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1.
J Neuroinflammation ; 21(1): 84, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582873

RESUMEN

Alzheimer's disease (AD) is recognized as the predominant cause of dementia, and neuroimmune processes play a pivotal role in its pathological progression. The involvement of long non-coding RNAs (lncRNAs) in AD has attracted widespread attention. Herein, transcriptomic analysis of 262 unique samples extracted from five hippocampal-entorhinal system subfields of individuals with AD pathology and without AD pathology revealed distinctive lncRNA expression profiles. Through differential expression and coexpression analyses, we identified 16 pivotal lncRNAs. Notably, RN7SL1 knockdown significantly modulated microglial responses upon oligomeric amyloid-ß stimulation, resulting in a considerable decrease in proinflammatory cytokine production and subsequent neuronal damage. These findings highlight RN7SL1 as an essential neuroimmune-related lncRNA that could serve as a prospective target for AD diagnosis and treatment.


Asunto(s)
Enfermedad de Alzheimer , ARN Largo no Codificante , Humanos , Enfermedad de Alzheimer/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Expresión Génica
2.
Angew Chem Int Ed Engl ; : e202409986, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38923276

RESUMEN

The utilization of hybrid aqueous electrolytes has significantly broadened the electrochemical and temperature ranges of aqueous batteries, such as aqueous zinc and lithium-ion batteries, but the design principles for extreme operating conditions remain poorly understood. Here, we systematically unveil the ternary interaction involving salt-water-organic co-solvents and its intricate impacts on both the atomic-level and macroscopic structural features of the hybrid electrolytes. This highlights a distinct category of micelle-like structure electrolytes featuring organic-enriched phases and nanosized aqueous electrolyte aggregates, enabled by appropriate low donor number co-solvents and amphiphilic anions. Remarkably, the electrolyte enables exceptional high solubility, accommodating up to 29.8 m zinc triflate within aqueous micelles. This configuration maintains an intra-micellar salt-in-water setup, allowing for a broad electrochemical window (up to 3.86 V), low viscosity, and state-of-the-art ultralow-temperature zinc ion conductivity (1.58 mS cm-1 at -80°C). Building upon the unique nature of the inhomogeneous localized aggregates, this micelle-like electrolyte facilitates dendrite-free Zn plating/stripping, even at -80°C. The assembled Zn||PANI battery showcases an impressive capacity of 71.8 mAh g-1 and an extended lifespan of over 3000 cycles at -80°C. This study opens up a promising approach in electrolyte design that transcends conventional local atomic solvation structures, broadening the water-in-salt electrolyte concept.

3.
Mol Cancer ; 22(1): 145, 2023 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-37660039

RESUMEN

BACKGROUND: Immunotherapy has recently emerged as a treatment strategy which stimulates the human immune system to kill tumor cells. Tumor immunotherapy is based on immune editing, which enhances the antigenicity of tumor cells and increases the tumoricidal effect of immune cells. It also suppresses immunosuppressive molecules, activates or restores immune system function, enhances anti-tumor immune responses, and inhibits the growth f tumor cell. This offers the possibility of reducing mortality in triple-negative breast cancer (TNBC). MAIN BODY: Immunotherapy approaches for TNBC have been diversified in recent years, with breakthroughs in the treatment of this entity. Research on immune checkpoint inhibitors (ICIs) has made it possible to identify different molecular subtypes and formulate individualized immunotherapy schedules. This review highlights the unique tumor microenvironment of TNBC and integrates and analyzes the advances in ICI therapy. It also discusses strategies for the combination of ICIs with chemotherapy, radiation therapy, targeted therapy, and emerging treatment methods such as nanotechnology, ribonucleic acid vaccines, and gene therapy. Currently, numerous ongoing or completed clinical trials are exploring the utilization of immunotherapy in conjunction with existing treatment modalities for TNBC. The objective of these investigations is to assess the effectiveness of various combined immunotherapy approaches and determine the most effective treatment regimens for patients with TNBC. CONCLUSION: This review provides insights into the approaches used to overcome drug resistance in immunotherapy, and explores the directions of immunotherapy development in the treatment of TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/terapia , Inmunoterapia , Ciclo Celular , Proliferación Celular , Terapia Genética , Microambiente Tumoral
4.
Plant Physiol ; 188(4): 1780-1794, 2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35238390

