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Tobacco alkaloid metabolism is regulated by various transcription factors (TFs). Here, we have characterized a non-NIC2 locus gene, Ethylene Response Factor 91 (ERF91), function in regulation of alkaloid accumulation in tobacco. NtERF91 was preferentially expressed in roots and induced by jasmonic acid. Additionally, NtERF91 was able to in vitro bind to the NtPMT2 and NtQPT2 promoters via directly targeting the GCC-box elements and transactivate NtQPT2 gene expression. Ectopic overexpression of NtERF91 not only increased the expression of most nicotine biosynthetic genes, but also altered alkaloid accumulation profile, resulting in dramatically anatabine accumulation. We conclude that NtERF91 plays an overlapped but distinct role in regulating tobacco alkaloid accumulations.
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Alcaloides/metabolismo , Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Alcaloides/genética , Sequência de Aminoácidos , Ciclopentanos/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Nicotina/genética , Nicotina/metabolismo , Oxilipinas/metabolismo , Filogenia , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Nicotiana/química , Nicotiana/genética , Fatores de Transcrição/química , Fatores de Transcrição/genética , Ativação TranscricionalRESUMO
Bacille Calmette-Guérin (BCG), a live attenuated vaccine prepared using Mycobacterium bovis, can prevent tuberculosis in children and is routinely administered to infants in China and many other countries. A serious complication following vaccination is disseminated BCG infection. The risk is greatly increased in patients with severe combined immunodeficiency disease (SCID), a syndrome characterized by deficiency of both humoral and cellular immunity. We report a case of disseminated BCG infection in an infant with SCID caused by two novel janus kinase 3 (JAK3) gene mutations.
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Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Janus Quinase 3/genética , Mutação/genética , Imunodeficiência Combinada Severa/complicações , Tuberculose/etiologia , Feminino , Humanos , Lactente , Mycobacterium bovis , Imunodeficiência Combinada Severa/genéticaRESUMO
Due to the important role of tourists' behavior plays in marine protected areas (MPAs) and the increasing popularity of ecological experiential learning (EEL) journeys, this study aims to investigate whether and how EEL impact tourists' pro-environmental behavior (PEB) intentions through both emotional and cognitive pathways. To achieve this, four nature education trips with EEL content were organized, and PEB intentions of 228 tourists to MPAs were analyzed using surveys. The findings revealed that the low-effort PEB intentions of individuals under 24 years old were significantly lower compared to those of older tourists. Furthermore, EEL was positively associated with both low and high effort PEB intentions. The sense of awe acted as a mediator between EEL and low-effort PEB intentions, whereas nature connection was found to mediate the relationship between EEL and both low and high-effort PEB intentions. This study contributes to the growing body of research on the drivers of tourists PEB and provides a theoretical framework for promoting PEB intentions in MPAs.''''.
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Nanomaterials with a large chiroptical response and high structural stability are desirable for advanced miniaturized optical and optoelectronic applications. One-dimensional (1D) nanotubes are robust crystals with inherent and continuously tunable chiral geometries. However, their chiroptical response is typically weak and hard to control, due to the diverse structures of the coaxial tubes. Here we demonstrate that as-grown multiwalled boron nitride nanotubes (BNNTs), featuring coherent-stacking structures including near monochirality, homo-handedness and unipolarity among the component tubes, exhibit a scalable nonlinear chiroptical response. This intrinsic architecture produces a strong nonlinear optical response in individual multiwalled BNNTs, enabling second-harmonic generation (SHG) with a conversion efficiency up to 0.01% and output power at the microwatt level-both excellent figures of merit in the 1D nanomaterials family. We further show that the rich chirality of the nanotubes introduces a controllable nonlinear geometric phase, producing a chirality-dependent SHG circular dichroism with values of -0.7 to +0.7. We envision that our 1D chiral platform will enable novel functions in compact nonlinear light sources and modulators.
