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1.
J Neurochem ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38705582

RESUMO

Fear overgeneralization is widely accepted as a pathogenic marker of post-traumatic stress disorder (PTSD). Recently, GABAergic interneurons have been regarded as key players in the regulation of fear memory. The role of hippocampal GABAergic interneurons in contextual fear generalization of PTSD remains incompletely understood. In the present study, we established a rat model of PTSD with inescapable foot shocks (IFS) and observed the loss of GABAergic interneuron phenotype in the hippocampal cornu ammonis-1 (CA1) subfield. To determine whether the loss of GABAergic interneuron phenotype was associated with fear generalization in PTSD rats, we used adeno-associated virus (AAV) to reduce the expression of GAD67 in CA1 and observed its effect on fear generalization. The results showed that the reduction of GAD67 in CA1 enhanced contextual fear generalization in rats. We investigated whether the PERK pathway was involved in the GABAergic interneuron injury. Increased expression of p-PERK, CHOP, and Caspase12 in GABAergic interneurons of PTSD rats was observed. Then, we used salubrinal, an endoplasmic reticulum stress inhibitor, to modulate the PERK pathway. The salubrinal treatment significantly protected the GABAergic interneurons and relieved fear generalization in PTSD rats. In addition, the results showed that salubrinal down-regulated the expression of CHOP and Caspase12 in GABAergic interneurons of PTSD rats. In conclusion, this study provided evidence that the loss of GABAergic interneuron phenotype in CA1 may contribute to contextual fear generalization in PTSD. The PERK pathway is involved in the GABAergic interneuron injury of PTSD rats and modulating it can protect GABAergic interneurons and constrain contextual fear generalization.

2.
Hippocampus ; 34(3): 156-165, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38100162

RESUMO

The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67-immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα-immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV-immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN-coated PV-positive interneurons in CA1. The number of PSD95-positive excitatory synaptic puncta on the soma of PNN-free PV-positive interneurons was significantly higher than that of PNN-coated PV-positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell-type-specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV-PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety-like behavior.


Assuntos
Neurônios , Parvalbuminas , Humanos , Ratos , Animais , Parvalbuminas/metabolismo , Matriz Extracelular/metabolismo , Interneurônios/metabolismo , Hipocampo/metabolismo , Ansiedade
3.
Physiol Plant ; 176(2): e14237, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433182

RESUMO

Trehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus-induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose-6-phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W-box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.


Assuntos
Fabaceae , Trealose , Pressão Osmótica , Folhas de Planta/genética , Osmose
4.
Nature ; 554(7690): 77-80, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29342132

RESUMO

The unique properties of organic semiconductors, such as flexibility and lightness, are increasingly important for information displays, lighting and energy generation. But organics suffer from both static and dynamic disorder, and this can lead to variable-range carrier hopping, which results in notoriously poor electrical properties, with low electron and hole mobilities and correspondingly short charge-diffusion lengths of less than a micrometre. Here we demonstrate a photoactive (light-responsive) organic heterostructure comprising a thin fullerene channel sandwiched between an electron-blocking layer and a blended donor:C70 fullerene heterojunction that generates charges by dissociating excitons. Centimetre-scale diffusion of electrons is observed in the fullerene channel, and this can be fitted with a simple electron diffusion model. Our experiments enable the direct measurement of charge diffusivity in organic semiconductors, which is as high as 0.83 ± 0.07 square centimetres per second in a C60 channel at room temperature. The high diffusivity of the fullerene combined with the extraordinarily long charge-recombination time yields diffusion lengths of more than 3.5 centimetres, orders of magnitude larger than expected for an organic system.

