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  • MDPI AG  (1,785)
  • 2020-2024  (1,785)
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  • MDPI AG  (1,785)
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  • 2020-2024  (1,785)
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  • 1
    Online Resource
    Online Resource
    Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 20 ( 2021-10-15), p. 6250-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 20 ( 2021-10-15), p. 6250-
    Abstract: Androgens have been shown to have a beneficial effect on brain injury and lower reactive astrocyte expression after TBI. Androgen receptors (ARs) are known to mediate the neuroprotective effects of androgens. However, whether ARs play a crucial role in TBI remains unknown. In this study, we investigated the role of ARs in TBI pathophysiology, using AR knockout (ARKO) mice. We used the controlled cortical impact model to produce primary and mechanical brain injuries and assessed motor function and brain-lesion volume. In addition, the AR knockout effects on necrosis and autophagy were evaluated after TBI. AR knockout significantly increased TBI-induced expression of the necrosis marker alpha-II-spectrin breakdown product 150 and astrogliosis marker glial fibrillary acidic protein. In addition, the TBI-induced astrogliosis increase in ARKO mice lasted for three weeks after a TBI. The autophagy marker Beclin-1 was also enhanced in ARKO mice compared with wild-type mice after TBI. Our results also indicated that ARKO mice showed a more unsatisfactory performance than wild-type mice in a motor function test following TBI. Further, they were observed to have more severe lesions than wild-type mice after injury. These findings strongly suggest that ARs play a role in TBI.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26206250
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2008644-1
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  • 2
    Online Resource
    Online Resource
    Synthesis and In Vitro Photocytotoxicity of 9-/13-Lipophilic Substituted Berberine Derivatives as Potential Anticancer Agents
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 3 ( 2020-02-05), p. 677-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 3 ( 2020-02-05), p. 677-
    Abstract: The objective of this study was to synthesize the 9-/13-position substituted berberine derivatives and evaluate their cytotoxic and photocytotoxic effects against three human cancer cell lines. Among all the synthesized compounds, 9-O-dodecyl- (5e), 13-dodecyl- (6e), and 13-O-dodecyl-berberine (7e) exhibited stronger growth inhibition against three human cancer cell lines, (HepG2, HT-29 and BFTC905), in comparison with structurally related berberine (1). These three compounds also showed the photocytotoxicity in human cancer cells in a concentration-dependent and light dose-dependent manner. Through flow cytometry analysis, we found out a lipophilic group at the 9-/13-position of berberine may have facilitated its penetration into test cells and hence enhanced its photocytotoxicity on the human liver cancer cell HepG2. Further, in cell cycle analysis, 5e, 6e, and 7e induced HepG2 cells to arrest at the S phase and caused apoptosis upon irradiation. In addition, photodynamic treatment of berberine derivatives 5e, 6e, and 7e again showed a significant photocytotoxic effects on HepG2 cells, induced remarkable cell apoptosis, greatly increased intracellular ROS level, and the loss of mitochondrial membrane potential. These results over and again confirmed that berberine derivatives 5e, 6e, and 7e greatly enhanced photocytotoxicity. Taken together, the test data led us to conclude that berberine derivatives with a dodecyl group at the 9-/13-position could be great candidates for the anti-liver cancer medicines developments.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25030677
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 3
    Online Resource
    Online Resource
    A Genome-Wide Association Study of the Chest Circumference Trait in Xinjiang Donkeys Based on Whole-Genome Sequencing Technology
    MDPI AG ; 2023
    In:  Genes Vol. 14, No. 5 ( 2023-05-14), p. 1081-
    Details
    In: Genes, MDPI AG, Vol. 14, No. 5 ( 2023-05-14), p. 1081-
