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1.
Food Funct ; 12(20): 9527-9548, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664581

RESUMO

Since ancient times, litchi has been well recognized as a functional food for the management of various ailments. Many bioactives, including flavanoids, anthocyanins, phenolics, sesquiterpenes, triterpenes, and lignans, have been identified from litchi with a myriad of biological properties both in vitro and in vivo. In spite of the extensive research progress, systemic reviews regarding the bioactives of litchi are rather scarce. Therefore, it is crucial to comprehensively analyze the pharmacological activities and the structure-activity relationships of the abundant bioactives of litchi. Besides, more and more studies have focused on litchi preservation and development of its by-products, which is significant for enhancing the economic value of litchi. Based on the analysis of published articles and patents, this review aims to reveal the development trends of litchi in the healthcare field by providing a systematic summary of the pharmacological activities of its extracts, its phytochemical composition, and the nutritional and potential health benefits of litchi seed, pulp and pericarp with structure-activity relationship analysis. In addition, its by-products also exhibited promising development potential in the field of material science and environmental protection. Furthermore, this study also provides an overview of the strategies of the postharvest storage and processing of litchi.

2.
Adv Mater ; : e2105170, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561907

RESUMO

3D organic-inorganic hybrid halide perovskite solar cells (pero-SCs) inherently face severe instability issue due to ion migration under operational conditions. This ion migration inevitably results from the decomposition of ionic bonds under lattice strain and is accelerated by the existence of excess charge carriers. In this study, a 1D-3D mixed-dimensional perovskite material is explored by adding an organic salt with a bulk benzimidazole cation (Bn+ ). The Bn+ can induce 3D perovskite crystalline growth with the preferred orientation and form a 1D BnPbI3 perovskite spatially distributed in the 3D perovskite film. For the first time, the electro-strictive response, which has a significant influence on the lattice strain under an electric field, is observed in polycrystalline perovskite. The 1D-3D perovskite can effectively suppress electro-strictive responses and unbalanced charge carrier extraction, providing an intrinsically stable lattice with enhanced ionic bonds and fewer excess charge carriers. As a result, the ion migration behavior of the p-i-n 1D-3D based pero-SC is dramatically suppressed under operational conditions, showing ultra-long-term stability that retains 95.3% of its initial power conversion efficiency (PCE) under operation for 3072 h, and simultaneously achieving an excellent PCE with a hysteresis-free photovoltaic behavior.

3.
Methods Enzymol ; 657: 223-247, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34353489

RESUMO

Benzobisthiadiazole as a typical electron acceptor, has been widely used to design fluorescent dyes and photoacoustic (PA) agents. With the strategy of constructing donor-acceptor-donor (D-A-D) type of electron characteristics, benzobisthiadiazole derivatives tend to behave stable in near-infrared absorption and emission, which is beneficial to PA imaging. In this chapter, two molecular design strategies are combined to improve the photoacoustic imaging effects of new PA contrast agent IR-1302 NPs, by installing strengthened conjugated bridges and electron donors. The nanoparticles exhibit high-contrast noninvasive photoacoustic imaging in tumor models with longer wavelength absorption and emission and show potential as a clinic contrast agent.


Assuntos
Nanopartículas , Técnicas Fotoacústicas , Corantes Fluorescentes , Análise Espectral
4.
Nat Commun ; 12(1): 4664, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341353

RESUMO

Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1ß and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.


Assuntos
COVID-19/metabolismo , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , SARS-CoV-2/metabolismo , Animais , COVID-19/virologia , Células Cultivadas , Citocinas/metabolismo , Células HEK293 , Humanos , Inflamassomos/genética , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fosfoproteínas/metabolismo , Ligação Proteica , SARS-CoV-2/fisiologia , Células THP-1
5.
Neurochem Res ; 46(11): 3050-3058, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34347266

RESUMO

Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.

6.
Am J Physiol Endocrinol Metab ; 321(3): E392-E409, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34370593

RESUMO

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB), and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (pAS160), AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups whereas the Exe-9 and Glp-1r KD were opposite. Known to activate insulin-signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.NEW & NOTEWORTHY The improvement of cognitive function following bariatric surgery has been highlighted while its mechanisms remain elusive. The brain glucose uptake of patients was improved after RYGB, and the DJB and sham surgery performed on obese and diabetic Wistar rats revealed that the elevated central GLP-1 contributes to the dramatic improvement of cognitive function, brain glucose uptake, transport, glucose sensing, and neuronal activation.


