Insights into spinal muscular atrophy from molecular biomarkers.

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

Poly(Lysine)-Derived Carbon Quantum Dots Conquer Enterococcus faecalis Biofilm-Induced Persistent Endodontic Infections.

Introduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed. Methods: Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms. Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo. Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs.

Predicting fracture risk for elderly osteoporosis patients by hybrid machine learning model.

Background and Objective: Osteoporotic fractures significantly impact individuals's quality of life and exert substantial pressure on the social pension system. This study aims to develop prediction models for osteoporotic fracture and uncover potential risk factors based on Electronic Health Records (EHR). Methods: Data of patients with osteoporosis were extracted from the EHR of Xinhua Hospital (July 2012-October 2017). Demographic and clinical features were used to develop prediction models based on 12 independent machine learning (ML) algorithms and 3 hybrid ML models. To facilitate a nuanced interpretation of the results, a comprehensive importance score was conceived, incorporating various perspectives to effectively discern and mine critical features from the data. Results: A total of 8530 patients with osteoporosis were included for analysis, of which 1090 cases (12.8%) were fracture patients. The hybrid model that synergistically combines the Support Vector Machine (SVM) and XGBoost algorithms demonstrated the best predictive performance in terms of accuracy and precision (above 90%) among all benchmark models. Blood Calcium, Alkaline phosphatase (ALP), C-reactive Protein (CRP), Apolipoprotein A/B ratio and High-density lipoprotein cholesterol (HDL-C) were statistically found to be associated with osteoporotic fracture. Conclusions: The hybrid machine learning model can be a reliable tool for predicting the risk of fracture in patients with osteoporosis. It is expected to assist clinicians in identifying high-risk fracture patients and implementing early interventions.

Facile Bond Exchanging Strategy for Engineering Wet Adhesion and Antioxidant/Antibacterial Thin Layer over a Dynamic Hydrogel via the Carbon Dots Derived from Tannic Acid/ε-Polylysine.

Adhesive hydrogels, playing an essential role in stretchable electronics, soft robotics, tissue engineering, and so forth, upon functioning often need to adhere to various substrates in wet conditions and simultaneously exhibit antibacterial/antioxidant properties while possessing the intrinsic stretchability and elasticity of the hydrogel network intact. Therefore, simple approaches to conveniently access adhesive hydrogels with multifunctional surfaces are being pursued. Herein, a facile strategy has been proposed to construct multifunctional adhesive hydrogels via surface engineering of a multifunctional carbon dot (CD)-decorated polymeric thin layer by dynamic bond exchange. By this strategy, a double cross-linked network hydrogel of polyacrylamide (PAM) and oxidized dextran (ODA) was engineered with a unique dense layer over the Schiff base hydrogel matrix by aqueous solution immersion of PA-120, versatile CDs derived from tannic acid (TA) and ε-polylysine (PL). Without any additional agents, the PA-120 CDs with residual polyphenolic/catechol and amine moieties were incorporated into the surface structure of the hydrogel network by the combined action of the Schiff base and hydrogen bonds to form a dense surface layer that can exhibit high wet adhesive performance via the amine-polyphenol/catechol pair. The armor-like dense architecture also endowed hydrogels with considerably enhanced tensile/compression properties and excellent antioxidant/antibacterial abilities. Besides, the single-sided modified Janus hydrogel and completely surface-modified hydrogel can be flexibly developed through this approach. This strategy will provide new insights into the preparation and application of surface-modified hydrogels featuring multiple functions and tunable interfacial properties.

Enhancing effect of cobalt phthalocyanine dispersion on electrocatalytic reduction of CO2 towards methanol.

