2,207 results on '"ZHENG LI"'
Search Results
2. Integrated Risk Assessment of Mountainous Long-Distance Oil and Gas Pipelines Based on Multisource Spatial Data
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Benji Wang, Zheng Li, Baikang Zhu, Zijia Wang, Jian Guo, Cuicui Li, Li Chen, and Jiren Qian
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Chemistry ,QD1-999 - Published
- 2024
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3. pH-responsive berberine release from metal-organic framework based nanocarriers by regulating oxidative stress for targeted therapy of oral squamous cell carcinoma
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Mengyuan Li, Jingwen Yao, Jiaming Ge, Jinling Guo, Lin Ma, Zheng Li, Xiangli Han, Ming Liu, Fei Tian, and Jing Zhao
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Metal organic framework ,Oxidative stress ,Oral squamous cell carcinoma ,Berberine ,Tumor microenvironment ,Chemistry ,QD1-999 - Abstract
Excessive generation of reactive oxygen species (ROS) induces cellular oxidative stress damage, resulting in mitochondrial dysfunction and subsequent promotion of apoptosis. Induction of oxidative stress damage through chemo-dynamic therapy within the tumor microenvironment (TME) represents a promising therapeutic strategy for cancer treatment. Herein, folic acid-polyethylene glycol (FA-PEG)-modified MIL-101 NPs loaded with berberine (BER) were constructed to develop a nanoplatform based on the modulation of oxidative stress for the treatment of Oral squamous cell carcinoma (OSCC). Comprehensive characterizations based on TEM, DLS, XRD, FTIR, TGA and UV–vis spectroscopy confirmed the successful synthesis of MIL-101/PEG-FA with uniform size, high drug loading efficiency (32.59 %) and superior pH-responsive drug release (Ber release of 24.44 % and 70.22 % within 96h at pH 7.4 and 5.0, respectively). Cellular experiments revealed that MIL-101/PEG-FA achieved the pH-responsiveness release of the BER in the TME, thereby improving the bioavailability of BER. Moreover, Fe3+ in MIL-101(Fe) showed strong ability to consume GSH and provide a continuous supply of H2O2, which decreased SOD activity, and contributed to the generation of MDA, thereby increasing the production of toxic ROS in CAL27 cells. Meanwhile, MIL-101@BER/PEG-FA up-regulated inflammatory cytokine levels (TNF-α and IL-1β), promoted inflammatory response in TME, induced CAL27 cells apoptosis by regulating the LKB1/AMPK pathway. Finally, MIL-101@BER/PEG-FA showed good efficiency against OSCC in vivo. Consequently, MIL-101/PEG-FA can be applied as a nanocarrier platform for the treatment of OSCC.
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- 2024
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4. Dynamic Modeling and Observer-Based Fixed-Time Backstepping Control for a Hypersonic Morphing Waverider
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Zheng Fang, Zheng Li, Zhenyue Jia, Jiaxun Li, and Jianqiao Yu
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fixed-time stability ,backstepping control ,hypersonic morphing waverider ,disturbance observer ,variable-span wing ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
This paper proposes a fixed-time backstepping control method based on a disturbance observer for a hypersonic morphing waverider (HMW). Firstly, considering the disturbance of attitude channels, a dynamic model of a variable-span-wing HMW considering additional forces and moments is established, and an aerodynamic model of the aircraft is constructed using the polynomial fitting method. Secondly, the fixed-time stability theory and backstepping control method are combined to design an HMW fixed-time attitude controller. Based on the fixed-time convergence theory, a fixed-time disturbance observer is designed to achieve an accurate online estimation of disturbance and to compensate for the control law. In order to solve the problem of the “explosion of terms”, a nonlinear first-order filter is used instead of a traditional linear first-order filter to obtain the differential signal, ensuring the overall fixed-time stability of the system. The fixed-time stability of the closed-loop system is strictly proven via Lyapunov analysis. The simulation results show that the proposed method has good adaptability under different initial conditions, morphing speeds, and asymmetric morphing rates of the HMW.
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- 2024
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5. Enhancing SERS Sensitivity in N‐Graphene Hydrangea by Synergistic Charge‐Transfer and Excitation Light Absorption
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Bingkun Wang, Zheng Li, Huijuan Wu, Shan Zhang, Guanglin Zhang, Jinqiu Zhang, Shanshui Lian, Li Zheng, Zhongying Xue, Siwei Yang, Guqiao Ding, Wenwu Xu, Shiwei Tang, and Gang Wang
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charge transfer ,environmental hormone ,nano‐cavity ,N‐graphene hydrangea ,surface‐enhanced Raman scattering ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Surface‐enhanced Raman scattering (SERS) is a versatile spectroscopic technique, which plays a crucial role in enhancing analytical sensitivity, investigating interfacial reaction mechanisms, enabling biosensing, and fostering efficient catalysis. Currently, the common SERS substrates are primarily metal nanostructures, which entail high manufacturing costs, complex processes, and the metal surface undergo change over time and with environmental conditions. These issues limit the development of SERS technology. In this work, a nitrogen‐doped graphene (N‐graphene) hydrangea was synthesized on a silicon (Si) substrate using plasma‐assisted chemical vapor deposition (PACVD), forming an N‐graphene hydrangea/Si hybrid structure as a SERS substrate. This substrate offers the advantages of high stability, ultra‐sensitivity, and reusability. The three‐dimensional nano‐cavity structure of graphene can increase the interaction between light and graphene, resulting in an increased localized electric field. Combining theoretical simulation analysis, the introduction of nitrogen (N) elements adjusts the Fermi level of graphene, promoting efficient charge transfer. In practical scenarios, Di(2‐ethylhexyl) phthalate (DEHP), a commonly used plasticizer, has raised concerns due to its potential as an endocrine disruptor and carcinogen. The as‐prepared SERS substrate achieves a remarkable detection limit of as low as 10−8 m for DEHP, providing significant support for environmental conservation and human health.
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- 2024
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6. Analysis of the Spatial Distribution Characteristics of Crude Oils with Different Freezing Points and the Genetic Mechanism of High-Freezing-Point Crude Oils in the Dongying Sag
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Zicheng Niu, Yongshi Wang, Zheng Li, Ru Wang, Xin Wang, and Xiuhong Wang
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Chemistry ,QD1-999 - Published
- 2023
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7. Identification of Indicator Genes for Agar Accumulation in Gracilariopsis lemaneiformis (Rhodophyta)
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Zheng Li, Mengge Tu, Feng Qin, Guangqiang Shui, Di Xu, and Xiaonan Zang
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Gracilariopsis lemaneiformis ,agar biosynthesis ,indicator genes ,qPCR ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Agar, as a seaweed polysaccharide mainly extracted from Gracilariopsis lemaneiformis, has been commercially applied in multiple fields. To investigate factors indicating the agar accumulation in G. lemaneiformis, the agar content, soluble polysaccharides content, and expression level of 11 genes involved in the agar biosynthesis were analysed under 4 treatments, namely salinity, temperature, and nitrogen and phosphorus concentrations. The salinity exerted the greatest impact on the agar content. Both high (40‰) and low (10‰, 20‰) salinity promoted agar accumulation in G. lemaneiformis by 4.06%, 2.59%, and 3.00%, respectively. The content of agar as a colloidal polysaccharide was more stable than the soluble polysaccharide content under the treatments. No significant correlation was noted between the two polysaccharides, and between the change in the agar content and the relative growth rate of the algae. The expression of all 11 genes was affected by the 4 treatments. Furthermore, in the cultivar 981 with high agar content (21.30 ± 0.95%) compared to that (16.23 ± 1.59%) of the wild diploid, the transcriptional level of 9 genes related to agar biosynthesis was upregulated. Comprehensive analysis of the correlation between agar accumulation and transcriptional level of genes related to agar biosynthesis in different cultivation conditions and different species of G. lemaneiformis, the change in the relative expression level of glucose-6-phosphate isomerase II (gpiII), mannose-6-phosphate isomerase (mpi), mannose-1-phosphate guanylyltransferase (mpg), and galactosyltransferase II (gatII) genes was highly correlated with the relative agar accumulation. This study lays a basis for selecting high-yield agar strains, as well as for targeted breeding, by using gene editing tools in the future.
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- 2024
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8. Hydrazide–pillar[5]arene-mediated silver nanoparticles for highly efficient reductive degradation of organic dyes
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Chun-Li Song, Zheng Li, Yi-Nan Zhang, Ge Zhang, and Ying-Wei Yang
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Nanomaterials ,Organic dyes degradation ,Pillararene ,Silver nanoparticles ,Supramolecular chemistry ,Chemistry ,QD1-999 - Abstract
A new supramolecular approach toward the reductive degradation of organic dyes by hybridizing hydrophilic hydrazide-pillar[5]arene (HP5A) as surface-modifiers with silver nanoparticles (AgNPs) has been demonstrated. The fabricated supramolecular hybrid nanomaterial (denoted as HP5A-AgNPs) with ideal mono-dispersity, improved stability, and smaller size, show high catalytic activity in boosting organic dyes degradation, as delivered by a broad spectrum of organic dyes, including rhodamine B, rhodamine 6G, methylene blue, and methyl orange. This work expands the application scope of macrocycles-derived organic-inorganic nanohybrids into catalytic degradation and environmental protection areas.
