Specific Binding Capability Research Articles

Engineering Adhesion of the Probiotic Strain Escherichia coli Nissle to the Fungal Pathogen Candida albicans.

Engineering live biotherapeutic products against fungal pathogens such as Candida albicans has been suggested as a means to tackle the increasing threat of fungal infections and the development of resistance to classical antifungal treatments. One important challenge in the design of live therapeutics is to control their localization inside the human body. The specific binding capability to target organisms or tissues would greatly increase their effectiveness by increasing the local concentration of effector molecules at the site of infection. In this study, we utilized surface display of carbohydrate binding domains to enable the probiotic E. coli Nissle 1917 to adhere specifically to the pathogenic yeast Candida albicans. Binding was quantified using a newly developed method based on the automated analysis of microscopic images. In addition to a rationally selected chitin binding domain, a synthetic peptide of identical length but distinct sequence also conferred binding. Efficient binding was specific to fungal hyphae, the invasive form of C. albicans, while the yeast form, as well as abiotic cellulose and PET particles, was only weakly recognized.

A comprehensive study on the multifunctional properties of galectin-4 in red-lip mullet (Planiliza haematocheilus): Insights into molecular interactions, antimicrobial defense, and cell proliferation

Galectin-4 belongs to the galactoside-binding protein family and is a type of tandem repeat galectin. Despite previous studies indicating its importance in fish immunology, a comprehensive investigation is necessary to fully understand its role in immunomodulatory functions and cellular dynamics. Therefore, this study aimed to explore the immunomodulatory functions of galectin-4 with a particular focus on its antimicrobial and cellular proliferative properties. The open reading frame of PhGal4 spans 1092 base pairs and encodes a soluble protein of 363 amino acids with a theoretical isoelectric point (IEP) of 6.39 and a molecular weight of 39.411 kDa. Spatial expression analysis under normal physiological conditions revealed ubiquitous expression of PhGal4 across all examined tissues, with the highest level observed in intestinal tissue. Upon stimulation with poly I:C, LPS, and L. garvieae, a significant increase (p < 0.05) in PhGal4 expression was observed in both blood and spleen tissues. Subsequent subcellular localization assay demonstrated that PhGal4 was predominantly localized in the cytoplasm. The recombinant PhGal4 (rPhGal4) exhibited specific binding capabilities to pathogen-associated molecular patterns (PAMPs), including LPS and peptidoglycan, but not poly I:C. The rPhGal4 negatively affected the bacterial growth kinetics. Additionally, rPhGal4 demonstrated complete hemagglutination of fish erythrocytes, which could be inhibited by the presence of D-galactose and α-lactose. The overexpression of PhGal4 in FHM epithelial cells demonstrated a significant suppression of viral replication during VHSV infection. Furthermore, the in vitro scratch assay and WST-1 assay demonstrated a wound healing effect of PhGal4 overexpression in FHM cells, potentially achieved through the promotion of cell proliferation by activating genes involved in cell cycle regulation. In conclusion, the responsive expression to immune stimuli, antimicrobial properties, and cell proliferation promotion of PhGal4 suggest that it plays a crucial role in immunomodulation and cellular dynamics of red-lip mullet. The findings in this study shed light on the multifunctional nature of galectin-4 in teleost fish.

