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The traditional freeway safety studies with “poststatic” thinking basically use cross-sectional data or panel data, which find it difficult to figure out real-time traffic crash risk factors. With the development of information collection technology, it is possible to obtain high-resolution traffic flow data currently, which provide a data basis for the dynamic traffic safety research towards freeways. This research aims at accurately identifying the real-time traffic crash precursors on freeways and addressing the shortcomings of conventional dynamic traffic safety research with the thinking of limited factor dimensions. In this research, dimensional data were applied as input model variables, the input dataset includes traffic crash data and the matched dynamic traffic flow data, and weather information and road characteristics were also considered to figure out the interaction effects between these dimensional factors. The XGBoost (eXtreme Gradient Boosting) was carried out to identify the dynamic crash-prone variables and the SHAP (SHapley Additive exPlanations) interpreter was introduced to interpret the XGBoost model, as well as the visualization of the influence of each eigenvalue on the traffic crash was realized. The results indicate that, in addition to traffic flow variables, road, weather, and temporal characteristics also have an impact on the traffic crash risk, and there is an interaction between each feature. The results of this research can provide the theoretical basis for freeway real-time traffic crash prediction and safety control.

Recognition mechanism of the APN–SUB nanoprobe as the color-convertible probe toward APN.

This tutorial review summarizes recent advances in salient features of digital synthetic polymers for data storage, including encoding, decoding, editing, erasing, encrypting, and repairing.

Electron-ion transduction is the cornerstone for electronic devices interfacing with biological organisms and promoting emerging ionotronic devices, ranging from basic electronic elements to wearable electronics and energy harvesting devices. However, with commonly used metal electrodes, the electron-ion transduction suffers from high impedance, signal distortion and poor voltage tolerance. Surface modification with conductive porous materials could partially remedy these issues but is inevitably accompanied by weak interfacial adhesion and mechanical weakness. Therefore, freestanding electrodes integrating high mechanical and electrical properties are highly demanded. Herein, a general strategy is discovered to ameliorate these issues by introducing a conducting polymer (CP) hydrogel electrode of ultrahigh strength (~30 MPa) and conductivity (up to ~1200 S cm−1) with a capacitive behavior. These features are derived from the conductive nanoporous matrix with π-π interactions as both crosslinking sites and electron-transfer pathways, through surface gelation coupled with secondary-doping and densification. This strategy significantly decreased the low-frequency impedance and improved the signal fidelity, without affecting its high-frequency response. Furthermore, excellent biocompatibility, multifunctionality, and heart pacing upon ultra-low voltage (60% reduction) have also been demonstrated, showing the great potential of this CP material for bioelectronic applications and various human-machine interfaces.

Accurate and reliable detection of exosomal miRNA can serve as a promising method for early diagnosis of disease and evaluation of therapeutic effects. However, current exosomal miRNA detection methods commonly involve exosome enrichment, containing RNA extraction, and qRT-PCR based quantification, which are expensive and time-consuming. Herein, we develop a DNA zipper-mediated membrane fusion approach for rapid exosomal miRNA detection and cancer diagnosis. First, a lipid vesicle probe containing miR21-targeting molecular beacons (MBs) is constructed and further loaded with zipper DNA constructs (ZDCs) on its surface. Meanwhile, complementary zipper DNA constructs (cZDCs) are introduced on the exosome of interest. Upon mixing them together, zipping between ZDC and cZDC induces the membrane fusion of exosomes and vesicle probes, triggering the recognition of exosomal miR21 by contained MBs and fluorescence emission that can be conveniently detected within 30 min. Importantly, with the assistance of flow cytometry, miR21-overexpressed tumor exosomes derived from either cell culture medium or clinical patient serums can be distinguished from exosomes secreted from normal cells. This approach provides a convenient way to accurately detect the exosomal miRNA, which may hold great potential in liquid biopsy for early cancer diagnosis and monitoring the therapeutic effects during the treatments.

A well-defined virus-like cage hybrid (VCH) with 24 covalent organic cages (COCs) attached to one metal organic cage (MOC) is presented here. The quantitative assembly of VCH was completed through coordination between soluble anisotropic COC bearing one bipyridine moiety and Pd(II) ions. The obtained VCH exhibited discrete, uniform and stable structures with good solubility and was well characterized by NMR, FT-IR, TEM, AFM, DLS, TGA, and so on. This designable cage hybrid promotes a new strategy to expand the structural and functional complexities of porous molecular cages.

