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  • 1
    Online Resource
    Online Resource
    Artificial Intelligence-Assisted Transcriptomic Analysis to Advance Cancer Immunotherapy
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 4 ( 2023-02-06), p. 1279-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 4 ( 2023-02-06), p. 1279-
    Abstract: The emergence of immunotherapy has dramatically changed the cancer treatment paradigm and generated tremendous promise in precision medicine. However, cancer immunotherapy is greatly limited by its low response rates and immune-related adverse events. Transcriptomics technology is a promising tool for deciphering the molecular underpinnings of immunotherapy response and therapeutic toxicity. In particular, applying single-cell RNA-seq (scRNA-seq) has deepened our understanding of tumor heterogeneity and the microenvironment, providing powerful help for developing new immunotherapy strategies. Artificial intelligence (AI) technology in transcriptome analysis meets the need for efficient handling and robust results. Specifically, it further extends the application scope of transcriptomic technologies in cancer research. AI-assisted transcriptomic analysis has performed well in exploring the underlying mechanisms of drug resistance and immunotherapy toxicity and predicting therapeutic response, with profound significance in cancer treatment. In this review, we summarized emerging AI-assisted transcriptomic technologies. We then highlighted new insights into cancer immunotherapy based on AI-assisted transcriptomic analysis, focusing on tumor heterogeneity, the tumor microenvironment, immune-related adverse event pathogenesis, drug resistance, and new target discovery. This review summarizes solid evidence for immunotherapy research, which might help the cancer research community overcome the challenges faced by immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12041279
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 2
    Online Resource
    Online Resource
    MAPK CcSakA of the HOG Pathway Is Involved in Stipe Elongation during Fruiting Body Development in Coprinopsis cinerea
    MDPI AG ; 2022
    In:  Journal of Fungi Vol. 8, No. 5 ( 2022-05-20), p. 534-
    Details
    In: Journal of Fungi, MDPI AG, Vol. 8, No. 5 ( 2022-05-20), p. 534-
    Abstract: Mitogen-activated protein kinase (MAPK) pathways, such as the high-osmolarity glycerol mitogen-activated protein kinase (HOG) pathway, are evolutionarily conserved signaling modules responsible for transmitting environmental stress signals in eukaryotic organisms. Here, we identified the MAPK homologue in the HOG pathway of Coprinopsis cinerea, which was named CcSakA. Furthermore, during the development of the fruiting body, CcSakA was phosphorylated in the fast elongating apical part of the stipe, which meant that CcSakA was activated in the apical elongating stipe region of the fruiting body. The knockdown of CcSakA resulted in a shorter stipe of the fruiting body compared to the control strain, and the expression of phosphomimicking mutant CcSakA led to a longer stipe of the fruiting body compared to the control strain. The chitinase CcChiE1, which plays a key role during stipe elongation, was downregulated in the CcSakA knockdown strains and upregulated in the CcSakA phosphomimicking mutant strains. The results indicated that CcSakA participated in the elongation of stipes in the fruiting body development of C. cinerea by regulating the expression of CcChiE1. Analysis of the H2O2 concentration in different parts of the stipe showed that the oxidative stress in the elongating part of the stipe was higher than those in the non-elongating part. The results indicated that CcSakA of the HOG pathway may be activated by oxidative stress. Our results demonstrated that the HOG pathway transmits stress signals and regulates the expression of CcChiE1 during fruiting body development in C. cinerea.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    URL: Article
    DOI: 10.3390/jof8050534
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2784229-0
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  • 3
    Online Resource
    Online Resource
    Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 9 ( 2023-04-22), p. 7709-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 9 ( 2023-04-22), p. 7709-
    Abstract: Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24097709
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Synthesis of Imidazole-Based Molecules under Ultrasonic Irradiation Approaches
    MDPI AG ; 2023
    In:  Molecules Vol. 28, No. 12 ( 2023-06-19), p. 4845-
    Details
    In: Molecules, MDPI AG, Vol. 28, No. 12 ( 2023-06-19), p. 4845-
