Publications by authors named "Lei Ying"

301 Publications

Amidinothiourea as a new deposition-regulating additive for dendrite-free lithium metal anodes.

Chem Commun (Camb) 2021 Sep 10. Epub 2021 Sep 10.

College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Lithium (Li) dendrite growth seriously hinders the practical application of Li metal batteries. Here, we report molecular amidinothiourea (ATU) as a new electrolyte additive to regulate Li stripping/plating behaviors of Li metal anodes. The molecular ATU in the electrolyte can act as a shielding layer on the Li metal surface to suppress the decomposition of electrolytes as verified by XPS and adsorption energy calculation, which improves the electrochemical reversibility of the Li plating/stripping behaviors and inhibits lithium dendrite growth.
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http://dx.doi.org/10.1039/d1cc02829dDOI Listing
September 2021

Phase partitioning, transport and sources of Benzotriazole Ultraviolet Stabilizers during a runoff event.

Water Res X 2021 Dec 19;13:100115. Epub 2021 Aug 19.

Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Ontario M1C 1A4, Canada.

Benzotriazole Ultraviolet Stabilizers (BT-UVs) are ubiquitous in the environment, given their wide use as additives in consumer products. Their bio-accumulative and toxic properties are increasingly being scrutinised, evinced by the recent proposition to add UV328 to the Stockholm Convention on Persistent Organic Pollutants. Here, we measured concentrations of six BT-UVs in the dissolved and particulate phases of stream water collected from an urban and rural stream during a runoff event. Under baseflow conditions, the less hydrophobic BT-UVs were present at low concentrations in the dissolved phase, while much higher loads of particulate BT-UVs occurred during stormflow, especially in the urban creek. Time-weighted average BT-UV concentrations were up to 4 times higher in the urban than in the rural creek. BT-UVs were found to be prevalent in water obtained from laundering textiles, which plausibly constitutes a major portion of domestic wastewater, and can serve as a BT-UV source to aquatic waterways. However, the observed dilution of a sewage tracer during the run-off event suggests that unregulated wastewater seepage is not responsible for the high BT-UV loads in storm water. High levels of UV328 and UV234 were detected in a select few plastic debris items collected from the urban watershed and in artificial turf grass, respectively. Whereas this may allow for the leaching of those BT-UVs into the creek, most plastic debris is more likely a sink than a source of BT-UVs. The observed input of particle-bound BT-UVs at the onset of the rain event indicates that most of the BT-UVs reach the creek with contaminated particles that had built up on surfaces during the antecedent dry period. UV328 was the dominant BT-UV in those particles. If such particle build-up occurs on road surfaces, it may suggest that the use of UV328 in automotive applications contributes to their presence in urban storm water.
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http://dx.doi.org/10.1016/j.wroa.2021.100115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403763PMC
December 2021

High thermoelectric performance of half-Heusler ZrPb (= Ni, Pd, and Pt) compounds from first principle calculation.

J Phys Condens Matter 2021 Sep 1;33(46). Epub 2021 Sep 1.

Department of Materials Science and Technology, Kunming University of Science and Technology, Kunming 650093, People's Republic of China.

Half-Heusler compounds have distinguished themselves as outstanding thermoelectric materials on account of high temperature stability and large thermopower. However, the dimensionless figure of merit of traditional half-Heusler alloys remains low. In this study, we investigate the thermoelectric performance of novel ZrPb (= Ni, Pd, and Pt) ternary compounds by semi-classical Boltzmann transport theory combining with deformation potential. The n-type ZrNiPb and ZrPtPb exhibits obviously largevalues of 1.71 around 650 K and 1.75 around 1200 K, with 1.17 × 10 cmand 3.43 × 10 cm, respectively. The electron and phonon structure calculations demonstrate that for the n-type ZrPb (= Ni, Pd, and Pt) compounds, doping at Pb site can not only modify the carrier concentrations but also significantly decrease the lattice thermal conductivity. These investigations are expected to be beneficial to the exploration of novel highthermoelectric materials.
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http://dx.doi.org/10.1088/1361-648X/ac1e48DOI Listing
September 2021

Cardioprotective effects of corilagin on doxorubicin induced cardiotoxicity via P13K/Akt and NF-κB signaling pathways in rats model.

Toxicol Mech Methods 2021 Aug 9:1-26. Epub 2021 Aug 9.

Department of Cardiology, Ankang Hospital of Traditional Chinese Medicine, Ankang, 725000, China.

Even though doxorubicin (DOX) is a potential chemotherapeutic drug, its usage is restricted due to its ability to induce cardiac damage. In order to prevent this damage, a potent cardioprotective agent should be associated with DOX treatment. Corilagin is a natural polyphenol tannic acid which unveils enormous pharmacological activities predominantly as an antitumor agent. Hence, the current work is designed to study the precise mechanisms of corilagin upon administration in doxorubicin induced cardiotoxicity in experimental rats. DOX treated rats showed diminished level of blood pressures and heart rate, whereas corilagin along with DOX treatment improved the status. Cardiotoxicity enzymes and biomarkers were found to be increased in the serum of DOX induced rats. Upon treatment, corilagin could reduce the cardiotoxicity enzymes and biomarkers in serum. Histopathological examination of cardiac tissue also revealed the anti-toxic effects of corilagin in contrast to DOX. Injection of DOX in rats showed inflammatory cells infiltration, necrosis and fragmented myofibrils. Corilagin treatment reverted the cardiac histology to near normal. Inflammatory mediators and P13K, Akt, and NF-κB were upregulated in DOX administered rats. Corilagin repressed the levels of P13K, Akt, and NF-κB in DOX induced rats. In the present investigations, corilagin improved cardiac function via reducing injury, inflammation and promoting apoptosis thereby suggesting that corilagin would be recommended for DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1080/15376516.2021.1965274DOI Listing
August 2021

Occurrence of Positive Strains and Molecular Characteristics of Two Positive and from a Chinese Women's and Children's Hospital.

