Cytotoxicity endpoints showed differences in sensitivity and predictability. The hepatocyte cell line depicted closer proximity to the embryo data. Conclusively, the high positive correlation between the cell- and embryo-based test systems emphasizes the appropriate modulation of toxicity when linked to bioavailable concentrations. Furthermore, it highlights the potential of fish cell lines to be utilized in integrated testing strategies.Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for natural products that inhibit soluble epoxide hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC50 ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1-5, 8-12) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC50 ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics but effectively reduced lipopolysaccharide-induced inflammatory pain. selleck products Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.High-valent transition metal-oxo, -peroxo, and -superoxo complexes are crucial intermediates in both biological and synthetic oxidation of organic substrates, water oxidation, and oxygen reduction. While high-valent oxygenated complexes of Mn, Fe, Co, and Cu are increasingly well-known, high-valent oxygenated Ni complexes are comparatively rarer. Herein we report the isolation of such an unusual high-valent species in a thermally unstable NiIII2(μ-1,2-peroxo) complex, which has been characterized using single-crystal X-ray diffraction and X-ray absorption, NMR, and UV-vis spectroscopies. Reactivity studies show that this complex is stable toward dissociation of oxygen but reacts with simple nucleophiles and electrophiles.Two organic-inorganic hybrid complexes, (CH3NH3)Na[Fe(CN)5NO]·H2O (1) and (CH3NH3)2[Fe(CN)5NO] (2), which exhibit stepwise dielectric switching as well as photo-induced structural transformation, are synthesized and examined. In these two compounds, the photo-responsive complex anions, [Fe(CN)5NO]2-, connected by Na+ through N-Na coordination bonds or CH3NH3+ through N···H-N hydrogen bonds, form two-dimensional structures. One organic cation, CH3NH3+, that resides in the intralaminar cavity and plays a role as a template, undergoes a temperature-controlled order-disorder structural phase transition. As the frozen-thawed state change of the polar organic cations modifies the polarizability of materials, stepwise dielectric switching is observed at the phase transition temperature. link2 Furthermore, the photo-induced linkage isomerism of [Fe(CN)5NO]2- building block survives in the new compounds at the low-temperature range, which is verified by variable-temperature IR spectra after photo-irradiation. The coexistence of switchable dielectric properties and photo-induced structural variation suggests multiple optical-electric roles of the present materials.Waterborne diarrheal diseases such as travelers’ diarrhea and cholera remain a threat to public health in many countries. Rapid diagnosis of an infectious disease is critical in preventing the escalation of a disease outbreak into an epidemic. Many of the diagnostic tools for infectious diseases employed today are time-consuming and require specialized laboratory settings and trained personnel. There is hence a pressing need for fit-for-purpose point-of-care diagnostic tools with emphasis in sensitivity, specificity, portability, and low cost. We report work toward thermally reversible biosensors for detection of the carbohydrate-binding domain of the Escherichia coli heat-labile enterotoxin (LTB), a toxin produced by enterotoxigenic E. coli strains, which causes travelers’ diarrhea. The biosensing platform is a hybrid of two materials, combining the optical properties of porous silicon (pSi) interferometric transducers and a thermoresponsive multivalent glycopolymer, to enable recognition of LTB. Analytical performance of our biosensors allows us to detect, using a label-free format, sub-micromolar concentrations of LTB in solution as low as 0.135 μM. Furthermore, our platform shows a temperature-mediated “catch-and-release” behavior, an exciting feature with potential for selective protein capture, multiple readouts, and regeneration of the sensor over consecutive cycles of use.Nanofibrous poly(l-lactic acid) (PLLA) membrane-simulated extracellular matrices (ECMs) can be used in the biomedical field. However, the hydrophobic nature and poor osteoinductive property of PLLA limit its application in guided bone regeneration (GBR). In this work, a methacrylated gelatin/nano-HA (GelMA/nHA) complex was first synthesized in situ and then introduced into PLLA to fabricate biomimetic GelMA/nHA/PLLA membranes, mimicking the nanofibrous architecture and composition of ECMs by electrospinning and photocrosslinking. Compared to PLLA and GelMA/PLLA membranes, the novel GelMA/nHA/PLLA membranes demonstrated better tensile, hydrophilic, water sorption, and degradation properties. An in vitro biological evaluation indicated that the membranes promoted human bone marrow-derived mesenchymal stem cell (hBMSC) proliferation, adhesion, and osteogenic differentiation. Critical-sized defects in rat models were used to evaluate the bone regeneration performances of the three kinds of membranes in vivo, and the GelMA/nHA/PLLA membranes demonstrated excellent osteogenic regeneration potential. Therefore, GelMA/nHA/PLLA membranes have wide application prospects in bioengineering applications such as GBR treatment.Silk nanoparticles have demonstrated utility across a range of biomedical