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- 2023
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9. A Distributed Deep Learning Network Based on Data Enhancement for Few-Shot Raman Spectral Classification of Litopenaeus vannamei Pathogens
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Yanan Chen, Zheng Li, and Ming Chen
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Litopenaeus vannamei ,generative adversarial network ,distributed deep learning ,few-shot classification ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Litopenaeus vannamei is a common species in aquaculture and has a high economic value. However, Litopenaeus vannamei are often invaded by pathogenic bacteria and die during the breeding process, so it is of great significance to study the identification of shrimp pathogenic bacteria. The wide application of Raman spectroscopy in identifying directions of inquiry provides a new means for this. However, the traditional Raman spectroscopy classification task requires a large amount of data to ensure the accuracy of its classification. Therefore, the question of how to obtain higher classification accuracy through the means of a small amount of Raman spectrum data is a difficult point in the research. This paper proposes a distributed deep learning network based on data enhancement for few-shot Raman spectral classification of Litopenaeus vannamei pathogens. The network consists of RSEM, RSDM, and DLCM modules. The RSEM module uses an improved generative adversarial network combined with transfer learning to generate a large amount of spectral data. The RSDM module uses improved U-NET to denoise the generated data. In addition, we designed a distributed learning classification model (DLCM) which significantly speeds up model training, improves the efficiency of the algorithm, and solves the network degradation problem that often occurs during deep learning model training. The average classification accuracy of our proposed network on four shrimp pathogenic bacteria reaches 98.9%, which is higher than several models commonly used in Raman spectroscopy classification tasks. The method proposed in this article only needs the Raman spectra of a small number of microorganisms to complete the efficient and rapid identification of shrimp pathogenic bacteria, and this method certainly has the potential to solve the problem of the spectral classification of other microorganisms.
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- 2024
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10. Characterization of the key volatile organic components of different parts of fresh and dried perilla frutescens based on headspace-gas chromatography-ion mobility spectrometry and headspace solid phase microextraction-gas chromatography-mass spectrometry
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Jingyi Xie, Xuejuan Li, Wei Li, Hui Ding, Jiaxin Yin, Songtao Bie, Fangyi Li, Chengwang Tian, Lifeng Han, Wenzhi Yang, Xinbo Song, Heshui Yu, and Zheng Li
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Different parts ,Headspace-gas chromatography-ion mobility spectrometry ,Headspace solid phase microextraction-gas chromatography-mass spectrometry ,Perilla frutescens ,Volatile organic compounds ,Chemistry ,QD1-999 - Abstract
Perilla frutescens was an annual herb considered as one of the “One Root of Medicine and Food”, and it was used widely for food and medical treatment. Its main active ingredients were volatile organic compounds (VOCs), but it was easily affected during drying and storage. The leaves, seeds and stems had shown differences in therapeutic effects, but the underlying reason remained unclear. In the present work, headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC–MS) were utilized to effectively and comprehensively analyze VOCs of fresh and dried P. frutescens between the leaves, stems and seeds. Meanwhile, chemometric analysis was applied to compare and identify characteristic volatile markers. As a result, 60 VOCs were identified by HS-GC-IMS and 115 VOCs were identified by HS-SPME-GC–MS from P. frutescen. 25 potential volatile markers were selected based on a combination model of orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF). The models could be used to analyze the variation between fresh and dried P. frutescens and distinguish the differences in different parts effectively and comprehensively. It was the first research regarding the method development of HS-GC-IMS and HS-SPME-GC–MS that comprehensively analyzes the VOCs characterization of fresh and dried P. frutescens in different parts and the findings obtained would evaluate the quality and provide a reference for further exploration of the edible and medicinal effects of P. frutescens.
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- 2023
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11. Research on Bidirectional Reservation Method for Anti-Permeation Geomembrane Slack
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Wansheng Wang, Xia Xue, Wanglin Li, Ruichen Han, and Zheng Li
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geomembrane ,slackness ,bidirectional reservation ,groove-shaped ,Z-shaped ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Geomembrane relaxation can effectively prevent the geomembrane from being damaged by tensile stresses caused by temperature changes and uneven settlement of the foundation. Existing and commonly used reservation methods, such as wave-shaped, groove-shaped, and Z-shaped techniques, are unidirectional and cannot resist multidirectional tensile stresses in geomembranes. Therefore, we propose three methods for reserving bidirectional geomembranes, including the cross-groove-shaped, cross-Z-shaped, and combined Z- and groove-shaped techniques. Additionally, we investigate the key issues of these methods and their practicality through field tests and theoretical analyses. The results of the study show that the cross-groove-shaped technique is prone to geomembrane folding at the corners of the cross-intersection, and it is necessary to set a wiping angle of approximately 35° to solve the problem. The cross-Z-shaped technique does not require grooving and reduces the amount of civil construction performed. However, the neoprene rods cannot be folded 180° or restored after being separated once. The combined Z- and groove-shaped technique has no folding phenomenon and does not require 180° of folding. With a lack of folding, including 180° folding, the number of grooves can be reduced by half, but the cross-Z-shaped specimen cannot be restored after separation. In practical applications, it is recommended to use the cross-groove-shaped method or to choose a suitable bidirectional reservation method according to the actual requirements.
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- 2023
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12. Design of an Energy Harvester Based on a Rubber Bearing Floating Slab Track
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Shuo Yu, Zheng Li, Hao Jin, Donghao Yin, and Jiajia Yan
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rail transit ,sensor ,floating slab track ,energy harvester ,piezoelectric layer dimension ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
It is known that a large amount of vibration mechanical energy will be generated during train operation. If the mechanical energy can be obtained from the track structure, it can greatly optimize the energy configuration of the metro. Currently, most sensors are limited to disk or cymbal structures and are not used in the track bed; different from existing structures, this paper designs a spherical energy harvester based on a rubber bearing floating slab track, wherein the size range of the spherical energy harvesting structure was approximately determined based on the geometric spatial relationships of the actual track bed internal structure. Compared to the traditional disk and cymbal energy harvesters, the mechanical and electrical properties of the spherical energy harvesting structure was studied by a numerical simulation method, and the optimal size of the spherical energy was determined by calculation. The main conclusions are as follows: (1) Compared with the traditional disk harvester and cymbal harvester, the spherical harvester had better mechanical and electrical properties. (2) By calculating the output power of energy harvesters under load matching, we found that the output power of the spherical harvester was two orders of magnitude higher than that of the disk harvester and 53% higher than that of the cymbal harvester. (3) The optimum size of the spherical harvester was when the thickness of piezoelectric layer was 2 mm, the radius was 16 mm, the axial ratio of the spherical shell was 0.4, and the thickness of the spherical shell was 4 mm.
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- 2023
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13. A localized view on molecular dissociation via electron-ion partial covariance
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Felix Allum, Valerija Music, Ludger Inhester, Rebecca Boll, Benjamin Erk, Philipp Schmidt, Thomas M. Baumann, Günter Brenner, Michael Burt, Philipp V. Demekhin, Simon Dörner, Arno Ehresmann, Andreas Galler, Patrik Grychtol, David Heathcote, Denis Kargin, Mats Larsson, Jason W. L. Lee, Zheng Li, Bastian Manschwetus, Lutz Marder, Robert Mason, Michael Meyer, Huda Otto, Christopher Passow, Rudolf Pietschnig, Daniel Ramm, Kaja Schubert, Lucas Schwob, Richard D. Thomas, Claire Vallance, Igor Vidanović, Clemens von Korff Schmising, René Wagner, Peter Walter, Vitali Zhaunerchyk, Daniel Rolles, Sadia Bari, Mark Brouard, and Markus Ilchen
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Chemistry ,QD1-999 - Abstract
Coincidence experiments at free-electron lasers enable time resolved site-specific investigations of molecular photochemistry at high signal rates, but isolating individual dissociation processes still poses a considerable technical challenge. Here, the authors use electron-ion partial covariance imaging to isolate otherwise elusive chemical shifts in UV-induced photofragmentation pathways of the prototypical chiral molecule 1-iodo-2-methylbutane.
