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  • MDPI AG  (9)
  • 1
    Online Resource
    Online Resource
    The Future of Targeted Treatment of Primary Sjögren’s Syndrome: A Focus on Extra-Glandular Pathology
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 22 ( 2022-11-16), p. 14135-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 22 ( 2022-11-16), p. 14135-
    Abstract: Primary Sjögren’s syndrome (pSS) is a chronic, systemic autoimmune disease defined by exocrine gland hypofunction resulting in dry eyes and dry mouth. Despite increasing interest in biological therapies for pSS, achieving FDA-approval has been challenging due to numerous complications in the trials. The current literature lacks insight into a molecular-target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and the latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term “Primary Sjögren’s syndrome”. Articles published in English between 2000 and 2021 were included. Our findings revealed potential targets for pSS treatment in clinical trials and the most recent advances in understanding the molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is in overlooking the treatment of extraglandular symptoms such as fatigue, depression, and anxiety, which are present in most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways, and immune reaction have been studied and their efficacy and safety have been proven. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grading systems that add extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene, stem-cell, and tissue-engineering therapies.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232214135
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Site-Specific Radioiodination of Oligonucleotides with a Phenolic Element in a Programmable Approach
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 19 ( 2022-09-23), p. 6257-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 19 ( 2022-09-23), p. 6257-
    Abstract: Radioiodination of oligonucleotides provides an extra modality for nucleic acid-based theranostics with potential applications. Herein, we report the design and synthesis of a phosphoramidite embedded with a phenolic moiety and demonstrate that oligonucleotides can be readily functionalized with phenol as a precursor by general DNA synthesis. It was identified that the introduction of the precursor does not block the specificity of an aptamer, and the radioiodination is applicable to both DNA and RNA oligonucleotides in a site-specific approach with a commercial kit.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27196257
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 3
    Online Resource
    Online Resource
    Cu-Based Catalysts with Enhanced Thermal Stability for Cyclohexyl Acetate Hydrogenation: Studies on Cu+ and Cu0 Sites at Different Reduction Temperatures
    MDPI AG ; 2023
    In:  Catalysts Vol. 13, No. 4 ( 2023-04-13), p. 737-
    Details
    In: Catalysts, MDPI AG, Vol. 13, No. 4 ( 2023-04-13), p. 737-
    Abstract: Cyclohexene esterification–hydrogenation for the efficient production of cyclohexanol will be commercialized for the first time. Cu/MgO/Al2O3 catalysts with layered double hydroxides as precursors were developed, and the effect of altering the reduction temperature on the catalytic activity was explored. Fresh and spent Cu/MgO/Al2O3 catalysts exhibited excellent catalytic performance after thermal treatment during the hydrogenation of cyclohexyl acetate to cyclohexanol. STEM images showed that the Cu particles grew slightly, without obvious aggregation. Based on the results of XAES and in situ FTIR of the adsorbed CO method, optimal performance (conversion rate of 99.59% with 98.94% selectivity) was achieved, which was attributed to the synergistic effect on the surface-active Cu0 and Cu+ sites with Cu0/(Cu0 + Cu+) of around 0.70, and the ratios could be maintained at temperatures of 513–553 K. The morphology of Cu/MgO/Al2O3 catalysts was well preserved during the hydrogenation of cyclohexyl acetate, indicating potential industrial applications. The well-dispersed Cu/MgO/Al2O3 catalyst with a stable microstructure possesses an adjustable valence state and thermal stability during the hydrogenation of cyclohexyl acetate, giving it industrial application prospects.
