Transdermal gene delivery.

Gene delivery has revolutionized conventional medical approaches to vaccination, cancer, and autoimmune diseases. However, current gene delivery methods are limited to either intravenous administration or direct local injections, failing to achieve well biosafety, tissue targeting, drug retention, and transfection efficiency for desired therapeutic outcomes. Transdermal drug delivery based on various delivery strategies can offer improved therapeutic potential and superior patient experiences. Recently, there has been increased foundational and clinical research focusing on the role of the transdermal route in gene delivery and exploring its impact on the efficiency of gene delivery. This review introduces the recent advances in transdermal gene delivery approaches facilitated by drug formulations and medical devices, as well as discusses their prospects.

Lanthanum interferes with the fundamental rhythms of stomatal opening, expression of related genes, and evapotranspiration in Arabidopsis thaliana.

The accumulation of rare earth elements (REEs) in the global environment poses a threat to plant health and ecosystem stability. Stomata located on leaves serve as the primary site for plant responses to REE-related threats. This study focused on lanthanum [La(III)], a prevalent REE in the atmospheric environment. Using interdisciplinary techniques, it was found that La(III) (≤80 µM) interfered with the fundamental rhythms of stomatal opening, related gene expression, and evapotranspiration in plants. Specifically, when exposed to low concentrations of La(III) (15 and 30 µM), the expression levels of six genes were increased, stomatal opening was enhanced, and the evapotranspiration rate was accelerated. The interference on stomatal rhythms was enhanced with higher concentrations of La(III) (60 and 80 µM), increasing the expression levels of six genes, stomatal opening, and evapotranspiration rate. To counter the interference of low concentrations of La(III) (15 and 30 µM), plants accelerated nutrient replenishment through La(III)-induced endocytosis, which the redundant nutrients enhanced photosynthesis. However, replenished nutrients failed to counter the disruption of plant biological rhythms at higher concentrations of La(III) (60 and 80 µM), thus inhibiting photosynthesis due to nutrient deficit. The interference of La(III) on these biological rhythms negatively affected plant health and ecosystem stability.

Armored Superhydrophobic Surfaces with Excellent Drag Reduction in Complex Environmental Conditions.

Superhydrophobic surfaces (SHSs) have possibilities for achieving significantly reduced solid-liquid frictional drag in the marine sector due to their excellent water-repelling properties. Although the stability of SHSs plays a key role in drag reduction, little consideration was given to the effect of extreme environments on the ability of SHSs to achieve drag reduction underwater, particularly when subjected to acidic conditions. Here, we propose interconnected microstructures to protect superhydrophobic coatings with the aim of enhancing the stability of SHSs in extreme environments. The stability of armored SHSs (ASHSs) was demonstrated by the contact angle and bounce time of droplets on superhydrophobic surfaces treated by various methods, resulting in an ASHS surface with excellent stability under extreme environmental conditions. Additionally, inspired by microstructures protecting superhydrophobic nanomaterials from frictional wear, the armored superhydrophobic spheres (ASSPs) were designed to explain from theoretical and experimental perspectives why ASSPs can achieve sustainable drag reduction and demonstrate that the ASSPs can achieve drag reduction of over 90.4% at a Reynolds number of 6.25 × 104 by conducting water entry experiments on spheres treated in various solutions. These studies promote a fundamental understanding of what drives the application of SHSs under extreme environmental conditions and provide practical strategies to maximize frictional drag reduction.

Suppressed Droplet Splashing on Positively Skewed Surfaces for High-Efficiency Evaporation Cooling.

Two types of functional surfaces with the same roughness but completely different surface topographies are prepared, namely positively skewed surfaces filled with micropillar arrays (Sa ≈4.4 µm, Ssk >0) and negatively skewed surfaces filled with microcavity arrays (Sa ≈4.4 µm, Ssk <0), demonstrating promoting droplet splashing. Remarkably, the critical Weber number for generating satellite droplets on the negatively skewed surfaces is significantly lower than that on the positively skewed surfaces, indicating that the negatively skewed surface with microcavity arrays is more likely to promote droplet splashing. It is mainly attributed to the fact that air on the negatively skewed surface can make the liquid film take on a Cassie-Baxter state on the surface so that the stabilizing capillary force of the liquid film exceeds the destabilizing stress of the air film. Moreover, the surface topography promoting droplet spreading and the mechanical properties of three-phase moving contact lines are analyzed from the perspective of microscopic interface mechanics. Finally, it is demonstrated the designed positively skewed surfaces can be employed for large-area heat dissipation by means of high-efficiency evaporation.