5.
J Xray Sci Technol ; 32(2): 285-301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38217630

RESUMO

Diabetic retinopathy (DR) is one of the leading causes of blindness. However, because the data distribution of classes is not always balanced, it is challenging for automated early DR detection using deep learning techniques. In this paper, we propose an adaptive weighted ensemble learning method for DR detection based on optical coherence tomography (OCT) images. Specifically, we develop an ensemble learning model based on three advanced deep learning models for higher performance. To better utilize the cues implied in these base models, a novel decision fusion scheme is proposed based on the Bayesian theory in terms of the key evaluation indicators, to dynamically adjust the weighting distribution of base models to alleviate the negative effects potentially caused by the problem of unbalanced data size. Extensive experiments are performed on two public datasets to verify the effectiveness of the proposed method. A quadratic weighted kappa of 0.8487 and an accuracy of 0.9343 on the DRAC2022 dataset, and a quadratic weighted kappa of 0.9007 and an accuracy of 0.8956 on the APTOS2019 dataset are obtained, respectively. The results demonstrate that our method has the ability to enhance the ovearall performance of DR detection on OCT images.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Teorema de Bayes , Tomografia de Coerência Óptica/métodos , Aprendizado de Máquina
6.
Mol Cell ; 59(2): 309-20, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-26166706

RESUMO

Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species.


Assuntos
Adenosina Difosfato Ribose/metabolismo , Proteínas de Bactérias/classificação , Sirtuínas/classificação , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Domínio Catalítico , Cristalografia por Raios X , Genes Bacterianos , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Lactobacillales/enzimologia , Lactobacillales/genética , Lipoilação , Modelos Moleculares , Óperon , Estresse Oxidativo , Filogenia , Conformação Proteica , Sirtuínas/química , Sirtuínas/genética , Staphylococcus aureus/enzimologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Streptococcus pyogenes/enzimologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade
7.
Physiol Plant ; 174(3): e13709, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35580210

RESUMO

Soybean (Glycine max) is an important crop globally for food and edible oil production. Soybean plants are sensitive to salinity (NaCl), with significant yield decreases reported under saline conditions. GmSALT3 is the dominant gene underlying a major QTL for salt tolerance in soybean. GmSALT3 encodes a transmembrane protein belonging to the plant cation/proton exchanger (CHX) family, and is predominately expressed in root phloem and xylem associated cells under both saline and non-saline conditions. It is currently unknown through which molecular mechanism(s) the ER-localised GmSALT3 contributes to salinity tolerance, as its localisation excludes direct involvement in ion exclusion. In order to gain insights into potential molecular mechanism(s), we used RNA-seq analysis of roots from two soybean NILs (near isogenic lines); NIL-S (salt-sensitive, Gmsalt3), and NIL-T (salt-tolerant, GmSALT3), grown under control and saline conditions (200 mM NaCl) at three time points (0 h, 6 h, and 3 days). Gene ontology (GO) analysis showed that NIL-T has greater responses aligned to oxidation reduction. ROS were less abundant and scavenging enzyme activity was greater in NIL-T, consistent with the RNA-seq data. Further analysis indicated that genes related to calcium signalling, vesicle trafficking and Casparian strip (CS) development were upregulated in NIL-T following salt treatment. We propose that GmSALT3 improves the ability of NIL-T to cope with saline stress through preventing ROS overaccumulation in roots, and potentially modulating Ca2+ signalling, vesicle trafficking and formation of diffusion barriers.


Assuntos
Fabaceae , Glycine max , Fabaceae/metabolismo , Regulação da Expressão Gênica de Plantas , Oxigênio/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tolerância ao Sal/genética , Cloreto de Sódio/metabolismo , Cloreto de Sódio/farmacologia , Glycine max/metabolismo
8.
Chem Soc Rev ; 50(3): 1587-1616, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33403373