This paper focuses on enhancing the performance of electrocatalytic CO2 reduction reaction (CO2RR) by improving the dispersion of cobalt phthalocyanine (CoPc), especially for the methanol formation with multi-walled carbon nanotubes (CNTs) as a support. The promising CNTs-supported CoPc hybrid was prepared based on ball milling technique, and the surface morphology was characterized by means of those methods such as scanning electron microscopy (SEM), Fourier transform infrared spectrometer (FT-IR) and X-ray photoelectron spectra (XPS). Then, the synergistic effect of CNTs and ball milling on CO2RR performance was analyzed by those methods of cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS), gas chromatography (GC), and proton nuclear magnetic resonance spectroscopy (1HNMR). Subsequently, the reduction mechanism of CO2 on ball-milled CoPc/CNTs was revealed based on the DFT calculations. The results showed that the electrocatalyst CoPc/CNTs hybrid prepared with sonication exhibited a conversion efficiency of CO2 above 60% at -1.0 V vs. RHE, accompanied by the Faradaic efficiencies of nearly 50% for CO and 10% for methanol, respectively. The addition of CNTs as the support improved the utilization efficiency of CoPc and reduced the transfer resistance of species and electrons. Then the ball-milling method further improved the dispersion of CoPc on CNTs, which resulted in the fact that the methanol efficiency was raised by 6% and partial current density was increased by nearly 433%. The better dispersion of CoPc on CNTs adjusted the reduction pathway of CO2 and resulted in the enhancement of methanol selectivity and catalytic activity of CO2. The probable pathway for methanol production was proposed as CO2 → *CO2- → *COOH → *CO → *CHO → *CH2O → *OCH3 → CH3OH. This suggests the significance of the ball-milling method during the preparation of better supported catalysts for CO2RR towards those high-valued products.

Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects.

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, posing significant challenges in terms of early prevention, clinical diagnosis, and treatment. Consequently, it has emerged as a major contributor to end-stage renal disease. The glomerular filtration barrier, composed of podocytes, endothelial cells, and the glomerular basement membrane, plays a vital role in maintaining renal function. Disruptions in podocyte function, including hypertrophy, shedding, reduced density, and apoptosis, can impair the integrity of the glomerular filtration barrier, resulting in elevated proteinuria, abnormal glomerular filtration rate, and increased creatinine levels. Hence, recent research has increasingly focused on the role of podocyte injury in DN, with a growing emphasis on exploring therapeutic interventions targeting podocyte injury. Studies have revealed that factors such as lipotoxicity, hemodynamic abnormalities, oxidative stress, mitochondrial dysfunction, and impaired autophagy can contribute to podocyte injury. This review aims to summarize the underlying mechanisms of podocyte injury in DN and provide an overview of the current research status regarding experimental drugs targeting podocyte injury in DN. The findings presented herein may offer potential therapeutic targets and strategies for the management of DN associated with podocyte injury.

Recent Progress on Chiral Carbon Dots: Synthetic Strategies and Biomedical Applications.

The discovery of chiral carbon dots (Ch-CDs) has opened up an exciting new research direction in the field of carbon dots. It not only retains the chirality of the precursor and exhibits highly symmetric chiral optical properties but also has properties such as chemical stability, antibacterial and antitumor properties, and good biocompatibility of carbon dots. Based on these advantages, the application of Ch-CDs in the biomedical field has attracted significant interest among researchers. However, a comprehensive review of the selection of precursors for Ch-CDs, preparation methods, and applications in biomedical fields is still lacking. Here, we summarize their precursor selection and preparation methods based on recent reports on Ch-CDs and provide the first comprehensive review for specific applications in biomedical engineering, such as biosensing, bioimaging, drug carriers, antibacterial and antibiofilm, and enzyme activity modulation. Finally, we discuss application prospects and challenges that need to be overcome. We hope this review will provide valuable guidance for researchers to prepare novel Ch-CDs and facilitate their application in biomedical engineering.

A Hybrid Quantum-Classical Algorithm for Multichannel Quantum Scattering of Atoms and Molecules.

We propose a hybrid quantum-classical algorithm for solving the time-independent Schrödinger equation for atomic and molecular collisions. The algorithm is based on the S-matrix version of the Kohn variational principle, which computes the fundamental scattering S-matrix by inverting the Hamiltonian matrix expressed in the basis of square-integrable functions. The computational bottleneck of the classical algorithm─symmetric matrix inversion─is addressed here using the variational quantum linear solver (VQLS), a recently developed noisy intermediate-scale quantum (NISQ) algorithm for solving systems of linear equations. We apply our algorithm to single- and multichannel quantum scattering problems, obtaining accurate vibrational relaxation probabilities in collinear atom-molecule collisions. We also show how the algorithm could be scaled up to simulate collisions of large polyatomic molecules. Our results demonstrate that it is possible to calculate scattering cross sections and rates for complex molecular collisions on NISQ quantum processors, opening up the possibility of scalable digital quantum computation of gas-phase bimolecular collisions and reactions of relevance to astrochemistry and ultracold chemistry.