Since cooling and heating loads are recognized as key characteristics for evaluating the energy efficiency of buildings, it appears indisputable that they must be predicted and analyzed for residential structures. Accordingly, the multi-layer perceptron neural network is applied for predicting the heating and cooling loads using the experimental dataset. The used dataset is obtained by monitoring the impact of the building's dimensions on energy consumption. To optimize the training process of the multi-layer perceptron neural network, several optimizers are employed. Besides, different statistical performance indicators are considered to see which selected optimizer outperforms the rest in terms of accuracy and authenticity. The obtained results emphasize the remarkable performance of adaptive chaotic grey wolf optimization, which can be used to train the multi-layer perceptron neural network and forecast the buildings’ energy consumption with the highest accuracy. According to the obtained results, the hybrid multi-layer perceptron neural network- adaptive chaotic grey wolf optimization method demonstrates the best performance. The optimum number of neurons in the hidden layer is obtained to be 15. Also, based on the statistical performance indicators, the selected method reveals an R2 of 0.9123 and 0.9419 for cooling and heating loads, respectively.

Small interfering RNA (siRNA) has been emerging as a highly selective and effective pharmaceutics for treating broad classes of diseases. However, the practical application of siRNA agent is often hampered by its poor crossing of the cellular membrane barrier and ineffective releasing from endosome to cytoplasm, leading to low gene silencing efficacy for clinical purposes. Thus far, cationic lipid and polymer-based vectors have been extensively explored for gene delivery. Yet condensing the rigid and highly negatively charged siRNA duplex to form a stable complex vehicle usually requires a large load of cationic carriers, prone to raising the toxicity issue for delivery. Herein, we develop a simple strategy that can efficiently condense the siRNAs into nanoparticle vehicles for target gene regulation. In this approach, we first employ a DNA-grafted polycaprolactone (DNA

DTX-AI effectively suppresses the growth of HeLa-tumor and A549-tumor xenografts in vivo and increases the survival rate of mice. It is expected to be a promising ‘me-better’ anti-tumor drug with higher efficiency and lower toxicity in clinic.

Anionic ring-opening polymerization (AROP) of N-sulfonyl aziridines is an important synthetic route to linear polyethyleneimine (PEI) and its derivatives. In most cases, inert atmosphere and dry solvent were needed because of the oxygen- and water-sensitive initiators/catalysts used. Therefore, the AROP of N-sulfonyl aziridines that can be entirely operated in air atmosphere is still a challenging task. Herein, we report a series of sulfanions, including xanthates, dithiocarbamates, dithiobenzoates, thioacetates, and thiolates, as the initiators for the AROP of N-sulfonyl aziridines. Due to their good stability, open-vessel polymerization was achieved with high livingness, affording a range of well-defined α-, ω-telechelic poly(N-sulfonyl aziridine) homopolymers and block copolymers with narrow dispersities and tunable molecular weights. The α-end group of these polyaziridines was readily converted to thiol group, which enabled further post-polymerization functionalization with benzyl acrylate and poly(ethylene glycol) via thiol-ene click chemistry. The establishment of open-vessel sulfanion-initiated AROP of N-sulfonyl aziridines thus lays a solid foundation for the bulk preparation and application of poly(N-sulfonyl aziridine)s and PEI derivatives.

The unique tripeptide structure of green fluorescent protein (GFP), a Ser-Tyr-Gly motif, generates the mature chromophore in situ to define the emission profiles of GFP. Here, we describe the rational design and discovery of a biomimetic fluorescent emitter, MBP, by mimicking the key structure of the Ser-Tyr-Gly motif. Through systematically tailoring the tripeptide, a family of four chromophores were engineered, while only MBP exhibited bright fluorescence in different fluid solvents with highly enhanced quantum yields. Distinct to previous hydrogen-bonding-induced fluorescence quenching of GFP chromophore analogues, the emission of MBP was only slightly decreased in protic solvents. Heteronuclear multiple bond correlation techniques demonstrated the fundamental mechanism for enhanced fluorescence emission owing to the synergy of the formation of the intramolecular hydrogen-bonding-ring structure and the self-restricted effect, which was further illustrated via theoretical calculations. This work puts forward an extraordinary approach toward highly emissive biomimicking fluorophores, which gives new insights into the emission mechanisms and photophysics of GFP-like chromophores.