RESUMO

Biofilms are complex three-dimensional structures formed at interfaces by the vast majority of bacteria and fungi. These robust communities have an important detrimental impact on a wide range of industries and other facets of our daily lives, yet their removal is challenging owing to the high tolerance of biofilms towards conventional antimicrobial agents. This key issue has driven an urgent search for new innovative antibiofilm materials. Amongst these emerging approaches are highly promising materials that employ aqueous-soluble macromolecules, including peptides, proteins, synthetic polymers, and nanomaterials thereof, which exhibit a range of functionalities that can inhibit biofilm formation or detach and destroy organisms residing within established biofilms. In this Review, we outline the progress made in inhibiting and removing biofilms using macromolecular approaches, including a spotlight on cutting-edge materials that respond to environmental stimuli for "on-demand" antibiofilm activity, as well as synergistic multi-action antibiofilm materials. We also highlight materials that imitate and harness naturally derived species to achieve new and improved biomimetic and biohybrid antibiofilm materials. Finally, we share some speculative insights into possible future directions for this exciting and highly significant field of research.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Substâncias Macromoleculares/química , Anti-Infecciosos/química , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Portadores de Fármacos/química , Substâncias Macromoleculares/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/fisiologia , Nanopartículas/química , Nanopartículas/toxicidade , Polímeros/química , Pseudomonas aeruginosa/fisiologia
9.
Int Ophthalmol ; 42(12): 3789-3801, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35781598

RESUMO

PURPOSE: We assessed the relationship between acute primary angle closure glaucoma (APACG) severity and macular microcirculation, as well as the diagnostic ability of blood flow and macular structural parameters on optical coherence tomography angiography (OCTA) for APACG. METHODS: APACG patients were assigned to mild, moderate, and severe groups in this cross-sectional study. Age-matched primary angle closure suspect (PACS) and healthy control groups were also recruited. The vessel density (VD) and foveal avascular zone (FAZ) in each macular superficial area were measured using OCTA. The retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex thickness (GCCT) of the corresponding regions were measured using OCT. RESULTS: All parameters in the control, PACS, and mild APACG groups differed significantly from those in the moderate and severe APACG groups (all P < 0.05). VD and RNFLT showed high and moderate diagnostic ability, respectively, to distinguish moderate APACG from PACS, with significant differences (P < 0.05) in areas under the receiver operating characteristic curve (AUCs) for VD and RNFLT in six macular areas. The diagnostic abilities of VD and RNFLT for distinguishing severe APACG from PACS were increased, with significant differences in the AUCs for VD and RNFLT in five macular areas (P < 0.05). All macular VDs and GCCTs were similar among the three APACG groups (P > 0.05). CONCLUSIONS: Damage to the VD and FAZ in the macula increased with APACG severity. VD in the macular superficial layer showed a higher diagnostic ability than RNFLT, which was equivalent to that of GCCT.


Assuntos
Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Glaucoma , Macula Lutea , Humanos , Angiofluoresceinografia/métodos , Vasos Retinianos , Testes de Campo Visual , Glaucoma de Ângulo Fechado/diagnóstico , Estudos Transversais , Pressão Intraocular , Macula Lutea/irrigação sanguínea , Tomografia de Coerência Óptica/métodos
10.
Anal Chem ; 93(29): 10132-10140, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34255490

RESUMO

Herein, SnTe nanobelts (NBs) with efficient oxidase-mimetic activity were synthesized by the simple electrochemical exfoliation method. A specific inhibition effect of Cl- on the enzymatic behavior of the pure SnTe NBs was discovered, which was accordingly used for establishing a highly feasible, sensitive, selective, and stable Cl- colorimetric assay. The detection concentration range was 50 nM to 1 mM, and the lowest detection limit was 20 nM for Cl-. In addition, a signal on-off-on route based on the SnTe NB nanozyme was designed to realize the reliable and specific detection of Hg2+. Therein, the SnTe NBs were grafted with gold nanoparticles to form a hybrid of SnTe/Au, resulting in the depression of the oxidase-like activity, which can then be recovered in the presence of the Hg2+ due to the formation of a gold amalgam. Especially, it was found that the high concentration of Cl- over 3 mM could again exert suppression influence toward the enzymatic activity of the SnTe/Au-Hg system. Based on the to-love-and-to-kill interaction between Cl- and Hg2+, the detection range for Cl- can be extended to 40 to 250 mM. In return, the assays of Cl- could avoid in advance its interference toward the accurate Hg2+ assays. We systematically clarified the oxidase-like catalytic mechanism of the SnTe-derived nanozyme systems. The as-proposed colorimetry can be successfully applied in practical samples including the sweat, human serum, or seawater/tap water, relating to cystic fibrosis, hyper-/hypochloremia, or environmental control, respectively.