RESUMEN

Beneficial alleles derived from local landraces or related species, or even orthologs from other plant species, are often caused by differences of one or several single-nucleotide polymorphisms or indels in either the promoter region or the encoding region of a gene and often account for major differences in agriculturally important traits. Clustered regularly interspaced short palindromic repeats-associated endonuclease Cas9 system (CRISPR/Cas9)-mediated precision genome editing enables targeted allele replacement or insertion of flag or foreign genes at specific loci via homology-directed repair (HDR); however, HDR efficiency is low due to the intrinsic rare occurrence of HDR and insufficient DNA repair template in the proximity of a double-stranded break (DSB). Precise replacement of the targeted gene with elite alleles from landraces or relatives into a commercial variety through genome editing has been a holy grail in the crop genome editing field. In this update, we briefly summarize CRISPR/Cas-mediated HDR in plants. We describe diverse strategies to improve HDR efficiency by manipulating the DNA repair pathway, timing DSB induction, and donor delivery, and so on. Lastly, we outline open questions and challenges in HDR-mediated precision genome editing in both plant biological research and crop improvement.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Sistemas CRISPR-Cas/genética , Roturas del ADN de Doble Cadena , Reparación del ADN por Unión de Extremidades , Reparación del ADN/genética , Reparación del ADN por Recombinación/genética
5.
Opt Express ; 31(20): 32227-32240, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859030

RESUMEN

Ultraviolet detection has advantages over radar and infrared detection, such as low background radiation and high resolution. The UV spectral radiation characteristics of exhaust plume are of extremely great research significance as the main parameters for aircraft detection. We used the BEM-2 two-phase flow plume as the object of study, calculated the scattering characteristics of alumina particles and the UV absorption coefficient of OH in the plume based on the MIE theory and the line-by-line integration method, established the UV radiation transfer model of aircraft plume under gas-solid coupling, simulated the UV spectral radiation characteristics of the plume, and compared them with experimental results. The results show that due to the drastic changes of temperature and pressure at the Mach and non-Mach disks in the plume, the value of OH absorption coefficient fluctuates up and down along the axial direction with the position of the Mach disk; at 261nm, 282nm, and 306nm, the spectral radiation intensity of alumina particles accounts for approximately 96%, 85%, and 73% of the total spectral radiation intensity of the plume, respectively, which are much higher than the proportion of OH gas spectral radiation intensity, but in the infrared wave band, the influence of particle scattering characteristics on the spectral radiation intensity of the plume is much lower compared to the UV wave band; the overall radial range of the UV spectral radiation intensity of the plume is relatively narrow and its tail exhibits a converging shape, showing a good consistency with the experimental results.

6.
BMC Cancer ; 23(1): 133, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36759763

RESUMEN

BACKGROUND: Transporter associated with antigen processing 1 (TAP1) is a molecule involved in processing and presentation of major histocompatibility complex class I restricted antigens, including tumor-associated antigens. TAP1 participates in tumor immunity, and is aberrantly expressed in multiple cancer types; METHODS: Transcriptome profiles were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Genetic alterations, protein distribution, and interaction information for TAP1 were downloaded from cBioPortal, Human Protein Atlas and Compartmentalized Protein-Protein Interaction, respectively. Single-cell analyses of TAP1 across cancers were conducted via the Tumor Immune Single-cell Hub website. Gene set enrichment analysis was employed to investigate TAP1-associated functional mechanisms and processes. Immune cell infiltration was explored using Tumor Immune Estimation Resource 2.0. Pan-cancer correlations between TAP1 expression and immunotherapy biomarkers were explored using the Spearman's correlation test. Associations with immunotherapy responses were also investigated using clinicopathological and prognostic information from cohorts of patients with cancer receiving immune checkpoint inhibitors. RESULTS: TAP1 expression was elevated in most cancer types and exhibited distinct prognostic value. Immune cells expressed more TAP1 than malignant cells within most tumors. TAP1 expression was significantly correlated with immune-related pathways, T-lymphocyte infiltration, and immunotherapeutic biomarkers. Clinical cohort validation revealed a significant correlation with immune therapeutic effects and verified the prognostic role of TAP1 in immunotherapy. Western blot assay indicated that TAP1 is upregulated in glioblastoma compared with adjacent normal brain tissues. CONCLUSION: TAP1 is a robust tumor prognostic biomarker and a novel predictor of clinical prognosis and immunotherapeutic responses in various cancer types.


