Electrochemiluminescence Immunosensors Based on ECL-RET Triggering between Mn SANE/PEI-Luminol and PtCu/h-MPF for Ultrasensitive Detection of CEA.

In this paper, a novel donor-acceptor pair was creatively proposed based on the principle of electrochemiluminescence resonance energy transfer (ECL-RET): luminol immobilized on polyethyleneimine (PEI)-functionalized manganese-based single-atom nanozymes (Mn SANE/PEI-luminol, donor) and a PtCu-grafted hollow metal polydopamine framework (PtCu/h-MPF, acceptor). A quenched ECL immunosensor was constructed for the ultrasensitive analysis of carcinoembryonic antigen (CEA). Mn SANE, as an efficient novel coreaction accelerator with the outstanding performance of significantly activating H2O2 to produce large amounts of ROS, was further modified by the coreactant PEI, which efficiently immobilized luminol to form a self-enhanced emitter. As a result, the electron transport distance was effectively shortened, the energy loss was reduced, and luminol achieved a high ECL efficiency. More importantly, PtCu-grafted h-MPF (PtCu/h-MPF) was proposed as a novel quencher. The UV-vis spectra of PtCu/h-MPF partially overlap with the ECL spectra of Mn SANE/PEI-luminol, which can effectively trigger the ECL-RET behavior between the donor and the acceptor. The multiple quenching effect on Mn SANE/PEI-luminol was achieved, which significantly improved the sensitivity of the immunosensor. The prepared immunosensor exhibited good linearity in the concentration range of 10-5 to 80 ng/mL. The results indicate that this work provides a new method for the early detection of CEA in clinical diagnosis.

Injectable Hybrid-Crosslinked Hydrogels as Fatigue-Resistant and Shape-Stable Skin Depots.

Injectable hydrogels have gained considerable attention, but they are typically mechanically weak and subject to repeated physiological stresses in the body. Herein, we prepared polyurethane diacrylate (EPC-DA) hydrogels, which are injectable and can be photocrosslinked into fatigue-resistant implants. The mechanical properties can be tuned by changing photocrosslinking conditions, and the hybrid-crosslinked EPC-DA hydrogels exhibited high stability and sustained release properties. In contrast to common injectable hydrogels, EPC-DA hydrogels exhibited excellent antifatigue properties with >90% recovery during cyclic compression tests and showed shape stability after application of force and immersion in an aqueous buffer for 35 days. The EPC-DA hydrogel formed a shape-stable hydrogel depot in an ex vivo porcine skin model, with establishment of a temporary soft gel before in situ fixing by UV crosslinking. Hybrid crosslinking using injectable polymeric micelles or nanoparticles may be a general strategy for producing hydrogel implants resistant to physiological stresses.

Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis.

Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.

Flexible Cationic Nanoparticles with Photosensitizer Cores for Multifunctional Biomedical Applications.

One challenge for multimodal therapy is to develop appropriate multifunctional agents to meet the requirements of potential applications. Photodynamic therapy (PDT) is proven to be an effective way to treat cancers. Diverse polycations, such as ethylenediamine-functionalized poly(glycidyl methacrylate) (PGED) with plentiful primary amines, secondary amines, and hydroxyl groups, demonstrate good gene transfection performances. Herein, a series of multifunctional cationic nanoparticles (PRP) consisting of photosensitizer cores and PGED shells are readily developed through simple dopamine-involving processes for versatile bioapplications. A series of experiments demonstrates that PRP nanoparticles are able to effectively mediate gene delivery in different cell lines. PRP nanoparticles are further validated to possess remarkable capability of combined PDT and gene therapy for complementary tumor treatment. In addition, because of their high dispersities in biological matrix, the PRP nanoparticles can also be used for in vitro and in vivo imaging with minimal aggregation-caused quenching. Therefore, such flexible nanoplatforms with photosensitizer cores and polycationic shells are very promising for multimodal tumor therapy with high efficacy.

Polystyrene Nanoplastics-Enhanced Contaminant Transport: Role of Irreversible Adsorption in Glassy Polymeric Domain.

