Passive Spatial Mapping of Inertial Cavitation During HIFU Exposure

A novel method for mapping inertial cavitation activity during high-intensity focused ultrasound (HIFU) exposure is presented. Inertial cavitation has been previously shown to result in increased heat deposition and to be associated with broadband noise emissions that can be readily monitored using a passive receiver without interference from the main HIFU signal. In the present study, the signals received passively by each of 64 elements on a standard diagnostic array placed coaxially with the HIFU transducer are combined using time exposure acoustics to generate maps of inertially cavitating regions during HIFU exposure of an agar-based tissue-mimicking material. The technique is shown to be effective in localizing single-bubble activity, as well as contiguous and disjoint cavitating regions instigated by creating regions of lower cavitation threshold within the tissue phantom. The cavitation maps obtained experimentally are also found to be in good agreement with computational simulations and theoretical predictions. Unlike B-mode imaging, which requires interleaving with the HIFU pulse, passive array-based mapping of cavitation activity is possible during HIFU exposure. If cavitating regions can be directly correlated to increased tissue damage, this novel cavitation mapping technique could enable real-time HIFU treatment monitoring.      

Vibroacoustography imaging of kidney stones in vitro

Vibroacoustography (VA) is an ultrasound-based modality sensitive to stiffness and free from speckle and possesses some advantages over conventional ultrasound imaging in terms of image quality. The primary objective here is to show its feasibility in detecting/imaging kidney stones (KSs) in vitro . In VA, two intersecting ultrasound beams driven at two different frequencies f (1) and f (2), respectively, are focused within a freshly excised porcine kidney attached to a solid frame with elastic rubber bands, while the amplitude of the acoustic emission pressure field produced at the difference frequency Δf = | f(1) - f(2) | is detected by a low-frequency hydrophone. The received low-frequency signal is bandpass filtered and amplified, then digitized by a 14-bits/sample digitizer. The data are then recorded on a computer and processed numerically to construct the images. 2-D magnitude VA images are obtained at different depths within the kidney before and after stone implantation, showing kidney features and stones shapes. Experiments conducted in a water tank on a chalk sphere as well as a series of excised kidneys in which stones are artificially embedded show that all the implanted stones are detected at all chosen depths, when compared with an X-ray fluoroscopy taken to be the reference image. The resulting VA images, obtained from a nonionizing type of radiation (i.e., ultrasound waves) as compared to fluoroscopy, are speckle free unlike conventional ultrasound images. The results presented in this preliminary feasibility study show that VA allows imaging KSs in vitro, and provide the impetus to further develop and investigate VA imaging in a clinical setting for in vivo applications.     

Combining Photothermal-Photodynamic Therapy Mediated by Nanomaterials with Immune Checkpoint Blockade for Metastatic Cancer Treatment and Creation of Immune Memory

The pursuit of effective treatments for metastatic cancer is still one of the most intensive areas of research in the biomedical field. In a not-so-distant past, the scientific community has witnessed the rise of immunotherapy based on immune checkpoint inhibitors (ICIs). This therapeutic modality intends to abolish immunosuppressive interactions, re-establishing T cell responses against metastasized cancer cells. Despite the initial enthusiasm, the ICIs were later found to be associated with low clinical therapeutic outcomes and immune-related side effects. To address these limitations, researchers are exploring the combination of ICIs with nanomaterial-mediated phototherapies. These nanomaterials can accumulate within the tumor and produce, upon interaction with light, a temperature increase (photothermal therapy) and/or reactive oxygen species (photodynamic therapy), causing damage to cancer cells. Importantly, these photothermal-photodynamic effects can pave the way for an enhanced ICI-based immunotherapy by inducing the release of tumor-associated antigens and danger-associated molecular patterns, as well as by relieving tumor hypoxia and triggering a pro-inflammatory response. This progress report analyses the potential of nanomaterial-mediated photothermal-photodynamic therapy in combination with ICIs, focusing on their ability to modulate T cell populations leading to an anti-metastatic abscopal effect and on their capacity to generate immune memory that prevents tumor recurrence.     

