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Oral delivery of protein drugs is considered a life-changing solution for patients who require regular needle injections. However, clinical translation of oral protein formulations has been hampered by inefficient penetration of drugs through the intestinal mucus and epithelial cell layer, leading to low absorption and bioavailability, and safety concerns owing to tight junction openings. Here we report a zwitterionic micelle platform featuring a virus-mimetic zwitterionic surface, a betaine side chain and an ultralow critical micelle concentration, enabling drug penetration through the mucus and efficient transporter-mediated epithelial absorption without the need for tight junction opening. This micelle platform was used to fabricate a prototype oral insulin formulation by encapsulating a freeze-dried powder of zwitterionic micelle insulin into an enteric-coated capsule. The biocompatible oral insulin formulation shows a high oral bioavailability of >40%, offers the possibility to fine tune insulin acting profiles and provides long-term safety, enabling the oral delivery of protein drugs.A zwitterionic micelle platform enables the oral delivery and high bioavailability of insulin by transporting the protein across mucus and epithelial barriers in the gut without opening tight junctions.

Postoperative adhesions are most common issues for almost any types of abdominal and pelvic surgery, leading to adverse consequences. Pharmacological treatments and physical barrier devices are two main approaches to address postoperative adhesions but can only alleviate or reduce adhesions to some extent. There is an urgent need for a reliable approach to completely prevent postoperative adhesions and to significantly improve the clinical outcomes, which, however, is unmet with current technologies. Here we report that by applying a viscous, cream-like yet injectable zwitterionic polymer solution to the traumatized surface, postoperative adhesion was completely and reliably prevented in three clinically relevant but increasingly challenging models in rats. The success rate of full prevention is over 93% among 42 animals tested, which is a major leap in antiadhesion performance. Clinically used Interceed film can hardly prevent the adhesion in any of these models. Unlike current antiadhesion materials serving solely as physical barriers, the “nonfouling” zwitterionic polymer functioned as a protective layer for antiadhesion applications with the inherent benefit of resisting protein/cell adhesions. The nonfouling nature of the polymer prevented the absorption of fibronectins and fibroblasts, which contribute to the initial and late-stage development of the adhesion, respectively. This is the key working mechanism that differentiated our “complete prevention” approach from current underperforming antiadhesion materials. This work implies a safe, effective, and convenient way to fully prevent postoperative adhesions suffered by current surgical patients.

Conventional micellar carriers disassemble into free surfactants when diluted at concentrations below the critical micelle concentration (CMC). This limits the bioavailability in vivo of injected hydrophobic drugs encapsulated in micellar systems. Here, we show that a micelle comprising a superhydrophilic zwitterionic polymer domain and a superhydrophobic lipid domain has an undetectable CMC below 10 − 6  mM—a value that is orders of magnitude lower than the CMCs ( >10 −3  mM) of typical micellar systems. We also show that zwitterionic moieties or zwitterionic polymers added to a micelle solution stabilize the micelles at concentrations below their inherent CMC. In a mouse model of melanoma, ultralow-CMC micelles encapsulating docetaxel led to the complete eradication of tumours, whereas conventional docetaxel micellar formulations did not reverse tumour growth. Ultralow-CMC micelles might become next-generation carriers for drug delivery. Polymer–lipid micelles with an ultralow undetectable critical micelle concentration make ultrastable drug carriers that significantly enhance therapeutic outcomes in a mouse model of melanoma.

Continuous subcutaneous insulin infusion (CSII) is an essential insulin replacement therapy in the management of diabetes. However, the longevity of clinical CSII is limited by skin complications, by impaired insulin absorption and by occlusions associated with the subcutaneous insertion of CSII catheters, which require replacement and rotation of the insertion site every few days. Here we show that a biodegradable zwitterionic gel covering the tip end of commercial off-the-shelf CSII catheters fully resolves early skin irritations, extends the longevity of catheters and improves the rate of insulin absorption (also with respect to conventional syringe-based subcutaneous injection) for longer than 6 months in diabetic mice, and by 11 days in diabetic minipigs (from 2 to 13 days, under standard CSII-wearing conditions of insulin pump therapy and in a continuous basal-plus-bolus-infusion setting). The implanted gel displayed anti-inflammatory and anti-foreign-body-reaction properties and promoted the local formation of new blood vessels. The gel is subcutaneously injected before the tip of catheter is inserted into it, and should be generally applicable to CSII catheters and other implantable devices. A biodegradable zwitterionic gel covering the tip end of commercial catheters for the continuous and subcutaneous infusion of insulin extends the longevity of the catheters and improves the rate of insulin absorption in diabetic mice and minipigs.

Micelles have been studied as drug delivery carriers for decades. Their use can potentially result in high drug accumulation at the target site through the enhanced permeability and retention effect. Nevertheless, the lack of stability of micelles in the physiological environment limits their efficacy as a drug carrier. In particular, micelles tend to disassociate and prematurely release the encapsulated drugs, lowering delivery efficacy and creating toxicity concerns. Many efforts to enhance the stability of micelles have focused mainly on decreasing the critical micelle forming concentration and improving blood circulation. Herein, we review different strategies including crosslinking and non-crosslinking approaches designed to stabilize micelles and offer perspectives on future research directions.