Assuntos
Mercúrio , Nanopartículas Metálicas , Cloretos , Colorimetria , Ouro , Humanos , Oxirredutases
11.
Plant Cell Environ ; 44(3): 856-869, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33190315

RESUMO

Soybean (Glycine max) yields are threatened by multiple stresses including soil salinity. GmSALT3 (a cation-proton exchanger protein) confers net shoot exclusion for both Na+ and Cl- and improves salt tolerance of soybean; however, how the ER-localized GmSALT3 achieves this is unknown. Here, GmSALT3's function was investigated in heterologous systems and near isogenic lines that contained the full-length GmSALT3 (NIL-T; salt-tolerant) or a truncated transcript Gmsalt3 (NIL-S; salt-sensitive). GmSALT3 restored growth of K+ -uptake-defective Escherichia coli and contributed towards net influx and accumulation of Na+ , K+ and Cl- in Xenopus laevis oocytes, while Gmsalt3 was non-functional. Time-course analysis of NILs confirmed shoot Cl- exclusion occurs distinctly from Na+ exclusion. Grafting showed that shoot Na+ exclusion occurs via a root xylem-based mechanism; in contrast, NIL-T plants exhibited significantly greater Cl- content in both the stem xylem and phloem sap compared to NIL-S, indicating that shoot Cl- exclusion likely depends upon novel phloem-based Cl- recirculation. NIL-T shoots grafted on NIL-S roots contained low shoot Cl- , which confirmed that Cl- recirculation is dependent on the presence of GmSALT3 in shoots. Overall, these findings provide new insights on GmSALT3's impact on salinity tolerance and reveal a novel mechanism for shoot Cl- exclusion in plants.


Assuntos
Cloretos/metabolismo , Glycine max/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Sódio/metabolismo , Animais , Escherichia coli , Transporte de Íons , Microscopia Eletrônica de Transmissão , Oócitos , Organismos Geneticamente Modificados , Folhas de Planta/fisiologia , Proteínas de Plantas/fisiologia , Raízes de Plantas/fisiologia , Brotos de Planta/fisiologia , Potássio/metabolismo , Tolerância ao Sal , Glycine max/fisiologia , Xenopus laevis , Xilema/metabolismo
12.
Mol Pharm ; 18(4): 1806-1818, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33734705

RESUMO

Type 1 diabetes (T1D) is an autoimmune subtype of diabetes, mainly caused by the immune attack of self-insulin-producing cells. Immune modulation that delays the onset of T1D is able to reduce diabetic complications and mortality. We have previously reported that mannosylated sodium alginate nanoparticles (MAN-ALG) exhibited excellent dendritic cell targeting and in vivo antigen delivery efficacy. To investigate the role of MAN-ALG in an autoimmune context, we loaded the MAN-ALG with Ins29-23, a T1D autoantigen [MAN-ALG(PEP)], for T1D immune tolerance induction in nonobese diabetic (NOD) mice. We observed the delayed onset of T1D occurrence and some degree of blood glucose reduction accompanied by a larger islet area, attributable to augmented T-regulatory cell proportion in mice treated with MAN-ALG(PEP). However, MAN-ALG was also found to elicit lysosomal escape and cross-presentation of Ins29-23 in bone marrow-derived dendritic cells, leading to the immune activation of Ins29-23-recognizing T cells and destruction of Ins29-23-expressing islet cells. This dual impact resulted in delayed but a nonpreventive effect of MAN-ALG(PEP) on the T1D onset in NOD mice. Considering the potent immune stimulatory property of MAN-ALG, cautions should be implemented when using alginate-based biomaterials in an autoimmune context. Moreover, it is also noted that regarding the in vivo outcome of immune therapies, biomaterial-based delivery systems and their detailed role on immune regulation need to be examined.


