Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on "bio-orthogonal chemistry", combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

A "Dual-Key-and-Lock" MRI Contrast Agent with T1-T2 Switchable Function for Accurate Diagnosis of Tumors.

Extremely small iron oxide nanoparticle (ESIONP)-based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dual-key-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T1 to T2 contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.

Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging.

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

Insecticide-mediated changes in the population and toxicity of the thrips species, Frankliniella occidentalis (Pergande) and Thrips flavus (Schrank) (Thysanoptera: Thripidae).

Frankliniella occidentalis (Pergande) and Thrips flavus (Schrank) (Thysanoptera: Thripidae) cause considerable damage to agricultural crops. In this study, we investigated the variations in the population density of these 2 thrips species in 2 sites (Dabai and Heilongtan) with different insecticide application levels. Bioassays were performed to determine the susceptibility of both thrips species to imidacloprid, abamectin, and high-bromine cyhalothrin in summer. The results showed that the F. occidentalis species were more abundant in Dabai than in Heilongtan during both winter and summer. The proportions of F. occidentalis in winter and summer were 28.32-43.35% and 61.79-76.02%, respectively. Moreover, F. occidentalis resistance against the 3 insecticides was significantly higher than that of T. flavus in both 2017 and 2019. Compared with 2017, the LC50 values of F. occidentalis populations in Dabai to imidacloprid, abamectin, and lambda-cyhalothrin increased to 100.076, 16.52, and 130.44 mg/liter, respectively. The number of F. occidentalis, reaching the proportion of 91.63% in 90 days, was significantly higher than that of the control after imidacloprid treatment. In conclusion, thrips interspecies competition is affected by the irrational use of insecticides, which may cause the replacement of native species by invasive species, thereby leading to an outbreak.

Hypoxia-Responsive T2-to-T1 Dynamically Switchable Extremely Small Iron Oxide Nanoparticles for Sensitive Tumor Imaging In Vivo.

To realize the accurate diagnosis of tumors by magnetic resonance imaging (MRI), switchable magnetic resonance contrast agents (CAs) between T1 and T2 contrast enhancement that are constructed based on extremely small iron oxide nanoparticles (ESIONPs) have been developed in recent years. We herein report, for the first time, a novel ESIONP-based nanocluster (named EAmP), which exhibited hypoxia responsiveness to the tumor microenvironment and offered a T2-to-T1-switchable contrast enhancement function, effectively distinguishing between the normal tissue and tumor tissue. In detail, active perfluorophenyl ester-modified ESIONPs with a diameter of approximately 3.6 nm were initially synthesized, and then 4,4'-azodianiline was used as a cross-linker to facilitate the formation of nanoclusters from ESIONPs through the reaction between the active ester and amine. Finally, poly(ethylene glycol) was further modified onto nanoclusters by utilizing the remaining active ester residues. The resulting EAmP demonstrated satisfactory colloidal stability and favorable biosafety and exhibited a desired T2-to-T1-switchable function, as evidenced by conversion from nanocluster to the dispersed state and a significant decrease in the r2/r1 ratio from 14.86 to 1.61 when exposed to a mimical hypoxic environment in the solution. Moreover, EAmP could decompose into dispersed ESIONPs at the tumor region, resulting in a switch from T2 to T1 contrast enhancement. This T2-to-T1-switchable contrast agent offers high sensitivity and signal-to-noise ratio to realize the accurate diagnosis of tumors. In conclusion, hypoxia-responsive EAmP is a potential MRI nanoprobe for improving the diagnostic accuracy of solid tumors.

Effects of short-term extreme temperature treatment on the development and reproductive capacity of Encarsia formosa.

Encarsia formosa is a natural enemy of the invasive pest Bemisia tabaci and is known to be a dominant parasitic. The frequency and magnitude of climate extremes, particularly temperature extremes, have increased, which has put insect populations at risk. However, the effects of temperature extremes on E. formosa are not well understood. To examine the impact of short-term extreme temperature exposure on the development and reproduction of E. formosa, eggs, larvae, pupae, and adults were exposed to high/low temperature treatments (HLT25, HLT50, LLT25, and LLT50). Our findings indicate that the pupal stage of E. formosa exhibited the strongest tolerance to both heat and cold, while adults exhibited a weaker tolerance. The shortest egg-to-adult development period of 12.65 days was observed in E. formosa exposed to HLT50 treatment during the egg-larval stage. The parasitism peak of the adult stage was delayed by 1-6 days after exposure to extreme temperatures during the egg-larval stage. Conversely, the parasitism peak was advanced by 1-3 days after exposure to extreme temperatures during the pupal and adult stages. The eclosion rate, total parasitism, eclosion rate of the F1 generation, and adult longevity of the F1 generation were lower in the treatment groups than in the control groups. The F1 generation's development period was prolonged to 15.49 and 15.19 days after exposure to HLT25 and HLT50 treatments, respectively, during the egg-larval stage. The F1 generation's development period was shortened to 13.33 days after exposure to LLT50 treatment during the pupal stage. Male individuals appeared in the F1 generation after exposure to HLT50 treatment during the pupal stage, with females accounting for only 56.38%. Our results demonstrate that short-term exposure to extreme temperatures has detrimental effects on the growth and reproduction of E. formosa. In field biocontrol against E. formosa, the release of E. formosa should be avoided as much as possible when the ambient temperature is higher than 35°C or lower than 0°C. During extreme temperature conditions, timely supplementation and release of E. formosa population, along with ventilation and cooling in greenhouse facilities during summer, are necessary for better pest control efficacy.

