Low Loading Capacity Research Articles

Antibody–siRNA conjugates (ARC): Emerging siRNA drug formulation

Antibody–drug conjugates (ADC) utilizing the targeting properties of antibodies and therapeutic effects of drugs have emerged a rapid development in recent years. However, the relatively low drug loading capacity of ADC systems commonly results in failure in delivering enough chemical drugs to the desired areas given a safe antibody dose, therefore the therapeutic efficacy of ADC systems is restricted. With the FDA approval of four siRNA drugs, patisiran, givosiran, lumasiran and inclisiran, the development of siRNAs has regained huge attention of researchers, where the design of delivery system for siRNAs is the key issue for further clinical applications. Inspired by the concept of ADC, the antibody–siRNA conjugates (ARC) have emerged as a potential vehicle for targeted siRNA drug delivery, with the ability to overcome the current obstacles in siRNA delivery. In this review, we summarized the efforts in the development of antibody–siRNA conjugates and hope to provide a basic view for researchers who are interested in this field.

Redox-responsive self-assembled polymeric nanoprodrug for delivery of gemcitabine in B-cell lymphoma therapy

Gemcitabine, as a standard and classic strategy for B-cell lymphoma in the clinic, is limited by its poor pharmacodynamics. Although stimuli-responsive polymeric nanodelivery systems have been widely investigated in the past decade, issues such as complicated procedures, low loading capacity, and uncontrollable release kinetics still hinder their clinical translation. In view of the above considerations, we attempt to construct hyperbranched polyprodrug micelles with considerable drug loading via simple procedures and make use of the particularity of the tumor microenvironment to ensure that the micelles are “inactivated” in normal tissues and “activated” in the tumor microenvironment. Hence, in this work, a redox-responsive polymeric gemcitabine-prodrug (GEM-S-S-PEG) was one-pot synthesized via facile esterification and acylation. The self-assembled subsize (< 100 nm) GEM-S-S-PEG (GSP NPs) with considerable loading capacity (≈ 24.6%) exhibited on-demand and accurate control of gemcitabine release under a simulated tumor microenvironment and thus significantly induced the apoptosis of B-cell lymphoma in vitro. Moreover, in the A20 tumor xenograft murine model, GSP NPs efficiently decreased the expansion of tumor tissues with minimal systemic toxicity. In summary, these redox-responsive and self-assembling GSP NPs with a facile one-pot synthesis procedure may hold great potency in clinical translation for enhanced chemotherapy of B-cell lymphoma. Statement of significanceA redox-responsive polymeric gemcitabine-prodrug (GEM-S-S-PEG) was one-pot synthesized via facile esterification and acylation.The self-assembled subsize (< 100 nm) GEM-S-S-PEG (GSP NPs) exhibited significant tumor therapeutic effects in vitro and in vivo.The polyprodrug GEM-S-S-PEG prepared in this study shows the great potential of redox-responsive nanodrugs for antitumor activity, which provides a reference value for the optimization of the design of functional polyprodrugs.

