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1.
Mol Cell ; 73(1): 7-21.e7, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30472188

RESUMO

The transcriptional regulators YAP and TAZ play important roles in development, physiology, and tumorigenesis and are negatively controlled by the Hippo pathway. It is yet unknown why the YAP/ TAZ proteins are frequently activated in human malignancies in which the Hippo pathway is still active. Here, by a gain-of-function cancer metastasis screen, we discovered OTUB2 as a cancer stemness and metastasis-promoting factor that deubiquitinates and activates YAP/TAZ. We found OTUB2 to be poly-SUMOylated on lysine 233, and this SUMOylation enables it to bind YAP/TAZ. We also identified a yet-unknown SUMO-interacting motif (SIM) in YAP and TAZ required for their association with SUMOylated OTUB2. Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP/TAZ. Our results establish OTUB2 as an essential modulator of YAP/TAZ and also reveal a novel mechanism via which YAP/TAZ activity is induced by oncogenic KRAS.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/enzimologia , Movimento Celular , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células-Tronco Neoplásicas/enzimologia , Fosfoproteínas/metabolismo , Tioléster Hidrolases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/agonistas , Receptores ErbB/metabolismo , Feminino , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lisina , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Metástase Neoplásica , Células-Tronco Neoplásicas/patologia , Fenótipo , Fosfoproteínas/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteólise , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais , Sumoilação , Tioléster Hidrolases/genética , Fatores de Tempo , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP
2.
Phys Rev Lett ; 130(14): 143004, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37084455

RESUMO

We introduce well-separated ^{87}Rb^{+} ions into an atomic ensemble by microwave ionization of Rydberg excitations and realize single-shot imaging of the individual ions with an exposure time of 1 µs. This imaging sensitivity is reached by using homodyne detection of ion-Rydberg-atom interaction induced absorption. We obtain an ion detection fidelity of (80±5)% from analyzing the absorption spots in acquired single-shot images. These in situ images provide a direct visualization of the ion-Rydberg interaction blockade and reveal clear spatial correlations between Rydberg excitations. The capability of imaging individual ions in a single shot is of interest for investigating collisional dynamics in hybrid ion-atom systems and for exploring ions as a probe for measurements of quantum gases.

3.
Opt Lett ; 47(17): 4399-4402, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048663

RESUMO

We study telecom-wavelength spectra of a Rydberg state in an atomic vapor with a three-photon excitation scheme. Two lasers of 780 nm and 776 nm are used to pump rubidium-85 atoms in a vapor cell to the 5D5/2 state, from which a probe beam of 1292 nm in the O-band telecommunication wavelength drives a transition to the 21F7/2 Rydberg state. We investigate the probe spectra over the power of pump lasers. The simulation based on a 4-level theoretical model captures the main features of the experimental results. This spectroscopic study paves the way for future experiments of making a direct link between fiber optics and radio transmission via Rydberg atoms.

4.
J Craniofac Surg ; 33(7): e744-e747, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35765142

RESUMO

PURPOSE: Extraction of mesiodens in high site is complicated. Here we introduce some technical skills to simply the process and achieve high success rate meanwhile. METHODS: All patients should accept radiographic examination before surgery. According to the position of mesiodens based on cone-beam computed tomography, we choose the appropriate method and tool. RESULTS: A series of cases have proved that these skills are applicable and convenient. CONCLUSIONS: Dentists should analyze the inspection results seriously and select the optimal strategy to extract mesiodens in high site.


Assuntos
Dente Supranumerário , Tomografia Computadorizada de Feixe Cônico , Humanos , Projetos de Pesquisa , Dente Supranumerário/cirurgia
5.
J Craniofac Surg ; 33(5): e481-e482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35286055

RESUMO

PURPOSE: Introduce Kuhn anemia as a complication during the inferior alveolar nerve block (IANB). METHODS: Here, the authors reported a lesser-known complication called Kuhn anemia during the IANB. Then, the authors searched and reviewed relevant literature on the Web of Science. RESULTS: Vasospasm of the maxillary artery results in the phenomenon. Reasons, such as inaccurate injection, anatomical variation, drug diffusion, and so on, may account for the complication during the IANB. CONCLUSIONS: All in all, doctors should be prudent before and during the surgery.


Assuntos
Anestesia Dentária , Bloqueio Nervoso , Anestésicos Locais , Método Duplo-Cego , Humanos , Injeções , Nervo Mandibular , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos
6.
Opt Express ; 28(5): 6835-6845, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32225922

RESUMO

We present a scheme for realizing deterministic single-photon subtraction in a coupled single quantum dot-cavity solid-state system. The device consists of a charged quantum dot and its coupled bimodal photonic crystal cavity with a moderate magnetic field applied in a Voigt configuration. We numerically simulate injection of optical pulses into one of the cavity modes and show that the system deterministically transfers one photon into the second cavity mode for input pulses in the form of both Fock states and coherent states. This device has potential in the application of a compact and integrated solid-state based device for quantum information processing.

7.
Opt Lett ; 43(8): 1674-1677, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29652337

RESUMO

We present a novel approach to enhance the spontaneous emission rate of single quantum emitters in an optical nanofiber-based cavity by introducing a narrow air-filled groove into the cavity. Our results show that the Purcell factor for single quantum emitters inside the groove of the nanofiber-based cavity can be at least six times greater than for such an emitter on the fiber surface when using an optimized cavity mode and groove width. Moreover, the coupling efficiency of single quantum emitters into the guided mode of this nanofiber-based cavity can reach up to ∼80% with only 35 cavity-grating periods. This new system has the potential to act as an all-fiber platform to realize efficient coupling of photons from single emitters into an optical fiber for quantum information applications.

