With the aging population, treating age-related osteoporosis remains challenging due to the dysfunctional bone marrow microenvironment characterized by chronic inflammation, metabolic dysregulation, and impaired mitochondrial function in senescent cells. While mitochondrial transfer from macrophages to bone marrow mesenchymal stem cells (BMSCs) offers a promising therapeutic avenue, its efficacy is limited in aged niches where donor mitochondria exhibit functional deficits and poor recipient compatibility. We engineered KGM-PEG-SPIONs, functionalized Fe3O4 nanoparticles that enhance donor mitochondrial quality via autophagy activation and Fe-S cluster biogenesis, promote M2 macrophage polarization, and improve compatibility with the oxidative and inflammatory environment of senescent BMSCs. These M2-like mitochondria are transferred through connexin 43 gap junctions, restoring membrane potential, ATP production, calcium homeostasis, and osteogenic differentiation in recipient cells. In aged osteoporotic models, KGM-PEG-SPION-functionalized scaffolds remodel immune niches and promote bone formation. By integrating organelle quality control with environment-adapted mitochondrial transfer, this strategy surpasses approaches focusing solely on transfer quantity or polarization, establishing a programmable nanoplatform for organelle-based regeneration.

Abstract Cellular senescence significantly impairs tissue repair through disrupting tissue homeostasis and limiting regenerative capacity. Biomaterial based microenvironment modulation has emerged as a promising strategy to counteract senescence and promote tissue regeneration. While mechanical properties such as matrix stiffness are known to influence cell fate, whether different tissue-derived cells exhibit distinct mechanical requirements for senescence resistance remains poorly understood. Here, we used stiffness-tunable polyacrylamide hydrogels spanning physiologically relevant elastic moduli and systematically evaluated senescence responses in neuronal (SH-SY5Y), dermal fibroblast (NIH3T3), and osteoblast precursor (MC3T3-E1) cells. Our results revealed tissue-specific stiffness windows that maximally suppressed senescence, with optimal senescence resistance responses observed at 1 kPa, 10 kPa, and 250 kPa for SH-SY5Y, NIH3T3, and MC3T3-E1 cells, respectively. Mechanistically, integrin α1, a collagen-binding integrin, was identified as a key mechanosensor mediating these effects. Optimal stiffness conditions enhanced integrin α1-mediated mechanotransduction, cytoskeletal remodeling, and activation of PI3K–Akt and YAP signaling pathways, leading to the downregulation of senescence markers (p16, p21) and upregulation of proliferation related genes. These findings provide a mechanistic framework for the design of stiffness-matched biomaterials to counteract senescence and enhance tissue regeneration. Graphical Abstract

Small-diameter vascular grafts (SDVGs) are prone to thrombosis and have low long-term patency rates for various reasons, which cannot meet the clinical requirements. In this work, Human amniotic mesenchymal stem cell (hAMSC) seeding electrospun polylactic acid-co-polycaprolactone (PLCL) SDVGs are fabricated and their application potential is systematically evaluated. The SDVG has excellent mechanical properties. PLCL eletrospinning membrane has no cytotoxicity. The SDVG has a porous fibrous tube wall, uniform distribution of hAMSCs, and good cell compatibility, blood compatibility, histocompatibility and mechanical properties. hAMSCs loading can improve the acute antithrombotic ability, patency and in vivo regeneration effect of PLCL electrospun SDVGs. The mechanism is related to hAMSCs increasing the content of endothelial cells, contractile smooth muscle cells, and M2 macrophages, as well as activating extracellular matrix production.