ОСЛІДЖЕННЯ НАПРУЖЕНО-ДЕФОРМОВАНОГО СТАНУ ЗАЛІЗОБЕТОННОЇ МОНОЛІТНОЇ ПРОГОНОВОЇ БУДОВИ МОСТУ ПІСЛЯ ТРИВАЛОЇ ЕКСПЛУАТАЦІЇ

Introduction. The vast majority of reinforced concrete bridges built in Ukraine until the 1950s were mostly monolithic. Spans were built of monolithic concrete with a length of 2, ..., 6 m and ribbed structures with a length of 8, ..., 15 m. Monolithic spans were provided with good spatial work and considerable durability. Problems Statement. The main disadvantage of reinforced concrete monolithic spans of bridges built before the 50s of the last century was the low design strength of concrete, which over time led to defects and thus reduce their durability. In addition, the vast majority of such bridges with monolithic spans were built according to technical standards of 1962 and earlier, and at this time the load capacity does not meet the requirements of modern regulations. The need to study the stress-strain state, to determine the bearing capacity of the spans of bridges after long-term operation, given the above, is an important factor in deciding on the feasibility of their repair. Purpose. Research of the stress-strain state of the structures of the monolithic spans of the bridge after its long operation. Materials and Methods. A survey of the monolithic reinforced concrete span of the bridge, built in 1940, was carried out. It was established that the span of the bridge, in accordance with the identified defects, is in a limited working condition (condition 4). And given the low load capacity of the span, condition 5 (inoperable) was finally adopted. The main defects found during the inspections of the span significantly reduce its durability and bearing capacity. Destruction of the protective layer of beams of the span with exposure and intensive corrosion of reinforcement with weakening of the area by more than 10% was revealed. Based on the data from the inspection of the bridge, it was decided to conduct additional tests to determine the stress-strain state of the spans, the availability of strength reserves and the possibility of strengthening them or the need for replacement. Results. Based on the test of the bridge, the parameters of spatial work and stress-strain state of the span were determined by measuring the absolute deformations (deflections) under the action of static load. According to the test results, the value of the design coefficient k, which is in the range of 0.1… 0.79, was determined. The values of the transverse distribution coefficients (CRC) for each beam were experimentally determined and the numerical analysis of the field and analytical spatial work of the span of the bridge on the transverse distribution coefficients was performed. Conclusion. The results of the analysis of experimentally and analytically obtained test data of the bridge indicate the normal spatial operation of the bridge spans, which corresponds to the nature of the idealized finite element scheme, good spatial rigidity and the presence of strength reserves in the bridge spans. Key words: bridges, span, tests, deformability, technical condition.

Robust online operation of power systems with advanced adiabatic compressed air energy storage and renewable generation

With the rapid growth of renewable generation in power system, the share of dispatchable power reduces, raising the need for large-scale energy storage to compensate for volatile renewable output. Advanced adiabatic compressed air energy storage (AA-CAES), advantageous in large capacity and emission-free, is promising for grid-level use. This paper studies the operation of power systems with renewable generation and AA-CAES. The off-design characteristics of AA-CAES are featured by variable efficiencies and limited low-load capacity. A battery-like linear model of AA-CAES is suggested, in which the coefficients can be calibrated from experiments or simulations. A robust online operation scheme is proposed which only requires the currently observable information and makes no reference to renewable forecast. In the day-ahead stage, the unit on–off status as well as lower and upper bounds of unit output and storage levels in all periods are derived from a robust unit commitment model. In the real-time dispatch stage, an optimal power flow problem with pre-allocated operation bounds is solved. Feasibility is guaranteed by the setting of operation bounds obtained from the robust model. Case studies illustrate the precision of the simplified AA-CAES model and validate the performance of the operation method. The results indicate that a linear model is suitable when AA-CAES operates in near constant-pressure conditions, whose error is 0.4% for the charging part and 1.4% for the discharging part. A non-anticipative robust formulation is superior to conventional two-stage robust optimization in feasibility enforcement under uncertainty, the later encounters an infeasible probability up to 42% when the power system lacks limited regulation sources.

Nanostructure and Morphology of the Surface as Well as Micromechanical and Sclerometric Properties of Al2O3 Layers Subjected to Thermo-Chemical Treatment

The article presents the effect of the thermo-chemical treatment of Al2O3 layers on their nanostructure, surface morphology, chemical composition as well as their micromechanical and sclerometric properties. Oxide layers were produced on EN AW-5251 aluminium alloy (AlMg2) by the method of direct current anodizing in a three-component electrolyte. The thermo-chemical treatment was carried out in distilled water and aqueous solutions of Na2SO4·10H2O and Na2Cr2O7·2H2O. It was shown that the thermo-chemical treatment process changes the morphology of the surface of the layers (the formation of a sub-layer from the Na2SO4·10H2O and Na2Cr2O7·2H2O solutions), which directly increases the thickness of the layers by 0.37 and 1.77 µm, respectively. The thermo-chemical treatment in water also resulted in the formation of a 0.63 µm thick sub-layer. The micromechanical tests indicated a rise in the surface microhardness of the layers in the case of their thermo-chemical treatment in water and the Na2SO4·10H2O solution and a decrease in the case of the layers modified in the Na2Cr2O7·2H2O solution. The highest microhardness (7.1 GPa) was exhibited by the layer modified in the Na2SO4·10H2O solution. Scratch tests demonstrated that the thermo-chemically treated layers had better adhesive properties than the reference layer. The best scratch resistance was exhibited by the layer after thermo-chemical treatment in the Na2SO4·10H2O solution (the highest values, practically for all the critical loads) which, together with its low roughness and high load capacity, predispose it to sliding contacts.