Synergistic effects of multidrug/material combination deliver system for anti-mutidrug-resistant tumor.

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.

Protein corona, influence on drug delivery system and its improvement strategy: A review.

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a 'Protein Corona'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs.

Dynamic Behavior of Droplet Impact on Laminar Superheated Particles.

The impact of droplets on particles involves a wide range of complex phenomena and mechanisms, including bubble nucleation, crater formation, fluidization, and more intricate changes in the boiling regime when impacting superheated particles. In this study, we focus on droplet impact behavior on superheated laminar particles at various temperatures and define six typical characteristic patterns of a single droplet impact on superheated laminar particles, including film evaporation, bubbly boiling, immersion boiling, sputter boiling, transition boiling, and film boiling. It is worth noting that the variations of inertial force FI caused by gravity, the capillary force FC generated by the pores of the droplets, and the dewetting force by the vapor phase FV are the main contributors to different evaporation regimes. Interestingly, we find that the Leidenfrost point (LFP) of droplets on the laminar superheated particles decreases with particle size, which is related to the effect of the pore space generated between the laminar particles. Finally, the effect of temperature, particle size, and Weber number (We) on the dynamic behavior of droplet impact is revealed. Experimental results show that the instantaneous diameter of droplets is inversely proportional to the change of height, with different patterns of maximum spreading diameter and maximum bounce height at different particle sizes, while the maximum spreading velocity and maximum bounce velocity are independent of particle size. We believe the present work would provide a broader knowledge and comprehension of the droplet impact on heated particles and promote the development of the safety and productivity of industrial processes such as fluid catalytic cracking, spray drying, and spray cooling.

Delayed Leidenfrost Effect of a Cutting Droplet on a Microgrooved Tool Surface.

Regulation over the generation of the Leidenfrost phenomenon in liquids is vitally important in a cutting fluid/tool system, with benefits ranging from optimizing the heat transfer efficiency to improving the machining performance. However, realizing the influence mechanism of liquid boiling at various temperatures still faces enormous challenges. Herein, we report a kind of microgrooved tool surface by laser ablation, which could obviously increase both the static and dynamic Leidenfrost point of cutting fluid by adjusting the surface roughness (Sa). The physical mechanism that delays the Leidenfrost effect is primarily due to the ability of the designed microgroove surface to store and release vapor during droplet boiling so that the heated surface requires higher temperatures to generate sufficient vapor to suspend the droplet. We also find six typical impact regimes of cutting fluid under various contact temperatures; it is worth noting that Sa has a great influence on the transform threshold among six impact regimes, and the likelihood that a droplet will enter the Leidenfrost regime decreases with increasing Sa. In addition, the synergistic effect of Sa and tool temperature on the droplet kinetics of cutting droplets is investigated, and the relationship between the maximum rebound height and the dynamic Leidenfrost point is correlated for the first time. Significantly, cooling experiments on the heated microgrooved surface are performed and demonstrate that it is effective to improve the heat dissipation ability of cutting fluid by delaying the Leidenfrost effect on the microgrooved heated surface.

Active Droplet Transport Induced by Moving Meniscus on a Slippery Magnetic Responsive Micropillar Array.

Intelligent droplet manipulation plays a crucial role in both scientific research and industrial technology. Inspired by nature, meniscus driving is an ingenious way to spontaneously transport droplets. However, the shortages of short-range transport and droplet coalescence limit its application. Here, an active droplet manipulation strategy based on the slippery magnetic responsive micropillar array (SMRMA) is reported. With the aid of a magnetic field, the micropillar array bends and induces the infusing oil to form a moving meniscus, which can attract nearby droplets and transport them for a long range. Significantly, clustered droplets on SMRMA can be isolated by micropillars, avoiding droplet coalescence. Moreover, through adjusting the arrangement of the micropillars of SMRMA, multi-functional droplet manipulation such as unidirectional droplet transport, multi-droplet transport, droplet mixing, and droplet screening can be achieved. This work provides a promising approach for intelligent droplet manipulation and unfolds broad application prospects in microfluidics, microchemical reaction, biomedical engineering, and other fields.

Sharply and simultaneously increasing pollutant accumulations in cells of organisms induced by rare earth elements in the environment of Nanjing.

