Quantitatively Fine-Tuning the Physicochemical and Biological Properties of Peptidic Polymers through Monodisperse PEGylation.

In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.

Peptidic Monodisperse PEG "combs" with Fine-Tunable LCST and Multiple Imaging Modalities.

Thermosensitive and imaging-traceable materials with fine-tunable lower critical solution temperature (LCST) around body temperature are highly valuable in biomedicine. However, such materials are rare because it is challenging to fine-tune the LCST and incorporate suitable imaging modalities. Herein, peptidic monodisperse polyethylene glycol (M-PEG) "combs" with fine-tunable LCST, "hot spot" fluorine-19 magnetic resonance imaging (19F MRI), thermoresponsive fluorescent imaging, and drug loading ability were developed through accurately programming their structures during solid phase peptide synthesis (SPPS). The easy availability, structural accuracy, biocompatibility, and versatility provide the M-PEG "combs" with promising prospects as thermoresponsive and imaging-traceable biomaterials for controlled drug delivery.

Effects of Chitin Whiskers on Physical Properties and Osteoblast Culture of Alginate Based Nanocomposite Hydrogels.

Novel nanocomposite hydrogels composed of polyelectrolytes alginate and chitin whiskers with biocompatibility were successfully fabricated based on the pH-induced charge shifting behavior of chitin whiskers. The chitin whiskers with mean length and width of 300 and 20 nm were uniformly dispersed in negatively charged sodium alginate aqueous solution, leading to the formation of the homogeneous nanocomposite hydrogels. The experimental results indicated that their mechanical properties were significantly improved compared to alginate hydrogel and the swelling trends were inhibited as a result of the strong electrostatic interactions between the chitin whiskers and alginate. The nanocomposite hydrogels exhibited certain crystallinity and hierarchical structure with nanoscale chitin whiskers, similar to the structure of the native extracellular matrix. Moreover, the nanocomposite hydrogels were successfully applied as bone scaffolds for MC3T3-E1 osteoblast cells, showing their excellent biocompatibility and low cytotoxicity. The results of fluorescent micrographs and scanning electronic microscope (SEM) images revealed that the addition of chitin whiskers into the nanocomposite hydrogels markedly promoted the cell adhesion and proliferation of the osteoblast cells. The biocompatible nanocomposite hydrogels have potential application in bone tissue engineering.

Highly biocompatible nanofibrous microspheres self-assembled from chitin in NaOH/urea aqueous solution as cell carriers.

In this work, chitin microspheres (NCM) having a nanofibrous architecture were constructed using a "bottom-up" fabrication pathway. The chitin chains rapidly self-assembled into nanofibers in NaOH/urea aqueous solution by a thermally induced method and subsequently formed weaved microspheres. The diameter of the chitin nanofibers and the size of the NCM were tunable by controlling the temperature and the processing parameters to be in the range from 26 to 55 nm and 3 to 130 µm, respectively. As a result of the nanofibrous surface and the inherent biocompatibility of chitin, cells could adhere to the chitin microspheres and showed a high attachment efficiency, indicating the great potential of the NCM for 3D cell microcarriers.

Consumption of Citric Acid by Bees Promotes the Gland Development and Enhances Royal Jelly Quality.

The glands of bees are responsible for generating and secreting various biologically active substances that significantly impact bee physiological health and adaptability. This study aimed to investigate the effects of adding citric acid (CA) to bee feed on gland development and royal jelly quality. By formulating feed with varying proportions of CA, evaluation was undertaken of pollen feeding by honeybees under laboratory conditions, along with the impact of CA on the development of major glands, to determine suitable addition proportions. Further optimization of the CA proportion involved feeding colonies and evaluating royal jelly production and quality. The results indicated that feed containing 0.75% CA significantly extended the lifespan of bees and increased their pollen consumption. Gland development in bees showed a positive correlation with CA addition within the range of 0.25% to 0.75%, especially at 0.50% and 0.75%, which notably accelerated the development of mandibular, hypopharyngeal, and cephalic salivary glands, with active proliferation and differentiation of glandular cells and maintenance of normal gland size and morphology. CA added to feed stimulated vigorous secretion of wax glands in worker bees, resulting in prolific wax construction. Colonies consuming feed containing 0.50% CA produced royal jelly with significantly reduced moisture and total sugar content and increased levels of 10-HDA, total phenolic acids, total proteins, and acidity. These findings demonstrate that CA consumption significantly prolongs bee lifespan, increases consumption, promotes gland development, and enhances royal jelly quality. This research provides theoretical guidance for beekeeping practices and feed development, contributing to the sustainable advancement of apiculture.

