Hydrophobic Segments Research Articles

CO2-Responsive Water-Soluble Conjugated Polymers as a Multifunctional Fluorescent Probe for Bioimaging Applications.

We describe important progress in the synthesis and development of gas-responsive water-soluble conjugated polymers (WSCPs) with potential as multifunctional fluorescent materials for biomedical imaging and probes. A water-soluble WSCP (I-PT) composed of a hydrophobic fluorescent polythiophene backbone and a hydrophilic imidazole side chain was successfully prepared through a facile and efficient two-step synthetic route. Owing to the repulsive force between the hydrophilic and hydrophobic segments and the highly sensitive carbon dioxide (CO2)- and nitrogen (N2)-responsive imidazole groups in its structure, I-PT can spontaneously self-assemble into spherical-like nanoparticles in an aqueous environment, and thus exhibits unique light absorption and fluorescence properties as well as rapid responsiveness to CO2 and N2. In addition, its structure, optical absorption/fluorescence behavior, and surface potential can be quickly turned on and off through alternating cycles of CO2 and N2 bubbling and exhibit controllable cyclic switching stability, thereby allowing effective manipulation of its hierarchical structure and chemical-physical characteristics. More importantly, a series of in vitro cell experiments confirmed that, compared to the significant cytotoxicity of pristine and N2-treated I-PT nanoparticles, CO2-treated I-PT nanoparticles exhibit extremely low cytotoxicity in normal and cancer cells and undergo greatly accelerated cellular uptake, resulting in a significant increase in the intensity and stability of their fluorescence signal in the intracellular environment. Overall, this newly discovered CO2/N2-responsive system provides new insights to effectively enhance the biocompatibility, cellular internalization, and intracellular fluorescence characteristics of WSCPs and holds great potential for biomedical imaging/sensing applications.

Chemical synthesis of a 28 kDa full-length PET degrading enzyme ICCG by the removable backbone modification strategy

Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.

Integrated Conversion of Lignocellulosic Biomass to Bio-Based Amphiphiles using a Functionalization-Defunctionalization Approach.

Concerns over the sustainability and end-of-life properties of fossil-derived surfactants have driven interest in bio-based alternatives. Lignocellulosic biomass with its polar functional groups is an obvious feedstock for surfactant production but its use is limited by process complexity and low yield. Here, we present a simple two-step approach to prepare bio-based amphiphiles directly from hemicellulose and lignin at high yields (29 % w/w based on the total raw biomass and >80 % w/w of these two fractions). Acetal functionalization of xylan and lignin with fatty aldehydes during fractionation introduced hydrophobic segments and subsequent defunctionalization by hydrogenolysis of the xylose derivatives or acidic hydrolysis of the lignin derivatives produced amphiphiles. The resulting biodegradable xylose acetals and/or ethers, and lignin-based amphiphilic polymers both largely retained their original natural structures, but exhibited competitive or superior surface activity in water/oil systems compared to common bio-based surfactants.

Integrated Conversion of Lignocellulosic Biomass to Bio‐Based Amphiphiles using a Functionalization‐Defunctionalization Approach

AbstractConcerns over the sustainability and end‐of‐life properties of fossil‐derived surfactants have driven interest in bio‐based alternatives. Lignocellulosic biomass with its polar functional groups is an obvious feedstock for surfactant production but its use is limited by process complexity and low yield. Here, we present a simple two‐step approach to prepare bio‐based amphiphiles directly from hemicellulose and lignin at high yields (29 % w/w based on the total raw biomass and >80 % w/w of these two fractions). Acetal functionalization of xylan and lignin with fatty aldehydes during fractionation introduced hydrophobic segments and subsequent defunctionalization by hydrogenolysis of the xylose derivatives or acidic hydrolysis of the lignin derivatives produced amphiphiles. The resulting biodegradable xylose acetals and/or ethers, and lignin‐based amphiphilic polymers both largely retained their original natural structures, but exhibited competitive or superior surface activity in water/oil systems compared to common bio‐based surfactants.

Nanoparticles with Active Targeting Ability and Acid Responsiveness for an Enhanced Antitumor Effect of Docetaxel.