Assuntos
Autoantígenos/administração & dosagem , Diabetes Mellitus Tipo 1/prevenção & controle , Portadores de Fármacos/química , Insulina/imunologia , Peptídeos/administração & dosagem , Alginatos/química , Animais , Autoantígenos/genética , Autoantígenos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Tolerância Imunológica , Insulina/genética , Ilhotas Pancreáticas/imunologia , Camundongos , Camundongos Endogâmicos NOD , Nanopartículas/química , Peptídeos/genética , Peptídeos/imunologia
13.
BMC Med Inform Decis Mak ; 21(1): 184, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107920

RESUMO

BACKGROUND: Heart disease diagnosis is a challenging task and it is important to explore useful information from the massive amount of electrocardiogram (ECG) records of patients. The high-precision diagnostic identification of ECG can save clinicians and cardiologists considerable time while helping reduce the possibility of misdiagnosis at the same time.Currently, some deep learning-based methods can effectively perform feature selection and classification prediction, reducing the consumption of manpower. METHODS: In this work, an end-to-end deep learning framework based on convolutional neural network (CNN) is proposed for ECG signal processing and arrhythmia classification. In the framework, a transformer network is embedded in CNN to capture the temporal information of ECG signals and a new link constraint is introduced to the loss function to enhance the classification ability of the embedding vector. RESULTS: To evaluate the proposed method, extensive experiments based on real-world data were conducted. Experimental results show that the proposed model achieve better performance than most baselines. The experiment results also proved that the transformer network pays more attention to the temporal continuity of the data and captures the hidden deep features of the data well. The link constraint strengthens the constraint on the embedded features and effectively suppresses the effect of data imbalance on the results. CONCLUSIONS: In this paper, an end-to-end model is used to process ECG signal and classify arrhythmia. The model combine CNN and Transformer network to extract temporal information in ECG signal and is capable of performing arrhythmia classification with acceptable accuracy. The model can help cardiologists perform assisted diagnosis of heart disease and improve the efficiency of healthcare delivery.


Assuntos
Algoritmos , Eletrocardiografia , Arritmias Cardíacas/diagnóstico , Humanos , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador
14.
J Cell Physiol ; 235(4): 3721-3730, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31583720

RESUMO

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used for over 30 years in NSCLC treatment while its effects are diminished by drug resistance. Therefore, we aimed to study the potential role of UCA1 in the development of chemoresistance against cisplatin. Real-time polymerase chain reaction, western-blot analysis, and immunofluorescence were used to study the involvement of UCA1, miR-495, and NRF2 in chemoresistance against cisplatin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the effect of cisplatin on cell proliferation. Computational analysis and luciferase assay were carried out to explore the interaction among UCA1, miR-495, and NRF2. The cisplatin-R group exhibited lower levels of UCA1 and NRF2 expression but a higher level of miR-495 expression than the cisplatin-S group. The growth rate and half-maximal inhibitory concentration of cellular dipeptidyl peptidase (cisplatinum) of the cisplatin-R group were much higher than those in the cisplatin-S group. MiR-495 contained a complementary binding site of UCA1, and the luciferase activity of wild-type UCA1 was significantly reduced after the transfection of miR-495 mimics. MiR-495 directly targeted the 3'-untranslated region (3'-UTR) of NRF2, and the luciferase activity of wild-type NRF2 3'-UTR was evidently inhibited by miR-495 mimics. Finally, UCA1 and NRF2 expressions in the effective group were much lower than that in the ineffective group, along with a much higher level of miR-495 expression. We suggested for the first time that high expression of UCA1 contributed to the development of chemoresistance to cisplatin through the UCA1/miR-495/NRF2 signaling pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/genética , RNA Longo não Codificante/genética , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Transdução de Sinais/efeitos dos fármacos
15.
Cancer Cell Int ; 20: 71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32165861