A tumor-targeting and ROS-responsive iron-based T1 magnetic resonance imaging contrast agent for highly specific tumor imaging.

T1 contrast agents (CAs) exhibit outstanding capacity in enhancing the magnetic resonance imaging (MRI) contrast between tumor tissues and normal tissues for generating bright images. However, the clinical application of representative gadolinium(III) chelate-based T1 CAs is limited due to their potential toxicity and low specificity for pathological tissues. To obtain MRI CAs with a combination of low toxicity and high tumor specificity, herein, we report a reactive oxygen species (ROS)-responsive T1 CA (GA-Fe(II)-PEG-FA), which was constructed by chelating Fe(II) with gallic acid (GA), and modified with tumor-targeted folic acid (FA). The resultant CA could accumulate in tumor tissues via the affinity between FA and their receptors on the tumor cell membrane. It realized the switch from Fe(II) to Fe(III), and further enhancing the longitudinal relaxation rate (r1) under the stimuli of ROS in the tumor microenvironment. The r1 of GA-Fe(II)-PEG-FA on a 0.5 T nuclear magnetic resonance analyzer increased to 2.20 mM-1 s-1 under ROS stimuli and was 5 times greater than the r1 (0.42 mM-1 s-1) before oxidation. The cell and in vivo experiments demonstrated that GA-Fe(II)-PEG-FA exhibited good biocompatibility and significant targeting specificity to tumor cells and tumor tissues. Furthermore, in vivo MRI studies demonstrated that the enhanced T1 contrast effect against tumors could be achieved after injecting the CA for 3 h, indicating that GA-Fe(II)-PEG-FA has the potential as an ideal tumor MRI CA to increase the contrast and improve the diagnostic precision.

Colorimetric assay of phosphate using a multicopper laccase-like nanozyme.

A new nanozyme (Cu-NADH) is reported composed of Cu-coordinated nicotinamide adenine dinucleotide (NADH) exhibiting laccase-like activity. The Cu-NADH nanozyme had higher heat tolerance and catalytic efficiency than natural laccase, and its catalytic activity can be enhanced by high concentration of Cl ions and it is intensely inhibited by phosphate. Therefore, a colorimetric method based on Cu-NADH and indigo carmine was successfully developed to detect phosphate in water. This method showed an excellent selectivity for phosphate, and it had a linear relationship in the phosphate concentration range 2-50 µM with a detection limit of 0.37 µM. We believe that this example of coordination between metal ions and biomolecules to mimic natural enzymes can inspire more effective and alternative strategies in nanozyme design and expand their use in sensing and determination.

Dietary taurine reduces retinal damage produced by photochemical stress via antioxidant and anti-apoptotic mechanisms in Sprague-Dawley rats.

Taurine has been shown to be tissue protective in many models of oxidant-induced injury. However, its protective role against retinal damage induced by photochemical stress is less well known. The purpose of the present study was to investigate whether dietary taurine reduced retinal photochemical damage in Sprague-Dawley rats and to further explore the underlying molecular mechanisms of this action. Twenty rats fed AIN-93 formulation and maintained in the dark for 48 h were used as controls (n 20). Another forty rats were randomly divided into two groups and then treated with (n 20) or without 4 % taurine (n 20) for 15 d respectively. After treatment, these two groups were exposed to fluorescent light (3000 +/- 200 lux and 25 degrees C), and the protective effects of dietary taurine were then evaluated. The present results showed that dietary taurine effectively prevented retinal photochemical damage as assessed by changes of morphology. Also, the supplementation caused an increase of taurine in the retina, a decrease of malondialdehyde (P < 0.01), and elevation of superoxide dismutase (P < 0.01) and glutathione peroxidase activities in the retina (P < 0.01). Moreover, dietary taurine inhibited activator protein-1 (AP-1) (c-fos/c-jun subunits) expression (P < 0.05), up regulated NF-kappaB (p65) expression (P < 0.05), and decreased caspase-1 expression (P < 0.05) so as to reduce the apoptosis of photoreceptors in the retina (P < 0.05). These results suggest that dietary taurine reduced retinal damage produced by photochemical stress via antioxidant and anti-AP-1-NF-kappaB-caspase-1 apoptotic mechanisms in rats.