors' attention that Figs. 3A and 5A contained the same image derived under a light microscope. Fig. 3A was intending to show the cell morphology of primary cultured human lung fibroblasts. In examining their source data, the authors have come to realize that, during the process of figure preparation, an incorrect image for Fig. 3A was selected, and the figure was compiled incorrectly. The corrected version of Fig. 3, containing the correct microscopic image for Fig. 3A, is shown opposite. Note that this error did not affect understanding of the morphology of human lung fibroblasts, either in terms of the results or the conclusions reported in this paper. The authors apologize to the Editor of International Journal of Molecular Medicine and to readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 32: 430-438, 2013; DOI: 10.3892/ijmm.2013.1415].
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http://dx.doi.org/10.3892/ijmm.2020.4660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388839PMC
September 2020

Assessment of three types of intranasal nebulization devices in three-dimensional printed models and volunteers: a pilot study.

Int Forum Allergy Rhinol 2020 12 20;10(12):1300-1308. Epub 2020 Jul 20.

Department of Rhinology, The ENT Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Intranasal nebulization is an effective treatment for chronic rhinosinusitis and allergic rhinitis; however, terminal inhalation devices have not been fully studied. We compared the sinonasal aerosol distributions and adverse effects of different inhalation units.

Methods: A mask, double-head nozzle, and single-head nozzle were applied to atomize the methylene blue solution to 3-dimensional printed models of the pediatric nasal cavity, adult nasal cavity with septal deviation, and postsurgical paranasal sinuses, and staining of the different sites was scored. Volunteers received nebulization of normal saline via different devices; thereafter, the adverse effects were assessed using the visual analogue scale (VAS).

Results: After nebulization, the staining scores for the middle turbinate and middle meatus of the pediatric and adult nasal cavity models and the score for the anterior ethmoid sinus of the sinus model with the single-head nozzle were significantly higher than those with the mask and double-head nozzle (all p < 0.05; η for effect size estimates were above 0.68). Among the 31 volunteers, the adverse effects, including nasal irritation, facial pressure/pain, ear fullness/pain, postnasal drip, and throat irritation/cough, were mild. The variations in the incidence and VAS scores of the adverse effects among the devices were not significant (all p > 0.05).

Conclusion: The single-head nozzle was the most effective device in aerosol delivery to the lateral wall of the nasal cavity and sinuses; conversely, the mask yielded limited sinonasal deposition. Intranasal nebulization was well tolerated, and the adverse effects among the devices were comparable. These findings are meaningful for selecting and developing inhalation units.
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http://dx.doi.org/10.1002/alr.22657DOI Listing
December 2020
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