Infect Drug Resist 2021 27;14:2925-2932. Epub 2021 Jul 27.

Department of Laboratory Medicine, Quanzhou Women's and Children's Hospital, Quanzhou, People's Republic of China.

Background: The purpose of this study was to evaluate the prevalence of mobile colistin resistance genes () in Gram-negative bacteria and to analyze the molecular characteristics of positive 75 and 107 from the Quanzhou Women's and Children's Hospital in China.

Methods: The genes through were screened via multiplex PCR. Antibiotic susceptibility was detected using a GN11 card with the VITEK-2 compact automated system. Whole genomes were sequenced using PacBio's single molecule real-time (SMRT) technology.

Results: In this study, was detected in only four strains, with a positivity rate of 0.65% (4/616). All the four strains were resistant to more than three different kinds of antibiotics. The positive strain 75 harbored IncHI2 plasmid, which carried gene, while the positive strain 107 contained four plasmids including one harboring IncHI2 plasmid, one IncFII plasmid and two IncI1-I (Alpha) plasmids. Mobile elements carrying in the 75_plasmid and 107_plasmid-1 were located in the IS1086(ISA)-IS30A()- and IS1086(ISA)--1- regions, respectively. Tn6010 carrying drug efflux pump genes was found in 75_plasmid, while cn_31611_IS26 carrying multi-drug resistance (MDR) genes were found in 107_plasmid-1.

Conclusion: This study found that was prevalent at a low frequency in the Quanzhou Women's and Children's Hospital. A similar genetic pattern of transmission was found in both and .
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http://dx.doi.org/10.2147/IDR.S322686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327187PMC
July 2021

High-Throughput Screening to Identify Small Molecules That Selectively Inhibit APOL1 Protein Level in Podocytes.

SLAS Discov 2021 Oct 3;26(9):1225-1237. Epub 2021 Jul 3.

Screening, Target and Compound Profiling, Merck & Co., Inc., Kenilworth, NJ, USA.

High-throughput phenotypic screening is a key driver for the identification of novel chemical matter in drug discovery for challenging targets, especially for those with an unclear mechanism of pathology. For toxic or gain-of-function proteins, small-molecule suppressors are a targeting/therapeutic strategy that has been successfully applied. As with other high-throughput screens, the screening strategy and proper assays are critical for successfully identifying selective suppressors of the target of interest. We executed a small-molecule suppressor screen to identify compounds that specifically reduce apolipoprotein L1 (APOL1) protein levels, a genetically validated target associated with increased risk of chronic kidney disease. To enable this study, we developed homogeneous time-resolved fluorescence (HTRF) assays to measure intracellular APOL1 and apolipoprotein L2 (APOL2) protein levels and miniaturized them to 1536-well format. The APOL1 HTRF assay served as the primary assay, and the APOL2 and a commercially available p53 HTRF assay were applied as counterscreens. Cell viability was also measured with CellTiter-Glo to assess the cytotoxicity of compounds. From a 310,000-compound screening library, we identified 1490 confirmed primary hits with 12 different profiles. One hundred fifty-three hits selectively reduced APOL1 in 786-O, a renal cell adenocarcinoma cell line. Thirty-one of these selective suppressors also reduced APOL1 levels in conditionally immortalized human podocytes. The activity and specificity of seven resynthesized compounds were validated in both 786-O and podocytes.
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http://dx.doi.org/10.1177/24725552211026245DOI Listing
October 2021

Single-Cell Analysis of Ploidy and Transcriptome Reveals Functional and Spatial Divergency in Murine Megakaryopoiesis.

Blood 2021 Jun 11. Epub 2021 Jun 11.

Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation, Beijing, China.

Megakaryocytes (MKs), the platelet progenitor cell, play important roles in hematopoietic stem cell (HSC) maintenance and immunity. However, it is not known whether these diverse programs are executed by a single population or by distinct subsets of cells. Here, we manually-isolated primary CD41+ MKs from the bone marrow (BM) of mice and human donors based on ploidy (2N-32N), performed single-cell RNA sequencing analysis. We found that cellular heterogeneity existed within three distinct subpopulations possessing gene signatures related to platelet-generation, HSC niche interaction, and inflammatory responses, respectively. In situ immunostaining of mouse BM demonstrated that platelet-generation and HSC-niche related MKs were physically in close proximity to blood vessels and HSCs, respectively. Proplatelets, which could give rise to platelets under the blood shear forces, were predominantly formed on platelet-generation subset. Remarkably, the inflammatory responses subpopulation, consisting generally of low-ploidy LSP1+ and CD53+ MKs (≤8N), represented approximately 5% of total MKs in the BM. These MKs could specifically respond to pathogen infections in mice. Rapid expansion of this population was accompanied by strong upregulation of a pre-existing PU.1 and IRF-8-associated monocytic-like transcriptional program involved in pathogen recognition and clearance, as well as antigen presentation. Consistently, isolated primary CD53+ cells were capable to engulf and digest bacteria and to stimulate T cells in vitro. Together, our findings uncover new molecular, spatial, and functional heterogeneity within MKs in vivo and demonstrate the existence of a specialized MK subpopulation that may act as a new type of immune cell.
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http://dx.doi.org/10.1182/blood.2021010697DOI Listing
June 2021

Synergistic Optimization of Electrical-Thermal-Mechanical Properties of the In-Filled CoSb Material by Introducing BiSbTe Nanoparticles.

ACS Appl Mater Interfaces 2021 May 17;13(20):23894-23904. Epub 2021 May 17.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.

