Publications by authors named "Songlin Wang"

193 Publications

Identification and profiles of microRNAs in different development stages of miniature pig secondary palate.

Genomics 2021 Jun 9. Epub 2021 Jun 9.

Department of geriatric dentistry, Capital Medical University School of Stomatology, Tiantan Xili No.4, Beijing 100050, China; Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No.4, Beijing 100050, China. Electronic address:

Cleft palate is one of the most frequent craniofacial malformation birth defects. Miniature pigs (Sus scrofa) are a valuable alternative large animal model to explore human palate development. Presently, the microRNA (miRNA) expression profiles in miniature pigs during palatogenesis from embryonic day (E) 30 to 50 were identified. A total of 2044 known miRNAs and 192 novel miRNAs were identified. The functional characteristics of their potential target genes were identified using Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway analysis. MiRNAs displayed diverse expression levels among the different stages. Using Short Time-series Expression Miner software to investigate the expression patterns of miRNAs from E30-50, all miRNAs were clustered into 20 profiles. The profiles showing miRNAs expression decreased (profile 0)/increased (profile 19) from E30-50 were the main patterns during palatogenesis. Hub genes of four significant modules were identified by weighted correlation network analysis, including ssc-miR-98, ssc-miR-27a_R + 1, and ssc-miR-150, etc. which might be novel potential targets for regulating palate development. The data are expected to improve the understanding of palate development and the etiology of cleft palate in further studies.
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http://dx.doi.org/10.1016/j.ygeno.2021.06.009DOI Listing
June 2021

The intact parasympathetic nerve promotes submandibular gland regeneration through ductal cell proliferation.

Cell Prolif 2021 Jun 7:e13078. Epub 2021 Jun 7.

Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.

Objectives: Salivary gland regeneration is closely related to the parasympathetic nerve; however, the mechanism behind this relationship is still unclear. The aim of this study was to evaluate the relationship between the parasympathetic nerve and morphological differences during salivary gland regeneration.

Materials And Methods: We used a duct ligation/deligation-induced submandibular gland regeneration model of Sprague-Dawley (SD) rats. The regenerated submandibular gland with or without chorda lingual (CL) innervation was detected by haematoxylin-eosin staining, real-time PCR (RT-PCR), immunohistochemistry and Western blotting. We counted the number of Ki67-positive cells to reveal the proliferation process that occurs during gland regeneration. Finally, we examined the expression of the following markers: aquaporin 5, cytokeratin 7, neural cell adhesion molecule (NCAM) and polysialyltransferases.

Results: Intact parasympathetic innervation promoted submandibular gland regeneration. The process of gland regeneration was significantly repressed by cutting off the CL nerve. During gland regeneration, Ki67-positive cells were mainly found in the ductal structures. Moreover, the expression of NCAM and polysialyltransferases-1 (PST) expression in the innervation group was significantly increased during early regeneration and decreased in the late stages. In the denervated submandibular glands, the expression of NCAM decreased during regeneration.

Conclusions: Our findings revealed that the regeneration of submandibular glands with intact parasympathetic innervation was associated with duct cell proliferation and the increased expression of PST and NCAM.
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http://dx.doi.org/10.1111/cpr.13078DOI Listing
June 2021

Adipose-mesenchymal stromal cells suppress experimental Sjögren syndrome by IL-33-driven expansion of ST2 regulatory T cells.

iScience 2021 May 16;24(5):102446. Epub 2021 Apr 16.

Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA.

Adipose-derived mesenchymal stromal cells (ADSCs) play important roles in the alleviation of inflammation and autoimmune diseases. Interleukin-33 (IL-33), a member of the IL-1 family, has been shown to regulate innate and adaptive immunity. However, it is still unknown whether ADSCs regulate immune responses via IL-33. We show here that ADSCs produced IL-33 in response to IL-1β stimulation, which depended on TAK1, ERK, and p38 pathways. ADSCs-derived IL-33 drove the proliferation of CD4Foxp3ST2 regulatory T cells (Tregs) and alleviated experimental autoimmune Sjögren syndrome in mice. Importantly, human ADSCs also produced IL-33 in response to IL-1β. Thus, we have revealed a previously unrecognized immunoregulatory function of ADSCs by IL-33 production in experimental autoimmunity, which may have clinical applications for human immunopathology.
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http://dx.doi.org/10.1016/j.isci.2021.102446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105666PMC
May 2021

Structural basis for allosteric control of the SERCA-Phospholamban membrane complex by Ca and phosphorylation.

Elife 2021 May 12;10. Epub 2021 May 12.

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States.

Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca-transport response to β-adrenergic stimulation, thus modulating cardiac output during the fight-or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca-ATPase (SERCA), keeping this enzyme's function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN's cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at the transmembrane binding interface of the SERCA-PLN complex that are propagated to the enzyme's active site, augmenting Ca transport. Our findings address long-standing questions about SERCA regulation, epitomizing a signal transduction mechanism operated by posttranslationally modified bitopic membrane proteins.
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http://dx.doi.org/10.7554/eLife.66226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184213PMC
May 2021

A LiDAR Sensor-Based Spray Boom Height Detection Method and the Corresponding Experimental Validation.

Sensors (Basel) 2021 Mar 17;21(6). Epub 2021 Mar 17.

Beijing Research Center of Intelligent Equipment for Agriculture, Beijing 100097, China.

