Injectable Hydrogel System Incorporating Black Phosphorus Nanosheets and Tazarotene Drug for Enhanced Vascular and Nerve Regeneration in Spinal Cord Injury Repair.

Spinal cord injury (SCI) often leads to cell death, vascular disruption, axonal signal interruption, and permanent functional damage. Currently, there are no clearly effective therapeutic options available for SCI. Considering the inhospitable SCI milieu typified by ischemia, hypoxia, and restricted neural regeneration, a novel injectable hydrogel system containing conductive black phosphorus (BP) nanosheets within a lipoic acid-modified chitosan hydrogel matrix (LAMC) is explored. The incorporation of tannic acid (TA)-modified BP nanosheets (BP@TA) into the LAMC hydrogel matrix significantly improved its conductivity. Further, by embedding a bicyclodextrin-conjugated tazarotene drug, the hydrogel showcased amplified angiogenic potential in vitro. In a rat model of complete SCI, implantation of LAMC/BP@TA hydrogel markedly improved the recovery of motor function. Immunofluorescence evaluations confirmed that the composite hydrogel facilitated endogenous angiogenesis and neurogenesis at the injury site. Collectively, this work elucidates an innovative drug-incorporated hydrogel system enriched with BP, underscoring its potential to foster vascular and neural regeneration.

A modified laser ablation-isotope ratio mass spectrometry method for in situ analysis of sulfur isotope composition of sulfides.

RATIONALE: A novel laser ablation-isotope ratio mass spectrometry (LA-IRMS) method for in situ analysis of sulfur isotopes in sulfides has been developed. Instead of the in situ reaction applied by the traditional laser microprobe, the analyte gas preparation in this method is separated temporally and spatially from the LA, resulting in improved precision and accuracy. METHODS: Our LA-IRMS system combines an ultraviolet LA system, an elemental analyzer (EA), a custom-built cryogenic concentration system, a continuous-flow interface, and an IRMS. The sulfide aerosol particles generated from LA were transferred by a helium carrier gas from the ablation cell into the reaction tube and were then converted into SO2 . Subsequently, SO2 was enriched in two cold traps and was finally introduced into the ion source of the IRMS through the continuous-flow interface. RESULTS: We measured three synthetic and four natural sulfide reference materials to test the performance of this method. Precisions of ±0.25‰-±0.48‰ and ±0.32‰-±0.64‰ (1SD, n = 5) for δ34 S values of synthetic and natural sulfide standards can be obtained for spot sizes ranging from 64 to 80 µm. Measured values and their recommended values showed a good linear relationship (R2 within 0.998 and 0.9995) with the slope of approaching unity (within 1.0509 and 1.1313). CONCLUSIONS: Data from the measurement of reference materials showed that the precision and accuracy of our method were satisfactory. This method is a powerful tool for in situ sulfur isotope measurement of sulfides and can be further applied to in situ carbon and oxygen isotope analyses.

Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy.

Osteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1ß-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.Clinical trial registration: Not applciable.

Epac-2 ameliorates spontaneous colitis in Il-10-/- mice by protecting the intestinal barrier and suppressing NF-κB/MAPK signalling.

Intestinal barrier dysfunction and intestinal inflammation interact in the progression of Crohn's disease (CD). A recent study indicated that Epac-2 protected the intestinal barrier and had anti-inflammatory effects. The present study examined the function of Epac-2 in CD-like colitis. Interleukin-10 gene knockout (Il-10-/- ) mice exhibit significant spontaneous enteritis and were used as the CD model. These mice were treated with Epac-2 agonists (Me-cAMP) or Epac-2 antagonists (HJC-0350) or were fed normally (control), and colitis and intestinal barrier structure and function were compared. A Caco-2 and RAW 264.7 cell co-culture system were used to analyse the effects of Epac-2 on the cross-talk between intestinal epithelial cells and inflammatory cells. Epac-2 activation significantly ameliorated colitis in mice, which was indicated by reductions in the colitis inflammation score, the expression of inflammatory factors and intestinal permeability. Epac-2 activation also decreased Caco-2 cell permeability in an LPS-induced cell co-culture system. Epac-2 activation significantly suppressed nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signalling in vivo and in vitro. Epac-2 may be a therapeutic target for CD based on its anti-inflammatory functions and protective effects on the intestinal barrier.