As the gold standard for stealth polymer materials, poly(ethylene glycol) (PEG) has been widely used in drug delivery with excellent properties such as low toxicity, reduced immunogenicity, good water solubility, and so forth. However, lack of understanding for the fate of PEG and PEGylated delivery systems at the cellular level has limited the application of PEGylated molecules in diagnosis and therapy. Here, we chose linear PEG 5k as a representative model and focused on the internalization behavior and mechanism, intracellular trafficking, sub-cellular localization, and cellular exocytosis of PEG and PEGylated molecules in living cells. Our investigation showed that PEG could be internalized into cells in 1 h. The internalized PEG was localized to lysosome, cytosol, endoplasmic reticulum (ER) and mitochondria. Importantly, the fate of PEG in cells could be regulated by conjugating different small molecules. PEGylated rhodamine B (PEG-RB) as the positively charged macromolecule was internalized into cells by micropinocytosis and then transported in lysosomes, ER, and mitochondria via vesicles sequentially. In contrast, PEGylated pyropheophorbide-a (PEG-PPa) as the negatively charged macromolecule was internalized into cells and transported to lysosomes ultimately. PEGylation slowed down the exocytosis process of RB and PPa and significantly prolonged their residence time inside the cells. These findings improve the understanding of how PEG and PEGylated molecules interact with the biological system at cellular and sub-cellular levels, which is of significance to rational PEGylation design for drug delivery.

Nucleic acid sensors have realized much success in detecting positively charged and neutral molecules, but have rarely been applied for measuring negatively charged molecules, such as fluoride, even though an effective sensor is needed to promote dental health while preventing osteofluorosis and other diseases. To address this issue, we herein report a quantitative fluoride sensor with a portable fluorometer readout based on fluoride riboswitch-regulated transcription coupled with CRISPR-Cas13-based signal amplification. This tandem sensor utilizes the fluoride riboswitch to regulate in vitro transcription and generate full-length transcribed RNA that can be recognized by CRISPR-Cas13a, triggering the collateral cleavage of the fluorophore-quencher labeled RNA probe and generating a fluorescence signal output. This tandem sensor can quantitatively detect fluoride at ambient temperature in aqueous solution with high sensitivity (limit of detection (LOD) ≈ 1.7 μM), high selectivity against other common anions, a wide dynamic range (0–800 μM) and a short sample-to-answer time (30 min). This work expands the application of nucleic acid sensors to negatively charged targets and demonstrates their potential for the on-site and real-time detection of fluoride in environmental monitoring and point-of-care diagnostics., A fluoride sensor based on riboswitch-regulated transcription coupled with Cas13a sensor can detect fluoride in water with a portable fluorometer. This sensor expands nuclei acid sensors to an anion, with high sensitivity and selectivity against other common anions.

Developments of soft network materials with rationally distributed wavy microstructures have enabled many promising applications in bio-integrated electronic devices, due to their abilities to reproduce precisely nonlinear mechanical properties of human tissues/organs. In practical applications, the soft network materials usually serve as the encapsulation layer and/or substrate of bio-integrated electronic devices, where deterministic holes can be utilized to accommodate hard chips, thereby increasing the filling ratio of the device system. Therefore, it is essential to understand how the hole-type imperfection affects the stretchability of soft network materials with various geometric constructions. This work presents a systematic investigation of the imperfection sensitivity of mechanical properties in soft network materials consisting of horseshoe microstructures, through combined computational and experimental studies. A factor of imperfection insensitivity of stretchability is introduced to quantify the influence of hole imperfections, as compared to the case of perfect soft network materials. Such factor is shown to have different dependences on the arc angle and normalized width of horseshoe microstructures for triangular network materials. The soft triangular and Kagome network materials, especially with the arc angle in the range of (30 $$^{\circ }$$ , 60 $$^{\circ }$$ ), are found to be much more imperfection insensitive than corresponding traditional lattice materials with straight microstructures. Differently, the soft honeycomb network materials are not as imperfection insensitive as traditional honeycomb lattice materials.

A combinatorial strategy based on nucleic acid assembly and electrostatic complexation is developed for efficient small interfering ribonucleic acid(siRNA) delivery. In this approach, siRNAs are first loaded into a well-defined nanotube through programmable nucleic acid self-assembly. Compared to small rigid siRNA duplex, the obtained siRNA-bearing nanotube with large architecture is more readily to complex with cationic and ionizable poly(β-amino ester), resulting in the formation of a novel platform for efficient siRNA delivery.