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- 2022
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14. Rockburst Hazard Evaluation Using an Extended COPRAS Method with Interval-Valued Fuzzy Information
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Zheng Li, Weizhang Liang, and Guoyan Zhao
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rockburst ,hazard evaluation ,multicriteria decision making ,uncertainty ,interval-valued fuzzy numbers ,mining engineering ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Rockburst is a major disaster in deep mining engineering, which can cause serious injury, death and economic losses. This study aims to solve rockburst hazard evaluation problems and determine the hazard levels of mines under uncertain circumstances. To this end, a novel multicriteria decision-making (MCDM) method was proposed in an interval-valued fuzzy context. The main contributions are three-fold. First, considering the heterogeneity of rock masses and the complexity of mining engineering, interval-valued fuzzy numbers (IVFNs) were adopted to express initial indicator information. Second, accounting for the uncertainty of indicator weights, the decision-making trial and evaluation laboratory (DEMATEL) and entropy methods were extended with IVFNs to determine fuzzy indicator weights comprehensively. Third, the complex proportional assessment (COPRAS) approach was extended with IVFNs to determine the rockburst hazard level. Finally, the proposed method was applied to evaluate rockburst hazards in the Jiaojia gold mine, and the ranking results were consistent with field status. Meanwhile, sensitivity and comparison analyses were performed to reveal the stability and effectiveness of the proposed method. The results indicated that the extended COPRAS method was reliable for rockburst hazard evaluation in deep mining engineering.
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- 2023
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15. Expression Profiling Reveals the Possible Involvement of the Ubiquitin–Proteasome Pathway in Abiotic Stress Regulation in Gracilariopsis lemaneiformis
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Feng Qin, Guangqiang Shui, Zheng Li, Mengge Tu, and Xiaonan Zang
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Gracilariopsis lemaneiformis ,ubiquitin–proteasome pathway ,abiotic stress ,gene expression ,molecular mechanism ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Gracilariopsis lemaneiformis is an economically important red macroalga, the cultivation of which is affected by abiotic stresses. This research intends to study the response mechanism of various components of the ubiquitin-protease pathway to abiotic stress in G. lemaneiformis. The algae were treated with five common external stresses (high temperature, low temperature, O3, PEG, and water shortage) to study the macroscopic and microscopic manifestations of the ubiquitin–proteasome pathway. Firstly, the changes in soluble protein and ubiquitin were detected during the five treatments, and the results showed that the content of soluble protein and ubiquitin significantly increased under most stresses. The content of the soluble protein increased the most on the second day after 20% PEG treatment, which was 1.38 times higher than that of the control group, and the content of ubiquitin increased the most 30 min after water shortage treatment, which was 3.6 times higher than that of the control group. Then, 12 key genes (E1, E2, UPL1, HRD1, UFD1, Cul3, Cul4, DDB2, PIAS1, FZR1, APC8, and COP1) of the ubiquitin–proteasome pathway were studied, including an estimation of the probably regulatory elements in putative promoter regions and an analysis of transcript levels. The results showed that CAAT box, LTR, GC motif, and MBS elements were present in the putative promoter regions, which might have endowed the genes with the ability to respond to stress. The transcript analysis showed that under high temperature, low temperature, PEG, O3, and water shortage, all of the genes exhibited instant and significant up-regulation, and different genes had different response levels to different stresses. Many of them also showed the synergistic effect of transcript up-regulation under various stress treatments. In particular, E1, E2, Cul3, Cul4, UPL1, HRD1, and COP1 performed most significantly under the five stresses. Collectively, our exploration of the ubiquitin–proteasome pathway and the transcript levels of key genes suggest a significant role to cope with adversity, and potential candidate genes can be selected for transformation to obtain stress-resistant strains.
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- 2023
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16. Discrimination and characterization of the volatile organic compounds of Acori tatarinowii rhizoma based on headspace-gas chromatography-ion mobility spectrometry and headspace solid phase microextraction-gas chromatography-mass spectrometry
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Xinlong Wu, Wei Li, Chao Li, Jiaxin Yin, Tong Wu, Min Zhang, Limin Zhu, Hanjiang Chen, Xilian Zhang, Songtao Bie, Fangyi Li, Xinbo Song, Xingchu Gong, Heshui Yu, and Zheng Li
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Headspace-gas chromatography-ion mobility spectrometry ,Headspace solid phase microextraction-gas chromatography-mass spectrometry ,Acori tatarinowii rhizome ,Volatile organic compounds ,Quantification ,Chemistry ,QD1-999 - Abstract
Acori tatarinowii rhizome (ATR) is a Traditional Chinese Medicine (TCM), which has multiple effects, such as neuroprotective activity, antidepressant and other activity. However, the widespread cultivation of ATR has led to it varying quality. Therefore, it is important to find a method to quickly identify the components of ATR. Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC–MS) were applied to analyze and characterize the volatile organic compounds (VOCs) of ATR. 33 VOCs were identified by HS-GC-IMS and 95 VOCs were identified by HS-SPME-GC–MS from 15 batches of ATR. Then, quantification of estragole, methyleugenol, γ-asarone, β-asarone and asarone by gas chromatography-mass spectrometry (GC–MS). The fingerprint of HS-GC-IMS and the heatmap of HS-SPME-GC–MS were established. Which compared differential components of ATR. In addition, principal component analysis (PCA) was performed on the results of both instruments. The VOCs in the ATR were significantly correlated with β-asarone and asarone by PatternHunter analysis. It assisted HS-GC-IMS determine ATR quality. It is the first report regarding the method development of HS-GC-IMS and HS-SPME-GC–MS that targets the VOCs characterization of ATR, and the findings obtained would benefit the quality control and distinguish the complex analytical objects of ATR.
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- 2022
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17. A Course of Hands-On Nanopore Experiments for Undergraduates: Single-Molecule Detection with Portable Electrochemical Instruments
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Hu, Zheng-Li, Ying, Yi-Lun, Huo, Ming-Zhu, Kong, Xuan-Feng, Yu, Xiao-Dong, Zhang, Jian-Rong, and Long, Yi-Tao
- Abstract
The prompt introduction of single-molecule science into undergraduates' curricula is an urgent but challenging task. However, the research experiments are often too complicated and the instruments are too expensive to be widely transferred into a compulsory course of undergraduate students. Herein, we introduce a recently developed nanopore technique into an accessible laboratory course for students with the advantages of simple operation, high repeatability, and low cost. The nanopore course serves to help undergraduates in practice to understand single-molecule behaviors, think at a single molecule level, and gradually develop single-molecule solutions for scientific issues. The learning activities for undergraduate students include setup of the instrument, fabrication of a biological nanopore on an artificial lipid bilayer membrane, detection of individual oligonucleotides, and data analysis. An experiment example is single-molecule detection of the model DNA sample poly(dA)[subscript n] (n = 4, 5) using the aerolysin nanopore. As our developed nanopore sensing system is simple, portable, and easy to handle, the experiment course could be implemented and popularized in undergraduates' laboratory education. For the undergraduate students who have taken general chemistry and/or biochemistry courses, this hands-on experience of nanopore experiments would benefit them with a better understanding of the chemical world at a single-molecule level and further using single-molecule tools in various applications including DNA and/or protein sequencing.
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- 2020
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18. Site-specific interrogation of an ionic chiral fragment during photolysis using an X-ray free-electron laser
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Markus Ilchen, Philipp Schmidt, Nikolay M. Novikovskiy, Gregor Hartmann, Patrick Rupprecht, Ryan N. Coffee, Arno Ehresmann, Andreas Galler, Nick Hartmann, Wolfram Helml, Zhirong Huang, Ludger Inhester, Alberto A. Lutman, James P. MacArthur, Timothy Maxwell, Michael Meyer, Valerija Music, Heinz-Dieter Nuhn, Timur Osipov, Dipanwita Ray, Thomas J. A. Wolf, Sadia Bari, Peter Walter, Zheng Li, Stefan Moeller, André Knie, and Philipp V. Demekhin
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Chemistry ,QD1-999 - Abstract
Ultrashort circularly polarised light pulses from free-electron lasers offer a route for exploring chiral molecules and their dynamics, but remain challenging to harness. Here, X-ray pump-probe experiments enable a site-specific photoelectron circular dichroism measurement on a dissociating chiral molecule.
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- 2021
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19. Advances in IgA glycosylation and its correlation with diseases
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Li Ding, Xiangqin Chen, Hongwei Cheng, Tiantian Zhang, and Zheng Li
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IgA ,glycosylation ,immunoglobulin ,antibody ,therapy ,Chemistry ,QD1-999 - Abstract
Immunoglobulin A (IgA) is the most abundant immunoglobulin synthesized in the human body. It has the highest concentration in the mucosa and is second only to IgG in serum. IgA plays an important role in mucosal immunity, and is the predominant antibody used to protect the mucosal surface from pathogens invasion and to maintain the homeostasis of intestinal flora. Moreover, The binding IgA to the FcαRI (Fc alpha Receptor I) in soluble or aggregated form can mediate anti- or pro- inflammatory responses, respectively. IgA is also known as one of the most heavily glycosylated antibodies among human immunoglobulins. The glycosylation of IgA has been shown to have a significant effect on its immune function. Variation in the glycoform of IgA is often the main characteration of autoimmune diseases such as IgA nephropathy (IgAN), IgA vasculitis (IgAV), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). However, compared with the confirmed glycosylation function of IgG, the pathogenic mechanism of IgA glycosylation involved in related diseases is still unclear. This paper mainly summarizes the recent reports on IgA’s glycan structure, its function, its relationship with the occurrence and development of diseases, and the potential application of glycoengineered IgA in clinical antibody therapeutics, in order to provide a potential reference for future research in this field.