Asunto(s)
Presentación de Antígeno , Glioblastoma , Humanos , Biomarcadores de Tumor , Western Blotting , Inmunoterapia , Proteínas de Transporte de Membrana , Pronóstico , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2/genética
7.
Biomed Eng Online ; 22(1): 62, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37337190

RESUMEN

Decellularized vascular matrix is a natural polymeric biomaterial that comes from arteries or veins which are removed the cellular contents by physical, chemical and enzymatic means, leaving only the cytoskeletal structure and extracellular matrix to achieve cell adhesion, proliferation and differentiation and creating a suitable microenvironment for their growth. In recent years, the decellularized vascular matrix has attracted much attention in the field of tissue repair and regenerative medicine due to its remarkable cytocompatibility, biodegradability and ability to induce tissue regeneration. Firstly, this review introduces its basic properties and preparation methods; then, it focuses on the application and research of composite scaffold materials based on decellularized vascular matrix in vascular tissue engineering in terms of current in vitro and in vivo studies, and briefly outlines its applications in other tissue engineering fields; finally, it looks into the advantages and drawbacks to be overcome in the application of decellularized vascular matrix materials. In conclusion, as a new bioactive material for building engineered tissue and repairing tissue defects, decellularized vascular matrix will be widely applied in prospect.


Asunto(s)
Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Medicina Regenerativa/métodos , Matriz Extracelular/metabolismo
8.
Odontology ; 111(4): 870-882, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36879181

RESUMEN

Periodontal tissue regeneration engineering based on human periodontal ligament stem cells (hPDLSCs) provides a broad prospect for the treatment of periodontal disease. N-Acetyltransferase 10 (NAT10)-catalyzed non-histone acetylation is widely involved in physiological or pathophysiological processes. However, its function in hPDLSCs is still missing. hPDLSCs were isolated, purified, and cultured from extracted teeth. Surface markers were detected by flow cytometry. Osteogenic, adipogenic, and chondrogenic differentiation potential was detected by alizarin red staining (ARS), oil red O staining, and Alcian blue staining. Alkaline phosphatase (ALP) activity was assessed by ALP assay. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of key molecules, such as NAT10, Vascular endothelial growth factor A (VEGFA), PI3K/AKT pathway, as well as bone markers (RUNX2, OCN, OPN). RNA-Binding Protein Immunoprecipitation PCR (RIP-PCR) was used to detect the N4-acetylcytidine (ac4C) mRNA level. Genes related to VEGFA were identified by bioinformatics analysis. NAT10 was highly expressed in the osteogenic differentiation process with enhanced ALP activity and osteogenic capability, and elevated expression of osteogenesis-related markers. The ac4C level and expression of VEGFA were obviously regulated by NAT10 and overexpression of VEGFA also had similar effects to NAT10. The phosphorylation level of PI3K and AKT was also elevated by overexpression of VEGFA. VEGFA could reverse the effects of NAT10 in hPDLSCs. NAT10 enhances the osteogenic development of hPDLSCs via regulation of the VEGFA-mediated PI3K/AKT signaling pathway by ac4C alteration.


Asunto(s)
Ligamento Periodontal , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/farmacología , Osteogénesis/genética , Factor A de Crecimiento Endotelial Vascular , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Diferenciación Celular , Células Madre , Células Cultivadas , Proliferación Celular , Acetiltransferasas N-Terminal
9.
Int J Mol Sci ; 24(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36769156