Nanoplastics (NPs) are becoming an emerging pollutant of global concern. A potential risk is that NPs may serve as carriers to increase the spreading of coexisting contaminants. In this study, we examined the effects of polystyrene nanoplastics (PSNPs, 100 nm), used as a model NP, on the transport of five organic contaminants of different polarity in saturated soil. The presence of low concentrations of PSNPs significantly enhanced the transport of nonpolar (pyrene) and weakly polar (2,2',4,4'-tetrabromodiphenyl ether) compounds, but had essentially no effects on the transport of three polar compounds (bisphenol A, bisphenol F, and 4-nonylphenol). The strikingly different effects of NPs on the transport of nonpolar/weakly polar versus polar contaminants could not be explained with different adsorption affinities, but was consistent with the polarity-dependent extents of desorption hysteresis. Notably, desorption hysteresis was only observed for nonpolar/weakly polar contaminants, likely because nonpolar compounds tended to adsorb in the inner matrices of glassy polymeric structure of polystyrene (resulting in physical entrapment of adsorbates), whereas polar compounds favored surface adsorption. This hypothesis was verified with supplemental adsorption and desorption experiments of pyrene and 4-nonylphenol using a dense, glassy polystyrene polymer and a flexible, rubbery polyethylene polymer. Overall, the findings of this study underscore the potentially significant environmental implication of NPs as contaminant carriers.

The Hemodynamic Changes in Patients with Cerebral Arteriovenous Malformations before and after Interventional Embolization Therapy with Glubran 2 Acrylic Glue.

The study explored hemodynamic changes in patients with cerebral arteriovenous malformations (CAVM) before and -after interventional embolization therapy with Glubran 2 acrylic glue and analyzed the related factors. CAVM patients received endovascular embolization therapy with Glubran 2. Patients' systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), blood flow velocity (BFV), and pulsatility index (PI) were measured. The location of malformed vessels, Spetzler-Martin (SM) grade, CAVM size, and type of feeding artery and venous drainage were analyzed. CAVM patients showed increased DBP, SBP, MAP, and PI and decreased average BFV compared to before therapy. CAVM patients with big CAVM size, SM grade IV/V, deep location malformed vessels, deep, and mixed venous drainage, and cortical branch and mixed artery blood-supply exhibited lower DBP, SBP, MAP, and PI but higher average BFV. Hypertensive CAVM patients showed lower DBP, SBP, MAP, average BFV, and PI before or after embolization. Hypertension, SM grade, CAVM size, malformed vessels location, venous drainage, and artery blood-supply were correlated to the hemodynamic changes of CAVM patients. Embolization with Glubran 2 acrylic glue could enhance hemodynamics in CAVM patients, and the hemodynamic changes were in correlation with the SM grade, CAVM size, and malformed vessels location.

A Review of Structure Construction of Silk Fibroin Biomaterials from Single Structures to Multi-Level Structures.

The biological performance of artificial biomaterials is closely related to their structure characteristics. Cell adhesion, migration, proliferation, and differentiation are all strongly affected by the different scale structures of biomaterials. Silk fibroin (SF), extracted mainly from silkworms, has become a popular biomaterial due to its excellent biocompatibility, exceptional mechanical properties, tunable degradation, ease of processing, and sufficient supply. As a material with excellent processability, SF can be processed into various forms with different structures, including particulate, fiber, film, and three-dimensional (3D) porous scaffolds. This review discusses and summarizes the various constructions of SF-based materials, from single structures to multi-level structures, and their applications. In combination with single structures, new techniques for creating special multi-level structures of SF-based materials, such as micropatterning and 3D-printing, are also briefly addressed.

Real-Time Quantification of Nanoplastics-Induced Oxidative Stress in Stretching Alveolar Cells.

Nanoplastics from air pollutants can be directly inhaled into the alveoli in the lungs and further enter blood circulation, and numerous studies have revealed the close relation between internalized nanoplastics with many physiological disorders via intracellular oxidative stress. However, the dynamic process of nanoplastics-induced oxidative stress in lung cells under breath-mimicked conditions is still unclear, due to the lack of methods that can reproduce the mechanical stretching of the alveolar and simultaneously monitor the oxidative stress response. Here, we describe a biomimetic platform by culturing alveoli epithelial cells on a stretchable electrochemical sensor and integrating them into a microfluidic device. This allows reproducing the respiration of alveoli by cyclic stretching of the alveoli epithelial cells and monitoring the nanoplastics-induced oxidative stress by the built-in sensor. By this device, we prove that cyclic stretches can greatly enhance the cellular uptake of nanoplastics with the dependencies of strain amplitude. Importantly, oxidative stress evoked by internalized nanoplastics can be quantitatively monitored in real time. This work will promote the deep understanding about the cytotoxicity of inhaled nanoplastics in the pulmonary mechanical microenvironment.