Assuntos
Cognição , Diabetes Mellitus Experimental/metabolismo , Derivação Gástrica , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Obesidade/metabolismo , Animais , Encéfalo/metabolismo , Duodeno/cirurgia , Glucose , Jejuno/cirurgia , Obesidade/cirurgia , Ratos Wistar
7.
Chemosphere ; 286(Pt 1): 131652, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34315075

RESUMO

Glass fiber and liquid-modified polyvinyl alcohol polymer (SH Polymer) are used to reinforce granite residual soil. In this paper, scanning electron microscopy (SEM) tests and drop-weight tests were used to study the microscopic interaction mechanism and impact resistance of granite residual soil specimens reinforced by glass fiber and SH Polymer. Combined with the equivalent confining pressure theory, Mohr-Coulomb intensity lines were used to quantitatively analyze the reinforcement effect of glass fiber. The SEM results showed that the granite residual soil solidified by a 3.5 % SH polymer had a tighter bond between the flake clay particles. In addition, with the incorporation of glass fiber, these flake clay particles were cemented on the glass fiber along the long axis, forming a cementing system of flake clay particles and glass fiber. When the glass fiber content was 3.0 %, the impact resistance of the specimen reached its maximum, 32.16 kN. Using the equivalent confining pressure theory, the reinforcement effect of glass fiber on soil could be quantified by Δσ3.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34282540

RESUMO

Increased sympathetic nervous activity is one of main contributors to pathogenesis and progression of hypertension. Renal denervation (RDN) has been demonstrated as a potential therapy for treatment of hypertension; however, lack of indicators of intra-/post-procedure results in inconsistent clinical outcomes. Renal nerve stimulation (RNS), a simple and promising method, could evoke elevated blood pressure as an intraoperative indicator for RDN. But related researches on patterns of blood pressure responses to RNS are still incomplete. To investigate and categorize the phenotypes of blood pressure response to RNS and heart rate alteration before and after RNS, 24 Chinese Kunming dogs were used to perform RNS from bifurcation to ostium of renal arteries after angiography, and a total of 483 stimulated sites were complete. We identified five different patterns of blood pressure response to RNS in 483 stimulated sites, (1) continuous ascending and finally keeping steady above baseline (26.9%), (2) declining and then rising over baseline (11.8%), (3) declining and then rising but below baseline (14.5%), (4) fluctuating in the vicinity of baseline (39.5%), and (5) continuous declining and finally keeping steady below baseline (7.2%), and found no difference in RR intervals among five blood pressure responses before and after renal nerve stimulation. Renal nerve stimulation could elicit different patterns of blood pressure response, which could potentially assist in distinguishing sympathetic-excitatory sites and sympathetic-inhibitory sites from mixed nerve components, which might help to improve the efficacy of RDN.

9.
J Magn Reson Imaging ; 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184337

RESUMO

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) has been shown to be effective in diagnosing muscle invasion of bladder cancer (BC) in primary patients. PURPOSE: To evaluate the diagnostic efficacy of VI-RADS in a BC target population which included post-treatment patients, and to determine the repeatability. STUDY TYPE: Prospective. POPULATION: Seventy-three patients (42 with primary BC, 31 with post-treatment BC). FIELD STRENGTH/SEQUENCE: 3.0 T MRI with propeller fast spin-echo T2 WI, echo planer imaging diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI). ASSESSMENT: VI-RADS scores were independently assessed by five radiologists with different levels of experience. The diagnostic efficiency in each group (primary and post-treatment) and of each radiologist was assessed. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and area under the curve (AUC) in receiver operating characteristic curve analysis were calculated to evaluate VI-RADS diagnostic performance. Interobserver agreement was assessed using weighted Kappa statistics. A P value <0.05 was considered statistically significant. RESULTS: At the corresponding cut-off, AUC values of three groups range from 0.936 to 0.947 and AUC values of five observers range from 0.901 to 0.963. There was no significant difference between the AUCs in the primary and post-treatment groups (P = 0.870). The cut-off of the whole group and the post-treatment group was ≥4, and the cut-off of the primary group was ≥3. The Kappa values of interobserver agreements range from 0.709 to 0.923. CONCLUSIONS: After expanding the target population to include post-treatment patients, VI-RADS still has good diagnostic efficacy and repeatability. VI-RADS could potentially be a preoperative staging tool for post-treatment patients. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