    Abstract: Imidazole-based compounds are a series of heterocyclic compounds that exhibit a wide range of biological and pharmaceutical activities. However, those extant syntheses using conventional protocols can be time-costly, require harsh conditions, and result in low yields. As a novel and green technique, sonochemistry has emerged as a promising method for organic synthesis with several advantages over conventional methods, including enhancing reaction rates, improving yields, and reducing the use of hazardous solvents. Contemporarily, a growing body of ultrasound-assisted reactions have been applied in the preparation of imidazole derivatives, which demonstrated greater benefits and provided a new strategy. Herein, we introduce the brief history of sonochemistry and focus on the discussion of the multifarious approaches for the synthesis of imidazole-based compounds under ultrasonic irradiation and its advantages in comparison with conventional protocols, including typical name-reactions and various sorts of catalysts in those reactions.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules28124845
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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  • 5
    Online Resource
    Online Resource
    New Triterpenoid Saponins from the Herb Hylomecon japonica
    MDPI AG ; 2017
    In:  Molecules Vol. 22, No. 10 ( 2017-10-23), p. 1731-
    Details
    In: Molecules, MDPI AG, Vol. 22, No. 10 ( 2017-10-23), p. 1731-
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules22101731
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2008644-1
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  • 6
    Online Resource
    Online Resource
    Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses
    MDPI AG ; 2021
    In:  Genes Vol. 12, No. 2 ( 2021-01-22), p. 141-
    Details
    In: Genes, MDPI AG, Vol. 12, No. 2 ( 2021-01-22), p. 141-
    Abstract: It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes12020141
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527218-4
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  • 7
    Online Resource
    Online Resource
    Analysis of miRNAs Targeted Storage Regulatory Genes during Soybean Seed Development Based on Transcriptome Sequencing
    MDPI AG ; 2019
    In:  Genes Vol. 10, No. 6 ( 2019-05-28), p. 408-
    Details
    In: Genes, MDPI AG, Vol. 10, No. 6 ( 2019-05-28), p. 408-
    Abstract: Soybeans are an important cash crop and are widely used as a source of vegetable protein and edible oil. MicroRNAs (miRNA) are endogenous small RNA that play an important regulatory role in the evolutionarily conserved system of gene expression. In this study, we selected four lines with extreme phenotypes, as well as high or low protein and oil content, from the chromosome segment substitution line (CSSL) constructed from suinong (SN14) and ZYD00006, and planted and sampled at three stages of grain development for small RNA sequencing and expression analysis. The sequencing results revealed the expression pattern of miRNA in the materials, and predicted miRNA-targeted regulatory genes, including 1967 pairs of corresponding relationships between known-miRNA and their target genes, as well as 597 pairs of corresponding relationships between novel-miRNA and their target genes. After screening and annotating genes that were targeted for regulation, five specific genes were identified to be differentially expressed during seed development and subsequently analyzed for their regulatory relationship with miRNAs. The expression pattern of the targeted gene was verified by Real-time Quantitative PCR (RT-qPCR). Our research provides more information about the miRNA regulatory network in soybeans and further identifies useful genes that regulate storage during soy grain development, providing a theoretical basis for the regulation of soybean quality traits.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes10060408
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527218-4
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  • 8
    Online Resource
    Online Resource
    Bacterial and Fungal Biocontrol Agents for Plant Disease Protection: Journey from Lab to Field, Current Status, Challenges, and Global Perspectives
    MDPI AG ; 2023
    In:  Molecules Vol. 28, No. 18 ( 2023-09-21), p. 6735-
    Details
    In: Molecules, MDPI AG, Vol. 28, No. 18 ( 2023-09-21), p. 6735-