Docetaxel (DOC) is commonly used in cancer treatment, especially for breast cancer. However, there are severe side effects in clinical application. In order to deliver docetaxel more effectively, a novel, active targeting acid-responsive polymer called cRGD-PAE-PEG-DSPE was developed. The polymer structure incorporated poly(ethylene glycol) (PEG) as the hydrophilic segment, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) as the hydrophobic segment, and poly(β-amino ester) (PAE) as the acid-responsive group, which was grafted onto the PEG. Furthermore, c(RGDyC) was grafted onto PAE to confer active targeting capability. Through self-assembly, docetaxel was encapsulated in RAED@DOC. Through in vitro experiments, it was confirmed that RAED@DOC had good serum stability and acid responsiveness, as well as enhanced uptake by MDA-MB-231 cells. Additionally, the antitumor efficiency in vivo and histopathological analysis showed that RAED@DOC exhibited higher antitumor activity and lower systemic toxicity in comparison to free docetaxel. These results suggested that RAED@DOC had considerable potential clinical use.

Self-assembling butyric acid prodrug acts as a sensitizer for cancer radiotherapy

Butyric acid, is reported to radiosensitize cancer cell lines in vitro. Their short systemic half-lives may explain their lack of in vivo efficacy. To manage the unsuitable pharmacokinetics of low-molecular-weight (LMW) butyric acid, we have designed a new polymeric prodrug comprising amphiphilic block copolymers, [poly(ethylene glycol)-b-poly(vinyl butyrate)s] (PEG-b-PV(BA)), with tens of butyric acid units conjugated through enzymatically metabolizable ester linkages as side chains in the hydrophobic segment. PEG-b-PV(BA) spontaneously forms self-assembling nanoparticles (NanoBA) with diameters of tens of nanometers. Pharmacological studies of intraperitoneal administration revealed that the retention of NanoBA in the plasma and tumors was extended up to 48–72 h compared to its LMW counterparts, as evidenced using in vivo imaging, immunoblotting of the PEG segment of the block copolymers, and radioisotope techniques. These results corroborated the LC-MS/MS-based study, validating the prominent in vivo liberation of butyric acid for a prolonged period (24 h) in NanoBA administered group compared to the LMW butyric acid, which cleared within approximately 0.5 h post-administration. Furthermore, radiation treatment after 24 h of intraperitoneal NanoBA administration toward tumor (B16-F10)-bearing mice exhibited significantly slower tumor growth in comparison with control irradiated tumors and LMW butyric acid-treated group, which was attributable to attenuated radioresistance Cox-2 and NF-κβ survival pathways. Current findings demonstrate that our self-assembling nanoparticle NanoBA prodrug substantially enhances the radiosensitizing effect of butyric acid in solid tumors in vivo, supporting the use of NanoBA for future clinical ramifications.

In silico discovery of the myxosortases that process MYXO-CTERM and three novel prokaryotic C-terminal protein-sorting signals that share invariant Cys residues.

The LPXTG protein-sorting signal, found in surface proteins of various Gram-positive pathogens, was the founding member of a growing panel of prokaryotic small C-terminal sorting domains. Sortase A cleaves LPXTG, exosortases (XrtA and XrtB) cleave the PEP-CTERM sorting signal, archaeosortase A cleaves PGF-CTERM, and rhombosortase cleaves GlyGly-CTERM domains. Four sorting signal domains without previously known processing proteases are the MYXO-CTERM, JDVT-CTERM, Synerg-CTERM, and CGP-CTERM domains. These exhibit the standard tripartite architecture of a short signature motif, a hydrophobic transmembrane segment, and an Arg-rich cluster. Each has an invariant cysteine in its signature motif. Computational evidence strongly suggests that each of these four Cys-containing sorting signals is processed, at least in part, by a cognate family of glutamic-type intramembrane endopeptidases related to the eukaryotic type II CAAX-processing protease Rce1. For the MYXO-CTERM sorting signals of different lineages, their sorting enzymes, called myxosortases, include MrtX (MXAN_2755 in Myxococcus xanthus), MrtC, and MrtP, all with radically different N-terminal domains but with a conserved core. Related predicted sorting enzymes were also identified for JDVT-CTERM (MrtJ), Synerg-CTERM (MrtS), and CGP-CTERM (MrtA). This work establishes a major new family of protein-sorting housekeeping endopeptidases contributing to the surface attachment of proteins in prokaryotes. IMPORTANCE Homologs of the eukaryotic type II CAAX-box protease Rce1, a membrane-embedded endopeptidase found in yeast and human ER and involved in sorting proteins to their proper cellular locations, are abundant in prokaryotes but not well understood there. This bioinformatics paper identifies several subgroups of the family as cognate endopeptidases for four protein-sorting signals processed by previously unknown machinery. Sorting signals with newly identified processing enzymes include three novel ones, but also MYXO-CTERM, which had been the focus of previous experimental work in the model fruiting and gliding bacterium Myxococcus xanthus. The new findings will substantially improve our understanding of Cys-containing C-terminal protein-sorting signals and of protein trafficking generally in bacteria and archaea.

