Publications by authors named "Meng Lei"

287 Publications

Achromatic anamorphic anastigmatic laser focusing.

Authors:
Lei Meng

Appl Opt 2021 Apr;60(12):3440-3445

This paper presents a simple method to focus multi-wavelength circular laser beams to elliptical spots (anamorphic) at a common waist location (achromatic) on both major and minor axes of the ellipse (anastigmatic), provided that each wavelength can be pre-shaped to appropriate waist sizes and locations. All lenses in the system are low-cost dispersive singlets and can be made out of the same material. The characteristics of Gaussian beam transformation through lenses are used to analyze how it works.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/AO.413477DOI Listing
April 2021

Discovery of novel tripeptide propylene oxide proteasome inhibitors for the treatment of multiple myeloma.

Bioorg Med Chem 2021 Jun 1;40:116182. Epub 2021 May 1.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China; Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd., No. 9 Weidi Road, Nanjing 210046, PR China. Electronic address:

The ubiquitin proteasome pathway (UPP) plays a critical role in the maintenance of cell homeostasis and the development of diseases, such as cancer and neurodegenerative disease. A series of novel tripeptide propylene oxide compounds as proteasome inhibitors were designed, synthesized and biologically investigated in this manuscript. The enzymatic activities of final compounds against 20S human proteasome were investigated and structure-activity relationship (SAR) was summarized. Some potent compounds were further evaluated to inhibit the proliferation of multiple myeloma (MM) cancer cell lines RPMI8226 and U266B. The results showed that some compounds were active against MM cancer cell lines with IC values of less than 50 nM. The microsomal metabolic stabilities in human, rat and mice species were carried out and the results showed that compounds 30 and 31 were stable enough to be in vivo investigated. The in vivo pharmacokinetic results showed that compounds 30 and 31 had acceptable biological parameters for both ig and iv administrations. In vivo antitumor activities of compounds 30 and 31 with the doses of 100 mg/kg and 50 mg/kg BIW were performed by using RPMI8226 xenograft nude mouse model. Toxicities of compounds 30 and 31 were not observed during the experiment and dose dependent effect was obvious and the tumor volume was greatly inhibited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2021.116182DOI Listing
June 2021

Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib.

Cell Death Dis 2021 Apr 30;12(5):429. Epub 2021 Apr 30.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Carfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087809PMC
April 2021

Etiological, epidemiological, and clinical features of acute diarrhea in China.

Nat Commun 2021 04 29;12(1):2464. Epub 2021 Apr 29.

The Institute for Disease Prevention and Control of PLA, Beijing, China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22551-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085116PMC
April 2021

Identification of a ferroptosis-related gene signature predictive model in colon cancer.

World J Surg Oncol 2021 Apr 29;19(1):135. Epub 2021 Apr 29.

Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui Province, People's Republic of China.

Background: The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear.

Methods: The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort.

Results: Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors.

Conclusion: A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-021-02244-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086290PMC
April 2021

A Quinoxaline-Based D-A Copolymer Donor Achieving 17.62% Efficiency of Organic Solar Cells.

Adv Mater 2021 Jun 29;33(23):e2100474. Epub 2021 Apr 29.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Side-chain engineering has been an effective strategy in tuning electronic energy levels, intermolecular interaction, and aggregation morphology of organic photovoltaic materials, which is very important for improving the power conversion efficiency (PCE) of organic solar cells (OSCs). In this work, two D-A copolymers, PBQ5 and PBQ6, are designed and synthesized based on bithienyl-benzodithiophene (BDTT) as the donor (D) unit, difluoroquinoxaline (DFQ) with different side chains as the acceptor (A) unit, and thiophene as the π-bridges. PBQ6 with two alkyl-substituted fluorothiophene side chains on the DFQ units possesses redshifted absorption, stronger intermolecular interaction, and higher hole mobility than PBQ5 with two alkyl side chains on the DFQ units. The blend film of the PBQ6 donor with the Y6 acceptor shows higher and balanced hole/electron mobilities, less charge carrier recombination, and more favorable aggregation morphology. Therefore, the OSC based on PBQ6:Y6 achieves a PCE as high as 17.62% with a high fill factor of 77.91%, which is significantly higher than the PCE (15.55%) of the PBQ5:Y6-based OSC. The PCE of 17.62% is by far one of the highest efficiencies for the binary OSCs with polymer donor and Y6 acceptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202100474DOI Listing
June 2021

Metagenomic sequencing reveals viral abundance and diversity in mosquitoes from the Shaanxi-Gansu-Ningxia region, China.

PLoS Negl Trop Dis 2021 Apr 26;15(4):e0009381. Epub 2021 Apr 26.

