Electrohydrodynamic Pulling Consolidated High-Efficiency 3D Printing to Architect Unusual Self-Polarized ß-PVDF Arrays for Advanced Piezoelectric Sensing.

Piezoelectric pressure sensors are important for applications in robotics, artificial intelligence, communication devices, etc. The hyperboloid is theoretically predicted to be an unusual 3D structure that allows concerted piezoelectric enhancement owing to its synergistic effects of geometrical stress confinement and stress concentration, but has not been experimentally fulfilled due to a lack of efficient architecting techniques. In this work, a 3D hyperboloidal arrayed self-polarized PVDF piezoelectric energy harvester (PEH) is successfully fabricated by incorporating electrohydrodynamic (EHD) pulling technology into fused deposition modeling (FDM) 3D printing. This strategy not only simplifies the layer-by-layer constructing procedure for arrays, but simultaneously realizes a self-polarized and high ß-phase (92%) PVDF PEH in a single electric-pulling step, saving posttreatment such as poling and removing excessive additives. Such a PEH delivers a significantly enhanced piezoelectric potential which is around 8 times that of a 2D flat film sensor. Moreover, this PEH featuring excellent linearity within a wide pressure regime, enables the sensing of human activities in a relatively large force range, which is otherwise difficult for traditional film sensors to differentiate. This work demonstrates a potential roadmap to advanced piezoelectric sensors exploiting unusual 3D structures enabled by the unique EHD pulling coupled 3D printing technique.

Living Artificial Skin: Photosensitizer and Cell Sandwiched Bacterial Cellulose for Chronic Wound Healing.

Chronic wounds pose a significant global public health challenge due to their suboptimal treatment efficacy caused by bacterial infections and microcirculatory disturbances. Inspired by the biofunctionality of natural skin, an artificial skin (HV@BC@TBG) is bioengineered with bacterial cellulose (BC) sandwiched between photosensitizers (PS) and functionalized living cells. Glucose-modified PS (TBG) and vascular endothelial growth factor (VEGF)-functionalized living cells (HV) are successively modified on each side of BC through biological metabolism and bio-orthogonal reaction. As the outermost layer, the TBG layer can generate reactive oxygen species (ROS) upon light illumination to efficiently combat bacterial infections. The HV layer is the inner layer near the diabetic wound, which servs as a living factory to continuously secrete VEGF to accelerate wound repair by promoting fibroblast proliferation and angiogenesis. The sandwiched structural artificial skin HV@BC@TBG is nontoxic, biocompatible, and demonstrated its ability to significantly accelerate the healing process of infected diabetic wounds, rendering it a promising next-generation medical therapy for chronic wound management.

Combined ecotoxicological effects of different-sized polyethylene microplastics and imidacloprid on the earthworms (Eisenia fetida).

Microplastics (MPs) and pesticides frequently coexist in farmland soil; however, there are relatively few studies on the ecological risk assessment of soil animals attributed to the combined pollution caused by MPs and pesticides. Moreover, the influence of particle size on the combined toxic effects of MPs and pesticides remains poorly understood. In this study, different-sized polyethylene MPs (PE MPs; 10 µm, 500 µm, and 2 mm) were combined with a series of imidacloprid concentrations (IMI; 0.10, 0.50 and 1.00 mg/kg), and earthworms (Eisenia fetida) were exposed to these MP and IMI combinations for 28 d to explore the combined toxic effects and mechanisms. The results showed, compared with IMI or PE MPs exposure alone, the combined exposure of IMI and PE MPs did not substantially increase the acute toxicity of earthworms but significantly inhibited weight increase and induced more serious epidermal damage to earthworms with a size effect; among these 10 µm PE MPs combined with IMI exhibited the strongest toxic effects. In addition, the combined exposure decreased antioxidant enzymes activity and caused oxidative damage in earthworms. Transcriptome results demonstrated most of the treatment combinations affected the ferroptosis pathway, which was further verified by the increase in the total iron content, reactive oxygen species, and malondialdehyde content in earthworms. Combined with the analysis of key signalling pathways, the above results revealed that the combined exposure to IMI and PE MPs showed stronger toxicity to earthworms than exposure to either IMI or MPs alone, which was mediated by the superimposed effect of ferroptosis and oxidative damage. Moreover, the effect was size-dependent, with 10 µm PE MPs combined with IMI exhibiting the strongest toxic effects. This study aimed to provide data to support the ecological risk assessment of soil animals caused by the combined pollution of MPs and coexisting pesticides.