Transformation of arginine into zero-dimensional nanomaterial endows the material with antibacterial and osteoinductive activity.

Implant-associated infection is a major threat affecting the success of orthopedic surgeries. Although various materials scavenge bacteria by generating reactive oxygen species (ROS), the intrinsic inability of ROS to distinguish bacteria from cells notably limits the therapeutic effects. Here, we found that the arginine carbon dots (Arg-CDs) that were transformed from arginine exhibited supreme antibacterial and osteoinductive activity. We further designed the Schiff base bond between Arg-CDs and aldehyde hyaluronic acid/gelatin methacryloyl (HG) hydrogel to release Arg-CDs in response to the acidic bone injury microenvironment. The free Arg-CDs could selectively kill bacteria by generating excessive ROS. Furthermore, the Arg-CD-loaded HG composite hydrogel showed excellent osteoinductive activity through inducing the M2 polarization of macrophages by up-regulating interleukin-10 (Il10) expression. Together, our findings revealed that transformation of the arginine into zero-dimensional Arg-CDs could endow the material with exceptional antibacterial and osteoinductive activity, favoring the regeneration of infectious bone.

Nuclear Spin Relaxation in Cold Atom-Molecule Collisions.

We explore the quantum dynamics of nuclear spin relaxation in cold collisions of 1Σ+ molecules with structureless atoms in an external magnetic field. To this end, we develop a rigorous coupled-channel methodology, which accounts for rotational and nuclear spin degrees of freedom of 1Σ+ molecules and their interaction with an external magnetic field as well as anisotropic atom-molecule interactions. We apply the methodology to study the collisional relaxation of the nuclear spin sublevels of 13CO molecules immersed in a cold buffer gas of 4He atoms. We find that nuclear spin relaxation in the ground rotational manifold (N = 0) of 13CO occurs extremely slowly due to the absence of direct couplings between the nuclear spin sublevels. The rates of collisional transitions between the rotationally excited (N = 1) nuclear spin states of 13CO are generally much higher due to the direct nuclear spin-rotation coupling between the states. These transitions obey selection rules, which depend on the values of space-fixed projections of rotational and nuclear spin angular momenta (MN and MI) for the initial and final molecular states. For some initial states, we also observe a strong magnetic field dependence, which can be understood by using the first Born approximation. We use our calculated nuclear spin relaxation rates to investigate the thermalization of a single nuclear spin state of 13CO(N = 0) immersed in a cold buffer gas of 4He. The calculated nuclear spin relaxation times (T1 ≃ 1 s at T = 1 K at a He density of 10-14 cm-3) display a steep temperature dependence decreasing rapidly at elevated temperatures due to the increased population of rotationally excited states, which undergo nuclear spin relaxation at a much faster rate. Thus, long relaxation times of N = 0 nuclear spin states in cold collisions with buffer gas atoms can be maintained only at sufficiently low temperatures (kBT ≪ 2Be), where Be is the rotational constant.

Effects of ultrasonic vibration on microstructure and mechanical properties of 1Cr12Ni3MoVN alloy fabricated by directed energy deposition.

Due to the rapid melting and solidification during directed energy deposition (DED) process, the defects and columnar crystals are likely to generate in the deposition layers, which reduce the quality and performance of the whole parts. Therefore, in order to improve the microstructure and mechanical properties of 1Cr12Ni3MoVN alloy manufactured by DED method, ultrasonic vibration (UV) has been employed to assist directed energy deposition process in this work. The results indicate that the high-intensity ultrasonic vibration can weaken the epitaxy growth tendency of crystal grains, and significantly improve plasticity while keeping an approximate strength. In addition, a two-dimensional numerical model is established to simulate the effect of ultrasonic vibration in the molten pool. The simulation results show that ultrasonic vibration remarkably improves the flow velocity and pressure in the molten pool, inducing the cavitation effect that breaks dendritic crystal and affects crystal characteristics. Meanwhile, the acoustic streaming effect changes the thermodynamic conditions and promotes high-temperature diffusion, which uniforms temperature distribution and reduces the temperature gradient in the molten pool. Thus the reduced temperature gradient G and raised solidification growth rate R promote the formation of fine equiaxed crystal characteristics after UV treatment. The product G × R increases and the ratio G/R decreases after UV treatment, resulting in the formation of fine equiaxed crystals.