New Genes Interacted With Recent Whole-Genome Duplicates in the Fast Stem Growth of Bamboos.

As drivers of evolutionary innovations, new genes allow organisms to explore new niches. However, clear examples of this process remain scarce. Bamboos, the unique grass lineage diversifying into the forest, have evolved with a key innovation of fast growth of woody stem, reaching up to 1 m/day. Here, we identify 1,622 bamboo-specific orphan genes that appeared in recent 46 million years, and 19 of them evolved from noncoding ancestral sequences with entire de novo origination process reconstructed. The new genes evolved gradually in exon-intron structure, protein length, expression specificity, and evolutionary constraint. These new genes, whether or not from de novo origination, are dominantly expressed in the rapidly developing shoots, and make transcriptomes of shoots the youngest among various bamboo tissues, rather than reproductive tissue in other plants. Additionally, the particularity of bamboo shoots has also been shaped by recent whole-genome duplicates (WGDs), which evolved divergent expression patterns from ancestral states. New genes and WGDs have been evolutionarily recruited into coexpression networks to underline fast-growing trait of bamboo shoot. Our study highlights the importance of interactions between new genes and genome duplicates in generating morphological innovation.

High-quality evergreen azalea genome reveals tandem duplication-facilitated low-altitude adaptability and floral scent evolution.

Azalea belongs to Rhododendron, which is one of the largest genera of flowering plants and is well known for the diversity and beauty in its more than 1000 woody species. Rhododendron contains two distinct groups: the most high-altitude and a few low-altitude species; however, the former group is difficult to be domesticated for urban landscaping, and their evolution and adaptation are little known. Rhododendron ovatum has broad adaptation in low-altitude regions but possesses evergreen characteristics like high-altitude species, and it has floral fragrance that is deficient in most cultivars. Here we report the chromosome-level genome assembly of R. ovatum, which has a total length of 549 Mb with scaffold N50 of 41 Mb and contains 41 264 predicted genes. Genomic micro-evolutionary analysis of R. ovatum in comparison with two high-altitude Rhododendron species indicated that the expansion genes in R. ovatum were significantly enriched in defence responses, which may account for its adaptability in low altitudes. The R. ovatum genome contains much more terpene synthase genes (TPSs) compared with the species that lost floral fragrance. The subfamily b members of TPS are involved in the synthesis of sesquiterpenes as well as monoterpenes and play a major role in flora scent biosynthesis and defence responses. Tandem duplication is the primary force driving expansion of defence-responsive genes for extensive adaptability to the low-altitude environments. The R. ovatum genome provides insights into low-altitude adaptation and gain or loss of floral fragrance for Rhododendron species, which are valuable for alpine plant domestication and floral scent breeding.

An Automatic Channel Selection Approach for ICA-Based Motor Imagery Brain Computer Interface.

Independent component analysis (ICA) is a potential spatial filtering method for the implementation of motor imagery brain-computer interface (MIBCI). However, ICA-based MIBCI (ICA-MIBCI) is sensitive to electroencephalogram (EEG) channels and the quality of the training data, which are two crucial factors affecting the stability and classification performance of ICA-MIBCI. To address these problems, this paper is mainly focused on the investigation of EEG channel optimization. As a reference, we constructed a single-trial-based ICA-MIBCI system with commonly used channels and common spatial pattern-based MIBCI (CSP-MIBCI). To minimize the impact of artifacts on EEG channel optimization, a data-quality evaluation method, named "self-testing" in this paper, was used in a single-trial-based ICA-MIBCI system to evaluate the quality of single trials in each dataset; the resulting self-testing accuracies were used for the selection of high-quality trials. Given several candidate channel configurations, ICA filters were calculated using selected high-quality trials and applied to the corresponding ICA-MIBCI implementation. Optimal channels for each dataset were assessed and selected according to the self-testing results related to various candidate configurations. Forty-eight MI datasets of six subjects were employed in this study to validate the proposed methods. Experimental results revealed that the average classification accuracy of the optimal channels yielded a relative increment of 2.8% and 8.5% during self-testing, 14.4% and 9.5% during session-to-session transfer, and 36.2% and 26.7% during subject-to-subject transfer compared to CSP-MIBCI and ICA-MIBCI with fixed the channel configuration. This work indicates that the proposed methods can efficiently improve the practical feasibility of ICA-MIBCI.

