Construct a Magnetic Pt/Ru Alloy Peroxidase Mimic As a Reusable and Cost-Effective "Signal-Off" Sensing Platform for Sensitive and Wide-Linear-Range Assay.

"Signal-off" nanozyme sensing platforms are usually employed to detect analytes (e.g., ascorbic acid (AA) and alkaline phosphatase (ALP)), which are mostly based on oxidase (OXD) nanozymes. However, their drawbacks, like dissolved oxygen-dependent catalysis capability, relatively low enzyme activity, limited amount, and kind, may not favor sensing platforms' optimization. Meanwhile, with the need for sustainable development, a reusable "signal-off" sensing platform is essential for cutting down the cost of the assay, but it is rarely developed in previous studies. Magnetic peroxidase (POD) nanozymes potentially make up the deficiencies and become reusable and better "signal-off" sensing platforms. As a proof of concept, we first construct Fe3O4@polydopamine-supported Pt/Ru alloy nanoparticles (IOP@Pt/Ru) without stabilizers. IOP@Pt/Ru shows high POD activity with Vmax of 83.24 × 10-8 M·s-1 for 3,3',5,5'-Tetramethylbenzidine (TMB) oxidation. Meanwhile, its oxidation rate for TMB is slower than the reduction of oxidized TMB by reducers, favorable for a more significant detection signal. On the other hand, IOP@Pt/Ru possesses great magnet-responsive capability, making itself be recycled and reused for at least 15-round catalysis. When applying IOP@Pt/Ru for AA (ALP) detection, it performs better detectable adaptability, with a linear range of 0.01-0.2 mM (0.1-100 U/L) and a limit of detection of 0.01 mM (0.05 U/L), superior to most of OXD nanozyme-based ALP sensing platform. Finally, IOP@Pt/Ru's reusable assay was demonstrated in real blood samples for ALP assay, which has never been explored in previous studies. Overall, this study develops a reusable "signal-off" nanozyme sensing platform with superior assay capabilities than traditional OXD nanozymes, paves a new way to optimize nanozyme-based "signal-off" sensing platforms, and provides an idea for constructing inexpensive and sustainable sensing platforms.

Development of Pd/In2O3 hybrid nanoclusters to optimize ethanol vapor sensing.

In this study, we successfully synthesize palladium-decorated indium trioxide (Pd/In2O3) hybrid nanoclusters (NCs) using an advanced dual-target cluster beam deposition (CBD) method, a significant stride in developing high-performance ethanol sensors. The prepared Pd/In2O3 hybrid NCs exhibit exceptional sensitivity, stability, and selectivity to low concentrations of ethanol vapor, with a maximum response value of 101.2 at an optimal operating temperature of 260 °C for 6 at% Pd loading. The dynamic response of the Pd/In2O3-based sensor shows an increase in response with increasing ethanol vapor concentrations within the range of 50 to 1000 ppm. The limit of detection is as low as 24 ppb. The sensor exhibits a high sensitivity of 28.24 ppm-1/2, with response and recovery times of 2.7 and 4.4 seconds, respectively, for 100 ppm ethanol vapor. Additionally, the sensor demonstrates excellent repeatability and stability, with only a minor decrease in response observed over 30 days and notable selectivity for ethanol compared to other common volatile organic compounds. The study highlights the potential of Pd/In2O3 NCs as promising materials for ethanol gas sensors, leveraging the unique capabilities of CBD for controlled synthesis and the catalytic properties of Pd for enhanced gas-sensing performance.

Progress of stimulus responsive nanosystems for targeting treatment of bacterial infectious diseases.

In recent decades, due to insufficient concentration at the lesion site, low bioavailability and increasingly serious resistance, antibiotics have become less and less dominant in the treatment of bacterial infectious diseases. It promotes the development of efficient drug delivery systems, and is expected to achieve high absorption, targeted drug release and satisfactory therapy effects. A variety of endogenous stimulation-responsive nanosystems have been constructed by using special infection microenvironments (pH, enzymes, temperature, etc.). In this review, we firstly provide an extensive review of the current research progress in antibiotic treatment dilemmas and drug delivery systems. Then, the mechanism of microenvironment characteristics of bacterial infected lesions was elucidated to provide a strong theoretical basis for bacteria-targeting nanosystems design. In particular, the discussion focuses on the design principles of single-stimulus and dual-stimulus responsive nanosystems, as well as the use of endogenous stimulus-responsive nanosystems to deliver antimicrobial agents to target locations for combating bacterial infectious diseases. Finally, the challenges and prospects of endogenous stimulus-responsive nanosystems were summarized.