Reversible, ultra-strong underwater adhesive based on supramolecular interaction for instant liquid leakage sealing and robust tissue adhesion

Underwater adhesives have great potential applications in biomedical fields. However, it is challenging to realize underwater adhesion due to screening by highly hydrated layer at the interface. To tackle this problem, here we present a novel strategy that combines hydrophobic association and supramolecular interactions to achieve robust adhesion at wet interfaces. Hydrophobic monomers (hexyl acrylate and styrene) are copolymerized with hydrophilic acrylic acid (AAc), and bifunctional host/guest assembly of β-cyclodextrin and adamantane to produce an adhesive. Herein, hydrophobic segments segregate to form hydrophobic microdomains both inside and at the interface. Internal hydrophobic clusters and host–guest interactions serve as physical crosslinks to improve the mechanical properties. Meanwhile, hydrophobic domains at surface play a critical role in expelling water and building a hydrophobic environment to minimize interference from water, where the hydrophilic units form hydrogen bonding, electrostatic attraction, coordination, and cation-π interactions to adhere on the surface. Lap shear tests indicate adhesion strength of about 92 ∼ 116 kPa on glass, copper, plastic, wood, and bone. Such a strong adhesion is independent of environment changes, including pH, PBS and NaCl solutions. More importantly, the adhesive shows excellent adhesion performance for bone, with adhesion strength up to 112.58 kPa in air and 91.51 kPa underwater. The strategy to combine hydrophobic interactions and supramolecular interactions may open a new avenue to the development of new adhesives for underwater adhesion and biological tissue.

Bioinspired durable interpenetrating network anti-icing coatings enabled by binders and hydrophobic-ion specific synergies

Designing a coating with a comprehensive range of anti-icing properties is a difficult challenge in the current complex and variable icing environment. Bionic anti-icing coatings have received widespread attention in recent years, but their exposure to mechanical damage conditions tends to result in insufficient durability. This work proposes a novel approach inspired by the antifreeze proteins (AFPs) found in fish, wherein a durable interpenetrating coating with excellent anti-icing and deicing performance is designed by combining a fluorinated amphiphilic ionic polymer with a biomimetic binder. The incorporation of hydrophobic fluorinated chain segments and amphiphilic ionic chain segments effectively inhibits ice nucleation (DT = 2010 s, TIN = − 22.1 °C), slows down ice propagation, and reduces ice adhesion (τ = 22.2 kPa) through the synergistic effect of hydrophobicity and ionic specificity. Furthermore, the addition of a bionic binder to create an interpenetrating network enhances the mechanical properties and anti-icing durability of the coating. Moreover, it can further function as anti-fogging, self-cleaning, and antibacterial for glass surfaces, demonstrating significant potential in the new generation of optical and medical devices.

Poly(N-methyl-N-vinylacetamide): A Strong Alternative to PEG for Lipid-Based Nanocarriers Delivering siRNA.

Lipid-based nanocarriers have demonstrated high interest in delivering genetic material, exemplified by the success of Onpattro and COVID-19 vaccines. While PEGylation imparts stealth properties, it hampers cellular uptake and endosomal escape, and may trigger adverse reactions like accelerated blood clearance (ABC) and hypersensitivity reactions (HSR). This work highlights the great potential of amphiphilic poly(N-methyl-N-vinylacetamide) (PNMVA) derivatives as alternatives to lipid-PEG for siRNA delivery. PNMVA compounds with different degrees of polymerization and hydrophobic segments, are synthesized. Among them, DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine)-PNMVA efficiently integrates into lipoplexes and LNP membranes and prevents protein corona formation around these lipid carriers, exhibiting stealth properties comparable to DSPE-PEG. However, unlike DSPE-PEG, DSPE-PNMVA24 shows no adverse impact on lipoplexes cell uptake and endosomal escape. In in vivo study with mice, DSPE-PNMVA24 lipoplexes demonstrate no liver accumulation, indicating good stealth properties, extended circulation time after a second dose, reduced immunological reaction, and no systemic pro-inflammatory response. Safety of DSPE-PNMVA24 is confirmed at the cellular level and in animal models of zebrafish and mice. Overall, DSPE-PNMVA is an advantageous substitute to DSPE-PEG for siRNA delivery, offering comparable stealth and toxicity properties while improving efficacy of the lipid-based carriers by minimizing the dilemma effect and reducing immunological reactions, meaning no ABC or HSR effects.