    Type of Medium: Online Resource
    ISSN: 2073-4344
    URL: Article
    DOI: 10.3390/catal13040737
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662126-5
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  • 4
    Online Resource
    Online Resource
    Down-Regulation of Double C2 Domain Alpha Promotes the Formation of Hyperplastic Nerve Fibers in Aganglionic Segments of Hirschsprung’s Disease
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 18 ( 2022-09-06), p. 10204-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 18 ( 2022-09-06), p. 10204-
    Abstract: Hirschsprung’s disease (HSCR) is a common developmental anomaly of the gastrointestinal tract in children. The most significant characteristics of aganglionic segments in HSCR are hyperplastic extrinsic nerve fibers and the absence of endogenous ganglion plexus. Double C2 domain alpha (DOC2A) is mainly located in the nucleus and is involved in Ca2+-dependent neurotransmitter release. The loss function of DOC2A influences postsynaptic protein synthesis, dendrite morphology, postsynaptic receptor density and synaptic plasticity. It is still unknown why hyperplastic extrinsic nerve fibers grow into aganglionic segments in HSCR. We detected the expression of DOC2A in HSCR aganglionic segment colons and established three DOC2A-knockdown models in the Neuro-2a cell line, neural spheres and zebrafish separately. First, we detected the protein and mRNA expression of DOC2A and found that DOC2A was negatively correlated with AChE+ grades. Second, in the Neuro-2a cell lines, we found that the amount of neurite outgrowth and mean area per cell were significantly increased, which suggested that the inhibition of DOC2A promotes nerve fiber formation and the neuron’s polarity. In the neural spheres, we found that the DOC2A knockdown was manifested by a more obvious connection of nerve fibers in neural spheres. Then, we knocked down Doc2a in zebrafish and found that the down-regulation of Doc2a accelerates the formation of hyperplastic nerve fibers in aganglionic segments in zebrafish. Finally, we detected the expression of MUNC13-2 (UNC13B), which was obviously up-regulated in Grade3/4 (lower DOC2A expression) compared with Grade1/2 (higher DOC2A expression) in the circular muscle layer and longitudinal muscle layer. The expression of UNC13B was up-regulated with the knocking down of DOC2A, and there were protein interactions between DOC2A and UNC13B. The down-regulation of DOC2A may be an important factor leading to hyperplastic nerve fibers in aganglionic segments of HSCR. UNC13B seems to be a downstream molecule to DOC2A, which may participate in the spasm of aganglionic segments of HSCR patient colons.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231810204
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Using Optical Flow Trajectories to Detect Whitecaps in Light-Polluted Videos
    MDPI AG ; 2022
    In:  Remote Sensing Vol. 14, No. 22 ( 2022-11-10), p. 5691-
    Details
    In: Remote Sensing, MDPI AG, Vol. 14, No. 22 ( 2022-11-10), p. 5691-
    Abstract: Whitecap formation is an important factor in the exchange of momentum, heat, and gas on the ocean surface. The long-term measurement of whitecaps is necessary to deepen our understanding of the mechanisms of ocean surface motion. However, traditional detection methods are highly sensitive to illumination. Under various illumination conditions, significant light pollution may be introduced into images. The poor performance caused by using images degraded with light pollution is not conducive to automated long-term whitecap measurement. In this study, we propose a two-step method for the detection of whitecaps under various illumination conditions. An abnormal detection method based on previous whitecap detection methods for the accurate detection of whitecaps in light-polluted areas is proposed as the first step. Using the detection results, we propose a post-processing method based on optical flow trajectories at two sampling rates to separate actual whitecap components in images containing false positives. Experiments show that the method proposed in this study can more accurately detect whitecaps in images with light pollution when compared to existing methods.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs14225691
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2513863-7
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  • 6
    Online Resource
    Online Resource
    Evaluation and Comparison of MODIS C6 and C6.1 Deep Blue Aerosol Products in Arid and Semi-Arid Areas of Northwestern China
    MDPI AG ; 2022
    In:  Remote Sensing Vol. 14, No. 8 ( 2022-04-17), p. 1935-
    Details
    In: Remote Sensing, MDPI AG, Vol. 14, No. 8 ( 2022-04-17), p. 1935-
    Abstract: The Moderate Resolution Imaging Spectroradiometer (MODIS) Deep Blue (DB) algorithm was developed for aerosol retrieval on bright surfaces. Although the global validation accuracy of the DB product is satisfactory, there are still some regions found to have very low accuracy. To this end, DB has updated the surface database in the latest version of the Collection 6.1 (C6.1) algorithm. Some studies have shown that DB aerosol optical depth (AOD) of the old version Collection 6 (C6) has been seriously underestimated in Northwestern China. However, the status of the new version of the C6.1 product in this region is still unknown. This study aims to comprehensively evaluate the performance of the MODIS DB product in Northwestern China. The DB AOD with high quality (Quality Flag = 2 or 3) was selected to validate against the 23 sites from the China Aerosol Remote Sensing Network (CARSNET) and Aerosol Robotic Network (AERONET) during the period 2002–2014. By the overall analysis, the results indicate that both C6 and C6.1 show significant underestimation with a large fraction of more than 54% of collocations falling below the Expected Error (EE = ±(0.05 + 20% AODground)) envelope and with a large negative Mean Bias (MB) of less than −0.14. Furthermore, the new C6.1 products failed to achieve reasonable improvements in the region of Northwestern China. Besides, C6.1 has slightly fewer collocations than C6 due that some pixels with systematic biases have been removed from the new surface reflectance database. From the analysis of the site scale, the scatter plot of C6.1 is similar to that of C6 in most sites. Furthermore, a significant underestimation of DB AOD was observed at most sites, with the most severe underestimation at two sites located in the Taklimakan Desert region. Among 23 sites in Northwestern China, there are only two sites where C6.1 has largely improved the underestimation of C6. Furthermore, it is interesting to note that there are also two sites where the accuracy of the new C6.1 has declined. Moreover, it is surprising that there is one site where a large overestimation was observed in C6 and improved in C6.1. Additionally, we found a constant value of about 0.05 for both C6 and C6.1 at several sites with low aerosol loading, which is an obvious artifact. The significant improvements of C6.1 were observed in the Middle East and Central Asia but not in most sites of Northwestern China. The results of this study will be beneficial to further improvements in the MODIS DB algorithm.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs14081935