Background: Chemokines play a pivotal role in the progression of osteoarthritis (OA), but their exact mechanisms remain unclear. This study aimed to identify potential chemokine-associated biomarkers and investigate their causal relationships with OA. Methods: Transcriptome and genome-wide association study (GWAS) data were obtained from public databases, while chemokine-related genes (CRGs) were sourced from the literature. Initially, CRGs were expanded, followed by Mendelian randomization (MR) analysis, differential expression analysis, machine learning, and receiver operating characteristic (ROC) curve plotting to identify potential biomarkers. The causal relationships between these biomarkers and OA, as well as their biological functions, were further explored. Results: Fourteen candidate genes were identified for machine learning analysis, with DDIT3, CEBPB, CX3CR1, and ARHGAP25 emerging as feature genes. CEBPB and CX3CR1, which exhibited AUCs > 0.7 in the GSE55235 and GSE55457 datasets, were selected as potential biomarkers. Notably, CEBPB expression was lower, while CX3CR1 expression was elevated in the case group. Furthermore, both genes were co-enriched in spliceosome, lysosome, and cell adhesion molecule pathways. MR analysis confirmed that CEBPB and CX3CR1 were causally linked to OA and acted as protective factors (IVW model for CEBPB: OR = 0.9051, p = 0.0001; IVW model for CX3CR1: OR = 0.8141, p = 0.0282). Conclusions: CEBPB and CX3CR1 were identified as potential chemokine-related biomarkers, offering insights into OA and suggesting new avenues for further investigation.

Effective regenerative strategies for spinal cord injury (SCI) depend on promoting neuronal regeneration and suppressing inflammation, both requiring substantial energy. Succinic acid-based materials have attracted attention for enhancing cellular energy through the tricarboxylic acid (TCA) cycle and mitochondrial electron transport. However, succinic potential to exacerbate inflammation complicates therapeutic use, making it crucial to understand how these materials regulate microglial polarization. Here, we presented a degradable bioenergy hydrogel system by integrating succinic acid (SA) into chitosan (CS), yielding an energy-active unit. Upon implantation, degradation of chitosan released energy-active units, which were transported into Bv2 microglial cells via SLC13A3, thereby engaging mitochondrial electron transport chain and the TCA cycle. At optimized concentrations, these energy-active units facilitated M2 polarization of Bv2 cells, augmenting adenosine triphosphate (ATP) levels and driving anti-inflammatory factor expression to support tissue repair. Conversely, excess concentrations triggered mitochondrial reverse electron transport, elevating reactive oxygen species (ROS) production, impairing ATP synthase, and enhancing pro-inflammatory factor release via SLC25A10mediated succinate export. This concentration-dependent effect underscores the nuanced role of succinic acid in modulating microglial polarization states. Furthermore, degradation of CSSA fragments activated the AMPKmTOR and cAMP signaling pathways, significantly boosting ATP synthesis and fostering M2 microglial polarization. Our findings offer a novel avenue to enhance SCI repair by modulating cellular energy balance and refining the inflammatory milieu, while establishing critical concentration parameters for the deployment of succinic acid-based biomaterials in tissue regeneration contexts.

Viscoelastic matrices enhance cell interactions, promoting aggregation to resist aging. This activates the integrin–cytoskeleton–YAP axis and inhibits aging pathways including Wnt/β-catenin, MAPK, NF-κB, and TGF-β.

Natural intercellular mitochondrial transfer has been recognized as a pivotal mechanism in the treatment of various diseases. Bone marrow mesenchymal stem cells (BMSCs), owing to their low bioenergetic demands and inherent homing capacity, are considered highly promising mitochondrial donor cells. However, this strategy is limited in senile osteoporosis (SOP) because large amounts of ROS produced by mitochondrial oxidative stress in senescent BMSCs (S-BMSCs) impairs their viability and function. Here, we report that in-situ treatment of senescent bone marrow-derived macrophages (S-BMDMs) with a cerium-based nanosystem (CNS) composed of antioxidant and energy-active units, which exhibits superior autophagy-activating capability, effectively restores the viability and osteogenic function of S-BMSCs by promoting mitochondrial biogenesis and transfer. Transcriptomic profiling revealed that the SIRT1-PGC-1α axis, significantly associated with autophagy activation, drives mitochondrial biogenesis in S-BMDMs. The efficient intercellular mitochondrial transfer ameliorates the senescent bone microenvironment, rescues S-BMSCs functionality, and enhances bone formation. In conclusion, the autophagy-activating CNS, by effectively rejuvenating S-BMDMs and promoting mitochondrial biogenesis and transfer, provides an innovative therapeutic strategy for SOP-associated bone regeneration.

