The periosteum is crucial in the processes of bone formation, regeneration, and remodelling. Specifically, periosteal progenitor cells contribute a major force to the initiation of bone healing. Biomimetic periosteum (BP), employed for treating bone defects, exhibits superior outcomes in terms of bone integrity, proper vascularization, and minimal heterotopic ossification when compared to conventional direct graft bone void fillers. Therefore, BP has emerged as a contemporary and effective approach for addressing bone defects. As an in vivo graft, BP necessitates excellent biocompatibility and appropriate mechanical properties. Furthermore, it should closely mirror the architecture and functionality of the natural periosteum. This review provides a detailed summary of recent research progress on BP, incorporating inspiring studies that contribute to the future development of this field. Initially, the review examines the structure and function of the periosteum in the context of bone defect repair. Subsequently, it analyzes the current research and design concept for BP construction and provides a comprehensive overview of the materials and techniques employed in constructing BP. Finally, it summarizes the construction strategies of BP used for treating bone defects from various perspectives including structural and functional biomimicry, and discusses the latest advances in current research.
In recent years, lignin has attracted substantial attention from researchers because of its diverse sources, low cost, and renewability. The effective functionalization and enhanced value-added utilization of lignin have successfully addressed the challenges associated with biomass resource waste, low utilization rate, high material cost, and underwhelming performance in energy, environmental protection, and medical applications. The emergence of lignin carbon quantum dots (LCQDs) has opened new avenues for the development and utilization of lignin by offering exciting opportunities for their applications. LCQDs possess unique characteristics such as fluorescence properties, size effect, surface effect, and interface effects, which are promising for applications in many fields. This paper provides a comprehensive overview of the structure and applications of lignin with a specific focus on the preparation method of LCQDs as well as their various applications in drug delivery systems, electrode material fabrication, and antibacterial agent development. Furthermore, this study offers valuable insights into the prospects of LCQDs and aims to contribute to their functional development. Finally, the challenges associated with leveraging the fluorescence properties of LCQDs are discussed, along with potential directions for future research.
Given the effectiveness of organic pollutants photodegradation and the excellent photovoltaic nature of organic solar cells (OSCs), this work first innovatively integrated the cross-fields of OSCs and environmental photocatalysis. Using knowledge of OSC morphology, an insertion strategy involved adding a suitable quantity of guest acceptor (Y6-O) to the PM6 donor polymer and BTP-2F-ThCl host small molecule acceptor system. Y6-O leads to tighter π-π packing, reduced domain size, and improved domain purity, resulting in favorable morphology for charge generation and transfer in devices and an improved power conversion efficiency (PCE) from 17.1% to 18.1%. Moreover, terpolymer organic photovoltaic films were applied to wastewater treatment, gaining ions Sb(III) and Sb(V) removals of 100% in 15 min, and guaiacol photodegradations of 90% in 1 h. This work significantly prompts the development of organic photovoltaics and wastewater treatment and opens views for multifunctional organic photovoltaic material applications.
Gold nanomaterials have been used in the diagnosis and treatment of different tumors due to their unique physical and chemical properties. Among them, gold nanoparticles with stimuli-responsive aggregation functions have attracted extensive attention because they can meet the unique needs of tumor diagnosis and treatment at different stages through structural changes. However, how to effectively modify gold nanoparticles to achieve structural transformation for specific stimuli, and the role of corresponding structural transformation in improving the effect of diagnosis and treatment still lack systematic summary. In this review, we comprehensively summarized the current strategies for inducing gold nanoparticles aggregation and its advances in tumor diagnosis and treatment.
The insufficient infiltration and functional inhibition of CD8+ T cells due to tumor microenvironment (TME) are considered enormous obstacles to anti-tumor immunotherapy. Herein, a pH-responsive core-shell manganese phosphate nanomodulator co-loading siPD-L1 and Mn2+ into nanoparticles coated with hyaluronic acid was prepared, which was aimed at the bidirectional reprogramming the tumor microenvironment: (1) “Brakes off,” restoring CD8+ T cells function by siPD-L1 knockdowning PD-L1 expression of tumor cells; (2) “Step on the accelerator,” promoting CD8+ T cells infiltration in tumors tissue based on the multidimensional immune effects of Mn2+ (immunogenic cell death induced the enhancing cGAS-STING pathway, the proliferation and maturation of relative immune cells). Additionally, this strategy could induce macrophage polarization and inhibit the regulatory T cells in tumor site. This work provided a manganese phosphate nanomodulator to reprogram the immune TME for an enhanced comprehensive anti-tumor effect of triple negative breast cancer, which offers a robust method for tumor immunotherapy in future clinical applications.