Self-Folding Macromolecular Drug Carrier for Cancer Imaging and Therapy.

Nano-sized contrast agents (NCAs) hold potential for highly specific tumor contrast enhancement during magnetic resonance imaging. Given the quantity of contrast agents loaded into a single nano-carrier and the anticipated relaxation effects, the current molecular design approaches its limits. In this study, a novel molecular mechanism to augment the relaxation of NCAs is introduced and demonstrated. NCA formation is driven by the intramolecular self-folding of a single polymer chain that possesses systematically arranged hydrophilic and hydrophobic segments in water. Utilizing this self-folding molecular design, the relaxivity value can be elevated with minimal loading of gadolinium complexes, enabling sharp tumor imaging. Furthermore, the study reveals that this NCA can selectively accumulate into tumor tissues, offering effective anti-tumor results through gadolinium neutron capture therapy. The efficacy and versatility of this self-folding molecular design underscore its promise for cancer diagnosis and treatment.

Alphafold2-Assisted Structure-Function Analysis of Human Erythroferrone Relevant for Its Iron-Regulatory Function

Erythroferrone (ERFE), an erythrokine that helps mobilize iron for developing erythrocytes, acts by decreasing the production of hepcidin, through sequestration of bone morphogenetic proteins (BMPs) that bind to BMP receptors to activate hepcidin transcription. We used Alphafold2 (AF2) to model the conformation of human erythroferrone monomers and various multimers, with or without interactions with BMPs, with emphasis on the principal ligand, the BMP2/6 heterodimer. We then tested the models by targeted mutations to disrupt key interactions suggested by the models, and assessed the effect of the mutations on bioactivity and BMP binding. ERFE is a member of the C1q/TNFa family of proteins known for containing N-terminal unstructured regions and C-terminal TNFa-like globular heads that promote the formation of a spectrum of biologically significant multimers. After cleavage by a prohormone convertase, the ERFE molecule consists of an unstructured N-terminal segment residues 43-185 and a globular TNF-like head 186-354. We found that a segment of the N-terminal region of the molecule-segment 43-148 of the 354 amino acid protein-was sufficient to bind BMPs and suppress hepcidin; the larger C-terminal region does neither. For bioassays, we prepared ERFE or its mutants in HEK293 mammalian cells and tested these without purification, so as not to disrupt their mixture of multimeric conformations. The Hep3B human liver cell line was used for bioactivity assays with the readout of hepcidin mRNA concentrations, measured by qRT-PCR. To avoid the confounding effects of ERFE multimerization driven by the TNFa-like globular regions on avidity, we purified untagged ERFE N-terminal (43-148) segments or their mutants from bacteria, and measured the binding between these and BMPs using surface plasmon resonance. These forms lacked TNFa-like heads and, unlike full length ERFE, did not form multimers in nondenaturing PAGE. We identified and explored several structural elements within the ERFE N-terminus. All models of BMP interaction with ERFE predicted the binding of a tryptophan-containing hydrophobic helix of ERFE to a deep groove formed at the interface of all BMP dimers (BMP2/6 in cyan/green, ERFE in magenta; interaction in callout box, left panel). The highly evolutionarily conserved hydrophobic region (residues 81-86) was required for bioactivity and for tight binding to BMPs. Deletion of the hydrophobic segment or W82A substitution of the strictly conserved tryptophan ablated bioactivity and greatly decreased the binding of ERFE to BMPs. In nearly all models, a positively-charged cationic segment and the collagen-like segment made no contact with BMPs. However, the cationic segment was required for activity (right panel) although its deletion had only minor effect on binding to BMP. The specific arrangement of arginines and lysines in this segment did not matter for bioactivity or binding. We showed that the segment was essential for heparin-binding and propose that it may serve to concentrate ERFE at the site of its activity. Deletion of the collagen segment or the more distal helical segment (green) impaired IC 50 much less (50-100fold) but also substantially disrupted monomeric binding. The collagen segment forms a triple helix in trimeric models of ERFE, but the helix is disrupted by BMP binding. Secondary binding contacts between ERFE and BMPs in AF2 varied depending on the oligomeric state of erythroferrone. In monomers and dimers, the helical segment made contact with the contralateral wing of the BMP dimer. Remarkably, both primary and secondary binding interactions of BMPs were structurally similar to the BMP interactions with their receptors or known antagonists. Nondenaturing PAGE suggested that the predominant form of ERFE was a hexamer. The AF2 structure of hexameric ERFE (magenta) with three molecules of BMP2/6 (cyan-green) showed that each BMP heterodimer bound two ERFE proximal helical segments including 81-86, within each of its two BMP2/6 interfacial grooves (left panel) but unlike in monomers and dimers, the secondary interaction did not involve the distal helical segment but the globular heads (red trimers on each side). Despite their reductionist nature, these studies provide useful structural predictions that should allow better pharmacologic targeting of this important erythroid regulator of iron homeostasis.