Exploring the factors that simultaneously increase the accumulation of various pollutants in cells of organisms to restrict the toxic effects of pollutants on organisms has become a focus of research aimed at protecting ecosystems. Here, we found that the accumulation of organic [e.g., benzo(a)pyrene (BaP)], inorganic [e.g., cadmium (Cd)] and emerging [e.g., rare earth elements (REEs)] pollutants in leaf cells of different plants grown in Nanjing was 567-1022%, 547-922% and 972-1392% of those grown in Haikou, respectively, when the concentration of REEs in rainwater of Nanjing and Haikou was 4.31 × 10-3 µg/L and 3.04 × 10-6 µg/L. Unprecedentedly, endocytosis in leaf cells of different plants grown in Nanjing was activated by REEs, and then extracellular BaP, Cd and REEs (e.g. terbium) were transported into these leaf cells together via endocytic vesicles. Particularly, the co-accumulation of those pollutants in these leaf cells was sharply increased, thus magnifying their toxic effects on these plants. Furthermore, the co-accumulation of those pollutants in human cells was also significantly increased by REEs, in a similar way to these leaf cells. Therefore, REEs in environments are key factors that greatly increase the co-accumulation of various pollutants in cells of organisms. These results provide new insights into how pollutants are accumulated in cells of organisms in ecosystems, informing a reference for making policy to ensure the safety of ecosystems.

Meniscus-Induced Directional Self-Transport of Submerged Bubbles on a Slippery Oil-Infused Pillar Array with Height-Gradient.

Directional manipulation of submerged bubbles is fundamental for both theoretical research and industrial production. However, most current strategies are limited to the upward motion direction, complex surface topography, and additional apparatuses. Here, we report a meniscus-induced self-transport platform, namely, a slippery oil-infused pillar array with height-gradient (SOPAH) by combining femtosecond laser drilling and replica mold technology. Owing to the unbalanced capillary force and Laplace pressure difference, bubbles on SOPAH tend to spontaneously transport along the meniscus gradient toward a higher elevation. The self-transport performances of bubbles near the pillars depend on the complex meniscus shape. Significantly, to understand the underlying transport mechanism, the 3D meniscus profile is simulated by solving the Young-Laplace equation. It is found that the concave valleys formed between the adjacent pillars can change the gradient direction of the meniscus and lead to the varied transport performances. Finally, by taking advantage of a water electrolysis system, the assembled SOPAH serving as a bubble-collecting device is successfully deployed. This work should not only bring new insights into the meniscus-induced self-transport dynamics but also benefit potential applications in the field of intelligent bubble manipulation.

Functional Microtextured Superhydrophobic Surface with Excellent Anti-Wear Resistance and Friction Reduction Properties.

The wear-resistant superhydrophobic (SHB) surfaces with excellent water-repellency ability were prepared by constructing a microtextured armor on an aluminum surface. With the assistance of laser-induced microtextures, the SHB surface could keep a longer water-repellency ability and a lower friction coefficient even after repeated friction tests under different loads and at different speeds. The mechanism of microtexture-protecting SHB coating is revealed based on both theoretical and elemental analysis. Additionally, we explore the relationship between the three-dimensional topography parameters (ISO 25178) and variation of water contact angles under different test recycles. The results show that the rough surface with appropriate Sa and higher Sku exhibits a better wear resistance, which is mainly related to the storing ability of SHB coating inside the microtextures. Moreover, the surface with appropriate Str exhibits excellent wear resistance, which is mainly associated with better chip-removal ability. Finally, the tribological properties of the microtextured SHB surface are researched. It is worth noting that compared with the microtextured surface without SHB coating and the SHB-coated surface without microtextures, the microtextured SHB surface has the lowest friction coefficient under dry friction because the SHB coating would largely decrease the surface energy of the interface, so the adhesion friction decreases. The microtexture armor on the surfaces would protect the wear of SHB coating, so the SHB coating inside the microtexture could continuously play the role of a particle lubricant at the sliding interface and decrease the friction force of the sliding interface. We believe that the present study would contribute to the further understanding of the constructing mechanism of anti-wear SHB surfaces and provide a new strategy for topography design of engineering surfaces with friction reduction properties.

Enzyme-responsive nano-drug delivery system for combined antitumor therapy.

Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.

Dramatically reducing the critical velocity of air cavity generation via biomimetic microstructure effects.

