Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The ...interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific ...drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in ...OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment. However, a major bottleneck to achieve the therapeutic potential of the CRISPR/Cas9 is the lack of in vivo tumor-targeted delivery systems. Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9. Our results demonstrated that LC09 facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective VEGFA genome editing in tumor, decreased VEGFA expression and secretion, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The delivery system simultaneously restrained autocrine and paracrine VEGFA signaling in tumor cells and could facilitate translating CRISPR-Cas9 into clinical cancer treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
When the finite control set model predictive control (FCS-MPC) is applied to the three-level converter, there are problems such as large current harmonics, high requirements for the computing ...efficiency of the microcontroller, complex multi-objective optimization and limited output vector switching. In addition,the mismatch of inductance parameter may directly affect the observation accuracy of FCS-MPC. To solve the above problem,a double vector model predictive control strategy with constant frequency strategy based on the inductance parameters on-line identification is presented.First, a single objective cost function based on the direct power is constructed by optimizing the redundant vector which is selected to balance the neutral-point potential, the design of weighting factor is avoided.At the same time, in order to effectively reduce the grid current ripple under single vector modulation, space vector pulse width modulation (SVPWM) is realized by combining with zero vector control mode. And, a parameter identification method based on model reference adaptive system(MARS) is proposed to overcome the effect of model parameter mismatch.Finally, the results show that the proposed F-MPCCF has good steady-state and dynamic performance from the static, transient and neutral-point potential control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human ...bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3'UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Tin-based perovskite solar cells (PSCs), with more consummate optical band gaps, lower exciton-binding energies, and higher charge-carrier mobility, have not attracted tremendous research efforts ...compared with the lead-based ones that have a record power conversion efficiency (PCE) of 24.2%. The major challenges for Sn-based research are significantly low open-circuit voltage, poor reproducibility, and environmental instability. It has been identified that the oxidation processes take place during the preparation of precursor solutions and fabrication of films, due to the low redox potential of the stannous absorption layer. Herein, we propose two strategies of crystal-resolving and recrystallization technology to reduce the oxidation process. As a result, PCEs of 8.9% (active area of 0.04 cm2) and 5.5% (active area = 1.01 cm2) are attained using the inverted p-i-n structure, which will lead to a revival of lead-free PSC research.
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•Efficient growth method of FASnI3 single crystals and recycling of mother liquid•Film is made using crystalline precursor solutions and anti-solvent-free method•PCEs of 8.9% (0.04 cm2) and 5.5% (1.01 cm2) are the highest 3D-based PCEs•Precursor solutions and fabricated lead-free solar cells show excellent stability
Tin-based perovskite solar cells possess largely preserved or even superior photoelectric semiconducting properties compared with the Pb-based counterparts except for the ultralow toxicity. However, the low redox potential of Sn2+ makes it more easily oxidized, leading to low energy conversion efficiency and stability. The oxidation process mainly occurs during preparation of precursor solutions and fabrication of films. Here, the introduced low-cost crystal precursor solution greatly improves the quality of film with large crystalline grain densification of the outside appearance through an anti-solvent-free method. As a result, efficient and stabilized spin-coated (8.9% for 0.04 cm2) and printed (5.5% for 1.01 cm2) solar cells are achieved for potential commercialization.
The existence of a mass oxidation of Sn2+ that takes place mainly during preparation of precursor solutions and fabrication of films creates a lead-free solar cell of low open-circuit voltage, which leads to low PCE. To reduce the oxidation process, we employed an innovative crystal fabrication method with anti-solvent-free recrystallization technology. As a result, to the best of our knowledge, both spin-coated and printed lead-free solar cells based on FASnI3 achieved the highest 3D-based PCE to date.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Emerging evidence indicates that the dysregulation of protein ubiquitination plays a crucial role in aging‐associated diseases. Smad‐dependent canonical BMP signaling pathway is indispensable ...for osteoblastic bone formation, which could be disrupted by the ubiquitination and subsequent proteasomal degradation of Smad1/5, the key molecules for BMP signaling transduction. However, whether the dysregulation of Smad1/5 ubiquitination and disrupted BMP signaling pathway is responsible for the age‐related bone formation reduction is still underexplored. Pleckstrin homology domain‐containing family O member 1 (PLEKHO1) is a previously identified ubiquitination‐related molecule that could specifically target the linker region between the WW domains of Smurf1 to promote the ubiquitination of Smad1/5. Here, we found an age‐related increase in the expression of PLEKHO1 in bone specimens from either fractured patients or aging rodents, which was associated with the age‐related reduction in Smad‐dependent BMP signaling and bone formation. By genetic approach, we demonstrated that loss of Plekho1 in osteoblasts could promote the Smad‐dependent BMP signaling and alleviated the age‐related bone formation reduction. In addition, osteoblast‐specific Smad1 overexpression had beneficial effect on bone formation during aging, which could be counteracted after overexpressing Plekho1 within osteoblasts. By pharmacological approach, we showed that osteoblast‐targeted Plekho1 siRNA treatment could enhance Smad‐dependent BMP signaling and promote bone formation in aging rodents. Taken together, it suggests that the increased PLEKHO1 could suppress Smad‐dependent BMP signaling to inhibit bone formation during aging, indicating the translational potential of targeting PLEKHO1 in osteoblast as a novel bone anabolic strategy for reversing established osteoporosis during aging.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
A three-level T-type grid-connected inverter has been widely used in the current medium power distributed PV inverters, charging station and active power filter system with the advantages of high ...equivalent switching frequency, high efficiency, small filter inductance and grid current harmonic. However, the grid-connected inverter with LCL-filter is a third-order and multi-variable system, to meet the high-performance requirements for grid-connected current, claiming a higher requirement for the grid-current control system. Aiming at this, a new control strategy named capacitive current feedforward control based on the carrier-based PWM modulation scheme on is put forward. Further, to improve the power density, the capacitor current is generated indirectly calculated by the capacitor voltage. Finally, to verify the correctness and effectiveness of the proposed control strategy, a complete digital simulation model and experimental prototype platform is established, the detailed theoretical analysis and design method of the proposed control strategy are presented. The simulation and experimental results show that the steady and the transient performance of the grid current with the proposed control strategy are effectively improved, and no additional sensors are needed.
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