Science-based evidence on pathways and effects of human exposure to micro- and nanoplastics.

Human exposure to plastic particles has raised great concern among all relevant stakeholders involved in the protection of human health due to the contamination of the food chain, surface waters, and even drinking water as well as due to their persistence and bioaccumulation. Now more than ever, it is critical that we understand the biological fate of plastics and their interaction with different biological systems. Because of the ubiquity of plastic materials in the environment and their toxic potential, it is imperative to gain reliable, regulatory-relevant, science-based data on the effects of plastic micro- and nanoparticles (PMNPs) on human health in order to implement reliable risk assessment and management strategies in the circular economy of plastics. This review presents current knowledge of human-relevant PMNP exposure doses, pathways, and toxic effects. It addresses difficulties in properly assessing plastic exposure and current knowledge gaps and proposes steps that can be taken to underpin health risk perception, assessment, and mitigation through rigorous science-based evidence. Based on the existing scientific data on PMNP adverse health effects, this review brings recommendations on the development of PMNP-specific adverse outcome pathways (AOPs) following the AOP Users' Handbook of the Organisation for Economic Cooperation and Development (OECD).

Examining the Temporal and Spatial Models of China's Circular Economy Based upon Detailed Data of E-Plastic Recycling.

Examining the circular economy model is crucial to enable the scaling up of industry and anthropogenic circularity practice. Electrical and electronic waste plastic (e-plastic) has become the focus of urban mining and circular economy due to its rapid growth, valuable resource and potential risks. This article focuses on the recycling companies' experience in China from 2012 to 2017. The average recycling rate was 33.3% and the recycling amount in 2017 was 558 kt. A two-dimensional coupling model of economic development and renewable resources is firstly constructed. Eventually, four typical resource-based regional models are summarized, namely for demonstration regional model, commissioned regional model, traditional model and potential regional model. It also puts forward differentiated suggestions in terms of maintaining demonstration, strengthening policies, promoting transformation, and tapping potential. At the same time, it is recommended to explore the construction of large-region resource-based recycling centers and big data centers in resource-based demonstration areas.

Giant panda age recognition based on a facial image deep learning system.

The conservation of the giant panda (Ailuropoda melanoleuca), as an iconic vulnerable species, has received great attention in the past few decades. As an important part of the giant panda population survey, the age distribution of giant pandas can not only provide useful instruction but also verify the effectiveness of conservation measures. The current methods for determining the age groups of giant pandas are mainly based on the size and length of giant panda feces and the bite value of intact bamboo in the feces, or in the case of a skeleton, through the wear of molars and the growth line of teeth. These methods have certain flaws that limit their applications. In this study, we developed a deep learning method to study age group classification based on facial images of captive giant pandas and achieved an accuracy of 85.99% on EfficientNet. The experimental results show that the faces of giant pandas contain some age information, which mainly concentrated between the eyes of giant pandas. In addition, the results also indicate that it is feasible to identify the age groups of giant pandas through the analysis of facial images.

Performance enhancement, membrane fouling mitigation and eco-friendly strategy by electric field coupled membrane bioreactor for treating mariculture wastewater.

An eco-friendly strategy for mariculture wastewater treatment using an electric field attached membrane bioreactor (E-MBR) was evaluated and compared with a conventional membrane bioreactor (C-MBR). The removal efficiencies of total nitrogen (TN) and chemical oxygen demand (COD) increased significantly and the membrane fouling rate reduced by 44.8% in the E-MBR. The underlying mechanisms included the enriched nitrifiers and denitrifiers, the enhanced salinity-resistance, the increased activities and upregulated genes of key enzymes involved in nitrification and denitrification for improving the performance of mariculture wastewater treatment, and the enriched extracellular polymeric substance (EPS)-degrading genera, the downregulated EPS biosynthesis genes, the repressed biofilm-forming bacteria, the enhanced zeta potential absolute value and the generated H2O2 for membrane fouling mitigation by electrical stimulation. Compared with the C-MBR, the energy consumption, carbon emissions, and nitrogen footprint were reduced. These findings provide novel insights into mariculture wastewater treatment using an applied electric field.