Paper-Based Electrochemical Sensors for Cancer Biomarkers Detection

Cancer is currently the third leading cause of death among the people of the Navajo Nation and is the most common cause of death worldwide. American Indians are often diagnosed when cancer has reached the advanced stages compared to other communities. Major contributors for the cancer inside the Navajo Nation is the exposure to uranium, other heavy metals, and radon gas. In the Navajo Nation, uranium mining boomed from 1944 to 1986; decades later, uranium tailings and toxic waste from the milling process have caused an increased rate of cancer in the Navajo Nation.Further cancer detection and monitoring remain critical challenges in healthcare. This research explores the fabrication of paper-based electrochemical sensors modified with nanoparticles and antigens at the Nanoelectrochemical Analysis and Energy Storage Laboratory (NEST LAB) at Navajo Technical University (NTU) for the sensitive and selective detection of cancer biomarkers.These electrochemical sensors harness the unique qualities of paper, such as low cost and ease of fabrication, combined with the specific binding capabilities of nanoparticles and antigens. Modifying paper electrode surfaces enhances sensitivity and selectivity, making these sensors a cost-effective and portable option for early cancer detection. In contrast to traditional methods like imaging and biopsies, electrochemical sensors are low-cost, offer minimally invasive screening, high sensitivity, and affordability, making them valuable tools in the early diagnosis and management of cancer. These sensors'accessibility and potential to detect cancer at its earliest stages can significantly improve patient outcomes, particularly in resource-limited areas such as Native American reservations.Keywords: Cancer biomarkers, paper-based electrochemical sensors, nanoparticle modification, antigen modification, early detection, point-of-care diagnostics, cost-effective healthcare.

Construction of dual receptors imprinted polymers by precise control of sequential assembly efficiency in confined sites to enhance specific separation of adenosine 5′-monophosphate

Sequential assembly strategies are employed to incorporate various monomers, thereby enhancing the specific binding capability of imprinting sites towards the target molecule and ultimately improving the selectivity of molecular imprinted polymers (MIPs). However, the effectiveness of sequential assembly in improving discriminative separation requires further investigation. For the specific functional groups present in AMP molecules, the utilization of confining metal ion sites guided by metal–organic frameworks (MOFs) material can effectively mitigate disordered competition, enhance the efficiency of imprinted assembly, and facilitate the controlled growth of imprinted sites. In this study, we have successfully achieved precise control over the efficiency of sequential assembly in hydrophilic Zr-MOFs nanosheets in order to fabricate dual receptor surface molecularly imprinted sorbents (D-MIPs) for selectively separating AMP. The hydrophilic Zr-MOFs nanosheets (D-PABA) possess a significantly high surface area of approximately 282.52 m2 g−1. The water contact angle of Zr-BTB-FA nanosheets was measured to be 32°, while that of D-MIPs was 25°. The hydrophilic surface properties of materials promote the dispersion of the adsorbent in aqueous solutions and enhance the rapid mass transfer of water-soluble target molecules. Additionally, the half-equilibrium time (t1/2) was found to be 0.578 h. The D-MIPs demonstrate a significant adsorption capacity (286.7 μmol g−1 at 298 K) for AMP compared to other nucleoside analogues, such as dC, dG, dA, ADP and ATP. Additionally, an imprinting factor (IF) of 2.764 was observed for D-MIPs compared to their non-imprinted counterpart. In addition, the selective extraction of 97 % AMP from the spiked diluted biofermentation broth sample can be achieved using D-MIPs. This finding highlights the potential of D-MIPs as an efficient solution for the selective capture of AMP from biological samples.

Nanobody-loaded nanobubbles targeting the G250 antigen with ultrasound/photoacoustic/fluorescence multimodal imaging capabilities for specifically enhanced imaging of RCC.

Clinicians have attempted to discover a noninvasive, easy-to-perform, and accurate method to distinguish benign and malignant renal masses. The targeted nanobubbles (NBs) we constructed that target the specific membrane antigen of renal cell carcinoma (RCC), G250, and contain indocyanine green (ICG) provide multimodal enhanced imaging capability in ultrasound/photoacoustic/fluorescence for RCC which may possibly solve this problem. In this study, we encapsulated ICG in the lipid shell of the NBs by mechanical oscillation, then anti-G250 nanobodies (AGN) were coupled to the surfaces by the biotin-streptavidin bridge method, and the nanobubble named AGN/ICG-NB was completely constructed. The average particle diameter of the prepared AGN/ICG-NBs was (427.2 ± 4.50) nm, and the zeta potential was (-13.33 ± 1.01) mV. Immunofluorescence and flow cytometry confirmed the specific binding capability of AGN/ICG-NBs to G250-positive cells. In vitro imaging experiments confirmed the multimodal imaging capability of AGN/ICG-NBs, and the in vivo imaging experiments demonstrated the specifically enhanced ability of AGN/ICG-NBs for ultrasound/photoacoustic/fluorescence imaging of human-derived RCC tumors. The biosafety of AGN/ICG-NB was verified by CCK-8 assay, organ H&E staining and blood biochemical indices. In conclusion, the targeted nanobubbles we prepared with ultrasound/photoacoustic/fluorescence multimodal imaging capabilities provide a potentially feasible approach to address the need for early diagnosis and differential diagnosis of renal masses.