DNA origami has been widely used to construct nanophotonic structures due to its unparallel capability in assembling photonic nanomaterials with nanometer precision. Nevertheless, the majority of fabricated fluorescence-based nanophotonic systems so far operate in the ultraviolet-visible (UV-Vis) region, which are accompanied by limitations of shallow penetration and potential light damage. Herein, we constructed a reconfigurable nanophotonic heterostructure by integrating an upconversion nanoparticle (UCNP) and a gold nanorod (AuNR) on a DNA origami switch (DOS) template. With the unique anti-Stokes luminescence of UCNP whose excitation wavelength is mostly located in the near-infrared (NIR) region, the obtained reconfigurable nanophotonic system can be excited by 980 laser light and generates visible light emission. In our nanophotonic system, the DNA origami template serves as a switch to reversibly tune the optical properties of UCNP. The construction of this nanophotonic heterostructure expands the toolbox of DNA origami-based nanophotonic systems that may hold great potential in optical biosensing and imaging.

With rapid advances in soft electronic devices, the demand for soft conductive materials, including hydrogels, with superior mechanical properties, high conductivity and functionality under extreme environmental conditions are increasing at an unprecedented rate. Although hydrogels have favorable properties such as softness and broad tunability ranges, they freeze at subzero temperatures, leading to materials failure and device malfunctions, and the introduction of antifreezing agents into hydrogels often severely compromises their conductive or mechanical properties. The tradeoff between simultaneously endowing antifreezing hydrogels with excellent mechanical properties and high conductivity severely limits their practical applicability over a broad range of conditions. Herein, we discovered that potassium acetate (KAc) induces a salting-out effect on polyvinyl alcohol (PVA), promoting aggregation of the polymer chains and significantly improving the mechanical properties of the hydrogels. Moreover, concentrated KAc exhibits excellent anti-freezing capacity and high conductivity. The hydrogels produced by soaking frozen PVA in KAc solutions show superior mechanical properties, with a tensile strength of 8.2 MPa, conductivity of 8.0 S/m and outstanding freeze tolerance to a temperature of −60 °C. This strategy also works for other polymers, such as poly(acrylamide) and poly(2-hydroxyethyl acrylate). Additionally, the as-prepared hydrogels possess excellent anti-dehydration capacity, which is another important feature that is desirable for further enhancing the applicability and durability of hydrogel-based devices.

Urine is a nitrogenous waste biomass but can be used as an appealing alternative substrate for H

Imaging and tracking macrophage behaviors in vivo are essential to reveal its biological function and fate in various diseases. Small molecular probes suffer from poor macrophage targeting and retention, rapid clearance, and deficient metabolizing stability. To overcome these limitations, a variety of functional nanoprobes have been developed for targeted imaging of macrophages in divergent diseases such as cancer, atherosclerosis and obesity. Generally, nanoprobes are functionalized with targeting peptides, ligands or antibodies to fulfill high macrophage affinity. In this review, the most recent advances of nanoprobes for imaging macrophages in vivo and ex vivo are systematically summarized. The challenges and perspectives of precisely imaging macrophages with improved signal-to-background ratios via nanoprobes are further discussed.

Enzymatic biofuel cells (EBFCs) are promising renewable and implantable power sources, but it exhibits low power output due to enzyme structure. The enzyme’s catalytic center is deeply buried insid...

Natural load-bearing materials such as tendons have a high water content of about 70 per cent but are still strong and tough, even when used for over one million cycles per year, owing to the hierarchical assembly of anisotropic structures across multiple length scales1. Synthetic hydrogels have been created using methods such as electro-spinning2, extrusion3, compositing4,5, freeze-casting6,7, self-assembly8 and mechanical stretching9,10 for improved mechanical performance. However, in contrast to tendons, many hydrogels with the same high water content do not show high strength, toughness or fatigue resistance. Here we present a strategy to produce a multi-length-scale hierarchical hydrogel architecture using a freezing-assisted salting-out treatment. The produced poly(vinyl alcohol) hydrogels are highly anisotropic, comprising micrometre-scale honeycomb-like pore walls, which in turn comprise interconnected nanofibril meshes. These hydrogels have a water content of 70–95 per cent and properties that compare favourably to those of other tough hydrogels and even natural tendons; for example, an ultimate stress of 23.5 ± 2.7 megapascals, strain levels of 2,900 ± 450 per cent, toughness of 210 ± 13 megajoules per cubic metre, fracture energy of 170 ± 8 kilojoules per square metre and a fatigue threshold of 10.5 ± 1.3 kilojoules per square metre. The presented strategy is generalizable to other polymers, and could expand the applicability of structural hydrogels to conditions involving more demanding mechanical loading. A strategy that combines freeze-casting and salting-out treatments produces strong, tough, stretchable and fatigue-resistant poly(vinyl alcohol) hydrogels.