Aptamers Entirely Built from Therapeutic Nucleoside Analogues for Targeted Cancer Therapy.

Owing to the specific and high binding affinity of aptamers to their targets, aptamer-drug conjugates (ApDCs) have emerged as a promising drug delivery system for targeted cancer therapy. However, in a conventional ApDC, the aptamer segment usually just serves as a targeting moiety, and only a limited number of drug molecules are sequentially conjugated to the oligonucleotide, giving a relatively low drug loading capacity. To address this challenge, herein we employ four clinically approved nucleoside analogues, including clofarabine (Clo), ara-guanosine (AraG), gemcitabine (Ge), and floxuridine (FdU), to replace all natural nucleosides in aptamer sequences, generating a series of whole drug-constituted DNA-like oligomers that are termed drugtamers. Similar to their parent aptamers, the obtained drugtamers maintain the targeting capability and can specifically bind to the target receptors overexpressed on the cancer cell surface. With 100% drug loading ratio, active targeting capability, and enzyme-mediated release of active therapeutics, our drugtamers can strongly induce the apoptosis of cancer cells and inhibit the tumor progression, which enables a new potential for a better targeted cancer therapy.

高碳含量新型亚微米无孔二氧化硅材料的修饰方法及其在反相加压毛细管电色谱平台上的应用

亚微米无孔二氧化硅(NPS)材料具有小粒径及表面光滑形状规整等特点,是一种性能优异的色谱材料,但其存在比表面积小、修饰效率低的问题。针对此设计了一种具有高碳含量的修饰方法:以3-缩水甘油基氧基丙基三甲氧基硅烷(GPTS)作为硅烷偶联剂,聚乙烯亚胺(PEI)作为聚合物包覆层,并以硬脂酰氯修饰得到一种氨基包覆的具有C18碳链结构的新型亚微米无孔二氧化硅材料(C18-NH2-GPTS-SiO2)。利用元素分析、傅里叶变换红外光谱、Zeta电势等进行表征,证明C18-NH2-GPTS-SiO2固定相的成功制备。该修饰方法将NPS的碳含量从0.55%提高到了8.29%,解决了过往NPS材料采用十八烷基氯硅烷等传统C18修饰方法时碳含量较低的问题。此外,29Si固体核磁显示:NPS与多孔二氧化硅(PS)微球相比不仅存在孔结构与比表面积区别,且表面硅羟基种类也不同。16%的PS微球硅原子带有一个硅羟基(孤立硅羟基,Q3)、19%带有两个硅羟基(偕硅羟基,Q2);而NPS微球不存在偕硅羟基,仅有30%硅原子处于孤立硅羟基状态。实验发现NPS微球存在硅羟基数量低且缺少偕硅羟基的特点,导致NPS材料表面修饰活性低,难以通过简单一步反应获得高碳含量。采用不同疏水物质如苯系物、多环芳烃对色谱性能及保留机理进行研究,结果表明C18-NH2-GPTS-SiO2色谱柱符合反相作用机理。氨基的包覆改变硅球表面电性,提高了NPS材料运用于加压毛细管电色谱平台(pCEC)时的电渗流大小,施加+15 kv时,显示出良好的分离能力,证实了C18-NH2-GPTS-SiO2材料通过多步反应提高碳含量的修饰方法在pCEC平台上应用的优异性。

Dynamic covalent hydrogel of natural product baicalin with antibacterial activities.