Construction and application of biotin-poloxamer conjugate micelles for chemotherapeutics.

Biotin was conjugated on poloxamer to prepare biotin-poloxamer (BP) conjugate micelles for chemotherapeutics. Epirubicin (EPI) was encapsulated in BP micelles. The EPI-loaded BP micelles were characterized in terms of size, ζ-potential, morphology, drug loading, drug encapsulation and drug release. Marrow leukemic HL-60 cells were used for evaluating the in vitro cytotoxicity of EPI-loaded BP micelles. Nude mice were axillainoculated subcutaneously HL-60 cells to establish tumour model for investigating the inhibition effects of EPI-loaded BP micelles. From the results, the sizes of these nanoparticles were about 100 nm. Fluorescence microscope observation supported the enhanced cellular uptake of the micelles. The order of the inhibition on tumour volume growth was: EPI-loaded BP micelles >EPI-loaded MATP micelles >EPI-loaded poloxamer micelles >EPI. BP micelles showed significant antitumour activity and low toxicity, compared with the non-targeted micelles. With the advantage of EPR effect and tumour-targeting potential, BP conjugate micelles might be developed as a new system for chemotherapeutics.

UV-induced microplastics (MPs) aging leads to comprehensive toxicity.

Herein, the toxicity of 4 MPs and additives released from MPs during UV-aging was quantitatively evaluated by the transcriptional effect level index (TELI) based on E. coli whole-cell microarray assay, and MPs-antibiotics complex pollutants. Results showed that MPs and these additives had high toxicity potential, the maximum TELI was 5.68/6.85 for polystyrene (PS)/bis(2-ethylhexyl) phthalate (DEHP). There were many similar toxic pathways between MPs and additives, indicating that part of the toxicity risk of MPs was caused by the release of additives. MPs were compounded with antibiotics, the toxicity value changed significantly. The TELI values of amoxicillin (AMX) + polyvinyl chloride (PVC) and ciprofloxacin (CIP) + PVC were as high as 12.30 and 14.58 (P < 0.05). Three antibiotics all decreased the toxicity of PS and had little effect on polypropylene (PP) and polyethylene (PE). The combined toxicity mechanism of MPs and antibiotics was very complicated, and the results could be divided into four types: MPs (PVC/PE + CIP), antibiotics (PVC + TC, PS + AMX/ tetracycline (TC)/CIP, PE + TC), both (PP + AMX/TC/CIP), or brand-new mechanisms (PVC + AMX).

Adsorption of antibiotics on different microplastics (MPs): Behavior and mechanism.

MPs can adsorb antibiotics to coexist and accumulate in the aquatic environment in the form of complexes, resulting in unforeseeable adverse consequences. The adsorption behavior and mechanism of three antibiotics amoxicillin (AMX), ciprofloxacin (CIP), and tetracycline (TC) by four MPs Polyvinyl chloride (PVC), polystyrene (PS), polypropylene (PP), and polyethylene (PE) were studied. Results showed that the adsorption of antibiotics onto MPs follows the pseudo-second-order kinetic and the Freundlich isotherm model, indicating a multilayer chemical adsorption. Combined with FTIR, XRD, and SEM analyses, the adsorption behavior was simultaneously governed by physical processes. Additionally, the equilibrium adsorption capacity was inhibited in the research concentration range of NaCl from 10 mg/L to 10 g/L. The higher the salt concentration, the more pronounced the inhibition phenomenon was. The high (9) and low (3) pH also inhibited the adsorption of antibiotics to MPs. The humic acid (HA) concentration in the range of 0-20 mg/L generally inhibited the MPs-antibiotics adsorption, but the higher HA concentration showed less inhabitation than the lower one. The adsorption inhibition of TC on the four MPs by SA also followed the above rule. However, the adsorption inhibition of sodium alginate (SA) on AMX and CIP on the four MPs was enhanced with its concentration (0-50 mg/L).