Theranostic agents based on magnetic resonance imaging (MRI) and photothermal therapy (PTT) play an important role in tumor therapy. However, the available theranostic agents are facing great challenges such as biocompatibility, MRI contrast effect and photothermal conversion efficiency (η). In this work, mesoporous polydopamine nanoparticles (MPDAPs/Mn) were prepared on MRI and PTT combined theranostic nanoplatforms, of which the high loading manganese ions and specific surface areas enable good MRI contrast and excellent photothermal conversion efficiency, respectively. The MPDAPs/Mn have uniform morphology, good stability and biocompatibility. Meanwhile, in vitro and in vivo studies have confirmed their superior T1-weighted MRI effect and photothermal conversion efficiency. Furthermore, MPDAPs/Mn have excellent antitumor efficacy in HeLa tumor-bearing mice. Therefore, this developed MPDAPs/Mn theranostic nanoplatform could be a promising candidate for MRI-guided photothermal cancer therapy.

A pH-responsive fluorinated chitosan-chlorin e6 (FC-Ce6) was employed here for the intracellular delivery of catalase to relieve the hypoxic micro-environment. Upon simple mixing, FC-Ce6 and catalase co-assemble to form stable nanoparticles, which show a greatly improved cross-membrane penetration capacity compared with catalase alone or nonfluorinated CS-Ce6/catalase nanoparticles. Under catalase catalysis, a high concentration of intracellular H2O2 can be transformed into O2. Upon irradiation, due to the continuous formation of cytotoxic singlet oxygen (1O2), our nanoparticles showed superior anti-cancer activity in contrast to free Ce6 and nonfluorinated CS-Ce6/catalase nanoparticles. Our study proposes an effective intracellular catalase delivery system to overcome hypoxia for enhanced PDT against oral cancer.

The immune system plays a key role in restraining tumor progression. Therefore, enhancing immune functions using immune stimulants, such as unmethylated CpG oligonucleotides, has emerged as a promising strategy for antitumor therapy. However, poor cellular uptake of negatively charged oligonucleotides and M2 polarization of tumor-associated macrophages remain two major challenges for CpG-based immunotherapy. Herein, we construct a spherical nucleic acid (SNA)-like nanogel assembled by a CpG-grafted polycaprolactone (CpG-g-PCL) brush and an anti-STAT3 siRNA crosslinker for synergistic tumor immunotherapy. After accumulation at the tumor site, this dual siRNA- and CpG-bearing nanogel (CpGgel-siSTAT3) can efficiently trigger M1 type macrophage activation and deter its M2 polarization via block STAT3 signaling, increase the intratumor CD8+ T cell infiltration, and thus successfully restrain tumor growth. Our study demonstrates the new potential of a nucleic acid nanogel platform for the co-delivery of different therapeutic oligonucleotides and combinatorial CpG-based immunotherapy.

Stimuli-responsive polypeptoids are promising peptidomimetic polymers that can regulate their physical/chemical properties by means of external stimuli and have drawn tremendous attention for potential biotechnological applications. Here, we report the preparation of photo-responsive polypeptoids via the ring-opening polymerization of the monomer N-azobenzene-ethyl-N-carboxyanhydride (Azo-NNCA). The obtained diblock polypeptoids bearing azobenzene side chains (PEG-b-PAzo) showed reversible photo-responsive behavior in both organic and aqueous solutions, demonstrated by proton nuclear magnetic resonance (1H NMR) measurements and ultraviolet–visible (UV–vis) spectroscopy. Depending on the chain length of PAzo, various polymeric assemblies were readily obtained, including spherical and rod-like micelles, which exhibited a reversible morphology transformation upon alternating UV–vis light irradiation. The detailed process of morphology transformation was systemically investigated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Moreover, the polypeptoids also presented an irreversible responsiveness to temperature, resulting in different morphology transitions of assemblies. The new photo-responsive and biocompatible polypeptoid-based materials hold appreciable potential for biomedical and bioengineering applications.

