A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

[Analysis of Key Points of Technical Review of Traditional Chinese Medicine Fumigation Treatment Device].

Traditional Chinese medicine fumigation device is the carrier of traditional Chinese medicine fumigation treatment. In recent years, with the rapid development of new technology and new materials, the development of fumigation device changes with each passing day, and a variety of new products continue to emerge. However, at present, the lack of corresponding evaluation norms, resulting in some difficulties in the registration, marketing, quality control, evaluation scale and other aspects of the product. Some products have many disadvantages in clinical use. From the perspective of technical review, this paper elaborates and analyzes the main concerns in technical review, such as product structure, main risks, performance requirements, clinical evaluation, etc., in order to provide a basis for the design, development, production, registration, use and post-marketing supervision of the devices.

[Discussion on the Authenticity Verification Method in the Verification of Medical Device Registration Quality Management System].

Authenticity verification is a very important aspect of medical device registration quality management system verification of medical device. How to verify the authenticity of samples is a problem worth discussing. This study analyzes the methods of authenticity verification from the aspects of product retention sample, registration inspection report, traceability of records, hardware facilities and equipment. In order to provide reference for relevant supervisors and inspectors in the verification of registration quality management system.

Mussel-Inspired Ligand Clicking and Ion Coordination on 2D Black Phosphorus for Cancer Multimodal Imaging and Therapy.

As a promising 2D nanocarrier, the biggest challenge of bare black phosphorus nanosheets (BP NSs) lies in the inherent instability, while it can be improved by surface modification strategies to a great extent. Considering the existing infirm BP NSs surface modification strategies, A mussels-inspired strong adhesive biomimetic peptide with azide groups for surface modification to increase the stability of BP NSs is synthesized. The azide groups on the peptide can quickly and precisely bind to the targeting ligand through click chemistry, solving the problem of nonspecificity of secondary modification of other mussel-mimicking materials. Besides, a catechol-Gd3+ coordination network is further constructed for magnetic resonance imaging (MRI) and inducing intracellular endo/lysosome escape. The fabricated BP-DOX@Gd/(DOPA)4 -PEG-TL nanoplatform exhibits enhanced antitumor abilities through synergetic chemo/photothermal effects both in vitro and in vivo.

A novel dual-flux immunochromatographic test strip based on luminescence resonance energy transfer for simultaneous detection of ochratoxin A and deoxynivalenol.

Mycotoxins are secondary metabolites of fungi, which seriously threaten human health. Among them, ochratoxin A (OTA) and deoxynivalenol (DON) have become the main factors that pollute cereals and by-products. In order to achieve simultaneous detection of OTA and DON quantitatively, a novel dual-flux immunochromatographic assay (dICA) was established. The dual-flux assay is based on upconversion nanoparticles (UCNPs) as fluorescence tags to label antigens and gold nanoparticles (AuNPs) as fluorescence quencher to label monoclonal antibodies (mAbs). The intensity of the green fluorescence (540 nm) of UCNPs can be used as an analytical signal, indicating the formation of antigen-antibody immune complexes, thereby indicating the presence or absence of the target analyte. The intensity of the red fluorescence (660 nm) of UCNPs is not affected and can be used as a quality control signal, and the dual-flux bidirectional single-line labeling mode allows for the simultaneous detection of two different mycotoxins on two test lines. This work indicated that the developed dICA provided a sensitive, rapid, and reliable on-site simultaneous detection of multiple mycotoxins.

Self-Assembled Aza-Boron-Dipyrromethene for Ferroptosis-Boosted Sonodynamic Therapy.

The presence of apoptosis inhibition proteins renders the cancer cells resistant to apoptosis, severely compromising the antitumor efficacy of sonodynamic therapy (SDT). Here, an intelligent anticancer nanoplatform based on an Aza-boron-dipyrromethene dye (denoted as Aza-BDY) is elaborately established for ferroptosis augmented SDT through cysteine (Cys) starvation. After endocytosis by tumor cells, Aza-BDY serves as both a ferroptosis inducing agent and a sonosensitizer for tumor treatment. The specific Cys response facilitates the disruption of redox homeostasis and initiation of cellular ferroptosis. Meanwhile, the released sonosensitizer causes efficient SDT and augments ferroptosis under ultrasound irradiation. Detailed in vitro and in vivo investigations demonstrate that the synergistic effect of Cys depletion and singlet oxygen (1 O2 ) generation significantly induces cancer-cell death and suppresses tumor proliferation with a high inhibition rate of 97.5 %.

