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BACKGROUND: Increasing evidence had proved that some circular RNA (circRNA) exerted critical roles in tumors progression by functioning as "microRNAs (miRNAs) sponges" to regulate their targeted genes. METHODS: circFAM114A2 and miR-647 expression was measured in CRC tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR), and the prognostic value of circFAM114A2 evaluated by Kaplan-Meier survival curve. Subsequently, wounding healing and transwell assays were performed to assess cell proliferation, migration, and invasion. RNA pull-down and dual-luciferase reporter assays were used to confirm the interactions between circFAM114A2, miR-647, and DAB2IP. RESULTS: CircFAM114A2 was notably downregulated in CRC tissues and cells, and low circFAM114A2 expression indicated the poor prognosis of CRC patients. Next, overexpression of circFAM114A2 suppressed CRC cells proliferation, migration, and invasion in vitro and impede CRC tumor growth in vivo. Mechanically, circFAM114A2 competitively bound to miR-647 and upregulated its target gene DAB2IP expression in CRC cells. CONCLUSION: Our results indicated that circFAM114A2/miR-647/DAP2IP axis played an important role in CRC progression, suggesting that circFAM114A2 might be a novel therapeutic target in patients with CRC.
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The first enantioselective total synthesis of (+)-lucidumone is described through a 13-step synthetic pathway (longest linear sequence). The key steps involve the formation of a bridged bicyclic lactone by an enantioselective inverse-electron-demand Diels-Alder cycloaddition, C-O bond formation to assemble two fragments, and a one-pot retro-[4 + 2]/[4 + 2] cycloaddition cascade. The synthesis is scalable, and more than one gram of natural product was synthesized in one batch.
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Productos Biológicos , Productos Biológicos/química , Reacción de Cicloadición , Electrones , Lactonas , EstereoisomerismoRESUMEN
A broadly applicable diastereo- and enantioselective inverse-electron-demand Diels-Alder reaction of 2-pyrones and acyclic enol ethers is reported herein. Using a copper(II)-BOX catalytic system, bridged bicyclic lactones are obtained in very high yields (up to 99 % yield) and enantioselectivities (up to 99 % ee) from diversely substituted 2-pyrones and acyclic enol ethers. Mechanistic experiments as well as DFT calculations indicate the occurrence of a stepwise mechanism. The synthetic potential of the bridged bicyclic lactones is showcased by the enantioselective synthesis of polyfunctional cyclohexenes and cyclohexadienes, as well as a carbasugar unit.
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Carba-azúcares , Pironas , Catálisis , Cobre , Reacción de Cicloadición , Ciclohexenos , Electrones , Éteres , Lactonas , EstereoisomerismoRESUMEN
Inverse-electron-demand Diels-Alder (IEDDA) reactions of electron-poor 2-pyrones as electrophilic dienes have been extensively studied in the past fifty years. These reactions provide an efficient access to bridged bicyclic lactones and their derivatives, such as densely functionalized 1,3-cyclohexadienes after CO2 extrusion and polysubstituted aromatic compounds through elimination. This reaction has been used for the synthesis of many biologically active natural products and drug candidates. In this review, the developments of these IEDDA reactions including non-catalytic, Lewis acid-catalyzed and organocatalytic IEDDA reactions, and their applications in total synthesis are discussed in detail.
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A reflective quadrature interferometer was constructed by integrating polymeric optical waveguide components, to demonstrate an optical current sensor that could operate without bias feedback control. In order to obtain two interference signals with a phase difference of 90°, half-wave and quarter-wave plates were inserted in the polymeric optical waveguide chip, and a polarization-dependent birefringence modulator was used for the initialization of the optical sensor, including detector gain adjustment. During the bias-free operation of the sensor, the measurement error was less than ± 0.2%, and it was confirmed that the sensor output was stable for 15 h even if the operating point was not maintained.