p53 is a common tumor suppressor, and its mutation drives tumorigenesis. What is more, p53 mutations have also been reported to be indicative of poor prognosis in lung cancer, but the detailed mechanism has not been elucidated. In this study, we found that DNA primase subunit 2 (PRIM2) had a high expression level and associated with poor prognosis in lung cancer. Furthermore, we found that PRIM2 expression was abnormally increased in lung cancer cells with p53 mutation or altered the p53/RB pathway based on database. We also verified that PRIM2 expression was elevated by mutation or deletion of p53 in lung cancer cell lines. Lastly, silence p53 increased the expression of RPIM2. Thus, these data suggest that PRIM2 is a cancer-promoting factor which is regulated by the p53/RB pathway. The p53 tumor-suppressor gene integrates numerous signals that control cell proliferation, cell cycle, and cell death; and the p53/RB pathway determines the cellular localization of transcription factor E2F, which regulates the expression of downstream targets. Next, we explored the role of PRIM2 in lung cancer and found that knockdown of PRIM2 induced cell cycle arrest, increased DNA damage, and increased cell senescence, leading to decreased lung cancer cell proliferation. Lastly, the positive correlation between PRIM2 and E2F/CDK also indicated that PRIM2 was involved in promoting cell cycle mediated by p53/RB pathway. These results confirmed that the expression of PRIM2 is regulated by the p53/RB pathway in lung cancer cells, promotes DNA replication and mismatch repair, and activates the cell cycle. Overall, we found that frequent p53 mutations increased PRIM2 expression, activated the cell cycle, and promoted lung cancer progression.

Osteosarcoma (OS) is one of the most common bone malignant tumors which mainly develops in adolescents. Although neoadjuvant chemotherapy has improved the prognosis of patients, numerous chemotherapeutic challenges still limit their use. Here, inspired by the Watson-Crick base pairing in nucleic acids, hydrophobic (methotrexate) and hydrophilic (floxuridine) chemo-drugs are mixed and self-assembled into M:F nanoparticles (M:F NPs) through molecular recognition. Then, the obtained NPs are co-extruded with membranes derived from OS cells to form cancer-cell membrane-coated NPs (CCNPs). With protected membranes at the outer layer, CCNPs are highly stable in both physiological and weak acid tumor conditions and possess homologous tumor targeted capability. Furthermore, the proteomic analysis first identifies over 400 proteins reserved in CCNPs, most of them participating in tumor cell targeting and adhesion processes. In vitro studies reveal that CCNPs significantly inhibit the PI3K/AKT/mTOR pathway, which promotes cell apoptosis and cell cycle arrest. More importantly, cell membrane camouflage significantly prolongs the circulation half-life of CCNPs, elevates the drug accumulation at tumor sites, and promotes anti-tumor efficacy in vivo. As a convenient and effective strategy to construct a biomimetic NP with high drug loading ratio, the CCNPs provide new potentials for precise and synergistic antitumor treatment.

Packaging multiple drugs into a nanocarrier with rational design to achieve synergistic cancer therapy remains a challenge due to the intrinsically varied pharmacodynamics of therapeutic agents. Especially difficult is combining small-molecule drugs and macromolecular biologics. Here, we successfully graft pheophorbide A (PPA) photosensitizers on DNA backbone at predesigned phosphorothioate modification sites. The synthesized four PPA-grafted DNAs are assembled into a tetrahedron framework, which further associates with a programmed death ligand-1 (PD-L1) small interfering RNA (siRNA) linker through supramolecular self-assembly to form an siRNA and PPA copackaged nanogel. With dual therapeutic agents inside, the nanogel can photodynamically kill tumor cells and induce remarkable immunogenic cell death. Also, it simultaneously silences the PD-L1 expression of the tumor cells, which substantially promotes the antitumor immune response and leads to an enhanced antitumor efficacy in a synergistic fashion.

Hybrid polymerization of reversible complexation mediated polymerization (RCMP) and reversible addition–fragmentation chain-transfer (RAFT) polymerization was designed via introducing the chain-tra...

In vitro-transcribed messenger RNA (mRNA) can efficiently express the therapeutic proteins in target cells without the concern of mutagenesis, which holds great promise for the treatment of a broad...