Copper (Cu) is the most promising catalyst for electrochemical CO2-to-C2+ conversion, whereas performance remains below practical thresholds due to the high energy barrier of C−C coupling and lack of effective approaches to steer the reaction pathway. Recent advances show that metal-organic frameworks (MOF) could be a promising platform as support, pre-catalyst, and co-catalyst to modify the electronic structure and local reaction environment of Cu catalysts for promoting CO2-to-C2+ reduction by virtue of their great tunability over compositions and pore architectures. In this review, we discussed general design principles, catalytic mechanisms, and performance achievements of MOF-based Cu catalysts, aiming to boost catalyst refinement for steering CO2 reduction pathway to C2+ products. The fundamentals and challenges of CO2-to-C2+ reduction are first introduced. Then, we summarized design conceptions of MOF-based Cu catalysts from three aspects: engineering the electronic properties of Cu, regulating the local reaction environment, and managing site exposure and mass transport. Further, the latest progress of CO2 reduction to C2+ products over MOF-based Cu catalysts, namely Cu-based MOF, MOF-derived Cu, and Cu@MOF hybrid catalysts, are discussed. Finally, future research opportunities and strategies are suggested to innovate the rational design of advanced MOF-based Cu catalysts for electrifying CO2-to-C2+ transformation.
Preserved/rescued mitochondrial functions have a significant effect on maintaining neurogenesis, axonal carriage, and synaptic plasticity following spinal cord injury (SCI). We fabricated an ingenious redox-responsive strategy for commanded liberation of NADH (reduced form of nicotinamide-adenine dinucleotide) by bioactive diselenide-containing biodegradable mesoporous silica nanoparticles (Se@NADH). The nanocarrier-embedded NADH can be liberated in a controlled pattern through the cleavage of diselenide bonds in the presence of reactive oxygen species (ROS) or glutathione (GSH). The NAD+ was regenerated by the reactions between released NADH and harmful ROS to antagonize mitochondrial dysfunction and increase ATP synthesis, promoting axon regeneration across SCI areas. This nanosystem increased the stability of NADH during prolonged blood circulation time, reduced the clearance rate, exhibited significant anti-inflammatory as well as neuroprotective effects and enhanced the regeneration of electrophysiological conduction capacity across SCI areas. Importantly, Se@NADH suppressed glial scar formation and promoted neuronal generation as well as stretching of long axons throughout the glial scar, thereby improving actual restoration of locomotor functions in mice with SCI and exerting ascendant therapeutic effects. Targeting of mitochondrial dysfunction is a potential approach for SCI treatment and may be applied to other central nervous system diseases.
In children, hyper-IgM syndrome type 1 (HIGM1) is a type of severe antibody disorder, the pathogenesis of which remains unclear. The antibody diversity is partially determined by the alternative splicing (AS) in the germline, which is mainly regulated by RNA-binding proteins, including Breast cancer amplified sequence 2 (Bcas2). However, the effect of Bcas2 on AS and antibody production in activated B cells, the main immune cell type in the germline, remains unknown. To fill this gap, we created a conditional knockout (cKO, B cell-specific AID-Cre Bcas2fl/fl) mouse model and performed integrated mechanistic analysis on alternative splicing (AS) and CSR in B cells through the RNA-sequencing approach, cross-linking immunoprecipitation and sequencing (CLIP-seq) analysis, and interactome proteomics. The results demonstrate that Bcas2-cKO significantly decreased CSR in activated B cells without inhibiting the B cell development. Mechanistically, Bcas2 interacts with SRSF7 at a conservative circular domain, forming a complex to regulate the AS of genes involved in the post-switch transcription, thereby causing broad-spectrum changes in antibody production. Importantly, we identified GAAGAA as the binding motif of Bcas2 to RNAs and revealed its essential role in the regulation of Bcas2-dependent AS and CSR. In addition, we detected a mutation of at the 3’UTR of Bcas2 gene in children with HIGM1 and observed similar patterns of AS events and CSR in the patient that were discovered in the Bcas2-cKO B cells. Combined, our study elucidates the mechanism by which Bcas2-mediated AS affects CSR, offering potential insights into the clinical implications of Bcas2 in HIGM1.