Cationic amphiphilic acrylic copolymer retanning agent for metal-free eco-leather production

Producing metal-free leather is an effective approach to eliminate Cr pollution and achieve sustainable development of the leather industry. However, the high water sorption of the metal-free leather and the mismatching of the charge properties between the metal-free tanned leather and anionic post-tanning chemicals result in the unsatisfactory properties of the leather products, thereby restricting the industrial application of metal-free tanning technologies. Herein, a series of cationic amphiphilic acrylic copolymers (PSD) with different molar ratios of hydrophobic monomer to cationic hydrophilic monomer were synthesized and applied in the retanning of a metal-free tanned leather. PSD can effectively penetrate to the hierarchy of collagen fibril of leather and firmly bind to collagen carboxyls to form a thin hydrophobic coating on the fibril surface due to their small particle size (< 70 nm), excellent surface activity and cationic amine groups (3–27 μmol/g). Molecular dynamics (MD) simulations confirm that the primary driving force between PSD and collagen is electrostatic interaction. MD simulations and water resistance tests demonstrate that the amphiphilic PSD provides the metal-free leather with moderate hydrophobicity, which indicates the upgrade of the comprehensive properties of leather. PSD retanning enhances the uptake rate of anionic dyes and fatliquors (> 90 %) and endows the metal-free leather with excellent filling effect and bright color. The molar ratio of hydrophilic monomer and hydrophobic monomer plays an important role in the performance of PSD. The hydrophobic segments contribute to the hydrophobicity enhancement of leather, and the cationic hydrophilic segments in PSD contribute to the charge regulation of leather and robust binding of post-tanning chemicals. Hence, the multifunctional PSD retanning agents can fulfill the demands for versatile metal-free leather types and promise to boost the sustainable development of the leather industry.

PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy.

Activating a tumor antigen-specific immune response is key to the success of tumor immunotherapy and the development of personalized antitumor therapy. Nanocarriers can capture, enrich, and protect in situ produced tumor antigens due to immunogenic cell death (ICD), thus enhancing the tumor-specific immune response. Developing multifunctional nanocarriers that combine multiple antigen capturing mechanisms is crucial to the activation of tumor-specific immune responses. In this study, polyethylenimine (PEI) was employed as a main building block to construct a series of multifunctional indocyanine green (ICG)-loaded nanoparticles to capture antigens via multiple mechanisms: electrostatic interactions with PEI, hydrophobic interactions with the thermosensitive segment (POEGMA300), and covalent bonding with the pyridyl disulfide (PDS) groups, respectively. Their capacity of ICD induction, tumor antigen-capture, and antitumor immune responses were evaluated. Both the intrinsic toxicity of PEI and the ICG-mediated photothermal effect were responsible for inducing ICD. The positively charged PEI segment exhibited the best antigen-capturing ability via electrostatic interactions, promoted bone marrow-derived dendritic cell maturation and CD8+ T cell proliferation, and elicited antitumor immune responses in vivo. PDS groups bonded antigens covalently and significantly contributed to the suppression of distant tumor growth. Although the thermosensitive hydrophobic polymer segment did not contribute positively to antigen capture or tumor growth inhibition, NPs containing all of the functional modules prolonged the survival of tumor-bearing mice more than other treatments. This study provides more chemical insights into the design of polymer-based in situ nanovaccines against cancer.