Tumor accumulation and intratumoral singlet oxygen (1O2) generation efficiency of photosensitizers (PSs) are two essential factors that determine their photodynamic therapy (PDT) efficacies. How to maximize the PS performance at the tumor site is of great research interest. Herein, we report a metal-organic framework (ZIF-8, ZIF = zeolitic imidazolate framework) assisted in vivo self-assembly nanoplatform, ZIF-8-PMMA-S-S-mPEG, as an effective tool for organic PS payloads to achieve efficient PDT. Using an organic PS with aggregation-induced emission as an example, under intratumoral bioreduction, PS-loaded ZIF-8-PMMA-S-S-mPEG (PS@ZIF-8-PMMA-S-S-mPEG) was self-assembled into large ordered hydrophobic clusters, which greatly enhance tumor retention and accumulation of the PS. Moreover, hydrophobic ZIF-8 assemblies greatly isolate the loaded PSs from water and improve O2 transport for the PSs to effectively produce 1O2 inside tumors under light irradiation. The organic PS is therefore endowed with optimal tumor accumulation and intratumoral 1O2 production, demonstrating the effectiveness of the developed self-assembly strategy in PDT application.

The degradation effect of ultrasound (US)/hydrogen peroxide (H2O2) on Tremella fuciformis polysaccharide (TFP) were studied. The main process parameters of degradation were evaluated and the structural changes and antioxidant activities of TFP before and after US/H2O2 were analyzed. The results showed that the degradation effect of US/H2O2 was significantly higher than that of US or H2O2 alone, and the degradation of TFP was dependent on the duration of its exposure to US, the ultrasonic amplitude, and the H2O2 and TFP concentrations. US/H2O2 reduced the molecular weight (from 8.14 × 105 Da to 1.27 × 104 Da) and particle size (from 710 nm to 182 nm) of the TFP within 50 min and narrowed its molecular weight and particle size distribution. High performance liquid chromatography, Fourier-transform infrared spectroscopy, Carbon-13 nuclear magnetic resonance, scanning electron microscopy, atomic force microscopy, and Congo red results indicated that the treatment could break down the polysaccharide chains, hinder the aggregation, and improve the conformation flexibility of the TFP molecules without changing the primary structure and monosaccharide composition of TFP. Additionally, the degraded TFPs with low molecular weight exhibited a higher antioxidant activity than the original TFP. These findings suggest that the US/H2O2 treatment is a simple and effective method to prepare a TFP of low molecular weight and high bioactivity.

Developing non-cationic gene carriers and achieving efficient endo/lysosome escape of functional nucleic acids in cytosol are two major challenges faced by the field of gene delivery. Herein, we demonstrate the concept of self-escape spherical nucleic acid (SNA) to achieve light controlled non-cationic gene delivery with sufficient endo/lysosome escape capacity. In this system, Bcl-2 antisense oligonucleotides (OSAs) were conjugated onto the surface of aggregation-induced emission (AIE) photosensitizer (PS) nanoparticles to form core-shell SNA. Once the SNAs were taken up by tumor cells, and upon light irradiation, the accumulative 1 O2 produced by the AIE PSs ruptured the lysosome structure to promote OSA escape. Prominent in vitro and in vivo results revealed that the AIE-based core-shell SNA could downregulate the anti-apoptosis protein (Bcl-2) and induce tumor cell apoptosis without any transfection reagent.

Combinatorial antitumor therapies using different combinations of drugs and genes are emerging as promising ways to overcome drug resistance, which is a major cause for the failure of cancer treatment. However, dramatic pharmacokinetic differences of drugs greatly impede their combined use in cancer therapy, raising the demand for drug delivery systems (DDSs) for tumor treatment. By employing fluorescent dithiomaleimide (DTM) as a linker, we conjugate two paclitaxel (PTX) molecules with a floxuridine (FdU)-integrated antisense oligonucleotide (termed chemogene) to form a drug-chemogene conjugate. This PTX-chemogene conjugate can self-assemble into a spherical nucleic acid (SNA)-like micellular nanoparticle as a carrier-free DDS, which knocks down the expression of P-glycoprotein and subsequently releases FdU and PTX to exert a synergistic antitumor effect and greatly inhibit tumor growth.