Purpose In recent years, the application of extended reality (XR) technology in acupuncture-related research and practice has gained increasing popularity. This article aimed to conduct a bibliometric analysis in this field. Methods Publications between 1996 and 2024 in this field were searched in Web of Science Core Collection and Scopus. Software used for data preprocessing and analysis included Microsoft Excel, RStudio, CiteSpace, and VOSviewer. Results A total of 143 articles were selected. Publications in this field were increasing rapidly. The top three countries by publication volume were China, the United States and Canada. The top three most-cited countries were the United States, Belgium and China. The overall cooperation network was loose and mainly dominated by China, the United States, and the United Kingdom. The top three affiliations by publication volume were University of Toronto, Emory University, and Southern Medical University. KU Leuven had the highest total and average citations. The author with the most publications and total citations was Moseley G. The source with the most publications was Frontiers in Neurology, whereas the top cited source was Frontiers in Human Neuroscience. Hatem SM (Front Hum Neurosci, 2016) was the top cited publication with the highest average annual citation rate. The most frequent keywords included “virtual reality”, “acupuncture”, “cognitive behavioral therapy”, “stroke” and “pain”. Keyword clusters mainly focused on three aspects: neurological rehabilitation, mental health and pain management. An isolated sub-cluster existed in mental health cluster with “simulation” as its core keyword. Conclusion As a specialized domain, the field is expected to progress by forging a more direct integration of XR with acupuncture and a deeper convergence of basic science and clinical practice, indicating substantial progress in the future.

The effects of calcium phosphate (CaP) materials on macrophage polarization state vary with their physicochemical properties. The study aims to elucidate the impact of phosphate ion-mediated energy metabolism on M2 macrophage polarization and the corresponding regulatory mechanism. The phosphate ions released from CaP ceramic as bioenergetic factor is identified; its concentration is closely associated with the polarized state. After being taken up by the sodium-dependent phosphate transporter 1, extracellular phosphate ions produce energy via oxidative phosphorylation by facilitating tricarboxylic acid flux, thereby contributing to M2 macrophage polarization. Further mechanistic analysis reveals that the elevation of the bioenergetic basis can drive macrophage M2 polarization via the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) axis. Another regulatory effect is that of the adenosine triphosphate (ATP), a signaling molecule. Intracellular ATP is released into the extracellular space and degraded to adenosine, which serves as a signaling molecule through the A2b adenosine receptor to activate the cyclic adenosine monophosphate (cAMP) pathway, thereby promoting M2 macrophage polarization. Overall, these findings may transform the existing knowledge on cell metabolism and energy homeostasis from bystanders to pivotal factors guiding M2 macrophage polarization and have implications for the future design of biomimetic CaP scaffolds.

As a natural cationic polymer material, the application of chitosan hydrogel for bone tissue engineering has been greatly limited due to its poor mechanical strength. Enzymatic mineralization has drawn increased attention to effectively improve the mechanical properties of hydrogels. In this study, carboxymethyl chitosan (CMCS) hydrogels cross-linked with different concentrations of genipin (2.5 %, 5 % and 10 %) were prepared and further mineralized through enzyme-induced biomimetic mineralization. The mechanical properties of the CMCS hydrogels were significantly increased as a result of mineralization, showing improvement of 1200-1500 % on storage moduli, and even exhibiting certain tensile behavior with the elongation rate of 30-35 %, likely due to the uniform formation and small size of mineralized products. Interestingly, the cationicity of chitosan also exerted an important modulation effect and the mineralization behavior and mechanical properties of mineralized hydrogels. In addition, the enzymatic mineralized hydrogels showed enhanced biocompatibility and osteogenic differentiation in-vitro, likely due to its superior mechanical properties and the introduction of calcium phosphate biominerals. In vivo experiments further suggest excellent bone-forming activity for the enzymatic mineralized hydrogels. Overall, tuning cationicity and enzymatic mineralization provide an effective approach for the preparation of chitosan hydrogels with superior mechanical and biological properties for bone tissue engineering application.