Effect of Membrane Pore Size on Membrane Fouling of Corundum Ceramic Membrane in MBR.

Ceramic membrane has emerged as a promising material to address the membrane fouling issue in membrane bioreactors (MBR). In order to optimize the structural property of ceramic membrane, four corundum ceramic membranes with the mean pore size of 0.50, 0.63, 0.80, and 1.02 µm were prepared, which were designated as C5, C7, C13, and C20, respectively. Long-term MBR experiments showed that the C7 membrane with medium pore size experienced the lowest trans-membrane pressure development rate. Both the decrease and increase of membrane pore size would lead to more severe membrane fouling in the MBR. It was also interesting that with the increase of membrane pore size, the relative proportion of cake layer resistance in total fouling resistance was gradually increased. The content of dissolved organic foulants (i.e., protein, polysaccharide and DOC) on the surface of C7 was quantified as the lowest among the different ceramic membranes. Microbial community analysis also revealed the C7 had a lower relative abundance of membrane fouling associated bacteria in its cake layer. The results clearly demonstrated that ceramic membrane fouling in MBR could be effectively alleviated through optimizing the membrane pore size, which was a key structural factor for preparation of ceramic membrane.

Acute impact of salinity and C/N ratio on the formation and properties of soluble microbial products from activated sludge.

The present study investigated the shock of NaCl and C/N ratio on properties of soluble microbial products (SMPs), focusing on their sized fractions. The results indicated that the NaCl stress increased the content of biopolymers, humic substances, building blocks, and LMW substances in SMPs, while the addition of 40 g NaCl L-1 significantly changed their relative abundance in SMPs. The acute impact of both N-rich and N-deficient conditions accelerated the secretion of SMPs, but the characteristics of LMW substances differed. Meanwhile, the bio-utilization of SMPs has been enhanced with the increase of NaCl dosage but decreased with the increase of the C/N ratio. The mass balance of sized fractions in SMPs + EPS could be set up when NaCl dosage <10 g/L and C/N ratio >5, which indicates the hydrolysis of sized fractions in EPS mainly compensated for their increase/reduction in SMPs. Besides, the results of the toxic assessment indicated that the oxidative damage caused by the NaCl shock was an important factor affecting the property of SMPs, and the abnormal expression of DNA transcription cannot be neglected for bacteria metabolisms with the change of C/N ratio.

Face mask derived micro(nano)plastics and organic compounds potentially induce threat to aquatic ecosystem security revealed by toxicogenomics-based assay.

Micro(nano)plastics widely detected in aquatic environments have caused serious threat to water quality security. However, as a potential important source of micro(nano)plastics in surface water during the COVID-19 pandemic, the ecological risks of face mask waste to aquatic environments remain poorly understood. Herein, we comprehensively characterized the micro(nano)plastics and organic compounds released from four daily used face masks in aqueous environments and further evaluated their potential impacts on aquatic ecosystem safety by quantitative genotoxicity assay. Results from spectroscopy and high-resolution mass spectrum showed that plastic microfibers/particles (∼11%-83%) and leachable organic compounds (∼15%-87%) were dominantly emitted pollutants, which were significantly higher than nanoplastics (< ∼5%) based on mass of carbon. Additionally, a toxicogenomics approach using green fluorescence protein-fused whole-cell array revealed that membrane stress was the primary response upon the exposure to micro(nano)plastics, whereas the emitted organic chemicals were mainly responsible for DNA damage involving most of the DNA repair pathways (e.g., base/nucleotide excision repair, mismatch repair, double-strand break repair), implying their severe threat to membrane structure and DNA replication of microorganisms. Therefore, the persistent release of discarded face masks derived pollutants might exacerbate water quality and even adversely affect aquatic microbial functions. These findings would contribute to unraveling the potential effects of face mask waste on aquatic ecosystem security and highlight the necessity for more developed management regulations in face mask disposal.