Control over the generation of air cavities in liquids is vitally important in numerous underwater marine systems, with behaviors ranging from largely reducing the fluid resistance to minimizing the energy consumption. However, reducing the critical velocity of air cavity generation simultaneously on both original and hydrophobic materials can be mutually exclusive. In strong contrast to the view that the surface wettability is what determines the critical velocity of air cavity entrainment, we report a facile method to dramatically reduce the critical velocity of air cavity generation by etching a kind of biomimetic microstructure on the sphere surface. It is worth noting that the generation of air cavities induced by the microstructure effect is almost independent of surface wettability; even for the hydrophilic spheres, the critical velocity of air cavity generation is reduced by over 86.3%. The physical mechanism is mainly related to the pinning of the moving contact line and the regulable transition of the wetting state from the Wenzel model to the Cassie-Baxter model at the solid-liquid-air interface. We also investigated the stability of the microstructured spheres to induce underwater air cavities and found that a continuous and robust air cavity could still be produced even after 1200 repeated impacts. This research provides a simple, economical and energy-efficient method for minimizing the critical velocity for generating air cavity entrainment to reduce hydrodynamic drag.

Magnetic-Actuated Robot Enables High-Performance Underwater Bubble Maneuvering on Laser-Textured Biomimetic Slippery Surfaces.

Controllable underwater gas bubble (UGB) transport on a surface is realized by geography-/stimuli-induced wettability gradient force (Fwet-grad). Unfortunately, the high-speed maneuvering of UGBs along free routes on planar surfaces remains challenging. Herein, a regime of magnetism-actuated robot (MAR) mounting on biomimetic laser-ablated lubricant-impregnated slippery surfaces (LA-LISS) is reported. Leveraging on LA-LISS, MAR-entrained UGBs can move along arbitrary directions through the loading of a tracing magnetic trigger. The underlying hydrodynamics is that MAR-entrained UGBs would be actuated slipping upon a giant magnetic-induced towing force (FM//). Once the magnetism stimuli is discharged, FM// vanishes immediately to immobilize the UGBs on LA-LISS. Thanks to the MAR's robust bubble affinity, a typical UGB (20 µL) on the optimized LA-LISS can be accelerated at 500 mm/s2 and gain an ultrafast velocity of over 205 mm/s that far exceeds previously reported figures. Moreover, fundamental physics renders MAR antibuoyancy, steering locomotive UGBs on the inclined LA-LISS. Significantly, an MAR propelling UGBs to configure desirable patterns, realize on-demand coalescence, remedy the cutoff switch, as well as facilitate a programmable light-control-light optical shutter is successfully deployed. Compared with previous smart surfaces, the current multifunctional regime is more competent for harnessing UGBs featuring an unparalleled transport velocity independent of the feeble Fwet-grad.

A Biocompatible Vibration-Actuated Omni-Droplets Rectifier with Large Volume Range Fabricated by Femtosecond Laser.

High-performance droplet transport is crucial for diverse applications including biomedical detection, chemical micro-reaction, and droplet microfluidics. Despite extensive progress, traditional passive and active strategies are restricted to limited liquid types, small droplet volume ranges, and poor biocompatibilities. Moreover, more challenges occur for biological fluids due to large viscosity and low surface tension. Here, a vibration-actuated omni-droplets rectifier (VAODR) consisting of slippery ratchet arrays fabricated by femtosecond laser and vibration platforms is reported. Through the relative competition between the asymmetric adhesive resistance originating from the lubricant meniscus on the VAODR and the periodic inertial driving force originating from isotropic vibration, the fast (up to ≈60 mm s-1 ), programmable, and robust transport of droplets is achieved for a large volume range (0.05-2000 µL, Vmax /Vmin  ≈ 40 000) and in various transport modes including transport of liquid slugs in tubes, programmable and sequential transport, and bidirectional transport. This VAODR is general to a high diversity of biological and medical fluids, and thus can be used for biomedical detection including ABO blood-group tests and anticancer drugs screening. These strategies provide a complementary and promising platform for maneuvering omni-droplets that are fundamental to biomedical applications and other high-throughput omni-droplet operation fields.

A new mechanism by which environmental hazardous substances enhance their toxicities to plants.