Sprayer boom height () variations affect the deposition and distribution of droplets. An control system is used to adjust to maintain an optimum distance between the boom and the crop canopy, and an detection sensor is a key component of the control system. This study presents a new, low-cost light detection and ranging (LiDAR) sensor for detection developed based on the principle of single-point ranging. To examine the detection performance of the LiDAR sensor, a step height detection experiment, a field ground detection experiment, and a wheat stubble (WS) height detection experiment as well as a comparison with an ultrasonic sensor were performed. The results showed that the LiDAR sensor could be used to detect . When used to detect the WS height (), the LiDAR sensor primarily detected the WS roots and the inside of the WS canopy. and movement speed of the LiDAR sensor () has a greater impact on the detection performance of the LiDAR sensor for the WS canopy than that for the WS roots. The detection error of the LiDAR sensor for the WS roots is less than 5.00%, and the detection error of the LiDAR sensor for the WS canopy is greater than 8.00%. The detection value from the LiDAR sensor to the WS root multiplied by 1.05 can be used as a reference basis for adjusting , and after the WS canopy height is added to the basis, the value can be used as an index for adjusting in WS field spraying. The results of this study will promote research on the boom height detection method and autonomous control system.
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http://dx.doi.org/10.3390/s21062107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002541PMC
March 2021

Quantitative evaluation of infectious health care wastes from numbers of confirmed, suspected and out-patients during COVID-19 pandemic: A case study of Wuhan.

Waste Manag 2021 May 22;126:323-330. Epub 2021 Mar 22.

School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, PR China.

The fight against coronavirus disease 2019 (COVID-19) is still running its courses. Proper management and disposal of health care wastes (HCWs) are critical to win the fight. To achieve aforementioned tasks, prediction of their production is highly desired. In this study, primary data of production of three kinds of HCWs collected from Wuhan, the first epidemic epicenter worldwide and a mega city with more than 10 million population who has went through a lockdown period of 78 days, were reported for their first time. HCWs were classified into routine HCWs, infectious HCWs (IHCWs) and infectious municipal solid wastes. Among them, infectious HCWs from designated hospitals for COVID-19 were recognized as the most dangerous one. A multiple linear regression (MLR) model was built to predict the production of IHCWs with high significance. Numbers of patients were demonstrated high correlations with the production of IHCWs in an order of confirmed patients > out-patients > suspected patients. By the MLR model, production rates of IHCWs by confirmed, suspected and out patients were determined as 3.2, 1.8 and 0.1 kg/patient, respectively. In addition, constant production of IHCWs during the pandemic period was determined as 13 tons/d. This is the first study on quantitative evaluation of infectious HCWs during COVID-19 pandemic. The achievements in this study have potentials to shed light on global efforts to the prediction, management and disposal of vast HCWs generated in the war against COVID-19.
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http://dx.doi.org/10.1016/j.wasman.2021.03.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983547PMC
May 2021

LncRNA, PLXDC2-OT promoted the osteogenesis potentials of MSCs by inhibiting the deacetylation function of RBM6/SIRT7 complex and OSX specific isoform.

Stem Cells 2021 Mar 8. Epub 2021 Mar 8.

Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People's Republic of China.

Bone regeneration and remodeling are complex physiological processes that are regulated by key transcription factors. Understanding the regulatory mechanism of key transcription factors on the osteogenic differentiation of mesenchymal stem cells (MSCs) is a key issue for successful bone regeneration and remodeling. In the present study, we investigated the regulatory mechanism of the histone deacetylase Sirtuin 7 (SIRT7) on the key transcription factor OSX and osteogenesis of MSCs. In this study, we found that SIRT7 knockdown increased ALP activity and in vitro mineralization and promoted the expression of the osteogenic differentiation markers DSPP, DMP1, BSP, OCN, and the key transcription factor OSX in MSCs. In addition, SIRT7 could associate with RNA binding motif protein 6 (RBM6) to form a protein complex. Moreover, RBM6 inhibited ALP activity, the expression of DSPP, DMP1, BSP, OCN, and OSX in MSCs, and the osteogenesis of MSCs in vivo. Then, the SIRT7/RBM6 protein complex was shown to downregulate the level of H3K18Ac in the OSX promoter by recruiting SIRT7 to the OSX promoter and inhibiting the expression of OSX isoforms 1 and 2. Furthermore, lncRNA PLXDC2-OT could associate with the SIRT7/RBM6 protein complex to diminish its binding and deacetylation function in the OSX promoter and its inhibitory function on OSX isoforms 1 and 2 and to promote the osteogenic potential of MSCs.
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http://dx.doi.org/10.1002/stem.3362DOI Listing
March 2021

Solid-State NMR of Membrane Proteins in Lipid Bilayers: To Spin or Not To Spin?

Acc Chem Res 2021 03 3;54(6):1430-1439. Epub 2021 Mar 3.

Membrane proteins mediate a plethora of cellular functions and represent important targets for drug development. Unlike soluble proteins, membrane proteins require native-like environments to fold correctly and be active. Therefore, modern structural biology techniques have aimed to determine the structure and dynamics of these membrane proteins at physiological temperature and in liquid crystalline lipid bilayers. With the flourishing of new NMR methodologies and improvements in sample preparations, magic angle spinning (MAS) and oriented sample solid-state NMR (OS-ssNMR) spectroscopy of membrane proteins is experiencing a new renaissance. Born as antagonistic approaches, these techniques nowadays offer complementary information on the structural topology and dynamics of membrane proteins reconstituted in lipid membranes. By spinning biosolid samples at the magic angle (θ = 54.7°), MAS NMR experiments remove the intrinsic anisotropy of the NMR interactions, increasing spectral resolution. Internuclear spin interactions (spin exchange) are reintroduced by RF pulses, providing distances and torsion angles to determine secondary, tertiary, and quaternary structures of membrane proteins. OS-ssNMR, on the other hand, directly detects anisotropic NMR parameters such as dipolar couplings (DC) and anisotropic chemical shifts (CS), providing orientational constraints to determine the architecture (i.e., topology) of membrane proteins relative to the lipid membrane. Defining the orientation of membrane proteins and their interactions with lipid membranes is of paramount importance since lipid-protein interactions can shape membrane protein conformations and ultimately define their functional states.In this Account, we report selected studies from our group integrating MAS and OS-ssNMR techniques to give a comprehensive view of the biological processes occurring at cellular membranes. We focus on the main experiments for both techniques, with an emphasis on new implementation to increase both sensitivity and spectral resolution. We also describe how the structural constraints derived from both isotropic and anisotropic NMR parameters are integrated into dynamic structural modeling using replica-averaged orientational-restrained molecular dynamics simulations (RAOR-MD). We showcase small membrane proteins that are involved in Ca transport and regulate cardiac and skeletal muscle contractility: phospholamban (PLN, 6 kDa), sarcolipin (SLN, 4 kDa), and DWORF (4 kDa). We summarize our results for the structures of these polypeptides free and in complex with the sarcoplasmic reticulum (SR) Ca-ATPase (SERCA, 110 kDa). Additionally, we illustrate the progress toward the determination of the structural topology of a six transmembrane protein associated with succinate and acetate transport (SatP, hexamer 120 kDa). From these examples, the integrated MAS and OS-ssNMR approach, in combination with modern computational methods, emerges as a way to overcome the challenges posed by studying large membrane protein systems.
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http://dx.doi.org/10.1021/acs.accounts.0c00670DOI Listing
March 2021