Recent advances indicate the surface-enhanced Raman scattering (SERS) sensitivity of semiconductors is generally lower than that of noble metal substrates, and developing ultra-sensitive semiconductor SERS substrates is an urgent task. Here, SnS2 with better SERS performance is screened out from sulfides and selenides by density functional theory (DFT) calculations. Through adjusting the concentration of reactants to control the growth driving force without any surfactants or templates, SnS2 nanostrctures of stacked nanosheets (SNSs), microspheres (MSs) and microflowers (MFs) are developed, which all exhibit ultra-low limit of detections (LODs) of 10−12, 10−13, and 10−11 M, respectively. To the best of our knowledge, the SERS sensitivity of these three kinds of SnS2 nanostrctures are superior to most of the reported pure semiconductors and even can be parallel to the noble metals with a “hot spot” effect. This extraordinary SERS enhancement of SnS2 nanostrctures is originated from the dominated contribution of photo-induced charge transfer (PICT) resonance with different wavelength excitation lasers. Benefitting to the excellent SERS enhanced uniformity, generality, stability, ultra-high sensitivity of SnS2 nanostrctures, and the advantages that the PICT resonance enhancement excited for different probe molecules is not limited by its morphology, it is expected to provide a class of potential commercial SERS-active materials for the practical application of semiconductor-based SERS technology.
Wound healing in movable parts poses challenges owing to frequent activities, leading to delayed recovery and heightened susceptibility to bacterial infections and inflammation. Although hydrogel-based dressings have been explored, their therapeutic effectiveness is limited by poor resistance to stimuli and low mechanical strength. Here, we present a novel multifunctional PHC bandage that prevents bacterial infection and capitalizes on the inherent mobility of the affected area to expedite the wound-healing process. A PHC bandage was fabricated by incorporating photothermal copper bismuth sulfide (Cu3BiS3) nanomaterials into piezoelectric and pyroelectric polyvinylidene fluoride (PVDF). Upon exposure to alternating near-infrared light, the embedded Cu3BiS3 generated localized heat, activated PVDF, and induced the production of abundant reactive oxygen species for bacterial inactivation. Furthermore, continuous movement of the wound area triggers the PVDF to generate a sustained electrical field, promoting cell migration and proliferation to facilitate wound healing. The wound healing rate of PHC was 13.17 ± 2.09% higher than medical gauze. The robust encapsulation of PVDF ensured secure containment of the loaded Cu3BiS3 nanoparticles, improving the biocompatibility and sustainable utilization of this innovative wound dressing. This innovative design offers a promising and effective solution for improving wound healing in movable parts, potentially revolutionizing wound care technology.
Metal nitrides have emerged as promising materials for photoelectrochemical and electrochemical catalysis due to their unique electronic properties and structural versatility, offering high electrical conductivity and abundant active sites for catalytic reactions. Herein, we comprehensively explore the characteristics, synthesis, and application of diverse metal nitride catalysts. Fundamental features and catalytic advantages of metal nitrides are presented in terms of electronic structure and surface chemistry. We deal with synthetic principles and parameters of metal nitride catalysts in terms of nitrogen source, introducing synthesis strategies of metal nitrides with various morphologies and phases. Recent progress of metal nitride catalysts in (photo)electrochemical reactions, such as hydrogen evolution, oxygen evolution, oxygen reduction, nitrogen reduction, carbon dioxide reduction, and biomass valorization reactions, is discussed with their tailored roles. By providing future direction for remaining challenges, this review aims to guide the design of metal nitride catalysts from a materials point of view, contributing to expanding into energy and environmental technologies.
The advancements in early stratification and timely evaluation of therapeutic effects have revolutionized the ability to assess curative outcomes promptly. The separation between diagnosis/treatment and timely assessment of treatment response, along with delays in evaluating therapy efficacy, are significant contributors to treatment failures. Traditional approaches for evaluating curative effects face challenges posed by tumor heterogeneity and resistance, making it challenging to determine the effectiveness of a given therapeutic regimen at an early stage in clinical practice. However, molecular imaging using activatable probes has overcome these obstacles and transformed the field by shifting focus towards developing functional probes for visualizing tumors as well as enabling early stratification or timely evaluation of therapy effects. In this article, we emphasize the importance of diverse activatable molecular imaging probes and provide insights into early stratification or timely evaluation of various therapies’ effects. Finally, we discuss the challenges faced in this field and propose future research directions.