RESUMEN

The complexity of genetic circuits has not seen a significant increase over the last decades, even with the rapid development of synthetic biology tools. One of the bottlenecks is the limited number of orthogonal transcription factor-operator pairs. Researchers have tried to use aptamer-ligand pairs as genetic parts to regulate transcription. However, most aptamers selected using traditional methods cannot be directly applied in gene circuits for transcriptional regulation. To that end, we report a new method called CIVT-SELEX to select DNA aptamers that can not only bind to macromolecule ligands but also undergo significant conformational changes, thus affecting transcription. The single-stranded DNA library with affinity to our example ligand human thrombin protein is first selected and enriched. Then, these ssDNAs are inserted into a genetic circuit and tested in the in vitro transcription screening to obtain the ones with significant inhibitory effects on downstream gene transcription when thrombins are present. These aptamer-thrombin pairs can inhibit the transcription of downstream genes, demonstrating the feasibility and robustness of their use as genetic parts in both linear DNAs and plasmids. We believe that this method can be applied to select aptamers of any target ligands and vastly expand the genetic part library for transcriptional regulation.


Asunto(s)
Aptámeros de Nucleótidos , Redes Reguladoras de Genes , Humanos , Trombina/genética , Trombina/metabolismo , Ligandos , Sistema Libre de Células/metabolismo , Técnica SELEX de Producción de Aptámeros , Aptámeros de Nucleótidos/metabolismo , ADN de Cadena Simple
10.
J Integr Plant Biol ; 65(2): 444-467, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36479615

RESUMEN

Precise replacement of an allele with an elite allele controlling an important agronomic trait in a predefined manner by gene editing technologies is highly desirable in crop improvement. Base editing and prime editing are two newly developed precision gene editing systems which can introduce the substitution of a single base and install the desired short indels to the target loci in the absence of double-strand breaks and donor repair templates, respectively. Since their discoveries, various strategies have been attempted to optimize both base editor (BE) and prime editor (PE) in order to improve the precise editing efficacy, specificity, and expand the targeting scopes. Here, we summarize the latest development of various BEs and PEs, as well as their applications in plants. Based on these progresses, we recommend the appropriate BEs and PEs for both basic plant research and crop improvement. Moreover, we propose the perspectives for further optimization of these two editors. We envision that both BEs and PEs will become the routine and customized precise gene editing tools for both plant biological research and crop improvement in the near future.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Plantas/genética , Alelos
11.
J Integr Plant Biol ; 65(9): 2194-2203, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37402157

RESUMEN

Exploiting novel endogenous glyphosate-tolerant alleles is highly desirable and has promising potential for weed control in rice breeding. Here, through fusions of different effective cytosine and adenine deaminases with nCas9-NG, we engineered an effective surrogate two-component composite base editing system, STCBE-2, with improved C-to-T and A-to-G base editing efficiency and expanded the editing window. Furthermore, we targeted a rice endogenous OsEPSPS gene for artificial evolution through STCBE-2-mediated near-saturated mutagenesis. After hygromycin and glyphosate selection, we identified a novel OsEPSPS allele with an Asp-213-Asn (D213N) mutation (OsEPSPS-D213N) in the predicted glyphosate-binding domain, which conferred rice plants reliable glyphosate tolerance and had not been reported or applied in rice breeding. Collectively, we developed a novel dual base editor which will be valuable for artificial evolution of important genes in crops. And the novel glyphosate-tolerant rice germplasm generated in this study will benefit weeds management in rice paddy fields.


Asunto(s)
Oryza , Oryza/genética , Alelos , Adenina , Citosina , Fitomejoramiento , Edición Génica , Glifosato
12.
J Cell Mol Med ; 26(22): 5565-5579, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36317423

RESUMEN

Ferroptosis is a type of regulated cell death (RCD), and it plays an important role in the occurrence of diseases, especially the development of tumors. Ferroptosis of tumor cells affects the antitumor immunity and the immune response to treatment to varying degrees. Ferroptosis also plays a key role in immune cells. This review outlines the mechanism of the immune-related effects of ferroptosis pathways in tumor progression and treatment, and it discusses potential methods for improving antitumor immunity and enhancing the efficacy of current cancer treatments by targeting ferroptosis.