Circularly Polarized Organic Room Temperature Phosphorescence from Amorphous Copolymers.

Organic optoelectronic functional materials featuring circularly polarized emission and persistent luminescence represent a novel research frontier and show promising applications in data encryption, displays, biological imaging, and so on. Herein, we present a simple and universal approach to achieve circularly polarized organic phosphorescence (CPP) from amorphous copolymers by the incorporation of axial chiral chromophores into polymer chains via radical cross-linked polymerization. Our experimental data reveal that copolymers (R/S)-PBNA exhibit a maximum CPP efficiency of 30.6% and the largest dissymmetric factor of 9.4 × 10-3 and copolymers (R/S)-PNA show the longest lifetime of 0.68 s under ambient conditions. Given the CPP property of these copolymers, their potential applications in multiple information encryption and displays are demonstrated, respectively. These findings not only lay the foundation for the development of amorphous polymers with superior CPP but also expand the outlook of room-temperature phosphorescent materials.

Self-Assembled Single-Site Nanozyme for Tumor-Specific Amplified Cascade Enzymatic Therapy.

Nanomaterials with enzyme-mimicking activity (nanozymes) show potential for therapeutic interventions. However, it remains a formidable challenge to selectively kill tumor cells through enzymatic reactions, while leaving normal cells unharmed. Herein, we present a new strategy based on a single-site cascade enzymatic reaction for tumor-specific therapy that avoids off-target toxicity to normal tissues. A copper hexacyanoferrate (Cu-HCF) nanozyme with active single-site copper exhibited cascade enzymatic activity within the tumor microenvironment: Tumor-specific glutathione oxidase activity by the Cu-HCF single-site nanozymes (SSNEs) led to the depletion of intracellular glutathione and the conversion of single-site CuII species into CuI for subsequent amplified peroxidase activity through a Fenton-type Harber-Weiss reaction. In this way, abundant highly toxic hydroxyl radicals were generated for tumor cell apoptosis. The results show that SSNEs could amplify the tumor-killing efficacy of reactive oxygen species and suppress tumor growth in vivo.

Cross-Linked Polyphosphazene Hollow Nanosphere-Derived N/P-Doped Porous Carbon with Single Nonprecious Metal Atoms for the Oxygen Reduction Reaction.

Heteroatom-doped polymers or carbon nanospheres have attracted broad research interest. However, rational synthesis of these nanospheres with controllable properties is still a great challenge. Herein, we develop a template-free approach to construct cross-linked polyphosphazene nanospheres with tunable hollow structures. As comonomers, hexachlorocyclotriphosphazene provides N and P atoms, tannic acid can coordinate with metal ions, and the replaceable third comonomer can endow the materials with various properties. After carbonization, N/P-doped mesoporous carbon nanospheres were obtained with small particle size (≈50 nm) and high surface area (411.60 m2 g-1 ). Structural characterization confirmed uniform dispersion of the single atom transition metal sites (i.e., Co-N2 P2 ) with N and P dual coordination. Electrochemical measurements and theoretical simulations revealed the oxygen reduction reaction performance. This work provides a solution for fabricating diverse heteroatom-containing polymer nanospheres and their derived single metal atom doped carbon catalysts.

Occurrence of Chiral Nanostructures Induced by Multiple Hydrogen Bonds.

Developing artificial systems to mimic the emergence of chirality is of vital importance in better understanding the mysterious origin of natural homochirality and guiding the design of advanced chiroptical materials. Herein, we present a DNA-inspired control over the emergence of supramolecular nanoscale chirality in multiple hydrogen-bonded self-assemblies. N-Terminated aromatic amino acids bearing serine and aromatic domains could self-assemble into lamellar microsheets without nanoscale chirality, ascribed to their pronounced molecular stacking preference on two-dimensional orientations. Significantly, when achiral bipyridine-, melamine-, and imidazole-based molecular binders that could potentially form hydrogen-bonded complexes with these aromatic amino acids were introduced, the induced chiral nanostructures from the resulting coassemblies were observed. Melamine and its derivatives presented an excellent capability to generate ordered supramolecular structures and induce the nanoscale chirality. Assisted by the key duplex hydrogen bonds between the melamine core and serine segments, chiral nanotubes and ribbons were obtained. This study reveals that multiple hydrogen bonds are the prerequisite for inducing the emergence of chiral nanostructures from integrated coassemblies.