Chinese Center for Disease Control and Prevention -Wuhan Institute of Virology, Chinese Academy of Sciences Joint Research Center for Emerging Infectious Diseases and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China.

Background: Mosquitoes host and transmit numerous arthropod-borne viruses (arboviruses) that cause disease in both humans and animals. Effective surveillance of virome profiles in mosquitoes is vital to the prevention and control of mosquito-borne diseases in northwestern China, where epidemics occur frequently.

Methods: Mosquitoes were collected in the Shaanxi-Gansu-Ningxia region (Shaanxi Province, Gansu Province, and Ningxia Hui Autonomous Region) of China from June to August 2019. Morphological methods were used for taxonomic identification of mosquito species. High-throughput sequencing and metagenomic analysis were used to characterize mosquito viromes.

Results: A total of 22,959 mosquitoes were collected, including Culex pipiens (45.7%), Culex tritaeniorhynchus (40.6%), Anopheles sinensis (8.4%), Aedes (5.2%), and Armigeres subalbatus (0.1%). In total, 3,014,183 (0.95% of clean reads) viral sequences were identified and assigned to 116 viral species (including pathogens such as Japanese encephalitis virus and Getah virus) in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. Mosquitoes collected in July (86 species in 26 families) showed greater viral diversity than those from June and August. Culex pipiens (69 species in 25 families) and Culex tritaeniorhynchus (73 species in 24 families) carried more viral species than Anopheles sinensis (50 species in 19 families) or Aedes (38 species in 20 families) mosquitoes.

Conclusion: Viral diversity and abundance were affected by mosquito species and collection time. The present study elucidates the virome compositions of various mosquito species in northwestern China, improving the understanding of virus transmission dynamics for comparison with those of disease outbreaks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0009381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101993PMC
April 2021

Low-loss c-axis oriented ZnMgO nonlinear planar optical waveguides on silicon.

Opt Express 2021 Mar;29(7):11301-11313

A material platform of highly c-axis oriented ZnMgO thin films is developed for nonlinear planar waveguides and electro-optic modulators on Si. Mg content in the film greatly influences the quality of film growth. The second harmonic generation measurement and Maker-fringe analysis reveal that the second-order nonlinear susceptibility tensor element χ of the annealed ZnMgO is approximately 4.2 times larger than that of ZnO. The propagation loss of 633 nm wavelength light in the annealed air/ZnMgO/SiO slab waveguide is 0.68 ± 0.09 dB/cm and 0.48 ± 0.03 dB/cm for the TE0 and TM0 modes, respectively. These results suggest the great potential of the c-axis oriented ZnMgO nonlinear planar waveguides for applications in on-chip optical interconnects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.421932DOI Listing
March 2021

An Improved UNet++ Model for Congestive Heart Failure Diagnosis Using Short-Term RR Intervals.

Diagnostics (Basel) 2021 Mar 16;11(3). Epub 2021 Mar 16.

School of Computer Science and Engineering (SCSE), Nanyang Technological University (NTU), Singapore 639798, Singapore.

Congestive heart failure (CHF), a progressive and complex syndrome caused by ventricular dysfunction, is difficult to detect at an early stage. Heart rate variability (HRV) was proposed as a prognostic indicator for CHF. Inspired by the success of 2-D UNet++ in medical image segmentation, in this paper, we introduce an end-to-end encoder-decoder model to detect CHF using HRV signals. The developed model enhances the UNet++ model with Squeeze-and-Excitation (SE) residual blocks to extract deep features hierarchically and distinguish CHF patients from normal subjects. Two open-source databases are utilized for evaluating the proposed method, and three segment lengths of intervals between successive R-peaks are employed in comparison with state-of-the-art methods. The proposed method achieves an accuracy of 85.64%, 86.65% and 88.79% when 500, 1000 and 2000 RR intervals are utilized, respectively. It demonstrates that HRV evaluation based on deep learning can be an important tool for early detection of CHF, and may assist clinicians in achieving timely and accurate diagnoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11030534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002263PMC
March 2021

Nilotinib, A Tyrosine Kinase Inhibitor, Suppresses the Cell Growth and Triggers Autophagy in Papillary Thyroid Cancer.

Anticancer Agents Med Chem 2021 Apr 1. Epub 2021 Apr 1.

The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei. China.

Background: Papillary thyroid carcinoma (PTC) represents for the most common thyroid cancer. Until recently, treatment options for PTC patients are limited. Nilotinib is the second-generation tyrosine kinase inhibitor, and has been widely used in the treatment of chronic myeloid leukemia (CML).

Objectives: We aimed to explore whether nilotinib is effective in PTC cancer progression and the underlying mechanisms.