Crystallization-driven formation poly (l-lactic acid)/poly (d-lactic acid)-polyethylene glycol-poly (l-lactic acid) small-sized microsphere structures by solvent-induced self-assembly

Improving hydrophobicity through the regulation of surface microstructures has attracted significant interest in various applications. This research successfully prepared a surface with microsphere structures using the Non-solvent induced phase separation method (NIPS). Poly(D-Lactic acid)-block-poly(ethylene glycol)-block-poly(D-Lactic acid) (PDLA-PEG-PDLA) block polymers were synthesized by ring-opening polymerization of D-Lactic acid (D-LA) using polyethylene glycol (PEG) as initiator. PLLA/PDLA-PEG-PDLA membrane with microscale microsphere morphology was fabricated using a nonsolvent-induced self-assembly method by blending the triblock copolymer with a poly(L-lactic acid) (PLLA) solution. In phase separation processes, the amphiphilic block copolymers self-assemble into micellar structures to minimize the Gibbs free energy, and the hydrophilic segments (PEG) aggregate to form the core of the micelles, while the hydrophobic segments (PDLA) are exposed on the outer corona resulting in a core-shell structure. The Stereocomplex Crystalline (SC), formed by the hydrogen bonding between PLLA and PDLA, can facilitate the transition from liquid-liquid phase separation to solid-liquid phase separation, and the PEG chain segments can enhance the formation of SC. The membrane, prepared by adjusting the copolymer content and PEG chain length, exhibited adjustable microsphere quantity, diameter, and surface roughness, enabling excellent hydrophobicity and controlled release of oil-soluble substances.

Characterization of erythroferrone structural domains relevant to its iron-regulatory function

Iron delivery to the plasma is closely coupled to erythropoiesis, the production of red blood cells, as this process consumes most of the circulating plasma iron. In response to hemorrhage and other erythropoietic stresses, increased erythropoietin stimulates the production of the hormone erythroferrone (ERFE) by erythrocyte precursors (erythroblasts) developing in erythropoietic tissues. ERFE acts on the liver to inhibit bone morphogenetic protein (BMP) signaling and thereby decrease hepcidin production. Decreased circulating hepcidin concentrations then allow the release of iron from stores and increase iron absorption from the diet. Guided by evolutionary analysis and Alphafold2 protein complex modeling, we used targeted ERFE mutations, deletions, and synthetic ERFE segments together with cell-based bioassays and surface plasmon resonance to probe the structural features required for bioactivity and BMP binding. We define the ERFE active domain and multiple structural features that act together to entrap BMP ligands. In particular, the hydrophobic helical segment 81 to 86 and specifically the highly conserved tryptophan W82 in the N-terminal region are essential for ERFE bioactivity and Alphafold2 modeling places W82 between two tryptophans in its ligands BMP2, BMP6, and the BMP2/6 heterodimer, an interaction similar to those that bind BMPs to their cognate receptors. Finally, we identify the cationic region 96-107 and the globular TNFα-like domain 186-354 as structural determinants of ERFE multimerization that increase the avidity of ERFE for BMP ligands. Collectively, our results provide further insight into the ERFE-mediated inhibition of BMP signaling in response to erythropoietic stress.

Carbon quantum dots as fluorescent probes in the measurement of the critical micelle concentration of surfactants

The critical micelle concentration (CMC) is one main parameter of surfactants, so an accurate, rapid, and convenient method for CMC determination is of great significance for surfactant applications. In this paper, three samples of carbon quantum dots (CQDs) with different fluorescence properties were developed as fluorescent probes for the CMC determination of CTAB, SDS, Triton X-100, perfluoro OBS and Pluronics® P-123. The fluorescence excitation and emission spectra of a constant amount of the CQDs in different concentrations of the surfactant solution were recorded, and then the CMC values of the surfactant were deduced from the fluorescence intensity change and the Stokes shift variation. The obtained CMC data using three samples of the CQDs agree well with those in the published literature. It is also demonstrated that in the micellization process the interaction between the CQDs and the surfactant molecules is complicated, because the fluorescence properties of the CQDs are found to be related to the characteristics of the CQDs, the head group type of ionic surfactants, the chemical structure between the hydrophobic and hydrophilic segment, and the chemical nature of the hydrophobic chains of the surfactants. So, the CQDs are demonstrated to be located at the palisade layer in the surfactant micelles due to the surface-attached polar groups on the CQDs although the CQDs are mainly hydrophobic as fluorescent probes. The fluorescent CQDs are considered to be new choices of the fluorescent probes in the facile CMC measurement of the surfactants.

