Ingenious Synergy of a Pathology-Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis.

Based on the pathological characteristics of rheumatoid arthritis, including the overproduction of reactive oxygen species (ROS), inflammatory responses, and osteoclast differentiation, a biomimetic multifunctional nanomedicine (M-M@I) is designed. Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M-M@I nanoparticles are taken up well by lipopolysaccharide-induced RAW 264.7 macrophages or bone marrow-derived macrophages (BMDMs). In vitro, the M-M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast-related enzymes. They also reduce the polarization of macrophages to a pro-inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen-induced arthritis, the M-M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology-specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.

Infant sustained attention differs by context and social content in the first 2 years of life.

Sustained attention (SA) is an endogenous form of attention that emerges in infancy and reflects cognitive engagement and processing. SA is critical for learning and has been measured using different methods during screen-based and interactive contexts involving social and nonsocial stimuli. How SA differs by measurement method, context, and stimuli across development in infancy is not fully understood. This 2-year longitudinal study examines attention using one measure of overall looking behavior and three measures of SA-mean look duration, percent time in heart rate-defined SA, and heart rate change during SA-in N = 53 infants from 1 to 24 months across four unique task conditions: social videos, nonsocial videos, social interactions (face-to-face play), and nonsocial interactions (toy engagement). Results suggest that developmental changes in attention differ by measurement method, task context (screen or interaction), and task stimulus (social or nonsocial). During social interactions, overall looking and look durations declined after age 3-4 months, whereas heart rate-defined attention measures remained stable. All SA measures were greater for videos than for live interaction conditions throughout the first 6 months, but SA to social and nonsocial stimuli within each task context were equivalent. In the second year of life, SA measured with look durations was greater for social videos compared to other conditions, heart rate-defined SA was greater for social videos compared to nonsocial interactions, and heart rate change during SA was similar across conditions. Together, these results suggest that different measures of attention to social and nonsocial stimuli may reflect unique developmental processes and are important to compare and consider together, particularly when using infant attention as a marker of typical or atypical development. RESEARCH HIGHLIGHTS: Attention measure, context, and social content uniquely differentiate developmental trajectories of attention in the first 2 years of life. Overall looking to caregivers during dyadic social interactions declines significantly from 4 to 6 months of age while sustained attention (SA) to caregivers remains stable. Heart rate-defined SA generally differentiates stimulus context where infants show greater SA while watching videos than while engaging with toys.

Biological Transformation of AgI on MOF-on-MOF-Derived Heterostructures: Toward Polarity-Switchable Photoelectrochemical Biosensors for Neuron-Specific Enolase.

The sensitive detection of neuron-specific enolase (NSE) as a biomarker for lung cancer at an early stage is critical but has long been a challenge. The emergence of polarity-switchable photoelectrochemical (PEC) bioanalysis has opened up new avenues for developing highly sensitive NSE sensors. In this study, we present such a biosensor depending on the bioinduced AgI transition on MOF-on-MOF-derived semiconductor heterojunctions. Specifically, treatment of ZnO@In2O3@AgI by bioproduced H2S can in situ generate the ZnO@In2O3@In2S3@Ag2S heterojunction, with the photocurrent switching from the cathodic to anodic one due to the changes in the carrier transfer pathway. Linking an NSE-targeted sandwich immunorecognition with labeled alkaline phosphatase (ALP) catalyzed generation of H2S, such a phenomenon was correlated to NSE concentration with good performance in terms of selectivity and sensitivity and a low detection limit of 0.58 pg/mL. This study offered a new perspective on the use of MOF-on-MOF-derived heterostructures for advanced polarity-switchable PEC bioanalysis.

Functional molecule-mediated assembled copper nanozymes for diabetic wound healing.