99mTc-Tilmanocept performance for sentinel node mapping in breast cancer, melanoma, and head and neck cancer: a systematic review and meta-analysis from a European expert panel.

Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99mTc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of 99mTc-tilmanocept for SN biopsy. A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of 99mTc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer. Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the 99mTc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88-1.01) and 0.99 (0.98-1.00) for breast cancer, 0.98 (0.96-0.99) and 1.00 (0.99-1.00) for melanoma, and 0.97 (0.93-1.02) and 0.99 (0.96-1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92-1.03). 99mTc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if 99mTc-tilmanocept is superior to other radiotracers used in clinical routine.

Plasmodium falciparum rhoptry neck protein 4 has conserved regions mediating interactions with receptors on human erythrocytes and hepatocyte membrane

Plasmodium falciparum-related malaria represents a serious worldwide public health problem due to its high mortality rates. P. falciparum expresses rhoptry neck protein 4 (PfRON4) in merozoite and sporozoite rhoptries, it participates in tight junction-TJ formation via the AMA-1/RON complex and is refractory to complete genetic deletion. Despite this, which PfRON4 key regions interact with host cells remain unknown; such information would be useful for combating falciparum malaria. Thirty-two RON4 conserved region-derived peptides were chemically synthesised for determining and characterising PfRON4 regions having high host cell binding affinity (high activity binding peptides or HABPs). Receptor-ligand interaction/binding assays determined their specific binding capability, the nature of their receptors and their ability to inhibit in vitro parasite invasion. Peptides 42477, 42479, 42480, 42505 and 42513 had greater than 2% erythrocyte binding activity, whilst peptides 42477 and 42480 specifically bound to HepG2 membrane, both of them having micromolar and submicromolar range dissociation constants (Kd). Cell-peptide interaction was sensitive to treating erythrocytes with trypsin and/or chymotrypsin and HepG2 with heparinase I and chondroitinase ABC, suggesting protein-type (erythrocyte) and heparin and/or chondroitin sulphate proteoglycan receptors (HepG2) for PfRON4. Erythrocyte invasion inhibition assays confirmed HABPs’ importance during merozoite invasion. PfRON4 800–819 (42477) and 860–879 (42480) regions specifically interacted with host cells, thereby supporting their inclusion in a subunit-based, multi-antigen, multistage anti-malarial vaccine.

4-Mercaptopyridine-Modified Sensor for the Sensitive Electrochemical Detection of Mercury Ions

As a highly toxic heavy metal ion, mercury ion (Hg2+) pollution has caused serious harm to the environment and human health. In this paper, 4-mercaptopyridine (4-MPY) was selected as the sensing material and decorated on the surface of a gold electrode. Trace Hg2+ could be detected by both differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) methods. The proposed sensor displayed a wide detection range from 0.01 μg/L to 500 μg/L with a low limit of detection (LOD) of 0.002 μg/L by EIS measurements. Combined with molecular simulations and electrochemical analyses, the chelating mechanism between Hg2+ and 4-MPY was explored. Through the analysis of binding energy (BE) values and stability constants, 4-MPY showed an excellent selectivity for Hg2+. In the presence of Hg2+, the coordination of Hg2+ with the pyridine nitrogen of 4-MPY was generated at the sensing region, which caused a change in the electrochemical activity of the electrode surface. Due to the strong specific binding capability, the proposed sensor featured excellent selectivity and an anti-interference capability. Furthermore, the practicality of the sensor for Hg2+ detection was validated with the samples of tap water and pond water, which demonstrated its potential application for on-site environmental detection.