The modern technical era demands sustainable and green energy production and storage methods that overcome the limitations of conventional fuel resources. Electrochemical energy storage (ECS) technologies are widely anticipated to store and release energy on repeated cycles for domestic and commercial utilization. Several ECS devices were developed over the years to achieve higher energy density and energy sustainability. Zn-air batteries are developed to deliver higher energy density and their lower maintenance, flexibility, and rechargeability made them the significant sustainable energy device. However, the Zn anodes face several issues due to dendrite formation during several discharge cycles, HER at higher negative potentials, and corrosion behavior. Therefore, Zn-anode design strategies and significant electrolyte modifications were adopted to limit the critical issues. The review promptly exhibits the significance of Zn-air battery and their construction strategies. The present review highlights the rational design strategies for the stabilization of the Zn anode, such as coating with a passive layer, heterostructure and alloy-composite formation, and the major electrolyte modifications, such as using organic electrolytes, additives in aqueous electrolytes, and solid-state polymer gel electrolytes. The review is expected to attract a wide range of readers, from beginners to industrialists, which serve as a guide for developing Zn-air batteries.
Cochlear implants (CI) are the premier intervention for individuals with severe to profound hearing impairment. Worldwide, an estimated 600,000 individuals have enhanced their hearing through cochlear implantation, with nearly half being children. The evaluations after implantation are crucial for appropriate clinical interventions and care. Current clinical practice lacks methods to assess the recovery of advanced auditory functions in cochlear-implanted children. Yet, recent advancements in electroencephalographic (EEG) techniques show promise in accurately evaluating auditory rehabilitation in this demographic. This review elucidates the evolution of brain-computer interface (BCI) technology for auditory assessment, focusing primarily on its application in pediatric cochlear implant recipients. Emphasis is placed on promising clinical biomarkers for auditory rehabilitation and the neural adaptability accompanying cortical adjustments after implantation. Additionally, we discuss emerging challenges and prospects in applying BCI technology to these children.
The tumor microenvironment is characterized by immunosuppression and compromised intratumoral perfusion, which impairs the effectiveness of immune checkpoint inhibitors and nanomedicines. A significant challenge is the role of activated platelets, as they increase transfer-mediated PD-L1 expression from tumor cells and maintain the integrity of tumor vasculature. These platelets support tumor growth by stabilizing the vasculature and enabling immune evasion, as well as shielding tumor cells from immune detection. To address these platelet-mediated negative antitumor effects, we have developed bioengineered platelets (PTNPs) with surface-anchored ticagrelor-loaded gelatin nanoparticles. This study utilizes the natural tendency of platelets to localize their activated counterparts into tumors. Upon binding to tumor-associated activated platelets, the PTNPs release ticagrelor in response to the secreted matrix metalloproteinases by activated platelet, inhibiting further platelet activation. This reduction in platelet activation lessens platelet-facilitated immunosuppression and diminishes the transferred-PD-L1 expression from cancer cells to platelets, thus enhancing the immune response of anti-PD-L1 therapy. Additionally, this strategy weakens the activated platelets’ contribution to tumor vascular integrity, improving the extravasation and chemotherapeutic efficacy of nanomedicines. Our findings highlight the crucial role of platelet activation in tumor biology and introduce PTNPs as an effective approach to disrupt tumor-supporting platelet activities and enhance anticancer treatments efficacy.
Perovskite solar cells (PSCs) have attracted considerable attention due to their potential for high-efficiency conversion and cost-effective fabrication. Although the fabrication of perovskite films in ambient air offers environmental and cost advantages, the presence of water vapor and oxygen may induce instability in these films, thereby affecting device performance. This review aims to comprehensively explore recent advancements in the fabrication of PSCs in ambient air, while investigating various factors contributing to perovskite degradation. Addressing these challenges, diverse fabrication strategies are outlined, encompassing compositional, additive, solvent, and interface engineering to enhance the performance and stability of PSCs fabricated under ambient air. To facilitate the commercialization of PSCs, this paper summarizes several widely employed methods for the large-scale manufacturing of PSCs. Through this review, we aim to offer some invaluable insights and guidance for the commercialization trajectory of PSCs, as well as the pros and cons to their widespread applications in the field of renewable energy.