RESUMO

BACKGROUND: Gliomas represent the largest class of primary central nervous system neoplasms, many subtypes of which exhibit poor prognoses. Surgery followed by radiotherapy and chemotherapy has been used as a standard strategy but yielded unsatisfactory improvements in patient survival outcomes. The S-phase kinase protein 2 (Skp2), a critical component of the E3-ligase SCF complex, has been documented in tumorigenesis in various cancer types but its role in glioma has yet to be fully clarified. In this study, we investigated the function of Skp2 in the proliferation, stem cell maintenance, and drug sensitivity to temozolomide (TMZ) of glioma. METHODS: To investigate the role of Skp2 in the prognosis of patients with glioma, we first analyzed data in databases TCGA and GTEx. To further clarify the effect of Skp2 on glioma cell proliferation, we suppressed its level in glioblastoma (GBM) cell lines through knockdown and small molecule inhibitors (lovastatin and SZL-P1-41). We then detected cell growth, colony formation, sphere formation, drug sensitivity, and in vivo tumor formation in xenograft mice model. RESULTS: Skp2 mRNA level was higher in both low-grade glioma and GBM than normal brain tissues. The knockdown of Skp2 increased cell sensitivity to TMZ, decreased cell proliferation and tumorigenesis. In addition, Skp2 level was found increased upon stem cells enriching, while the knockdown of Skp2 led to reduced sphere numbers. Downregulation of Skp2 also induced senescence. Repurposing of lovastatin and novel compound SZL-P1-41 suppressed Skp2 effectively, and enhanced glioma cell sensitivity to TMZ in vitro and in vivo. CONCLUSION: Our data demonstrated that Skp2 modulated glioma cell proliferation in vitro and in vivo, stem cell maintenance, and cell sensitivity to TMZ, which indicated that Skp2 could be a potential target for long-term treatment.

16.
J Med Internet Res ; 22(7): e18697, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32673247

RESUMO

BACKGROUND: The number of patients with neurological diseases is currently increasing annually, which presents tremendous challenges for both patients and doctors. With the advent of advanced information technology, digital medical care is gradually changing the medical ecology. Numerous people are exploring new ways to receive a consultation, track their diseases, and receive rehabilitation training in more convenient and efficient ways. In this paper, we explore the use of facial expression recognition via artificial intelligence to diagnose a typical neurological system disease, Parkinson disease (PD). OBJECTIVE: This study proposes methods to diagnose PD through facial expression recognition. METHODS: We collected videos of facial expressions of people with PD and matched controls. We used relative coordinates and positional jitter to extract facial expression features (facial expression amplitude and shaking of small facial muscle groups) from the key points returned by Face++. Algorithms from traditional machine learning and advanced deep learning were utilized to diagnose PD. RESULTS: The experimental results showed our models can achieve outstanding facial expression recognition ability for PD diagnosis. Applying a long short-term model neural network to the positions of the key features, precision and F1 values of 86% and 75%, respectively, can be reached. Further, utilizing a support vector machine algorithm for the facial expression amplitude features and shaking of the small facial muscle groups, an F1 value of 99% can be achieved. CONCLUSIONS: This study contributes to the digital diagnosis of PD based on facial expression recognition. The disease diagnosis model was validated through our experiment. The results can help doctors understand the real-time dynamics of the disease and even conduct remote diagnosis.


Assuntos
Inteligência Artificial/normas , Expressão Facial , Reconhecimento Facial/fisiologia , Aprendizado de Máquina/normas , Doença de Parkinson/diagnóstico , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravação de Videoteipe
17.
Semin Cell Dev Biol ; 69: 40-57, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28579450

RESUMO

Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit fly Drosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of the Drosophila spectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work on Drosophila Shot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas dos Microfilamentos/metabolismo , Animais , Orientação de Axônios , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Mamíferos/metabolismo , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/genética , Homologia de Sequência de Aminoácidos , Sinapses/metabolismo
18.
J Cell Physiol ; 234(12): 22657-22665, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31111480