Non-contact, synchronous dynamic measurement of respiratory rate and heart rate based on dual sensitive regions.

BACKGROUND: Currently, many imaging photoplethysmography (IPPG) researches have reported non-contact measurements of physiological parameters, such as heart rate (HR), respiratory rate (RR), etc. However, it is accepted that only HR measurement has been mature for applications, and other estimations are relatively incapable for reliable applications. Thus, it is worth keeping on persistent studies. Besides, there are some issues commonly involved in these approaches need to be explored further. For example, motion artifact attenuation, an intractable problem, which is being attempted to be resolved by sophisticated video tracking and detection algorithms. METHODS: This paper proposed a blind source separation-based method that could synchronously measure RR and HR in non-contact way. A dual region of interest on facial video image was selected to yield 6-channels Red/Green/Blue signals. By applying Second-Order Blind Identification algorithm to those signals generated above, we obtained 6-channels outputs that contain blood volume pulse (BVP) and respiratory motion artifact. We defined this motion artifact as respiratory signal (RS). For the automatic selections of the RS and BVP among these outputs, we devised a kurtosis-based identification strategy, which guarantees the dynamic RR and HR monitoring available. RESULTS: The experimental results indicated that, the estimation by the proposed method has an impressive performance compared with the measurement of the commercial medical sensors. CONCLUSIONS: The proposed method achieved dynamic measurement of RR and HR, and the extension and revision of it may have the potentials for more physiological signs detection, such as heart rate variability, eye blinking, nose wrinkling, yawn, as well as other muscular movements. Thus, it might provide a promising approach for IPPG-based applications such as emotion computation and fatigue detection, etc.

[Online brain-computer interface system based on independent component analysis].

In the research of non-invasive brain-computer interface(BCI), independent component analysis(ICA) has been considered as a promising method of electroencephalogram(EEG) preprocessing and feature enhancement. However, there have been few investigations and implements about online ICA-BCI system up till now.This paper reports the investigation of the ICA-based motor imagery BCI(MIBCI) system, combining the characteristics of unsupervised learning of ICA and event-related desynchronization(ERD) related to motor imagery. We constructed a simple and practical method of ICA spatial filter calculation and discriminate criterion of three-type motor imageries in the study. To validate the online performance of proposed algorithms, an ICA-MIBCI experimental system was fully established based on Neuro Scan EEG amplifier and VC++ platform. Four subjects participated in the experiment of MIBCI testing and two of them took part in the online experiment. The average classification accuracies of the three-type motor imageries reached 89.78% and 89.89% in the offline and online testing, respectively. The experimental results showed that the proposed algorithm produced high classification accuracy and required less time consumption, which would have a prospect of cross platform application.

[Comparison and applicability study of blood volume pulse extraction based on facial video].

Blind source separation technique based on independent component analysis (ICA) can separate blood volume pulse (BVP) from the facial video and then realize the telemetry of heart rate, blood oxygen saturation, respiratory rate and other vital signs parameters. However, the superiority of ICA in BVP extraction has not been demonstrated in the existing researches. Some researchers suggested using traditional G-channel method for BVP extraction (G-BVP) instead of ICA method (ICA-BVP). This study investigated the applicability of ICA-BVP comparatively. To solve the inherent permutation problem of ICA, a spectral kurtosis-based method was proposed for BVP identification. The experimental results based on the facial video datasets from 9 subjects shows that ICA-BVP method has apparent advantages in motion artifacts attenuation and ambient light changes elimination. The kurtosis-based method achieved a good performance in BVP identification and dynamic heart rate (HR) estimation. In practical application, the proposed ICA-BVP method could present a better stability and accuracy in vital signs parameters extraction.