Methods: In this study, the three human PTC cell lines (KTC-1, BCPAP, and TPC1) were used to verify the effects of nilotinib on cell growth. The half maximal inhibitory concentration (IC50) was calculated according to the growth curve post nilotinib treatment at different concentrations. Cell counting kit-8 and colony formation analysis were used to monitor cell growth after nilotinib treatment. Cell apoptosis and autophagy related proteins and phosphorylation of PI3K/Akt/mTOR were detected by Western blotting analysis.

Results: Nilotinib treatment can effectively inhibit PTC cell growth, which was accompanied by increase of apoptosis and induction of autophagy. Mechanistically, nilotinib treatment repressed the phosphorylation of PI3K/Akt/mTOR pathway.

Conclusion: Collectively, our results demonstrated that nilotinib may display anti-tumor effect against PTC via inhibiting of PI3K/Akt/mTOR pathway and inducing apoptosis and autophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520621666210402110331DOI Listing
April 2021

Upregulation of Extracellular Vesicles-Encapsulated miR-132 Released From Mesenchymal Stem Cells Attenuates Ischemic Neuronal Injury by Inhibiting Smad2/c-jun Pathway Acvr2b Suppression.

Front Cell Dev Biol 2020 8;8:568304. Epub 2021 Mar 8.

Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Ischemic cerebrovascular disease is a significant and common public health issue worldwide. The emerging roles of mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) in ischemic neuronal injury continue to be investigated. The current study aimed to investigate the role of EV-derived miR-132 from MSCs in ischemic neuronal injury. EVs were initially isolated from bone MSCs (BMSCs) and subsequently evaluated. A middle cerebral artery occlusion (MCAO) mouse model was constructed with the neurological function evaluated through a series of neurological scores, a pole test, and a foot fault test. Histopathological changes, neuron viability, and apoptosis, as well as cerebral infarction, were detected by hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The targeting relationship between microRNA (miR)-132 and Activin receptor type IIB (Acvr2b) was further confirmed based on dual-luciferase reporter gene assay results. Loss- and gain-of-function assays were conducted to elucidate the role of miR-132, EV-derived miR-132, Acvr2b, and Smad2 in oxygen-glucose deprivation (OGD)-treated neurons, and in mice models. Neuronal cell viability and apoptosis were evaluated via Cell Counting kit-8 (CCK-8) and flow cytometry. Our results indicated that Acvr2b was highly expressed, while miR-132 was poorly expressed in the MCAO mice and OGD-treated neurons. Acvr2b silencing or upregulation of miR-132 led to an elevation in neuronal activity, decreased neuronal apoptosis, reduced expression of Bax, and cleaved-caspase 3, as well as increased Bcl-2 expression. Acvr2b expression was targeted and inhibited by miR-132. EV-derived Acvr2b promoted activation of phosphorylated-Smad2 (p-Smad2)/c-jun signaling pathway, ultimately inducing neuronal injury. Our study provides evidence demonstrating that the overexpression of c-jun inhibits the protective role of MSCs-derived EV-miR-132 in neuronal injury. Upregulation of EV-derived miR-132 released from MSCs attenuates ischemic neuronal injury by inhibiting Smad2/c-jun pathways the suppression of Acvr2b.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.568304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982537PMC
March 2021

Relation between Blood Pressure Variability within a Single Visit and Stroke.

Int J Hypertens 2021 2;2021:2920140. Epub 2021 Mar 2.

Division of Cardiology, Peking University First Hospital, Dahongluochang Street, Xicheng District, Beijing 100034, China.

Blood pressure variability (BPV) has been identified as an important risk factor for cardiovascular events. The white coat effect (WCE), which is measured as the first systolic blood pressure (SBP) measurement minus the mean of the second and third measurements, is a BPV indicator within a single visit. In total, 2,972 participants who had three measurements of BP within a single visit were included. The participants were divided into three groups based on their WCE percentiles: Group 1 (WCE, 2.5-97.5th percentiles of WCE), Group 2 (WCE, 0-2.4th percentiles of WCE), and Group 3 (WCE, 97.6-100th percentiles of WCE). A multiple logistic regression model was used to analyze the relationship between WCE and stroke after adjusting for cardiovascular disease risk factors. Compared with the WCE group, the OR for stroke in the WCE group was 2.78 (95% CI: 1.22, 6.36, =0.015). After adjusting for cardiovascular factors, OR increased to 3.12 (95% CI: 1.22, 7.96, =0.017). The OR of WCE for stroke was 0.93 (95%CI: 0.87, 0.99, =0.036). BPV within a single visit is associated with stroke. The value and direction of the change may be important as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/2920140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943313PMC
March 2021

HDAC9 Silencing Exerts Neuroprotection Against Ischemic Brain Injury miR-20a-Dependent Downregulation of NeuroD1.