Baicalin has been demonstrated to have multiple pharmacological activities but low solubility. Various baicalin hydrogels have been used to improve its solubility and break its limitation in clinical applications. However, traditional baicalin hydrogels contain numerous ingredients and usually show low baicalin loading capacity. Herein, we discovered a dynamic covalent hydrogel only consisting of baicalin and inorganic borate, in which baicalin is considered as the carrier and drug without other ingredients. The dynamic boronate bonds endow the hydrogel with excellent degradability and multi-stimuli-responsiveness. Moreover, the hydrogel displayed remarkable thixotropy, moldability, and self-healing properties. And the biocompatible baicalin hydrogel exhibited significant antibacterial activities, and can be considered as a potential drug delivery system for biomedical applications.

Linear-rotary direct drive for multi-functional machine tools

By combining linear and rotary movement in one single drive, the overall dynamics of machine axes can be enhanced, and the installation space can be reduced. Existing concepts for linear-rotary drives either have low power density or load capacity, and the installation space of the guideways are not sufficient for applications in machine tools. Thus, this paper presents a novel linear-rotary direct drive for machine tools. The electromagnetic coupling between the linear and rotary direction is analyzed, and the control performance is evaluated. The developed drive is characterized by stiffness of up to 205 N/µm, acceleration dynamics of 3,100 mm/s2 in linear and 24,100 °/s2 in rotary direction, and fine positioning in 0.2 µm and 3.6″ steps.

Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity.

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.

Metal-free honeycomb-like electrocatalyst with high specific mass activity for accelerated oxygen reduction reaction in both alkaline and acidic media

The fabrication of superior oxygen reduction reaction (ORR) electrocatalysts, a challenging process, is currently focuses on expensive and rare platinum (Pt) group based metals. However, these noble metals-based electrocatalysts often suffer from disadvantages, including poor stability, exorbitant price, and low selectivity. Here, we report a simple strategy to synthesize a porous honeycomb-like carbon-based electrocatalyst codoped with nitrogen (N) and phosphorus (P) without any template. Benefiting from the synergistic impact of N, P co-doping, the as-developed honeycomb-like carbon (N,P-HLC) displays splendid ORR electrochemical activity with a large onset potential of 1.0 V (vs. RHE), and half-wave potential (E1/2) of 0.85 V (vs. RHE). What's more, N,P-HLC displays remarkable ORR performance under the super low electrocatalyst loading capacity of 0.15 mg cm−2, which is highly comparable to benchmark Pt/C (E1/2 = 0.83 V, loading capacity 0.38 mg cm−2). Meanwhile, N,P-HLC also exhibits exceptional ORR activity in the harsh acid conditions. This work introduces a robust, low-cost and superb electrocatalytic materials to replace the noble metal-based ORR electrocatalysts.

Prototype design and development of low-load-roof photovoltaic modules for applications in on-grid systems

Four prototypes of lightweight photovoltaic modules for applications in on-grid systems have been designed, developed, manufactured and tested for compliance with relevant IEC standards. Selected, commercially available materials characterized by thermogravimetry, differential scanning calorimetry, dilatometry, scanning electron microscopy and nanoindentation technique were used in frameless, adhesively-bonded sandwich-structures carrying the interdigitated back contact solar cells. With dedicated manufacturing processes the prototype-dependent weight between 3.37 and 3.77 kg/m 2 , the STC-maximum power in the range of 221–239 Wp together with power conversion efficiencies of 19.98–20.71% were obtained. Millimetre-sized texture improved module's performance for steeper solar incidence angles. The self-cleaning capability of modules was enhanced by a hydrophobic material utilized in front linings. The structure of the prototypes helps to build non-intrusive installations on low-load capacity roofs, even in large-scale lightweight buildings. • Four prototypes of lightweight photovoltaic modules were designed and developed. • Thermal and mechanical parameters of base materials were determined. • The results of the prototypes' complete IEC test sequence were presented. • Construction details and manufacturing processes were described.

