Fluorescent Silicon Nanorods-Based Nanotheranostic Agents for Multimodal Imaging-Guided Photothermal Therapy

The utilization of diagnosis to guide/aid therapy procedures has shown great prospects in the era of personalized medicine along with the recognition of tumor heterogeneity and complexity.Herein,a kind of multifunctional silicon-based nanostructure,i.e.,gold nanoparticles-decorated fluorescent silicon nanorods(Au@SiNRs),is fabricated and exploited for tumor-targeted multimodal imaging-guided photothermal therapy.In particular,the prepared Au@SiNRs feature high photothermal conversion efficiency(~43.9%)and strong photothermal stability(photothermal performance stays constant after five-cycle NIR laser irradiation),making them high-performance agents for simultaneously photoacoustic and infrared thermal imaging.The Au@SiNRs are readily modified with targeting peptide ligands,enabling an enhanced tumor accumulation with a high value of^8.74%ID g?1.Taking advantages of these unique merits,the Au@SiNRs are superbly suitable for specifically ablating tumors in vivo without appreciable toxicity under the guidance of multimodal imaging.Typically,all the mice treated with the Au@SiNRs remain alive,and no distinct tumor recurrence is observed during 60-day investigation.

Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of siRNA and Doxorubicin to Drug-Resistant Cancer Cells

The development of effective and safe vehicles to deliver small interfering RNA(siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics,which has emerged as a powerful platform to treat drug-resistant cancer cells.Herein,we describe the development of novel all-in-one fluorescent silicon nanoparticles(SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin(DOX).This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells(i.e.,MCF-7/ADR cells).Typically,the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment(i.e.,medium or RNase A) and imparted the responsive release behavior of siRNA,resulting in approximately 80% down-regulation of P-glycoprotein expression.Co-delivery of P-glycoprotein siRNA and DOX led to>35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX,indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells.The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs.These data provide valuable information for designing effective RNA interference-based co-delivery carriers.

Coordinated Damping Optimization Control of Sub-synchronous Oscillation for DFIG and SVG

Currently, the power electronics-based devices, includinglarge-scale non-synchronized generators and reactivepower compensators, are widely used in power grids. This helpsintroduce the coupling interactions between the devices andthe power grid, resulting in a new sub-synchronous oscillationphenomenon. It is a critical element for the stability operation ofthe power grid and its devices. In this paper, the sub-synchronousoscillation phenomenon of the power grid connected with largescalewind power generation is analyzed in detail. Then, inorder to damp the sub-synchronous oscillation, a coordinateddamping optimization control strategy for wind power generatorsand their reactive power compensators is proposed. The proposedcoordinated control strategy tracks the sub-synchronousoscillation current signal to correct the corresponding controlsignal, which increases the damping of power electronics. Theresponse characteristics of the proposed control strategy areanalyzed, and a self-optimization parameter tuning method basedon sensitivity analysis is proposed. The simulation results validatethe effectiveness and the availability of the proposed controlstrategy.

The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury

Sentrin-specific protease 3（SENP3）, a member of the desumoylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, its implication in myocardial ischemia reperfusion（MIR） injury is unclear. Here, we observed that SENP3 was expressed and upregulated in the mouse heart depending on reactive oxygen species（ROS） production in response to MIR injury. By utilizing si RNA-mediated cardiac specific gene silencing, SENP3 knockdown was demonstrated to significantly reduce MIR-induced infarct size and improve cardiac function. Mechanistic studies indicated that SENP3 silencing ameliorated myocardial apoptosis mainly via suppression of endoplasmic reticulum（ER） stress and mitochondrial-mediated apoptosis pathways. By contrast, adenovirusmediated cardiac SENP3 overexpression significantly exaggerated MIR injury. Further molecular analysis revealed that SENP3 promoted mitochondrial translocation of dynamin-related protein 1（Drp1） in reperfused myocardium. In addition, mitochondrial division inhibitor-1（Mdivi-1）, a pharmacological inhibitor of Drp1, significantly attenuated the exaggerated mitochondrial abnormality and cardiac injury by SENP3 overexpression after MIR injury. Taken together, we provide the first direct evidence that SENP3 upregulation pivotally contributes to MIR injury in a Drp1-dependent manner, and suggest that SENP3 suppression may hold therapeutic promise for constraining MIR injury.

Doxorubicin-loaded silicon nanoparticles impregnated into red blood cells featuring bright fluorescence, strong photostability, and lengthened blood residency

基于唯一的优点荧光灯硅 nanoparticles (SiNPs ) ，长发行量红血房间(RBC ) ，和反癌症药分子(即， doxorubicin (纪录影片)) ，我们开发了使妊娠进 RBC 的多功能的装载纪录影片的 SiNPs。重要地，产生的药交货系统(DDS ) 同时展出了结合的明亮的荧光柔韧的 photostability (即， 24% 损失荧光灯在 25 min 以后的紧张连续激光照耀) 并且显著地变长的血住处(即， t 1/2= 7.31 吗？？

Fluorescent silicon nanoparticles-based nanotheranostic agents for rapid diagnosis and treatment of bacteria-induced keratitis