10.
J Comput Assist Tomogr ; 45(4): 637-642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34176877

RESUMO

OBJECTIVE: To demonstrate the utility of deep learning enhancement (DLE) to achieve diagnostic quality low-dose positron emission tomography (PET)/magnetic resonance (MR) imaging. METHODS: Twenty subjects with known Crohn disease underwent simultaneous PET/MR imaging after intravenous administration of approximately 185 MBq of 18F-fluorodeoxyglucose (FDG). Five image sets were generated: (1) standard-of-care (reference), (2) low-dose (ie, using 20% of PET counts), (3) DLE-enhanced low-dose using PET data as input, (4) DLE-enhanced low-dose using PET and MR data as input, and (5) DLE-enhanced using no PET data input. Image sets were evaluated by both quantitative metrics and qualitatively by expert readers. RESULTS: Although low-dose images (series 2) and images with no PET data input (series 5) were nondiagnostic, DLE of the low-dose images (series 3 and 4) achieved diagnostic quality images that scored more favorably than reference (series 1), both qualitatively and quantitatively. CONCLUSIONS: Deep learning enhancement has the potential to enable a 90% reduction of radiotracer while achieving diagnostic quality images.


Assuntos
Aprendizado Profundo , Fluordesoxiglucose F18 , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Adulto Jovem
11.
J Org Chem ; 86(14): 9711-9722, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34189921

RESUMO

The efficient couplings of diverse N-arylureas and gem-difluoromethylene alkynes have been realized via Rh(III)-catalyzed chemoselective C-H alkenylation and [5 + 1] annulation, which were induced by the distinctive fluorine effect to provide the different coordination mode of the Rh(III) catalyst binding to the directing group, thereby giving the direct access to difluorinated 2-alkenyl arylureas and 3,4-dihydroquinazolin-2(1H)-ones bearing both an α-quaternary carbon center and a monofluoroalkenyl moiety with broad substrate compatibility and good functional group tolerance. The synthetic application in C-H alkenylation of the N-pyridylaniline, the late-stage [3 + 2] annulation, and the derivation of the obtained products has been also demonstrated to further strengthen the synthetic utility of the chemodivergent transformations.


Assuntos
Ródio , Alcinos , Carbono , Catálise , Flúor
12.
Neural Netw ; 142: 73-91, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33984737

RESUMO

Recent advances show that two-dimensional linear discriminant analysis (2DLDA) is a successful matrix based dimensionality reduction method. However, 2DLDA may encounter the singularity issue theoretically, and also is sensitive to outliers. In this paper, a generalized Lp-norm 2DLDA framework with regularization for an arbitrary p>0 is proposed, named G2DLDA. There are mainly two contributions of G2DLDA: one is G2DLDA model uses an arbitrary Lp-norm to measure the between-class and within-class scatter, and hence a proper p can be selected to achieve robustness. The other one is that the introduced regularization term makes G2DLDA enjoy better generalization performance and avoid singularity. In addition, an effective learning algorithm is designed for G2LDA, which can be solved through a series of convex problems with closed-form solutions. Its convergence can be guaranteed theoretically when 1≤p≤2. Preliminary experimental results on three contaminated human face databases show the effectiveness of the proposed G2DLDA.

13.
Chem Soc Rev ; 50(13): 7725-7744, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34013918

RESUMO

Food fermentation, antibiotics, and pollutant degradation are closely related to bacteria. Bacteria play an irreplaceable role in life. However, some bacteria seriously threaten human health and cause large-scale infectious diseases. Therefore, there is a pressing need to develop strategies to accurately monitor bacteria. Technology based on molecular probes and fluorescence imaging is noninvasive, results in little damage, and has high specificity and sensitivity, so it has been widely applied in the detection of bacteria. In this review, we summarize the recent progress in bacterial detection using fluorescence. In particular, we generalize the mechanisms commonly used to design organic fluorescent probes for detecting and imaging bacteria. Moreover, a perspective regarding fluorescent probes for bacterial detection is discussed.

14.
Transl Stroke Res ; 12(5): 695-710, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34050491

RESUMO

Stroke is one of the world's leading causes of death and disability, posing enormous burden to the society. However, the pathogenesis and mechanisms that underlie brain injury and brain repair remain largely unknown. There's an unmet need of in-depth mechanistic research in this field. Zebrafish (Danio rerio) is a powerful tool in brain science research mainly due to its small size and transparent body, high genome synteny with human, and similar nervous system structures. It can be used to establish both hemorrhagic and ischemic stroke models easily and effectively through different ways. After the establishment of stroke model, research methods including behavioral test, in vivo imaging, and drug screening are available to explore mechanisms that underlie the brain injury and brain repair after stroke. This review focuses on the advantages and the feasibility of zebrafish stroke model, and will also introduce the key methods available for stroke studies in zebrafish, which may drive future mechanistic studies in the pursuit of discovering novel therapeutic targets for stroke patients.