Front Cell Neurosci 2020 11;14:544285. Epub 2021 Jan 11.

Department of Neurosurgery, Shandong Provincial Hospital, Jinan, China.

Cerebral stroke is an acute cerebrovascular disease that is a leading cause of death and disability worldwide. Stroke includes ischemic stroke and hemorrhagic strokes, of which the incidence of ischemic stroke accounts for 60-70% of the total number of strokes. Existing preclinical evidence suggests that inhibitors of histone deacetylases (HDACs) are a promising therapeutic intervention for stroke. In this study, the purpose was to investigate the possible effect of HDAC9 on ischemic brain injury, with the underlying mechanism related to microRNA-20a (miR-20a)/neurogenic differentiation 1 (NeuroD1) explored. The expression of HDAC9 was first detected in the constructed middle cerebral artery occlusion (MCAO)-provoked mouse model and oxygen-glucose deprivation (OGD)-induced cell model. Next, primary neuronal apoptosis, expression of apoptosis-related factors (Bax, cleaved caspase3 and bcl-2), LDH leakage rate, as well as the release of inflammatory factors (TNF-α, IL-1β, and IL-6) were evaluated by assays of TUNEL, Western blot, and ELISA. The relationships among HDAC9, miR-20a, and NeuroD1 were validated by analysis and ChIP assay. HDAC9 was highly-expressed in MCAO mice and OGD-stimulated cells. Silencing of HDAC9 inhibited neuronal apoptosis and inflammatory factor release . HDAC9 downregulated miR-20a by enriching in its promoter region, while silencing of HDCA9 promoted miR-20a expression. miR-20a targeted Neurod1 and down-regulated its expression. Silencing of HDAC9 diminished OGD-induced neuronal apoptosis and inflammatory factor release as well as ischemic brain injury by regulating the miR-20a/NeuroD1 signaling. Overall, our study revealed that HDAC9 silencing could retard ischemic brain injury through the miR-20a/Neurod1 signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2020.544285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873949PMC
January 2021

Screening Traditional Chinese Medicine Combination for Cotreatment of Alzheimer's Disease and Type 2 Diabetes Mellitus by Network Pharmacology.

J Alzheimers Dis 2021 ;80(2):787-797

Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People's Republic of China.

Background: In recent years, the efficacy of type 2 diabetes mellitus (T2DM) drugs in the treatment of Alzheimer's disease (AD) has attracted extensive interest owing to the close associations between the two diseases.

Objective: Here, we screened traditional Chinese medicine (TCM) and multi-target ingredients that may have potential therapeutic effects on both T2DM and AD from T2DM prescriptions.

Methods: Network pharmacology and molecular docking were used.

Results: Firstly, the top 10 frequently used herbs and corresponding 275 active ingredients were identified from 263 T2DM-related TCM prescriptions. Secondly, through the comparative analysis of 208 potential targets of ingredients, 1,740 T2DM-related targets, and 2,060 AD-related targets, 61 common targets were identified to be shared. Thirdly, by constructing pharmacological network, 26 key targets and 154 representative ingredients were identified. Further enrichment analysis showed that common targets were involved in regulating multiple pathways related to T2DM and AD, while network analysis also found that the combination of Danshen (Radix Salviae)-Gancao (Licorice)-Shanyao (Rhizoma Dioscoreae) contained the vast majority of the representative ingredients and might be potential for the cotreatment of the two diseases. Fourthly, MAPK1, PPARG, GSK3B, BACE1, and NR3C1 were selected as potential targets for virtual screening of multi-target ingredients. Further docking studies showed that multiple natural compounds, including salvianolic acid J, gancaonin H, gadelaidic acid, icos-5-enoic acid, and sigmoidin-B, exhibited high binding affinities with the five targets.

Conclusion: To summarize, the present study provides a potential TCM combination that might possess the potential advantage of cotreatment of AD and T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-201336DOI Listing
January 2021

A Meaning-Aware Cultural Tourism Intelligent Navigation System Based on Anticipatory Calculation.

Authors:
Lei Meng Yuan Liu

Front Psychol 2020 22;11:611383. Epub 2021 Jan 22.

School of Artificial Intelligence and Computer Science, Jiangnan University, Wuxi, China.