Chemiexcited Photodynamic Therapy Integrated in Polymeric Nanoparticles Capable of MRI Against Atherosclerosis.

Background: Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers. Methods: In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+-catechol complex for stabilization and magnetic resonance imaging (MRI). Results: The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T 1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T 1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta-iliac bifurcation. Conclusion: This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.

Efficacy and safety of drug-coated balloon in the treatment of acute myocardial infarction: a meta-analysis of randomized controlled trials.

Acute myocardial infarction (AMI) is one of the main causes of death in the world, and the incidence of AMI is increasing in the young population. Drug-coated balloon (DCB) has become an effective concept for the treatment of in-stent restenosis, small vessel disease, bifurcation lesions, high blood risk conditions, and even de novo large vessel disease. To ensure whether DCB can play an alternative role in AMI, we conducted a comprehensive meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of DCB in the treatment of AMI. Electronic databases were searched for RCTs that compared DCB with stent for AMI. The primary outcome was major adverse cardiac events (MACEs), the secondary outcome was late lumen loss (LLL). RevMan 5.3 software and RStudio software were used for data analysis. Five RCTs involving 528 patients with 6-12 months of follow-up were included. There was no significant difference in the incidence of MACEs between DCB group and stent group (RR, 0.85; 95% CI 0.42 to 1.74; P = 0.66). Lower LLL was shown in DCB group (WMD, - 0.29; 95% CI - 0.46 to - 0.12; P < 0.001). This meta-analysis of RCT showed that DCB might provide a promising way on AMI compared with stents. Rigorous patients' selection and adequate predilation of culprit lesions are necessary to optimize results and prevent bailout stent implantation.PROSPERO registration number: CRD42020214333.

Degradable branched polycationic systems for nucleic acid delivery.

Nowadays, nucleic acid-based therapy has become a promising way for the treatment of various malignant diseases like cancers. However, the process of nucleic acid delivery is hampered by several extracellular and intracellular obstacles. To overcome these obstacles, many nucleic acid delivery carriers have been developed to achieve improved safety and enhanced gene transfection performance. Among these carriers, degradable branched polycations have attracted much attention due to their good responsive degradability and impressive transfection performances. In this review, we mainly summarized the redox- and pH-responsive degradable branched polycationic systems used for nucleic acid delivery. For responsive degradable branched polycationic systems, the preparation methods were introduced, where amino-epoxy ring-opening reaction as a novel step growth approach was mainly presented. The properties of redox- and pH-responsive degradable branched polycationic systems were subsequently introduced and highlighted. We hope this brief review will motivate the delicate design of responsive degradable branched polycationic systems for potential clinical applications. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.

Expanding the clinical and genetic spectrum of Heimler syndrome.

BACKGROUND: Heimler syndrome (HS) is a rare hereditary systemic disorder, partial clinically overlapping with Usher syndrome. So far, our knowledge of HS is very limited, many cases are misdiagnosed or may not even be diagnosed at all. This study aimed to analyze the clinical and genetic characteristics of HS, and to evaluate potential phenotype-genotype correlations. RESULTS: Two HS cases caused by PEX1 mutations were identified, and a novel likely pathogenic mutation, PEX1 c.895_896insTATA, was found. The main ophthalmic finding of the two patients was consistent with retinitis pigmentosa accompanied by cystoid macular edema, but short axial length and hyperopia were also observed as two previously unreported ocular phenotypes. Analysis of the literature showed that of the 29 HS patients previously reported, 12 had PEX6 mutations, 10 had PEX1 mutations, two had PEX26 mutations, and the remaining patients were not genetically tested. Three novel genotype-phenotype correlations were revealed from analysis of these patients. First, most genotypes of every HS patient include at least one missense variant; second, at least one mutation in PEX1 or PEX6 gene affects the AAA-ATPase region in every HS patient with retinal dystrophy, suggesting AAA-ATPase region is a hypermutable region in patients with a retinal dystrophy; third, there are no significant differences between PEX1-, PEX6-, and PEX26-associated phenotypes. CONCLUSION: Next-generation sequencing is important for the diagnosis of HS. This study expands the clinical and genetic spectrum of HS, and provides additional insights into genotype-phenotype correlations, which is vital for accurate clinical practice, genetic counseling, and pathogenesis studies.