Atomic-level differences between brain parenchymal- and cerebrovascular-seeded Aβ fibrils.

Sci Rep 2021 01 8;11(1):247. Epub 2021 Jan 8.

Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA.

Alzheimer's disease is characterized by neuritic plaques, the main protein components of which are β-amyloid (Aβ) peptides deposited as β-sheet-rich amyloid fibrils. Cerebral Amyloid Angiopathy (CAA) consists of cerebrovascular deposits of Aβ peptides; it usually accompanies Alzheimer's disease, though it sometimes occurs in the absence of neuritic plaques, as AD also occurs without accompanying CAA. Although neuritic plaques and vascular deposits have similar protein compositions, one of the characteristic features of amyloids is polymorphism, i.e., the ability of a single pure peptide to adopt multiple conformations in fibrils, depending on fibrillization conditions. For this reason, we asked whether the Aβ fibrils in neuritic plaques differed structurally from those in cerebral blood vessels. To address this question, we used seeding techniques, starting with amyloid-enriched material from either brain parenchyma or cerebral blood vessels (using meninges as the source). These amyloid-enriched preparations were then added to fresh, disaggregated solutions of Aβ to make replicate fibrils, as described elsewhere. Such fibrils were then studied by solid-state NMR, fiber X-ray diffraction, and other biophysical techniques. We observed chemical shift differences between parenchymal vs. vascular-seeded replicate fibrils in select sites (in particular, Ala2, Phe4, Val12, and Gln15 side chains) in two-dimensional C-C correlation solid-state NMR spectra, strongly indicating structural differences at these sites. X-ray diffraction studies also indicated that vascular-seeded fibrils displayed greater order than parenchyma-seeded fibrils in the "side-chain dimension" (~ 10 Å reflection), though the "hydrogen-bond dimensions" (~ 5 Å reflection) were alike. These results indicate that the different nucleation conditions at two sites in the brain, parenchyma and blood vessels, affect the fibril products that get formed at each site, possibly leading to distinct pathophysiological outcomes.
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http://dx.doi.org/10.1038/s41598-020-80042-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794565PMC
January 2021

Transformation of acetaminophen in solution containing both peroxymonosulfate and chlorine: Performance, mechanism, and disinfection by-product formation.

Water Res 2021 Feb 4;189:116605. Epub 2020 Nov 4.

School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China; Center for the Environmental Implications of Nanotechnology (CEINT), Duke University, Durham 27708-0287, USA. Electronic address:

With the fast development of peroxymonosulfate (PMS)-dominating processes in drinking water and wastewater treatment, residual PMS is easy to come across chlorine as these processes are usually followed by secondary chlorine disinfection. The synergistic effect of PMS and chlorine on the degradation of micro-organic pollutants is investigated by selecting acetaminophen (ACT) as a reference compound for the first time in this study. Unlike conventional PMS or chlorine activation which generates reactive species such as hydroxyl radical (HO), sulfate radical (SO), chlorine radical (Cl), and singlet oxygen (O), the efficient ACT removal is attributed to the direct catalytic chlorination by PMS due to the significantly enhanced consumption of chlorine along with negligible change of PMS concentration at neutral condition, and the same reaction pathways in both PMS/chlorine and chlorine processes. The kinetic study demonstrates that ACT oxidation by PMS/chlorine follows second order reaction, and the degradation efficiency can be promoted at alkaline conditions with peak rate constants at pH 9.0-10.0. The presence of chloride can enhance the removal of ACT, while ammonium and humic acid significantly retard ACT degradation. Higher formation of selected disinfection by-products (DBPs) is observed in the PMS/chlorine process than in the sole chlorination. This study highlights the important role of PMS in organic pollutants degradation and DBPs formation during the chlorination process.
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http://dx.doi.org/10.1016/j.watres.2020.116605DOI Listing
February 2021

Recycling application of modified waste electrolytic manganese anode slag as efficient catalyst for PMS activation.

Sci Total Environ 2021 Mar 17;762:143120. Epub 2020 Oct 17.

Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Hubei Key Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, PR China. Electronic address:

Electrolytic manganese anode slag (EMAS) is the waste residue produced by electrolytic manganese metal industry. At present, no mature recycling system has been established, which causes a waste of resources and threatens the environment. Therefore, the resource utilization of EMAS has attracted increased attention. In this paper, the in-situ resource utilization of EMAS can be realized by pickling treatment was reported. Specifically, EMAS after pickling treatment (PEMAS) was first used as catalyst to activate PMS to degrade tetrachlorophenol (4-CP). Pickling could remove the inert inorganic components on EMAS and increase the specific surface area, pore volume and Mn distribution of the catalyst, thus improving the catalytic performance of the catalyst. Under the conditions of 4-CP of 40 ppm, PMS of 1 mM and PEMAS of 0.3 g L, 85% of 4-CP could be degraded within 50 min. Mechanism studies proved that the main active species were O and O. Some O contributed to the generation of O and some O directly contributed to the degradation of 4-CP. During the reaction, the valence state of Mn transformed between Mn(III)/Mn(IV) and Mn(II)/Mn(III) and kept the cycle. Moreover, PEMAS/PMS system exhibited excellent independence of the solution pH, resistance to the versatile inorganic ions and background organic matters, and stability of recycling. In a word, this study has achieved the resource utilization of EMAS and the goal of treating waste with waste, which is a win-win strategy of economic and environmental benefits.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143120DOI Listing
March 2021

Detection of SARS-CoV-2 in saliva and characterization of oral symptoms in COVID-19 patients.

Cell Prolif 2020 Dec 19;53(12):e12923. Epub 2020 Oct 19.

Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China.

Objectives: In order to provide a more comprehensive understanding of the effects of SARS-CoV-2 on oral health and possible saliva transmission, we performed RNA-seq profiles analysis from public databases and also a questionnaire survey on oral-related symptoms of COVID-19 patients.

Materials And Methods: To analyse ACE2 expression in salivary glands, bulk RNA-seq profiles from four public datasets including 31 COVID-19 patients were recruited. Saliva and oropharyngeal swabs were collected. SARS-CoV-2 nucleic acids in saliva were detected by real-time polymerase chain reaction (RT-PCR). Additionally, a questionnaire survey on various oral symptoms such as dry mouth and amblygeustia was also carried out on COVID-19 patients.

Results: ACE2 expression was present at detectable levels in the salivary glands. In addition, of four cases with positive detection of salivary SARS-CoV-2 nucleic acids, three (75%) were critically ill on ventilator support. Furthermore, we observed the two major oral-related symptoms, dry mouth (46.3%) and amblygeustia (47.2%), were manifested by a relatively high proportion of 108 COVID-19 patients who accepted the questionnaire survey.

Conclusions: This study confirms the expression of ACE2 in the salivary glands and demonstrates the possibility of SARS-CoV-2 infection of salivary glands. Saliva may be a new source of diagnostic specimens for critically ill patients, since it can be easily collected without any invasive procedures. In addition, dry mouth and amblygeustia can be considered as initial symptoms of COVID-19 infection.
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http://dx.doi.org/10.1111/cpr.12923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645955PMC
December 2020

Editorial-Regenerative medicine and oral rehabilitation.

Authors:
Songlin Wang

J Oral Rehabil 2020 Nov 18;47 Suppl 1. Epub 2020 Sep 18.

School of Stomatology, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1111/joor.13086DOI Listing
November 2020

Rebalancing glucolipid metabolism and gut microbiome dysbiosis by nitrate-dependent alleviation of high-fat diet-induced obesity.

BMJ Open Diabetes Res Care 2020 08;8(1)

Capital Medical University School of Stomatology, Beijing, China

Introduction: High-fat diet (HFD)-induced obesity is accompanied by compromised nitric oxide (NO) signaling and gut microbiome dysregulation. Inorganic dietary nitrate, which acts as a NO donor, exerts beneficial effects on metabolic disorders. Here, we evaluated the effects of dietary nitrate on HFD-induced obesity and provided insights into the underlying mechanism.

Research Design And Methods: To investigate the preventive effect of dietary nitrate on HFD-induced obesity, C57BL/6 mice were randomly assigned into four groups (n=10/group), including normal control diet group (normal water and chow diet), HFD group (normal water and HFD), HFD+NaNO group (water containing 2 mM NaNO and HFD), and HFD+NaCl group (water containing 2 mM NaCl and HFD). During the experiment, body weight was monitored and glucolipid metabolism was evaluated. The mechanism underlying the effects of nitrate on HFD-induced obesity was investigated by the following: the NO-NO-NO pathway; endothelial NO synthase (eNOS) and cyclic guanosine monophosphate (cGMP) levels; gut microbiota via 16SRNA analysis.

Results: Dietary nitrate reduced the body weight gain and lipid accumulation in adipose and liver tissues in HFD-fed mice. Hyperlipidemia and insulin resistance caused by HFD were improved in mice supplemented with nitrate. The level of eNOS was upregulated by nitrate in the serum, liver, and inguinal adipose tissue. Nitrate, nitrite, and cGMP levels were decreased in mice fed on HFD but reversed in the HFD+NaNO group. Nitrate also rebalanced the colon microbiota and promoted a normal gut microbiome profile by partially attenuating the impacts of HFD. , , , and abundances were altered, and and abundances were higher in the HFD+NaNO group than that in the HFD group.

Conclusions: Inorganic dietary nitrate alleviated HFD-induced obesity and ameliorated disrupted glucolipid metabolism via NO-NO-NO pathway activation and gut microbiome modulation.
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http://dx.doi.org/10.1136/bmjdrc-2020-001255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449567PMC
August 2020

Stiffening, strengthening, and toughening of biodegradable poly(butylene adipate-co-terephthalate) with a low nanoinclusion usage.