Magnetically Controlled Nanorobots Based on Red Emissive Peptide Dots and Artificial Antibodies for Specific Recognition and Smart Scavenging of Nε-(Carboxymethyl)lysine in Dairy Products

Food-borne advanced glycation end products (AGEs) are highly related to various irreversible diseases, and Nε-(carboxymethyl)lysine (CML) is the typical hazardous AGE. The development of feasible strategies to monitor and reduce CML exposure has become desirable to address the problems. In this work, we proposed magnetically controlled nanorobots by integrating an optosensing platform with specific recognition and binding capability, realizing specific anchoring and accurate determination as well as efficient scavenging of CML in dairy products. The artificial antibodies offered CML imprinted cavities for highly selective absorption, and the optosensing strategy was designed based on electron transfer from red emissive self-assembling peptide dots (r-SAPDs) to CML, which was responsible for the identity, response, and loading process. The r-SAPDs overcame the interference from autofluorescence, and the limit of detection was 0.29 μg L-1, which bestowed accuracy and reliability for in situ monitoring. The selective binding process was accomplished within 20 min with an adsorption capacity of 23.2 mg g-1. Through an external magnetic field, CML-loaded nanorobots were oriented, moved, and separated from the matrix, which enabled their scavenging effects and reusability. The fast stimuli-responsive performance and recyclability of the nanorobots provided a versatility strategy for effective detection and control of hazards in food.

Protein nanoarrays using the annexin A5 two-dimensional crystal on supported lipid bilayers.

Protein nanoarrays are regularly ordered patterns of proteins fixed on a solid surface with a periodicity on the order of nanometers. They have significant potential applications as highly sensitive bioassays and biosensors. While several researchers have demonstrated the fabrication of protein nanoarrays with lithographic techniques and programmed DNA nanostructures, it has been difficult to fabricate a protein nanoarray containing a massive number of proteins on the surface. We now report the fabrication of nanoarrays of streptavidin molecules using a two-dimensional (2D) crystal of annexin A5 as a template on supported lipid bilayers that are widely used as cell membranes. The 2D crystal of annexin A5 has a six-fold symmetry with a period of about 18 nm. There is a hollow of a diameter of about 10 nm in the unit cell, surrounded by six trimers of annexin A5. We found that a hollow accommodates up to three streptavidin molecules with their orientation controlled, and confirmed that the molecules in the hollow maintain their specific binding capability to biotinylated molecules, which demonstrates that the fabricated nanoarray serves as an effective biosensing platform. This methodology can be directly applied to the fabrication of nanoarrays containing a massive number of any other protein molecules.

Application of 2D Materials for Adsorptive Removal of Air Pollutants.

Air pollution is on the priority list of global safety issues, with the concern of fatal environmental and public health deterioration. 2D materials are potential adsorbent materials for environmental decontamination, owing to their high surface area, manageable interlayer binding, large surface-to-volume ratio, specific binding capability, and chemical, thermal, and mechanistic stability. Specifically, graphene oxide and reduced graphene oxide have been attracting attention, taking advantage of their low cost synthesis, excessive oxygen containing surface functionalities, and intrinsic aqueous dispersibility, making them desirable for the development of cost-effective, high performance air filters. Many different material designs have been proposed to expand their filtration capability, including the functionalization and integration with other metals and metal oxides, which act not only as binding agents to the target pollutants but also as antimicrobial agents. This review highlights the advantages and drawbacks of 2D materials for air filtration and summarizes the interrelationships among various strategies and the resultant filtration performance in terms of structural engineering, morphology control, and material compositions. Finally, potential future directions are suggested toward the idealized designs of 2D material based air filters.