Math attitudes and math anxiety predict students' perception of teacher support in primary school, but not vice versa.

BACKGROUND: Both teacher support and math attitudes have been identified as associated with math anxiety in primary school children. However, little is known about how they are interrelated longitudinally. AIMS: The study was designed to examine the associations among perceived teacher support, math attitudes, and math anxiety in Chinese primary school students. SAMPLE: The sample included 1802 students (56.16% boys) initially in the third and fourth grades in two public schools in China. METHODS: A three-year cross-lagged panel design was conducted to examine the associations among perceived teacher support, math attitudes, and math anxiety. Moreover, a multigroup analysis was used to examine whether the associations varied by gender. RESULTS: There were reciprocal associations over time between math attitudes and math anxiety. Meanwhile, both math attitudes and math anxiety significantly predicted perceived teacher support one year later, but not vice versa. Further, the association between T1 math anxiety and T3 perceived teacher support was mediated by T2 math attitudes; the association between T1 math attitudes and T3 perceived teacher support, on the other hand, was mediated by T2 math anxiety. Moreover, there were no significant gender differences in these associations. CONCLUSIONS: Math anxiety and math attitudes objectively affected each other, and both of them significantly predicted later perceived teacher support, but not vice versa. This study demonstrates that children are not merely passive recipients of environmental influences and offers theoretical guidance for intervention practices that aim to reduce the risk of math anxiety.

Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms.

The resistance and immune escape of methicillin-resistant Staphylococcus aureus (MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO- and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating icdA and icaA. It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO- penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.

Core-shell nanosystems designed for effective oral delivery of polypeptide drugs.

The stomach acid degradation, mucus clearance and intestinal epithelial impermeability severely limit the oral delivery of polypeptide drugs. To simultaneously address the three major barriers, novel self-assembled core-shell nanosystems (CA-NPs) were designed. The fabricated shell of citric acid cross-linked carboxymethyl cellulose (CA-CMC) wrapped on core nanoparticles (HA-NPs) maintained the integrity of CA-NPs in the stomach. When CA-NPs passed through the stomach, the CA-CMC shell was gradually degraded to release the core HA-NPs in the intestine. HA-NPs with numerous hydrophilic groups and mannose side chains rapidly penetrated through the mucus layer and efficiently transcellular transported via the glucose transporter (GLUT)-mediated and paracellular transport through reversible opening of tight junctions (TJs) by CA-CMC. The oral bioavailability and therapeutic effects of CA-NPs-loaded polypeptide colistin against Escherichia coli (E. coli) bacteremia in mice were significantly increased compared with the native colistin, respectively. Good safety was observed following oral daily delivery for 14 consecutive days. Thus, CA-NPs may offer a promising strategy for the oral delivery of polypeptide drugs.

Ultra-compact polarization-independent 3 dB power splitter in silicon.

We experimentally demonstrate an ultra-compact polarization-independent 3 dB power splitter on the silicon-on-insulator platform. Subwavelength structure engineering is employed to balance the coupling coefficients of TE and TM polarizations as well as a footprint reduction. The device possesses ultra-compact (1.2µm×2.62µm) and polarization-independent features with an operating bandwidth over 50 nm (from 1540 to 1590 nm).

Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights.