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- 2022
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20. ZIM1 Combined with Hydrogel Inhibits Senescence of Primary PαS Cells during In Vitro Expansion
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Yueming Tian, Menglong Hu, Xuenan Liu, Xu Wang, Dazhuang Lu, Zheng Li, Yunsong Liu, Ping Zhang, and Yongsheng Zhou
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stem cells ,cellular senescence ,transcriptomics ,Wnt pathway ,hydrogel ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Bone marrow stem cells (BMSCs) are a promising source of seed cells in bone tissue engineering, which needs a great quantity of cells. Cell senescence occurs as they are passaged, which could affect the therapeutic effects of cells. Therefore, this study aims to explore the transcriptomic differences among the uncultured and passaged cells, finding a practical target gene for anti-aging. We sorted PαS (PDGFR-α+SCA-1+CD45-TER119-) cells as BMSCs by flow cytometry analysis. The changes in cellular senescence phenotype (Counting Kit-8 (CCK-8) assay, reactive oxygen species (ROS) test, senescence-associated β-galactosidase (SA-β-Gal) activity staining, expression of aging-related genes, telomere-related changes and in vivo differentiation potential) and associated transcriptional alterations during three important cell culture processes (in vivo, first adherence in vitro, first passage, and serial passage in vitro) were studied. Overexpression plasmids of potential target genes were made and examed. Gelatin methacryloyl (GelMA) was applied to explore the anti-aging effects combined with the target gene. Aging-related genes and ROS levels increased, telomerase activity and average telomere length decreased, and SA-β-Gal activities increased as cells were passaged. RNA-seq offered that imprinted zinc-finger gene 1 (Zim1) played a critical role in anti-aging during cell culture. Further, Zim1 combined with GelMA reduced the expression of P16/P53 and ROS levels with doubled telomerase activities. Few SA-β-Gal positive cells were found in the above state. These effects are achieved at least by the activation of Wnt/β-catenin signaling through the regulation of Wnt2. The combined application of Zim1 and hydrogel could inhibit the senescence of BMSCs during in vitro expansion, which may benefit clinical application.
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- 2023
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21. Integrative Analysis Reveals the Diverse Effects of 3D Stiffness upon Stem Cell Fate
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Muxin Yue, Yunsong Liu, Ping Zhang, Zheng Li, and Yongsheng Zhou
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extracellular matrix ,mesenchymal stem cells ,stiffness ,metabolism ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The origin of life and native tissue development are dependent on the heterogeneity of pluripotent stem cells. Bone marrow mesenchymal stem cells (BMMSCs) are located in a complicated niche with variable matrix stiffnesses, resulting in divergent stem cell fates. However, how stiffness drives stem cell fate remains unknown. For this study, we performed whole-gene transcriptomics and precise untargeted metabolomics sequencing to elucidate the complex interaction network of stem cell transcriptional and metabolic signals in extracellular matrices (ECMs) with different stiffnesses, and we propose a potential mechanism involved in stem cell fate decision. In a stiff (39~45 kPa) ECM, biosynthesis of aminoacyl-tRNA was up-regulated, and increased osteogenesis was also observed. In a soft (7~10 kPa) ECM, biosynthesis of unsaturated fatty acids and deposition of glycosaminoglycans were increased, accompanied by enhanced adipogenic/chondrogenic differentiation of BMMSCs. In addition, a panel of genes responding to the stiffness of the ECM were validated in vitro, mapping out the key signaling network that regulates stem cells’ fate decisions. This finding of “stiffness-dependent manipulation of stem cell fate” provides a novel molecular biological basis for development of potential therapeutic targets within tissue engineering, from both a cellular metabolic and a biomechanical perspective.
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- 2023
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22. Standing NiFe LDH nanosheets on stainless steel fibers felt: A synergistic impact on the oxygen evolution reaction (OER) for the water splitting
- Author
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Yanqi Liu, Zhaohai Song, Zheng Li, Minmin Han, Yongliang Cheng, and Zongmin Zheng
- Subjects
Stainless steel ,NiFe LDH ,OER ,Water splitting ,Alkaline seawater ,Chemistry ,QD1-999 - Abstract
Controllable preparation of NiFe layered double hydroxides (LDH) on suitable conductive substrate is always a key precondition for their wide applications. Standing NiFe LDH nanosheets were successfully grown on stainless steel fibers felt (SSFF) at room temperature. The prepared SSFF@ NiFe LDH electrocatalyst displayed a high electrocatalytic performance for the oxygen evolution reaction (OER) in alkaline electrolyte as well as alkaline seawater. The effects of mass loading and molar ratio of Ni/Fe on the electrocatalytic activity were also evaluated. With the optimized electrode, the overpotential for the anodic OER process only needs 198 and 260 mV at a current density of 10 and 300 mA cm−2, respectively.
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- 2022
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23. Quality differentiation method of similar phytomedicines with high sugar content based on the sugar-marker: Taking Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus as an example
- Author
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Hongmei Zhang, Fengshu Zhou, Fangyi Li, Chunxia Zhao, Haixia Wang, Heshui Yu, Songtao Bie, Tongchuan Suo, Zheng Li, Guoqiang Li, and Chunhua Wang
- Subjects
Schisandrae Chinensis Fructus ,Schisandrae Sphenantherae Fructus ,Contents determination ,Molecular weight ,Monosaccharide composition ,Quality evaluation ,Chemistry ,QD1-999 - Abstract
Quality evaluation of phytomedicines is limited to small molecules as quality markers, even for herbs with high sugar contents. We established a high-resolution method for distinguishing similar medicinal materials using sugar as quality marker, taking Schisandrae Chinensis Fructus (SCF) and Schisandrae Sphenantherae Fructus (SSF) as an example. High performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD), high performance size exclusion chromatography coupled with multi-angle laser light scattering detector and refractive index detector (HPSEC-MALLS-RID) and high performance liquid chromatography with photo-diode array (HPLC-PDA) after 1-phenyl-3-methyl-5-pyrazolone (PMP) pre-column derivatization were used respectively to determine monosaccharide contents, molecular weights and monosaccharide compositions of polysaccharides in this study. The differences of SCF and SSF from ten producing areas were compared by principal component analysis (PCA) and hierarchical cluster analysis (HCA). Results showed that contents of fructose and glucose were similar between SCF and SSF. Molecular weight (Mw) of SCF polysaccharides was ranging from 1.561 × 102 to 6.599 × 102 kDa, and that of SSF polysaccharides was ranging from 8.524 × 102 to 1.7416 × 103 kDa. Schisandra polysaccharides were mainly composed of mannose, galacturonic acid, glucose, galactose and arabinose. Based on PCA and HCA, SCF and SSF from ten different areas were classified into three categories. With great accuracy, sensitivity and stability, the methods established in this study had important reference value for quality evaluation, development and utilization of saccharide components in medicinal materials.
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- 2022
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24. Wds-Mediated H3K4me3 Modification Regulates Lipid Synthesis and Transport in Drosophila
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Tujing Zhao, Min Wang, Zheng Li, Hao Li, Dongqin Yuan, Xing Zhang, Mengge Guo, Wenliang Qian, and Daojun Cheng
- Subjects
H3K4me3 ,Wds ,Hsf ,lipid synthesis ,lipid transport ,fat body ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Lipid homeostasis is essential for insect growth and development. The complex of proteins associated with Set 1 (COMPASS)-catalyzed Histone 3 lysine 4 trimethylation (H3K4me3) epigenetically activates gene transcription and is involved in various biological processes, but the role and molecular mechanism of H3K4me3 modification in lipid homeostasis remains largely unknown. In the present study, we showed in Drosophila that fat body-specific knockdown of will die slowly (Wds) as one of the COMPASS complex components caused a decrease in lipid droplet (LD) size and triglyceride (TG) levels. Mechanistically, Wds-mediated H3K4me3 modification in the fat body targeted several lipogenic genes involved in lipid synthesis and the Lpp gene associated with lipid transport to promote their expressions; the transcription factor heat shock factor (Hsf) could interact with Wds to modulate H3K4me3 modification within the promoters of these targets; and fat body-specific knockdown of Hsf phenocopied the effects of Wds knockdown on lipid homeostasis in the fat body. Moreover, fat body-specific knockdown of Wds or Hsf reduced high-fat diet (HFD)-induced oversized LDs and high TG levels. Altogether, our study reveals that Wds-mediated H3K4me3 modification is required for lipid homeostasis during Drosophila development and provides novel insights into the epigenetic regulation of insect lipid metabolism.