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Tumors are a major cause of human mortality worldwide, and the rapid development of nanomaterials (NMs) for tumor therapy and drug delivery has provided new treatment methods. However, NMs' high immunogenicity, short circulation time, and low specificity limit their application in tumor therapy. In recent years, bionanomaterials using cell membranes have emerged to overcome the shortcomings of monomeric NMs. Cell membrane-encapsulated NMs extracted from multiple cells not only retain the physicochemical properties of NMs but also inherit the biological functions of the source cells, aiding in drug delivery. The combination of the cell membrane and drug-loading NMs offers an efficient and targeted drug delivery system tailored to the tumor microenvironment. The research and application of this method have been widely carried out in the academic field of tumor diagnosis and treatment. This review presents the recent research progress of cell membrane-coated NMs as drug carriers in tumor therapy, including cell membrane extraction methods, encapsulation strategies, and the applications of cell membrane-encapsulated NMs in tumor therapy. We believe that biomimetic nanomaterials will be a promising and novel anticancer strategy in the future, and their wide application will certainly bring vitality to the field of tumor diagnosis and treatment. The combination of membrane and drug-loading nanomaterials embodies a highly efficient and target drug delivery system tailored to the tumor microenvironment, which broadens a new path of drug delivery for future cancer treatment. Meanwhile, it is also a perfect combination and application of biomedical nanomaterials, which is of great significance.
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Nanoestruturas , Neoplasias , Humanos , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Membrana Celular/patologia , Microambiente TumoralRESUMO
Autophagy, a self-renewal mechanism, can help to maintain the stability of the intracellular environment of organisms. Autophagy can also regulate several cellular functions and is strongly related to the onset and progression of several diseases. Wound healing is a biological process that is coregulated by different types of cells. However, it is troublesome owing to prolonged treatment duration and poor recovery. In recent years, biomaterials have been reported to influence the skin wound healing process by finely regulating autophagy. Biomaterials that regulate autophagy in various cells involved in skin wound healing to regulate the differentiation, proliferation and migration of cells, inflammatory responses, oxidative stress and formation of the extracellular matrix (ECM) have emerged as a key method for improving the tissue regeneration ability of biomaterials. During the inflammatory phase, autophagy enhances the clearance of pathogens from the wound site and leads to macrophage polarization from the M1 to the M2 phenotype, thus preventing enhanced inflammation that can lead to further tissue damage. Autophagy plays important roles in facilitating the formation of extracellular matrix (ECM) during the proliferative phase, removing excess intracellular ROS, and promoting the proliferation and differentiation of endothelial cells, fibroblasts, and keratinocytes. This review summarizes the close association between autophagy and skin wound healing and discusses the role of biomaterial-based autophagy in tissue regeneration. The applications of recent biomaterials designed to target autophagy are highlighted, including polymeric materials, cellular materials, metal nanomaterials, and carbon-based materials. A better understanding of biomaterial-regulated autophagy and skin regeneration and the underlying molecular mechanisms may open new possibilities for promoting skin regeneration. Moreover, this can lay the foundation for the development of more effective therapeutic approaches and novel biomaterials for clinical applications.
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Células Endoteliais , Pele , Cicatrização , Materiais Biocompatíveis/farmacologia , AutofagiaRESUMO
Exposure of human skin to ultraviolet (UV) radiation causes erythema and pigmentation. Guinea pigs are recognized as having pigmentation similar to that of humans, after exposure to UV radiation. Recently, the curative effect of oral treatment of tranexamic acid in skin pigmentation was confirmed by many doctors in China. Our aim was to investigate the effects of tranexamic acid on pigmentation in the skin of guinea pigs exposed to UV irradiation and its possible mechanism. Guinea pigs were exposed to UVB radiation (60 min per day) for 30 days, skin pigmentation was clearly observed after that. 30 days later, tranexamic acid (5 mg/mL) was intradermally injected into the exposed regions every day after radiation to prevent or inhibit the pigmentation process. After 30 days the skin was removed and stained by HMB45 immunohistochemistry and the Masson Fontana-Ponceau method. HMB45 positive expression melanocytes in the basal layer of UV-exposed epidermis showed no significant differences in the regions to which tranexamic acid solutions had been applied compared with the control. But the melanin content was significantly reduced. We concluded that tranexamic acid has no effect on the number of melanocytes, it is likely that it affects the function of melanocytes, to inhibit the melanin expression in order to lighten moth patches.