Carbohydr Polym 2020 Nov 25;247:116687. Epub 2020 Jun 25.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou, 310027, China; Institute of Zhejiang University - Quzhou, 78 Jiuhua Boulevard North, Quzhou, 324000, China. Electronic address:

Simultaneous stiffening, strengthening, and toughening of biodegradable polymers, such as poly(butylene adipate-co-terephthalate) (PBAT) and others, is necessary for their use in packaging and agriculture applications. However, a high content of nanoinclusions is usually required, leading to a tradeoff between composite toughness and strength or stiffness in the reinforcement. Herein, we report an iterative reinforcement strategy that uses one nanocomposite to reinforce PBAT. An in-situ grafting polymerized cellulose nanocrystal (CNC)/PBAT (CNC-g-PBAT) nanocomposite consisting of ungrafted/free PBAT (PBAT) was used as an inclusion directly to reinforce a commercial PBAT. At an exceptionally low CNC usage of 0.02 wt.%, we achieved a simultaneous enhancement of the Young's modulus by 26 %, tensile strength by 27 %, elongation at break by 37 %, and toughness by 56 % over those for PBAT. To the best of our knowledge, such reinforcement efficiency is the highest among similar biodegradable polymer nanocomposites reported in the literature. The rheology, differential scanning calorimetry, and wide-angle X-ray diffraction measurements confirmed the mechanical reinforcement attributed to a synergistic contribution from PBAT and CNC-g-PBAT. In particular, the use of PBAT enhanced both stiffness and toughness of the composites, while the CNC-g-PBAT interacted within the polymer matrix and increased the crystallinity of the polymer matrix, leading to the strengthening and toughening effect. The strategy proposed here is greatly beneficial to producing high-performance biodegradable polymer nanocomposite films for packaging and agricultural applications using a very low amount of nanoinclusion.
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http://dx.doi.org/10.1016/j.carbpol.2020.116687DOI Listing
November 2020

NEAT1 Decreasing Suppresses Parkinson's Disease Progression via Acting as miR-1301-3p Sponge.

J Mol Neurosci 2021 Feb 25;71(2):369-378. Epub 2020 Jul 25.

Department of Neurology, TaiHe Hospital, Hubei University of Medicine, No. 32 Renmin South Road, Shiyan, 442000, Hubei Province, China.

Long non-coding RNA (lncRNA) plays a crucial role in multiple disorders, while the role of it in Parkinson's disease (PD) is still unclear. Here, the increased lncRNA NEAT1 was discovered in MPP-induced SH-SY5Y cells. Then, we proved that NEAT1 decreasing suppressed MPP-induced neuronal apoptosis, upregulation of α-syn and activation of NLRP3 inflammasome. Rescue experiments shown that the inhibition of NEAT1 decreasing to MPP-induced activation of NLRP3 inflammasome and subsequent neuronal apoptosis can be reversed by overexpressed α-syn. Subsequently, we indicated the interaction between NEAT1 and miR-1301-3p, as well as between NEAT1 and miR-5047. Interesting, we found that NEAT1 decreasing repressed the expression of GJB1, a downstream target of miR-1301-3p and miR-5047, through promoting miR-1301-3p rather than miR-5047 expression. Finally, we transfected miR-1301-3p inhibitor to MPP-induced SH-SY5Y cells following si-NEAT1, and found that downregulation of NEAT1 repressed α-syn-mediated the activation of NLRP3 inflammasome through regulating miR-1301-3p/GJB1 signaling pathway. Overall, our data demonstrated that NEAT1 decreasing effectively suppressed MPP-induced neuronal apoptosis. Mechanismly, downregulation of NEAT1 repressed α-syn-induced activation of NLRP3 inflammasome via inhibiting the expression of GJB1 by targeting miR-1301-3p. Our study supported a new and reliable evidence for lncRNA NEAT1 as a potential target for PD treatment.
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http://dx.doi.org/10.1007/s12031-020-01660-2DOI Listing
February 2021

Retinoic Acid Signal Negatively Regulates Osteo/Odontogenic Differentiation of Dental Pulp Stem Cells.

Stem Cells Int 2020 27;2020:5891783. Epub 2020 Jun 27.

Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.

Retinoic acid (RA) signal is involved in tooth development and osteogenic differentiation of mesenchymal stem cells (MSCs). Dental pulp stem cells (DPSCs) are one of the useful MSCs in tissue regeneration. However, the function of RA in osteo/odontogenic differentiation of DPSCs remains unclear. Here, we investigated the expression pattern of RA in miniature pig tooth germ and intervened in the RA signal during osteo/odontogenic differentiation of human DPSCs. Deciduous canine (DC) germs of miniature pigs were observed morphologically, and the expression patterns of RA were studied by hybridization (ISH). Human DPSCs were isolated and cultured in osteogenic induction medium with or without RA or BMS 493, an inverse agonist of the pan-retinoic acid receptors (pan-RARs). Alkaline phosphatase (ALP) activity assays, alizarin red staining, quantitative calcium analysis, CCK8 assay, osteogenesis-related gene expression, and transplantation were conducted to determine the osteo/odontogenic differentiation potential and proliferation potential of DPSCs. We found that the expression of and decreased during crown calcification of DCs of miniature pigs. Activation of RA signal inhibited ALP activities and mineralization of human DPSCs and decreased the mRNA expression of , , , and a transcription factor, . With BMS 493 treatment, the results were opposite. Interference in RA signal decreased the proliferation of DPSCs. transplantation experiments suggested that osteo/odontogenic differentiation potential of DPSCs was enhanced by inversing RA signal. Our results demonstrated that downregulation of RA signal promoted osteo/odontogenic differentiation of DPSCs and indicated a potential target pathway to improve tissue regeneration.
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http://dx.doi.org/10.1155/2020/5891783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336240PMC
June 2020

The Cytokine TGF-β Induces Interleukin-31 Expression from Dermal Dendritic Cells to Activate Sensory Neurons and Stimulate Wound Itching.

Immunity 2020 08 15;53(2):371-383.e5. Epub 2020 Jul 15.