Target-modulated competitive binding and exonuclease I-powered strategy for the simultaneous and rapid detection of biological targets

Simultaneous multiple-target detection is essential for the prevention, identification, and treatment of numerous diseases. In this study, a novel strategy based on target-modulated competitive binding and exonuclease I (Exo I)-powered signal molecule release was established with the advantages of rapid response and high selectivity and sensitivity. The strategy holds substantial potential for the development of versatile platforms for the simultaneous detection of biological targets. To mitigate the low load capacity and time-consuming responsive process of the Zr-MOF system, UiO-67 was chosen to replace UiO-66 (a typical Zr-MOF) as the nanocarrier for encapsulating more signal molecules, whereby the assembled double-stranded DNA (dsDNA) structures of UiO-67 acted as gatekeepers to form dsDNA-functionalized MOFs. Additionally, Exo I was introduced into the system to accelerate the release of the signal molecules. In the presence of biological targets, the competitive binding between the targets and aptamers caused the hydrolysis of the free DNA sequence by Exo I, promoting the release of signal molecules and leading to a rapid and significant increase in the fluorescence intensity. For adenosine triphosphate (ATP) and cytochrome c (cyt c), which were chosen as model biological targets, this sensor displayed detection limits as low as 5.03 and 6.11 fM, respectively. Moreover, the developed biosensor was successfully applied to the simultaneous detection of ATP and cyt c in spiked serum samples. Therefore, this strategy provides guidance for further research of biosensors for simultaneous multiple-target detection and propels the application of MOF carriers in biomedicine.

Numerical and experimental study on the static performance of externally pressurized thrust bearings lubricated with refrigerant gases

Purpose Oil-free heat pumps that use the system refrigerant gases as lubricants are preferred for thermal management in future space applications. This study aims to numerically and experimentally investigate the static performance of externally pressurized thrust bearings lubricated with refrigerant gases. Design/methodology/approach The refrigerant gases R22, R410A and CO2 were chosen as the research objects, while N2 was used for comparison. Computational fluid dynamics was used to solve the full 3 D Navier–Stokes equations to determine the load capacity, static stiffness and static pressure distribution in the bearing film. The numerical results were experimentally verified. Findings The results showed that the refrigerant-gas-lubricated thrust bearings had a lower load capacity than the N2-lubricated bearings, but they presented a higher static stiffness when the bearing clearance was less than 9 µm. Compared with the N2-lubricated bearings, the optimal static stiffness of the R22- and CO2-lubricated bearings increased by more than 46% and more than 21%, respectively. The numerical and experimental results indicate that a small bearing clearance would be preferable when designing externally pressurized gas thrust bearings lubricated with the working medium of heat pump systems for space applications. Originality/value The findings of this study can serve as a basis for the further investigation of refrigerant gases as lubricants in heat pump systems, as well as for the future design of such gas bearings in heat pump systems for space applications.

Electrically Controlled Neurochemical Delivery from Microelectrodes for Focal and Transient Modulation of Cellular Behavior.

Electrically controlled drug delivery of neurochemicals and biomolecules from conducting polymer microelectrode coatings hold great potentials in dissecting neural circuit or treating neurological disorders with high spatial and temporal resolution. The direct doping of a drug into a conducting polymer often results in low loading capacity, and the type of molecule that can be released is limited. Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with sulfonated silica nanoparticles (SNP) has been developed as a more versatile platform for drug delivery. In this work, we demonstrate that neurochemicals with different surface charge, e.g., glutamate (GLU), gamma-Aminobutyric acid (GABA), dopamine (DA), 6,7-Dinitroquinoxaline- 2,3-dione (DNQX) and bicuculline, can be, respectively, incorporated into the SNP and electrically triggered to release repeatedly. The drug loaded SNPs were incorporated in PEDOT via electrochemical deposition on platinum microelectrodes. After PEDOT/SNP(drug) coating, the charge storage capacity (CSC) increased 10-fold to 55 ± 3 mC/cm2, and the impedance at 1 kHz was also reduced approximately 6-fold. With the aid of a porous SNP, the loading capacity and number of releases of GLU was increased >4-fold and 66-fold, respectively, in comparison to the direct doping of PEDOT with GLU (PEDOT/GLU). The focal release of GLU and GABA from a PEDOT/SNP (drug) coated microelectrode were tested in cultured neurons using Ca imaging. The change in fluo-4 fluorescence intensity after electrically triggered GLU (+6.7 ± 2.9%) or GABA (−6.8 ± 1.6%) release indicated the successful modulation of neural activities by neurotransmitter release. In addition to activating neural activities, glutamate can also act on endothelial cells to stimulate nitric oxide (NO) release. A dual functional device with two adjacent sensing and releasing electrodes was constructed and we tested this mechanism in endothelial cell cultures. In endothelial cells, approximately 7.6 ± 0.6 nM NO was detected in the vicinity of the NO sensor within 6.2 ± 0.5 s of GLU release. The rise time of NO signal, T0–100, was 14.5 ± 2.2 s. In summary, our work has demonstrated (1) a platform that is capable of loading and releasing drugs with different charges; (2) proof of concept demonstrations of how focal release of drugs can be used as a pharmacological manipulation to study neural circuitry or NO’s effect on endothelial cells.