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Antifibrinolíticos/uso terapêutico , Transtornos da Pigmentação/tratamento farmacológico , Pigmentação da Pele/efeitos da radiação , Ácido Tranexâmico/uso terapêutico , Raios Ultravioleta/efeitos adversos , Animais , Antifibrinolíticos/administração & dosagem , Antígenos de Neoplasias/análise , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Cobaias , Imuno-Histoquímica , Injeções Intradérmicas , Antígenos Específicos de Melanoma , Proteínas de Neoplasias/análise , Transtornos da Pigmentação/etiologia , Transtornos da Pigmentação/patologia , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Pigmentação da Pele/efeitos dos fármacos , Ácido Tranexâmico/administração & dosagem , Resultado do TratamentoRESUMO
Substantial progress had been made in reducing nornicotine accumulation in burley tobacco, as nornicotine is a precursor of the carcinogen N-nitrosonornicotine (NNN). Three members of the CYP82E2 family encoding nicotine N-demethylase (NND) have been reported to be responsible for the majority of nicotine demethylation that forms nornicotine in burley tobacco. We had obtained a nonsense mutant of each NND member in flue-cured tobacco from an ethyl methanesulfonate (EMS)-mutagenized population. In this study, we developed dCAPS markers for each nonsense mutation. Using marker-assisted selection, NND mutants were crossed with each other to generate a triple mutant GP449. In line with previous reports, the triple knockout caused significantly decreased levels of nornicotine and NNN in flue-cured tobacco. With the decreased nornicotine, the nicotine level was expected to accumulate. However, the nicotine level in GP449 was significantly decreased to 72.80% of wild type. Realtime RT-PCR analysis showed that the nicotine reduction was correlated with inhibited expression of nicotine biosynthetic pathway genes. The triple mutant and dCAPS markers can be utilized to develop new flue-cured tobacco varieties with lower levels of nornicotine and NNN.
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Nicotiana/metabolismo , Nicotina/análogos & derivados , Nitrosaminas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Metanossulfonato de Etila/metabolismo , Nicotina/metabolismo , Folhas de Planta/enzimologia , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Interferência de RNA , Nicotiana/enzimologiaRESUMO
OBJECTIVE: To investigate the feasibility of stable transfection of human hypoxia inducible factor-1alpha (HIF-1alpha) gene into fibroblasts cells and the effects of supernatant from the transfected cell culture on hair follicle cells. METHODS: PcDNA-HIF1alpha was stably transfected into fibroblasts cells with lipofectamine 2000. Expression of HIF-1alpha was observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The supernatant was obtained to detect the expression of vascular endothelial growth factor (VEGF) by ELISA. The mRNA expression of basic fibroblast growth factor (bFGF) was detected by RT-PCR. MTT was used to detect the activity of fibroblasts cells and dermal sheath cells added with supernatant. RESULTS: PcDNA-HIF1alpha was successfully transfected into fibroblasts cells. HIF-1alpha could be detected by RT-PCR and Western blot. The expression of VEGF in the supernatant of cells transfected with PcDNA-HIF1alpha was detected. The mRNA expression of bFGF was significantly higher than in the control group (P < 0.01). MTT showed the activity of cells added with supernatant was enhanced (P < 0.05). CONCLUSION: PcDNA-HIF1alpha can stably transfected into fibroblasts cells, and the expressed HIF-1alpha induces the expression of VEGF and bFGF, and the expressed VEGF enhances the activity of cells.