Mucosal Immunology Section, NIDCR, NIH, Bethesda, MD 20892, USA. Electronic address:

Cutaneous wound healing is associated with the unpleasant sensation of itching. Here we investigated the mechanisms underlying this type of itch, focusing on the contribution of soluble factors released during healing. We found high amounts of interleukin 31 (IL-31) in skin wound tissue during the peak of itch responses. Il31 mice lacked wound-induced itch responses. IL-31 was released by dermal conventional type 2 dendritic cells (cDC2s) recruited to wounds and increased itch sensory neuron sensitivity. Transfer of cDC2s isolated from late-stage wounds into healthy skin was sufficient to induce itching in a manner dependent on IL-31 expression. Addition of the cytokine TGF-β1, which promotes wound healing, to dermal DCs in vitro was sufficient to induce Il31 expression, and Tgfbr1 CD11c-Cre mice exhibited reduced scratching and decreased Il31 expression in wounds in vivo. Thus, cDC2s promote itching during skin would healing via a TGF-β-IL-31 axis with implications for treatment of wound itching.
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http://dx.doi.org/10.1016/j.immuni.2020.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362873PMC
August 2020

Total body irradiation-induced colon damage is prevented by nitrate-mediated suppression of oxidative stress and homeostasis of the gut microbiome.

Nitric Oxide 2020 09 26;102:1-11. Epub 2020 May 26.

Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China. Electronic address:

Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3/NO2/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for mice with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury.
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http://dx.doi.org/10.1016/j.niox.2020.05.002DOI Listing
September 2020

Characterizing Micromechanical Properties of Friction Welding Interface between TiAl Alloy and GH3039 Superalloy.

Materials (Basel) 2020 Apr 30;13(9). Epub 2020 Apr 30.

Key Laboratory of High Performance Manufacturing for Aero Engine, School of Mechanical Engineering, Northwestern Polytechnical University, Xi'an 710072, China.

To explore the macro-fracture mechanism of a friction welded joint between TiAl alloy and GH3039 superalloy, the micromechanical properties of intermediate phases at the joint interface are characterized and the relationship between the macro-fracture and micro-fracture of the joint is established. The indentation technique has been employed to calculate the nano-hardness and fracture toughness of the intermediate phases. The dynamic in-situ tensile test in SEM has been applied to observe the initiation and propagation process of cracks at the interface. It has been found that AlNiTi and AlNiTi have the highest nano-hardness and elastic recovery rates, while TiAl and GH3039 base metals have the lowest nano-hardness and elastic recovery rates. This indicates that the harder the materials, the more prone they are to elastic deformation. Nevertheless, the fracture toughness of AlNiTi and AlNiTi are the two lowest, which were 1.7 MPa·m and 2.7 MPa·m, respectively. The cracks sprouted from AlNiTi and AlNiTi and then spread throughout the entire intermediate phase zone. In other words, the fracture mainly happened in these two phase layers. It has been concluded that AlNiTi and AlNiTi were the two weakest phases at the interface and their poor fracture toughness results in low joint strength.
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http://dx.doi.org/10.3390/ma13092072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254247PMC
April 2020

Saliva Microbiome Changes in Patients With Periodontitis With and Without Chronic Obstructive Pulmonary Disease.

Front Cell Infect Microbiol 2020 15;10:124. Epub 2020 Apr 15.

Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China.

The oral microbiota plays a key part in the initial colonization by pathogens and the chronic inflammatory reaction of the host. We measured variations in the salivary microbiota and evaluated their potential associations with periodontitis and chronic obstructive pulmonary disease (COPD). We investigated the salivary microbiota of patients with COPD and periodontitis ( = 21) compared with that in patients with periodontitis alone ( = 36) and with healthy controls (HCs; = 14), using pyrosequencing of polymerase chain reaction-amplified 16s rRNA genes. Bacterial richness and diversity were significantly higher in patients suffering from COPD, and the bacterial family Lachnospiraceae was observed frequently only among patients with COPD and periodontitis. , and were the core bacterial genera that showed significant differences among patients with coincident COPD and periodontitis, patients with periodontitis alone, and HCs ( < 0.05). , and were observed much more frequently in patients with COPD and periodontitis, compared with that in HCs. All tested populations were divided into subgroups based on sex, smoking, or periodontitis index. In the subgroup with a bleeding index >2, was significantly different in periodontitis with and without COPD groups compared with HCs. In the subgroup with a plaque index >2.5, and showed significant differences in periodontitis with and without COPD groups compared with HCs. Variations in salivary microbiota may be associated with COPD and periodontitis.
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http://dx.doi.org/10.3389/fcimb.2020.00124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175749PMC
April 2020

Comparison of dynamic mechanical properties of dentin between deciduous and permanent teeth.

Connect Tissue Res 2020 Apr 30:1-9. Epub 2020 Apr 30.

Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, P. R. China.

: Even though differences between deciduous and permanent dentin have been widely studied, their dynamic mechanical behavior has never been compared. The objective of the present study was to quantify the differences between deciduous and permanent dentin under cyclic mechanical loading, which is similar to masticatory stress.: Deciduous and permanent teeth, respectively from children (9 ~ 12 years old) and young people (18 ~ 25 years old), were wet-sectioned perpendicular to the longitudinal axis and the central specimens of coronal dentin were evaluated by nanoscopic dynamic mechanical analysis (nanoDMA).: The average storage, loss, and complex moduli, as well as the hardness of deciduous dentin were significantly (p < 0.05) lower than those of permanent dentin. Moreover, the tan δ value of permanent dentin was significantly (p < 0.05) lower than that of deciduous dentin across the loading frequency range, indicating that viscoelastic behavior and loss of elastic energy were significantly reduced in the stiffer permanent dentin. All the nanoDMA responses showed a significant influence of the dynamic loading frequency (p < 0.05): Both deciduous and permanent dentin showed reduced viscoelasticty with increased loading frequencies.: Compared with deciduous dentin, permanent dentin exhibits higher stiffness with reduced energy loss during deformation, and therefore superior mechanical characteristics for the mastication process.
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http://dx.doi.org/10.1080/03008207.2020.1758684DOI Listing
April 2020

Novel insight into theacrine metabolism revealed by transcriptome analysis in bitter tea (Kucha, Camellia sinensis).