A nitroreductase-responsive nanoprobe with homogeneous composition and high loading for preoperative non-invasive tumor imaging and intraoperative guidance

Tumor microenvironment (TME)-activatable probes have been proven to effectively increase signal-to-background ratios (SBRs) and improve the success rate of complete tumor resection. However, many fluorescence probes have to be loaded into a nanocarrier for tumor targeted delivery, which consequently encounters poor drug loading, heterogeneous composition and non-encapsulated drug aggregates occurred during nanoformulation fabrications. Herein, a nitroreductase (NTR)-activated “OFF-ON” near-infrared fluorescence nanoprobe, named NanoBodipy, was synthesized by the spontaneous self-assembling of NTR-responsive dye-polyethylene glycol (PEG) amphiphilic polymer in water. The NTR-responsive dye acted as the hydrophobic segment in the amphiphilic polymer, yielding a homogeneous composition and a high loading of 12.2 wt% (according to calculation) in the synthesized NanoBodipy. The synthesized NanoBodipy can efficiently accumulate in tumors via the enhanced permeability and retention (EPR) effect, enabling non-invasive tumor-targeted fluorescence imaging and guiding complete tumor resection. Once the synthesized NanoBodipy entered the tumor cells, they dissociated and were activated by overexpressed NTR. With the real-time fluorescence guide of NanoBodipy, complete tumor resection surgery was performed successfully.

Superhydrophobic and Photocatalytic Synergistic Self-Cleaning Coating Constructed by Hierarchically Structured Flower-like Hollow SiO2@TiO2 Spheres with Oxygen Vacancies.

The self-cleaning coating has both superhydrophobic physical and photocatalytic chemical self-cleaning properties, which has attracted the wide attention of researchers in recent years. First, the flower-like hollow SiO2@TiO2 spheres with oxygen vacancies (rFHSTs) were prepared by the liquid-phase reduction method, in which several different functional components were integrated. Meanwhile, the influence mechanisms of the physical structure and chemical composition on the photocatalytic properties are discussed in detail. The results proved that rFHSTs exhibited the enhanced photoresponse range and photocatalytic degradation performance in visible light because of the synergistic effect of the microstructure (internal cavity, 3D flower-like nanosheet), SiO2/TiO2 heterojunction structure, and oxygen vacancies. After that, superhydrophobic modified rFHSTs were used as fillers to fabricate PVA/PFDTS-rFHSTs composite coatings with both physical and chemical self-cleaning properties. The self-cleaning performances and principles of the composite coating were examined and explored. The results showed that the low surface energy of the hydrophobic chain segment, the inherent particle effect, and the photocatalytic activity of rFHSTs were responsible for the superhydrophobic and photocatalytic effects, finally endowing the composite coating with self-cleaning performance. In short, this study is profound for the development and application of self-cleaning coatings with both physical and chemical performances.

Design of DNA-Based Artificial Transmembrane Channels for Biosensing and Biomedical Applications

Biomolecular channels on the cell membrane are essential for transporting substances across the membrane to maintain cell physiological activity. Artificial transmembrane channels used to mimic biological membrane channels can regulate intra/extracellular ionic and molecular homeostasis, and they elucidate cellular structures and functionalities. Due to their program design, facile preparation, and high biocompatibility, DNA nanostructures have been widely used as scaffolds for the design of artificial transmembrane channels and exploited for ionic and molecular transport and biomedical applications. DNA-based artificial channels can be designed from two structural modules: DNA nanotubes/nanopores as transport modules for mass transportation and hydrophobic segments as anchor modules for membrane immobilization. In this review, various lipophilic modification strategies for the design of DNA channels and membrane insertion are outlined. Several types of DNA transmembrane channels are systematically summarized, including DNA wireframe channels, DNA helix bundle channels, DNA tile channels, DNA origami channels, and so on. We then discuss efforts to exploit them in biosensor and biomedical applications. For example, ligand-gated and environmental stimuli-responsive artificial transmembrane channels have been designed for transmembrane signal transduction. DNA-based artificial channels have been developed for cell mimicry and the regulation of cell behaviors. Finally, we provide some perspectives on the challenges and future developments of artificial transmembrane channel research in biomimetic science and biomedical applications.