Hemodynamic Characteristics of Cardiovascular System in Simulated Zero and Partial Gravities Based on CFD Modeling and Simulation.

Zero and partial gravities (ZPG) increase cardiovascular risk, while the corresponding theoretical foundation remains uncertain. In the article, the ZPG were generated through a rotating frame with two degrees of freedom in combination with the random walk algorithm. A precise 3D geometric configuration of the cardiovascular system was developed, and the Navier-Stokes laminar flow and solid mechanics were used as governing equations for blood flow and the surrounding tissue in the cardiovascular system. The ZPG were designed into governing equations through the volume force term. The computational fluid dynamics' (CFD) simulations in combination with proper boundary conditions were carried out to investigate the influences of ZPG on the distribution of blood flow velocity, pressure, and shear stress in the cardiovascular system. The findings show that as simulated gravity gradually decreases from 0.7 g to 0.5 g to 0.3 g to 0 g, as opposed to normal gravity of 1 g, the maximum values of blood flow velocity, pressure, and shear stress on the walls of the aorta and its ramification significantly increase, which would lead to cardiovascular diseases. The research will lay a theoretical foundation for the comprehension of the ZPG effect on cardiovascular risk and the development of effective prevention and control measures under the circumstance of ZPG.

Antibacterial and antibiofilm mechanisms of carbon dots: a review.

Due to the increasing bacterial resistance to conventional antibiotics, developing safe and effective approaches to combat infections caused by bacteria and biofilms has become an urgent clinical problem. Recently, carbon dots (CDs) have received great attention as a promising alternative to conventional antimicrobial agents due to their excellent antimicrobial efficacy and biocompatibility. Although CDs have been widely used in the field of antibacterial applications, their antibacterial and antibiofilm mechanisms have not been systematically discussed. This review provides a systematic overview on the complicated mechanisms of antibacterial and antibiofilm CDs based on recent development.

Mussel-inspired polymer with catechol and cationic Lys functionalities for dentin wet bonding.

Mussels can form tough and long-lasting adhesions to organic and inorganic surfaces in saline and impactive severe aquatic environments. Similar to mussel adhesion, dentin bonding occurs in a wet environment. However, unlike mussels, it is difficult to achieve long-lasting bonds with dentin. Moreover, water is considered a major hindrance in dentin bonding. Inspired by the synergistic effect of cationic lysine (Lys) and catechol on the elimination of the hydration layer during mussel adhesion, a catechol- and Lys-functionalized polymerizable polymer (catechol-Lys-methacrylate [CLM]) was synthesized to replicate the complex synergy between amino acids and catechol. The bond-promoting potential of 5 â€‹mg/mL CLM primer was confirmed using an in vitro wet dentin-bonding model, which was characterized by an improvement in bond strength and durability. CLM can adhere to wet demineralized dentin, with Lys acting as a molecular vanguard to expel water. Subsequently, a myriad of interfacial interactions can be obtained by introducing the catechol group into the interface. Additionally, tough and long-lasting adhesion, similar to that formed by mussels, can be achieved by grafting CLM onto type I collagen via covalent bonds, hydrogen bonds, Van der Waals interactions, and cation-π interactions, which can enhance the mechanical and chemical stability of collagen, increase the enzymatic resistance of collagen, and provide additional physical/chemical adhesion to dentin bonds. Catechol- and cationic Lys-functionalized polymers can improve the stability of the resin-dentin interface under wet conditions.

Closed-Loop Microbial Fuel Cell Control System Designed for Online Monitoring of TOC Dynamic Characteristics in Public Swimming Pool.