Sci Rep 2020 04 14;10(1):6286. Epub 2020 Apr 14.

Tea Research Institute of Chinese Academy of Agricultural Sciences, Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture and Rural Affairs, 9 South Meiling Road, Hangzhou, Zhejiang, 310008, China.

Kucha (Camellia sinensis) is a kind of unique wild tea resources in southwest China, containing sizeable amounts of theacrine (1,3,7,9-tetramethyluric acid) and having a special bitter taste both in fresh leaves and made tea. Theacrine has good healthy function locally. But the molecular mechanism of theacrine metabolism in Kucha was still unclear. In order to illuminate the biosynthesis and catabolism of theacrine in Kucha plants, three tea cultivars, C. sinensis 'Shangyou Zhongye' (SY) with low-theacrine, 'Niedu Kucha 2' (ND2) with middle-theacrine and, 'Niedu Kucha 3' (ND3) with high-theacrine, were used for our research. Purine alkaloid analysis and transcriptome of those samples were performed by High Performance Liquid Chromatography (HPLC) and RNA-Seq, respectively. The related gene expression levels of purine alkaloid were correlated with the content of purine alkaloid, and the results of quantitative real-time (qRT) PCR were also confirmed the reliability of transcriptome. Based on the data, we found that theacrine biosynthesis is a relatively complex process, N-methyltransferase (NMT) encoded by TEA024443 may catalyze the methylation at 9-N position in Kucha plant. Our finding will assist to reveal the molecular mechanism of theacrine biosynthesis, and be applied to selection and breeding of Kucha tea cultivars in the future.
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http://dx.doi.org/10.1038/s41598-020-62859-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156766PMC
April 2020

Cost-benefit analysis of rehabilitating old landfills: A case of Beiyangqiao landfill, Wuhan, China.

J Air Waste Manag Assoc 2020 05;70(5):522-531

School of Environment Science and Engineering, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

A comprehensive approach for evaluating the feasibility of landfill rehabilitation should be developed to allow landfill owners to thoroughly examine the feasibility of a landfill soil remediation project in advance. With a view of contributing to the development of a common framework for the evaluation of landfill rehabilitation projects, this paper presents the results of a case study in which the issue of assessing the costs and benefits of rehabilitating the Beiyangqiao simple landfill is addressed. Based on the results of a survey, the cost-benefit assessment criteria and candidate remediation methods were selected. The alternatives included are, in-situ landfill closure; in-situ aerobic stabilization combined with in-situ screening and classification of recovered materials, transport for off-site disposal; and ectopic mining combined with recycling and incineration. Results show that the costs of landfill rehabilitation would range from 11.23 to 32.02 million United States dollars (USD). The key benefits would be land reclamation, heat, or electricity generation by incineration, and recycling of waste materials. The total benefits would range in value from 59.62 to 61.47 million USD. The net present value of the three scenarios would be positive and would range from 8.6 to 10.02 million USD. The results suggest that all three scenarios were positive. Nevertheless, "in-situ aerobic stabilization, in-situ screening, transportation, and off-site disposal" was most beneficial considering all parameters.: This study applied a cost-benefit analysis model for assessing the economic feasibility of landfill rehabilitation, which is important to promoting landfill rehabilitation, and the market potential was assessed based on an actual project. The findings can be useful for providing landfill owners choices in a landfill rehabilitation project to achieve least quantified costs and overhead.
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http://dx.doi.org/10.1080/10962247.2020.1744488DOI Listing
May 2020

Biomechanical stress regulates mammalian tooth replacement.

Cell Stress 2020 Feb 18;4(3):64-65. Epub 2020 Feb 18.

Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050, China.

Cyclical renewal of integumentary organs, including hair, feathers, and teeth occurs throughout an organism's lifetime. Transition from the resting to the initiation stage is critical for each cycle, but the mechanism remains largely unknown. Humans have two sets of dentitions-deciduous and permanent-and tooth replacement occurs only once. Prior to eruption of the permanent tooth (PT), the successional dental lamina (SDL) of the PT can be detected as early as the embryonic stage, even though it then takes about 6-12 years for the SDL to develop to late bell stage. Little is known about the mechanism by which resting SDL transitions into the initiation stage inside the mandible. As a large mammal, the miniature pig, which is also a diphyodont, was a suitable model for our recent study (EMBO J (2020)39: e102374). Using this model, we found that the SDL of PT did not begin the transition into the bud stage until the deciduous tooth (DT) began to erupt.
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http://dx.doi.org/10.15698/cst2020.03.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063841PMC
February 2020

Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren's syndrome.

Cell Death Dis 2020 03 5;11(3):172. Epub 2020 Mar 5.

Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, 100050, China.

Mesenchymal stem cell (MSCs) transplantation has been used to treat Sjögren's syndrome (SS) based on the immunoregulatory properties of MSCs. However, the effectiveness need improving and its underlying intrinsic mechanisms remain largely unknown. Here, we show that Id3 is upregulated in bone marrow-derived MSCs (BMMSCs) isolated from NOD/ShiLtJ mice, a widely used SS model, compared with ICR mice as control, suggesting that it functions in SS development and therapy. Transplantation of Id3-deficient BMMSCs rescues salivary gland function more effective than wild-type BMMSCs in NOD/ShiLtJ mice. Mechanistically, we show that ID3 negatively regulated BMP4 expression by preventing binding of basic helix-loop-helix protein E2A to the promoter of the Bmp4 gene. BMP4 in turn promoted PGE2 production in MSCs, and exhibited enhanced suppressive activities of T-cell proliferation and Th1 differentiation. Importantly, BMMSCs from SS patients showed significantly lower BMP4 and PGE2 expression than those from healthy individuals. Taken together, our findings revealed the targeting Id3 may be therapeutically useful for improving MSC immunoregulation and effectiveness of MSCs therapy for SS.
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http://dx.doi.org/10.1038/s41419-020-2359-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058624PMC
March 2020

One-step preparation of ZVI-sludge derived biochar without external source of iron and its application on persulfate activation.