15.
Adipocyte ; 10(1): 275-284, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33975515

RESUMO

Dysfunction of adipose tissue could lead to insulin resistance, obesity and type 2 diabetes. Thus, our present study aimed to investigate metabolites alterations in white adipose tissue (WAT) of diabetic GK rats after IT surgery. Ten-week-old male diabetic GK rats were randomly subjected to IT and Sham-IT surgery. Six weeks later, the untargeted metabolomics in WAT of diabetic GK rats was performed. Differential metabolites were selected according to the coefficient of variation (CV) of quality control (QC) sample <30%, variable importance in the projection (VIP) >1 and P < 0.05. Then, the hierarchical clustering of differential metabolites was conducted and the KEGG database was used for metabolic pathway analysis. A total of 50 (in positive ion mode) and 68 (in negative ion mode) metabolites were identified as differential metabolites in WAT of diabetic GK rats between IT group and Sham-IT group, respectively. These differential metabolites were well clustered, which in descending order of the number of involved differential metabolites is ubiquinone and other terpenoid-quinone biosynthesis, AMPK signalling pathway, pantothenate and CoA biosynthesis, ferroptosis, vitamin digestion and absorption, glycerophospholipid metabolism, phenylalanine metabolism, steroid hormone biosynthesis, neuroactive ligand-receptor interaction, porphyrin and chlorophyll metabolism and bile secretion, and correlated with the parameters of body weight, food intake, WAT mass and glucose metabolism, which were significantly improved after IT surgery. The differential metabolites in WAT of diabetic GK rats were mainly related to the pathway of energy metabolism, and correlated with the improved phenotypes of diabetic GK rats after IT surgery.


Assuntos
Tecido Adiposo Branco/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Íleo/metabolismo , Intestino Delgado/metabolismo , Metabolômica , Animais , Íleo/cirurgia , Intestino Delgado/cirurgia , Masculino , Ratos , Ratos Wistar
16.
J Cancer Res Clin Oncol ; 147(10): 3113-3121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33963905

RESUMO

PURPOSE: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC). METHODS: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Kaplan-Meier curves with log-rank tests were used to evaluate survival. RESULTS: We identified 8 (1.5%), 35(6.7%) and 109 (20.8%) cases with a NTRK1 rearrangement using 15%, 10% and 5% as cut-off values, respectively. We observed copy number (CN) variation of NTRK1 in some cases: 79 (15.1%) cases had a gain in NTRK1 CN ≥ 3, and 24 (4.6%) cases had NTRK1 CN ≥ 4. A NTRK1 rearrangement at the above-mentioned thresholds was not related to disease-free survival (DFS, P = 0.45, 0.47, 0.87) and overall survival (OS, P = 0.80, 0.74, 0.57), respectively. Gain in NTRK1 CN was associated with a poor prognosis irrespective of whether NTRK1 CN ≥ 4 (DFS, P = 0.015; OS, P = 0.035) or NTRK1 CN ≥ 3 (DFS, P = 0.039; OS, P = 0.025). CONCLUSION: A NTRK1 rearrangement occurred rarely in ESCC. The increased CN of NTRK1 might be a prognostic indicator for DFS and OS in patients with ESCC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia/mortalidade , Rearranjo Gênico , Hibridização in Situ Fluorescente/métodos , Receptor trkA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
17.
World J Surg Oncol ; 19(1): 136, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33941195

RESUMO

BACKGROUND: Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Further, even unclassified tumors can have therapeutic targets. NTRK gene fusions are sporadic genetic alterations that occur across tumor entities. If NTRK gene fusions are detected, TRK inhibitors can be used regardless of the tumor entity. CASE PRESENTATION: This report describes a case with an unclassifiable mesenchymal sarcoma carrying a neurotrophic tyrosine receptor kinase NTRK1-KHDRBS1 gene fusion that was diagnosed and treated at multiple hospitals. Diagnostic work-up included pathological and immunohistochemical analysis, which excluded angiosarcoma, dendritic cell sarcoma, and pseudomyogenic hemangioendothelioma. The patient achieved a long-term survival without tumor relapse after treatment with crizotinib. CONCLUSIONS: This case will be of significant interest to pathologists because, despite the tumor being unclassified, a molecular target was identified. Although the FDA does not currently approve crizotinib for treatment of patients harboring NTRK gene fusions, this case provides new insights for diagnosis and treatment of mesenchymal sarcomas with NTRK1 gene translocations. Similar to ALKomas, which can be successfully treated using NTRK molecular-targeted therapy, tumors with NTRK gene translocations can be classified as NTRKomas, even when they occur at different organ sites, and with varying histological morphologies, and immunophenotypes.