    Abstract: Animal genotyping by means of genome-wide association studies is important for connecting phenotypes of interest with their underlying genetics in livestock. However, the use of whole genome sequencing to investigate chest circumference (CC) in donkeys has rarely been reported. We aimed to use the genome-wide association study approach to detect significant single nucleotide polymorphisms (SNPs) and key genes associated with chest circumference traits in Xinjiang donkeys. We assessed 112 Xinjiang donkeys in this study. The chest circumference of each was measured 2 h before milking. We re-sequenced blood samples from the Xinjiang donkeys, and genome-wide association study analyses were performed using a mixed model with the PLINK, GEMMA, and REGENIE programs. We tested 38 donkeys for candidate SNPs for genome-wide association study using three software programs. Additionally, 18 SNP markers reached genome-wide significance (p 〈 1.61 × 10−9). On the basis of these, 41 genes were identified. Previously proposed candidate genes for CC traits were supported by this study, including NFATC2 (Nuclear Factor of Activated T Cells 2), PROP1 (PROP Paired-Like Homeobox 1), UBB (Ubiquitin B), and HAND2 (Heart and Neural Crest Derivatives Expressed 2). These promising candidates provide a valuable resource for validating potential meat production genes and will facilitate the development of high-yielding Xinjiang donkey breeds through marker-assisted selection or gene editing.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes14051081
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527218-4
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  • 4
    Online Resource
    Online Resource
    Target-Specific Machine Learning Scoring Function Improved Structure-Based Virtual Screening Performance for SARS-CoV-2 Drugs Development
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 19 ( 2022-09-20), p. 11003-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 19 ( 2022-09-20), p. 11003-
    Abstract: Leveraging machine learning has been shown to improve the accuracy of structure-based virtual screening. Furthermore, a tremendous amount of empirical data is publicly available, which further enhances the performance of the machine learning approach. In this proof-of-concept study, the 3CLpro enzyme of SARS-CoV-2 was used. Structure-based virtual screening relies heavily on scoring functions. It is widely accepted that target-specific scoring functions may perform more effectively than universal scoring functions in real-world drug research and development processes. It would be beneficial to drug discovery to develop a method that can effectively build target-specific scoring functions. In the current study, the bindingDB database was used to retrieve experimental data. Smina was utilized to generate protein-ligand complexes for the extraction of InteractionFingerPrint (IFP) and SimpleInteractionFingerPrint SIFP fingerprints via the open drug discovery tool (oddt). The present study found that randomforestClassifier and randomforestRegressor performed well when used with the above fingerprints along the Molecular ACCess System (MACCS), Extended Connectivity Fingerprint (ECFP4), and ECFP6. It was found that the area under the precision-recall curve was 0.80, which is considered a satisfactory level of accuracy. In addition, our enrichment factor analysis indicated that our trained scoring function ranked molecules correctly compared to smina’s generic scoring function. Further molecular dynamics simulations indicated that the top-ranked molecules identified by our developed scoring function were highly stable in the active site, supporting the validity of our developed process. This research may provide a template for developing target-specific scoring functions against specific enzyme targets.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231911003
    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
    Numerical Investigation into the Development Performance of Gas Hydrate by Depressurization Based on Heat Transfer and Entropy Generation Analyses
    MDPI AG ; 2020
    In:  Entropy Vol. 22, No. 11 ( 2020-10-26), p. 1212-
    Details
    In: Entropy, MDPI AG, Vol. 22, No. 11 ( 2020-10-26), p. 1212-
    Abstract: The purpose of this study is to analyze the dynamic properties of gas hydrate development from a large hydrate simulator through numerical simulation. A mathematical model of heat transfer and entropy production of methane hydrate dissociation by depressurization has been established, and the change behaviors of various heat flows and entropy generations have been evaluated. Simulation results show that most of the heat supplied from outside is assimilated by methane hydrate. The energy loss caused by the fluid production is insignificant in comparison to the heat assimilation of the hydrate reservoir. The entropy generation of gas hydrate can be considered as the entropy flow from the ambient environment to the hydrate particles, and it is favorable from the perspective of efficient hydrate exploitation. On the contrary, the undesirable entropy generations of water, gas and quartz sand are induced by the irreversible heat conduction and thermal convection under notable temperature gradient in the deposit. Although lower production pressure will lead to larger entropy production of the whole system, the irreversible energy loss is always extremely limited when compared with the amount of thermal energy utilized by methane hydrate. The production pressure should be set as low as possible for the purpose of enhancing exploitation efficiency, as the entropy production rate is not sensitive to the energy recovery rate under depressurization.
