RESUMO
The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.
Assuntos
Berberina , Quadruplex G , Berberina/química , Berberina/análogos & derivados , Berberina/farmacologia , Humanos , DNA/química , Ácidos Nucleicos Peptídicos/químicaRESUMO
Semiconductive metal-organic frameworks (MOFs) with donor-acceptor (D-A) characteristics have garnered attractive attention due to their capacity for separating and transferring photogenerated charges, making them promising candidates for high-performance X-ray detectors. However, the low charge transfer efficiency between the metal nodes and organic ligands limits the X-ray-to-electricity conversion efficiency of these materials. Herein, an additional photoactive donor (D') is introduced by incorporating a heavy atom-containing polyoxometalate (POM) [α-SiW12O40]4- into a binary {[Ni·bcbp·(H2O)2]·(H2O)4·Cl}n (Ni-bcbp, bcbp: H2bcbp·2Cl = 1,1'-bis(4-carboxyphenyl)(4,4'-bipyridinium) dichloride) MOF, resulting in a semiconductive ternary D-D'-A framework {[Ni2(bcbp)2·(H2O)4·(DMA)]·(SiW12O40)}n (SiW@Ni-bcbp, DMA: dimethylacetamide). The obtained material features an unprecedented porous 8-connected bcu-net structure that accommodates nanoscale [α-SiW12O40]4- counterions, displaying uncommon optoelectronic responses. In contrast to binary Ni-bcbp, the SiW@Ni-bcbp framework exhibits distinctive photochromism and robust X-ray responsiveness, which can be attributed to the synergistic effects of the electron reservoir and multiple photoinduced electron transfer originating from the POMs. As a result, the X-ray detector based on SiW@Ni-bcbp demonstrates a sensitivity of 5741.6 µC Gyair -1 cm-2 with a low detection limit of 0.49 µGyair s-1. Moreover, the devices demonstrated the capability of producing clearness X-ray images, providing a feasible and stable solution for constructing high-performance direct X-ray detectors.
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Synaptic devices that mimic biological synapses are considered as promising candidates for brain-inspired devices, offering the functionalities in neuromorphic computing. However, modulation of emerging optoelectronic synaptic devices has rarely been reported. Herein, a semiconductive ternary hybrid heterostructure is prepared with a D-D'-A configuration by introducing polyoxometalate (POM) as an additional electroactive donor (D') into a metalloviologen-based D-A framework. The obtained material features an unprecedented porous 8-connected bcu-net that accommodates nanoscale [α-SiW12 O40 ]4- counterions, displaying uncommon optoelectronic responses. Besides, the fabricated synaptic device based on this material can achieve dual-modulation of synaptic plasticity due to the synergetic effect of electron reservoir POM and photoinduced electron transfer. And it can successfully simulate learning and memory processes similar to those in biological systems. The result provides a facile and effective strategy to customize multi-modality artificial synapses in the field of crystal engineering, which opens a new direction for developing high-performance neuromorphic devices.
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DNA double-strand break (DSB) is the most dangerous type of DNA damage. In addition, DSBs are also common consequences of various therapeutic and genetic modifications. Therefore, quantification of DSB is of great importance in many fields including DNA damage repair, cancer therapy, gene editing, and radiation biology. Current methods are either low-throughput, laborious, or high cost. Here, we developed dc-BLIS (digital counting of breaks labeling in situ), a new method that can rapidly and precisely quantify the number of intracellular DSBs at a low cost by digital polymerase chain reaction. Using dc-BLIS, we quantified and compared the amount of DSBs induced by anti-cancer drugs, Cas9 variants, and different radiation doses, proving the capacity of dc-BLIS to quantify DSBs. We propose that dc-BLIS is suitable for various application scenes that require rapid and precise quantification of DSBs, including drug screening, gene-editing tool modification, and radiation effect assessment.
Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Dano ao DNA , Reação em Cadeia da Polimerase , DNA/genéticaRESUMO
Just as the heterojunctions in physics, donor-acceptor (D-A) heterostructures are an emerging class of photoactive materials fabricated from two semiconductive components at the molecular level. Among them, D-A hybrid heterostructures from organic and inorganic semiconductive components have attracted extensive attention in the past decades due to their combined advantages of high stability for the inorganic semiconductors and modifiability for the organic semiconductors, which are particularly beneficial to efficiently achieve photoinduced charge separation and transfer upon irradiations. In this review, by analogy with the heterojunctions in physics, a definition of the D-A heterostructures and their general design and synthetic strategies are given. Meanwhile, the D-A hybrid heterostructures are focused on and their recent advances in potential applications of photochromism, photomodulated luminescence, and photocatalysis summarized.
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To evaluate the efficacy and safety of thermal ablation (radiofrequency, microwave, and laser) for treating lymph node metastasis from papillary thyroid carcinoma. A literature search was performed in the Medline, Embase, and Cochrane Library databases. Thirteen studies focusing on the efficacy and safety of thermal ablation for treating lymph node metastasis were eligible. The assessed outcomes were primarily pooled using a random- or fixed-effects model based on the results of the heterogeneity test. A total of 235 patients with 445 metastatic lymph nodes were included. Laser, microwave, and radiofrequency ablation all showed a significant reduction in maximum diameter and volume of metastatic lymph nodes (P < 0.0001). Microwave ablation had a higher volume reduction rate (99%; 95% CI, 98-100%) comparing to the other two techniques (P = 0.0057). For all ablations, the pooled completely disappear rate was 70% (95% CI, 45-87%) and the recurrent rate was 3% (95% CI, 2-5%). Thyroglobulin levels significantly decreased (P < 0.0001). No major complications were encountered; the pooled proportion of voice change was low to 4% (95% CI, 2-7%). Thermal ablation is acceptable treatments to manage lymph nodes metastasis from papillary thyroid carcinoma in terms of efficacy and safety for non-surgical candidates.
Assuntos
Neoplasias da Glândula Tireoide , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Estrogen, the predominant sex hormone, has been found to be related to the occurrence of vaginal infectious diseases. However, its role in the occurrence and development of bacterial vaginitis caused by Escherichia coli is still unclear. The objective of this study was to investigate the role of 17ß-estrogen in E. coli adhesion on human vaginal epithelial cells. The vaginal epithelial cell line VK2/E6E7 was used to study the molecular events induced by estrogen between E. coli and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation with cell adhesion. The phosphorylation status of FAK and estrogen receptor α (ERα) upon estrogen challenge was assessed by Western blotting. Specific inhibitors for ERα were used to validate the involvement of ERα-FAK signaling cascade. The results showed that, following stimulation with 1,000 nM estrogen for 48 h, transient activation of ERα and FAK was observed, as was an increased average number of E. coli cells adhering to vaginal epithelial cells. In addition, estrogen-induced activation of ERα and FAK was inhibited by the specific inhibitor of ERα, especially when the inhibitor reached a 10 µM concentration and acted for 1 h, and a decrease in the number of adherent E. coli cells was observed simultaneously. However, this inhibitory effect diminished as the concentration of estrogen increased. In conclusion, FAK and ERα signaling cascades were associated with the increasing E. coli adherence to vaginal epithelial cells, which was promoted by a certain concentration of estrogen.