Asunto(s)
Ferroptosis , Neoplasias , Humanos , Peroxidación de Lípido , Neoplasias/patología
13.
J Am Chem Soc ; 144(21): 9264-9270, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35583938

RESUMEN

Current therapeutic strategies for Alzheimer's disease (AD) mainly focus on amyloid ß oligomer (AßO) formation or clearance. However, most of them have failed to yield good clinical results. There is an urgent need to explore an alternative therapeutic target for AD treatments. Recent studies have indicated that the cellular prion protein (PrPC) is one of the cell-surface receptors of AßO that mediates related neurotoxicity. Besides, as a neuroprotective protein, the dimerization of PrPC seems to be critical for its trophic activity. We presume that modulating PrPC receptor activity could be another potential approach to abrogate AßO toxicity. In the present work, using an aptamer-induced dimerization (AID) strategy, we enforce PrPC dimerization and modulate its neurotrophic signaling. The AID strategy can attenuate AßO toxic action by (i) interfering with AßO-PrPC interaction and promoting neuroprotective shedding of PrPC; (ii) preventing the AßO-induced mitochondrial dysfunction and the caspase-3-induced apoptosis; and (iii) reducing the secretion of inflammatory cytokines and relieving the neuroinflammation microenvironment. Our findings suggest that the strategy targeting PrPC signaling may shed light on validating new therapeutic strategies in AD.


Asunto(s)
Enfermedad de Alzheimer , Proteínas PrPC , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Dimerización , Humanos , Proteínas PrPC/metabolismo , Proteínas Priónicas
14.
Anal Chem ; 94(2): 1101-1107, 2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-34968407

RESUMEN

The protein nanoenvironment on the plasma membrane is intimately linked to cellular biological functions. Elucidation of the protein nanoenvironment contributes to understanding the pathological mechanism and discovery of disease biomarkers. However, methods enabling characterization of the protein nanoenvironment in the endogenous biological environment have been rarely developed. Toward this end, we created a nucleic acid tool called Apt-Gq/h for proximity labeling to decipher the endogenous protein nanoenvironment. Here, the aptamer acts as an anchor for binding the protein of interest (POI). The G-quadruplex/hemin complex induces proximity labeling of POI via catalyzing the conversion of inert small-molecule substrates into short-lived reactive species. The labeled proteins enable the subsequent affinity-based enrichment and proteomic analysis. We first characterized Apt-Gq/h-mediated POI labeling in vitro and tested its utility by interrogating the protein nanoenvironment of POI in living cells. Taking advantage of the nongenetic, multiple reaction sites, and rapid proximity labeling, Apt-Gq/h was further utilized to imaging the cell-cell connection and amplification detection of biomarkers in living cells and tissue sections. We believe that Apt-Gq/h will be a potential tool for basic science and clinical applications.


Asunto(s)
Ácidos Nucleicos , Hemina/química , Proteínas de la Membrana , Peroxidasa , Proteómica
15.
Cancer Cell Int ; 22(1): 275, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36064705

RESUMEN

BACKGROUND: The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored. METHODS: We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx). RESULTS: Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells. CONCLUSIONS: Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.

16.
BMC Cancer ; 22(1): 973, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36096781

RESUMEN

BACKGROUND: Although intrinsic immune-evasion is important in cancer proliferation, metastasis and response to treatment, it is unclear whether intrinsic immune-evasion patterns of gliomas can aid in predicting clinical prognosis and determining treatment. METHODS: A total of 182 immune-evasion genes intrinsic to cancer were subjected to consensus clustering to identify immune-evasion patterns in 1421 patients with lower-grade glioma (LGG). The levels of each cancer hallmark were determined by the Gene Set Variant Analysis (GSVA) method, and immune cell infiltrations were quantified using two algorithms, the single-sample Gene Set Enrichment Analysis (ssGSEA) and the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methods. IEVscore was determined by a method that combined univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression and principal component analysis (PCA). RESULTS: Transcriptional and genomic analysis showed that most immune evasion genes (IEVGs) were upregulated in LGGs, with aberrant expression driven by alterations in copy number variants (CNV). Based on the mRNA expression profiles of cancer-intrinsic IEVGs could be divided into three LGG subgroups with distinct prognosis, clinicopathological features and immune infiltrations. A combined scoring scheme designed to assess the immune-evasion levels of LGGs divided these 1421 patients into two subgroups that differed in IEVscores. LGG patients with low-IEVscore had a better prognosis, would be more likely to benefit from immune check-point inhibitors and would be more susceptible to temozolomide (TMZ) chemotherapy. CONCLUSION: Intrinsic immune evasion in the tumor microenvironment (TME) has a crucial effect on glioma formation. Quantitatively assessing the IEV scores of individual LGG patients could enhance knowledge about the intra-glioma microenvironment and lead to the development of individualized therapeutic strategies for patients with LGG.