How to realize the synergistic optimization of electrical-thermal-mechanical properties of thermoelectric materials is a key challenge. Using the BiSbTe nanoparticle as a mixed agent provides an effective way to address this challenge. Here, BiSbTe/InCoSb nanocomposites with different contents of BiSbTe nanoparticles were successfully prepared by ultrasonic dispersion combined with spark plasma sintering. Phase and microstructure characterization presented that Te nanoparticles were precipitated from BiSbTe during the SPS sintering process. Transport measurement results showed that the electrical conductivity was increased due to the increased carrier concentration induced by the charge transfer between Te nanoparticles and the matrix. The Seebeck coefficient was also increased due to the selected electron scattering and increased scattering factor. The lattice thermal conductivity was dramatically suppressed because of the enhanced phonon scattering induced by the BiSbTe nanoparticles and in situ-precipitated Te nanoparticles and increased dislocations. As a result, a higher average value of 1 was obtained in the range of 300-700 K by the decoupling of the electrical and thermal transport properties for the nanocomposite with 0.1 wt % of BiSbTe nanometer suspension. Furthermore, the flexural strength, fracture toughness, and hardness of the nanocomposites were also improved significantly. This work demonstrates that using the BiSbTe nanoparticle as a mixed agent can realize the synergistic optimization of electrical-thermal-mechanical properties of the In-filled CoSb thermoelectric material.
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http://dx.doi.org/10.1021/acsami.1c03351DOI Listing
May 2021

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.

Protein Cell 2021 Apr 17. Epub 2021 Apr 17.

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC values ranging from 1.39 to 5.63 μmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.
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http://dx.doi.org/10.1007/s13238-021-00836-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052528PMC
April 2021

Characterization of inhalation exposure to gaseous elemental mercury during artisanal gold mining and e-waste recycling through combined stationary and personal passive sampling.

Environ Sci Process Impacts 2021 Apr 10;23(4):569-579. Epub 2021 Feb 10.

Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario, Canada M1C 1A4.

While occupational inhalation exposure to gaseous elemental mercury (GEM) has decreased in many workplaces as mercury is being removed from most products and processes, it continues to be a concern for those engaged in artisanal and small-scale gold mining or in recycling mercury-containing products. Recently, stationary and personal passive air samplers based on activated carbon sorbents and radial diffusive barriers have been shown to be suitable for measuring GEM concentrations across the range relevant for chronic health effects. Here, we used a combination of stationary and personal passive samplers to characterize the inhalation exposure to GEM of individuals living and working in two Ghanaian gold mining communities and working at a Norwegian e-waste recycling facility. Exposure concentrations ranging from <7 ng m to >500 μg m were observed, with the higher end of the range occurring in one gold mining community. Large differences in the GEM exposure averaged over the length of a workday between individuals can be rationalized by their activity and proximity to mercury sources. In each of the three settings, the measured exposure of the highest exposed individuals exceeded the highest concentration recorded with a stationary sampler, presumably because those individuals were engaged in an activity that generated or involved GEM vapors. High day-to-day variability in exposure for those who participated on more than one day, suggests the need for sampling over multiple days for reliable exposure characterization. Overall, a combination of personal and stationary passive sampling is a cost-effective approach that cannot only provide information on exposure levels relative to regulatory thresholds, but also can identify emission hotspots and therefore guide mitigation measures.
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http://dx.doi.org/10.1039/d0em00494dDOI Listing
April 2021

Identification of Methicillin-Resistant Staphylococcus Aureus From Methicillin-Sensitive Staphylococcus Aureus and Molecular Characterization in Quanzhou, China.

Front Cell Dev Biol 2021 21;9:629681. Epub 2021 Jan 21.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

To distinguish Methicillin-Resistant Staphylococcus aureus (MRSA) from Methicillin-Sensitive Staphylococcus aureus (MSSA) in the protein sequences level, test the susceptibility to antibiotic of all Staphylococcus aureus isolates from Quanzhou hospitals, define the virulence factor and molecular characteristics of the MRSA isolates. MRSA and MSSA Pfam protein sequences were used to extract feature vectors of 188D, n-gram and 400D. Weka software was applied to classify the two Staphylococcus aureus and performance effect was evaluated. Antibiotic susceptibility testing of the 81 Staphylococcus aureus was performed by the Mérieux Microbial Analysis Instrument. The 65 MRSA isolates were characterized by Panton-Valentine leukocidin (), X polymorphic region of Protein A (), multilocus sequence typing test (), staphylococcus chromosomal cassette mec (mec) typing. After comparing the results of Weka six classifiers, the highest correctly classified rates were 91.94, 70.16, and 62.90% from 188D, n-gram and 400D, respectively. Antimicrobial susceptibility test of the 81 Staphylococcus aureus: Penicillin-resistant rate was 100%. No resistance to teicoplanin, linezolid, and vancomycin. The resistance rate of the MRSA isolates to clindamycin, erythromycin and tetracycline was higher than that of the MSSAs. Among the 65 MRSA isolates, the positive rate of gene was 47.7% (31/65). Seventeen sequence types () were identified among the 65 isolates, and was the most prevalent. type III and IV were observed at 24.6 and 72.3%, respectively. Two isolates did not be typed. Twenty-one types were identified, 437 (34/65, 52.3%) was the most predominant type. MRSA major clone type of molecular typing was (28/65, 43.1%). Overall, 188D feature vectors can be applied to successfully distinguish MRSA from MSSA. In Quanzhou, the detection rate of virulence factor was high, suggesting a high pathogenic risk of MRSA infection. The cross-infection of CA-MRSA and HA-MRSA was presented, the molecular characteristics were increasingly blurred, HA-MRSA with typical CA-MRSA molecular characteristics has become an important cause of healthcare-related infections. was the main clone type in Quanzhou, which was rare in other parts of mainland China.
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http://dx.doi.org/10.3389/fcell.2021.629681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858276PMC
January 2021

Constructing a new polymer acceptor enabled non-halogenated solvent-processed all-polymer solar cell with an efficiency of 13.8.