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Optical wavelength filters with large tuning range and narrow bandwidth are crucial for enhancing the capability of WDM communication systems. A polymeric tunable filter for C-band, comprising a tilted Bragg grating and a mode sorting waveguide junction is proposed in this work. For dropping a certain wavelength signal, the tilted Bragg grating reflects an odd mode into an even mode and then the reflected even mode propagates towards an output port of the asymmetric Y-junction due to the mode sorting. Consequently, the output port is separated from the input port, which is not possible in an ordinary Bragg reflector. The tilted Bragg reflector with an odd-even mode coupling efficiency of 61% exhibited a maximum reflectivity of 95% for a grating of 6 mm. A linear wavelength tuning of over 10 nm was achieved for an applied thermal power of 312 mW.
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An integrated optic polarization splitter with large fabrication tolerance and high reliability is required for optical signal processing in quantum-encrypted communication systems. A polarization splitter based on total internal reflection from a highly birefringent polymer-reactive mesogen-is proposed and demonstrated in this work. The device consists of a mode expander for reducing the wave vector distribution of the guided mode, and an interface with a large birefringence. Several polymers with suitable refractive indexes were used for fabricating the device. We obtained a polarization splitter with a low crosstalk (less than -30 dB), and a large fabrication tolerance.
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To produce a compact low-cost tunable filter required for WDM optical communications, a polymeric Bragg reflection filter with an apodized grating structure is proposed. A high-contrast polymeric waveguide is incorporated in order to obtain high reflectivity from a short Bragg grating. To overcome the bandwidth broadening, an apodized grating with a gradually changing depth of surface relief grating along the propagation direction is fabricated through the dry etching with a shadow mask. The apodized polymer grating exhibits 3-dB, 20-dB bandwidths of 0.36 nm, and 0.72 nm, respectively with a 95% reflection. The reflection wavelength is tunable over 14 nm for an applied thermal power of 500 mW.
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Array-type optical devices are important for wavelength-division multiplexing optical communication system to achieve small footprint, mass production, and reliability. For fabricating transmitter module in an array configuration, it is difficult to achieve a passive alignment of isolator, collimating lens, and laser diode. To facilitate array isolator integration, a waveguide collimator is proposed in this work by using a low-contrast, large-core polymer waveguide. The diffraction of a guided mode propagating through a free-space region is suppressed by enlarging the guided mode. The fiber coupling loss due to the enlarged mode was overcome by incorporating an adiabatic taper structure. The excess loss of waveguide collimator including the loss through a 400-µm free-propagation region was less than 1.0 dB.
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Highly integrated optical components are strongly demanded because they enable wavelength-division multiplexing optical communication systems to achieve smaller footprints, lower power consumption, and enhanced reliability. Variable optical attenuator (VOA) arrays are often used with optical switches in cascaded form for reconfigurable optical add-drop multiplexer systems. Although VOAs and optical switches based on polymer waveguide technology are commercially available, it is still not viable to integrate these two array devices on a single chip because of significant interchannel crosstalk. In this work, we resolved the issue of crosstalk and integrated the arrays of optical switch and VOA on a single chip by incorporating a self-assembled scattering monolayer (SASM). The SASM was effective for scattering the planar guided mode; consequently, the crosstalk into an adjacent channel was significantly reduced, to less than -35 dB.
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Three new resveratrol derivatives, namely, resveratrodehydes A-C (1-3), were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds showed broad-spectrum inhibitory activities against three human cancer cell lines including human breast MDA-MB-435, human liver HepG2, and human colon HCT-116 by MTT assay (IC50 < 50 µM). Among them, compounds 1 and 2 both exhibited marked cytotoxic activities against MDA-MB-435 and HCT-116 cell lines (IC50 < 10 µM). Additionally, compounds 1 and 3 showed moderate antioxidant activity by DPPH radical scavenging assay.