Asunto(s)
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/patología , Humanos , Evasión Inmune/genética , Factores Inmunológicos , Inmunoterapia , Temozolomida/uso terapéutico , Microambiente Tumoral
17.
J Immunol ; 205(8): 2137-2145, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32929042

RESUMEN

IgG subclass diversification is common in placental mammals. It has been well documented in humans and mice that different IgG subclasses, with diversified functions, synergistically regulate humoral immunity. However, our knowledge on the genomic and functional diversification of IgG subclasses in the pig, a mammalian species with high agricultural and biomedical importance, is incomplete. Using bacterial artificial chromosome sequencing and newly assembled genomes generated by the PacBio sequencing approach, we characterized and mapped the IgH C region gene locus in three indigenous Chinese breeds (Erhualian, Xiang, and Luchuan) and compared them to that of Duroc. Our data revealed that IGHG genes in Chinese pigs differ from the Duroc, whereas the IGHM, IGHD, IGHA, and IGHE genes were all single copy and highly conserved in the pig breeds examined. Most striking were differences in numbers of IGHG genes: there are seven genes in Erhualian pigs, six in the Duroc, but only five in Xiang pigs. Phylogenetic analysis suggested that all reported porcine IGHG genes could be classified into nine subclasses: IGHG1, IGHG2a, IGHG2b, IGHG2c, IGHG3, IGHG4, IGHG5a, IGHG5b, and IGHG5c. Using sequence information, we developed a mouse mAb specific for IgG3. This study offers a starting point to investigate the structure-function relationship of IgG subclasses in pigs.


Asunto(s)
Cruzamiento , Sitios Genéticos , Cadenas Pesadas de Inmunoglobulina/genética , Filogenia , Animales , Cadenas Pesadas de Inmunoglobulina/inmunología , Porcinos
18.
Plant Dis ; 2022 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-35939754