Accumulation of epoxiconazole from soil via oleic acid-embedded cellulose acetate membranes and bioavailability evaluation in earthworms (Eisenia fetida).

A passive sampler in the soil environment is a relatively novel technique and has had quite limited applications, especially for pesticides. Oleic acid-embedded cellulose acetate membranes (OECAMs) were developed to evaluate the bioavailability of epoxiconazole (EPO) to earthworms (Eisenia fetida). The uptake of EPO by OECAMs (R2 = 0.975) and earthworms (R2 = 0.938) was compared and found to follow a two-compartment kinetic model. EPO sampling by OECAMs reached equilibrium (94%) within 2 d. OECAM could be used to determine the concentration of EPO in soil porewater. Furthermore, a significant linear relationship (R2 = 0.990) was observed between the EPO concentrations in earthworms and the OECAMs. The EPO concentrations in the porewater and OECAMs were lower in soils with a higher organic matter (OM) content. The EPO concentrations in the porewater, earthworms, and OECAMs decreased by 64.4, 49.0, and 56.1%, respectively, in the presence of 0.5% biochar, compared with the control. Furthermore, the use of OECAMs versus earthworms for soil testing also allows you to avoid factors that increase variance in organisms, such as avoidance behaviors or feeding. Therefore, OECAMs show good potential for use as a passive sampler to evaluate the bioavailability of EPO.

Direct Synthesis of Photosensitizable Bacterial Cellulose as Engineered Living Material for Skin Wound Repair.

Living materials based on bacterial cellulose (BC) represent a natural and promising candidate for wound dressing. Both physical adsorption and chemical methods have been applied to BC for realizing antibacterial function. However, effective and long-lasting incorporation of bactericidal moieties to BC remains challenging. Herein, a Komagataeibacter sucrofermentans-based direct synthetic method to fabricate photosensitizer-grafted BC through in situ bacterial metabolism in the presence of TPEPy-modified glucose is explored. The results verify that the direct biosynthesis method is efficient and convenient to endow BC with outstanding fluorescence and light-triggered photodynamic bactericidal activity for skin wound repair. This work presents a new approach to fabricate eco-friendly and active wound dressing with light-controlled bactericidal activity by microbial metabolism. The successful modification of the glucose carbon source of microorganisms also offers insights for biosyntheses of other living materials through microbial metabolism.

Enhanced specificity of bimetallic ions via mesoporous confinement for phosphopeptides in human saliva.

Phosphopeptides were of great significance in disease diagnosis and monitoring its dynamic changes. In this article, we proposed a more efficient method to synthesize a kind of bimetallic mesoporous silica nanomaterials (Fe3O4@mSiO2-PO3-Ti4+/Zr4+) and applied it to the analysis of phosphopeptides in human saliva samples based on IMAC technology. The chelation group was introduced into mesopores at the same time as the formation of mesoporous silica which significantly reduced the synthesis procedure and improved the synthesis efficiency. The as-prepared materials showed great sensitivity, selectivity and size-exclusion performance for phosphopeptides in standard ß-casein digests. More importantly, the materials identified 85 phosphopeptides in disease saliva samples which provided a candidate choice in future clinical examination.

HClO-Activated Fluorescence and Photosensitization from an AIE Nanoprobe for Image-Guided Bacterial Ablation in Phagocytes.

Bacteria hiding in host phagocytes are difficult to kill, which can cause phagocyte disorders resulting in local and systemic tissue damage. Effective accumulation of activatable photosensitizers (PSs) in phagocytes to realize selective imaging and on-demand photodynamic ablation of bacteria is of great scientific and practical interests for precise bacteria diagnosis and treatment. Herein, HClO-activatable theranostic nanoprobes, DTF-FFP NPs, for image-guided bacterial ablation in phagocytes are introduced. DTF-FFP NPs are prepared by nanoprecipitation of an HClO-responsive near-infrared molecule FFP and an efficient PS DTF with aggregation-induced emission characteristic using an amphiphilic polymer Pluronic F127 as the encapsulation matrix. As an energy acceptor, FFP can quench both fluorescence and production of reactive oxygen species (ROS) of DTF, thus eliminating the phototoxicity of DTF-FFP NPs in normal cells and tissues. Once delivered to the infection sites, DTF-FFP NPs light up with red fluorescence and efficiently generate ROS owing to the degradation of FFP by the stimulated release of HClO in phagocytes. The selective activation of fluorescence and photosensitization is successfully confirmed by both in vitro and in vivo results, demonstrating the effectiveness and theranostic potential of DTF-FFP NPs in precise bacterial therapy.