Assuntos
Aderência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Estradiol/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/fisiologia , Vagina/microbiologia , Células Cultivadas , Células Epiteliais/microbiologia , Escherichia coli/fisiologia , Receptor alfa de Estrogênio/fisiologia , Feminino , Fulvestranto/farmacologia , Humanos , FosforilaçãoRESUMO
Protein phosphorylation and dephosphorylation have been reported to play important roles in plant cold responses. In addition, phospho-regulatory feedback is a conserved mechanism for biological processes and stress responses in animals and plants. However, it is less well known that a regulatory feedback loop is formed by the protein kinase and the protein phosphatase in plant responses to cold stress. Here, we report that OPEN STOMATA 1 (OST1) and PROTEIN PHOSPHATASE 2C G GROUP 1 (PP2CG1) reciprocally regulate the activity during the cold stress response. The interaction of PP2CG1 and OST1 is inhibited by cold stress, which results in the release of OST1 at the cytoplasm and nucleus from suppression by PP2CG1. Interestingly, cold-activated OST1 phosphorylates PP2CG1 to suppress its phosphatase activity, thereby amplifying cold signaling in plants. Mutations of PP2CG1 and its homolog PP2CG2 enhance freezing tolerance, whereas overexpression of PP2CG1 decreases freezing tolerance. Moreover, PP2CG1 negatively regulates protein levels of C-REPEAT BINDING FACTORs (CBFs) under cold stress. Our results uncover a phosphor/dephosphor-regulatory feedback loop mediated by PP2CG1 phosphatase and OST1 protein kinase in plant cold responses.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Temperatura Baixa , Proteínas Quinases/metabolismo , Proteína Fosfatase 2C/metabolismo , Adaptação Fisiológica , Sequência de Aminoácidos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Resposta ao Choque Frio , Epistasia Genética , Congelamento , Modelos Biológicos , Fosforilação , Ligação Proteica , Proteína Fosfatase 2C/genética , Estabilidade ProteicaRESUMO
Salmon calcitonin (sCT) is a potent calcium-regulating peptide hormone and widely applied for the treatment of some bone diseases clinically. However, the therapeutic usefulness of sCT is hindered by the frequent injection required, owing to its short plasma half-life and therapeutic need for a high dose. Oral delivery is a popular modality of administration for patients because of its convenience to self-administration and high patient compliance, while orally administered sCT remains a great challenge currently due to the existence of multiple barriers in the gastrointestinal (GI) tract. Here, we introduced an orally targeted delivery system to increase the transport of sCT across the intestine through both the paracellular permeation route and the bile acid pathway. In this system, sCT-based glycol chitosan-taurocholic acid conjugate (GC-T)/dextran sulfate (DS) ternary nanocomplexes (NC-T) were produced by a flash nanocomplexation (FNC) process in a kinetically controlled mode. The optimized NC-T exhibited well-controlled properties with a uniform and sub-60 nm hydrodynamic diameter, high batch-to-batch reproducibility, good physical or chemical stability, as well as sustained drug release behaviors. The studies revealed that NC-T could effectively improve the intestinal uptake and permeability, owing to its surface functionalization with the taurocholic acid ligand. In the rat model, orally administered NC-T showed an obvious hypocalcemia effect and a relative oral bioavailability of 10.9%. An in vivo assay also demonstrated that NC-T induced no observable side effect after long-term oral administration. As a result, the orally targeted nanocomplex might be a promising candidate for improving the oral transport of therapeutic peptides.
Assuntos
Calcitonina/administração & dosagem , Hormônios e Agentes Reguladores de Cálcio/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Absorção Intestinal/efeitos dos fármacos , Nanocompostos/química , Administração Oral , Animais , Disponibilidade Biológica , Transporte Biológico , Células CACO-2/efeitos dos fármacos , Células CACO-2/metabolismo , Calcitonina/efeitos adversos , Calcitonina/sangue , Calcitonina/farmacocinética , Cálcio/sangue , Hormônios e Agentes Reguladores de Cálcio/efeitos adversos , Hormônios e Agentes Reguladores de Cálcio/sangue , Hormônios e Agentes Reguladores de Cálcio/farmacocinética , Quitosana/química , Sulfato de Dextrana/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Meia-Vida , Humanos , Hipocalcemia/induzido quimicamente , Injeções Subcutâneas , Masculino , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico/químicaRESUMO