A Versatile Hydrophilic and Antifouling Coating Based on Dopamine Modified Four-Arm Polyethylene Glycol by One-Step Synthesis Method.

A versatile hydrophilic and antifouling coating was designed and prepared based on catechol-modified four-arm polyethylene glycol. The dopamine (DA) molecules were grafted onto the end of the four-arm polyethylene glycol carboxyl (4A-PEG-COOH) through the amidation reaction, which was proven by 1H NMR and FTIR analysis, assisting the strong adhesion of PEG on the surface of various types of materials, including metallic, inorganic, and polymeric materials. The reduction of the water contact angle and the bacteria-repellent and protein-repellent effects indicated that the coating had good hydrophilicity and antifouling performance. Raman spectroscopy analysis demonstrated the affinity between the polymeric surface and water, which further confirmed the hydrophilicity of the coating. Finally, in vitro cytotoxicity assay demonstrated good biocompatibility of the coating layer.

Biodegradable poly(D, L-lactide-co-glycolide) (PLGA) microspheres for sustained release of risperidone: Zero-order release formulation.

The preparation and investigation of sustained-release risperidone-encapsulated microspheres using erodible poly(D, L-lactide-co-glycolide) (PLGA) of lower molecular weight were performed and compared to that of commercial Risperdal Consta™ for the treatment of schizophrenia. The research included screening and optimizing of suitable commercial polymers of lower molecular weight PLGA50/50 or the blends of these PLGA polymers to prepare microspheres with zero-order release kinetics properties. Solvent evaporation method was applied here while studies of the risperidone loaded microsphere were carried out on its drug encapsulation capacity, morphology, particle size, as well as in vitro release profiles. Results showed that microspheres prepared using 50504A PLGA or blends of 5050-type PLGAs exerted spherical and smooth morphology, with a higher encapsulation efficiency and nearly zero-order release kinetics. These optimized microspheres showed great potential for a better depot preparation than the marketed Risperdal Consta™, which could further improve the patient compliance.

Importance of origin and characteristics of biopolymers in reversible and irreversible fouling of ultrafiltration membranes.

The present work compares the chemical properties of isolated biopolymers of different origins and their fouling potential during ultrafiltration (UF). The biopolymers were extracted from secondary wastewater effluent as effluent organic matter (EfOM) and from surface water as natural organic matter (NOM). Multiple analytical techniques were used to characterize the isolates. The characterization results revealed that EfOM biopolymers were more enriched in protein-type structures compared to the NOM organics, and they presented significant differences in the reversibility of membrane fouling. Dissolved in pure water, EfOM biopolymers led to more irreversible fouling than that caused by NOM isolates. Dosing divalent cations (e.g., Ca2+) into the solutions increased the irreversibility of both types of fouling, while aggravating NOM fouling more significantly. Further investigation was conducted to understand the interaction between EfOM and NOM biopolymers during formation of the fouling layer. The results showed that the interaction between these two types of organics was negligible in the absence of salts. These findings highlight the importance of a comprehensive understanding of biopolymers from different origins, considering their chemical properties and water chemistry, which have valuable implications for selecting suitable membrane fouling control strategies for treating water from different origins.

Biochemical characteristics and membrane fouling behaviors of soluble microbial products during the lifecycle of Escherichia coli.