Evaluation of biochars in reducing the bioavailability of flubendiamide in water/sediment using passive sampling with polyoxymethylene.

An equilibrium passive sampler based on POM was first used to determine the Cfree of flubendiamide in water/sediment systems. The adsorption of flubendiamide by POM followed a first-order one-compartment uptake model and the POM-water partition coefficient was 1.90. The method was used to compare the efficiency of three biochars which were produced from crofton weed (BC-1, ∼500°C), macadamia (BC-2, 550-660°C) and wheat straw (BC-3, 550°C). The Freundlich fit the sorption isotherm data well and the adsorption capacity was BC-1>BC-3>BC-2. The percent removal of the BC-1 was higher in acidic solutions. When different doses of BC-1 were added to two sediments, the Cfree of the flubendiamide was higher in the sediment with a low organic matter content (S-1). With an increase of BC-1, the Cfree was significantly reduced in S-1. A 30-day period of biochar-sediment contact time was sufficient for a reduction of freely dissolved flubendiamide in the case of the two sediments tested. In the combination of biochar addition (5%) and aging time (30days), the maximum reductions were 87% and 60% in S-1 and S-2. Therefore, the reduction of bioavailability of the flubendiamide and pollution repair can be achieved by this process.

Polyoxymethylene passive samplers to assess the effectiveness of biochar by reducing the content of freely dissolved fipronil and ethiprole.

An equilibrium passive sampler based on polyoxymethylene (POM) was used to determine the freely dissolved concentrations (Cfree) of fipronil and ethiprole. The sorption equilibrium times of fipronil and ethiprole in POM were 14.2d and 24.0d, respectively. The POM-water partitioning coefficients (logKPOM-water) were 2.6 for fipronil and 1.4 for ethiprole. The method was further used to evaluate the sorption behavior of biochars which produced by pyrolysis of Magnolia wood (Magnolia denudata) at 300°C, 500°C and 700°C. The amounts of target compounds adsorbed increased with increasing pyrolysis temperature of the biochars. Biochars characterized by a low polarity index had better sorption capacity for the target compounds. The additions of biochars to sediment were effective in reducing Cfree, and the enhancement was found to be more pronounced with high biochar content. Cfree in sediment with more organic matter was significantly higher after biochar addition. Increasing the sediment-biochar contact time from 7 to 30d resulted in an increase in sorption of the compounds. We conclude that Magnolia wood biochar effectively reduces the content of freely dissolved fipronil and ethiprole content in sediment.

Targeting ETS1 with RNAi-based supramolecular nanoassemblies for multidrug-resistant breast cancer therapy.

Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically. In this study, we developed a supramolecular nanoassembly that could deliver siRNA targeting ETS1 (siETS1) and doxorubicin (DOX) as an effective nanomedicine to achieve successful chemotherapy towards multidrug-resistant breast cancer. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (AD) into polyethyleneimine-modified (2-hydroxypropyl)-γ-cyclodextrin (HP) through the supramolecular assembly to form AD-loaded HP (HPAD), followed by electrostatically-driven self-assembly between siETS1 and HPAD. When the HPAD/siETS1 nanoassemblies were delivered into drug-resistant MCF-7/ADR cells, the drug efflux was significantly reduced as a result of simultaneous silencing of ETS1 and MDR1 genes. Importantly, the HPAD/siETS1 nanoassembly could enhance drug residence time at tumor site, and effectively inhibit drug-resistant tumor growth due to the inhibition of angiogenesis and necrosis in tumor tissues. Western blot analysis indicated that the gene expression of both ETS1 and MDR1 in vivo was considerably downregulated after the drug-resistant tumor-bearing mouse was treated with HPAD/siETS1 nanoassemblies. This study offers a new therapeutic delivery strategy targeting ETS1 for the effective multidrug-resistant chemotherapy.