RESUMO

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used in the NSCLC treatment for over 30 years, and its effects are impaired by drug resistance. This study aimed to investigate the potential role of lncRNA-AC078883.3 in the development of chemoresistance against cisplatin. Real-time PCR, Western blot analysis, Immunohistochemistry (IHC) assay, bioinformatic analysis, and luciferase assay were collaboratively used to establish the lncRNA-AC078883.3/miR-19a/PTEN/AKT pathway. Also, the effect of cisplatin on cell proliferation was observed via an MTT assay. Furthermore, Cox regression and Kaplan-Meier analyses were used to study whether lncRNA-AC078883.3 is involved in the survival of NSCLC. Compared with the Cisplatin-Sensitive group, the Cisplatin-Resistance group exhibited lower levels of lncRNA-AC078883.3 and PTEN and higher levels of miR-19a and p-Akt. The growth rate of A549 and H460 cells and the IC 50 of DPP in the Cisplatin-Resistance group were higher than those in the Cisplatin-S group. miR-19a contains a putative binding site of lncRNA-AC078883.3, which enabled the luciferase activity of wild-type lncRNA-AC078883.3 to be reduced by miR-19a. In addition, by directly targeting PTEN 3'-untranslated region (UTR), miR-19a repressed the luciferase activity of wild-type PTEN 3'-UTR. The median OS of patients with reduced lncRNA-AC078883.3 expression was longer than that of patients with higher lncRNA-AC078883.3 expression. Finally, compared with low lncRNA-AC078883.3-expression patients, the high lncRNA-AC078883.3-expression patients were associated with lower miR-19a expression and higher PTEN expression. Therefore, we suggested for the first time that the low expression of lncRNA-AC078883.3 contributed to the development of chemoresistance against cisplatin.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Células A549 , Sítios de Ligação , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , Transdução de Sinais
19.
Opt Express ; 27(21): 30763-30772, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684319

RESUMO

All-InSb film-based and spiral antenna-assisted Au-InSb-Au metal-semiconductor-metal detector is reported with dual-band photoresponse in the infrared (IR) and millimeter wave range. At IR, the detector exhibits a long wavelength 100% cut-off at 7.3 µm. Under an applied bias of 5 mA, the uncooled blackbody responsivity and specific detectivity are 3.5 A/W and 1×108 Jones, respectively. The f-3dB value measured at 2.94 µm is 75 KHz, corresponding to a detector rise speed of 4.7 µs. At millimeter wave range, the detector shows a narrowband response determined by the coupling of the antenna. A voltage responsivity of 25 V/W is achieved at 167 GHz (1.796 mm) under an applied bias of 25 mA, and the corresponding noise equivalent power (NEP) is 1.0×10-10 WHz-1/2, which can be improved to 1.8×10-12 WHz-1/2 if normalized to the real active semiconductor area. A f-3dB value of 17.5 KHz, corresponding to a detector rise speed of 20 µs is achieved in this range. A proof of principle for IR-modulated photoresponse for millimeter wave is achieved with a maximum modulation depth of 47.5%. This All-InSb film-based detector and the modulation are promising for future novel optoelectronic devices in IR and millimeter waves.

20.
Genetica ; 147(2): 185-196, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30905050

RESUMO

The amino acid/auxin permease (AAAP) gene family plays an important role in the long-distance amino acid transport pathway and takes part in various stages of plant growth and development. However, little is known about the AAAP gene family in Medicago truncatula. Here, we identified 86 putative MtAAAP family members using genome sequence information. Based on phylogenetic analysis, these MtAAAP genes were categorized into eight distinct subfamilies. The MtAAAP genes were mapped on 8 chromosomes and duplication events appeared widely, with 19 and 21 pairs of MtAAAP genes showing segment and tandem duplication events, respectively. Ratio of Ka/Ks indicated that duplicated genes underwent purifying selection. Analysis of RNA-seq data showed that MtAAAP genes exhibited specific expression patterns among different tissues and abiotic stress, indicating that MtAAAP members were involved in plant developmental regulation and stress responses. Expression patterns of 16 MtAAAP genes under abiotic stress were verified by qRT-PCR. The present study provides a foundation for the functional analysis of MtAAAPs in developmental regulation and stress responses.


Assuntos
Sistemas de Transporte de Aminoácidos/genética , Regulação da Expressão Gênica de Plantas , Medicago/genética , Proteínas de Plantas/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Duplicação Gênica , Genoma de Planta , Medicago/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/metabolismo , Seleção Genética , Estresse Fisiológico
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