Treatment based on meridian differentiation is a characteristic method in clinical acupuncture diagnosis and treatment. Accurately defining and explaining its main content and core concepts is essential for effective clinical guidance. This paper reviews the historical and contemporary understanding, concepts, and primary content of treatment based on meridian differentiation. It proposes a four-step process for clinical application: meridian examination, treatment based on meridian differentiation, acupoint selection, and appropriate treatment methods, with TCM syndrome differentiation applied throughout. Constructing a diagnostic and treatment system which is based on meridian differentiation and suited to clinical acupuncture is significant for enhancing therapeutic efficacy and maximizing the benefits of acupuncture in disease treatment.

Brain metastases and lung metastases are major causes of treatment failure and related mortality in melanoma. Fluoxetine hydrochloride (FXT), a widely-used antidepressant, has emerged as a potential anticancer agent in preclinical studies. Previous research has shown its potential to inhibit melanoma. However, its efficacy and the underlying mechanisms in melanoma metastasis, especially concerning brain metastases and lung metastases, remain underexplored. This study investigates FXT's inhibitory effects on melanoma growth and metastasis to the lung and brain. Employing a combination of in vitro assays, we demonstrate FXT's potent suppression of melanoma growth through induction of intrinsic apoptosis, disruption of autophagic flux, and cell cycle arrest at the G0/G1 phase. In in vivo mouse models, we found that FXT exhibits strong inhibitory activity against melanoma brain metastases and lung metastases. Our findings provide a foundation for future clinical exploration of FXT as a novel treatment strategy for melanoma, underscoring its ability to target both primary and metastatic lesions.

The limitations of traditional drug therapy have driven the creation and development of novel cell membrane-coated nanoparticle (CMNP) platforms. Since the introduction of the CMNP concept and method in 2011, an increasing number of studies focusing on this field have been widely conducted. Despite the growing body of literature, comprehensive bibliometric analysis in this field is still lacking. This study conducted a bibliometric analysis of CMNP-related publications sourced from the Web of Science Core Collection database, covering the period from January 1, 2011, to December 31, 2023. The analysis included co-authorships, co-citations, and co-occurrences of countries, institutions, authors, references, and keywords. Visualized tools such as Citespace, VOSviewer, and R Package Bibliometrix were employed to present the data. A total of 780 studies were included, with China contributing the highest number of publications (75.64%, n = 590). The number of annual publications increased consistently from 2011 to 2023, indicating a growing global interest in the CMNP field. Prof. Liangfang Zhang from the United States is recognized as the founder and leading figure in this area. The top three academic journals in this field, based on publication volume, are ACS Nano (32 publications, IF 2022 = 17.1), ACS Applied Materials Interfaces (32 publications, IF 2022 = 9.5), and Advanced Functional Materials (31 publications, IF 2022 = 19) among 185 scholarly journals. Reference and keyword analysis revealed that erythrocytes and macrophage membranes are significant research hotspots. The primary diseases targeted by CMNP research are cancer and pulmonary inflammation. In addition, CMNPs are frequently studied in conjunction with photothermal and photodynamic therapy. Furthermore, this study also summarized the timelines for various cell membrane coating methods and the three-step preparation process for CMNP. This comprehensive bibliometric analysis provides valuable insights to guide future research in the CMNP field, highlighting the importance of clinical application. Research on cell membrane-coated nanomaterials, particularly those related to cancer and pulmonary inflammation, is expected to remain a focal point. In addition, there is a need for the further development of other potential cell membrane-coated nanomaterials. This bibliometric analysis serves as a resource for researchers to quickly and comprehensively understand the current hotspots and emerging frontiers in this field.