BACKGROUND: The complex hyperglycemic, hypoxic, and reactive oxygen species microenvironment of diabetic wound leads to vascular defects and bacterial growth and current treatment options are relatively limited by their poor efficacy. RESULTS: Herein, a functional molecule-mediated copper ions co-assembled strategy was constructed for collaborative treatment of diabetic wounds. Firstly, a functional small molecule 2,5-dimercaptoterephthalic acid (DCA) which has symmetrical carboxyl and sulfhydryl structure, was selected for the first time to assisted co-assembly of copper ions to produce multifunctional nanozymes (Cu-DCA NZs). Secondly, the Cu-DCA NZs have excellent multicatalytic activity, and photothermal response under 808 nm irradiation. In vitro and in vivo experiments showed that it not only could efficiently inhibit bacterial growth though photothermal therapy, but also could catalyze the conversion of intracellular hydrogen peroxide to oxygen which relieves wound hypoxia and improving inflammatory accumulation. More importantly, the slow release of copper ions could accelerate cellular proliferation, migration and angiogenesis, synergistically promote the healing of diabetic wound furtherly. CONCLUSIONS: The above results indicate that this multifunctional nanozymes Cu-DCA NZs may be a potential nanotherapeutic strategy for diabetic wound healing.

Evaluating Head Models for Cortical Source Localization of the Face-Sensitive N290 Component in Infants.

Accurate cortical source localization of event-related potentials (ERPs) requires using realistic head models constructed from the participant's structural magnetic resonance imaging (MRI). A challenge in developmental studies is the limited accessibility of participant-specific MRIs. The present study compared source localization of infants' N290 ERP activities estimated using participant-specific head models with a series of substitute head models. The N290 responses to faces relative to toys were measured in 36 infants aged at 4.5, 7.5, 9, and 12 months. The substitutes were individual-based head models constructed from age-matched MRIs with closely matched ("close") or different ("far") head measures with the participants, age-appropriate average template, and age-inappropriate average templates. The greater source responses to faces than toys at the middle fusiform gyrus (mFG) estimated using participant-specific head models were preserved in individual-based head models, but not average templates. The "close" head models yielded the best fit with the participant-specific head models in source activities at the mFG and across face-processing-related regions of interest (ROIs). The age-appropriate average template showed mixed results, not supporting the stimulus effect but showed topographical distributions across the ROIs like the participant-specific head models. The "close" head models are the most optimal substitute for participant-specific MRIs.

Do you see what I mean?: Using mobile eye tracking to capture parent-child dynamics in the context of anxiety risk.

Temperamental behavioral inhibition (BI) is a robust endophenotype for anxiety characterized by increased sensitivity to novelty. Controlling parenting can reinforce children's wariness by rewarding signs of distress. Fine-grained, dynamic measures are needed to better understand both how children perceive their parent's behaviors and the mechanisms supporting evident relations between parenting and socioemotional functioning. The current study examined dyadic attractor patterns (average mean durations) with state space grids, using children's attention patterns (captured via mobile eye tracking) and parental behavior (positive reinforcement, teaching, directives, intrusion), as functions of child BI and parent anxiety. Forty 5- to 7-year-old children and their primary caregivers completed a set of challenging puzzles, during which the child wore a head-mounted eye tracker. Child BI was positively correlated with proportion of parent's time spent teaching. Child age was negatively related, and parent anxiety level was positively related, to parent-focused/controlling parenting attractor strength. There was a significant interaction between parent anxiety level and child age predicting parent-focused/controlling parenting attractor strength. This study is a first step to examining the co-occurrence of parenting behavior and child attention in the context of child BI and parental anxiety levels.

Dimeric Acylphloroglucinol Derivatives with New Skeletons from Leptospermum scoparium.

Leptosparones A-F (1-6), six new dimeric acylphloroglucinol derivatives with unprecedented skeletons, were isolated from Leptospermum scoparium. Compounds 1-3 and 5-6 are phenylpropanoyl-phloroglucinol dimers, while 4 is a phenylpropanoylphloroglucinol-isovalerylphloroglucinol hybrid. Structurally, these compounds represent the first examples of dimeric phloroglucinols with unprecedented C(7')-C(8) linkage between the phloroglucinol core and the acyl side chain. Their structures were elucidated by comprehensive analyses of spectroscopic data, single crystal X-ray diffraction and chemical calculations. In addition, all compounds showed inhibitory effects against α-glucosidase with IC50 values ranging from 39.5 to 186.8 µM.

A systematic review and meta-analysis of serum cholesterol and triglyceride levels in patients with Parkinson's disease.