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Alternaria/química , Antioxidantes/química , Estilbenos/química , Alternaria/metabolismo , Antibióticos Antineoplásicos/biosíntesis , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Fermentación , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Humanos , Myoporum/microbiología , ResveratrolRESUMEN
Transcranial electrical stimulation has demonstrated the potential to enhance cognitive functions such as working memory, learning capacity, and attentional allocation. Recently, it was shown that periodic stimulation within a specific duration could augment the human brain's neuroplasticity. This study investigates the effects of repetitive transcranial alternating current stimulation (tACS; 1 mA, 5 Hz, 2 min duration) on cognitive function, functional connectivity, and topographic changes using both electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Fifteen healthy subjects were recruited to measure brain activity in the pre-, during-, and post-stimulation sessions under tACS and sham stimulation conditions. Fourteen trials of working memory tasks and eight repetitions of tACS/sham stimulation with a 1-minute intersession interval were applied to the frontal cortex of the participants. The working memory score, EEG band-wise powers, EEG topography, concentration changes of oxygenated hemoglobin, and functional connectivity (FC) were individually analyzed to quantify the behavioral and neurophysiological effects of tACS. Our results indicate that tACS increases: i) behavioral scores (i.e., 15.08, ) and EEG band-wise powers (i.e., theta and beta bands) compared to the sham stimulation condition, ii) FC of both EEG-fNIRS signals, especially in the large-scale brain network communication and interhemispheric connections, and iii) the hemodynamic response in comparison to the pre-stimulation session and the sham condition. Conclusively, the repetitive theta-band tACS stimulation improves the working memory capacity regarding behavioral and neuroplasticity perspectives. Additionally, the proposed fNIRS biomarkers (mean, slope), EEG band-wise powers, and FC can be used as neuro-feedback indices for closed-loop brain stimulation.
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Memoria a Corto Plazo , Estimulación Transcraneal de Corriente Directa , Humanos , Memoria a Corto Plazo/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Electroencefalografía , Encéfalo/fisiología , Lóbulo Frontal/fisiologíaRESUMEN
Activated channels of functional near-infrared spectroscopy are typically identified using the desired hemodynamic response function (dHRF) generated by a trial period. However, this approach is not possible for an unknown trial period. In this paper, an innovative method not using the dHRF is proposed, which extracts fluctuating signals during the resting state using maximal overlap discrete wavelet transform, identifies low-frequency wavelets corresponding to physiological noise, trains them using long-short term memory networks, and predicts/subtracts them during the task session. The motivation for prediction is to maintain the phase information of physiological noise at the start time of a task, which is possible because the signal is extended from the resting state to the task session. This technique decomposes the resting state data into nine wavelets and uses the fifth to ninth wavelets for learning and prediction. In the eighth wavelet, the prediction error difference between the with and without dHRF from the 15-s prediction window appeared to be the largest. Considering the difficulty in removing physiological noise when the activation period is near the physiological noise, the proposed method can be an alternative solution when the conventional method is not applicable. In passive brain-computer interfaces, estimating the brain signal starting time is necessary.
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With the emergence of an increasing number of functional near-infrared spectroscopy (fNIRS) devices, the significant deterioration in measurement caused by motion artifacts has become an essential research topic for fNIRS applications. However, a high requirement for mathematics and programming limits the number of related researches. Therefore, here we provide the first comprehensive review for motion artifact removal in fNIRS aiming to (i) summarize the latest achievements, (ii) present the significant solutions and evaluation metrics from the perspective of application and reproduction, and (iii) predict future topics in the field. The present review synthesizes information from fifty-one journal articles (screened according to three criteria). Three hardware-based solutions and nine algorithmic solutions are summarized, and their application requirements (compatible signal types, the availability for online applications, and limitations) and extensions are discussed. Five metrics for noise suppression and two metrics for signal distortion were synthesized to evaluate the motion artifact removal methods. Moreover, we highlight three deficiencies in the existing research: (i) The balance between the use of auxiliary hardware and that of an algorithmic solution is not clarified; (ii) few studies mention the filtering delay of the solutions, and (iii) the robustness and stability of the solution under extreme application conditions are not discussed.