Inorganic protein hybrid materials (IPHMs) due to editable structure present unrivalled potential at the intersection of synthetic biology and materials science. The synthesis of IPHMs with a high degree of biosafety from bioactive units represents a shift in material design and synthesis. This paper focuses on a review of the structural basis and design principles of proteins for the synthesis of IPHMs with specific physical and chemical functions. It also provides a valuable reference for the design of emerging IPHMs through the conformational relationship of the IPHMs, which extends the potential applications of IPHMs. In addition, the construction strategy of the reaction system for the synthesis of hybrid materials is analyzed from the perspective of synthetic biology. The possibility of engineering and batch synthesis of IPHMs is discussed. Based on the physicochemical properties of different hybrid materials and the applied-oriented research on biomedical optical imaging and multimodal therapy, the idea of synthesis of in situ hybrid materials is proposed. Ultimately, the trends and challenges of synthetic biology for IPHMs are speculated in detail.
This study investigated a Chinese family with congenital posterior polar cataracts linked to the βB2-R188C mutation. βB2-crystallin, a key structural component of the lens, is crucial for maintaining lens transparency and stability. We examined the effects of the R188C mutation on βB2-crystallin's structural stability and resistance to environmental stressors using purified proteins and cellular models. The βB2-R188C mutant showed poor stability and a tendency to aggregate under physiological and pathological conditions. The mutation disrupted the oligomerization equilibrium, causing dissociation of dimers into monomers. Molecular dynamics simulations and spectroscopic experiments revealed abnormal protein folding induced by the R188C mutation, increasing susceptibility to environmental stressors. Aggregation was observed in both prokaryotic and eukaryotic models under normal conditions, with enhanced severity under environmental stressors. Notably, lanosterol treatment or αB-crystallin partially reversed aggregation. In summary, the R188C mutation promotes abnormal aggregation by destabilizing βB2-crystallin and disrupting oligomerization equilibrium, potentially leading to cataract formation. Targeting aggregate formation with small molecules like lanosterol or enhancing molecular chaperone activity offers a promising strategy for cataract prevention and treatment.
Nanozyme-based immunogenic cell death (ICD) inducers that effectively induce a strong immune response via enzyme-like process have attracted great attention, but how to ensure controllable active sites and maximize site utilization remains a problem. Here, we report a structurally well-defined and highly functional single-site copper(I) nanomodulators termed CuNTD, constructed by precisely anchoring atomically dispersed self-assembly S-Cu(I)-S sites onto a two-dimensional Ti3C2 surface. Leveraging Cu+ with a higher catalytic efficiency than Cu2+, CuNTD generates reactive oxygen species (ROS) storms through photothermal-enhanced cascade catalysis, further inducing mitochondrial dysfunction, ferroptosis and cuproptosis. Multifunctional CuNTD triggers strong ICD through cascade-regulatory pathways of photothermal-amplified ROS storms, cuproptosis and ferroptosis, effectively promoting dendritic cell maturation while reducing monotherapies side effects and resistance. In vivo, CuNTD combined with FDA-approved immunoadjuvants significantly prolong the survival of mice. With its demonstrated biosafety and high efficiency as an ICD inducer, this study provides a promising framework for advancing augmented tumor immunotherapy with significant clinical potential.
Stroke remains the leading cause of neurological mortality and disability worldwide, with post-stroke inflammation significantly hindering neural repair. Despite its critical impact, mechanism-based therapeutic strategies are scarce. In this study, we uncovered a critically important yet previously unexamined cell population, p21+CD86+ microglia, which accumulated in ischemic region. Unexpectedly, we discovered that p21 interacted with C/EBPβ, driving C/EBPβ-dependent transcription and upregulating key pro-inflammatory factors such as Il6, Il1β, Cxcl2, and Cxcl10. To specifically target and eliminate these pathogenic p21+CD86+ microglia, we engineered exosomes with a peptide that selectively binds CD86+ microglia and loaded them with the senolytic Quercetin. Furthermore, we developed an optimized, stable Que@micro-Exo therapeutic formulation. Systemic administration of Que@micro-Exo robustly reduced p21+CD86+ microglia and suppressed their pro-inflammatory phenotype. Notably, functional analyses revealed that Que@micro-Exo treatment mitigated blood-brain barrier disruption, promoted beneficial microglial polarization, decreased neutrophil infiltration, and significantly enhanced functional recovery following cerebral ischemia, all with a favorable safety profile. Our preclinical findings lay the foundation for targeting p21+CD86+ microglia as a novel therapeutic strategy, highlighting the potential of exosome-based senolytic anti-inflammatory therapy for stroke and other central nervous system disorders.