applications, especially as drug delivery vehicles. Their fabrication by bottom-up methods such as nanoprecipitation, rather than top-down manufacture, can improve critical nanoparticle quality attributes. Here, we establish a simple semi-batch method using drop-by-drop nanoprecipitation at the lab scale that reduces special-cause variation and improves mixing efficiency. The stirring rate was an important parameter affecting nanoparticle size and yield (400 less then 200 less then 0 rpm), while the initial dropping height (5.5 vs 7.5 cm) directly affected nanoparticle yield. Varying the nanoparticle standing time in the mother liquor between 0 and 24 h did not significantly affect nanoparticle physicochemical properties, indicating that steric and charge stabilizations result in high-energy barriers for nanoparticle growth. Manufacture across all tested formulations achieved nanoparticles between 104 and 134 nm in size with high β-sheet content, spherical morphology, and stability in aqueous media for over 1 month at 4 °C. This semi-automated drop-by-drop, semi-batch silk desolvation offers an accessible, higher-throughput platform for standardization of parameters that are difficult to control using manual methodologies.Although cell membrane-coated nanoparticles are widely used as a promising nanodelivery platform, a few studies reported their application in developing the teleost nanovaccine delivery system. Here, we present a biomimetic vaccine delivery platform by encapsulating chitosan-loaded DNA vaccine with teleost erythrocytes membrane modified by mannose. The developed CS-G@M-M nanovaccine delivery platform shows good biocompatibility in vivo and in vitro. With further modification of mannose moiety, the constructed CS-G@M-M showed enhanced uptake by antigen-presenting cells (APCs) and increased accumulation of CS-G@M-M in immune tissues including spleen, kidney, and hindgut. Critically, using a quantitative real-time polymerase chain reaction (qRT-PCR) assay, increased mRNA levels of immune-related genes were detected in spleen and hindgut of vaccinated fish. Moreover, through enzyme-linked immunosorbent assay (ELISA), we found that the levels of CD80/86, TNF-α, IgM, and IgZ in spleen and hindgut were significantly increased. To evaluate the immunoprotection efficacy of the constructed nanovaccine, spring viremia of carp virus (SVCV), a rhabdovirus of worldwide importance that requires notification within 48 h to the International Office of Epizootics once detected, was used as a model for virus challenge. We carried out three challenge tests on 3rd, 21st, and 70th days post vaccination, respectively. Notably, CS-G@M-M nanovaccine showed durability of immunoprotection efficacy that could protect zebrafish from SVCV challenge. This work presents a novel design of smart teleost erythrocytes membrane-coated nanoparticles, which are inherently biocompatible, promising for eliciting robust adaptive immune responses in preventing fish viral diseases.Conventional strategies of stem cell injection in treating myocardial infarction (MI) remain a challenge because of low retention rate and insufficient secretion of exogenous cytokines for efficiently improving the microenvironment in the infarcted myocardium, thus hampering the therapeutic effect. link3 Herein, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human VE-cad-Fc fusion protein are fabricated and integrated with human mesenchymal stem cells (hMSCs) to construct functionalized MSC aggregates (FMAs). This fusion protein can effectively promote the paracrine activity of MSCs. The FMA is encapsulated with an injectable hyaluronic acid (HA)-based hydrogel, which is prepared by Schiff base reaction between oxidized HA (OHA) and hydrazided HA (HHA). The OHA@HHA hydrogel loading FMA is injected into the infarcted myocardium of rats, thereby efficiently improving the MI microenvironment in terms of decreased expressions of inflammatory cytokines and upregulated secretion of angiogenic factors compared to the plain hydrogel only and hydrogel encapsulating MSCs. The results of both echocardiography and histological analyses demonstrate the efficient reconstruction of cardiac function and structure and revascularization in the infarct myocardium. The delivery of functionalized stem cell aggregates with an injectable hydrogel offers a promising strategy for treating myocardial infarction and may be expanded to other tissue repair and reconstruction.Intermediate water (IW) is known to play an important role in the antifouling property of biocompatible polymers. However, how IW prevents protein adsorption is still unclear. To understand the role of IW in the antifouling mechanism, molecular dynamics simulation was used to investigate the dynamic properties of water and side-chains for hydrated poly(ω-methoxyalkyl acrylate)s (PMCxA, where x indicates the number of methylene carbons) with x = 1-6 and poly(n-butyl acrylate) (PBA) in this study. Since the polymers uptake more water than their equilibrium water content (EWC) at the polymer/water interface, we analyzed the hydrated polymers at a water content higher than that of EWC. It was found that the water molecules interacting with one polymer oxygen atom (BW1), of which most are IW molecules, in PMC2A exhibit the lowest mobility, while those in PBA and PMC1A show a higher mobility. The result was consistent with the expectation that the biocompatible polymer with a long-resident hydration layer possesses good antifouling property.