8.
BMC Oral Health ; 18(1): 8, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321070

RESUMO

BACKGROUND: Dental diseases are among the most frequently reported health problems in drug abusers. However, few studies have been conducted on oral health of methamphetamine (meth) abusers in China. The aim of the present study was to investigate the caries and periodontal health profile of former meth abusers in Eastern China. METHODS: A cross-sectional study was conducted on 162 former meth abusers in the male Zhoushan Compulsory Detoxification Center. A standardized questionnaire, which collected information about age, drug-use duration / pattern, oral hygiene habit and systemic diseases, was administered. Then, a dental examination was performed to investigate the severity of dental caries and periodontal diseases. In evaluating dental caries, the prevalence of dental caries, the scores of decayed teeth (DT), missing teeth (MT), filled teeth (FT), and decayed, missing, filled teeth (DMFT) were recorded. In evaluating periodontal diseases, community periodontal index (CPI), and the prevalence of gingival bleeding, dental calculus, periodontal pocket and loose teeth, were recorded. Additionally, the non-parametric test was adopted to analyze the potential risk factors via SPSS. RESULTS: All the participants abused meth by inhalation. The mean scores of DT, MT, FT and DMFT in the former meth users were 2.72 ± 2.78, 3.07 ± 3.94, 0.33 ± 1.03 and 6.13 ± 5.20 respectively. The prevalence of gingival bleeding, dental calculus, periodontal pocket and loose teeth was 97.53%, 95.68%, 51.23% and 9.26% respectively. The DT, DMFT and CPI scores in those who had abused meth for longer than 4 years were significantly higher than those who abused for less than 4 years (P = 0.039, 0.045, P < 0.001, respectively). The DT score in those who brushed their teeth more than twice a day were significantly lower than those who brushed less (P = 0.018). CONCLUSIONS: The status of caries and periodontal diseases among former male meth users in Eastern China was poor. Prolonged drug abuse and lower frequency of tooth brushing may be the risk factors of their poor status of caries and periodontal diseases.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/complicações , Cárie Dentária/etiologia , Doenças Periodontais/etiologia , Adulto , China/epidemiologia , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Humanos , Masculino , Metanfetamina , Pessoa de Meia-Idade , Doenças Periodontais/epidemiologia , Índice Periodontal , Bolsa Periodontal/epidemiologia , Bolsa Periodontal/etiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários , População Urbana , Adulto Jovem
9.
Elife ; 122023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38131301

RESUMO

General anesthesia leads to a loss of consciousness and an unrousable state in patients. Although general anesthetics are widely used in clinical practice, their underlying mechanisms remain elusive. The potential involvement of nonneuronal cells is unknown. Microglia are important immune cells in the central nervous system (CNS) that play critical roles in CNS function and dysfunction. We unintentionally observed delayed anesthesia induction and early anesthesia emergence in microglia-depleted mice. We found that microglial depletion differentially regulates neuronal activities by suppressing the neuronal network of anesthesia-activated brain regions and activating emergence-activated brain regions. Thus, microglia facilitate and stabilize the anesthesia status. This influence is not mediated by dendritic spine plasticity. Instead, it relies on the activation of microglial P2Y12 and subsequent calcium influx, which facilitates the general anesthesia response. Together, we elucidate the regulatory role of microglia in general anesthesia, extending our knowledge of how nonneuronal cells modulate neuronal activities.


Assuntos
Encéfalo , Microglia , Humanos , Camundongos , Animais , Microglia/fisiologia , Neurônios/fisiologia , Estado de Consciência , Anestesia Geral
10.
Nat Commun ; 13(1): 4461, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915084

RESUMO

Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-ß type II receptor (TßRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-ß signaling in recipient cells. Up-take of extracellular vesicle-TßRII (EV-TßRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TßRII delivered as cargo to CD8+ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8+ T cell exhaustion, resulting in failure of immunotherapy. The levels of TßRII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Neoplasias da Mama/patologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Proteínas Serina-Treonina Quinases/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
11.
Shanghai Kou Qiang Yi Xue ; 20(4): 385-9, 2011 Aug.
Artigo em Zh | MEDLINE | ID: mdl-21909603

RESUMO

PURPOSE: To investigate the effects of TiN and TiCN coating on corrosion resistance of pure titanium in the simulated oral environment. METHODS: The dental pure titanium commonly used in making removable denture was casted with 15 specimens, 10mm × l0mm × 1mm in size. The specimens were randomly divided into group A, group B and group C. In the group B and group C, the specimens were coated with a thickness of 2.5µm TiN and TiCN coating on surface by multi-arc physical vapor deposition, respectively. After microscopic energy spectrum analysis, microstructure and phase diffraction were examined by FESEM. Hardness and Young modulus of the various coating were determined by nanoindentation. The polarization curves of all specimens in artificial saliva were measured by PARSTAT' 2273 electrochemical station. The data were analyzed with SPSS 17.0 software package for t test, one-way ANOVA and nonparametric test. RESULTS: Both the microhardness and elastic modulus in the group B and group C were significantly superior to those in the group A (P<0.001). Meanwhile, both the microhardness and elastic modulus in the group C were significantly higher than those in the group B (P<0.01). Corrosion potential (Ecorr) was group A > group B > group C (P<0.05). However, corrosion current density (Icorr) was significantly lower in the group A than in the group B, and in the group A than in the group C (P<0.01), while not significantly different between the B and group C (P>0.05).Breakdown potential (Ebreak) was group A

Assuntos
Corrosão , Titânio , Teste de Materiais , Propriedades de Superfície , Estanho
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