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2513863-7
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  • 7
    Online Resource
    Online Resource
    Current Situation and Optimization Countermeasures of Cotton Subsidy in China Based on WTO Rules
    MDPI AG ; 2022
    In:  Agriculture Vol. 12, No. 8 ( 2022-08-17), p. 1245-
    Details
    In: Agriculture, MDPI AG, Vol. 12, No. 8 ( 2022-08-17), p. 1245-
    Abstract: Cotton plays an important role in China’s agricultural production structure and international trade; therefore, China has implemented a variety of cotton subsidy policies. Since China joined the WTO in 2001, WTO rules have become substantive constraints on its agricultural subsidy policy. Therefore, in order to prevent appeal cases of China’s cotton subsidy, in this article, we investigate the current situation and optimization countermeasures with respect to China’s cotton subsidies based on WTO rules. According to calculation of the level of China’s cotton subsidy support under WTO rules, it currently exceeds 8.5% of the cotton production value. Secondly, we estimate the change in cotton subsidy effect when the support level of China’s cotton subsidy policy is directly reduced to 8.5%; the results show that such a reduction would have a considerable impact on the production scale. However, due to the constraints of the political and economic goals of cotton subsidies, the Chinese government can only “box shift” subsidies by changing the subsidy method and object in order to comply with WTO rules. Finally, from the perspective of how to use cotton subsidies to improve the efficiency of production factors, the Chinese government should focus on optimizing the cotton subsidy policy according to three aspects: improving the Amber Box subsidies, expanding the Green Box subsidies and increasing the Blue Box subsidies so as to maintain the existing level of cotton subsidy support.
    Type of Medium: Online Resource
    ISSN: 2077-0472
    URL: Article
    DOI: 10.3390/agriculture12081245
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2651678-0
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  • 8
    Online Resource
    Online Resource
    The Molecular Composition of Peptide Toxins in the Venom of Spider Lycosa coelestis as Revealed by cDNA Library and Transcriptomic Sequencing
    MDPI AG ; 2023
    In:  Toxins Vol. 15, No. 2 ( 2023-02-10), p. 143-
    Details
    In: Toxins, MDPI AG, Vol. 15, No. 2 ( 2023-02-10), p. 143-
    Abstract: In the so-called “struggle for existence” competition, the venomous animals developed a smart and effective strategy, envenomation, for predation and defense. Biochemical analysis revealed that animal venoms are chemical pools of proteinase, peptide toxins, and small organic molecules with various biological activities. Of them, peptide toxins are of great molecular diversity and possess the capacity to modulate the activity of ion channels, the second largest group of drug targets expressed on the cell membrane, which makes them a rich resource for developing peptide drug pioneers. The spider Lycosa coelestis (L. coelestis) commonly found in farmland in China is a dominant natural enemy of agricultural pests; however, its venom composition and activity were never explored. Herein, we conducted cDNA library and transcriptomic sequencing of the venom gland of L. coelestis, which identified 1131 high-quality expressed sequence tags (ESTs), grouped into three categories denoted as toxin-like ESTs (597, 52.79%), cellular component ESTs (357, 31.56%), and non-matched ESTs (177, 15.65%). These toxin-like ESTs encode 98 non-reductant toxins, which are artificially divided into 11 families based on their sequence homology and cysteine frameworks (2–14 cysteines forming 1–7 disulfide bonds to stabilize the toxin structure). Furthermore, RP-HPLC purification combined with off-line MALDI-TOF analysis have detected 147 different peptides physically existing in the venom of L. coelestis. Electrophysiology analysis confirmed that the venom preferably inhibits the voltage-gated calcium channels in rat dorsal root ganglion neurons. Altogether, the present study has added a great lot of new members to the spider toxin superfamily and built the foundation for characterizing novel active peptides in the L. coelestis venom.
    Type of Medium: Online Resource
    ISSN: 2072-6651
    URL: Article
    DOI: 10.3390/toxins15020143
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518395-3
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  • 9
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    Artificial Base-Directed In Vivo Formulation of Aptamer–Drug Conjugates with Albumin for Long Circulation and Targeted Delivery
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 12 ( 2022-12-13), p. 2781-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 12 ( 2022-12-13), p. 2781-
    Abstract: Aptamer–drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were prepared, Sgc8-paclitaxel by conjugation and Sgc8-gemcitabine, by automated solid-phase synthesis. In vitro experiments showed that F-base-modified ApDCs retain the specificity of the aptamer to target cells and the biological stability is improved. In vivo studies demonstrated that the circulatory time is increased by up to 55 h or longer, as the incorporated F base leads to a stable ApDC-albumin complex as the formulation for targeted delivery. Moreover, conjugated drug molecules were released efficiently and the drug (paclitaxel) concentration in the tumor site was improved. The results demonstrate that an F-base-directed ApDC-albumin complex is a potential platform for drug delivery and targeted cancer therapy.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14122781
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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