RESUMEN

Sansevieria trifasciata var. laurentii (De Wild.) N.E. Brown, commonly known as variegated snake plant or variegated mother-in-law's tongue, is a popular landscape and house plant. In September and October 2019, the obvious leaf spot symptoms were observed on the plants in a 0.2 hm2 of nursery in Qingdao city of China with incidence of 55%. The disease usually starts from the tip or edge of the leaf, initially have slightly water-soaked semi-circular or round brown lesions, which gradually expanded and coalesced into irregular shapes about 3-8 cm in diameter. Grayish brown sunken spots with dark margins that evolve into concentric rings of acervuli which were characteristic of anthracnose, and orange sticky conidial masses were observed under the moist condition. The leaves with typical anthracnose symptoms were collected and deposited in the herbarium of Qingdao agricultural university under accessions no. QDHB074-QDHB087. Subsequently 20 isolates with the same colony and morphological characteristics were obtained from ten diseased leaves by placing surface-sterilized tissue pieces with typical spots on potato dextrose agar (PDA). Colonies are floccose with grayish-white to dark olivaceous gray color, and gray black on the reverse after 14 days at 28°C. Straight conidia [15.0 to 27.5 × 3.5 to 7.0 µm in size (average 18.2 × 6.1 µm) (n = 50)] were cylindrical, aseptate, hyaline, slippery surface, most with one tapering end and the other oval. Setae were black, 185-230 µm in length, with a thin tip and septate in the middle. Appressoria [6.5 to 7.3 × 7.8 to 9.2 µm in size (average 6.8 × 8.1 µm) (n = 15)] were black to dark brown, solitary, spherical with smooth wall. The fungal isolates were identified as Colletotrichum sansevieriae Nakamura (Nakamura et al. 2006), based on the morphological characteristics. To confirm the identification, the internal transcribed spacer (ITS) and calmodulin (CAL) regions of a representative isolate HWL-1016 were amplified by primers ITS1/ITS4 (White et al. 1990) and CMD5/CMD6 (Weir et al. 2012), respectively. The 549 bp ITS (MN922517) and 597 bp CAL (OM994078) sequences had respectively 100% and 99.30% identity with the sequences from holotype species of C. sansevieriae MAFF 239721 (no. NR_152313 and LC180125). Phylogenetic tree based on ITS and CAL sequences respectively or jointly constructed by PAUP4.0 (Swofford 2002) revealed that the fungus in this study clustered with C. sansevieriae isolates (NR_152313, KC790947, HQ433226, JF911349, MN386823). Pathogenicity test of isolate HWL1016 was evaluated on five 3- to 4-month-old potted S. trifasciata var. laurentii under greenhouse conditions (27±2 °C, 16-hr light/8-hr dark photoperiod, 80% relative humidity). Conidial suspension (1×106 conidia/mL) of the isolated fungus from PDA colonies cultured for 15 days and sterile distilled water (as control) were sprayed on pin-pricked surface-sterilized (70% alcohol) leaves of potted plants, respectively. Three replications (three plants) were done for each treatment, and the experiment was repeated twice. The inoculated plants were covered with plastic films for 2 days and obvious water-soaked wounds were observed on the sixth day. After 16 days, the symptoms of the inoculated plants were similar to those in the nursery, with disease incidence reached 100%, while controls remained symptomless. C. sansevieriae was subsequently reisolated from the symptomatic tissues. Anthracnose on S. trifasciata var. laurentii caused by C. sansevieriae has been reported in Australia, Iran, Japan, Malaysia (Kee et al. 2020), South Korea, USA (Talhinhas & Baroncelli 2021), India (Gautam et al. 2012) and Thailand (Li et al. 2020). To our knowledge, this is the first report of C. sansevieriae causing anthracnose on S. trifasciata var. laurentii in China. This study will contribute to guide effective management based on pathogen.

19.
Chem Soc Rev ; 50(22): 12551-12575, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34604889

RESUMEN

Nucleic acids, with the advantages of programmability and biocompatibility, have been widely used to design different kinds of novel biocomputing devices. Recently, nucleic acid-based molecular computing has shown promise in making the leap from the test tube to the cell. Such molecular computing can perform logic analysis within the confines of the cellular milieu with programmable modulation of biological functions at the molecular level. In this review, we summarize the development of nucleic acid-based biocomputing devices that are rationally designed and chemically synthesized, highlighting the ability of nucleic acid-based molecular computing to achieve cellular applications in sensing, imaging, biomedicine, and bioengineering. Then we discuss the future challenges and opportunities for cellular and in vivo applications. We expect this review to inspire innovative work on constructing nucleic acid-based biocomputing to achieve the goal of precisely rewiring, even reconstructing cellular signal networks in a prescribed way.


Asunto(s)
Computadores Moleculares , Ácidos Nucleicos , Bioingeniería , ADN , Lógica
20.
Angew Chem Int Ed Engl ; 61(11): e202113795, 2022 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-34990055

RESUMEN

Systematic interrogation of correlative signaling components in their native environment is of great interest for dissecting sophisticated cellular signaling. However, it remains a challenge because of the lack of versatile and effective approaches. Herein, we propose a cell membrane-anchored DNA multitasking processor acting as a "traffic light" for integrated analyses of cellular signal transduction. Enhanced and controllable inhibition of c-Met signaling was achieved by membrane-anchoring of DNA processors. Moreover, the multitasking capability of the DNA processor allowed the monitoring of correlative VEGF secretion induced by c-Met activity regulation directly. By exploiting versatile aptameric nucleic acids, this modular designed DNA multitasking processor dissected how cell surface receptors coordinated with related components in live cells systematically. Therefore, it provides a powerful chemical tool for both fundamental cell biology research and precision medicine applications.


Asunto(s)
Membrana Celular/metabolismo , ADN/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Línea Celular Tumoral , Membrana Celular/química , ADN/química , Humanos , Proteínas Proto-Oncogénicas c-met/química , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/química
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