Red-Blood-Cell-Membrane-Coated Metal-Drug Nanoparticles for Enhanced Chemotherapy.

To overcome high toxicity, low bioavailability and poor water solubility of chemotherapeutics, a variety of drug carriers have been designed. However, most carriers are severely limited by low drug loading capacity and adverse side effects. Here, a new type of metal-drug nanoparticles (MDNs) was designed and synthesized. The MDNs self-assembled with Fe(III) ions and drug molecules through coordination, resulting in nanoparticles with high drug loading. To assist systemic delivery and prolong circulation time, the obtained MDNs were camouflaged with red blood cell (RBCs) membranes (RBCs@Fe-DOX MDNs) to improve their stability and dispersity. The RBCs@Fe-DOX MDNs presented pH-responsive release functionalities, resulting in drug release accelerated in acidic tumor microenvironments. The outstanding in vitro and in vivo antitumor therapeutic outcome was realized by RBCs@Fe-DOX MDNs. This study provides an innovative design guideline for chemotherapy and demonstrates the great capacity of nanomaterials in anticancer treatments.

Enhanced microwave absorption properties of biomass-derived carbon decorated with transition metal alloy at improved graphitization degree

In this work, absorbers with lightweight, low loading, and strong absorption capacity have been made by biomass-derived carbon (BC) with magnetic alloy. Because of an innovative synthetic method, not only the NiFe and CoFe alloy are successfully synthesized on the surface of the BC, but also the graphitization degree of the BC has been improved greatly by transition metals. This way makes the BC acquire superior dielectric, magnetic loss, better impedance matching, and excellent attenuation ability of electromagnetic waves. NiFe exhibits a higher catalytic performance, but the imbalance electromagnetic parameters lead to imperfect impedance matching. Due to the superior balance between attenuation ability and impedance matching, the BC/CoFe composite material shows excellent electromagnetic absorbing capacity. BC/CoFe has a minimum reflection loss of −54.4 dB with a thickness of 2.2 mm, and the widest effective bandwidth can reach 2.6 GHz with a thickness of 2.4 mm. Results indicate that the BC/CoFe composite material is expected to be a superior electromagnetic wave absorber. These innovative findings and preparation methods provided a new guideline for developing biomass-derived carbon as a low-cost, lightweight, and high-performance microwave absorber.

Recent Advances in Paclitaxel-based Self-Delivery Nanomedicine for Cancer Therapy.