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- 2023
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25. Photoprotective Effects of Dendrobium nobile Lindl. Polysaccharides against UVB-Induced Oxidative Stress and Apoptosis in HaCaT Cells
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Yunluan Long, Wuji Wang, Yanyan Zhang, Fanpan Du, Shiqian Zhang, Zheng Li, Jiang Deng, and Jingjie Li
- Subjects
ultraviolet B (UVB) ,HaCaT keratinocytes ,Dendrobium nobile Lindl polysaccharides ,antioxidant ,anti-apoptosis ,MAPK ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Acute ultraviolet (UV)-B radiation is the major external factor causing photodamage. In this study, we aimed to determine the effects of Dendrobium nobile Lindl. polysaccharides (DNPs) on photodamage in HaCaT keratinocytes after UVB irradiation and the underlying mechanisms. We found that DNPs significantly attenuated the decline in the viability and proliferation of HaCaT cells after UVB irradiation. Moreover, DNPs scavenged reactive oxygen species (ROS), improved the activities of endogenous antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, and reduced the levels of malondialdehyde, while partially attenuating cell cycle arrest, suggesting their antioxidant and anti-apoptotic properties. The mitogen-activated protein kinase (MAPK) pathway was found to be important for the attenuation of UVB-induced photodamage in the HaCaT cells. Furthermore, DNPs exerted cytoprotective effects by downregulating UVB-induced ROS-mediated phosphorylation of MAPKs, including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase, and by inhibiting p53 expression as well as the apoptotic cascade response. Therefore, DNPs ameliorated UVB-induced oxidative damage and apoptosis in HaCaT cells via the regulation of MAPKs. Our findings thus highlight the Dendrobium nobile Lindl polysaccharides as promising therapeutic candidates for UVB-induced photodamage.
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- 2023
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26. Oligo(β-peptoid)s with Backbone Chirality from Aspartic Acid Derivatives: Synthesis and Property Investigation
- Author
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Zheng Li, Xiaohui Fu, Saixi Huang, Jing Sun, and Zhibo Li
- Subjects
Chemistry ,QD1-999 - Published
- 2020
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27. Similarity and Specificity of Traditional Chinese Medicine Formulas for Management of Coronavirus Disease 2019 and Rheumatoid Arthritis
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Zheng Li, Hongwei Chen, Huixia Zhang, Yan Li, Caiyun Wang, Liping Bai, Wei Zhang, and Zhihong Jiang
- Subjects
Chemistry ,QD1-999 - Published
- 2020
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28. Biosynthesis and characterization of lead selenide semiconductor nanoparticles (PbSe NPs) and its antioxidant and photocatalytic activity
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Catherine Sekyerebea Diko, Yuanyuan Qu, Zhang Henglin, Zheng Li, Noor Ahmed Nahyoon, and Shuling Fan
- Subjects
Lead selenide nanoparticles ,Trichoderma sp. WL-Go ,Antioxidant activity ,Photocatalyst ,Rhodamine B ,Chemistry ,QD1-999 - Abstract
The current study fabricated novel lead selenide nanoparticles (PbSe NPs) by a simple biological benign process with Trichoderma sp. WL-Go. Ultraviolet–visible spectroscopy (UV–vis), Transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transfer infra-red (FTIR) spectroscopic analysis, Raman spectroscopy and Photoluminescence (PL) were used to characterize the physicochemical properties of the fabricated NPs. Synthesis at pH 8 with 0.5 g biomass of strain WL-Go and (1:1) mM of SeO2: Pb(NO3)2 were the optimal synthesis conditions to achieving 10–30 nm cubic faced centered NPs. The PbSe NPs served as catalyst for investigating the antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and photodegradation ability of rhodamine B dye (10 mg/L). The results indicated that the NPs could eliminate up to 88.60% of free radicals after adding 600 g/mL NPs and could photodegrade 82% of rhodamine B in 30 min. Thus, this study provides new knowledge and strategies for the future use of an environmentally benign bio- catalytic PbSe NPs to efficiently eliminate free radicals and in treatment of persistent organic pollutants in wastewaters.
- Published
- 2020
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29. Optimization in Chemical Modification of Single-Stranded siRNA Encapsulated by Neutral Cytidinyl/Cationic Lipids
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Zheng Li, Xixian Wang, Xinyang Zhou, Jie Wang, Zhu Guan, and Zhenjun Yang
- Subjects
single-stranded siRNA ,neutral cytidinyl lipid ,chemical modification ,gene silencing ,biodistribution ,Chemistry ,QD1-999 - Abstract
Single-stranded siRNA (ss-siRNA) refers to the antisense strand of siRNA, which plays the role of gene silencing. Since single-stranded RNA is unstable, the present study employed a homemade neutral cytidinyl/cationic lipid delivery system and chemical modifications to improve its stability. The results showed that with the aid of mixed lipids, ss-siRNA could knock down 40% of target mRNA at 25 nM. With 2ʹ-F/2ʹ-OMe, phosphorothioate and 5ʹ-terminal phosphorylation, the optimized ss-siRNA could knock down 80% of target mRNA at 25 nM. Further knocking down AGO2, the ss-siRNAs could not effectively silence target mRNAs. Analysis of the biodistribution in vivo showed that ss-siRNA was less durable than siRNA, but spread more quickly to tissues. This study provides a safe and efficient ss-siRNA delivery and modification strategy, which lays the foundation for future works.
- Published
- 2022
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30. Fully Printed Geranium-Inspired Encapsulated Arrays for Quantitative Odor Releasing
- Author
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Bingda Chen, Meng Su, Qi Pan, Zeying Zhang, Shuoran Chen, Zhandong Huang, Zheren Cai, Zheng Li, Xin Qian, Xiaotian Hu, and Yanlin Song
- Subjects
Chemistry ,QD1-999 - Published
- 2019
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31. Phytochemical and pharmacological studies on the genus Arcangelisia: A mini review
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Qian Cheng, Fangyi Li, Xiaohui Yan, Jingtao He, Hongmei Zhang, Chunhua Wang, Yongzhi He, and Zheng Li
- Subjects
Arcangelisia ,Alkaloid ,Natural medicinal chemistry ,Pharmacological activity ,Folk medicine ,13C NMR data ,Chemistry ,QD1-999 - Abstract
Only 3 plants in the genus Arcangelisia, belonging to the family Menispermaceae, are used as folk medicines for the treatment of various diseases by local residents. Alkaloids are main compounds of berberine analogues found in this genus and they demonstrate a wide range of pharmacological activities. The aim of this review is to compile the phytochemical progress including all the compounds isolated from this genus, their pharmacological activities together with the 13C NMR spectral data of the main bioactive components, which will bring more attention of other researchers to this genus for further study to find new active compounds.
- Published
- 2021
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32. The multicomponent characterization of Shuanghe decoction by dimension-enhanced data-independent HDMSE: Focusing on the performance comparison between MSE and HDMSE
- Author
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Mengfan Wu, Ruimei Lin, Jiaxin Yin, Hui Ding, Lifeng Han, Wenzhi Yang, Songtao Bie, Chunhua Wang, Wei Zheng, Xinbo Song, Baiping Ma, Heshui Yu, and Zheng Li
- Subjects
Traditional Chinese medicine ,Chemical profiling ,Ion mobility quadrupole time-of-flight mass spectrometry ,High-Definition MSE ,Automated peak annotation ,Chemistry ,QD1-999 - Abstract
The co-elution, pervasive isomers, and frequently occurring in-source fragmentation definitely hinder the comprehensive characterization of the multiple components from traditional Chinese medicine (TCM) by liquid chromatography/mass spectrometry. Herein, a dimension-enhanced strategy, by utilizing an ion mobility quadrupole time-of-flight mass spectrometer coupled to ultra-high performance liquid chromatography (UHPLC/IM-QTOF-MS) with the ability of offering four-dimensional information (retention time, Rt; drift time or collision cross section, CCS; accurate mass of precursors; and accurate MS2 product ions), is presented. Shuanghe Decoction (SHD) is a classic tonifying formula composed of nine herbs, however, little is known to its chemical complexity, hitherto. Good chromatographic separation was achieved on an HSS T3 column, and by the Vion™ IMS-QTOF high-resolution mass spectrometer, data-independent MSE and High-Definition MSE (HDMSE) in both the negative and positive electrospray ionization modes were employed for acquiring the collision-induced dissociation-MS2 data. A self-built database, including 642 known compounds, was established, which assisted to perform the automated peak annotation by UNIFI™. By reference to 55 compounds, totally 236 components were identified or tentatively characterized from SHD with 4D data recorded. The combination of negative and positive modes could yield more information complementary to structural elucidation. Compared with the conventional MSE, HDMSE exhibit of merits in the provision of CCS, better separation and detection those easily co-eluting components, and reduction of the false positives in the identification results. Conclusively, the combination of HDMSE acquisition, in-house library, and UNIFI-facilitated automated peak annotation, renders a potent approach dedicated to deconvoluting the chemical composition of complex systems like TCM formulae.