OBJECTIVES: To assess the diagnostic yields of elastography in thyroid nodules reported as indeterminate in FNAC according to guidelines. METHODS: Databases of Medline, Embase, and Cochrane Central were searched till 31 October 2019. Two different reviewers check the studies and extracted the data. The diagnostic accuracy and yield were quantitatively synthesized using Bayesian bivariate model in R. RESULTS: Twenty studies with 1734 indeterminate thyroid nodules undergoing elastography were included. The summary estimates of sensitivity and specificity were 0.766 (95% credible interval (CrI), 0.686-0.835) and 0.867 (95% CrI, 0.780-0.931), respectively. The summary estimate for diagnostic odds ratio (DOR) was 25.9 (95% CrI, 12.8-46.2). Summary receiver operating characteristic plots for elastography showed a right-diagonal curvilinear relationship, suggesting a trade-off between sensitivity and specificity, and the estimate of area under curve (AUC) was 0.743. The summary estimates for positive and negative likelihood ratios were 6.6 (95% CrI, 4.2-11.3) and 0.27 (95% CrI, 0.21-0.36), respectively. CONCLUSIONS: Elastography had fair diagnostic yields in indeterminate thyroid nodules. Shear wave elastography and strain ratio elastography could be more efficient in diagnosis and should evolve in the next years while combing elastography with ultrasound would contribute more to sensitivity and specificity currently. KEY POINTS: ⢠Elastography has fair diagnostic yields in indeterminate thyroid nodules. ⢠Shear wave elastography and strain ratio elastography are more efficient than real-time elastography. ⢠Combining elastography and other ultrasound techniques improves evaluation of indeterminate thyroid nodules.
Assuntos
Técnicas de Imagem por Elasticidade , Nódulo da Glândula Tireoide , Teorema de Bayes , Biópsia por Agulha Fina , Diagnóstico Diferencial , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
To study the effects of mir-27b on angiogenesis and fibroblast activation and to explore its further mechanism. Humanmicrovascular endothelial cell (HMEC)-1 and humannormal skin fibroblast (BJ) cells were treated with mir-27b inhibitor negative control reagent, mir-27b inhibitor, LY294002, and mir-27b inhibitor + LY294002, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to detect the T-cell proliferation. The migration ability was detected by Scratch assays. The angiogenesis of HMEC-1 cells was observed by in vitro tube formation assay. The mRNA and protein expression of vascular endothelial growth factor (VEGF) in HMEC-1 cells and the mRNA and protein expression of collagen I, collagen III, α-SMA, and MMP1 in BJ cells were detected by quantitativereal-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Meanwhile, the PI3K/protein kinase B (AKT) pathway-related proteins were also detected by Western blot. The proliferation, migration, angiogenesis, the mRNA and protein expression of VEGF and the protein expression of p-PI3K and p-AKT in HMEC-1 cells were increased after treated with mir-27b inhibitor. Meanwhile, the proliferation, migration, and the protein expression of collagen I, collagen III, α-SMA, MMP1, p-PI3K, and p-AKT in BJ cells were increased after treated with mir-27b inhibitor. However, the angiogenesis and fibroblast activation of mir-27b inhibitor was reversed by LY294002, and the activate effect to PI3K/AKT pathway was also inhibited. Down-regulation of mir-27b could promote angiogenesis and fibroblast activation, and its mechanism is related to activate PI3K/AKT signaling pathway.
Assuntos
Proliferação de Células/genética , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Neovascularização Fisiológica/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Actinas/efeitos dos fármacos , Actinas/genética , Actinas/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Colágeno Tipo I/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/efeitos dos fármacos , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Regulação para Baixo , Células Endoteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Morfolinas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Transdução de Sinais , Pele/citologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , CicatrizaçãoRESUMO
This experiment was carried out to observe and analyze the effect of floium ginkgo extract and tertram ethypyrazine sodium chloride injection in patients with cerebral infarction. A total of 200 patients diagnosed with cerebral infarction were enrolled in the study. They were randomly divided into a research group and control group, each containing 100 patients. The control group was given routine treatment measures while the research group was given floium ginkgo extract and tertram ethypyrazine sodium chloride injection on the basis of routine treatment. The therapeutic effects of the two groups were observed and compared. After implementing different treatment schemes, the levels of MMP-9, SOD, CBV and CBF in the research group were significantly higher than those in the control group, p<0.05. The research group was lower in hs-CRP, MDA, MTT, TTP and TNF-α as compared with the control group, p<0.05. In terms of the quality of life of the two groups after six months of treatment, the scores of various indicators in the research group were all significantly superior, p<0.05. Conclusion: The treatment of cerebral infarction patients with floium ginkgo extract and tertram ethypyrazine sodium chloride injection can significantly improve the therapeutic effect, which is a relatively ideal treatment.