Chemotherapy can significantly prolong the survival of patients with breast cancer; Nevertheless, the majority of patients receiving chemotherapy such as doxorubicin may have cognitive deficits that manifest as impairments in learning, reasoning, attention, and memory. The phenomenon of chemotherapy-induced cognitive decline is termed as chemotherapy-related cognitive impairment (CRCI) or chemo-brain. Doxorubicin (DOX), a commonly used drug in adjuvant chemotherapy for patients with breast cancer, has been reported to induce chemo-brain through a variety of mechanisms including DNA damage, oxidative stress, inflammation, dysregulation of apoptosis and autophagy, changes in neurotransmitter levels, mitochondrial dysfunction, glial cell interactions, neurogenesis inhibition, and epigenetic factors. These mechanisms do not operate independently but are inter-related, coordinately contributing to the development of chemo-brain. Here we review the relationships of these mechanisms and pathways in attempt to provide mechanistic insights into the doxorubicin-induced cognitive impairment.

Clinical study on the effect of intramedullary fixation and extramedullary fixation on unstable intertrochanteric fractures.

BACKGROUND: Intertrochanteric fracture of femur is a common fracture in the elderly, and the number of intramedullary nails used to manage intertrochanteric fractures has steadily increased, but the evidence for the clinical efficacy of this practice is lacking. The present study retrospectively compared the clinical outcomes and imaging features of patients with unstable intertrochanteric hip fractures treated with traditional extramedullary hip screws (AO/OTA 31-A2) and patients with the same injury treated with newer intramedullary screws. METHODS: Lower limb measurement (LLM) for the main results of the hip-specific tools, functional independence measure (FIM), and "timed up and go" (TUG) to test the scale and timing of the 2-minute walk test were used as secondary tools for clinical outcomes. Other detailed radiological parameters to evaluate the fracture movement, such as heterotopic ossification, and implant failure, were also recorded. RESULTS: There were no significant differences between the intramedullary and extramedullary treatment groups in terms of the measures acquired by the primary or secondary clinical outcome tools (P>0.05), but the radiographic parameters favored the intramedullary treatment group as it showed reduced femoral neck shortening. CONCLUSIONS: Although treatment with intramedullary nailing resulted in better radiographic assessment results, this did not translate into better functional recovery outcomes.

Composite inclusion complexes containing hyaluronic acid/chitosan nanosystems for dual responsive enrofloxacin release.

In order to overcome treatment difficulty of S. aureus infections, a pH/hyaluronidase dual responsive enrofloxacin-cyclodextrin (ß-CD) inclusion complexes (IC) containing hyaluronic acid/chitosan (HA/CS) self-assemble composite nanosystems covered by poloxamer 188 (F68) was firstly explored for targeted "on-demand" delivery. The FTIR, DSC and PXRD showed that enrofloxacin was embedded into IC and then distributed into F68 coating nanogels formulated by electrostatic interaction between CS and HA. The optimal nanosystems of 118.8 ± 30.7 nm showed excellent stability and responsive release in the acid medium, hyaluronidase containing medium, and LB broth medium where S. aureus present. The nanosystems displayed strong surface adsorption on S. aureus and enhanced activity against S. aureus. It had stronger sustained release than the polymeric nanoparticles formulated by entrapping of IC into F68 and the single HA/CS nanogels. This study provides a promising multi-functionalized nanosystems to overcome the treatment challenge of S. aureus and other bacterial infections.

Absorption, distribution, metabolism, and excretion of nanocarriers in vivo and their influences.

As one of the most promising and effective delivery systems for targeted controlled-release drugs, nanocarriers (NCs) have been widely studied. Although the development of nanoparticle preparations is very prosperous, the safety and effectiveness of NCs are not guaranteed and cannot be precisely controlled due to the unclear processes of absorption, distribution, metabolism, and excretion (ADME), as well as the drug release mechanism of NCs in the body. Thus, the approval of NCs for clinical use is extremely rare. This paper reviews the research progress and challenges of using NCs in vivo based on a review of several hundred closely related publications. First, the ADME of NCs under different administration routes is summarized; second, the influences of the physical, chemical, and biosensitive properties, as well as targeted modifications of NCs on their disposal process, are systematically analyzed; third, the tracer technology related to the in vivo study of NCs is elaborated; and finally, the challenges and perspectives of nanoparticle research in vivo are introduced. This review may help readers to understand the current research progress and challenges of nanoparticles in vivo, as well as of tracing technology in nanoparticle research, to help researchers to design safer and more efficient NCs. Furthermore, this review may aid researchers in choosing or exploring more suitable tracing technologies to further advance the development of nanotechnology.