- Published
- 2021
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33. Low-Intensity Pulsed Ultrasound Alleviates Human Testicular Leydig Cell Senescence In Vitro
- Author
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Sha Han, Jiaqiang Luo, Shuai Xu, Liangyu Zhao, Chencheng Yao, Junwei Xu, Ruhui Tian, Erlei Zhi, Yuhua Huang, Shujie Xia, Zheng Li, and Peng Li
- Subjects
LIPUS ,Leydig cells ,aging ,testosterone ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Aging has a significant negative impact on human testicular function; steroidogenesis is gradually impaired, and testosterone replacement therapy still has many risks. Low-intensity pulsed ultrasound (LIPUS) has been used as a novel non-invasive treatment for male erectile dysfunction and other fields, and has been shown to increase testosterone levels in animal models. Testosterone is synthesized and secreted by Leydig cells (LCs), and the serum testosterone level decreases after aging due to the LCs senescence. However, the effect of LIPUS on human senescent LCs has not been reported. In this study, human senescent LCs were isolated and stimulated with different energy intensities in vitro, and cell morphology, cell apoptosis, cell proliferation, cell senescence levels, lipid droplet number, testosterone and INSL3 secretion levels were tested and analyzed. Quantitative Polymerase Chain Reaction (QPCR) and Western Blot were performed to compare cell senescence characteristics and the expression profile of key pathways of testosterone secretion, and transcriptome analysis was performed to explore the signaling pathways of LCs alteration after LIPUS stimulation. It was safe and effective to stimulate LCs with the 75 mW/cm2 energy of LIPUS in vitro, which not only improved the senescence phenotype, but also effectively enhanced the secretory function of LCs in vitro, and increased the expression of key pathways of the testosterone synthesis pathway. These results suggest that LIPUS could be used as a novel treatment to human senescent LCs with decreased testosterone secretion levels in vitro.
- Published
- 2022
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34. Ring Stiffened Cylindrical Shell Structures: State-of-the-Art Review
- Author
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Hartmut Pasternak, Zheng Li, Algirdas Juozapaitis, and Alfonsas Daniūnas
- Subjects
cylindrical shells ,buckling ,ring-stiffened ,geometrical imperfection ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
The cylindrical shell is a widely used structure in engineering practice, and its main form of failure is instability due to buckling. As a classical problem in the field of mechanics, the stability of cylindrical shells has been studied extensively. However, the large difference between the theoretically predicted results of the critical buckling load and the experimental results for the cylindrical shells subjected to uniform axial pressure has contributed to the continuous development of the shell stability theory. This paper briefly reviews the development of the shell stability theory, then presents an overview of the current status and trends of stability research on the stiffened cylindrical shell widely used in cylindrical shell structures in real engineering, and finally presents the difficulties and directions of future stability research on cylindrical shell structures in engineering applications.
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- 2022
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35. Standards-Based UPLC-Q-Exactive Orbitrap MS Systematically Identifies 36 Bioactive Compounds in Ampelopsis grossedentata (Vine Tea)
- Author
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Rongxin Cai, Xican Li, Chunhou Li, Jiayi Zhu, Jingyuan Zeng, Jianwu Li, Boxu Tang, Zheng Li, Shuqin Liu, and Yan Yan
- Subjects
Ampelopsis grossedentata ,polyphenol ,jervine ,UPLC-Q-Exactive Orbitrap MS ,systematic identification ,flavones ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Ampelopsis grossedentata (vine tea) has been used as a detoxifying beverage in China for centuries. To systematically identify its bioactive compounds, the study adopted standards-based ultra-high-performance liquid chromatography coupled with quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive Orbitrap MS) analysis. The analysis was conducted under a negative ion model and the data were collected using the Xcalibur 4.1 software package. Based on comparisons with authentic standards, 36 bioactive compounds were putatively identified by four parameters: retention time, molecular ion peak, MS/MS profile, and characteristic fragments. These bioactive compounds include two chromones (noreugenin and 3,5,7-trihydroxychromone), 15 flavonoids (S-eriodictyol, S-naringenin, luteolin, ampelopsin, taxifolin, myricetin, quercetin, viscidulin I, kaempferol, myricetin 3-O-galactoside, myricitrin, avicularin, quercitrin, isorhamnetin-3-O-β-D-glucoside, and afzelin), four phenolic acids (gallic acid, 3,4-dihydroxy-5-methoxybenzoic acid, syringic acid, and ellagic acid), five tea polyphenols (epigallocatechin, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate), three chalcones (phloridzin, phloretin, and naringenin chalcone), one stilbene (polydatin), two lipids (myristic acid and ethyl stearate), one sugar (D-gluconic acid), one amino acid (L-tryptophan), one triterpenoid (oleanolic acid) and one alkaloid (jervine). Notably, the jervine identification is the first report regarding the occurrence of alkaloid in the plant. Two chromones may be the parent skeleton to biosynthesize the flavonoid in A. grossedentata.
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- 2022
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36. The Perspective of Arbuscular Mycorrhizal Symbiosis in Rice Domestication and Breeding
- Author
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Renliang Huang, Zheng Li, Xianhua Shen, Jeongmin Choi, and Yangrong Cao
- Subjects
rice ,arbuscular mycorrhizal symbiosis ,domestication ,breeding ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In nature, symbiosis with arbuscular mycorrhizal (AM) fungi contributes to sustainable acquisition of phosphorus and other elements in over 80% of plant species; improving interactions with AM symbionts may mitigate some of the environmental problems associated with fertilizer application in grain crops such as rice. Recent developments of high-throughput genome sequencing projects of thousands of rice cultivars and the discovery of the molecular mechanisms underlying AM symbiosis suggest that interactions with AM fungi might have been an overlooked critical trait in rice domestication and breeding. In this review, we discuss genetic variation in the ability of rice to form AM symbioses and how this might have affected rice domestication. Finally, we discuss potential applications of AM symbiosis in rice breeding for more sustainable agriculture.
- Published
- 2022
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37. Joint Optimization of Ticket Pricing and Allocation on High-Speed Railway Based on Dynamic Passenger Demand during Pre-Sale Period: A Case Study of Beijing–Shanghai HSR
- Author
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Xiaofeng Yin, Di Liu, Wenyu Rong, and Zheng Li
- Subjects
high-speed railway ,dynamic pricing ,ticket allocation ,passenger ticket pre-sale period ,revenue management ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Against the background of the gradual deepening of China Railway’s market-oriented reform, and in order to improve the revenue and competitiveness for high-speed railway (HSR) passenger transport, this paper studies the joint optimization problem of the high-speed railway ticket pricing and allocation considering the dynamic demand characteristics of passengers during the pre-sale period. Firstly, we use the compound non-homogeneous Poisson process to describe the passengers’ ticket-purchasing process and use the sparse method to simulate the passengers’ ticket demand during the pre-sale period. Secondly, taking the ticket pricing and allocation as the decision variables and considering the full utilization of the train seat capacity, a stochastic nonlinear-programming mathematical model is established with the goal of maximizing the train revenue. A particle swarm algorithm is designed to solve the model. Finally, this study takes the G19 train running on the Beijing–Shanghai HSR in China as a case study to verify the effectiveness of the model and algorithm. The results show that the joint optimization scheme of ticket pricing and allocation considering dynamic demand yields a revenue of CNY 601,881, which increases the revenue by 1.01% with a small adjustment of the price compared with the fixed ticket price and pre-allocation scheme. This study provides scientific support for the decisions made by railway transportation enterprises, which is conducive to further increasing the potential ticket revenue and promoting sustainable development.
- Published
- 2022
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38. A Wild Rice Rhizobacterium Burkholderia cepacia BRDJ Enhances Nitrogen Use Efficiency in Rice
- Author
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Zheng Li, Ahmed R. Henawy, Asmaa A. Halema, Qiuling Fan, Deqiang Duanmu, and Renliang Huang
- Subjects
plant growth-promoting rhizobacterium ,biological nitrogen fixation ,nitrogen use efficiency ,wild rice ,Burkholderia ,comparative genomics ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Rice domestication has dramatically improved its agronomic traits, albeit with unavoidable significantly reduced genetic diversity. Dongxiang common wild rice, the wild rice species distributed in northernmost China, exhibits excellent resistance against stress and diseases and provides a rich genetic resource for rice breeding. Most of the studies focus on the function of the plant genes, often disregarding the role of the root microbes associated with the plants. In this work, we isolated a Burkholderia strain from the root of Dongxiang wild rice, which we identified as Burkholderia cepacia BRDJ, based on a phylogenetic analysis. This strain promoted the rice growth under greenhouse conditions. The grain yield was higher in a rice line containing a small genomic fragment derived from the Dongxiang wild rice, compared to the indica rice cultivar Zhongzao 35. This new strain also increased the plant biomass under limiting nitrogen conditions. Interestingly, this strain had a differential effect on indica and japonica rice varieties under full nitrogen supply conditions. By genome sequencing and comparison with another two B. cepacia strains, we observed enriched genes related with nitrogen fixation and phytohormone and volatiles biosynthesis that may account for the growth-promoting effects of the BRDJ. BRDJ has the potential to be used as a biofertilizer in promoting nitrogen use efficiency and overall growth in rice.