OBJECTIVES: Numerous studies have reported that lipid metabolic abnormalities may play an important role in the development of Parkinson's disease (PD), with mixed results. This meta-analysis aims to systematically assess the relationship between serum cholesterol or triglyceride and the PD risk and to further determine the role of dyslipidemia in potential predictive value. METHODS: This research systematically consulted and screened observational studies to evaluate the association of serum lipids with the risk of PD as of April 01, 2020 based on the inclusion and exclusion criteria. Two researchers screened and extracted the data independently. Then this article summarized the characteristics of all clinical studies and collected the corresponding data to perform pooled and sensitivity analyses. The meta-analysis was performed by using the RevMan 5.3 software after data extraction, quality assessment and analysis of publication bias. RESULTS: Twenty-one related studies (13 case-control and 8 cohort studies) were selected with a total of 980,180 subjects, including 11,188 PD patients. Meta-analysis showed that higher levels of serum triglyceride (S-TG) [standard mean different (SMD) = - 0.26 (95% confidence interval (CI): - 0.39 to - 0.13, p<0.00001), relative risk (RR) = 0.67 (95% CI: 0.60 to 0.75, p<0.00001)] could be considered as protective factors for the pathogenesis of PD. However, there was no significant association between serum high density lipoprotein cholesterol (S-HDL) and the risk of PD. Meanwhile, serum low density lipoprotein cholesterol (S-LDL) [SMD = -0.26 (95% CI: - 0.43 to - 0.07, p = 0.006), RR = 0.76 (95% CI: 0.59 to 0.97, p = 0.03)] and serum total cholesterol (S-TC) levels [SMD = -0.21 (95% CI: - 0.33 to - 0.10, p = 0.0002), RR = 0.86 (95% CI: 0.77 to 0.97, p = 0.01)] were negatively associated with PD risk. CONCLUSIONS: This systematic review suggests that elevated serum levels of TG, LDL and TC may be protective factors for the pathogenesis of PD. Further longitudinal and well-designed prospective studies with a large sample size are needed to confirm the findings in this meta-analysis.

Temperament moderates developmental changes in vigilance to emotional faces in infants: Evidence from an eye-tracking study.

Affect-biased attention reflects the prioritization of attention to stimuli that individuals deem to be motivationally and/or affectively salient. Normative affect-biased attention is early-emerging, providing an experience-expectant function for socioemotional development. Evidence is limited regarding how reactive and regulatory aspects of temperament may shape maturational changes in affect-biased attention that operate at the earliest stages of information processing. This study implemented a novel eye-tracking paradigm designed to capture attention vigilance in infants. We assessed temperamental negative affect (NA) and attention control (AC) using laboratory observations and parent-reports, respectively. Among infants (N = 161 in the final analysis) aged 4 to 24 months (Mean = 12.05, SD = 5.46; 86 males), there was a significant age effect on fixation latency to emotional versus neutral faces only in infants characterized with high NA and high AC. Specifically, in infants with these temperament traits, older infants showed shorter latency (i.e., greater vigilance) toward neutral faces, which are potentially novel and unfamiliar to infants. The age effect on vigilance toward emotional faces was not significant. The findings support the argument that the development of affect-biased attention is associated with multiple temperament processes that potentially interact over time.

Stationary and ambulatory attention patterns are differentially associated with early temperamental risk for socioemotional problems: Preliminary evidence from a multimodal eye-tracking investigation.

Behavioral Inhibition (BI) is a temperament type that predicts social withdrawal in childhood and anxiety disorders later in life. However, not all BI children develop anxiety. Attention bias (AB) may enhance the vulnerability for anxiety in BI children, and interfere with their development of effective emotion regulation. In order to fully probe attention patterns, we used traditional measures of reaction time (RT), stationary eye-tracking, and recently emerging mobile eye-tracking measures of attention in a sample of 5- to 7-year-olds characterized as BI (N = 23) or non-BI (N = 58) using parent reports. There were no BI-related differences in RT or stationary eye-tracking indices of AB in a dot-probe task. However, findings in a subsample from whom eye-tracking data were collected during a live social interaction indicated that BI children (N = 12) directed fewer gaze shifts to the stranger than non-BI children (N = 25). Moreover, the frequency of gazes toward the stranger was positively associated with stationary AB only in BI, but not in non-BI, children. Hence, BI was characterized by a consistent pattern of attention across stationary and ambulatory measures. We demonstrate the utility of mobile eye-tracking as an effective tool to extend the assessment of attention and regulation to social interactive contexts.

Case report: Shingles-associated probable Bickerstaff brainstem encephalitis with IgM anti-sulfatide positivity.