Total organic carbon (TOC) in the water of public swimming pools (PSPs) must be monitored online for public health. In order to address the shortcomings of conventional microbial fuel cell biosensor (MFC-biosensor), an innovative biosensor with peculiar closed-loop structure was developed for online monitoring of TOC in PSPs. Its design was based on experimental data, model identification, cybernetics, and digital and real-time simulation. The outcomes of the digital simulation demonstrated that the closed-loop MFC control system possesses the desired structure with a pair of dominant complex-conjugate closed-loop poles (-15.47 ± 7.73j), and the real-time simulation showed that its controller output signals can automatically and precisely track the variation in TOC concentration in PSP water with the desired dynamic response performances; for example, mean delay time was 0.06 h, rise time was 0.12 h, peak time was 0.18 h, maximum overshoot was 7.39%, settling time was 0.22 h, and best fit 0.98. The proposed principle and method of the closed-loop MFC-biosensor control system in the article can also be applied for online monitoring of other substances in water, such as heavy metal ions, chemical toxicants, and so forth, and lay a theoretical foundation for MFC-based online monitoring substances in an aquatic environment.

Abscisic acid induces the expression of AsKIN during the recovery period of garlic cryopreservation.

KEY MESSAGE: Abscisic acid induced the expression of AsKIN during the recovery period of garlic cryopreservation. AsKIN was identified as a gene involved in cold and osmotic stress resistance. Cryopreservation has been proven to be effective in removing viruses from garlic. However, oxidative damage in cryopreservation has a significant impact on the survival after preservation. Abscisic acid (ABA) has been shown to reduce oxidative stress and promote the survival after cryopreservation. However, it is not clear which genes play important roles in this process. In this study, we added ABA to the dehydration step and analyzed the transcriptomic divergences between the ABA-treated group and the control group in three cryogenic steps (dehydration, unloading and recovery). By short time-series expression miner (STEM) analysis and weighted gene co-expression network analysis (WGCNA), the recovery step was identified as the period of significant changes in gene expression levels in cryopreservation. The addition of ABA promoted the upregulated expression of microtubule-related genes in the recovery step. We further identified AsKIN as a hub gene in the recovery step and verified its function. The results showed that overexpression of AsKIN enhanced the tolerance of Arabidopsis to oxidative stress in cryopreservation, influenced the expression of genes in response to cold and osmotic stress and promoted plant growth after stress. The AsKIN gene is likely to be involved in the plant response to cold stress and osmotic stress. These results reveal the molecular mechanisms of ABA in cryopreservation and elucidate the potential biological functions of the kinesin-14 subfamily.

Formation Mechanism of Microbial Diversity in Artificial Intelligence Devices due to Intermediate Disturbance by Low-Dose UV Radiation for Complementary Medicine.

The development of artificial intelligence devices in the complementary medicine field is rapid and the surface microbial diversity pollution was found with periodic low-dose ultraviolet radiation (LDUVR). Since artificial intelligence devices do not have enough different types of substrates for microbial communities, it is unclear how the great microbial diversity can emerge and persist, as this clearly defies the competitive exclusion principle of ecology. In this study, the 5 most common genera in the artificial intelligence devices, Escherichia, Pseudomonas, Streptococcus, Staphylococcus and Aeromonas have been sampled without and with periodic LDUVR, respectively. A new hypothesis was put up to clarify the construction and maintenance process of high microbiological diversity in artificial intelligence devices by comparing and evaluating the variations between the dynamic response characteristics of their relative abundances in the two scenarios as follows: the periodic LDUVR can be regarded as an adverse factor with intermediate disturbance, causing stronger microbial stochastic growth responses (SGR) which would inevitably give rise to stronger random variation of the other important processes tightly correlated with SGR, such as intra- and interspecific competition process, and substrates production and consumption process, which could effectively diminish the auto- and cross-correlation of stochastic processes of microbial populations, alleviating the intra- and inter-specific competitions. In artificial intelligence devices with LDUVR, these crucial succession processes can propel the microbial communities to generate and sustain a high species diversity. Finally, thorough Monte Carlo simulations were used to thoroughly confirm the idea. This research can build the theoretical groundwork, offer fresh viewpoints, and suggest potential microbial prevention strategies for the succession of microbial communities in LDUVR.

Cytocompatible Amphipathic Carbon Quantum Dots as Potent Membrane-Active Antibacterial Agents with Low Drug Resistance and Effective Inhibition of Biofilm Formation.

