Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

Effective Capacity in Cognitive Radio Networks with Relay and Primary User Emulator

In this paper,the transmission performances are studied in cognitive radio networks with primary user emulator and relay existence.In the proposed network,the users include primary users,secondary users and primary user emulators.The decreasing access priority of the users are primary users,primary user emulators and secondary users.Different user access to the network results in different transmission effects.We impose interference power constraints on the secondary users to protect the primary users from being interfered.We also adopt the transmission mechanism that transits among more than one secondary transmitters,secondary receivers and relays.The transition models of the transmission states are proposed to describe the transmission mechanism.To investigate the transmission performances,the theory of effective capacity is adopted.The transmission performances in terms of effective capacity are expressed and demonstrated under different transmission policies.The overall effective capacity,as the overall data traffic in the cognitive radio network,is calculated.Besides,the overall effective capacity is demonstrated under different transmission strategies.The results show the greedy transmission strategy outperforms the rest of the transmission 8 policies in the overall effective capacity.For a larger number of the users,the effective capacity converges to a certain value.

Tolerance of neurite outgrowth to Rho kinase inhibitors decreased by cyclooxygenase-2 inhibitor

In this study, PC12 Adh cells and Neuro-2a cells were treated with Rho-associated kinase inhibitors （Y27632 and Fasudil）, a cyclooxygenase-1 selective inhibitor （SC560）, and a cyclooxygenase-2 inhibitor （NS398）. We found that these cells became tolerant to Rho-associated kinase inhibitors, as neurite outgrowth induced by these inhibitors diminished following more than 3 days of exposure in either cell line. The proteins cyclooxygenase-2 and cytosolic prostaglandin E synthetase were upregulated at day 3. NS398 decreased the tolerance to neurite outgrowth induction in both cell lines, whereas SC560 had almost no effect. These findings indicate that cells become tolerant to neurite outgrowth induced by Rho-associated kinase inhibitors, this is at least partly associated with upregulation of proteins involved in the cyclooxygenase-2 pathway, and cyclooxygenases-2 inhibition prevents this tolerance.

Patterning of large area nanoscale domains in as-grown epitaxial ferroelectric PbTiO_(3)films

Effective tuning of nanoscale domain structures provides fundamental basis for controlling and engineering of various functionalities in ferroelectric materials.In this work,we demonstrate the precise patterning of nanoscopic domain structures in as-grown epitaxial PbTiO_(3)(PTO)films by merely introducing an ultrathin pre-patterned doping layer(e.g.,Fe-doped PTO).The doping layer can effectively reverse the interfacial built-in bias,consequent to a reversed initial polarization reorientation in the as-grown film,which makes it possible to transfer the nano-patterns in the doping layer into the domain structure of ferroelectric films.For instance,we have successfully fabricated large area ordered array of nanoscale cylindrical domains(downward polarization)embedded in the matrix domain with opposite polarization(upward polarization)in PTO film.These nanoscale cylinder domains also allow deterministic and reversible erasure and creation induced by biased tip scanning.The results provide an effective pathway for on-demand patterning of large area nanoscale domains in the as-grown films,which may find applications in a wide range of nanoelectronic devices.

A new perspective of triptolide-associated hepatotoxicity:the relevance of NF-κB and NF-κB-mediated cellular FLICE-inhibitory protein

Previously,we proposed a new perspective of triptolide(TP)-associated hepatotoxicity:liver hypersensitivity upon lipopolysaccharide(LPS)stimulation.However,the mechanisms for TP/LPSinduced hepatotoxicity remained elusive.The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation.TSF-αinhibitor,etanercept,was injected intraperitoneally into mice to investigate whether induction of TNF-αby LPS participated in the liver injury induced by TP/LPS co-treatment.Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF-αto assess the function of TNF-αin TP/LPS co-treatment.Additionally,time-dependent MF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in vitro.Finally,overexpression of cellular FLICEinhibitory protein(FLIP),the most potent NF-κB-mediated pro-survival protein,was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity.Etanercept counteracted the toxic reactions induced by TP/LPS.TP-treatment sensitized mice and hepatocytes to TNF-α,revealing the role of TNF-αin TP/LPS-induced hepatotoxicity.Mechanistic studies revealed that TP inhibited NF-κB dependent pro-survival signals,especially FLIP,induced by LPS/TNF-α.Moreover,overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in vitro.Mice and hepatocytes treated with TP were sensitive to TNF-α,which was released from LPS-stimulated immune cells.These and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke,but how to control the overactive neuroinflammation is still a long-standing challenge.Here,we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia,which were abolished by silencing SIRT6.RNA-seq screening identified the forkhead box C1 (Foxc1) is a key gene evoked by MDL-811stimulation and is required for the anti-inflammatory effects of MDL-811.We found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of Foxc1 and upregulate its expression to modulate inflammation.Moreover,our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS,but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional recovery.Importantly,MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients,underlying an interesting translational perspective.Taken together,MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation.

Controlled manipulation of conductive ferroelectric domain walls and nanoscale domains in BiFeO_(3) thin films

Recently,there is a surge of research interest in configurable ferroelectric conductive domain walls which have been considered as possible fundamental building blocks for future electronic devices.In this work,by using piezoresponse force microscopy and conductive atomic force microscopy,we demonstrated the controlled manipulation of various conductive domain walls in epitaxial BiFeO_(3) thin films,e.g.neutral domain walls(NDW)and charged domain walls(CDWs).More interestingly,a specific type of nanoscale domains was also identified,which are surrounded by highly conductive circular CWDs.Similar nano-scale domains can also be controlled created and erasured by applying local field via conductive probe,which allow nondestructive current readout of different domain states with a large on/off resistance ratio up to 102.The results indicate the potential to design and develop high-density non-volatile ferroelectric memories by utilizing these programable conductive nanoscale domain walls.