Chem Commun (Camb) 2021 Jan;57(7):935-938

Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640, China.

A new polymer acceptor, PS1, was developed by connecting the non-fullerene acceptor building block of dithienothiophen[3,2-b]pyrrolobenzotriazole capped with 3-(dicyanomethylidene)-indan-1-one through a thiophene spacer. The solubilizing alkyl side groups in the central unit enabled PS1 to be readily dissolved in non-chlorinated solvents. By using 2-methyltetrahydrofuran as the processing solvent, the all-polymer solar cell (all-PSC) containing PS1 and a polymer donor PTzBI-oF in the light-harvesting layer exhibited an impressively high power conversion efficiency of 13.8%.
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http://dx.doi.org/10.1039/d0cc07213cDOI Listing
January 2021

Copper Thiocyanate as an Anode Interfacial Layer for Efficient Near-Infrared Organic Photodetector.

ACS Appl Mater Interfaces 2021 Jan 22;13(1):1027-1034. Epub 2020 Dec 22.

Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China.

Interfacial modification between the electrode and the overlying organic layer has significant effects on the charge injection and collection and thus the device performance of organic photodetectors. Here, we used copper(I) thiocyanate (CuSCN) as the anode interfacial layer for organic photodetector, which was inserted between the anode and an organic light-sensitive layer. The CuSCN layer processed with ethyl sulfide solution presented similar optical properties to the extensively used anode interlayer of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), while the relatively shallow conduction band of CuSCN resulted in a much higher electron-injection barrier from the anode and shunt resistance than those of PEDOT:PSS. Moreover, the CuSCN-based device also exhibited an increased depletion width for the PEDOT:PSS-based device, as indicated by the Mott-Schottky analysis. These features lead to the dramatically reduced dark current density of 2.7 × 10 A cm and an impressively high specific detectivity of 4.4 × 10 cm Hz W under -0.1 V bias and a working wavelength of 870 nm. These findings demonstrated the great potential of using CuSCN as an anode interfacial layer for developing high-performance near-infrared organic photodetectors.
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http://dx.doi.org/10.1021/acsami.0c18260DOI Listing
January 2021

Chemopreventive effect of dieckol against 7,12-dimethylbenz(a)anthracene induced skin carcinogenesis model by modulatory influence on biochemical and antioxidant biomarkers.

Environ Toxicol 2021 May 21;36(5):800-810. Epub 2020 Dec 21.

Department of Pathophysiology, Basic Medical School, North Sichuan Medical College, Nanchong, Sichuan, China.

Skin cancer is the commonly found type, which contributes to 40% of whole cancer incidences worldwide. Dieckol is an active compound occurs in the marine algae with many biological benefits. In this exploration, we intended to investigate the therapeutic potency of dieckol against the 7,12-dimethylbenz(a)anthracene (DMBA)-triggered skin carcinogenesis in mice. The skin cancer was stimulated to the animals via injecting the 25 μg of DMBA in 100 μL of acetone in shaved dorsal portion along with the 30 mg/kg of dieckol supplementation for 25 week. The antioxidant enzymes and phase-I and -II detoxifying enzymes in the test animals were inspected via standard protocols. Pro-inflammatory markers (IL-6, IL-1β, and TNF-α) level was examined via ELISA kits and the expression of inflammatory molecular markers like p-NF-ƙB, IƙBα and p-IƙBα were studied through western blotting. The expression status of pro- and anti-apoptotic proteins (p53, Bax, Bcl-2, caspase-3, caspase-9, COX-2, TGF-β1) was investigated via real-time polymerase chain reaction (RT-PCR). Our results revealed that the 30 mg/kg of dieckol supplementation noticeably regained the body and liver weight and also diminished the tumor incidence in the DMBA-incited animals. Dieckol treatment exhibited an enhanced antioxidants (SOD, CAT, GPx, and GSH) and reduced phase-I enzymes Cyt-p450 and Cyt-b5 in the DMBA-induced animals. Dieckol also diminished the pro-inflammatory modulators like IL-6, IL-1β and TNF-α. Western blotting result evidenced that the dieckol was inhibited the IƙB/NF-ƙB signaling pathway. RT-PCR study proved the enhanced expression of pro-apoptotic protein (p53, Bax, caspase-3 and -9) in the dieckol treated animals. Histological study also confirmed the therapeutic benefits of Dieckol. Altogether with these findings, it was clear that the dieckol has appreciably allayed the DMBA activated skin tumorigenesis in the mice and it could be a promising agent to treat the human skin cancer in future.
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http://dx.doi.org/10.1002/tox.23082DOI Listing
May 2021

In Vivo Bioimaging and Photodynamic Therapy Based on Two-Photon Fluorescent Conjugated Polymers Containing Dibenzothiophene-,-dioxide Derivatives.

ACS Appl Mater Interfaces 2020 Dec 9;12(51):57281-57289. Epub 2020 Dec 9.

Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China.