    Abstract: Plants are constantly exposed to various phytopathogens such as fungi, Oomycetes, nematodes, bacteria, and viruses. These pathogens can significantly reduce the productivity of important crops worldwide, with annual crop yield losses ranging from 20% to 40% caused by various pathogenic diseases. While the use of chemical pesticides has been effective at controlling multiple diseases in major crops, excessive use of synthetic chemicals has detrimental effects on the environment and human health, which discourages pesticide application in the agriculture sector. As a result, researchers worldwide have shifted their focus towards alternative eco-friendly strategies to prevent plant diseases. Biocontrol of phytopathogens is a less toxic and safer method that reduces the severity of various crop diseases. A variety of biological control agents (BCAs) are available for use, but further research is needed to identify potential microbes and their natural products with a broad-spectrum antagonistic activity to control crop diseases. This review aims to highlight the importance of biocontrol strategies for managing crop diseases. Furthermore, the role of beneficial microbes in controlling plant diseases and the current status of their biocontrol mechanisms will be summarized. The review will also cover the challenges and the need for the future development of biocontrol methods to ensure efficient crop disease management for sustainable agriculture.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules28186735
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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  • 9
    Online Resource
    Online Resource
    Flumazenil-Insensitive Benzodiazepine Effects in Recombinant αβ and Neuronal GABAA Receptors
    MDPI AG ; 2020
    In:  Brain Sciences Vol. 10, No. 3 ( 2020-03-05), p. 150-
    Details
    In: Brain Sciences, MDPI AG, Vol. 10, No. 3 ( 2020-03-05), p. 150-
    Abstract: Gamma-aminobutyric acid, type A (GABAA) receptors are complex heterogeneous pentamers with various drug binding sites. Several lines of evidence suggest that benzodiazepines modulate certain GABAA receptors in a flumazenil-insensitive manner, possibly via binding sites other than the classical ones. However, GABAA receptor subtypes that contain non-classical benzodiazepine binding sites are not systemically studied. The present study investigated the high-concentration effects of three benzodiazepines and their sensitivity to flumazenil on different recombinant (α1β2, α2β2, α3β2, α4β2, α5β2 and α1β3) and native neuronal GABAA receptors using the whole-cell patch-clamp electrophysiology technique. The classical benzodiazepine diazepam (200 μmol/L) and midazolam (200 μmol/L) produced flumazenil-insensitive effects on α1β2 receptor, whereas the imidazopyridine zolpidem failed to modulate the receptor. Flumazenil-insensitive effects of diazepam were also observed on the α2β2, α3β2 and α5β2, but not α4β2 receptors. Unlike β2-containing receptors, the α1β3 receptor was insensitive to diazepam. Moreover, the diazepam (200 μmol/L) effects on some cortical neurons could not be fully antagonized by flumazenil (200 μmol/L). These findings suggested that the non-classical (flumazenil-insensitive) benzodiazepine effects depended on certain receptor subtypes and benzodiazepine structures and may be important for designing of subtype- or binding site- specific drugs.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci10030150
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2651993-8
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  • 10
    Online Resource
    Online Resource
    Overexpression of TaMYB4 Confers Freezing Tolerance in Arabidopsis thaliana
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 13 ( 2023-07-04), p. 11090-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 13 ( 2023-07-04), p. 11090-
    Abstract: Freezing stress is one of the main factors limiting the growth and yield of wheat. In this study, we found that TaMYB4 expression was significantly upregulated in the tillering nodes of the strong cold-resistant winter wheat variety Dongnongdongmai1 (Dn1) under freezing stress. Weighted gene co-expression network analysis, qRT-PCR and protein–DNA interaction experiments demonstrated that monodehydroascorbate reductase (TaMDHAR) is a direct target of TaMYB4. The results showed that overexpression of TaMYB4 enhanced the freezing tolerance of transgenic Arabidopsis. In TaMYB4 overexpression lines (OE-TaMYB4), AtMDHAR2 expression was upregulated and ascorbate-glutathione (AsA–GSH) cycle operation was enhanced. In addition, the expression of cold stress marker genes such as AtCBF1, AtCBF2, AtCBF3, AtCOR15A, AtCOR47, AtKIN1 and AtRD29A in OE-TaMYB4 lines was significantly upregulated. Therefore, TaMYB4 may increase freezing tolerance as a transcription factor (TF) in Arabidopsis through the AsA–GSH cycle and DREB/CBF signaling pathway. This study provides a potential gene for molecular breeding against freezing stress.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241311090
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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