The dose regimen formulation of tilmicosin against Lawsonia intracellularis in pigs by pharmacokinetic-pharmacodynamic (PK-PD) model.

In this study, the rational dose regimens of tilmicosin against Lawsonia intracellularis (L. intracellularis) were studied using pharmacokinetic-pharmacodynamic (PK-PD) model approach to provide a maximal efficacy. The healthy and infected pigs were orally administrated the tilmicosin premix at a single dose of 10 mg/kg, and then the plasma and ileum content were collected at different time points. The time to peak (Tmax), the peak concentration (Cmax), the area under concentration time curve (AUC0-24h), the apparent volume of distribution by bioavailability (V/F), the body clearance rate by bioavailability (CL/F) and the mean residence time (MRT) of tilmicosin premix for plasma were 2.00 h, 1.08 ± 0.04 µg/mL, 9.61 ± 1.47 µg h/mL, 34.43 ± 1.02 L/kg, 0.71 ± 0.03 L/h/kg and 15.03 ± 0.04 h in healthy pigs, and 2.00 h, 0.99 ± 0.03 µg/mL, 9.30 ± 1.43 µg h/mL, 58.59 ± 1.81 L/kg, 0.44 ± 0.02 L/h/kg and 15.75 ± 0.03 h in infected pigs, respectively. The Tmax, Cmax, AUC0-24h, V/F, CL/F and MRT of tilmicosin premix for ileum content were 2.00 h, 3.78 ± 0.03 µg/mL, 20.41 ± 1.64 µg h/mL, 11.29 ± 0.97 L/kg, 0.44 ± 0.02 L/h/kg and 11.29 ± 0.09 h in healthy pigs, and 2.00 h, 3.41 ± 0.06 µg/mL, 22.65 ± 1.32 µg h/mL, 8.16 ± 1.51 L/kg, 0.41 ± 0.01 L/h/kg and 11.44 ± 0.05 h in infected pigs, respectively. Based on the intracellular minimum inhibitory concentration (MIC) of L. intracellularis isolate was 2 µg/mL, the results of the mutant prevention concentration (MPC), the post-antibiotic effect (PAE) and time-killing curves all showed strong concentration-dependenttendencies. Integrating the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation to obtain the ileum content AUC0-24h/MIC values of 6.87, 26.80, and 36.02 h to achieve the bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria, respectively. Based on these results, a dosage regimen of daily 14.39 mg/kg for 3 d could be sufficient in the treatment of L. intracellularis. This study will provide a guidance of dosage regimen formulation for drug against animal intracellular bacterial infections.

Intracellular delivery, accumulation, and discrepancy in antibacterial activity of four enrofloxacin-loaded fatty acid solid lipid nanoparticles.

Four fatty acid-solid lipid nanoparticles (SLNs) were formulated and evaluated for intracellular delivery, accumulation, as well as discrepancy in antimicrobial efficacy of their loaded enrofloxacin by using RAW 264.7 cells. The delivery efficacy of enrofloxacin into the macrophages by docosanoic acid SLNs (DAS), octadecanoic acid SLNs (OAS), hexadecanoic acid SLNs (HAS), and tetradecanoic acid SLNs (TAS) were 26.1-29.0, 9.3-10.3, 4.7-5.3 and 4.5-5.0 folds, respectively, compared to free drug when co-incubation for 0.25-4 h. The longer fatty acid prepared nanoparticles loaded enrofloxacin eliminated more slowly and accumulated in the cells for a longer time.The confocal microscopy also demonstrated that higher amount of fatty acid SLNs entered the cells with stronger accumulation performance and less amount SLNs absorbed on the cytomembrane as the carbon chain of fatty acids increased. The bactericidal activity of the four fatty acid SLNs against intracellular Salmonella CVCC541 significantly enhanced compared to the free enrofloxacin. These results revealed that fatty acid SLNs, especially docosanoic acid nanoparticles, might be effective nanocarriers to ferry enrofloxacin or other lipid soluble drugs into cells for intracellular bacterial infection treatment.