Nanowire Assisted Mechanotyping of Cellular Metastatic Potential

Nanotechnology has provided tools for next generation biomedical devices which rely on nanostructure interfaces with living cells. In vitro biomimetic structures have enabled observation of cell response to various mechanical and chemical cues, and there is a growing interest in isolating and harnessing the specific cues that 3D microenvironments can provide without the requirement for such culture and the experimental drawbacks associated with it. Here, a randomly oriented gold coated Si nanowire substrate with patterned hydrophobic–hydrophilic areas for the differentiation of isogenic breast cancer cells of varying metastatic potential is reported. When considering synthetic surfaces for the study of cell-nanotopography interfaces, randomly oriented nanowires more closely resemble the isotropic architecture of a natural extracellular matrix. In the study reported here, the authors show that primary cancer cells preferably attach to the hydrophilic region of randomly oriented nanowire substrate while secondary cancer cells do not adhere. Using machine learning analysis of fluorescence images, cells are found to spread and elongate on the nanowire substrates as compared to a flat substrate, where they mostly remain round. Such platforms can not only be used for developing bioassays but also as stepping stones for tissue printing technologies where cells can be selectively patterned at desired locations.     

Development of Citrate‐Based Dual‐Imaging Enabled Biodegradable Electroactive Polymers

Increasing occurrences of degenerative diseases, defective tissues, and severe cancers heighten the importance of advanced biomedical treatments, which in turn enhance the need for improved biomaterials with versatile theranostic functionalities yet using minimal design complexity. Leveraging the advantages of citrate chemistry, a multifunctional citrate‐based biomaterial platform is developed with both imaging and therapeutic capabilities utilizing a facile and efficient one‐pot synthesis. The resulting aniline tetramer doped biodegradable photoluminescent polymers (BPLPATs) not only possess programmable degradation profiles (<1 to > 6 months) and mechanical strengths (≈20 MPa to >400 MPa), but also present a combination of intrinsic fluorescence, photoacoustic (PA), and electrical conductivity properties. BPLPAT nanoparticles are able to label cells for fluorescence imaging and perform deep tissue detection with PA imaging. Coupled with significant photothermal performance, BPLPAT nanoparticles demonstrate great potential for thermal treatment and in vivo real‐time detection of cancers. The results on BPLPAT scaffolds demonstrate 3D high‐spatial‐resolution deep tissue PA imaging (23 mm), as well as promote growth and differentiation of PC‐12 nerve cells. It is envisioned that the biodegradable dual‐imaging‐enabled electroactive citrate‐based biomaterial platform will expand the currently available theranostic material systems and open new avenues for diversified biomedical and biological applications via the demonstrated multifunctionality.     

Near‐Infrared Laser‐Triggered Nitric Oxide Nanogenerators for the Reversal of Multidrug Resistance in Cancer

The potential therapeutic implications of nitric oxide (NO) for diverse diseases have been under consideration for years; however, the development of precisely controllable NO generation system with potential for clinical application has remained elusive. Herein, intelligent near‐infrared (NIR) laser‐triggered NO nanogenerators for the treatment of multidrug‐resistant (MDR) cancer are fabricated by integrating photothermal agents and heat‐sensitive NO donors into a single nanoparticle. Such nanogenerators can absorb 808 nm NIR photons and convert them into ample heat to trigger NO release. The generated NO molecules are demonstrated to successfully achieve multidrug‐resistance reversal by inhibiting the expression of P‐glycol protein. Consequently, the intracellular accumulation of doxorubicin is effectively increased, resulting in high toxicity to MDR cancer cells in vitro. By virtue of surface modification with targeting ligands, these nanoparticles are able to selectively accumulate in tumor tissue. The therapeutic effects of the nanogenerators are validated in a humanized MDR cancer model. The in vivo experiment indicates that the nanoparticles possess excellent tumor suppression functionality with few side effects upon NIR laser exposure. Therefore, this novel photothermal conversion‐based NO‐releasing platform is expected to be a potential alternative to clinical MDR cancer treatment and may provide insights with regard to other NO‐relevant medical treatments.     