Coating continuous glucose-monitoring sensors with zwitterionic polymer reduces early inflammatory responses and signal noise after sensor implantation in live animals, and improves the performance of the sensors without the need for additional recalibration.

As the construction industry is striding towards the industrialization of green buildings, a precast concrete frame beam-column joint with high-strength reinforcement was proposed. Simulate reversed cyclic loading was carried out on two precast connections and one cast-in-place connection to examine the seismic behavior of the proposed new precast connection. The main test variables between the two precast connections were the strength of the reinforcement at the bottom of the beam. The failure shape, hysteresis curve, skeleton curve, strength, deformation ability, stiffness degradation, and energy dissipation were monitored and compared with the cast-in-place connection. The findings of this paper showed that the precast joints had good strength reserve, and the seismic performance in the later stage of loading even exceeds the cast-in-place joints. It was also found that the plastic hinge zone of the beam could be moved away from the column surface via reinforcement method. Additionally, based on the experiment, a detailed nonlinear finite element analysis (FEA) method was developed to reproduce the test response of specific types of bending moment-resistant precast concrete beam-column connections under a reversed loading test, which provided a theoretical reference for further research of the connections.

Multifunctional drug carriers have great applications in biomedical field. In this study, we introduced both polydopamine (PDA) and zwitterionic polymer of poly(3-(3-methacrylamidopropyl-(dimethyl)-ammonio)propane-1-sulfonate) (PSPP) onto the surface of mesoporous silica nanoparticles (MSNs) to develop a novel nanoparticle (MSNs@PDA-PSPP), which was employed as a new kind of drug carrier for the delivery of doxorubicin (DOX). The PDA coating, as a gatekeeper, could endow the drug carrier with pH-sensitive drug release performance. The outermost PSPP layer would make the drug carrier possess protein resistance performance. The chemical structure and properties were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). MSNs@PDA-PSPP could keep good colloidal stability within 72 h in phosphate buffered saline (PBS) and protein solutions. Meanwhile, MSNs@PDA-PSPP exhibited a high drug loading for DOX. In vitro drug release experiments suggested MSNs-DOX@PDA-PSPP exhibited pH-dependent drug release behaviors. Besides, MSNs@PDA-PSPP had no cytotoxicity to human hepatocellular carcinoma cells (HepG2 cells) even at a concentration of 125 µg/mL. More importantly, cellular uptake and in vitro anticancer activity tests suggested that MSNs-DOX@PDA-PSPP could be taken up by HepG2 cells and DOX could be successfully released and delivered into the cell nuclei. Taken together, MSNs@PDA-PSPP have great potential in the biomedical field.

Background Using microbes and their metabolites as material to develop new biological fungicides is still vital for pesticide development. Our preliminary study found that the endophytic fungi Arthrinium sp. 2–65 of Thymus mongolicus (Ronniger) Ronniger showed a certain inhibitory effect on pathogenic fungi. Results In this study, the antifungal activity of Arthrinium sp. 2–65 was evaluated. The ethyl acetate extract of Arthrinium sp. 2–65 exhibited significant inhibitory activity against pathogenic fungi, especially Botrytis cinerea . The main compounds of Arthrinium sp. 2–65 metabolites were isolated and purified, and the two compounds were identified by infrared spectroscopy (IR), high-performance liquid chromatography (HPLC), 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrometry (HRMS) as 2-hexyl-3-methylmaleic anhydride (A) and 2-carboxymethyl-3- n -hexylmaleic acid anhydride (B). Conclusions The main compounds (A and B) isolated and characterised from the fermentation broth of Arthrinium sp. 2–65 showed satisfactory inhibitory effects against pathogenic fungi, especially B. cinerea . These compounds could be used as potential molecules for the development of novel pesticides to control grey mould.

As a new type of biological treatment process, membrane aerated biofilm reactors (MABRs), which have received extensive attention and research in recent years, could reduce energy consumption by 70% compared to the traditional activated sludge process. The MABR system uses bubble-free aeration membrane material as the carrier, the counter-diffusion mechanism of oxygen and pollutants enables ammonium oxidizing bacteria (AOB) and nitrate oxidizing bacteria (NOB) to adhere to the membrane surface so that simultaneous nitrification and denitrification (SND) can occur to achieve simultaneous nitrogen and carbon removal. Currently, MABR technology has been successfully applied to the treatment of municipal sewage, various industrial wastewater, pharmaceutical, high salinity, high ammonia, aquaculture wastewater, landfill leachate and black and odorous water bodies in rivers. Many laboratory experiments and pilot-scale MABR reactors have been used to study the performance of membrane materials, the mechanism of pollutant removal and the effects of different factors on the system. However, the performance of MABR is affected by factors such as dissolved oxygen (DO), pH, C/N, biofilm thickness, hydraulic retention time (HRT), temperature, etc., which limits large-scale promotion. Therefore, membrane materials, membrane modules, biofilm, application of MABR technology, influencing factors of MABR system performance, and limitations and perspectives of MABR are reviewed in this paper, and we expect to provide valuable information.