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Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/metabolismo , Citocinas/metabolismo , Ginkgo biloba/química , Extratos Vegetais/uso terapêutico , Pirazinas/farmacologia , Cloreto de Sódio/farmacologia , Idoso , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Proteínas/metabolismoRESUMO
In this study, the effects of miR-27b on angiogenesis in skin repair procedure in rats with deep II degree scald were explored. The rat model of deep II scald was established. miR-27b mimics and inhibitor were injected daily at the wound site for 3 weeks. The healing of scald was observed at 0, 3, 7, 14, and 21 days after the model was established, and the pathological changes of skin were observed by HE and Masson's trichrome stains. Skin tissues were taken 14 days after the operation; CD31 and Ki-67 immunohistochemistry was exerted to evaluate neovascularization and proliferation. Human microvascular endothelial cells (HMEC-1) cells were cultured in vitro. miR-27b mimics or inhibitor was transfected to construct over-expression or inhibition cell lines. MTT assay, scratch test, and angiogenesis test were used to evaluate cell proliferation, migration, and vascular regeneration. Finally, RT-PCR and Western blot were exerted to determine the expression of vascular endothelial growth factor C (VEGF-C), epidermal growth factor (EGF) mRNAs, and protein, respectively. Control, inhibitor, mi-NC, VEGF-C, inhibitor + si-NC, and inhibitor + VEGF-C siRNA groups were used to further analyze the mechanism of miR-27b on VEGF-C; the above experiments were repeated. In contrast to model group, miR-27b inhibitor could significantly promote the healing of scalded skin, alleviate the pathological status of scalded, and promote the angiogenesis and proliferation (p < 0.05). In vitro, miR-27b inhibitor evidently promoted cell proliferation, migration, and angiogenesis and increased the expression of VEGF-C, EGF genes, and protein, while miR-27b mimics significantly reversed the above trends. Further studies shown that downregulation of miR-27b expression can promote the proliferation, migration, and angiogenesis of HMEC-1 cells by promoting the expression of VEGF-C. miR-27b promotes angiogenesis and skin repair in scalded rats through regulating VEGF-C expression.
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Queimaduras/genética , Queimaduras/patologia , Regulação da Expressão Gênica , MicroRNAs/metabolismo , Neovascularização Fisiológica/genética , Pele/patologia , Fator C de Crescimento do Endotélio Vascular/genética , Cicatrização , Animais , Sequência de Bases , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Células Endoteliais/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Masculino , MicroRNAs/genética , Microvasos/patologia , Ratos Sprague-Dawley , Fator C de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/genéticaRESUMO
Plant responses to low temperature are tightly associated with defense responses. We previously characterized the chilling-sensitive mutant chs3-1 resulting from the activation of the Toll and interleukin 1 receptor-nucleotide binding-leucine-rich repeat (TIR-NB-LRR)-type resistance (R) protein harboring a C-terminal LIM (Lin-11, Isl-1 and Mec-3 domains) domain. Here we report the identification of a suppressor of chs3, ibr5-7 (indole-3-butyric acid response 5), which largely suppresses chilling-activated defense responses. IBR5 encodes a putative dual-specificity protein phosphatase. The accumulation of CHS3 protein at chilling temperatures is inhibited by the IBR5 mutation. Moreover, chs3-conferred defense phenotypes were synergistically suppressed by mutations in HSP90 and IBR5. Further analysis showed that IBR5, with holdase activity, physically associates with CHS3, HSP90 and SGT1b (Suppressor of the G2 allele of skp1) to form a complex that protects CHS3. In addition to the positive role of IBR5 in regulating CHS3, IBR5 is also involved in defense responses mediated by R genes, including SNC1 (Suppressor of npr1-1, Constitutive 1), RPS4 (Resistance to P. syringae 4) and RPM1 (Resistance to Pseudomonas syringae pv. maculicola 1). Thus, the results of the present study reveal a role for IBR5 in the regulation of multiple R protein-mediated defense responses.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Quitina Sintase/genética , Resistência à Doença/genética , Fosfatases de Especificidade Dupla/genética , Doenças das Plantas/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ciclo Celular/genética , Temperatura Baixa , Fosfatases de Especificidade Dupla/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Choque Térmico HSP90/genética , Mutação , Doenças das Plantas/microbiologia , Proteínas de Plantas/genéticaRESUMO