Different Aspects of Using Ultrasound to Combat Microorganisms

Growing resistance of microorganisms to antibiotics due to their widespread use has led to multiple bacterial infections posing a serious threat to health and human life. Low-frequency ultrasound is one of physical methods for inactivation of pathogenic microbial cells. Application of ultrasound is safe, demonstrates good tissue penetration without significant attenuation of energy, and does not induce microbial resistance. Bactericidal effect of ultrasound is based on acoustic cavitation—the growth and collapse of microbubbles in a liquid medium, resulting in shock waves, shear forces, and microjets which cause irreversible damage and inactivation of microorganisms. The present review combines and analyzes literature data on in vitro and in vivo studies and summarizes works demonstrating the ability of ultrasound, alone or in combination with other methods, to combat pathogenic microorganisms. The results of various studies presented in this review show that low-frequency ultrasound has a noticeable antimicrobial effect on planktonic cells of microorganisms and biofilms. Ultrasound synergistically enhances the effectiveness of other antibacterial agents and activates molecules called sonosensitizers, resulting in the formation of compounds toxic to microbial cells. Ultrasound can also promote local release of antimicrobial drugs from liposomes, as well as from medical implants.     

Enzyme-Degradable 3D Multi-Material Microstructures

There exists a growing need for smart materials suitable for use in biomedical applications. Herein, a photoresist that can be used to fabricate a biocompatible material entirely degradable by the enzyme chymotrypsin is introduced. The photoresist is based on a crosslinker with a tyramine moiety that is recognized and cleaved by the enzyme chymotrypsin. Macroscopic films as well as microstructures are fabricated via the use of direct laser writing. Multi-material boxing ring microstructures are generated and selectively degraded by the enzyme. Cell biocompatibility studies indicate that cells are able to attach and proliferate over one week on the material. A photoresist that is biocompatible and can be entirely removed by a biocompatible stimulus such as an enzyme can potentially be used as an easily removed tissue engineering scaffold and is especially promising for basic cell biology research.     

Tumor Intracellular‐Environment Responsive Materials Shielded Nano‐Complexes for Highly Efficient Light‐Triggered Gene Delivery without Cargo Gene Damage

Gene therapy has great potential to bring tremendous improvement to cancer therapy. Recently, photochemical internalization (PCI) has provided the opportunity to overcome endo‐lysosomal sequestration, which is one of the main bottlenecks in both gene and chemotherapeutic delivery. Despite PCI having shown great potential in gene delivery systems, it still remains difficult to perform due to the photo‐oxidation of exogenous cargo genes by reactive oxygen species (ROS) generated from activated photosensitizers (PSs). In this paper, a new type of a stable light‐triggered gene delivery system is demonstrated based on endo‐lysosomal pH‐responsive polymeric PSs, which serve as shielding material for the polymer/gene complex. By taking advantage of the endo‐lysosomal pH‐sensitive de‐shielding ability of the pH‐responsive shielding material incorporated in the ternary gene complexes (pH‐TCs), a more significant photo‐triggered gene expression effect is achieved without damage to the gene from ROS. In contrast, pH‐insensitive material‐shielded nanocarriers cause photo‐oxidation of the payload and do not generate a notable transfection efficacy. Importantly, with the benefit of our newly developed gene delivery system, the deep penetration issue can be resolved. Finally, the light‐triggered gene delivery system using pH‐TCs is applied to deliver the therapeutic p53 gene in melanoma K‐1735 bearing mice, showing excellent therapeutic potential for cancer.     

43例歼(强)击机飞行员肾结石的诊治及医学鉴定

目的探讨歼（强）击机飞行员肾结石的诊断治疗及医学鉴定原则。方法回顾分析1982年-2008年43名患肾结石的歼（强）击机飞行员病史资料、诊治过程及医学鉴定结论。结果23名肾结石飞行员经治疗结石排出,4例确诊为肾钙化,均飞行合格;3人因结石长期治疗无效予以停飞,1人因其他疾病停飞;12例处于治疗、观察期,结论为飞行暂不合格。结论歼（强）击机飞行员（含飞行教员）患肾结石影响飞行安全,应在结石排出后方可恢复飞行远离集合系统的肾钙化灶可放飞,但应定期复查,掌握其变化情况。     

Photoresponsive Protein–Graphene–Protein Hybrid Capsules with Dual Targeted Heat‐Triggered Drug Delivery Approach for Enhanced Tumor Therapy