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Myelofibrosis is a rare progressive cancer of the bone marrow that disrupts the normal production of healthy blood cells, leading to bone marrow failure. Patients with myelofibrosis and severe thrombocytopenia (platelet count below 50 × 109/L) have a wide range of unmet medical needs compared with those without thrombocytopenia. Usually, these patients have an increased disease burden, increased transfusion dependence, shorter overall survival, and limited treatment options. Pacritinib is a new oral kinase inhibitor specifically targeting Janus kinase 2 (JAK2), interleukin-1 receptor-associated kinase 1 (IRAK-1) and colony-stimulating factor 1 receptor (CSF-1R), and is indicated for the treatment of adults with moderate or high risk of primary or secondary myelofibrosis (post-polycythemia or post-primary thrombocytopenia) whose platelet count is less than 50 × 109/L. In this review, we introduce pacritinib and make a brief comparison of different JAK inhibitors in clinical application.
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Mielofibrosis Primaria , Inhibidores de Proteínas Quinasas , Trombocitopenia , Adulto , Humanos , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Trombocitopenia/tratamiento farmacológicoRESUMEN
Strong thermo-optic effect of polymers is useful for fabricating tunable phase-delay devices with low power consumption and wide tuning range. However, if the temperature change is increased to extend the tuning range, an attenuation of the guided light is accompanied by the refractive index gradient across the waveguide core. For three different waveguide structures, in this study, the optimal structure of the device for a variable phase delay line was found by investigating the attenuation and interference phenomena accompanying phase modulation. By improving the uniformity of thermal distribution across the waveguide core, a phase delay of 130π rad was obtained with an output attenuation less than 0.5 dB.
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A compact integrated optic polarization splitter is highly anticipated for polarization multiplexed optical communications, dual polarization optical sensors, single photon quantum signal processing, etc. In this work, we propose and demonstrate a polarization mode extracting device using a highly birefringent crosslinked liquid crystal polymer, reactive mesogen. The device includes the birefringent material inserted into a Y-branch optical waveguide to extract the TE polarized mode. A polarization splitting ratio of 27 dB was obtained, and a crosstalk of less than -25 dB was maintained for a wavelength range of 1500~1600 nm. The device exhibited good thermal stability at 100 °C for 12 hours. The broadband operating characteristic is a unique advantage of the proposed mode extracting polarization splitter.
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Aerobic oxidative α-arylation of furans with boronic acids via Pd(ii)-catalyzed C-C bond cleavage of primary furfuryl alcohols provides sustainable access to arylfurans. This protocol opens a new avenue for the transformation of readily available furans into other useful compounds.
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The objective of the study was to compare the therapeutic outcomes between the ultrasonography-guided (USG) and the fluoroscopy-guided (FG) mini-percutaneous nephrolithotomy (MPCNL) for the treatment of large or complex upper urinary tract stones (S.T.O.N.E. scores 5-11) in patients with autosomal dominant polycystic kidney disease (ADPKD). 45 ADPKD patients who were suffering from large or complex upper urinary tract stones (S.T.O.N.E. scores 5-11, mean score 7.6) in 45 renal units were accrued into this retrospective study. They were treated by either USG (20 patients) or FG (25 patients) MPCNL in our center. The treatment results as well as the complications according to the modified Clavien system were assessed and compared. The FG MPCNL group had a higher success rate in accessing the targeted calyces than the USG MPCNL group (96 vs. 70 %, p = 0.048). There was no significant difference observed between the two groups with respect to the operative time, the mean hemoglobin drop, and the stone free rate. The overall operative complications and the perioperative blood transfusion rates were significantly higher in the USG than the FG MPCNL groups, 71.4 vs. 29.2 %, p = 0.011, and 35.7 vs. 4.2 %, p = 0.018, respectively. There was no significant difference between these two groups in terms of major complications (Clavien score 3a-4a) (p = 0.542). In our center, the FG MPCNL was a superior modality to the USG MPCNL in the treatment of large or complex kidney stones in the ADPKD patients. It resulted in higher successful calyceal punctures and less operative complications.