To improve the personalized service of cultural tourism, anticipatory calculation has become an essential technology in the content design of intelligence navigation system. Culture tourism, as a form of leisure activity, is being favored by an increasing number of people, which calls for further improvements in the cultural consumption experience. An important component of cultural tourism is for tourists to experience intangible cultural heritage projects with local characteristics. However, from the perspective of user needs and the content adaptive system, there are few suitable intelligent navigation and user demand anticipatory systems for intangible cultural heritage content. Purple clay culture is one of the first batches of national intangible cultural heritage protection projects in China. Therefore, taking purple clay culture exhibition as an example, this paper attempts to analyze the personalized information demand of tourism consumption experience in intangible cultural heritage communication activities with affective computing and meaning-driven innovative design method, by taking the content design in the navigation system as the research object. This paper uses the theory of planned behavior to calculate the relationship between tourists' attitude, experience behavior, and display information demand. The findings indicate two issues. First, tourists' demand for the entertainment and leisure attributes of intangible cultural heritage is greater than the demand for educational function attributes. Second, the meaning elements of information can change tourists' beliefs in intangible cultural heritage and affect their attitude and behavior toward such heritage. According to the research results, strengthening the meaning elements of specific group information can improve people's cultural identity and tourism satisfaction. The research results provide the basis for the content design direction of future museum intelligent navigation systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2020.611383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862136PMC
January 2021

Copper(I)-Catalyzed Enyne Oxidation/Cyclopropanation: Divergent and Enantioselective Synthesis of Cyclopropanes.

Org Lett 2021 02 2;23(4):1285-1290. Epub 2021 Feb 2.

College of Sciences, Henan Agricultural University, Zhengzhou, Henan 450002, China.

An efficient copper(I)-catalyzed enyne oxidation/cyclopropanation for the modular synthesis of cyclopropane derivatives is described, which represents the first non-noble metal-catalyzed enynes oxidation/cyclopropanation by the in situ generated α-oxo copper carbenes. This protocol allows the assembly of valuable cyclopropane-γ-lactams in generally good to excellent yields with excellent diastereoselectivity. More significantly, the enantioselective version of enyne oxidation/cyclopropanation has been disclosed with chiral copper catalysts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c04268DOI Listing
February 2021

Associations Between Obesity and Alzheimer's Disease: Multiple Bioinformatic Analyses.

J Alzheimers Dis 2021 ;80(1):271-281

Institute of Biomedical Research, Shandong University of Technology, Zibo, Shandong, People's Republic of China.

Background: Identifying modifiable risk factors, such as obesity, to lower the prevalence of Alzheimer's disease (AD) has gained much interest. However, whether the association is causal remains to be evaluated.

Objective: The present study was designed: 1) to make a quantitative assessment of the association between obesity and AD; 2) to validate whether there was a causal association between them; and 3) to provide genetic clues for the association through a network-based analysis.

Methods: Two-sample Mendelian randomization (2SMR) analysis, meta-analysis, and protein-protein interaction (PPI) network analysis, were employed.

Results: Firstly, the meta-analysis based on 9 studies comprising 6,986,436 subjects indicated that midlife obesity had 33%higher AD odds than controls (OR = 1.33, 95%CI = [1.03, 1.62]), while late-life obesity were inversely associated with AD risk (OR = 0.57, 95%CI = [0.47, 0.68]). Secondly, 2SMR analysis indicated that there was no causal association between them. Thirdly, CARTPT was identified to be shared by the anti-obesity drug targets and AD susceptibility genes. Further PPI network analysis found that CARTPT interacted with CD33, a strong genetic locus linked to AD. Finally, 2SMR analysis showed that CNR1 could be a protective factor for AD.

Conclusion: Multiple bioinformatic analyses indicated that midlife obesity might increase the risk of AD, while current evidence indicated that there was no causal association between them. Further, CARTPT might be an important factor linking the two disease conditions. It could help to better understand the mechanisms underlying the associations between obesity and AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-201235DOI Listing
January 2021

High performance tandem organic solar cells via a strongly infrared-absorbing narrow bandgap acceptor.

Nat Commun 2021 Jan 8;12(1):178. Epub 2021 Jan 8.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China.

Tandem organic solar cells are based on the device structure monolithically connecting two solar cells to broaden overall absorption spectrum and utilize the photon energy more efficiently. Herein, we demonstrate a simple strategy of inserting a double bond between the central core and end groups of the small molecule acceptor Y6 to extend its conjugation length and absorption range. As a result, a new narrow bandgap acceptor BTPV-4F was synthesized with an optical bandgap of 1.21 eV. The single-junction devices based on BTPV-4F as acceptor achieved a power conversion efficiency of over 13.4% with a high short-circuit current density of 28.9 mA cm. With adopting BTPV-4F as the rear cell acceptor material, the resulting tandem devices reached a high power conversion efficiency of over 16.4% with good photostability. The results indicate that BTPV-4F is an efficient infrared-absorbing narrow bandgap acceptor and has great potential to be applied into tandem organic solar cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20431-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794321PMC
January 2021

Background-Free Chromatographic Detection of Sepsis Biomarker in Clinical Human Serum through Near-Infrared to Near-Infrared Upconversion Immunolabeling.