A novel photo‐responsive protein–graphene–protein (PGP) capsule that doubles as a photothermal agent with core/shell structure is constructed by anchoring reduced graphene oxide nanosheets on one‐component protein (lactoferrin) shell through a double emulsion method. PGP capsules can transport fully concealed hydrophilic anticancer cargo, doxorubicin (Dox), with a large payload (9.43 μmol g^‐1) to be later unloaded in a burst‐like manner by photo‐actuation triggered by near‐infrared irradiation. Being biocompatible yet with a high cancer cell targeting efficiency, PGP capsules have successfully eradicated subcutaneous tumors in 10 d following a single 5 min NIR irradiation without distal damage. Besides, the photochemothermal therapy of PGP capsules eradicates tumor cells not only in the light‐treating area but also widely light‐omitted tumor cells, overcoming the tumor recurrence due to efficient cell killing efficacy. These results demonstrate that the PGP capsule is a potential new drug delivery platform for local‐targeting, on‐demand, photoresponsive, combined chemotherapy/hyperthermia for tumor treatment and other biomedical applications.     

Recent Advances of Cell Membrane‐Coated Nanomaterials for Biomedical Applications

Surface modification of nanomaterials is essential for their biomedical applications owing to their passive immune clearance and damage to reticuloendothelial systems. Recently, a cell membrane‐coating technology has been proposed as an ideal approach to modify nanomaterials owing to its facile functionalized process and good biocompatibility for improving performances of synthetic nanomaterials. Here, recent advances of cell membrane‐coated nanomaterials are reviewed based on the main biological functions of the cell membrane in living cells. An overview of the cell membrane is introduced to understand its functions and potential applications. Then, the applications of cell membrane‐coated nanomaterials based on the functions of the cell membrane are summarized, including physical barrier with selective permeability and cellular communication via information transmission and reception processes. Finally, perspectives of biomedical applications and challenges about cell membrane‐coated nanomaterials are discussed.     

多功能光学微操纵平台及应用

多功能光学微操纵平台是一种新型的微操控、微加工和微测量系统,它集成了光镊、飞秒激光光刀、显微光谱仪等多种功能.它对微小"工件",如生物细胞、细胞器及其它微小粒子的夹持、操作和微加工都是通过光来实现的,没有任何机械接触.它具有研究个体活体,实时动态,无机械损伤,遥控,不干扰粒子周围环境等优点,可以用来进行细胞分选、细胞融合、染色体切割、细胞转基因操纵、微细手术、分子马达、微小样品光谱测量等精细操作,可以广泛应用于生物医学、材料化学、纳米科技等领域.     

Engineering DNA-Grafted Quatsomes as Stable Nucleic Acid-Responsive Fluorescent Nanovesicles

The development of artificial vesicles into responsive architectures capable of sensing the biological environment and simultaneously signaling the presence of a specific target molecule is a key challenge in a range of biomedical applications from drug delivery to diagnostic tools. Herein, the rational design of biomimetic DNA-grafted quatsome (QS) nanovesicles capable of translating the binding of a target molecule to amphiphilic DNA probes into an optical output is presented. QSs are synthetic lipid-based nanovesicles able to confine multiple organic dyes at the nanoscale, resulting in ultra-bright soft materials with attractiveness for sensing applications. Dye-loaded QS nanovesicles of different composition and surface charge are grafted with fluorescent amphiphilic nucleic acid-based probes to produce programmable FRET-active nanovesicles that operate as highly sensitive signal transducers. The photophysical properties of the DNA-grafted nanovesicles are characterized and the highly selective, ratiometric detection of clinically relevant microRNAs with sensitivity in the low nanomolar range are demonstrated. The potential applications of responsive QS nanovesicles for biosensing applications but also as functional nanodevices for targeted biomedical applications is envisaged.     