The complexity of production process and chemical compositions of soluble microbial products (SMPs) largely limits the understanding of membrane fouling in membrane bioreactors (MBRs). Herein, we used a model single-strain Escherichia coli to better understand the chemical natures of SMPs and their roles in membrane fouling. The effects of carbon source and growth phase on the chemical compositions of SMPs were identified at both the compound and molecular levels by using advanced techniques including excitation emission matrix and parallel factor analysis (EEM-PARAFAC), size exclusion chromatography coupled with organic carbon detection (LC-OCD), and untargeted ultra-performance liquid chromatography - Q-Exactive - mass spectrometry (UPLC-Q-Exactive-MS). Subsequently, the roles of SMPs in the propensity of membrane fouling during ultrafiltration (UF) were studied. The results showed that the chemical compositions and fouling potentials of SMPs were carbon source- and growth phase-dependent. In the exponential phase, SMPs mainly consisted of utilization-associated products (UAPs) and remaining substrates. As the microorganism progressed into the stationary and senescent phases, UAPs and biomass-associated products (BAPs) were the main components, respectively. The SMP contents generated in glucose medium were higher than those generated in acetate medium, and higher abundances of humic fluorescent components were observed in glucose-fed SMPs. Van Krevelen diagrams of the UPLC-MS results revealed that acetate-fed SMPs contained more carboxylic-rich alicyclic molecules, peptides-like, aromatic, and carbohydrates-like components than glucose-fed SMPs in the stationary and senescent phases. These components played a significant role in irreversible membrane fouling, as evidenced in UF experiments. Standard blocking and cake filtration were the main fouling mechanisms for the filtration of SMPs collected in the exponential and stationary/senescent phases, respectively. Our findings highlight linkages between SMP compositions and membrane fouling at both the compound and molecular levels and suggest that both the carbon source and growth phase strongly determine the production potential, chemical nature, and fouling behavior of SMPs.

Highly Conductive PPy-PEDOT:PSS Hybrid Hydrogel with Superior Biocompatibility for Bioelectronics Application.

Conductive polymer hydrogels (CPHs) hold significant promise in broad applications, such as bioelectronics and energy devices. Hitherto, the development of a facile and scalable synthesis method for CPHs with high electrical conductivity and biocompatibility has still been a challenge. Herein, we demonstrate highly conductive PPy-PEDOT:PSS hybrid hydrogels which are prepared by a simple solution-mixing method. This fabrication method involves the mixing of a pyrrole monomer with a PEDOT:PSS dispersion, followed by in situ chemical oxidative polymerization to form polypyrrole (PPy). The electrostatic interaction between negatively charged PSS and positively charged conjugated PPy facilitates the formation of PPy-PEDOT:PSS hybrid hydrogels. The conductivity of the PPy-PEDOT:PSS hybrid hydrogels is 867 S m-1. The PPy-PEDOT:PSS hybrid hydrogels show excellent biocompatibility. Moreover, the PPy-PEDOT:PSS hybrid hydrogels have a hierarchical porous structure which facilitates the 3D cell culture within the hydrogels. The PPy-PEDOT:PSS hybrid hydrogels exhibit excellent in situ biomolecular detection and real-time cell proliferation monitoring performance, indicating their potential as highly sensitive electrochemical biosensors for bioelectronics applications. Our strategy for the fabrication of CPHs with the electrostatic interaction between the negatively charged conductive polymer and positively charged conductive polymer would provide new opportunities for the design of highly conductive conjugated hydrogels for bioelectronics applications and energy devices.

Peptidic Monodisperse PEG "Comb" as Multifunctional "Add-On" Module for Imaging-Traceable and Thermo-Responsive Theranostics.