Background Growing evidence has indicated that microRNAs (miRNAs) are involved in the progression of calcific aortic valve disease (CAVD), a progressive pathological condition with no effective pharmacological therapy. This study was set out with the aim to investigate possible roles of miR-195 in CAVD. Methods and results Initially, the differential expressed genes (DEGs) associated with CAVD were screened out and miRNAs potentially regulating VWF were predicted from microarray analysis. Next, we quantified VWF and miR-195 expression in isolated aortic valve interstitial cells (AVICs) and aortic valve tissues, followed by confirmation of the target relationship between miR-195 and VWF using the dual luciferase reporter assay. Furthermore, we evaluated the biological functions of miR-195 and VWF on ALP activity, cell differentiation, and the levels of miR-195, VWF, Runx2, OCN, ALP, p38 and phosphorylated p38 in AVICs. VWF was highly expressed, while miR-195 was poorly expressed in CAVD. Furthermore, miR-195 targeted VWF and negatively regulated its expression. Upregulation of miR-195 or silencing VWF could reduce ALP activity, calcified deposition, and the mRNA and protein levels of Runx2, OCN, and ALP by inhibiting the p38-MAPK signaling pathway, thereby ameliorating aortic valve calcification in vitro. Conclusions On all accounts, miR-195 can potentially inhibit aortic valve calcification by repressing VWF and p38-MAPK signaling pathway, highlighting a theoretical basis for pharmacological treatment of CAVD.

Purpose Gd-encapsulated carbonaceous dots (Gd@C-dots) have excellent stability and magnetic properties without free Gd leakage, therefore they can be considered as a safe alternative T1 contrast agent to commonly used Gd complexes. To improve their potential for cancer diagnosis and treatment, affibody-modified Gd@C-dots targeting non-small-cell lung cancer (NSCLC) EGFR-positive tumors with enhanced renal clearance were developed and synthesized. Materials and methods Gd@C-dots were developed and modified with Ac-Cys-ZEGFR:1907 through EDC/NHS. The size, morphology, and optical properties of the Gd@C-dots and Gd@C-dots-Cys-ZEGFR:1907 were characterized. Targeting ability was evaluated by in vitro and in vivo experiments, respectively. Residual gadolinium concentration in major organs was detected with confocal imaging and inductively coupled plasma mass spectrometry (ICP-MS) ex vivo. H&E staining was used to assess the morphology of these organs. Results Gd@C-dots with nearly 20 nm in diameter were developed and modified with Ac-Cys-ZEGFR:1907. EGFR expression in HCC827 cells was higher than NCI-H520. In cell uptake assays, EGFR-expressing HCC827 cells exhibited significant MR T1WI signal enhancement when compared to NCI-H520 cells. Cellular uptake of Gd@C-dots-Cys-ZEGFR:1907 was reduced, when Ac-Cys-ZEGFR:1907 was added. In vivo targeting experiments showed that the probe signal was significantly higher in HCC827 than NCI-H520 xenografts at 1 h after injection. In contrast to Gd@C-dots, Gd@C-dots-Cys-ZEGFR:1907 nanoparticles can be efficiently excreted through renal clearance. No morphological changes were observed by H&E staining in the major organs after injection of Gd@C-dots-Cys-ZEGFR:1907. Conclusion Gd@C-dots-Cys-ZEGFR:1907 is a high-affinity EGFR-targeting probe with efficient renal clearance and is therefore a promising contrast agent for clinical applications such as diagnosis and treatment of NSCLC EGFR-positive malignant tumors.

Ice accumulation causes various problems in our daily life for human society. The daunting challenges in ice prevention and removal call for novel efficient antiicing strategies. Recently, photothermal materials have gained attention for creating icephobic surfaces owing to their merits of energy conservation and environmental friendliness. However, it is always challenging to get an ideal photothermal material which is cheap, easily fabricating, and highly photothermally efficient. Here, we demonstrate a low-cost, high-efficiency superhydrophobic photothermal surface, uniquely based on inexpensive commonly seen candle soot. It consists of three components: candle soot, silica shell, and polydimethylsiloxane (PDMS) brushes. The candle soot provides hierarchical nano/microstructures and photothermal ability, the silica shell strengthens the hierarchical candle soot, and the grafted low-surface-energy PDMS brushes endow the surface with superhydrophobicity. Upon illumination under 1 sun, the surface temperature can increase by 53 °C, so that no ice can form at an environmental temperature as low as −50 °C and it can also rapidly melt the accumulated frost and ice in 300 s. The superhydrophobicity enables the melted water to slide away immediately, leaving a clean and dry surface. The surface can also self-clean, which further enhances its effectiveness by removing dust and other contaminants which absorb and scatter sunlight. In addition, after oxygen plasma treatment, the surface can restore superhydrophobicity with sunlight illumination. The presented icephobic surface shows great potential and broad impacts owing to its inexpensive component materials, simplicity, ecofriendliness, and high energy efficiency.