高应变率加载条件下固体材料动态断裂的理论研究

本文利用一维理想弹塑性流体力学模型,通过数值方法,研究了高功率脉冲强激光辐照固休靶材时,表面烧蚀压在固体靶材中产生的激波的形成、稳定和衰减过程。并分别利用累计判断和动态断裂准则,计算了铝靶中产生的层裂损伤。所得结果与国外有关数值模拟及实测结果较为一致。     

35 GHz GaAs power MESFETs and monolithic amplifiers

GaAs MESFETs optimized for power operation at 35 GHz are described. Various doping levels and potential barrier layers at the interface between the buffer and the active layers were studied. The best power performance was obtained from an FET on a very heavily doped active layer. A device on an AlGaAs heterobuffer had further improved output power. The best devices delivered output power densities of 0.8 W/mm with 23% efficiency, 0.71 W/mm with 34% efficiency, and 0.61 W/mm with 41% efficiency. Monolithic power amplifiers with a 400-μm FET generated 200 mW of output power. These amplifiers were monolithically power combined, resulting in 600 mW of output power at 34 GHz     

Ascidian‐Inspired Fast‐Forming Hydrogel System for Versatile Biomedical Applications: Pyrogallol Chemistry for Dual Modes of Crosslinking Mechanism

Exploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self‐regeneration. Specific polypeptides containing 3,4,5‐trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA–PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA–PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian‐inspired HA–PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.     

High‐Strength,Durable All‐Silk Fibroin Hydrogels with Versatile Processability toward Multifunctional Applications

Hydrogels are the focus of extensive research due to their potential use in fields including biomedical, pharmaceutical, biosensors, and cosmetics. However, the general weak mechanical properties of hydrogels limit their utility. Here, pristine silk fibroin (SF) hydrogels with excellent mechanical properties are generated via a binary‐solvent‐induced conformation transition (BSICT) strategy. In this method, the conformational transition of SF is regulated by moderate binary solvent diffusion and SF/solvent interactions. β‐sheet formation serves as the physical crosslinks that connect disparate protein chains to form continuous 3D hydrogel networks, avoiding complex chemical and/or physical treatments. The Young's modulus of these new BSICT–SF hydrogels can reach up to 6.5 ± 0.2 MPa, tens to hundreds of times higher than that of conventional hydrogels (0.01–0.1 MPa). These new materials fill the “empty soft materials' space” in the elastic modulus/strain Ashby plot. More remarkably, the BSICT–SF hydrogels can be processed into different constructions through different polymer and/or metal‐based processing techniques, such as molding, laser cutting, and machining. Thus, these new hydrogel systems exhibit potential utility in many biomedical and engineering fields.     

Uptake and Release of Double‐Walled Carbon Nanotubes by Mammalian Cells

Efforts to develop carbon nanotubes (CNTs) as nano‐vehicles for precise and controlled drug and gene delivery, as well as markers for in vivo biomedical imaging, are currently hampered by uncertainties with regard to their cellular uptake, their fate in the body, and their safety. All of these processes are likely to be affected by the purity of CNT preparation, as well as the size and concentration of CNTs used, parameters that are often poorly controlled in biological experiments. It is demonstrated herein that under the experimental conditions of standard transfection methods, DWNTs are taken up by cultured cells but are then released after 24 h with no discernable stress response. The results support the potential therapeutic use of CNTs in many biomedical settings, such as cancer therapy.     

Engineering 2D Multifunctional Ultrathin Bismuthene for Multiple Photonic Nanomedicine

2D monoelemental nanomaterials (Xenes) have shown tremendous potential for versatile biomedical applications. Bismuth, as a heavy element in pnictogens, has acquired massive research interest due to its unique optical performance, high biocompatibility, stability, and relatively low cost. However, the utilization of 2D bismuthene in nanomedicine has not been achieved because of the difficulty in engineering bismuthene with crucial structural/compositional characteristics for satisfying strict biomedical requirements. Herein, to address this Gordian knot, a facile strategy to intercalate and delaminate Bi bulk for generating mass few-layered 2D bismuthene with high yield by employing a water molecule mediated freezing–thawing process and sodium borohydride-triggered reduction treatment is proposed. The resulting 2D bismuthene displays good optical performance in the near-infrared (NIR) biowindow and can be excited via red light for reactive oxygen species generation, enabling applications in multiple photonic cancer nanomedicine settings, including photothermal hyperthermia and photodynamic therapy. Utilizing the intrinsic desirable optical absorbance and strong X-ray attenuation of bismuthene, dual photonic therapy can be conducted under the supervision of photoacoustic/computed tomography guided multimodal imaging. This research not only offers a potential mass-production ready, cost-effective, and eco-efficient methodology for engineering 2D Xenes, but also exploits an innovative 2D bismuthene based photonic cancer nanomedicine.