Paclitaxel (PTX) is the first natural plant-derived chemotherapeutic drug approved by the Food and Drug Administration. However, the clinical applications of PTX are limited by some drawbacks, such as poor water solubility, rapid blood clearance, nonspecific distribution, and adverse side effects. Nanocarriers have made important contributions to drug delivery and cancer therapy in recent years. However, low drug loading capacity, nanocarrier excipients-induced toxicity or immunogenicity, and complicated synthesis technologies pose a challenge for the clinical application of nanocarriers. To address these issues, the self-delivery nanomedicine (SDNs), in which pure drug molecules directly self-assemble into nanomedicine, have been developed for drug delivery and enhancing antitumor efficacy. In this review, we comprehensively summarize the recent advances in PTX-based SDNs for cancer therapy. First, the self-assembly strategies to develop pure PTX nanodrugs are discussed. Then, the emerging strategies of co-assembly PTX and other therapeutic agents for effective combination therapy are presented, composing of combination chemotherapy, chemo-photothermal therapy, chemo-photodynamic therapy, chemo-immunotherapy, and chemo-gene therapy. Finally, the limitations and future outlook of SDNs are discussed. The rational design of these unique nanoplatforms may make a new direction to develop highly efficient drug delivery systems for cancer therapy.

Theoretical Efficiency Study of Output Lubricant Flow Rate Regulating Principle on the Example of a Two-Row Aerostatic Journal Bearing with Longitudinal Microgrooves and a System of External Combined Throttling

Due to their vanishingly low air friction, high wear resistance, and environmental friendliness, aerostatic bearings are used in machines, machine tools, and devices that require high accuracy of micro-movement and positioning. The characteristic disadvantages of aerostatic bearings are low load capacity, high compliance and an increased tendency for instability. In radial bearings, it is possible to use longitudinal microgrooves, which practically exclude circumferential air leakage, and contributes to a significant increase in load-bearing capacity. To reduce compliance to zero and negative values, inlet diaphragm and elastic airflow regulators are used. Active flow compensation is inextricably linked to the problem of ensuring the stability of bearings due to the presence of relatively large volumes of gas in the regulator, which have a destabilizing effect. This problem was solved by using an external combined throttling system. Bearings with input flow regulators have a number of disadvantages-they are very energy-intensive and have an insufficiently stable load capacity. A more promising way to reduce compliance is the use of displacement compensators for the movable element. Such bearings also allow for a decrease in compliance to zero and negative values, which makes it possible to use them not only as supports, but also as active deformation compensators of the technological system of machine tools in order to reduce the time and increase the accuracy of metalworking. The new idea of using active flow compensators is to regulate the flow rate not at the inlet, but at the outlet of the air flow. This design has the energy efficiency that is inherent to a conventional bearing, but the regulation of the lubricant output flow allows the compliance to be reduced to zero and negative values. This article discusses the results of a theoretical study of the static and dynamic characteristics of a two-row radial aerostatic bearing with longitudinal microgrooves and an output flow regulator. Mathematical modeling and theoretical study of stationary modes have been carried out. Formulas for determining static compliance and load capacity are obtained. Iterative finite-difference methods for determining the dynamic characteristics of a structure are proposed. The calculation of dynamic quality criteria was carried out on the basis of the method of rational interpolation of the bearing transfer function, as a system with distributed parameters, developed by the authors. It was found that the volumes of the microgrooves do not have a noticeable effect on the bearing dynamics. It is shown that, in this design, the external combined throttling system is an effective means of maintaining stability and high dynamic quality of the design operating in the modes of low, zero and negative compliance.

Designing a Soft Flat Crawling Robot With High Load Capacity

Traditional soft crawling robots have many disadvantages, including their complex structure, difficulty in manufacturing, and low load capacity. Inspired by the art form of kirigami, we opted to design a soft, flat crawling robot using only simple, fast laser cutting technology and a weaving method in this study. The robot mainly consists of two components: a piece of skin with scales and a flat balloon, which are weaved orthogonally to each other. The fully formed robot weighs only 5g, and the scales can tilt up after the balloon inflates. All the scales are distributed on one side of the robot, increasing the load capacity. The expansion of the balloon ensures that the robot becomes contract coupled. With the anisotropic friction provided by the scales, the robot can now crawl forward. This experimental work demonstrates that the crawling efficiency can be improved by choosing the appropriate pressure waveform. By shortening the period of the pressure waveform, the crawling speed can also be significantly improved. In terms of loading, the robot still has a high crawling ability when carrying a load over 400 times its weight.