ACS Nano 2020 Dec 9. Epub 2020 Dec 9.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering & Key Laboratory of Micro-systems and Micro-Structures, Ministry of Education, Harbin Institute of Technology, Harbin 150001, China.

Luminescence nanomaterial-based lateral flow assay (LFA) is promising for point-of-care tests. However, the detection sensitivity and accuracy are often affected by the interferences of autofluorescence and photon scattering from nitrocellulose membrane and colored plasma. Here, we describe a near-infrared to near-infrared upconversion nanoparticle (UCNP) immunolabeled LFA for background-free chromatographic detection of sepsis biomarker procalcitonin (PCT) in clinical human plasma. This upconversion immunolabeling enables both light excitation (at ∼980 nm) and anti-Stokes emission (at 800 nm) to be adopted within the first biological window (700-1000 nm), which eliminates background autofluorescence as well as photon scattering interferences, empowering a high-sensitivity detection without complicated procedures. After optimization, the described assay presented a limit of detection reaching down to 0.03 ng/mL, lower than the normal level (0.05 ng/mL), while having a detection range of 0.03-50 ng/mL that covers the clinical PCT level of interest (0.5-10 ng/mL). The assay recoveries in human serum samples were evaluated to be about 95-110%, whereas the inter- and intra-assay coefficient variations were both determined to be below 15%. Importantly, measured PCT concentrations in clinical samples are in good correlation with that of the electrochemiluminescence immunoassay (Roche) widely applied in large clinical settings. This near-infrared to near-infrared upconversion immunolabeling approach has direct implications for ultrasensitive and background-free point-of-care detection of other serum biomarkers in resource-limited clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c05700DOI Listing
December 2020

Tannic Acid-Silver Dual Catalysis Induced Rapid Polymerization of Conductive Hydrogel Sensors with Excellent Stretchability, Self-Adhesion, and Strain-Sensitivity Properties.

ACS Appl Mater Interfaces 2020 Dec 3;12(50):56509-56521. Epub 2020 Dec 3.

Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, China.

The application of conductive hydrogels in intelligent biomimetic electronics is a hot topic in recent years, but it is still a great challenge to develop the conductive hydrogels through a rapid fabrication process at ambient temperature. In this work, a versatile poly(acrylamide) @cellulose nanocrystal/tannic acid-silver nanocomposite (NC) hydrogel integrated with excellent stretchability, repeatable self-adhesion, high strain sensitivity, and antibacterial property, was synthesized via radical polymerization within 30 s at ambient temperature. Notably, this rapid polymerization was realized through a tannic acid-silver (TA-Ag) mediated dynamic catalysis system that was capable of activating ammonium persulfate and then initiated the free-radical polymerization of the acrylamide monomer. Benefiting from the incorporation of TA-Ag metal ion nanocomplexes and cellulose nanocrystals, which acted as dynamic connecting bridges by hydrogen bonds to efficiently dissipate energy, the obtained NC hydrogels exhibited prominent tensile strain (up to 4000%), flexibility, self-recovery, and antifatigue properties. In addition, the hydrogels showed repeatable adhesiveness to different substrates (e.g., glass, wood, bone, metal, and skin) and significant antibacterial properties, which were merits for the hydrogels to be assembled into a flexible epidermal sensor for long-term human-machine interfacial contact without concerns about the use of external adhesive tapes and bacterial breeding. Moreover, the remarkable conductivity (σ ∼ 5.6 ms cm) and strain sensitivity (gauge factor = 1.02) allowed the flexible epidermal sensors to monitor various human motions in real time, including huge movement of deformations (e.g., wrist, elbow, neck, shoulder) and subtle motions. It is envisioned that this work would provide a promising strategy for the rapid preparation of conductive hydrogels in the application of flexible electronic skin, biomedical devices, and soft robotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c18250DOI Listing
December 2020

and efficacy of the novel oral proteasome inhibitor NNU546 in multiple myeloma.

Aging (Albany NY) 2020 11 16;12(22):22949-22974. Epub 2020 Nov 16.

College of Life Science, Nanjing Normal University, Nanjing 210046, PR China.