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF-kappa B signaling pathway.

Cartilage cannot self-repair and thus regeneration is a promising approach to its repair. Here we developed new electrospun nanofibers, made of poly (ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem cells (MSCs) and the cartilage regeneration in vivo. We found that the PC nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers without collagen I from calf skin (termed P) (6.8 Mpa) although both values are within the range of the modulus of natural cartilage (1-10 MPa). Both P and PC nanofibers did not show obvious difference in the morphology and size. Surprisingly, in the absence of the additional chondrogenesis inducers, the softer PC nanofibers could induce the chondrogenic differentiation in vitro and cartilage regeneration in vivo more efficiently than the stiffer P nanofibers. Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P nanofibers in inducing chondrogenesis by specifically blocking the NF-kappa B signaling pathway to suppress inflammation. Our work shows that the PC nanofibers can serve as building blocks of new scaffolds for cartilage regeneration and provides new insights on the effect of the mechanical properties of the nanofibers on the cartilage regeneration.

Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity, biocompatibility and gene transfection capability.

There is an increasing demand in developing of multifunctional materials with good antibacterial activity, biocompatibility and drug/gene delivery capability for next-generation biomedical applications. To achieve this purpose, in this work series of hydroxyl-rich hyperbranched polyaminoglycosides of gentamicin, tobramycin, and neomycin (HP and SS-HP with redox-responsive disulfide bonds) were readily synthesized via ring-opening reactions in a one-pot manner. Both HP and SS-HP exhibit high antibacterial activity toward Escherichia coli and Staphylococcus aureus. Meanwhile, the hemolysis assay of the above materials shows good biocompatibility. Moreover, SS-HPs show excellent gene transfection efficiency in vitro due to the breakdown of reduction-responsive disulfide bonds. For an in vivo anti-tumor assay, the SS-HP/p53 complexes exhibit potent inhibition capability to the growth of tumors. This study provides a promising approach for the design of next-generation multifunctional biomedical materials.

Characterization of the Uptake Efficiency and Cytotoxicity of Tetrandrine-Loaded Poly(N-vinylpyrrolidone)-Block-Poly(ε-caprolactone) (PVP-b-PCL) Nanoparticles in the A549 Lung Adenocarcinoma Cell Line.

Tetrandrine (Tet) has been previously reported to induce apoptosis in several cancer cell lines. However, poor Tet solubility has limited its further application. The lipophilicity of Tet suggests that the development of Tet-loaded biodegradable polymeric micelle delivery systems may be possible. In our previous work, we demonstrated the superior antitumor efficiency of Tet-loaded mPEG-PCL nanoparticles (NPs) in colorectal cancer cell lines. In the present study, we report that a spherical core­shell Tet-loaded nanoparticle structure was prepared using a nanoprecipitation method by employing amphiphilic poly(N-vinylpyrrolidone)-block-poly(ε-caprolactone) (PVP-b-PCL) copolymers as drug carriers. Tet was incorporated into the NPs with high encapsulation efficiency and released in a sustained release pattern. Moreover, coumarin-6 (hydrophobic fluorescence)-loaded Tet-NP uptake was shown to be mediated mainly by endocytosis from the NPs and was more efficient than that of rhodamine B (hydrophilic fluorescence)-loaded NP uptake, which was mainly dependent upon infiltration. The endocytic uptake process was blocked by NaN3, a mitochondrial inhibitor. In vitro studies using the A549 cell line demonstrated the superior cytotoxicity and apoptosis induction ability of Tet-NPs in dose- and time-dependent manners compared to free Tet. The data obtained from this study, therefore, not only confirm the potential use of Tet to treat lung cancer but also suggest an effective manner by which to improve the anticancer efficiency of Tet in nano-drug delivery systems.

Recent Advances in Shape Memory Soft Materials for Biomedical Applications.

Shape memory polymers (SMPs) are smart and adaptive materials able to recover their shape through an external stimulus. This functionality, combined with the good biocompatibility of polymers, has garnered much interest for biomedical applications. In this review, we discuss the design considerations critical to the successful integration of SMPs for use in vivo. We also highlight recent work on three classes of SMPs: shape memory polymers and blends, shape memory polymer composites, and shape memory hydrogels. These developments open the possibility of incorporating SMPs into device design, which can lead to vast technological improvements in the biomedical field.