Cold temperatures, a major abiotic stress, threaten the growth and development of plants, worldwide. To cope with this adverse environmental cue, plants from temperate climates have evolved an array of sophisticated mechanisms to acclimate to cold periods, increasing their ability to tolerate freezing stress. Over the last decade, significant progress has been made in determining the molecular mechanisms underpinning cold acclimation, including following the identification of several pivotal components, including candidates for cold sensors, protein kinases, and transcription factors. With these developments, we have a better understanding of the CBF-dependent cold-signaling pathway. In this review, we summarize recent progress made in elucidating the cold-signaling pathways, especially the C-repeat binding factor-dependent pathway, and describe the regulatory function of the crucial components of plant cold signaling. We also discuss the unsolved questions that should be the focus of future work.
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Proteínas de Plantas/metabolismo , Plantas/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/genética , Plantas/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
Dielectric switches that can be converted between high and low dielectric states by thermal stimuli have attracted much interest owing to their many potential applications. Currently one main drawback for practical application lies in the non-tunability of their switch temperatures (TS ). We report here an ionic co-crystal (Me3 NH)4 [Ni(NCS)6 ] that contains a multiply rotatable Me3 NH+ ion and a solely rotatable one due to a more spacious supramolecular cage for the former one. This compound undergoes an isostructural order-disorder phase transition and it can function as a frequency-tuned dielectric switch with highly adjustable TS , which is further revealed by the variable-temperature structure analyses and molecular dynamics simulations. In addition, the distinct arrangements and molecular dynamics of two coexisting Me3 NH+ ions confined in different lattice spaces as well as the notable offset effect on the promoting/hindering of dipolar reorientation after dielectric transition provide a rarely observed but fairly good model for understanding and modulating the dipole motion in crystalline environment.
RESUMO
Toll/interleukin receptor (TIR)-nucleotide binding site (NB)-type (TN) proteins are encoded by a family of 21 genes in the Arabidopsis genome. Previous studies have shown that a mutation in the TN gene CHS1 activates the activation of defense responses at low temperatures. However, the underlying molecular mechanism remains unknown. To genetically dissect chs1-mediated signaling, we isolated genetic suppressors of chs1-2 (soc). Several independent soc mutants carried mutations in the same TIR-NB-leucine-rich repeat (LRR) (TNL)-encoding gene SOC3, which is adjacent to CHS1 on chromosome 1. Expression of SOC3 was upregulated in the chs1-2 mutant. Mutations in six soc3 alleles and downregulation of SOC3 by an artificial microRNA construct fully rescued the chilling sensitivity and defense defects of chs1-2. Biochemical studies showed that CHS1 interacted with the NB and LRR domains of SOC3; however, mutated chs1 interacted with the TIR, NB and LRR domains of SOC3 in vitro and in vivo. This study reveals that the TN protein CHS1 interacts with the TNL protein SOC3 to modulate temperature-dependent autoimmunity.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Arabidopsis/imunologia , Autoimunidade , Genes de Plantas , Receptores Imunológicos/metabolismo , Temperatura , Sequência de Aminoácidos , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Sequência de Bases , Clonagem Molecular , Regulação para Baixo/genética , Mutação com Ganho de Função/genética , Regulação da Expressão Gênica de Plantas , Genes Supressores , Mutação com Perda de Função/genética , Modelos Biológicos , Fenótipo , Ligação Proteica , Receptores Imunológicos/química , Frações Subcelulares/metabolismo , Supressão GenéticaRESUMO