Synthesis, characterization and investigation of photochemical and in vitro antiproliferative properties of novel Zn(II) phthalocyanine

In this study, a novel peripheral zinc(II) phthalocyanine (ZnPc) containing cyclic two triazole moieties which include 24 or 26-membered macrocyclic zinc(II) phthalocyanine was synthesized via multistep reactions. The precursor macrocyclic phthalonitrile was converted into the related phthalocyanine by cyclotetramerization reaction. The photochemical, in-silico selective targeting of cancer related genes and in vitro antiproliferative effect of this zinc(II) phthalocyanine was investigated. Singlet oxygen production properties of the synthesized phthalocyanine compound (ZnPc) indicated as singlet oxygen quantum yield (ΦΔ = 0.47). In- silico studies proved the efficient and specific binding capability of G-quadruplex nucleic acids. ZnPc compound demonstrated antiproliferative effect in vitro on human non-small cell lung carcinoma cell lines.

Multifunctional Nanoparticles Based on Iron Oxide and Gold-198 Designed for Magnetic Hyperthermia and Radionuclide Therapy as a Potential Tool for Combined HER2-Positive Cancer Treatment.

Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe3O4) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody—trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.

Multifunctional surface coating using chitosan and its chemical functionalization

AbstractBiologically active surfaces with spatio‐selective binding capabilities minimize nonspecific adsorption and are essential to fabricate biomedical devices. Chitosan is a potential material for such a functional surface because of its good biocompatibility. In this study, a chitosan‐based bioactive surface was prepared using a facile drop‐casting method. Nonbiofouling properties of the bare chitosan film were observed against fluorescent‐tagged proteins (streptavidin and bovine serum albumin). The interaction of streptavidin with biotin was used to assess the specific binding capabilities. Biotin was spatially and selectively immobilized onto the film through surface organic reactions. Fluorescence intensities of the streptavidin‐treated chitosan film proportionally changed with the biotin concentration, suggesting a good specific binding. Furthermore, the intrinsic amine groups in the chitosan coating provided antibacterial properties, which could be further enhanced by introducing quaternary ammonium cations. The combination of nonbiofouling, specific binding, and antibacterial properties renders chitosan a viable candidate for biomedical and analytical applications.

309-OR: Lipocalin 2 Deficiency Impairs Mitochondrial Dynamics and Phospholipid Metabolism in Brown Adipocytes

Impaired mitochondrial bioenergetics in brown adipocytes links to the disrupted energy metabolism and thermogenesis in obesity. Phospholipids, particularly cardiolipin and phosphatidic acid (PA) are critical regulators of mitochondrial membrane architecture and dynamics. Mitochondria-associated endoplasmic reticulum membranes (MAMs) serve as the platform for phospholipid biosynthesis. MAM dysfunction disturbs phospholipid metabolism, thereby disrupting mitochondrial function. However, little is known about the participating factors that regulate MAM phospholipid metabolism. We have previously characterized the role of lipocalin 2 (Lcn2) in thermogenesis and mitochondrial function in adipocytes. Herein, we found that Lcn2 was located at MAMs and had a specific PA binding capability. The mitochondrial fusion-fission process induced by the fasting-refeeding cycle was impaired in Lcn2 knockout (KO) brown adipocytes. We also observed that the levels of phosphorylated Drp1 (Ser616) and Opa1 were decreased in brown adipose tissue (BAT) of Lcn2 KO mice compared to WT controls upon acute cold stimulation, whereas Lcn2 overexpression in BAT led to an increase in Drp1 phosphorylation and Opa1 level. Moreover, Lcn2 deficiency significantly enhanced the cold-stimulated accumulation of Opa1 as well as MAM markers SigmaR1, Ip3R1, and Facl4 at MAMs in BAT, suggesting impaired MAM function. CL316,243, a β3-adrenergic receptor agonist has a cold mimic effect on mitochondrial bioenergetics. In brown adipocytes, Lcn2 deficiency significantly attenuated the CL316,243 induction of Drp1 phosphorylation. Intriguingly, lipidomic analysis of BAT mitochondria isolated from mice treated with CL316,243 for 14 days showed that Lcn2 deficiency blunted CL316,243-induced cardiolipin biosynthesis and altered phospholipid metabolism. Together, we discovered a role of Lcn2 as a novel PA transfer protein in mitochondrial bioenergetics via regulating phospholipid metabolism. Disclosure H.Su: None. H.Guo: None. X.Qiu: None. T.Lin: None. X.Chen: None. Funding This work was supported by NIDDK Grant (RDK123042) awarded to Xiaoli Chen.