NIR-Light-Activated Combination Therapy with a Precise Ratio of Photosensitizer and Prodrug Using a Host-Guest Strategy.

The co-delivery of photosensitizers with prodrugs sensitive to reactive oxygen species (ROS) for light-triggered ROS generation and cascaded prodrug activation has drawn tremendous attention. However, the absence of a feasible method to deliver the two components at a precise ratio has impaired the application potential. Herein, we report an efficient method to produce a nanosized platform for the delivery of an optimized ratio of the two components by the means of host-guest strategy for maximizing the combination therapy efficacy of cancer treatment. The key features of this host-guest strategy for the combination therapy are that the ratio between photosensitizer and ROS-sensitive prodrug can be easily tuned, near-infrared (NIR) irradiation can sensitize the photosensitizer and activate the paclitaxel prodrug for its release, and the accumulation process can be tracked by NIR imaging to maximize the efficacy of photodynamic and chemotherapy.

Water-Binding-Mediated Gelation/Crystallization and Thermosensitive Superchirality.

Determination of molecular structural parameters of hydrophobic cholesterol-naphthalimide conjugates for water binding capabilities as well as their moisture-sensitive supramolecular self-assembly were revealed. Water binding was a key factor in leading trace water-induced crystallization against gelation in apolar solvent. Ordered water molecules entrapped in self-assembly arrays revealed by crystal structures behave as hydrogen-bonding linkers to facilitate three-dimensional growth into crystals rather than one-dimensional gel nanofibers. Water binding was also reflected on the supramolecular chirality inversion of vesicle self-assembly in aqueous media via heating-induced dehydration. Structural parameters that favor water binding were evaluated in detail, which could help rationally design organic building units for advancing soft materials, crystal engineering, and chiral recognition.

Fast-Clearable Nanocarriers Conducting Chemo/Photothermal Combination Therapy to Inhibit Recurrence of Malignant Tumors.

Inhomogeneous heating by photothermal therapy (PTT) during cancer treatment often results in the recurrence of tumors. Thus, integrating PTT with chemotherapy (CHT) may provide a complementary treatment for enhanced therapeutic efficiency. Herein, this study develops a hollow structured polymer-silica nanohybrid (HPSN) as a nanocarrier to simultaneously deliver the anticancer drug paclitaxel and photothermal agent palladium phthalocyanine to tumors through enhanced permeation and the retention effect. A combinational CHT/PTT therapy on mice bearing aggressive tumor grafts is conducted. The highly malignant tumor model, which recurs after sole treatment of PTT, can be eradicated by the combined CHT/PTT treatment. In addition, most of the off-targeted HPSN nanocarriers can be excreted through a hepatobiliary pathway in about 10 d. Serology results show that the fast-clearable HPSN can significantly reduce the side effect of the loaded paclitaxel drug. The present work provides an alternative approach for combinational cancer treatment with high therapeutic efficiency.

[Discussion on the Existing Problems and Countermeasures of Medical Devices (â ¡) Clinical Trial].

To provide reference for further improve the level of medical devices clinical trial, to ensure the medical devices quality combing with the problems found in the medical devices clinical trial in Shandong province, the problems and countermeasures of medical devices (Ⅱ) clinical trial were explored. Four countermeasures were put forward to solve the problems of medical devices (Ⅱ) clinical trial from different angles including sponsors, clinical trials institutions and the important part of clinical trials:raising the threshold of entry, consummating relevant laws and regulations, establishing quality management system, strengthening personnel training, attaching great importance to CRA and CRC.

Host-Guest Interaction-Mediated Construction of Hydrogels and Nanovesicles for Drug Delivery.