Cold-dependent alternative splicing of a Jumonji C domain-containing gene MtJMJC5 in Medicago truncatula.

Histone methylation is an epigenetic modification mechanism that regulates gene expression in eukaryotic cells. Jumonji C domain-containing demethylases are involved in removal of methyl groups at lysine or arginine residues. The JmjC domain-only member, JMJ30/JMJD5 of Arabidopsis, is a component of the plant circadian clock. Although some plant circadian clock genes undergo alternative splicing in response to external cues, there is no evidence that JMJ30/JMJD5 is regulated by alternative splicing. In this study, the expression of an Arabidopsis JMJ30/JMJD5 ortholog in Medicago truncatula, MtJMJC5, in response to circadian clock and abiotic stresses were characterized. The results showed that MtJMJC5 oscillates with a circadian rhythm, and undergoes cold specifically induced alternative splicing. The cold-induced alternative splicing could be reversed after ambient temperature returning to the normal. Sequencing results revealed four alternative splicing RNA isoforms including a full-length authentic protein encoding variant, and three premature termination condon-containing variants due to alternative 3' splice sites at the first and second intron. Under cold treatment, the variants that share a common 3' alternative splicing site at the second intron were intensively up-regulated while the authentic protein encoding variant and the premature termination condon-containing variant only undergoing a 3' alternative splicing at the first intron were down regulated. Although all the premature termination condon-harboring alternative splicing variants were sensitive to nonsense-mediated decay, the premature termination codon-harboring alternative splicing variants sharing the 3' alternative splicing site at the second intron showed less sensitivity than the one only containing the 3' alternative slicing site at the first intron under cold treatment. These results suggest that the cold-dependent alternative splicing of MtJMJC5 is likely a species or genus-specific mechanism of gene expression regulation on RNA levels, and might play a role in epigenetic regulation of the link between the circadian clock and ambient temperature fluctuation in Medicago.

[Three-class Motor Imagery Classification Based on Optimal Sub-band Features of Independent Components].

In the study of the scalp electroencephalogram(EEG)-based brain-computer interface(BCI),individual differences and complex background noise are two main factors which affect the stability of BCI system.For different subjects,therefore,optimization of BCI system parameters is necessary,including the optimal designing of temporal and spatial filters parameters as well as the classifier parameters.In order to improve the accuracy of BCI system,this paper proposes a new BCI information processing method,which combines the optimization design of independent component analysis spatial filter(ICA-SF)with the multiple sub-band features of EEG signals.The four subjects' three-class motor imagery EEG(MI-EEG)data collected in different periods were analyzed with the proposed method.Experimental results revealed that,during the inner and outer cross-validation of single subject as well as the subject-to-subject validation,the proposed multiple sub-band method always had higher average classification accuracy compared to those with single-band method,and the maximum difference could achieve 6.08% and5.15%,respectively.

[Channel Selection for Multi-class Motor Imagery Based on Common Spatial Pattern].

High-density channels are often used to acquire electroencephalogram (EEG) spatial information in different cortical regions of the brain in brain-computer interface (BCI) systems. However, applying excessive channels is inconvenient for signal acquisition, and it may bring artifacts. To avoid these defects, the common spatial pattern (CSP) algorithm was used for channel selection and a selection criteria based on norm-2 is proposed in this paper. The channels with the highest M scores were selected for the purpose of using fewer channels to acquire similar rate with high density channels. The Dataset III a from BCI competition 2005 were used for comparing the classification accuracies of three motor imagery between whole channels and the selected channels with the present proposed method. The experimental results showed that the classification accuracies of three subjects using the 20 channels selected with the present method were all higher than the classification accuracies using all 60 channels, which convinced that our method could be more effective and useful.

Biomimetic fusion: Platyper's dual vision for predicting protein-surface interactions.

