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1.
Front Cell Dev Biol ; 8: 586581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195240

RESUMO

Mutations in the enzyme isocitrate dehydrogenase 1/2 (IDH1/2) are the most common somatic mutations in low-grade glioma (LGG). The Hippo signaling pathway is known to play a key role in organ size control, and its dysregulation is involved in the development of diverse cancers. Large tumor suppressor 1/2 (LATS1/2) are core Hippo pathway components that phosphorylate and inactivate Yes-associated protein (YAP), a transcriptional co-activator that regulates expression of genes involved in tumorigenesis. A recent report from The Cancer Genome Atlas (TCGA) has highlighted a frequent hypermethylation of LATS2 in IDH-mutant LGG. However, it is unclear if LATS2 hypermethylation is associated with YAP activation and prognosis of LGG patients. Here, we performed a network analysis of the status of the Hippo pathway in IDH-mutant LGG samples and determined its association with cancer prognosis. Combining TCGA data with our biochemical assays, we found hypermethylation of LATS2 promoter in IDH-mutant LGG. LATS2 hypermethylation, however, did not translate into YAP activation but highly correlated with IDH mutation. LATS2 hypermethylation may thus serve as an alternative for IDH mutation in diagnosis and a favorable prognostic factor for LGG patients.

2.
Cell Signal ; 75: 109775, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32916277

RESUMO

Proteasome inhibitors (PIs) are currently used in the clinic to treat cancers such as multiple myeloma (MM). However, cancer cells often rapidly develop drug resistance towards PIs due to a compensatory mechanism mediated by nuclear factor erythroid 2 like 1 (NFE2L1) and aspartic protease DNA damage inducible 1 homolog 2 (DDI2). Following DDI2-mediated cleavage, NFE2L1 is able to induce transcription of virtually all proteasome subunit genes. Under normal condition, cleaved NFE2L1 is constantly degraded by proteasome, whereas in the presence of PIs, it accumulates and induces proteasome synthesis which in turn promotes the development of drug resistance towards PIs. Here, we report that Nelfinavir (NFV), an HIV protease inhibitor, can inhibit DDI2 activity directly. Inhibition of DDI2 by NFV effectively blocks NFE2L1 proteolysis and potentiates cytotoxicity of PIs in cancer cells. Recent clinical evidence indicated that NFV can effectively delay the refractory period of MM patients treated with PI-based therapy. Our finding hence provides a specific molecular mechanism for combinatorial therapy using NFV and PIs for treating MM and probably additional cancers.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32203039

RESUMO

We develop a method for obtaining safe initial policies for reinforcement learning via approximate dynamic programming (ADP) techniques for uncertain systems evolving with discrete-time dynamics. We employ the kernelized Lipschitz estimation to learn multiplier matrices that are used in semidefinite programming frameworks for computing admissible initial control policies with provably high probability. Such admissible controllers enable safe initialization and constraint enforcement while providing exponential stability of the equilibrium of the closed-loop system.

5.
IEEE Trans Neural Netw Learn Syst ; 26(2): 409-14, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25576583

RESUMO

This brief studies the optimal codesign of nonlinear control systems: simultaneous design of physical plants and related optimal control policies. Nonlinearity of the optimal codesign problem could come from either a nonquadratic cost function or the plant. After formulating the optimal codesign into a nonconvex optimization problem, an iterative scheme is proposed in this brief by adding an additional step of system-equivalence-based policy improvement to the conventional policy iteration. We have proved rigorously that the closed-loop system performance can be improved after each step of the proposed policy iteration scheme, and the convergence to a suboptimal solution is guaranteed. It is also shown that under certain conditions, this additional policy improvement step can be conducted by solving a quadratic programming problem. The linear version of the proposed methodology is addressed in the context of linear quadratic regulator. Finally, the effectiveness of the proposed methodology is illustrated through the optimal codesign of a load-positioning system.

6.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 25(6): 657-8, 661, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24490410

RESUMO

OBJECTIVE: To explore a new monitoring method for schistosomiasis transmission interrupted areas, so as to evaluate the monitoring results in counties (districts) to improve the quality. METHODS: Specialized technicians were selected as survey teams to investigate the status of Oncomelania hupensis snails with the random sampling method combined with environmental sampling method every year from 1997 to 2013. RESULTS: From 1997 to 2013, 118 villages of 38 townships of 21 counties were investigated for the snail status, and there were 18 environments with snails in 10 townships of 7 counties. The snail area was 10.91 hm2. CONCLUSION: There are still small snail areas. Therefore, the snail monitoring should still be strengthened by specialized technicians.


Assuntos
Reservatórios de Doenças/parasitologia , Esquistossomose/prevenção & controle , Caramujos/parasitologia , Animais , Humanos , Densidade Demográfica , Esquistossomose/transmissão , Fatores de Tempo
7.
Artigo em Chinês | MEDLINE | ID: mdl-23236788

RESUMO

There were 240 newly advanced schistosomiasis patients in Huangshan City from 2004 to 2011. All the patients were clinically diagnosed and mainly distributed in the countries which were once heavy endemic areas in history. Most of the patients were diagnosed in 2007 and 2008, and those aged more than 60 years accounted for 79.16% of the total cases. Among all the cases, ascites type and splenomegaly type accounted for 66.25% and 31.66% respectively. In conclusion, there are still newly advanced schistosomiasis cases in areas of schistosomiasis transmission interruption, so the monitoring, diagnosis and treatment of historical schistosomiasis patients should be strengthened.


Assuntos
Esquistossomose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquistossomose/transmissão
8.
Artigo em Chinês | MEDLINE | ID: mdl-22379846

RESUMO

In Huangshan City, schistosomiasis surveillance from 1994 to 2010 showed that there were no patients and livestock newly infected with schistosome, no infected Oncomelania snails, but the snail status was stable. It is suggested that the schistosomiasis control strategy with emphasis on snail surveillance is effective, and snail surveillance is still a key measure of schistosomiasis surveillance in the future.


Assuntos
Doenças dos Bovinos/epidemiologia , Esquistossomose/epidemiologia , Esquistossomose/veterinária , Vigilância de Evento Sentinela , Adolescente , Adulto , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Criança , China/epidemiologia , Reservatórios de Doenças/parasitologia , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde da População Rural , Esquistossomose/parasitologia , Esquistossomose/transmissão , Caramujos/crescimento & desenvolvimento , Caramujos/parasitologia , Adulto Jovem
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