Resumo Objetivo Avaliar os efeitos do modelo de enfermagem de Newman na qualidade de vida e recuperação muscular do assoalho pélvico em pacientes com disfunção do assoalho pélvico pós-parto. Métodos Oitenta e oito pacientes com disfunção do assoalho pélvico pós-parto tratadas de janeiro a abril de 2023 foram divididas em grupo Observação e Controle (n=44) por meio de tabela de números aleatórios. O grupo Controle recebeu enfermagem de rotina e o grupo Observação recebeu cuidados de enfermagem de Newman. A qualidade de vida foi avaliada pelo Short Form-36 Health Status Questionnaire. A função do assoalho pélvico foi avaliada por meio do Pelvic Floor Impact Questionnaire-7 (PFIQ7) e da Pelvic Organ Prolapse Quantification (POPQ). Resultados Após a intervenção, as pontuações de aspectos físico, emocional, capacidade funcional, social e motor do grupo Observação foram superiores às do grupo Controle (P<0,05). As pontuações da Escala de Autoavaliação de Ansiedade e da Escala de Autoavaliação de Depressão do grupo Observação foram inferiores às do grupo Controle. O nível de conhecimento sobre a doença foi maior no grupo Observação do que no grupo Controle (P<0,05). O grupo Observação apresentou maior força das fibras musculares tipo I e II, e menores graus de fadiga das fibras musculares tipo I e II do que o grupo Controle (P<0,05). As pontuações PEIQ7 e POPQ do grupo Observação foram inferiores às do grupo Controle (P<0,05). Conclusão O modelo de enfermagem de Newman ajuda a melhorar a função do assoalho pélvico, a qualidade de vida e o conhecimento sobre a doença, além de aliviar a ansiedade, a depressão e outras emoções adversas.

A primary challenge in spinal cord injury repair is the presence of an energy deficit, exacerbated by the injury itself, thereby intensifying the dilemma of insufficient energy. Hence, we posit a hypothesis suggesting that the adoption of a direct energy-supply material strategy has the potential to enhance in situ cellular energy levels, facilitating the acceleration of neuronal differentiation and axonal elongation. We successfully designed a degradable bioenergetic hydrogel by introducing succinic acid (SA), a key intermediate in tricarboxylic acid (TCA) cycle, into chitosan (CS) as an energy-active unit, which was released in a sustained degradation-mediated fashion once implanted. The degraded energy-active units, after being internalized, increased bioenergetic levels via oxidative phosphorylation (OXPHOS) by facilitating TCA flux, thereby contributing to a at least 1.5-fold increase in the expression levels of neuronal differentiation-related markers in vitro, as well as the enhanced spinal cord injury repair and functional recovery in vivo. Further mechanism analysis demonstrated that the upregulation of the bioenergetic basis had the potential to induce neuronal differentiation through the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) axis. Additionally, the adenosine triphosphate (ATP) itself acted as a signaling molecule via the P2X7 receptor, leading to the upregulation of intracellular calcium ion-MAPK signal cascades, ultimately promoting neuronal differentiation. Overall, these findings have the potential to significantly alter our understanding of cell metabolism and energy homeostasis, transforming them from passive observers to critical factors in guiding nerve regeneration, and may have implications for future design of bioenergetic-active materials.

Early instigation and subsequent attenuation of inflammation are crucial for tissue regeneration, which poses a need for inflammatory regulation in the design of materials. In this work, a novel photocatalytic heterojunction consist of MXene, Zr-based porphyrinic metal-organic framework (named PCN-222), and Pt nanoparticles (termed MX/PCN@Pt HJs) is developed to achieve photo-controlled reactive oxygen species (ROS) generation and clearance. According to density function theory calculations and related experiments, the unique heterojunction formed by MXene and MOFs, abundant O-2 adsorption sites of metal oxide clusters, and porous features of MOFs promoted the adsorption of active reactants and accelerated electron transfer, thereby exhibiting excellent photocatalytic performance. Meanwhile, the PCN-222 with superoxide dismutase (SOD) activity and Pt nanoparticles with catalase (CAT) activity endowed the MX/PCN@Pt HJs with SOD/CAT mimetic cascade performance. Through the photo-controlled regulation, the MX/PCN@Pt HJs acted as a photoswitch that flexibly achieved the switch between ROS generation and clearance. Effective production of ROS not only enabled antimicrobial activity but also contributed to a pro-inflammatory state; while the timely ROS scavenging activity effectively prevented the detrimental effects of sustained inflammation. Both in vitro and in vivo evaluations had confirmed the inflammatory modulation and tissue regeneration potency of the MX/PCN@Pt HJs based on the ROS-regulated strategy, which offer a vital understanding of the MOF-based photocatalytic heterojunction for programmed inflammatory regulation.