Redox-Activated Light-Up Nanomicelle for Precise Imaging-Guided Cancer Therapy and Real-Time Pharmacokinetic Monitoring.

Simultaneous tumor imaging, therapy, and pharmacokinetic monitoring can offer a safe and effective strategy for cancer therapy. This work describes the design of a fluorescence light-up nanomicelle that can afford precise imaging-guided drug delivery and pharmacokinetic monitoring in a real-time fashion for cancer chemotherapy. The nanomicelle, which contains a boron dipyrromethene based fluorescent probe as the hydrophobic core and a redox-triggered detachable poly(ethylene glycol) (PEG) shell, can accumulate at the tumor site via enhanced permeation and retention effect. The PEG detachment induced by tumoral and intracellular glutathione can destabilize the nanomicelle, leading to fluorescence light up and simultaneous drug release. Importantly, the fluorescence intensities generated by the nanomicelles in different organs are well-correlated with released drug concentrations in both temporal and spatial manners, suggesting its precise role for imaging-guided drug delivery and pharmacokinetic monitoring in vivo. The tumor growth can be effectively inhibited by the docetaxel-loaded nanomicelle formulation, and the nanomicelles are monitored to be excreted via hepatobiliary routes. This nanomicelle for precise imaging-guided chemotherapy provides a safe and robust theranostic strategy for the evaluation of cancer nanomedicine.

Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model.

The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significantly higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of an antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy.

Synthesis of core-shell graphitic carbon@silica nanospheres with dual-ordered mesopores for cancer-targeted photothermochemotherapy.

Tumor site-directed multifunctional therapeutic platforms such as photothermochemotherapy that respond to tumor-focused physical and biological stimuli are highly demanded for effective cancer therapy. Herein, targeting peptide-conjugated core­shell graphitic carbon@silica nanospheres with dual-ordered mesopores (MMPS) were successfully fabricated and developed as antitumoral doxorubicin (DOX) delivery system (MMPSD) for synergistic targeted photothermal chemotherapy of breast cancer. The hydrophilic mesoporous silica shell guarantees good water dispersity of MMPSD. The hydrophobic graphitic mesoporous carbon core provides excellent hydrophobic drug loading, immediate contact between the drug and photothermal hotspots, and high NIR photothermal conversion efficiency. SP13 peptide facilitates MMPSD for targeted and enhanced delivery of DOX within HER2-positive SK-BR-3 breast cancer cells, while PEGylation ensures biocompatibility. Thus, the MMPSD system exhibited efficient drug loading capacity, high targeting ability, sensitive NIR/pH-responsive DOX release, sustained release, and excellent combined antitumor activity.

Development of a multi-residue enantiomeric analysis method for 9 pesticides in soil and water by chiral liquid chromatography/tandem mass spectrometry.

A novel and sensitive chiral liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous measuring individual enantiomers of 9 pesticides including herbicides, insecticides, and fungicides in soil and water. The separation and determination were performed using reversed-phase chromatography on an amylose chiral stationary phase, a Chiralpak AD-RH column, under gradient elution using a mixture of ACN-2mM ammonium acetate in water as the mobile phase at 0.45 mL/min flow rate. The effects of three cellulose-based columns and three amylose-based columns on the separation were also investigated. The QuEChERS (acronym for Quick, Easy, Cheap, Effective, Rugged and Safe) method and solid-phase extraction (SPE) were used for the extraction and clean-up of the soil and water samples, respectively. Parameters including the matrix effect, linearity, precision, accuracy and stability were undertaken. Under optimal conditions, the mean recoveries for all enantiomers from the soil and water samples were ranged from 77.8% to 106.2% with the relative standard deviations (RSD) less than 14.2%. Good linearity (at least R(2) ≥ 0.9986) was obtained for all studied analytes in the soil and water matrix calibration curves over the range from 2.0 to 125 µg/L. The limits of detection (LOD) for all enantiomers in the soil and water were less than 1.8 µg/kg or µg/L, whereas the limit of quantification (LOQ) did not exceed 5.0 µg/kg or µg/L. The results of the method validation confirm that this proposed method is convenient and reliable for the enantioselective determination of the enantiomers of 9 chiral pesticides in soil and water.