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Fator 2 de Crescimento de Fibroblastos/biossíntese , Folículo Piloso/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Técnicas de Cultura de Células , Fibroblastos/metabolismo , Folículo Piloso/citologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , TransfecçãoRESUMO
In this study, the complete mitochondrial genome of Cryptolestes pusillus (GenBank accession number KT070713) was sequenced by long PCR and primer walking methods. The total length of mitochondrial DNA is 15 502 bp and contains 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a A + T-rich region. The base composition of the genome is A (39.04%), T (37.07%), C (23.4%), and G (14.6%). Except for COI and ATP8 with TCC and ATC as start codon, respectively, the remaining protein-coding genes initiated with the three orthodox start codons. Two complete stop codons (TAA and TAG) and two incomplete stop codons (COIII stop with T and ND5 stop with TA) were used in the protein-coding genes. The A + T-rich region is located between 12s rRNA and tRNA(Ile) with the length of 859 bp. The phylogenetic relationships of Coleoptera species were constructed based on the nucleotide sequences of 13 protein-coding genes of mitogenome using the neighbor-joining method. The molecular-based phylogenetic analysis supported the traditional morphological classification on relationships within Coleoptera species.
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Besouros/genética , Genoma Mitocondrial , Sequência Rica em At , Animais , Códon/genética , Besouros/classificação , Proteínas de Insetos/genética , Filogenia , RNA Ribossômico/genética , RNA de TransferênciaRESUMO
Prostate cancer is one of the leading causes of cancer deaths among men, many miRNAs have been demonstrated to play critical role in the progression of prostate cancer, miR-186 suppresses the progression of many tumors, such as bladder cancer and glioma. Previous study shows miR-186 is downregulated in prostate cancer tissues, and is a good prognosis for prostate cancer patients. In this study, we found miR-186 was downregulated in prostate cancer cells and tissues, overexpression of miR-186 inhibited cell proliferation and tumorigenesis in vitro determined by MTT assay, colony formation assay and soft agar growth assay, whereas knockdown of miR-186 reduced these effects. Cell cycle analysis found miR-186 overexpression arrested cell cycle in G0/G1 phase, and reduced p21 and p27 levels, and enhanced Cyclin D1 and the phosphorylation of Rb levels, suggesting miR-186 blocked G1/S transition. A novel oncogene Golgi phhosphoprotein 3 (GOLPH3) was the target of miR-186, miR-186 bound to the 3'UTR of GOLPH3. Moreover, miR-186 was negatively correlated with GOLPH3 in prostate cancer tissues. In conclusion, our study suggested miR-186 inhibited cell proliferation through targeting oncogene GOLPH3.
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The perifollicular vasculature undergoes hair-cycle dependent expansion and degeneration. Multiple soluble factors derived from dermal papilla cells (DPCs) may act on surrounding blood vessels to influence angiogenesis, growth and differentiation, and thereby regulate cyclic hair growth. The goal of this study was to examine the expression of angiogenin, a potent angiogenic factor, in human DPCs, and to determine its role in hair growth. Reverse transcription polymerase chain reaction (RT-PCR), western blotting, immunofluorescence and ELISA analyzes were used to investigate the expression of angiogenin in human DPCs, while semi-quantitative RT-PCR was used to assess angiogenin mRNA expression in murine skin phased at different stages of the hair cycle. We detected angiogenin expression in DPCs, where it was found to be localized to the cytoplasm. Angiogenin mRNA was expressed in murine skin in a hair-cycle dependent manner, with maximum levels observed at the late anagen. Local injection of angiogenin promoted skin angiogenesis and induced anagen VI. In vitro studies showed that angiogenin significantly enhanced the elongation of hair follicles, and stimulated DPCs and ORS keratinocytes to proliferate. Taken together, these findings show that angiogenin is expressed in human DPCs, where it might contribute to hair growth directly, by stimulating DPCs and ORS keratinocytes to proliferate, or indirectly, by inducing local vascularization.