The reconstruction of bone defects following bone tumor resection pose significant challenges, including high risks for tumor recurrence. To address these challenges, we designed controlled-domain gels that possessed exceptional anti-tumorigenic effectiveness and osteogenic activity. This was achieved through the selection of an amino-acid-based low-molecular-weight gels (LMWGs) with superior biocompatibility and antitumor efficacy, and further construction of three-domain structure with a large -range stiffness gradient, through the assembly/ disassembly of LMWGs inside a stable methacrylated alginate (AlgMA) network using photopolymerization. Such layered design not only constructed a top anti-tumorigenic domain at 0.6 kPa and a bottom osteogenic domain at 500 kPa, allowing for selectively inducing tumor cell apoptosis and promoting osteogenic differentiation of mesenchymal stem cells (MSCs), but also generated a gradient selectively confining the migration of tumor cells along soft -to -hard direction, without affecting the recruiting of MSCs toward the injury sites. In particular, the critical involvement of the DAPK-mediated signaling cascades might lead to the selected apoptosis of tumor cells on LMWG domain. The in-vivo results further suggested that multi-domain gel effectively inhibited tumor growth and displayed excellent bone -forming activity. Overall, such strategies could advance our fundamental understanding of the bone tumor postoperative treatment, in addition to offering new therapeutic opportunities.

Increasing studies have revealed the importance of mechanical cues in tumor progression, invasiveness and drug resistance. During malignant transformation, changes manifest in either the mechanical properties of the tissue or the cellular ability to sense and respond to mechanical signals. The major focus of the review is the subtle correlation between mechanical cues and apoptosis in tumor cells from a mechanobiology perspective. To begin, we focus on the intracellular force, examining the mechanical properties of the cell interior, and outlining the role that the cytoskeleton and intracellular organelle-mediated intracellular forces play in tumor cell apoptosis. This article also elucidates the mechanisms by which extracellular forces guide tumor cell mechanosensing, ultimately triggering the activation of the mechanotransduction pathway and impacting tumor cell apoptosis. Finally, a comprehensive examination of the present status of the design and development of anti-cancer materials targeting mechanotransduction is presented, emphasizing the underlying design principles. Furthermore, the article underscores the need to address several unresolved inquiries to enhance our comprehension of cancer therapeutics that target mechanotransduction.

Objective Assessing rehabilitation effectiveness for persistent symptoms post-infection with emerging viral respiratory diseases.Data sources Systematic review of seven databases (MEDLINE, EMBASE, Cochrane Library, PEDro, MedRxiv, CNKI, Wanfang) until 30 December 2023.Review methods Evaluated 101 studies (9593 participants) on respiratory function, exercise capacity, and quality of life. Methodological quality was assessed using the Cochrane Collaboration's Risk of Bias tool for randomized controlled trials (RCTs), the Newcastle-Ottawa Scale (NOS) for observational studies and non-RCTs, and the NIH Quality Assessment Tools for before-after studies.Results The most common rehabilitation program combined breathing exercises with aerobic exercise or strength training. Rehabilitation interventions significantly enhanced respiratory function, as evidenced by improvements on the Borg Scale (MD, -1.85; 95% CI, -3.00 to -0.70, low certainty), the mMRC Dyspnea Scale (MD, -0.45; 95% CI, -0.72 to -0.18, low certainty), and the Multidimensional Dyspnoea-12 Scale (MD, -4.64; 95% CI, -6.54 to -2.74, moderate certainty). Exercise capacity also improved, demonstrated by results from the Six-Minute Walk Test (MD, 38.18; 95% CI, 25.33-51.03, moderate certainty) and the Sit-to-Stand Test (MD, 3.04; 95% CI, 1.07-5.01, low certainty).Conclusion Rehabilitation interventions are promising for survivors of viral respiratory diseases, yet gaps in research remain. Future investigations should focus on personalizing rehabilitation efforts, utilizing remote technology-assisted programs, improving research quality, and identifying specific subgroups for customized rehabilitation strategies to achieve the best outcomes for survivors.