BACKGROUND: There has been a growing need for a non-invasive imaging method for the accurate diagnosis and differentiation of endometrial malignancy (EM). PURPOSE: To study tissue characteristics of EM using an intravoxel incoherent motion (IVIM) model and to assess their diagnostic potential. MATERIAL AND METHODS: Sixty-eight EMs and 31 healthy participants were prospectively recruited for diffusion-weighted (13 b-values, b = 0-3,000 s/mm(2)) and standard magnetic resonance imaging (MRI). A bi-exponential analysis was performed to derive f (perfusion fraction), D* (pseudodiffusion coefficient), and D (true diffusion coefficient) in EM and normal endometrium (NE). Apparent diffusion coefficient (ADC) was calculated. Student's t test, the Mann-Whitney U test and a receiver operating characteristics (ROC) curve analysis were performed. RESULTS: EM had lower f (37.809 ± 12.158%) and was significantly different from NE (P < 0.001). However, the EMs had higher D (0.503 ± 0.155 × 10(-3) mm(2)/s) and D* (19.796 ± 20.029 × 10(-3) mm(2)/s) and were all significantly different from NE (P < 0.001). D was significantly lower than ADC in NE (P < 0.001) but not in EM (P > 0.05). f ≤ 48.5%, D > 0.432 × 10(-3) mm(2)/s, D* > 4.94 × 10(-3) mm(2)/s, and ADC ≤ 0.542 × 10(-3) mm(2)/s could diagnose EM (AUC 0.786-0.961). CONCLUSION: EM has distinctive IVIM perfusion and diffusion characteristics with promising potential for earlier non-invasive diagnosis.
Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias do Endométrio/patologia , Feminino , Humanos , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Neonatal lactose intolerance syndrome is a series of digestive system symptoms caused by the lack of lactase, and could not fully digest the lactose in breast milk or cow milk. Lactose is one of the disaccharides mainly existed in mammalian milk. Lactose content in breast milk is 7.2g/100ml, cow milk is 4.7g/100ml. Dairy products are the main energy sources for the newborn, and lactose provides 20% energy for infants. During the growth of the newborn, lactose not only play a significant role in energy supply, but also involve in the development of the brain growing. This study mainly studied the lactose development features, the reasons for lactose intolerance, and the measures to treat lactose deficiency.
Assuntos
Diarreia/terapia , Intolerância à Lactose/terapia , Leite , Animais , Diarreia/dietoterapia , Diarreia/etiologia , Humanos , Recém-Nascido , Intolerância à Lactose/complicações , Intolerância à Lactose/dietoterapia , PósRESUMO
To study the clinical practice of procalcitonin and hypersensitive c-reactive protein test in neonatal infection. Two hundred cases of our hospital treatment confirmed infection early newborn children were selected from February 2014 to March 2015. According to the condition, the children were divided into four groups as follows: severe infection group, local infection group, non-infection group and healthy newborns group. At the same time, the new healthy newborns were chosen as control group. The levels of serum procalcitonin and high-sensitivity C-reactive protein were detected in all children and the levels in severe infection group children before and after treatment were also quantitatively detected and the test results were analyzed. There was significant difference in procalcitonin among the four groups (pS<0.05). The positive rate of the high-sensitivity C-reactive protein in local infection group has no significant difference compared with the non-infection group (p>0.05). But there was significant difference between the local infection group and healthy newborn group. As for the severe infection group, both the levels of procalcitonin and positive rate of high-sensitivity C-reactive protein had significant difference compared with the other groups. The detection of procalcitonin and high-sensitivity C-reactive protein could contribute to the diagnose of the early infection neonatal children and has important values in diagnosis and treatment of infectious diseases in the newborns.