As a critical component for photodynamic therapy toward cancer treatment, photosensitizers require high photoinduced reactive oxygen species generation efficiency, good biocompatibility, and high phototoxicity. Herein, a series of donor-acceptor conjugated polymers containing dibenzothiophene-,-dioxide derivatives are designed and synthesized, which can be used as effective photosensitizers. The resulting copolymer PTA5 shows strong green light emission with high photoluminescence quantum yields owing to the intercrossed excited state of local existed and charge transfer states. The PTA5 nanoparticles can be fabricated by encapsulation with a biocompatible polymer matrix. Upon excitation at 800 nm, these nanoparticles present a relatively large two-photon absorption cross section of 3.29 × 10 GM. These nanoparticles also exhibit good photostability in water and thus can be utilized for bioimaging. The tissue-penetrating depths of up to 170 μm for hepatic vessels and 380 μm for blood vessels of mouse ear were achieved using PTA5 nanoparticles. Furthermore, PTA5 nanoparticles show impressive reactive oxygen species generation capability under the irradiation of a white light source. This can be attributed to the effective intersystem crossing between high-level excited state. Upon irradiation with white light (400-700 nm) at 50 mW cm for 5 min every other day, the tumor growth can be effectively suppressed in the presence of PTA5 nanoparticles. These findings demonstrate that PTA5 nanoparticles can be used as a photosensitizer for photodynamic therapy.
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http://dx.doi.org/10.1021/acsami.0c12955DOI Listing
December 2020

Development, characterization, and testing of a personal passive sampler for measuring inhalation exposure to gaseous elemental mercury.

Environ Int 2021 01 20;146:106264. Epub 2020 Nov 20.

Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4, Canada. Electronic address:

Inhalation of gaseous elemental mercury (GEM) is an occupational exposure concern for workers handling elemental mercury or mercury-containing waste. GEM is also often present near historically mercury-contaminated sites, potentially resulting in low-level, chronic exposure of the wider population. Here we introduce a passive sampler for personal GEM monitoring which combines a radial porous diffusive barrier with an activated carbon sorbent. A total mercury analyzer is used to quantify GEM sorbed to the carbon by thermal decomposition, amalgamation, and atomic absorption spectroscopy. A sampling rate of 0.070 m/day was determined by calibrating the sampler at low and high concentrations. Deployments lasting 8 h result in limits of quantification well below 200 ng/m. The sampler has a measurement range of at least four orders of magnitude. Derived air concentrations were not statistically significantly different from those obtained by active air sampling but were more precise than those obtained using a personal pump. If properly stored, the sampler maintains low blank levels in high GEM environments. Affordability, sturdiness, simplicity, and the wide availability of total mercury analyzers make this sampler highly suited for monitoring GEM inhalation exposure, including in developing countries.
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http://dx.doi.org/10.1016/j.envint.2020.106264DOI Listing
January 2021

Altered Inflammatory Pathway but Unaffected Liver Fibrosis in Mouse Models of Nonalcoholic Steatohepatitis Involving Interleukin-1 Receptor-Associated Kinase 1 Knockout.

Med Sci Monit 2020 Nov 18;26:e926187. Epub 2020 Nov 18.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, National Clinical Research Centre for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland).

BACKGROUND Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators in the signaling pathways of Toll-like receptors (TLRs)/IL1Rs. Targeting the IRAK4/IRAK1/TRAF6 axis and its associated pathway has therapeutic benefits in liver fibrosis. However, the function of IRAK1 itself in the development of liver fibrosis remains unknown. MATERIAL AND METHODS Irak1 global knockout (KO) mice were generated to study the functional role of Irak1 in liver fibrosis. Male Irak1 knockout and control mice were challenged with chronic carbon tetrachloride (CCl4) or fed a methionine- and choline-deficient diet (MCDD) to generate models of nonalcoholic steatohepatitis (NASH). Liver inflammation and collagen deposition were assessed by histological examination, quantitative real-time PCR (qRT-PCR), and western blotting of hepatic tissues. RESULTS The mRNA expression of the downstream inflammatory gene Il1b was significantly lower in Irak1-KO than in control mice. Irak1 ablation had little effect on inflammatory cell infiltration into livers of mice with NASH. Collagen deposition and the expression of genes related to fibrogenesis were similar in the livers of Irak1-KO and control mice exposed to CCl4 and MCDD. The loss of Irak1 did not affect lipid or glucose metabolism in these experimental models of steatohepatitis. CONCLUSIONS Irak1 knockout reduced the expression of inflammatory genes but had no effect on hepatic fibrogenesis. The Irak1-related pathway may regulate liver fibrosis via other pathways or be compensated for by other factors.
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http://dx.doi.org/10.12659/MSM.926187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682117PMC
November 2020

PDE1 or PDE5 inhibition augments NO-dependent hypoxic constriction of porcine coronary artery via elevating inosine 3',5'-cyclic monophosphate level.

J Cell Mol Med 2020 12 9;24(24):14514-14524. Epub 2020 Nov 9.

Department of Pathophysiology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

Hypoxic coronary vasospasm may lead to myocardial ischaemia and cardiac dysfunction. Inosine 3',5'-cyclic monophosphate (cIMP) is a putative second messenger to mediate this pathological process. Nevertheless, it remains unclear as to whether levels of cIMP can be regulated in living tissue such as coronary artery and if so, what is the consequence of this regulation on hypoxia-induced vasoconstriction. In the present study, we found that cIMP was a key determinant of hypoxia-induced constriction but not that of the subsequent relaxation response in porcine coronary arteries. Subsequently, coronary arteries were treated with various phosphodiesterase (PDE) inhibitors to identify PDE types that are capable of regulating cIMP levels. We found that inhibition of PDE1 and PDE5 substantially elevated cIMP content in endothelium-denuded coronary artery supplemented with exogenous purified cIMP. However, cGMP levels were far lower than their levels in intact coronary arteries and lower than cIMP levels measured in endothelium-denuded coronary arteries supplemented with exogenous cIMP. The increased cIMP levels induced by PDE1 or PDE5 inhibition further led to augmented hypoxic constriction without apparently affecting the relaxation response. In intact coronary artery, PDE1 or PDE5 inhibition up-regulated cIMP levels under hypoxic condition. Concomitantly, cGMP level increased to a comparable level. Nevertheless, the hypoxia-mediated constriction was enhanced in this situation that was largely compromised by an even stronger inhibition of PDEs. Taken together, these data suggest that cIMP levels in coronary arteries are regulated by PDE1 and PDE5, whose inhibition at a certain level leads to increased cIMP content and enhanced hypoxic constriction.
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http://dx.doi.org/10.1111/jcmm.16078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754025PMC
December 2020

Curtailing FGF19's mitogenicity by suppressing its receptor dimerization ability.