Hand-in-hand or head-to-head: A novel naphthalimide derivative is successfully designed and synthesized, which can self-assemble to produce hydrogels. When injecting this compound into CB[8] solution, the nanovesicles are obtained with a narrow size distribution. The cytotoxicity assay confirms that doxorubicin-loaded nanocarriers show therapeutic effects to cancer cells.

Clicked Isoreticular Metal-Organic Frameworks and Their High Performance in the Selective Capture and Separation of Large Organic Molecules.

Three highly porous metal-organic frameworks (MOFs) with a uniform rht-type topological network but hierarchical pores were successfully constructed by the assembly of triazole-containing dendritic hexacarboxylate ligands with Zn(II) ions. These transparent MOF crystals present gradually increasing pore sizes upon extension of the length of the organic backbone, as clearly identified by structural analysis and gas-adsorption experiments. The inherent accessibility of the pores to large molecules endows these materials with unique properties for the uptake of large guest molecules. The visible selective adsorption of dye molecules makes these MOFs highly promising porous materials for pore-size-dependent large-molecule capture and separation.

Molecular binding behavior of a bispyridinium-containing bis(ß-cyclodextrin) and its corresponding [2]rotaxane towards bile salts.

Bispyridinium-bridged bis(ß-cyclodextrin) () and its corresponding [2]rotaxane () were synthesized by a 'click' reaction, in which two different types of macrocycles, cucurbit[7]uril and ß-cyclodextrin, are employed as the wheel component and bulky stopper, respectively. Moreover, the molecular binding behaviors of hosts and with four bile salts, namely, the sodium salts of cholic acid (CA), deoxycholic acid (DCA), glycocholic acid (GCA), and taurocholic acid (TCA), were comparatively investigated by (1)H NMR spectroscopy and isothermal titration calorimetry experiments. The spectroscopic and microcalorimetric results can jointly demonstrate a cucurbituril-mediated binding process; that is, the introduction of cucurbit[7]uril has a pronounced impact on the electrostatic attraction and hydrogen-bonding interaction between the bispyridinium spacer in the host molecules and the hydrophilic terminal group in the guest molecules, ultimately giving a significant change in the thermodynamic origins of these supramolecular complexes.

OX40L-expressing M1-like macrophage exosomes for cancer immunotherapy.

With only limited clinical patient benefit, focusing on new immune checkpoint pathways could be an important complement to current immune checkpoint drugs. In addition, not only does T cell-mediated adaptive immunity play an important role, but also macrophage-mediated innate immunity, due to its abundant presence in solid tumors. Here, we developed an engineered M1-like macrophage exosome, OX40L M1-exos. OX40L M1-exos can activate the adaptive immunity by activating the OX40/OX40L pathway and can reprogram M2-like tumor-associated macrophages into M1-like macrophages, thereby restoring and enhancing macrophage-mediated innate immunity. Our OX40L M1-exos achieved an effective synergistic effect of innate and adaptive immunity and achieved a potent therapeutic effect in a mouse breast cancer model, effectively inhibiting tumor growth and metastasis. These results suggest that OX40L M1-exos are an attractive therapeutic strategy and may be an important complement to current cancer immunotherapies.

Supramolecular assembly with multiple preorganised π-electronic cages.

Kept in a cage: Complexation of phthalocyanine-grafted cyclodextrins and a sulfonated porphyrin leads to the formation of supramolecular nanowires through multivalent binding. These complexes contain multiple, preorganised π-electronic cages that efficiently capture C(60) in water.

Hierarchical organization of spherical assembly with reversibly photocontrollable cross-links.

A ternary photocontrollable assembly was hierarchically constructed by the "orthogonal" host-guest interaction of different types of cyclodextrins toward the porphyrin and azobenzene. Spectroscopic titrations and microscopic investigations demonstrate that the inclusion complex of azobenzene modified water-soluble porphyrin (1) with phthalocyanine-grafted permethyl ß-cyclodextrins (2) could be reversibly cross-linked to relatively larger nanospheres with naphthyl bridged bis(α-cyclodextrin)s (3). Moreover, the large-sized spheres (1·2·3) could be disassembled and switched to small-sized complex (1·2) upon the photoinduced isomerization of an azophenyl group.