It is very challenging to design nanomaterials with both excellent antibacterial activity and cytocompatibility when facing bacterial infection. Here, inspired by antimicrobial peptides (AMPs), we fabricate carbon quantum dots (CQDs) derived from hydrophobic tryptophan and hydrophilic lysine or arginine (Lys/Trp-CQDs and Arg/Trp-CQDs), which possess amphipathic properties. These CQDs could effectively destroy bacterial membranes without developing resistance, inhibit biofilms formed by Staphylococcus aureus, and exhibit good in vitro biocompatibility. The antibacterial activities are caused by not only surface cationic structures and excess intracellular reactive oxygen species (ROS) generated by the CQDs but also the effects of the surface hydrophobic groups. These combined mechanisms of actions lead to bacterial membrane disruption, which raises the hope for combating bacterial infection without concern about drug resistance. What's more, the effect of amphiphilicity on balancing sterilization with biocompatibility expands the research ideas for developing available antibacterial nanomaterials.

Ascorbic acid addition during dehydration improves garlic shoot tip cryopreservation but does not affect viral load.

Cryopreservation is known be an effective method for virus elimination in garlic. However, oxidative damage during the cryopreservation seriously affects the survival of garlic after cryopreservation. Ascorbic acid (AsA) can reduce oxidative damage and improve regrowth following cryopreservation, and its effect may be influenced by the step during which it is added. In this study, AsA was added at the osmoprotection (O) and dehydration (DE) steps of cryopreservation. By observing the dynamic changes in cell viability and reactive oxygen species (ROS) components with different AsA treatments, AsA has been linked to the reduced accumulation of ROS in the shoot tips. Increased gene expression levels of antioxidant enzymes also explained the ROS scavenging effect of AsA. The correlation analysis between cell viability, ROS, membrane lipid peroxidation-related indicators and antioxidant-related indicators showed that membrane lipid peroxidation caused by excess ROS was the main factor affecting cell viability. Ascorbic acid added during dehydration minimized the accumulation of ROS from dehydration to dilution and alleviated the oxidative damage during cryopreservation. Thus, the survival and regrowth of the garlic was significantly improved after cryopreservation. Dehydration was found to be the suitable step for the addition of AsA during garlic cryopreservation. We further evaluated the virus elimination effect under optimal AsA treatment. However, there was no significant difference in virus content in regenerated plants when compared with the control.

Photothermal-enhanced antibacterial and antioxidant hydrogel dressings based on catechol-modified chitosan-derived carbonized polymer dots for effective treatment of wound infections.

Bacterial infection and excessive reactive oxygen species (ROS) remain challenging factors contributing to the delayed healing of chronic wounds. Although various antibacterial and antioxidant hydrogel dressings have been developed to accelerate wound healing, multifunctional hydrogels fabricated by rationally designing and introducing carbonized polymer dots (CPDs) have rarely been reported. Herein, inspired by the mussel biomimetic approach, we synthesized 3,4-dihydroxybenzaldehyde functionalized chitosan (DFC), and then the polymeric precursor was pyrolyzed into CPDs with abundant amino and catechol groups on the surface, which endowed it with a highly positively charged surface that could activate the photothermal effect under near-infrared (NIR) light irradiation. Finally, the nanocomposite hydrogel (PVA@CPDs) was simply constructed by directly mixing polyvinyl alcohol (PVA) with CPDs, utilizing the freeze-thaw cycle method to form a gel, in which, CPDs as a center of polyfunctional nanoparticles drove the formation of PVA microcrystalline crosslinking and endowed the PVA substrate with versatile functionalities. Remarkable and comprehensive improvements in the swelling behavior, mechanical properties and adhesive strength of the hydrogel could be conveniently achieved with the suitable loading of CPDs. The in vitro experiments demonstrated that the PVA@CPDs hydrogel presented broad-spectrum and rapid bactericidal activity, concurrently acting as an effective antioxidant being able to scavenge free radicals. In addition, no obvious cytotoxicity was observed for the multifunctional hydrogel after incubation with L02 cells. In vivo evaluation in an infected full-thickness skin wound model demonstrated that the PVA@CPDs hydrogel promoted wound closure without any side effects. As a consequence, the current work manifests a facile yet versatile strategy to develop effective and biocompatible multifunctional hydrogel dressings for bacteria-infected wound healing.