Proteasome inhibition demonstrates highly effective impact on multiple myeloma (MM) treatment. Here, we aimed to examine anti-tumor efficiency and underlying mechanisms of a novel well tolerated orally applicable proteasome inhibitor NNU546 and its hydrolyzed pharmacologically active form NNU219. NNU219 showed more selective inhibition to proteasome catalytic subunits and less off-target effect than bortezomib . Moreover, intravenous and oral administration of either NNU219 or NNU546 led to more sustained pharmacodynamic inhibitions of proteasome activities compared with bortezomib. Importantly, NNU219 exhibited potential anti-MM activity in both MM cell lines and primary samples . The anti-MM activity of NNU219 was associated with induction of G2/M-phase arrest and apoptosis via activation of the caspase cascade and endoplasmic reticulum stress response. Significant growth-inhibitory effects of NNU219 and NNU546 were observed in 3 different human MM xenograft mouse models. Furthermore, such observation was even found in the presence of a bone marrow microenvironment. Taken together, these findings provided the basis for clinical trial of NNU546 to determine its potential as a candidate for MM treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.104023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746380PMC
November 2020

Hyperglycemia Induces Endoplasmic Reticulum Stress in Atrial Cardiomyocytes, and Mitofusin-2 Downregulation Prevents Mitochondrial Dysfunction and Subsequent Cell Death.

Oxid Med Cell Longev 2020 22;2020:6569728. Epub 2020 Oct 22.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.

Mitochondrial oxidative stress and dysfunction play an important role of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus. Endoplasmic reticulum (ER) stress has been linked to both physiological and pathological states including diabetes. The aim of this project is to explore the roles of ER stress in hyperglycemia-induced mitochondrial dysfunction and cell death of atrial cardiomyocytes. High glucose upregulated ER stress, mitochondrial oxidative stress, and mitochondria-associated ER membrane (MAM)- enriched proteins (such as glucose-regulated protein 75 (GRP75) and mitofusin-2 (Mfn2)) of primary cardiomyocytes . Sodium phenylbutyrate (4-PBA) prevented the above changes. Silencing of Mfn2 in HL-1 cells decreased the Ca transfer from ER to mitochondria under ER stress conditions, which were induced by the ER stress agonist, tunicamycin (TM). Electron microscopy data suggested that Mfn2 siRNA significantly disrupted ER-mitochondria tethering in ER stress-injured HL-1 cells. Mfn2 silencing attenuated mitochondrial oxidative stress and Ca overload, increased mitochondrial membrane potential and mitochondrial oxygen consumption, and protected cells from TM-induced apoptosis. In summary, Mfn2 plays an important role in high glucose-induced ER stress in atrial cardiomyocytes, and Mfn2 silencing prevents mitochondrial Ca overload-mediated mitochondrial dysfunction, thereby decreasing ER stress-mediated cardiomyocyte cell death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/6569728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603626PMC
May 2021

Alternation of soil bacterial and fungal communities by tomato-rice rotation in Hainan Island in Southeast of China.

Arch Microbiol 2021 Apr 19;203(3):913-925. Epub 2020 Oct 19.

Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.

Tomato-rice rotation is prevalent in subtropical and tropical regions in China. This practice enhances crop productivity and the disease suppression property of soils against soil-borne plant pathogens. To explore the variations and dynamics of bacterial and fungal communities, bulk soil samples were collected during two consecutive years under a rotation system between tomato and rice originated from the year of 2010 in Hainan Island, and 16S rDNA and ITS amplicons were sequenced by Illumina MiSeq. The results demonstrated that potentially beneficial bacterial phyla Acidobacteria, Chloroflexi and genus Paenibacillus, as well as the fungal genus Mortierella were significantly enriched, while the potentially pathogenic fungal genus Fusarium was significantly decreased during the crop rotation. Measurements of soil physicochemical properties indicated that the soil acidification was improved. Redundancy analysis (RDA) revealed the correlation of the microbial community with soil pH and identified soil total phosphorus (TP) level as the highest determinant factor for both bacterial and fungal communities. This work provides a preliminary description of changes of the bacterial and fungal communities related to tomato-rice rotation in China and offered experimental evidences for exploring the effects of this agricultural practice on soil ecology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00203-020-02086-5DOI Listing
April 2021

Transcriptome-wide analysis and modelling of prognostic alternative splicing signatures in invasive breast cancer: a prospective clinical study.

Sci Rep 2020 10 5;10(1):16504. Epub 2020 Oct 5.

Department of Endocrine and Breast Surgery, The First Affliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Aberrant alternative splicing (AS) has been highly involved in the tumorigenesis and progression of most cancers. The potential role of AS in invasive breast cancer (IBC) remains largely unknown. In this study, RNA sequencing of IBC samples from The Cancer Genome Atlas was acquired. AS events were screened by conducting univariate and multivariate Cox analysis and least absolute shrinkage and selection operator regression. In total, 2146 survival-related AS events were identified from 1551 parental genes, of which 93 were related to prognosis, and a prognostic marker model containing 14 AS events was constructed. We also constructed the regulatory network of splicing factors (SFs) and AS events, and identified DDX39B as the node SF gene, and verified the accuracy of the network through experiments. Next, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in triple negative breast cancer patients with different responses to neoadjuvant chemotherapy, and found that the exon-specific expression of EPHX2, C6orf141, and HERC4 was associated with the different status of patients that received neoadjuvant chemotherapy. In conclusion, this study found that DDX39B, EPHX2 (exo7), and HERC4 (exo23) can be used as potential targets for the treatment of breast cancer, which provides a new idea for the treatment of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-73700-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536242PMC
October 2020

AlzRiskMR database: an online database for the impact of exposure factors on Alzheimer's disease.