    Type of Medium: Online Resource
    ISSN: 1099-4300
    URL: Article
    DOI: 10.3390/e22111212
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2014734-X
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  • 6
    Online Resource
    Online Resource
    Neuroprotective Effect of Angiopoietin2 Is Associated with Angiogenesis in Mouse Brain Following Ischemic Stroke
    MDPI AG ; 2022
    In:  Brain Sciences Vol. 12, No. 11 ( 2022-10-24), p. 1428-
    Details
    In: Brain Sciences, MDPI AG, Vol. 12, No. 11 ( 2022-10-24), p. 1428-
    Abstract: Angiogenic factors play an important role in protecting, repairing, and reconstructing vessels after ischemic stroke. In the brains of transient focal cerebral ischemic mice, we observed a reduction in infarct volume after the administration of Angiopoietin 2 (Angpt2), but whether this process is promoted by Angpt2-induced angiogenesis has not been fully elaborated. Therefore, this study explored the angiogenic activities, in reference to CD34 which is a marker of activated ECs and blood vessels, of cultured ECs in vitro and in ischemic damaged cerebral area in mice following Angpt2 administration. Our results demonstrate that Angpt2 administration (100 ng/mL) is neuroprotective by significantly increasing the CD34 expression in in vitro-cultured ECs, reducing the infarct volume and mitigating neuronal loss, as well as enhancing CD34+ vascular length and area. In conclusion, these results indicate that Angpt2 promotes repair and attenuates ischemic injury, and that the mechanism of this is closely associated with angiogenesis in the brain after stroke.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci12111428
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2651993-8
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  • 7
    Online Resource
    Online Resource
    Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 7 ( 2021-07-16), p. 1803-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 7 ( 2021-07-16), p. 1803-
    Abstract: Objective: Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing, due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells; however, no research has yet been reported to scientifically investigate the effect of human dental pulp stem cells (HDPSCs) on the treatment of keloids. The objective is to provide an experimental basis for the application of stem cells in the treatment of keloids. Methods: Human normal fibroblasts (HNFs) and human keloid fibroblasts (HKFs) were cultured alone and in combination with HDPSCs using a transwell cell-contact-independent cell culture system. The effects of HDPSCs on HKFs were tested using a CCK-8 assay, live/dead staining assay, quantitative polymerase chain reaction, Western blot and immunofluorescence microscopy. Results: HDPSCs did not inhibit the proliferation nor the apoptosis of HKFs and HNFs. HDPSCs did, however, inhibit their migration. Furthermore, HDPSCs significantly decreased the expression of profibrotic genes (CTGF, TGF-β1 and TGF-β2) in HKFs and KNFs (p 〈 0.05), except for CTGF in HNFs. Moreover, HDPSCs suppressed the extracellular matrix (ECM) synthesis in HKFs, as indicated by the decreased expression of collagen I as well as the low levels of hydroxyproline in the cell culture supernatant (p 〈 0.05). Conclusions: The co-culture of HDPSCs inhibits the migration of HKFs and the expression of pro-fibrotic genes, while promoting the expression of anti-fibrotic genes. HDPSCs’ co-culture also inhibits the synthesis of the extracellular matrix by HKFs, whereas it does not affect the proliferation and apoptosis of HKFs. Therefore, it can be concluded that HDPSCs can themselves be used as a tool for restraining/hindering the initiation or progression of fibrotic tissue.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10071803
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 8
    Online Resource
    Online Resource
    New Terpenoids from Potentilla freyniana Bornm. and Their Cytotoxic Activities
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 12 ( 2022-06-07), p. 3665-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 12 ( 2022-06-07), p. 3665-
    Abstract: Two new A-ring contracted triterpenoids, madengaisu A and madengaisu B, and one undescribed ent-kaurane diterpenoid, madengaisu C, along with 20 known compounds were isolated from the roots of Potentilla freyniana Bornm. The structures were elucidated using extensive spectroscopic techniques, including 1D and 2D-NMR, HR-ESI-MS, ECD spectra, IR, and UV analysis. Moreover, all isolated constituents were evaluated for their anti-proliferative activity against RA-FLS cells and cytotoxic activities against the human cancer cell lines Hep-G2, HCT-116, BGC-823, and MCF-7. Ursolic acid and pomolic acid displayed moderate inhibitory activity in RA-FLS cells with IC50 values of 24.63 ± 1.96 and 25.12 ± 1.97 μM, respectively. Hyptadienic acid and 2α,3β-dihydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranoside exhibited good cytotoxicity against Hep-G2 cells with IC50 values of 25.16 ± 2.55 and 17.66 ± 1.82 μM, respectively. In addition, 2α,3β-dihydroxyolean-13(18)-en-28-oic acid and alphitolic acid were observed to inhibit HCT-116 cells (13.25 ± 1.65 and 21.62 ± 0.33 μM, respectively), while madengaisu B and 2α,3β-dihydroxyolean-13(18)-en-28-oic acid showed cytotoxic activities against BGC-823 cells with IC50 values of 24.76 ± 0.94 and 26.83 ± 2.52 μM, respectively, which demonstrated that triterpenes from P. freyniana may serve as therapeutic agents for RA and cancer treatment.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27123665