Proc Natl Acad Sci U S A 2020 11 3;117(46):29025-29034. Epub 2020 Nov 3.

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035 Zhejiang, China;

As a physiological regulator of bile acid homeostasis, FGF19 is also a potent insulin sensitizer capable of normalizing plasma glucose concentration, improving lipid profile, ameliorating fatty liver disease, and causing weight loss in both diabetic and diet-induced obesity mice. There is therefore a major interest in developing FGF19 as a therapeutic agent for treating type 2 diabetes and cholestatic liver disease. However, the known tumorigenic risk associated with prolonged FGF19 administration is a major hurdle in realizing its clinical potential. Here, we show that nonmitogenic FGF19 variants that retain the full beneficial glucose-lowering and bile acid regulatory activities of WT FGF19 (FGF19) can be engineered by diminishing FGF19's ability to induce dimerization of its cognate FGF receptors (FGFR). As proof of principle, we generated three such variants, each with a partial defect in binding affinity to FGFR (FGF19) and its coreceptors, i.e., βklotho (FGF19) or heparan sulfate (FGF19). Pharmacological assays in WT and mice confirmed that these variants incur a dramatic loss in mitogenic activity, yet are indistinguishable from FGF19 in eliciting glycemic control and regulating bile acid synthesis. This approach provides a robust framework for the development of safer and more efficacious FGF19 analogs.
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http://dx.doi.org/10.1073/pnas.2010984117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682408PMC
November 2020

Single-cell RNA profiling links ncRNAs to spatiotemporal gene expression during C. elegans embryogenesis.

Sci Rep 2020 11 2;10(1):18863. Epub 2020 Nov 2.

BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China.

Recent studies show that non-coding RNAs (ncRNAs) can regulate the expression of protein-coding genes and play important roles in mammalian development. Previous studies have revealed that during C. elegans (Caenorhabditis elegans) embryo development, numerous genes in each cell are spatiotemporally regulated, causing the cell to differentiate into distinct cell types and tissues. We ask whether ncRNAs participate in the spatiotemporal regulation of genes in different types of cells and tissues during the embryogenesis of C. elegans. Here, by using marker-free full-length high-depth single-cell RNA sequencing (scRNA-seq) technique, we sequence the whole transcriptomes from 1031 embryonic cells of C. elegans and detect 20,431 protein-coding genes, including 22 cell-type-specific protein-coding markers, and 9843 ncRNAs including 11 cell-type-specific ncRNA markers. We induce a ncRNAs-based clustering strategy as a complementary strategy to the protein-coding gene-based clustering strategy for single-cell classification. We identify 94 ncRNAs that have never been reported to regulate gene expressions, are co-expressed with 1208 protein-coding genes in cell type specific and/or embryo time specific manners. Our findings suggest that these ncRNAs could potentially influence the spatiotemporal expression of the corresponding genes during the embryogenesis of C. elegans.
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http://dx.doi.org/10.1038/s41598-020-75801-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606524PMC
November 2020

Efficient near-infrared anionic conjugated polyelectrolyte for photothermal therapy.

J Mater Chem B 2020 12;8(46):10609-10615

Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China.

In this work, an anionic conjugated polyelectrolyte (PCP-SO3K), in which the backbone contains alternating 4,4-bis-alkyl-4H-cyclopenta-[2,1-b;3,4-b']-dithiophene and benzene structural units and the charges are provided by pendant sulfonate groups, was synthesized. The ionic nature of PCP-SO3K renders it soluble in water, and PCP-SO3K aqueous solution exhibits good photostability, with two main absorbance bands centered at 490 nm and 837 nm before and after laser irradiation. Its NIR absorption in water, negligible photoluminescence and insignificant intersystem crossing endow PCP-SO3K with efficient photothermal therapy performance, and an effective photothermal conversion efficiency of 56.7% was realized. Thus, PCP-SO3K aqueous solution can be used as an effective photothermal agent for in vivo applications as its photoactivity can be triggered by NIR light and can convert laser energy into thermal energy in a water environment. Of particular importance is the fact that complete tumor remission without recurrence in 4T1 tumor-bearing mice was realized after intravenous injection of PCP-SO3K aqueous solution and laser irradiation (2.0 W cm-2, 808 nm). The results indicate that the application of anionic conjugated polyelectrolytes as photothermal agents in photothermal therapy provides a new platform for the design of photothermal agents for clinical cancer treatment.
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http://dx.doi.org/10.1039/d0tb02015jDOI Listing
December 2020

[Spectral Characteristics and Source Analysis of WSOC of PM in Winter of Xi'an].