- Published
- 2022
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39. Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review
- Author
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Zheng Li, Muxin Yue, Yunsong Liu, Ping Zhang, Jia Qing, Hao Liu, and Yongsheng Zhou
- Subjects
organoid ,hydrogel ,stem cells ,tissue engineering ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Organoids are novel in vitro cell culture models that enable stem cells (including pluripotent stem cells and adult stem cells) to grow and undergo self-organization within a three-dimensional microenvironment during the process of differentiation into target tissues. Such miniature structures not only recapitulate the histological and genetic characteristics of organs in vivo, but also form tissues with the capacity for self-renewal and further differentiation. Recent advances in biomaterial technology, particularly hydrogels, have provided opportunities to improve organoid cultures; by closely integrating the mechanical and chemical properties of the extracellular matrix microenvironment, with novel synthetic materials and stem cell biology. This systematic review critically examines recent advances in various strategies and techniques utilized for stem-cell-derived organoid culture, with particular emphasis on the application potential of hydrogel technology in organoid culture. We hope this will give a better understanding of organoid cultures for modelling diseases and tissue engineering applications.
- Published
- 2022
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40. Mechanism and Algorithm for Stable Trading Matching between Coal Mining and Power Generation Companies in China
- Author
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Ruyi Shi, Zheng Li, Zhenpeng Tang, and Di Wang
- Subjects
coal mining and power generation companies ,two-sided matching ,stable trading ,mechanism and algorithm ,stability and sensitivity ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
This paper is concerned with stable trading between the coal mining and power generation companies in China. Under the current marketized coal and planned electricity price systems, barriers to price shifting between coal and electricity are created and conflicts between the two sectors are aggravated. The stable trading matching between coal mining and power generation companies is not only an effective means to resolve the conflict in the coal trading market, but also a ballast stone for price stabilization and supply guarantees in coal trading. Based on the two-sided matching theory, this paper starts from the micro market preference and matching willingness of coal mining and power generation companies, puts forward the conceptual framework of the pairwise stable matching of both sides, innovates a mechanism for trading between coal mining and power generation companies, and designs a stable trading matching algorithm. The algorithm has certain theoretical innovation significance from the matching problem of non-separable commodities to that of separable commodities considering the trading volume between coal mining and power generation companies. Furthermore, it is a complement and perfection of the existing coal–power trading platform in its transaction mechanism and trading function. The results reveal that the trading relations between coal mining and power generation companies under the stable matching mechanism are resistant to disintegration and that the pairwise stable matching result is sensitive.
- Published
- 2022
- Full Text
- View/download PDF
41. The Abnormal Glycopatterns of Salivary Glycoproteins in Esophageal Squamous Cell Carcinoma Patients
- Author
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Jian Shu, Jun Ma, Xiameng Ren, Jian Wang, Yan Wang, Kun Zhang, Hanjie Yu, Xiangqian Guo, and Zheng Li
- Subjects
esophageal squamous cell carcinoma ,protein glycosylation ,saliva ,lectin microarrays ,MALDI-TOF/TOF-MS ,Chemistry ,QD1-999 - Abstract
Glycosylation is one of the most crucial posttranslational modifications of proteins, containing a remarkable amount of biological information. The alteration of glycosylation is closely associated with certain diseases. Exploring glyco-code in the development of diseases is a hot topic in recent years. Esophageal squamous cell carcinoma (ESCC) is the primary pathological histology in developing countries and a severe threat to human health. Although the glycan profiles in the blood samples of ESCC patients were analyzed using glycomic and glycoproteomic methods, the difference of salivary glycopatterns between healthy subjects and ESCC patients is not explicit yet. In the present study, ESCC patients (n = 16) and healthy volunteers (HVs, n = 25) were enrolled. The glycomic strategy combining lectin microarray and lectin blotting was employed to investigate and confirm the altered salivary glycopatterns. Datura stramonium (DSA) was selected to isolate the GlcNAc or Galβ1-4GlcNA-containing glycoproteins due to the distinct difference between ESCC patients and HVs. The N-glycans from DSA-enriched glycoproteins were released by PNGase F and further identified by MALDI-TOF/TOF-MS to obtain the precise structural information of the altered glycans. As a result, the glycopatterns recognized by 13 lectins (e.g., ECA, RCA120, and DSA) showed significant alterations in ESCC patients’ saliva. The ESCC patients showed higher levels of GalNAc and Gal, sialic acid, and GlcNAc expression profiles and lower levels of mannose and fucose expression profiles. The MALDI-TOF/TOF-MS results indicated that the proportion of the GlcNAc or Galβ1-4GlcNAc-containing N-glycans was increased in ESCC patients (79.04%) compared with HV (63.20%), which was consistent with the results of lectin microarrays. Our findings provide comprehensive information to understand the complex physiological changes in ESCC patients. And the altered salivary glycopatterns such as GlcNAc or Galβ1-4GlcNAc-containing N-glycans recognized by DSA might serve as potential biomarkers for the diagnosis of ESCC patients.
- Published
- 2021
- Full Text
- View/download PDF
42. Editorial: Array-Based Sensing Techniques for Clinical, Agricultural Biotechnology, and Environmental Analysis
- Author
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Zheng Li, Qingshan Wei, and Jinsong Han
- Subjects
array-based sensing ,pattern-recognition ,optoelectronic nose ,optical sensing ,biosensing ,Chemistry ,QD1-999 - Published
- 2021
- Full Text
- View/download PDF
43. Supramolecular Thixotropic Ionogel Electrolyte for Sodium Batteries
- Author
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Shipeng Chen, Li Feng, Xiaoji Wang, Yange Fan, Yubin Ke, Lin Hua, Zheng Li, Yimin Hou, and Baoyu Xue
- Subjects
low-molecular-weight gel ,shear thinning ,supramolecular interactions ,self-assembly ,thixotropic mechanism ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Owing to the potential of sodium as an alternative to lithium as charge carrier, increasing attention has been focused on the development of high-performance electrolytes for Na batteries in recent years. In this regard, gel-type electrolytes, which combine the outstanding ionic conductivity of liquid electrolytes and the safety of solid electrolytes, demonstrate immense application prospects. However, most gel electrolytes not only need a number of specific techniques for molding, but also typically suffer from breakage, leading to a short service life and severe safety issues. In this study, a supramolecular thixotropic ionogel electrolyte is proposed to address these problems. This thixotropic electrolyte is formed by the supramolecular self-assembly of D-gluconic acetal-based gelator (B8) in an ionic liquid solution of a Na salt, which exhibits moldability, a high ionic conductivity, and a rapid self-healing property. The ionogel electrolyte is chemically stable to Na and exhibits a good Na+ transference number. In addition, the self-assembly mechanism of B8 and thixotropic mechanism of ionogel are investigated. The safe, low-cost and multifunctional ionogel electrolyte developed herein supports the development of future high-performance Na batteries.
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- 2022
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44. CRPC Membrane-Camouflaged, Biomimetic Nanosystem for Overcoming Castration-Resistant Prostate Cancer by Cellular Vehicle-Aided Tumor Targeting
- Author
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Kai Lu, Zheng Li, Qiang Hu, Jianfei Sun, and Ming Chen
- Subjects
oncotherapy ,homotypic target ,drug delivery system ,nanoparticles ,docetaxel ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Castration-resistant prostate cancer (CRPC) is the most common malignant tumor of the male urinary system. Nanodrug delivery systems (NDDS) have been widely applied in drug delivery for tumor therapy; however, nanotherapeutics encounter various biological barriers that prevent successful accumulation of drugs, specifically at diseased sites. Therefore, there is an urgent need to develop a CRPC-targeting nanocomposite with fine biocompatibility for penetrating various biological barriers, delivering sufficient drugs to the targeting site and improving therapeutic efficiency. In this work, CRPC cell membranes were firstly adapted as biomimetic vectors for the encapsulating PEG−PLGA polymer containing the chemotherapy drug docetaxel (DTX). The CRPC membrane-camouflaged nanoparticles can easily escape early recognition by the immune system, penetrate the extracellular barrier, and evade clearance by the circulatory system. In addition to the characteristics of traditional nanoparticles, the CRPC cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize the same cancer cell types and increase the targeted drug delivery of DTX. In vivo fluorescence and radionuclide dual-model imaging were fulfilled by decorating the biomimetic nanosystem with near-infrared dye and isotope, which validated the homotypic targeting property offered by the CRPC cell membrane coating. Importantly, remarkably improved therapeutic efficacy was achieved in a mice model bearing CRPC tumors. This homologous cell membrane enabled an efficient drug delivery strategy and enlightened a new pathway for the clinical application of tumor chemotherapy drugs in the future.