A Novel CD3/BCMA Bispecific T-cell Redirecting Antibody for the Treatment of Multiple Myeloma.

Multiple myeloma (MM) is a B-cell malignancy for which new treatments are urgently needed. Redirecting the activity of T cells by bispecific antibodies against tumor cells is a potent approach. The B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein and therefore is an ideal therapeutic target for T-cell redirecting therapies. The main objective of this work is to target the BCMA by generating BCMA-specific murine monoclonal antibody and construct a cluster of differentiation 3 (CD3)/BCMA-directed tandem diabodies (Tandab). In brief, using standard hybridoma technology, we developed a novel BCMA-specific monoclonal antibody (clone 69G8), that specifically bind with BCMA+ cell lines and MM patient sample; whereas BCMA- cells were not recognized. For T cells by bispecific antibodies application, we constructed a Tandab (CD3/BCMA) simultaneously targeting both CD3 and BCMA and our studies demonstrated that Tandab (CD3/BCMA) was functional with specific binding capability both for CD3+ cells and BCMA+ cells. It induced selective, dose-dependent lysis of BCMA+ cell lines, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA- cells were not affected. Furthermore, we demonstrated that Tandab activity correlates with BCMA expression, with higher potency observed in highly BCMA expressing tumor cells. In vivo, the purified Tandab (CD3/BCMA) significantly inhibited the tumor growth in a subcutaneous NCI-H929 xenograft model. Taken together, these results show that the Tandab (CD3/BCMA) displays potent and selective anti-MM activities and represents a promising immunotherapeutic for the treatment of MM.

Sensitive and Selective Detection of N,N-Dimethyltryptamine with Molecularly Imprinted Polymer Coupled with Electrogenerated Chemiluminescence

One of the challenges in analytical chemistry is to develop a method that is not only sensitive but also selective for detection and quantification of a target analyte. Herein, we report a strategy that combines a molecularly imprinted polymer (MIP) as the selective element with electrogenerated chemiluminescence (ECL) as the sensitive analytical signal generator for detection of a hallucinogenic drug N,N-dimethyltryptamine (DMT). MIPs hold specific binding capability toward probed targets, and their molecular recognition behavior is similar to that of specific antibodies to antigens or probe single-strand DNAs to complemental target DNA sequencies. Additionally, MIPs are chemically stable, easily synthesized, and cost-effective. On the other hand, ECL has been regarded as one of the most sensitive analytical techniques for ultra-trace analyte determination. This is because ECL is a kind of spectroscopy initiated by electrochemistry without using any light source. For the present work, DMT specific MIPs were prepared by anodic electrodeposition of aminobenzoic acid as monomer mixed with DMT as template molecule on a glassy carbon electrode that had coated with a Ru(bpy)3 2+ trapped nafion film. ECL signals at the electrodes with DMT immobilized MIPs were acquired in a phosphate buffered solution upon the anodic potential scanning. A non-imprinted polymer (NIP) was also prepared in absence of template under similar conditions. The MIP-ECL sensor showed a wide dynamic range of 0.05 to 100 µM to DMT with an estimated detection limit of 0.05 µM. The reproducibility, stability, and selectivity of the sensor were also examined. Figure 1