Background: Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity. Case presentation: We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is the most appropriate diagnosis. Conclusions: We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles.

Infant Social Attention Associated with Elevated Likelihood for Autism Spectrum Disorder: A Multi-Method Comparison.

PURPOSE: The study aimed to compare eye tracking (ET) and manual coding (MC) measures of attention to social and nonsocial information in infants with elevated familial likelihood (EL) of autism spectrum disorder (ASD) and low likelihood of ASD (LL). ET provides a temporally and spatially sensitive tool for measuring gaze allocation. Existing evidence suggests that ET is a promising tool for detecting distinct social attention patterns that may serve as a biomarker for ASD. However, ET is prone to data loss, especially in young EL infants. METHODS: To increase evidence for ET as a viable tool for capturing atypical social attention in EL infants, the current prospective, longitudinal study obtained ET and MC measures of social and nonsocial attention in 25 EL and 47 LL infants at several time points between 3 and 24 months of age. RESULTS: ET data was obtained with a satisfactory success rate of 95.83%, albeit with a higher degree of data loss compared to MC. Infant age and ASD likelihood status did not impact the extent of ET or MC data loss. There was a significant positive association between the ET and MC measures of attention, and separate analyses of attention using ET and AC measures yielded comparable findings. These analyses indicated group differences (EL vs. LL) in age-related change in attention to social vs. nonsocial information. CONCLUSION: Together, the findings support infant ET as a promising approach for identifying very early markers associated with ASD likelihood.

Fatty acid degradation driven by heat during ripening contributes to the formation of the "Keemun aroma".

Ripening refers to the process of chemical change during the refinement of Keemun black tea (KBT) and is crucial in the formation of Keemun Congou black tea's quality. In this study, the aroma composition of KBT during the ripening was analyzed. Sensomics indicated that ripening strengthened the coconut and fatty aroma of KBT and contributed to the decrease of green aroma substances, resulting in a shift of the overall aroma type of KBT to an integrated aroma profile, which was consistent with sensory evaluation. Changes in fatty acid content and the results of in vitro addition simulation tests confirmed that heat causes highly degradation of fatty acids into fatty aroma volatiles, which is a key driver of the formation of "Keemun aroma" quality. This study revealed the mechanism behind the formation of KBT's integrated "Keemun aroma" quality and the mode of thermal degradation of major fatty acids.

Young Children of Mothers with a History of Depression Show Attention Bias to Sad Faces: An Eye-tracking Study.

Maternal depression is a predictor of the emergence of depression in the offspring. Attention bias (AB) to negative emotional stimuli in children may serve as a risk factor for children of depressed parents. The present study aimed to examine the effect of maternal major depressive disorder (MDD) history on AB to emotional faces in children at age four, before the age of onset for full-blown psychiatric symptoms. The study also compared AB patterns between mothers and their offspring. Fifty-eight mothers and their four-year-old children participated in this study, of which 27 high-risk (HR) children had mothers with MDD during their children's lifetime. Attention to emotional faces was measured in both children and their mothers using an eye-tracking visual search task. HR children exhibited faster detection and longer dwell time toward the sad than happy target faces. The low-risk (LR) children also displayed a sad bias but to a lesser degree. Children across both groups showed AB towards angry target faces, likely reflecting a normative AB pattern. Our findings indicate that AB to sad faces may serve as an early marker of depression risk. However, we provided limited support for the mother-child association of AB. Future research is needed to examine the longitudinal intergenerational transmission of AB related to depression and possible mechanisms underlying the emergence of AB in offspring of depressed parents.

Now it's your turn!: Eye blink rate in a Jenga task modulated by interaction of task wait times, effortful control, and internalizing behaviors.

Dopamine is a versatile neurotransmitter with implications in many domains, including anxiety and effortful control. Where high levels of effortful control are often regarded as adaptive, other work suggests that high levels of effortful control may be a risk factor for anxiety. Dopamine signaling may be key in understanding these relations. Eye blink rate is a non-invasive proxy metric of midbrain dopamine activity. However, much work with eye blink rate has been constrained to screen-based tasks which lack in ecological validity. We tested whether changes in eye blink rate during a naturalistic effortful control task differ as a function of parent-reported effortful control and internalizing behaviors. Children played a Jenga-like game with an experimenter, but for each trial the experimenter took an increasingly long time to take their turn. Blinks-per-second were computed during each wait period. Multilevel modeling examined the relation between duration of wait period, effortful control, and internalizing behaviors on eye blink rate. We found a significant 3-way interaction between effortful control, internalizing behaviors, and duration of the wait period. Probing this interaction revealed that for children with low reported internalizing behaviors (-1 SD) and high reported effortful control (+1 SD), eye blink rate significantly decreased as they waited longer to take their turn. These findings index task-related changes in midbrain dopamine activity in relation to naturalistic task demands, and that these changes may vary as a function of individual differences in effortful control and internalizing behaviors. We discuss possible top-down mechanisms that may underlie these differences.