Huan Jing Ke Xue 2020 Sep;41(9):3924-3931

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

The spectral characteristics and sources of water-soluble organic compounds (WSOC) in PM in winter were studied by using UV-vis absorption spectroscopy, three-dimensional fluorescence spectroscopy, parallel factor analysis, and backward trajectory model. The results showed that the concentration of WSOC in PM was 4.66-14.75 μg ·m. The values of /, /, , SUVA, AAE, and MAE of WSOC were, respectively, in the range of 2.85-4.32, 2.21-3.56, 0.0099-0.0127 nm, 2.35-3.89 m ·g, 2.66-4.60, and 1.51-2.60 m ·g. The /, /, , and AAE values of WSOC at the sampling site in the southern suburb of Xi'an, China (Xi'an University of Architecture and Technology) were higher than those at the sampling site in the northern suburb (sports park), while the values of SUVA and MAE were lower. There were four fluorescent components in WSOC identified by the EEMs-PARAFAC model: C1 and C2 were fulvic acid-like and protein-like, respectively, and C3 and C4 were humus-like components. The fluorescence intensities and the sum of the fluorescent components were positively correlated with the concentrations of PM, OC, WSOC, and value (<0.01). The fluorescence index (FI), biological source index (BIX), and humic index (HIX) values of WSOC were 1.75-2.12, 1.14-1.46, and 1.18-2.06, respectively. During the monitoring period, the air mass transmission trajectory was dominated by the local southwest of short-distance transmission, and its trajectory accounted for more than 50%. The pollutant emissions from Xinjiang, Inner Mongolia, and Gansu also made significant contributions to the air pollution levels in Xi'an in winter. There was a small difference in the carbon component content of PM in the northern and southern suburbs of Xi'an. The molecular weight, humification degree, and light absorption capacity of WSOC at the southern suburb sampling site were lower than those in the northern suburb where the wavelength dependence of light absorption intensity was relatively stronger. The WSOC mainly originated from biological sources or both from biological and terrestrial sources. Local transmission had the most significant contribution to PM and WSOC in winter.
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http://dx.doi.org/10.13227/j.hjkx.202001127DOI Listing
September 2020

Laser therapy in the treatment of cicatricial ectropion.

J Cosmet Dermatol 2021 Jan 16;20(1):84-92. Epub 2020 Nov 16.

Department of Plastic & Laser Cosmetic, Hunan Provincial People's Hospital, 1st Affiliated Hospital of Hunan Normal University, Changsha, China.

Introduction: The objective of this study was to investigate the clinical effects of laser therapy in treating cicatricial ectropion.

Methods: Seven patients with cicatricial ectropion were entered into this clinical study. The ectropions were pretreated with the 595-nm pulsed dye laser if the scar color was red. If there was no red, the UltraPulse fractional CO laser was used and parameters were adapted according to the height of scar. MEBT/MEBO was used after laser treatment for wound healing. The degree of ectropion was measured for changes before and after treatment, and the scars were evaluated for changes in melanin, height, vascularity, and pliability using the Vancouver Scar Scale (VSS) before and after treatment.

Results: All seven patients with cicatricial ectropion entered into this protocol were completely corrected after 1-2 treatment sessions. The total VSS score, as well as the score for melanin and pliability in 7 patients, showed a decrease following the treatments, and this was statistically significant (P < 0.05). The scores for height and vascularity showed a decrease following the treatments, but there was no significant difference by statistical analysis (P ≥ 0.05). There were no adverse reactions reported.

Conclusions: The treatment of cicatricial ectropion with laser therapy can not only correct the ectropion, but also improve the scars in the treatment area. Compared with the traditional repair of cicatricial ectropion, the use of fractional CO laser provides surgical precision and the advantage of a timely treatment without the need to wait for the scar to stabilize.
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http://dx.doi.org/10.1111/jocd.13821DOI Listing
January 2021

YY1 deficiency in β-cells leads to mitochondrial dysfunction and diabetes in mice.

Metabolism 2020 Sep 8;112:154353. Epub 2020 Sep 8.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, National Clinical Research Centre for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Research Center for Translational Medicine, National Key Scientific Infrastructure for Translational Medicine (Shanghai), Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Background: The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic β-cells, however, the physiological functions of YY1 in β-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism.

Methods: We established two models of β-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, β-cell mass and β-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of β-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in β-cells.

Results: Our results showed that loss of YY1 resulted in reduction of insulin production, β-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic β-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models.

Conclusion: Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in β-cells.
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http://dx.doi.org/10.1016/j.metabol.2020.154353DOI Listing
September 2020

High-Detectivity Non-Fullerene Organic Photodetectors Enabled by a Cross-Linkable Electron Blocking Layer.

ACS Appl Mater Interfaces 2020 Oct 24;12(40):45092-45100. Epub 2020 Sep 24.

Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China.

The anode interlayer plays a critical role in the performance of organic photodetectors, which requires sufficient electron-blocking ability to simultaneously attain a high photocurrent and low dark current. Here, we developed two cross-linkable polymers, which can be deposited on the top of the widely used poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) and form a robust layer that can effectively suppress the electron injection from the anode under reverse bias. The optimized device with the resulting cross-linkable XP2 exhibited the lowest dark current density of 5.81 × 10 A cm at -0.1 V, which is about 2 orders of magnitude lower than the control devices. A remarkable responsivity of 0.5 A W and a detectivity of >1 × 10 Jones at a near-infrared wavelength of 800 nm were achieved. Of particular importance is that the resulting device exhibited a linear dynamic range of >135 dB associated with a high working frequency that is shorter than typical commercial digital imagers. The planar heterojunction devices demonstrate that the dark current is closely correlated to the charge generation, which relied on the highest occupied molecular orbital energy levels of the developed cross-linked interlays. The Mott-Schottky analysis revealed that the optimized cross-linked interlayer increased the depletion width of the devices.
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http://dx.doi.org/10.1021/acsami.0c13833DOI Listing
October 2020

Toward Efficient Tandem Organic Solar Cells: From Materials to Device Engineering.

ACS Appl Mater Interfaces 2020 Sep 25;12(36):39937-39947. Epub 2020 Aug 25.

Institute of Polymer Optoelectronic Materials and Devices, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, P. R. China.