The coexistence of hazardous substances enhances their toxicities to plants, but its mechanism is still unclear due to the unknown cytochemical behavior of hazardous substance in plants. In this study, by using interdisciplinary methods, we observed the cytochemical behavior of coexisting hazardous substances {terbium [Tb(III)], benzo(a)pyrene (BaP) and cadmium [Cd(II)] in environments} in plants and thus identified a new mechanism by which coexisting hazardous substances in environments enhance their toxicities to plants. First, Tb(III) at environmental exposure level (1.70 × 10-10 g/L) breaks the inert rule of clathrin-mediated endocytosis (CME) in leaf cells. Specifically, Tb(III) binds to its receptor [FASCICLIN-like arabinogalactan protein 17 (FLA17)] on the plasma membrane of leaf cells and then docks to an intracellular adaptor protein [adaptor protein 2 (AP2)] to form ternary complex [Tb(III)-FLA17-AP2], which finally initiates CME pathway in leaf cells. Second, coexisting Tb(III), BaP and Cd(II) in environments are simultaneously transported into leaf cells via Tb(III)-initiated CME pathway, leading to the accumulation of them in leaf cells. Finally, these accumulated hazardous substances simultaneously poison plant leaf cells. These results provide theoretical and experimental bases for elucidating the mechanisms of hazardous substances in environments poisoning plants, evaluating their risks, and protecting ecosystems.

Underwater Drag Reduction and Buoyancy Enhancement on Biomimetic Antiabrasive Superhydrophobic Coatings.

A superhydrophobic (SHB) surface with an excellent self-cleaning ability is of great significance in both human survival and industrial fields. However, it is still a challenge to achieve large-area preparation of antiabrasive SHB surfaces with great mechanical robustness for broader applications. Thus, a kind of facile SHB coating with excellent liquid repellency and antiresistance is constructed by spraying a fluorine-free suspension consisting of epoxy resin, hexadecyltrimethoxysilane (HDTMS), and silica nanoparticles on a glass sheet. The SHB coating not only shows high adhesion on various materials but also has high water repellency under various test conditions, including tape peeling after blade scraping, sandpaper abrasion, and immersing in a complex environment. Additionally, the SHB spheres coated with laser-induced microstructure armor could form a continuous gas cavity during the water entry process, which is essential to prolonging the drag reduction ability of SHB coatings in liquid. Finally, the prepared robust SHB coatings have been employed in underwater buoyancy enhancement and reducing fluid resistance, which may open new avenues for underwater drag reduction in the field of marine applications.

Lateral and Normal Capillary Force Evolution of a Reciprocating Liquid Bridge.

Capillary forces of a shearing liquid bridge can significantly affect the friction and adhesion of interacting surfaces, but the underlying mechanisms remain unclear. We custom built a surface force apparatus (SFA, ±2 µN) equipped with in situ optical microscopy and performed normal and lateral force measurements on a reciprocating water bridge formed between two flat plates. A modified wedge method was developed to correct the unique force measurement errors caused by the changing bridge geometry and position. The results found (1) strong linear relations among the bridge shear displacement, the cosine difference between the left and right contact angles, and the lateral adhesion force and (2) the normal adhesion force increased monotonically up to 13% as the bridge geometry approached its axisymmetric state. Quasi-static force analyses based on a newly developed decahedral model showed good agreement with the experiments and improved accuracy compared with that of cylindrical or rectangular column models previously proposed in the literature. Although limited in certain aspects, this study may (1) prove helpful to the design and analysis of liquid bridge force experiments on platforms similar to the SFA used in this study and (2) help to bridge the gap between friction and liquid bridge physics in the literature.

Contactless Mechanical Power Transmission Through the High-T c Superconducting Pinning Effect.

Mechanical power transmission (MPT) components are almost indispensable for every engineering equipment with motions. In order to satisfy some rigorous requirements, such as contamination free and zero leakage in the mixing process of biomedical solutions, a contactless MPT mode was proposed in this study based on the high-T c superconducting flux pinning mechanism. It makes the stirring container with the driven part inside that can be totally isolated from the external environment. The physical principle of superconducting flux pinning effect was discussed firstly to explore a feasible structural scheme, which can completely restrain all the six degrees of freedom (DOFs) by the linkage of magnetic flux lines. Then, a measurement device was established to verify and investigate the proposed contactless MPT mode. The motion can be transferred synchronously from the superconducting driving part to the permanent magnet driven part since they are unified as an integrity through the pinned flux lines. The influence of driving speed, cooling clearance, and magnet arrangement on the transmitted torque was analyzed. The verified contactless MPT mode also has the advantages of self-stability and overload protection, which can avoid the drawbacks of traditional permanent magnetic transmission mode.