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 9
    Online Resource
    Online Resource
    Conserved Imprinted Genes between Intra-Subspecies and Inter-Subspecies Are Involved in Energy Metabolism and Seed Development in Rice
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 24 ( 2020-12-17), p. 9618-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 24 ( 2020-12-17), p. 9618-
    Abstract: Genomic imprinting is an epigenetic phenomenon in which a subset of genes express dependent on the origin of their parents. In plants, it is unclear whether imprinted genes are conserved between subspecies in rice. Here we identified imprinted genes from embryo and endosperm 5–7 days after pollination from three pairs of reciprocal hybrids, including inter-subspecies, japonica intra-subspecies, and indica intra-subspecies reciprocal hybrids. A total of 914 imprinted genes, including 546 in inter-subspecies hybrids, 211 in japonica intra-subspecies hybrids, and 286 in indica intra-subspecies hybrids. In general, the number of maternally expressed genes (MEGs) is more than paternally expressed genes (PEGs). Moreover, imprinted genes tend to be in mini clusters. The number of shared genes by R9N (reciprocal crosses between 9311 and Nipponbare) and R9Z (reciprocal crosses between 9311 and Zhenshan 97), R9N and RZN (reciprocal crosses between Zhonghua11 and Nipponbare), R9Z and RZN was 72, 46, and 16. These genes frequently involved in energy metabolism and seed development. Five imprinted genes (Os01g0151700, Os07g0103100, Os10g0340600, Os11g0679700, and Os12g0632800) are commonly detected in all three pairs of reciprocal hybrids and were validated by RT-PCR sequencing. Gene editing of two imprinted genes revealed that both genes conferred grain filling. Moreover, 15 and 27 imprinted genes with diverse functions in rice were shared with Arabidopsis and maize, respectively. This study provided valuable resources for identification of imprinting genes in rice or even in cereals.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21249618
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Suggestions for Chinese University Freshmen Based on Adaptability Analysis and Sustainable Development Education
    MDPI AG ; 2020
    In:  Sustainability Vol. 12, No. 4 ( 2020-02-13), p. 1371-
    Details
    In: Sustainability, MDPI AG, Vol. 12, No. 4 ( 2020-02-13), p. 1371-
    Abstract: Based on the theory of sustainable development education, this paper tested the adaptability of contemporary university freshmen. Using the compilation and revision of China’s College Student Adjustment Scale (CCSAS). This paper examines five dimensions: personal emotional adaptability, learning adaptability, interpersonal adaptability, university identity, and living adaptability. Using a sample of 640 freshmen (from more than 30 universities) and considering the three dimensions of gender, major, and origin, the paper reaches the following conclusions. Generally, the adaptability of freshmen was positive and their adaptation is good; from the perspective of gender, males and females are different in physiology and psychology; from the perspective of major, there are no significant differences; from the perspective of students’ origin, there was no significant difference in general, but there were significant differences in personal emotions and university identity. Based on the above results, this paper emphasizes that to achieve the goal of sustainable development education, universities should begin to pay attention to the adaptability of students as soon as they enter the university. In addition to paying attention to the quality of teaching and learning, universities should also pay attention to the individual differences among students and the related factors that hinder their sustainable development. To ensure that students can meet the challenges of society in the future, the university should cultivate students’ awareness of sustainable development and their ability to participate in and develop sustainable practices.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su12041371
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518383-7
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