Predicting protein binding with the material surface still remains a challenge. Here, a novel approach, platypus dual perception neural network (Platyper), was developed to describe the interactions in protein-surface systems involving bioceramics with BMPs. The resulting model integrates a graph convolutional neural network (GCN) based on interatomic potentials with a convolutional neural network (CNN) model based on images of molecular structures. This dual-vision approach, inspired by the platypus's adaptive sensory system, addresses the challenge of accurately predicting the complex binding and unbinding dynamics in steered molecular dynamics (SMD) simulations. The model's effectiveness is demonstrated through its application in predicting surface interactions in protein-ligand systems. Notably, Platyper improves computational efficiency compared to classical SMD-based methods and overcomes the limitations of GNN-based methods for large-scale atomic simulations. The incorporation of heat maps enhances model's interpretability, providing valuable insights into its predictive capabilities. Overall, Platyper represents a promising advancement in the accurate and efficient prediction of protein-surface interactions in the context of bioceramics and growth factors.

An injectable hydrogel dressing for controlled release of hydrogen sulfide pleiotropically mediates the wound microenvironment.

The healing of scalded wounds faces many challenges such as chronic inflammation, oxidative stress, wound infection, and difficulties in vascular and nerve regeneration. Treating a single problem cannot effectively coordinate the complex regenerative microenvironment of scalded wounds, limiting the healing and functional recovery of the skin. Therefore, there is a need to develop a multi-effect treatment plan that can adaptively address the issues at each stage of wound healing. In this study, we propose a scheme for on-demand release of hydrogen sulfide (H2S) based on the concentration of reactive oxygen species (ROS) in the wound microenvironment. This is achieved by encapsulating peroxythiocarbamate (PTCM) in the ROS-responsive polymer poly(ethylene glycol)-poly(L-methionine) (PMet) to form nanoparticles, which are loaded into a thermosensitive injectable hydrogel, F127-poly(L-aspartic acid-N-hydroxysuccinimide) (F127-P(Asp-NHS)), to create a scald dressing. The H2S released by the hydrogel dressing on demand regulates the wound microenvironment by alleviating infection, reducing oxidative stress, and remodeling inflammation, thereby accelerating the healing of full-thickness scalded wounds. This hydrogel dressing for the adaptive release of H2S has great potential in addressing complex scalded wounds associated with infection and chronic inflammation.

All-in-one strategy to develop a near-infrared triggered multifunctional bioactive magnesium phosphate bone cement for bone repair.

Bone cement is widely used in clinical with optimistic filling and mechanical properties. However, the setting time of bone cement is difficult to accurately control, and the existing bone cements exhibit limited therapeutic functionalities. In response to these challenges, we designed and synthesized Nd-doped whitlockite (Nd-WH), endowing bone cement with photothermal-responsive and fluorescence imaging capabilities. The doping amount and photothermal properties of Nd-doped whitlockite were studied, and the composite bone cement was prepared. The results showed that the setting time of bone cement could be regulated by near infrared irradiation, and the multiple functions of promoting osteogenic differentiation, antibacterial and anti-tumor could be realized by adjusting the power and irradiation time of near infrared. By incorporating Nd-doped whitlockite and bone cement, we developed an all-in-one strategy to achieve setting time control, enhanced osteogenic ability, tumor cell clearance, bacterial clearance, and bone tissue regeneration. The optimized physical and mechanical properties of composite bone cement ensure adaptability and plasticity. In vitro and in vivo experiments validated the effectiveness of this bone cement platform for bone repair, tumor cell clearance and bacterial clearance. The universal methods to regulate the setting time and function of bone cement by photothermal effect has potential in orthopedic surgery and is expected to be a breakthrough in the field of bone defect repair. Further research and clinical validation are needed to ensure its safety, efficacy and sustainability. STATEMENT OF SIGNIFICANCE: Bone cement is a valuable clinical material. However, the setting time of bone cement is difficult to control, and the therapeutic function of existing bone cement is limited. Various studies have shown that the bone repair capacity of bone cements can be enhanced by synergistic stimulatory effects in vivo and ex vivo. Unfortunately, most of the existing photothermal conversion materials are non-degradable and poorly biocompatible. This study provides a bone-like photothermal conversion material with photothermal response and fluorescence imaging properties, and constructed a platform for integrated regulation of the setting time of bone cement and diversification of its functions. Therefore, it helps to design multi-functional bone repair materials that are more convenient and effective in clinical operation.