Monodisperse polyethylene glycols-modified (M-PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine-tunable physicochemical properties. To develop "smart" drug delivery systems in a controllable and convenient manner, a peptidic M-PEG "comb" with fluorinated L-lysine side chains and a fluorescent N-terminal is conveniently prepared as a 19 F magnetic resonance imaging (19 F MRI) and fluorescence dual-imaging traceable and thermo-responsive "add-on" module for liposomal theranostics in cancer therapy. The peptidic M-PEG "comb" has high biocompatibility, thermo-responsivity with a sharp lower critical solution temperature, an aggregation-induced emission fluorescence, and high 19 F MRI sensitivity. As a highly branched amphiphile, it self-assembles and firmly anchors on the doxorubicin-loaded liposomal nanoparticles, which M-PEGylates the liposomes and facilitates the thermo-responsive drug release and drug tracking with dual-imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M-PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, "hot spot" 19 F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine-tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M-PEG "comb" is promising as a versatile "add-on" module for rapid and convenient formulation of various "smart" theranostics.

Acute impact of Hg2+, Cu2+, and Ag+ on the formation of biopolymers and nitrogenous soluble microbiological products in activated sludge for wastewater treatment.

In the present work, acute impact of heavy metals on activated sludge was investigated, specifically the release of biopolymers and nitrogenous soluble microbiological products (N-SMP) that significantly impact tertiary effluent quality. Based on the previously reported studies, Hg2+ and Ag+ were selected as representative "non-essential" heavy metals, while Cu2+ was selected as the "essential" heavy metal. Stress tests show that under the present experimental conditions, adding a higher concentration of heavy metals to the activated sludge increases the concentration of biopolymers and SMP in the supernatant; N-SMP increased more significantly than carbonaceous products, implying a greater risk of formation of toxic nitrogenous disinfection by-products or membrane fouling in relevant tertiary treatment processes. The severity of the release of SMP into the supernatant depended on the heavy metal, with an order of Hg2+ > Ag+ > Cu2+ ("non-essential" > "essential") under identical molar concentrations. The mass balance of typical organics (e.g., biopolymers) in SMP and extracellular polymeric substances (EPS) in activated sludge was analyzed, and a negative correlation between the organics in the SMP and tightly bound EPS was observed, implying that a significant fraction of the SMP could be quickly released from the tightly bound EPS under heavy metal shock conditions and could be related to cell response or damage.

Identification and quantification of major organic foulants in treated domestic wastewater affecting filterability in dead-end ultrafiltration.

Ultrafiltration (UF) membranes can be used after conventional wastewater treatment to produce particle free and hygienically safe water for reuse. However, membrane fouling affects the performance of UF to a large extent. Stirred cell tests with UF membrane show high flux decline filtering treated domestic wastewater. Investigation on the impact of size fractioned substances indicates that dissolved substances are major foulants affecting water filterability. Dissolved organic substances in feed and permeate samples of the stirred cell tests are analyzed by liquid chromatography with online organic carbon detection (LC-OCD). The resulting chromatograms displayed a significant difference of feed and permeate samples in the range of large molecules identified as biopolymer peak. The substances detected in this peak (mostly macro polysaccharide-like and protein-like molecules) are almost completely retained by UF membranes. Quantified investigation shows that biopolymer concentration influences filterability of corresponding water sample proportionally. The apparent magnitude of delivered biopolymer to membrane has a striking correlation with fouling resistance. The relationship was verified to be reproducible using different water samples. Mechanism analysis demonstrates that based on the delivered biopolymer load to membrane pore blocking or cake/gel fouling is the main fouling mechanism in the present experiment conditions.

Mechanisms of drug release in pH-sensitive micelles for tumour targeted drug delivery system: A review.

During the past decades, chemotherapy has been regarded as the most effective method for tumor therapy, but still faces significant challenges, such as poor tumor selectivity and multidrug resistance. The development of targeted drug delivery systems brings certain dramatic advantages for reducing the side effects and improving the therapeutic efficacy. Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for targeted therapy. Among these approaches, pH-sensitive micelles are regarded as the most general strategy with advantages of increasing solubility of water-insoluble drugs, pH-sensitive release, high drug loading, etc. This review will focus on the potential of pH-sensitive micelles in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations. Sufficient understanding of these mechanisms will help us to design more efficient pH-sensitive drug delivery system to address the challenges encountered in targeted drug delivery systems for tumor therapy.