Brief Bioinform 2021 May;22(3)

Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Institute of Biomedical Research, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, China.

In view of great difficulties in the pathogenesis analysis of Alzheimer's disease (AD) presently, profiling the modifiable risk factors is crucial for early detection and intervention of AD. However, the causal associations among them have yet to be identified, and the effective integration and application of these data also remain considerable challenges due to the lack of efficient collection and analysis procedures. To address this issue, we performed comprehensive analyses by two-sample Mendelian randomization (2SMR) and established the AlzRiskMR database (https://github.com/SDBMC/RiskFactors2AD). Four 2SMR analysis methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were used for the complementary calculation to test the reliability of the results. The database currently comprises 1870 sets of data of Genome-Wide Association Studies (GWAS) from the MR-Base and NHGRI-EBI GWAS Catalog database. AlzRiskMR database not only estimates causal associations between modifiable risk factors and AD but also offers a useful and timely resource for early intervention of AD development incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bib/bbaa213DOI Listing
May 2021

Magnetic Properties of NHHPO and KHPO: Emergence of Multiferroic Salts.

J Phys Chem Lett 2020 Oct 18;11(19):8297-8301. Epub 2020 Sep 18.

State Key Laboratory on Tunable Laser Technology, Ministry of Industry and Information Technology Key Laboratory of Micro-Nano Optoelectronic Information System and the School of Science, Harbin Institute of Technology, Shenzhen, University Town, Shenzhen, Guangdong 518055, P. R. China.

We observe sharp step-down discontinuities in the magnetic susceptibility of NHHPO and NHHPO- (60% deuterated) along the - and -axes occurring exactly at their antiferroelectric transition temperatures. For the case of KHPO, less pronounced discontinuities occur at the ferroelectric transition temperature. To explain this, we treat the acid protons as individual oscillators that generate current elements that translate to magnetic forces in near resonance with each other. With decreasing temperature, the resonant forces become more commensurate, which amplifies a disproportionate drop off of two types of magnetic forces to eventually trigger the structural phase transitions. For the case of NHHPO, the associated internal magnetic field appears to aid the NH to order at a higher temperature. At 49 K, a shoulder-like anomaly in both NHHPO and KHPO is attributed to a possible onset of macroscopic quantum tunneling of protons. Our findings bring forth a new category of intrinsic multiferroic systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.0c02634DOI Listing
October 2020

LiCO-affiliative mechanism for air-accessible interface engineering of garnet electrolyte via facile liquid metal painting.

Nat Commun 2020 Jul 24;11(1):3716. Epub 2020 Jul 24.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 585 He Shuo Road, 201899, Shanghai, China.

Garnet based solid-state batteries have the advantages of wide electrochemical window and good chemical stability. However, at Li-garnet interface, the poor interfacial wettability due to LiCO passivation usually causes large resistance and unstable contact. Here, a LiCO-affiliative mechanism is proposed for air-accessible interface engineering of garnet electrolyte via facile liquid metal (LM) painting. The natural LM oxide skin enables a superior wettability of LM interlayer towards ceramic electrolyte and Li anode. Therein the removal of LiCO passivation network is not necessary, in view of its delamination and fragmentation by LM penetration. This dissipation effect allows the lithiated LM nanodomains to serve as alternative Li-ion flux carriers at Li-garnet interface. This mechanism leads to an interfacial resistance as small as 5 Ω cm even after exposing garnet in air for several days. The ultrastable Li plating and stripping across LM painted garnet can last for 9930 h with a small overpotential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17493-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382479PMC
July 2020

LncRNA HOTAIR promotes the growth and metastasis of gastric cancer by sponging miR-1277-5p and upregulating COL5A1.

Gastric Cancer 2020 11 24;23(6):1018-1032. Epub 2020 Jun 24.

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, PR China.

Background: Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown.

Methods: HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas.

Results: We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1-mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC.

Conclusions: HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10120-020-01091-3DOI Listing
November 2020

Modeling the effects of lake-effect snow related weather conditions on daily traffic crashes: A time series count data approach.

Accid Anal Prev 2020 09 18;144:105510. Epub 2020 Jun 18.

Department of Civil and Construction Engineering, Western Michigan University, Mail Stop 5316 G-253 Floyd Hall, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aap.2020.105510DOI Listing
September 2020