[Formula: see text]-[Formula: see text]: A Nonparametric Model for Neural Power Spectra Decomposition.

The power spectra estimated from the brain recordings are the mixed representation of aperiodic transient activity and periodic oscillations, i.e., aperiodic component (AC) and periodic component (PC). Quantitative neurophysiology requires precise decomposition preceding parameterizing each component. However, the shape, statistical distribution, scale, and mixing mechanism of AC and PCs are unclear, challenging the effectiveness of current popular parametric models such as FOOOF, IRASA, BOSC, etc. Here, ξ- π was proposed to decompose the neural spectra by embedding the nonparametric spectra estimation with penalized Whittle likelihood and the shape language modeling into the expectation maximization framework. ξ- π was validated on the synthesized spectra with loss statistics and on the sleep EEG and the large sample iEEG with evaluation metrics and neurophysiological evidence. Compared to FOOOF, both the simulation presenting shape irregularities and the batch simulation with multiple isolated peaks indicated that ξ- π improved the fit of AC and PCs with less loss and higher F1-score in recognizing the centering frequencies and the number of peaks; the sleep EEG revealed that ξ- π produced more distinguishable AC exponents and improved the sleep state classification accuracy; the iEEG showed that ξ- π approached the clinical findings in peak discovery. Overall, ξ- π offered good performance in the spectra decomposition, which allows flexible parameterization using descriptive statistics or kernel functions. ξ- π is a seminal tool for brain signal decoding in fields such as cognitive neuroscience, brain-computer interface, neurofeedback, and brain diseases.

Strontium-Doped Hydroxyapatite Coating Improves Osteo/Angiogenesis for Ameliorative Graft-Bone Integration via the Macrophage-Derived Cytokines-Mediated Integrin Signal Pathway.

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.

Efficacy of melanin-loaded lipoic acid-modified chitosan hydrogel in diabetic wound healing.

The healing of diabetic wounds is significantly impeded due to severe oxidative stress and hindered angiogenesis, presenting a major challenge to clinical treatment. In this context, we introduces a novel hydrogel dressing strategy that uniquely combines α-lipoic acid-modified chitosan (LAMC) and melanin nanoparticles (MNPs). This innovative hydrogel, LAMC@MNPs, is formulated to gel under ultraviolet (UV) light without the need for a photoinitiator, simplifying the preparation process and potentially enhancing safety. Our experimental results demonstrate that the LAMC@MNPs hydrogel not only exhibits superior skin adhesion, with an average strength of 56.59 ± 3.16 KPa, but also effectively alleviates oxidative stress and accelerates vascular regeneration and wound healing. This is achieved by promoting cell migration and scavenging free radicals, addressing the critical barriers in diabetic wound care. The combination of these materials and their functional benefits presents a promising new approach to diabetic wound treatment.

Metabolic Control During Macrophage Polarization by a Citrate-Functionalized Scaffold for Maintaining Bone Homeostasis.

Metabolites, as markers of phenotype at the molecular level, can regulate the function of DNA, RNA, and proteins through chemical modifications or interactions with large molecules. Citrate is an important metabolite that affects macrophage polarization and osteoporotic bone function. Therefore, a better understanding of the precise effect of citrate on macrophage polarization may provide an effective alternative strategy to reverse osteoporotic bone metabolism. In this study, a citrate functional scaffold to control the metabolic pathway during macrophage polarization based on the metabolic differences between pro-inflammatory and anti-inflammatory phenotypes for maintaining bone homeostasis, is fabricated. Mechanistically, only outside M1 macrophages are accumulated high concentrations of citrate, in contrast, M2 macrophages consume massive citrate. Therefore, citrate-functionalized scaffolds exert more sensitive inhibitory effects on metabolic enzyme activity during M1 macrophage polarization than M2 macrophage polarization. Citrate can block glycolysis-related enzymes by occupying the binding-site and ensure sufficient metabolic flux in the TCA cycle, so as to turn the metabolism of macrophages to oxidative phosphorylation of M2 macrophage, largely maintaining bone homeostasis. These studies indicate that exogenous citrate can realize metabolic control of macrophage polarization for maintaining bone homeostasis in osteoporosis.