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- 2022
- Full Text
- View/download PDF
45. The Regulation of Nitrate Reductases in Response to Abiotic Stress in Arabidopsis
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Xianli Tang, Yang Peng, Zheng Li, Hongwei Guo, Xinli Xia, Bosheng Li, and Weilun Yin
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NIA1 ,NIA2 ,ABA ,protein degradation ,NaCl ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The two homologous genes, NIA1 and NIA2, encode nitrate reductases in Arabidopsis, which govern the reduction of nitrate to nitrite. This step is the rate-limiting step of the nitrate assimilation and utilization. Therefore, the regulation of NIA1 and NIA2 is important for plant development and growth. Although they are similar in sequence and structure, their regulations are different. Genetic analysis uncovers that NIA1, rather than NIA2, plays a predominant role in adopting to ABA stress. Although both long-term stress conditions can cause an improvement in NIA1 levels, a decrease in NIA1 levels under short-term treatments seems to be necessary for plants to switch from the growth status into the adopting status. Interestingly, the downregulation of the NR is distinct under different stress conditions. Under ABA treatment, the NR proteins are degraded via a 26S-proteasome dependent manner, while the transcriptional regulation is the main manner to rapidly reduce the NIA1 levels under nitrogen deficiency and NaCl stress conditions. These results indicate that under stress conditions, the regulation of NIA1 is complex, and it plays a key role in regulating the balance between growth and adaptation.
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- 2022
- Full Text
- View/download PDF
46. Portable Analytical Techniques for Monitoring Volatile Organic Chemicals in Biomanufacturing Processes: Recent Advances and Limitations
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Xiaofeng Chen, Runmen Hu, Luoyu Hu, Yingcan Huang, Wenyang Shi, Qingshan Wei, and Zheng Li
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biomanufacturing ,volatile organic chemicals ,bioprocess assessments ,analytical methods ,electronic noses ,sensors ,Chemistry ,QD1-999 - Abstract
It is essential to develop effective analytical techniques for accurate and continuous monitoring of various biomanufacturing processes, such as the production of monoclonal antibodies and vaccines, through sensitive and quantitative detection of characteristic aqueous or gaseous metabolites and other analytes in the cell culture media. A comprehensive summary toward the use of mainstream techniques for bioprocess monitoring is critically reviewed here, which illustrates the instrumental and procedural advances and limitations of several major analytical tools in biomanufacturing applications. Despite those drawbacks present in modern detection systems such as mass spectrometry, gas chromatography or chemical/biological sensors, a considerable number of useful solutions and inspirations such as electronic or optoelectronic noses can be offered to greatly overcome the restrictions and facilitate the development of advanced analytical techniques that can target a more diverse range of key nutritious components, products or potential contaminants in different biomanufacturing processes.
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- 2020
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47. Studies on the Separation and Purification of the Caulis sinomenii Extract Solution Using Microfiltration and Ultrafiltration
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Xi Wang, Huimin Feng, Halimulati Muhetaer, Zuren Peng, Ping Qiu, Wenlong Li, and Zheng Li
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Caulis sinomenii ,microfiltration ,ultrafiltration ,sinomenine hydrochloride ,separation and purification ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
The separation and purification process of alkaloids faces great challenges of pollution, high energy consumption and low continuity. In this study, the effects of ceramic microfiltration (MF) membrane (membrane pore size of 0.50 μm, 0.20 μm, 0.05 μm) and organic ultrafiltration (UF) membrane (membrane molecular weight cut-off of 10 KDa and 1 KDa) on the separation and purification of Caulis sinomenii extract solution in pilot scale were studied. The cleaning effects of different cleaning methods (pure water, 1% HCl-NaOH, 1% sodium hypochlorite) were investigated. The experimental results indicated that 0.05 μm ceramic membrane and 1 kDa UF membrane have higher sinomenine hydrochloride (SH) permeabilities and total solids (TS) removal rates. The ceramic membrane was circulating cleaned by 1% sodium hypochlorite solution for 1 h; the membrane flux can be restored to more than 90% of the original, the membrane flux of 1 kDa UF membrane can be restored to 99.2% of the original by pure water washing. From the above study, the optimal technic parameters was determined in which 0.05 μm ceramic MF membrane and 1 kDa UF membrane were used to separate and purify the Caulis sinomenii extract solution to remove the invalid ingredients, and the two kinds of membranes were cleaned with 1% sodium hypochlorite solution and pure water, respectively, to keep satisfactory membrane fluxes. The study provided an environment-friendly alternative for the separation and purification of alkaloids in natural products, which has a good prospect for the industrial application.
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- 2021
- Full Text
- View/download PDF
48. Quality Distinguish of Red Ginseng from Different Origins by HPLC–ELSD/PDA Combined with HPSEC–MALLS–RID, Focus on the Sugar-Markers
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Qian Cheng, Shuhuan Peng, Fangyi Li, Pengdi Cui, Chunxia Zhao, Xiaohui Yan, Tongchuan Suo, Chunhua Wang, Yongzhi He, and Zheng Li
- Subjects
compositional monosaccharides ,HPLC–ELSD/PDA combined with HPSEC–MALLS–RID ,molecular weight ,quality markers (Q-marker) ,red ginseng polysaccharides ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Red ginseng (RG) has been extensively utilized in Asian countries due to its pharmacological effects. For the quality evaluation of RG, small molecules, such as ginsenosides, have been widely considered as candidates of its quality markers (Q-markers), and various analytical techniques have been developed in order to identify these compounds. However, despite the efforts to analyze the hydrophobic constituents, it is worth pointing out that about 60% of the mass of RG is made of carbohydrates, including mono-, oligo- and polysaccharides. Consequently, the quality differentiation and identification of RG from the perspective of sugar-markers should be focused. High performance liquid chromatography and evaporative light scattering detector (HPLC–ELSD) method for the determination of disaccharides in RG was established. Furthermore, high performance size exclusion chromatography–multi-angle laser light scattering–refractive index detector (HPSEC–MALLS–RID) for the determination of molecular weight and high performance liquid chromatography photodiode array (HPLC–PDA) for the determination of compositional monosaccharides in RG polysaccharides were also established. HPLC–ELSD/PDA combined with HPSEC–MALLS–RID could be used to determine the contents of disaccharides, molecular weights, and compositional monosaccharides of RG polysaccharides, which could be used for quality control, and this is a new view on the sugar marker to quality differentiation of various origins of RG.
- Published
- 2021
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49. On IoT-Friendly Skewness Monitoring for Skewness-Aware Online Edge Learning
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Zheng Li and Jhon Galdames-Retamal
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edge computing ,online edge learning ,open methods ,running skewness ,Welford’s algorithm ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Machine learning techniques generally require or assume balanced datasets. Skewed data can make machine learning systems never function properly, no matter how carefully the parameter tuning is conducted. Thus, a common solution to the problem of high skewness is to pre-process data (e.g., log transformation) before applying machine learning to deal with real-world problems. Nevertheless, this pre-processing strategy cannot be employed for online machine learning, especially in the context of edge computing, because it is barely possible to foresee and store the continuous data flow on IoT devices on the edge. Thus, it will be crucial and valuable to enable skewness monitoring in real time. Unfortunately, there exists a surprising gap between practitioners’ needs and scientific research in running statistics for monitoring real-time skewness, not to mention the lack of suitable remedies for skewed data at runtime. Inspired by Welford’s algorithm, which is the most efficient approach to calculating running variance, this research developed efficient calculation methods for three versions of running skewness. These methods can conveniently be implemented as skewness monitoring modules that are affordable for IoT devices in different edge learning scenarios. Such an IoT-friendly skewness monitoring eventually acts a cornerstone for developing the research field of skewness-aware online edge learning. By initially validating the usefulness and significance of skewness awareness in edge learning implementations, we also argue that conjoint research efforts from relevant communities are needed to boost this promising research field.
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- 2021
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50. Automated Conditional Statements Checking for Complete Natural Language Requirements Specification
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Chun Liu, Zhengyi Zhao, Lei Zhang, and Zheng Li
- Subjects
software requirements specification ,requirements quality ,requirements analysis ,natural language ,incompleteness detection ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Defects such as the duality and the incompleteness in natural language software requirements specification have a significant impact on the success of software projects. By now, many approaches have been proposed to assist requirements analysts to identify these defects. Different from these approaches, this paper focuses on the requirements incompleteness implied by the conditional statements, and proposes a sentence embedding- and antonym-based approach for detecting the requirements incompleteness. The basic idea is that when one condition is stated, its opposite condition should also be there. Otherwise, the requirements specification is incomplete. Based on the state-of-the-art machine learning and natural language processing techniques, the proposed approach first extracts the conditional sentences from the requirements specification, and elicits the conditional statements which contain one or more conditional expressions. Then, the conditional statements are clustered using the sentence embedding technique. The conditional statements in each cluster are further analyzed to detect the potential incompleteness by using negative particles and antonyms. A benchmark dataset from an aerospace requirements specification has been used to validate the proposed approach. The experimental results have shown that the recall of the proposed approach reaches 68.75%, and the F1-measure (F1) 52.38%.
- Published
- 2021
- Full Text
- View/download PDF
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