Sci Total Environ 2020 Apr 17;714:136728. Epub 2020 Jan 17.

Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Hubei Key Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, PR China. Electronic address:

Zero Valent Iron (ZVI) is an important and widely employed environmental remediation material in brownfield. However, the instability of fine size ZVI and the strong aggregation of nanoscale-ZVI limited its further application. To overcome these drawbacks, ZVI-Sludge Derived Biochar (SDBC) was prepared without external iron source through the one-step process of pyrolysis. The characterization results including SEM-EDX, XRD and XPS confirmed the successful loading of Fe on the surface of SDBC. The activation efficiency of persulfate (PS) in in-situ chemical oxidation system was studied. The environmental remediation properties of ZVI-SDBC/PS system were evaluated employing acid orange (AO7) and landfill leachate as target pollutants. ZVI-SDBC/PS system was highly efficient as that 99.0% of AO7 (0.06 mM) was removed by 0.925 mM of PS and 0.5 g L of ZVI-SDBC. In addition, total organic carbon (TOC) and ammonia in leachate were removed by 62.8% and 99.8%, respectively. The removal efficiency of AO7 was nearly independent on initial pH as that 89.1% and 99.1% of AO7 were removed at pH of 9.08 and 2.13 respectively. Hydroxyl radicals dominated in the reaction under neutral and alkaline conditions with contribution rates of 71.9% and 86.1% respectively. Noticeably, not only free radicals but also non-radical species such as singlet oxygen contributed to the degradation, which favored the pH-independent performance. The reuse performance of ZVI-SDBC was higher than these of previously reported ZVI-based catalysts as that the first-order rate constant of AO7 removal decreased not much from 0.0718 to 0.0502 min after the three-cycle reuse assays. In summary, ZVI-SDBC showed advantages such as the facile and chemical-saving preparation method, reliable disposal of municipal sewage sludge, remarkable efficiency and stability. These advantages proved ZVI-SDBC/PS system as an effective strategy of controlling waste by waste, and implicated its potential application in full-scale for environmental remediation in brownfield.
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http://dx.doi.org/10.1016/j.scitotenv.2020.136728DOI Listing
April 2020

Erratum: Histological characteristics following a long-term nitrate-rich diet in miniature pigs with parotid atrophy.

Int J Clin Exp Pathol 2019;12(12):4405-4406. Epub 2019 Dec 1.

Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology Beijing, China.

[This corrects the article on p. 6225 in vol. 8, PMID: 26261499.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949886PMC
December 2019

PISA-SPARKY: an interactive SPARKY plugin to analyze oriented solid-state NMR spectra of helical membrane proteins.

Bioinformatics 2020 05;36(9):2915-2916

National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, WI 53706, USA.

Motivation: Two-dimensional [15N-1H] separated local field solid-state nuclear magnetic resonance (NMR) experiments of membrane proteins aligned in lipid bilayers provide tilt and rotation angles for α-helical segments using Polar Index Slant Angle (PISA)-wheel models. No integrated software has been made available for data analysis and visualization.

Results: We have developed the PISA-SPARKY plugin to seamlessly integrate PISA-wheel modeling into the NMRFAM-SPARKY platform. The plugin performs basic simulations, exhaustive fitting against experimental spectra, error analysis and dipolar and chemical shift wave plotting. The plugin also supports PyMOL integration and handling of parameters that describe variable alignment and dynamic scaling encountered with magnetically aligned media, ensuring optimal fitting and generation of restraints for structure calculation.

Availability And Implementation: PISA-SPARKY is freely available in the latest version of NMRFAM-SPARKY from the National Magnetic Resonance Facility at Madison (http://pine.nmrfam.wisc.edu/download_packages.html), the NMRbox Project (https://nmrbox.org) and to subscribers of the SBGrid (https://sbgrid.org). The pisa.py script is available and documented on GitHub (https://github.com/weberdak/pisa.py) along with a tutorial video and sample data.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203746PMC
May 2020

Biomechanical stress regulates mammalian tooth replacement via the integrin β1-RUNX2-Wnt pathway.

EMBO J 2020 02 12;39(3):e102374. Epub 2019 Dec 12.

Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.

Renewal of integumentary organs occurs cyclically throughout an organism's lifetime, but the mechanism that initiates each cycle remains largely unknown. In a miniature pig model of tooth development that resembles tooth development in humans, the permanent tooth did not begin transitioning from the resting to the initiation stage until the deciduous tooth began to erupt. This eruption released the accumulated mechanical stress inside the mandible. Mechanical stress prevented permanent tooth development by regulating expression and activity of the integrin β1-ERK1-RUNX2 axis in the surrounding mesenchyme. We observed similar molecular expression patterns in human tooth germs. Importantly, the release of biomechanical stress induced downregulation of RUNX2-wingless/integrated (Wnt) signaling in the mesenchyme between the deciduous and permanent tooth and upregulation of Wnt signaling in the epithelium of the permanent tooth, triggering initiation of its development. Consequently, our findings identified biomechanical stress-associated Wnt modulation as a critical initiator of organ renewal, possibly shedding light on the mechanisms of integumentary organ regeneration.
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http://dx.doi.org/10.15252/embj.2019102374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996503PMC
February 2020