Organic solar cells (OSCs) have demonstrated considerable potential in utilizing renewable solar energy because of their distinct advantages of light weight, low cost, and good flexibility. In the past decade, tremendous development in power conversion efficiency (PCE) from ∼7% to more than 17% has been witnessed. Among the various strategies of improving the PCE of OSCs, tandem structure is one of the most effective ways. In this Spotlight on Applications, we first introduce active-layer materials that we developed and selected for tandem OSC construction. We then emphasize an interconnecting layer (ICL) that we developed based on polymeric electron-transport layers. Benefiting from the organic nature of polymeric materials, the electron extraction ability and charge-transport ability of the organic electron-transport layer can be easily tuned by modifying the molecular structure or using a binary strategy, which enables us to obtain highly efficient tandem OSCs. Moreover, an ICL composed of a polymeric electron and hole-transport layer offers intrinsic advantage in obtaining a flexible tandem device and is compatible with the printing technique for fabricating large-area devices. After that, the application of the transfer matrix modeling method in predicting the best tandem OSCs architecture is introduced. Lastly, the possible research interests of tandem OSCs in the future from our point of view is discussed.
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http://dx.doi.org/10.1021/acsami.0c09909DOI Listing
September 2020

A Novel Sensor Prototype with Enhanced and Adaptive Sensitivity Based on Negative Stiffness Mechanism.

Sensors (Basel) 2020 Aug 18;20(16). Epub 2020 Aug 18.

Department of Civil Engineering, Xiamen University, Xiamen 361005, China.

Loess-mudstone/soil-rock interfacial landslide is one of the prominent landslide hazards that occurs in soil rock contacting zones. It is necessary to develop sensors with high sensitivity to weak and low frequency vibrations for the early warning of such interfacial landslides. In this paper, a novel monitoring sensor prototype with enhanced and adaptive sensitivity is developed for this purpose. The novelty of the sensitive sensor is based on the variable capacitances and negative stiffness mechanism due to the electric filed forces on the vibrating plate. Owing to the feedback control of adjustable electrostatic field by an embedded micro controller, the sensor has adaptive amplification characteristics with high sensitivity to weak and low frequency input and low sensitivity to high input. The design and manufacture of the proposed sensor prototype by Micro-Electro-Mechanical Systems (MEMS) with proper packaging are introduced. Post-signal processing is also presented. Some preliminary testing of the prototype and experimental monitoring of sand interfacial slide which mimics soil-rock interfacial landslide were performed to demonstrate the performance of the developed sensor prototype with adaptive amplification and enhanced sensitivity.
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http://dx.doi.org/10.3390/s20164644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472273PMC
August 2020

AMPK Ameliorates Tau Acetylation and Memory Impairment Through Sirt1.

Mol Neurobiol 2020 Dec 21;57(12):5011-5025. Epub 2020 Aug 21.

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Alzheimer's disease (AD) is the most common neurodegenerative disease, but its underlying mechanism is still unclear and the identities of drugs for AD also lack. Tau acetylation has become potentially important post-translational modification of tau. Levels of tau acetylation are significantly enhanced in AD patients and transgenic mouse models of AD, but the underlying mechanism and roles of tau hyperacetylation in AD onset maintain elusive. In the current study, we found that tau acetylation is obviously enhanced and the activities of AMP-activated protein kinase (AMPK) and sirtuin1 (Sirt1) are significantly decreased in APP/PS1 and streptozotocin (STZ) mice and high glucose (HG)-treated cells. Moreover, we demonstrated that activation of AMPK reduces the level of tau acetylation and ameliorates memory impairment, and its mechanism is associated with activation of Sirt1. Taken together, AMPK might be a crucial upstream molecular to regulate acetylation of tau and become a new target for AD therapy in the future.
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http://dx.doi.org/10.1007/s12035-020-02079-xDOI Listing
December 2020

Identification of free fatty acid receptor 2 agonists using virtual screening.

Bioorg Med Chem Lett 2020 11 2;30(21):127460. Epub 2020 Aug 2.

Merck & Co., Inc., Kenilworth, NJ, USA.

Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BEDROC and RIE. The results revealed that electrostatic similarity search protocol using EON (ET combo) outperformed all other protocols with outstanding enrichment of >95% in top 1% and 2% of the dataset with an AUC of 0.958. Interestingly, the hit lists that are obtained from different virtual-screening methods are generally highly complementary to hits found from electrostatic similarity searching. These results suggest that considering electrostatic similarity searching first increases the chance of identifying more (and more diverse) active compounds from a virtual-screening campaign. Accordingly, prospective virtual screening using electrostatic similarity searching was used to identify novel FFAR2 ligands. The discovered compounds provide new chemical matter starting points for the initiation of a medicinal chemistry campaign.
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http://dx.doi.org/10.1016/j.bmcl.2020.127460DOI Listing
November 2020

Recent anthropogenic curtailing of Yellow River runoff and sediment load is unprecedented over the past 500 y.

Proc Natl Acad Sci U S A 2020 08 20;117(31):18251-18257. Epub 2020 Jul 20.

The State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, Chinese Academy of Sciences, 710061 Xi'an, China.

The Yellow River (YR) is the fifth-longest and the most sediment-laden river in the world. Frequent historical YR flooding events, however, have resulted in tremendous loss of life and property, whereas in recent decades YR runoff and sediment load have fallen sharply. To put these recent changes in a longer-term context, we reconstructed natural runoff for the middle reach of the YR back to 1492 CE using a network of 31 moisture-sensitive tree-ring width chronologies. Prior to anthropogenic interference that started in the 1960s, the lowest natural runoff over the past 500 y occurred during 1926 to 1932 CE, a drought period that can serve as a benchmark for future planning of YR water allocation. Since the late 1980s, the low observed YR runoff has exceeded the natural range of runoff variability, a consequence of the combination of decreasing precipitation and increasing water consumption by direct and indirect human activities, particularly agricultural irrigation. This reduced runoff has resulted in an estimated 58% reduction of the sediment load in the upper reach of the YR and 29% reduction in the middle reach.
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http://dx.doi.org/10.1073/pnas.1922349117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414141PMC
August 2020
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