M2 macrophage-derived exosome-functionalized topological scaffolds regulate the foreign body response and the coupling of angio/osteoclasto/osteogenesis.

Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold-mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold-mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. STATEMENT OF SIGNIFICANCE: How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage-derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation.

A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Infant embodied attention in context: Feasibility of home-based head-mounted eye tracking in early infancy.

Social communication emerges from dynamic, embodied social interactions during which infants coordinate attention to caregivers and objects. Yet many studies of infant attention are constrained to a laboratory setting, neglecting how attention is nested within social contexts where caregivers dynamically scaffold infant behavior in real time. This study evaluates the feasibility and acceptability of the novel use of head-mounted eye tracking (HMET) in the home with N = 40 infants aged 4 and 8 months who are typically developing and at an elevated genetic liability for autism spectrum disorder (ASD). Results suggest that HMET with young infants with limited independent motor abilities and at an elevated likelihood for atypical development is highly feasible and deemed acceptable by caregivers. Feasibility and acceptability did not differ by age or ASD likelihood. Data quality was also acceptable, albeit with younger infants showing slightly lower accuracy, allowing for preliminary analysis of developmental trends in infant gaze behavior. This study provides new evidence for the feasibility of using in-home HMET with young infants during a critical developmental period when more complex interactions with the environment and social partners are emerging. Future research can apply this technology to illuminate atypical developmental trajectories of embodied social attention in infancy.

Chopped fibers and nano-hydroxyapatite enhanced silk fibroin porous hybrid scaffolds for bone augmentation.

Chopped fiber (CF)- and nano-hydroxyapatite (n-HA)-enhanced silk fibroin (SF) porous hybrid scaffolds (SHCF) were prepared by freeze-drying for bone augmentation. Compared with pristine SF scaffolds, the incorporation of CF and n-HA can significantly enhance the mechanical properties of the composite scaffold. The results of cell experiments and mouse subcutaneous implantation indicated that the SHCF could alleviate foreign body reactions (FBR) led by macrophages and neutrophils, promote the polarization of RAW264.7 cells to anti-inflammatory M2 macrophages, and inhibit the secretion of pro-inflammatory cytokine TNF-α. A rat femoral defect repair model and bulk-RNA-seq analysis indicated that the CF- and n-HA-enhanced SHCF promoted the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by the upregulation of Capns1 expression and regulated the calcium signaling pathway to mediate osteogenesis-related cell behavior, subsequently promoting bone regeneration.

Copper-rich multifunctional Prussian blue nanozymes for infected wound healing.

The healing process of infected wounds was limited by bacterial infection, excessive reactive oxygen species (ROS) accumulation, and tissue hypoxia. In order to alleviate the above situations, herein, a copper-rich multifunctional ultra-small Prussian blue nanozymes (HPP@Cu NZs) was constructed for infected wound synergistic treatment. Firstly, hyaluronic acid was modified by branched polyethyleneimine which could form a complex with copper ions, to construct copper-rich Prussian blue nanozymes. Secondly, the HPP@Cu NZs have a uniform ultra-small nano size and excellent photothermal response performance, exhibition of multifunctional enzymatic activity and anti-inflammatory properties. Finally, the slow release of copper ions in the HPP@Cu NZs could effectively promote the formation of new blood vessels, thus giving it multifunctional properties. In vitro and in vivo experiments showed that it not only could effectively inhibit and kill bacteria under 808 nm near-infrared laser but also could remove excessive ROS, regulate oxygen levels, and anti-inflammation. More importantly, the release of copper ions could synergistically promote the healing of infected wounds as well as good biocompatibility. Overall, our studies provide a multifunctional strategy for infected wounds with synergistic treatment based on carrier construction.