Assuntos
Receptor trkA , Sarcoma , Proteínas Adaptadoras de Transdução de Sinal , Crizotinibe/uso terapêutico , Proteínas de Ligação a DNA , Fusão Gênica , Humanos , Recidiva Local de Neoplasia , Proteínas de Fusão Oncogênica/genética , Prognóstico , Proteínas de Ligação a RNA , Receptor trkA/genética , Sarcoma/tratamento farmacológico , Sarcoma/genética
18.
Elife ; 102021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33884952

RESUMO

Powered by flagella, many bacterial species exhibit collective motion on a solid surface commonly known as swarming. As a natural example of active matter, swarming is also an essential biological phenotype associated with virulence, chemotaxis, and host pathogenesis. Physical changes like cell elongation and hyper-flagellation have been shown to accompany the swarming phenotype. Less studied, however, are the contrasts of collective motion between the swarming cells and their counterpart planktonic cells of comparable cell density. Here, we show that confining bacterial movement in circular microwells allows distinguishing bacterial swarming from collective swimming. On a soft agar plate, a novel bacterial strain Enterobacter sp. SM3 in swarming and planktonic states exhibited different motion patterns when confined to circular microwells of a specific range of sizes. When the confinement diameter was between 40 µm and 90 µm, swarming SM3 formed a single-swirl motion pattern in the microwells whereas planktonic SM3 formed multiple swirls. Similar differential behavior is observed across several other species of gram-negative bacteria. We also observed 'rafting behavior' of swarming bacteria upon dilution. We hypothesize that the rafting behavior might account for the motion pattern difference. We were able to predict these experimental features via numerical simulations where swarming cells are modeled with stronger cell-cell alignment interaction. Our experimental design using PDMS microchip disk arrays enabled us to observe bacterial swarming on murine intestinal surface, suggesting a new method for characterizing bacterial swarming under complex environments, such as in polymicrobial niches, and for in vivo swarming exploration.

19.
Org Lett ; 23(9): 3729-3734, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33881883

RESUMO

Polycyclic lactams are prepared in a single operation from o-toluamides and cyclic amines in a process that involves transient cyclic imines, species that are conveniently obtained in situ from the corresponding lithium amides and simple ketone oxidants. Imines thus generated, such as 1-pyrroline and 1-piperideine, engage lithiated o-toluamides in a facile annulation process. Undesired side reactions such as imine deprotonation and o-toluamide dimerization are suppressed through the judicious choice of reaction conditions.

20.
J Immunol ; 206(8): 1913-1922, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712519

RESUMO

The formation of neutrophil extracellular trap (NET) is a critical host defense when neutrophils migrate to infection sites. Pyroptosis is a newly identified programmed cell death, which is tightly regulated by inflammasome activation. However, the mechanism of pyroptotic signaling participating in NET production remains to be elucidated. In this study, the zebrafish larvae otic vesicle microinjection model was used to infect larvae with hemolysin-overexpressing Edwardsiella piscicida (EthA+), and a rapid migration of neutrophils to infection sites was observed. Intriguingly, EthA+ infection effectively induced significant neutrophil membrane rupture in vivo, which was dependent on caspase-B (caspy2) and gasdermin Eb (GSDMEb) but not caspase-A or gasdermin Ea. Specifically, the EthA+ E. piscicida infection induced pyroptosis along with NETosis in vitro, and depletion of either caspy2 or GSDMEb impaired NET formation in vivo. Consequently, inhibition of the caspy2-GSDMEb axis-gated NETosis impaired bacterial clearance in vivo. Altogether, these data provide evidence that teleost fish innate immune cells, including neutrophils, express features of pyroptosis that are critical for NETosis in teleost innate immunity.


Assuntos
Edwardsiella/fisiologia , Infecções por Enterobacteriaceae/imunologia , Armadilhas Extracelulares/imunologia , Doenças dos Peixes/imunologia , Neutrófilos/imunologia , Peixe-Zebra/imunologia , Animais , Animais Geneticamente Modificados , Caspases/genética , Células Cultivadas , Proteínas Hemolisinas/genética , Imunidade Inata , Larva , Piroptose , Receptores de Estrogênio/genética , Proteínas de Peixe-Zebra/genética
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