Recommended as a medical emergency,infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness.Herein,we present a kind of theranostic agents,which are made of vancomycin(Van)-modified fluorescent silicon nanoparticles(SiNPs-Van),enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner.Typically,the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro(5 min)and in vivo(10 min),making them an efficacious diagnostic agent for the detection of bacterial keratitis.In addition,the SiNPs-Van feature distinct antimicrobial activity,with superior activity of 92.5%at a concentration of 0.5 ng/mL against Staphylococcus aureus(S.aureus);comparatively,the antimicrobial rate of free vancomycin is 23.3%at the same concentration.We further explore the SiNPs-Van agents as eye drops for therapy of S.aureus-induced bacterial keratitis on rat model.Represented by slit-lamp scores,the keratitis severity of SiNPs-Van-treated corneas is 3.4,which is 59.6%and 77.3%slighter than vancomycin-(8.2 score)and PBS-treated corneas(15.0 score),respectively.The infected corneas recover to normal(1 score)after 7-d of SiNPs-Van treatment.Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents,especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis.

Traditional Chinese medicine molecule-assisted chemical synthesis of fluorescent anti-cancer silicon nanoparUcles

Fluorescent silicon （Si） nanopartides （SiNPs） hold great promise for innumerable biological and biomedical applications owing to their unique optical properties and negligible toxicity. In this article, we present a new traditional Chinese medicine （TCM） molecule-assisted chemical synthetic strateg36 suitable for the production of multifunctional small-sized （diameter： - 3.7 nm） SiNPs in a facile and rapid （- 10 min） manner. Of particular significance, the resultant SiNPs simultaneously exhibited robust and stable fluorescence （photoluminescence quantum yield （PLQY）： ~ 15%）, as well as intrinsic anti-cancer efficacy with excellent selectivity toward cancer cells. Taking advantage of these unique merits, we further employed these novel fluorescent anti-cancer SiNPs （AC-SiNPs） for the fluorescence tracking and treatment of tumors, demonstrating long-term （~ 18 days） inhibition of tumor growth in tumor-bearing mice. Consequently, we believe this new TCM-assisted chemical synthetic method is highly attractive for designing silicon nanostructures featuring multiple functionalities, and we suggest these AC-SiNPs as novel promising tools for providing visual evidence of TCM-based cancer treatment.

Investigation on layover imaging in synthetic aperture ladar

Due to the short laser wavelength, almost all practical targets are rough. Surface elevations in rough targets will result in layovers in synthetic aperture ladar （SAL）. High resolution SAL image with layovers will be different fi＇om the target picture taken by incoherent tools as digital camera. To investigate the layovers in SAL image, a simplified mathematical model is built by optics diffraction theory and a laboratory SAL is setup using 1550 mn tunable laser source. Layovers in SAL images, in both theoretical simulation and experimental demonstra- tion, are carefully observed. Detailed results on various targets are illustrated.

Long-term fundus fluorescence angiography and real-time diagnosis of retinal diseases in non-human primate-animal models

Fluorescein angiography(FA)is a standard imaging modality for evaluating vascular abnormalities in retina-related diseases,which is recognized as the major cause of vision loss.Long-term and real-time fundus angiography is of great importance in preclinical research,nevertheless remaining big challenges up to present.In this study,we demonstrate that long-term fluorescence imaging of retinal vessels is enabled through a kind of fluorescent nanoagents,which is made of small-sized(hydrodynamic diameter:∼3 nm)silicon nanoparticles(SiNPs)featuring strong fluorescence,robust photostability,lengthened blood residency and negligible toxicity.In particular,the presented SiNPs-based nanoagents are capable of imaging retinal capillaries in∼10 min,which is around 10-fold longer than that(∼1 min)of fluorescein sodium(FS,known as the most widely used contrast agents for FA in clinic).Taking cynomolgus macaques as non-human primate-animal model,we further demonstrate the feasibility of real-time diagnosis of retinal diseases(e.g.,age-related macular degeneration(AMD))through dynamic monitoring of vascular dysfunction.

The in vivo targeted molecular imaging of fluorescent silicon nanoparticles in Caenorhabditis elegans

Owing to their unique optical properties （e.g., bright fluorescence coupled with strong photostability） and negligible toxicity, fluorescent silicon nanoparticles （SiNPs） have been demonstrated to be promising probes for bioimaging analysis. Herein, we describe the use of Caenorhabditis elegans （C. elegans） as an animal model to investigate the in vivo behavior and molecular imaging capacity of ultrasmall fluorescent SiNPs （e.g., - 3.9 ± 0.4 nm）. Our studies show that （1） the internalized SiNPs do not affect the morphology and physiology of the worms, suggesting the superior biocompatibility of SiNPs in live organisms; （2） the internalized SiNPs cannot cross the basement membrane of C. elegans tissues and they display limited diffusion ability in vivo, providing the possibility of their use as nanoprobes for specific tissue imaging studies in intact animals; （3） more than 80% of the fluorescence signal of internalized SiNPs remains even after 120 min of continuous laser bleaching, whereas only - 20% of the signal intensity of mCherry or cadmium telluride quantum dots remains under the same condition, indicating the robust photostability of SiNPs in live organisms; and （4） cydic RGD-peptide-conjugated SiNPs can specifically label muscle attachment structures in live C. elegans, which is the first proof-of-concept example of SiNPs for targeted molecular imaging in these live worms. These finding raise exciting opportunities for the design of high-quality SiNP-based fluorescent probes for long-term and real-time tracking of biological events in vivo.