Zwitterionic polymer modified xanthan gum with collagen II-binding capability for lubrication improvement and ROS scavenging

High friction of damaged cartilage requires long-acting lubricated additive, which can also effectively scavenge reactive oxidative species (ROS) produced by mechanically stimulated chondrocytes. In this study, xanthan gum (XG) was grafted by poly (sulfobetaine methacrylate) (PSBMA) (the [XG]/[SBMA] molar ratio is 1:5 or 1:10), forming nanoparticles and then conjugated with collagen II-binding peptide, finally obtaining CBPXGSB1/5 or CBPXGSB1/10. Therein, the CBPXGSB1/5 was chosen as optimal lubricated additive. The results show that hydrated effect of PSBMA side chains endows CBPXGSB1/5 with favorable lubrication property (COF is 0.063). Furthermore, the CBPXGSB1/5 combining lubrication property and specific binding capability together may achieve the long-acting lubrication for injured cartilage in medical field. The CBPXGSB1/5 also possesses antioxidation verified by DPPH assay and exhibits synergistically enhanced ROS (OH, O2− and H2O2) scavenging. Besides, cytotoxicity experiment demonstrates that CBPXGSB1/5 has good biocompatibility. Therefore, multifunctional CBPXGSB1/5 developed here may have promising application potential in osteoarthritis treatment.

OX40L blockade cellular nanovesicles for autoimmune diseases therapy

Current clinical agents for autoimmunity disorders treatment often cause substantial adverse effects and safety concerns, owing to non-specific immune modulation. Due to the prominent contribution of effector T cells in pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), and preferential location of co-stimulatory receptor-ligand pair OX40-OX40L at the inflamed sites, selectively targeting autoaggressive T cells by blockade OX40-OX40L, might represent an alternative strategy. Herein, we developed a new strategy to antagonize OX40-OX40L interaction by engineering a cell membrane derived nanovesicles (NVs) expressing OX40 receptors (OX40 NVs), and explored their potential for autoimmune disorders therapy. OX40 NVs showed specific binding capability to inflamed HUVECs in vitro, it also possessed distinct arthritic-targeting capacity in RA inflamed joints, and preferential accumulation in IBD inflamed colon. OX40 NVs efficiently suppressed the progression of both RA and IBD diseases through reducing CD4+OX40+ T cells population, and proinflammatory cytokines (i.e., TNF-α and IL-1β), while reinforcing Tregs immune-suppressive effect, with superior therapeutic efficacy than anti-OX40L. Additionally, dexamethasone (DEX) loading can further enhance the potential of OX40 NVs for RA treatment. Owing to their preferential localization to inflamed sites, and potent immune-suppression ability, targeting OX40-OX40L blockade by OX40 NVs for autoimmune therapy is highly promising.

In Silico Analysis of Ethanol Binding Activity in Neuronal Nicotinic Acetylcholine Receptors

Ethanol and nicotine are two common substances that are often linked to complications in alcoholic smokers. The high number of the co-consumptions in alcoholic smokers suggested a possible interaction between ethanol and nicotine in the central nervous system and a potential similar mechanism of action. Both ethanol and nicotine are shown to bind with neuronal nicotinic acetylcholine receptors (nAChRs), a ligand gated cation channel specifically targeted by the endogenous acetylcholine. Ethanol has a much less specific binding capability to modulate the receptors, however, emerging reports indicates that ethanol can interact with nAChRs both directly and indirectly. This study focuses on the analysis of ethanol binding sites with nAChRs using molecular docking techniques obtained from the Protein Data Bank. The obtained data showed a possible binding site for ethanol in nAChRs, however, upon validation, result is not substantial. Nevertheless, the obtained data should be useful for future reference for the basis of ethanol interactions with the human nAChRs proteins.