The regeneration of infected diabetic bone defects is impeded by metabolic niche dysregulation, driven by a self-reinforcing negative feedback loop between the disordered extracellular microenvironment and intracellular mitochondrial dysfunction. To address this issue, we developed a bio-heterojunction engineered workshop (MoSe2/PtCu@LOx) that simultaneously remodels the extracellular metabolic microenvironment and restores intracellular mitochondrial bioenergetics to promote infected diabetic bone repair. The MoSe2/PtCu heterojunction enables NIR-responsive photothermal and photodynamic antibacterial activity, while PtCu nanoparticles and lactate oxidase (LOx) effectively eliminate excessive reactive oxygen species (ROS) and accumulated lactate, thereby alleviating oxidative stress and acidosis. Crucially, the released selenium activates SIRT3 signaling, upregulating selenoprotein Gpx1 expression and stabilizing mitofusin 2 (Mfn2), which enhances mitophagic flux and restores mitochondrial bioenergetics. This recovery boosts oxidative phosphorylation (OXPHOS) efficiency and ATP production, driving osteogenic differentiation and bone matrix mineralization of BMSCs at the bioenergetic level. Collectively, this bio-heterojunction engineered workshop bridges extracellular metabolic normalization with intracellular energy recovery, effectively disrupting the metabolic negative feedback loop in the infected diabetic microenvironment. In vivo results authenticate that this workshop promotes infected diabetic bone repair, providing a metabolic-oriented therapeutic paradigm for bone regeneration under infected and diabetic conditions.

The regeneration of aging-associated bone defects is severely compromised by elevated oxidative stress and impaired mitochondrial function, which collectively undermine osteogenic capacity. Herein, we developed a biomimetic antioxidase based on a Cu/Zn synergistic metal-organic framework (CZpz-MOF) that structurally and functionally mimics the active center of natural Cu/Zn superoxide dismutase (SOD). The Zn-modulated Cu sites significantly enhanced the SOD-like activity, achieving a high catalytic efficiency of 45,173 U/mg, along with notable catalase (CAT)-like activity, enabling effective scavenging of multiple reactive oxygen species (ROS). By eliminating excess ROS, the CZpz-MOF ameliorated the pathological microenvironment and regulated macrophage polarization toward antiinflammatory phenotype. In addition, the CZpz-MOF effectively scavenged mitochondrial ROS, restored mitochondrial membrane potential, and rebalanced mitochondrial dynamics, thereby interrupting the "ROS-induced ROS release" vicious cycle. It alleviated cellular senescence by reducing SA-beta-gal activity and down-regulating p21 and p16 expression. Significantly, the integration of Zn active element endowed the CZpz-MOF antioxidases with significant ability to promote osteogenesis. In an aged rat model of osteoporosis, the CZpz-MOF loaded hydrogel significantly accelerated bone regeneration. This study demonstrates that the biomimetic CZpz-MOF system synergistically integrates antioxidative and osteogenic functions via Cu/Zn cooperation, providing an effective strategy for treating aging-related bone defects.

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.

The poor healing of diabetic wounds is attributed to infection, oxidative stress, and inflammation, representing a substantial clinical burden. Conventional nanozyme therapies are often constrained by inefficient catalytic cascades due to antagonistic or competitive interference. To overcome these limitations, we have developed a nanozyme composed of herb-derived carbon dots loaded with Fe single atoms (Fe SA@CDs) with the capability of mimicking multi-enzyme activity for ROS elimination and ROS generation in a pH-dependent manner, enabling an "intelligent switching" therapeutic function. Under acidic conditions, it displays NIR light-enhanced POD-like activity (up to 656.6 U/mg) to generate ROS for antibacterial applications. In neutral environment, it exhibits SOD-like activity (up to 2341.9 U/mg) and CAT-like activity to eliminate endogenous ROS for reducing oxidative stress and alleviating inflammation. In vivo experiments show that Fe SA@CDs can dynamically adjust its treatment strategy based on the pH changes in microenvironment: exerting strong antibacterial effects in the early acidic stage, shifting towards anti-inflammatory and regenerative functions in the neutral middle and late stages, thereby achieving a wound healing rate of 92.3 % on day 14. This study demonstrates a smart and microenvironment-responsive nanocatalytic therapy strategy for infected diabetic wound treatment.

Reactive oxygen species (ROS) mediated redox imbalance stands as an important factor contributing to the pathological bone loss, which is characterized by osteoclast hyperactivation and inflammatory activation. Developing ROS-scavenging nanocatalysts emerges as an intriguing strategy to regulate redox balance and bone homeostasis. Herein, this study reveals that Mn-atom-modulation strategy could introduce oxygen vacancy defects and further regulate electronic structure of CeO2 nanocatalysts with an increased ratio of Ce3+/Ce4+ (named Mn@CeO2), which promote electron redistribution and enhance comprehensive ROS-scavenging performances. Consequently, the Mn@CeO2 nanocatalysts show significant inhibition of osteoclastogenesis activity and ameliorate the inflammatory state through the NF-kappa B and MAPK pathways. Notably, exogenous supplementation of Mn element can promote the osteogenesis activation through the Wnt/beta-catenin pathway. Both in vitro/vivo evaluations, this proposed bistimulatory strategy significantly facilitate pathological bone reconstruction via macrophage polarization, osteoclastogenesis inhibition, and osteogenesis activation. This work not only proposes versatile nanocatalysts for pathological bone therapy but also provides novel solution to develop biocatalytic metal oxides through rational regulation of electronic structure.

Regeneration of diabetic bone defects remains a formidable challenge due to the chronic hyperglycemic state, which triggers the accumulation of advanced glycation end products (AGEs) and reactive oxygen species (ROS). To address this issue, we have engineered a bimetallic metal-organic framework-derived Mn@Co3O4@Pt nanoenzyme loaded with alendronate and Mg2+ ions (termed MCPtA) to regulate the hyperglycemic microenvironment and recover the osteogenesis/osteoclast homeostasis. Notably, the Mn atom substitution in the Co3O4 nanocrystalline structure could modulate the electronic structure and significantly improve the SOD/CAT catalytic activity for ROS scavenging. By integration with GOx-like Pt nanoparticles, the MCPtA achieved effective multiple cascade catalytic performance that facilitated the clearance of glucose and ROS. Furthermore, the MCPtA was encapsulated within a glucose-responsive hydrogel cross-linked via a borate ester bond, termed PAM, to evaluate the potential of the composite hydrogel for cranial defect repair in diabetic rats. The in vitro/vivo experiments as well as the RNA sequencing analysis demonstrated that the nanoenzyme composite hydrogel could disrupt the glucose-ROS-induced inflammation and promoted osteogenesis and angiogenesis, in consequence, improving the therapeutic effects for diabetic bone regeneration. This study provided crucial insights into nanoenzyme-mediated microenvironmental regulation for diabetic bone regeneration.

Immunotherapy holds promise as an alternative to antibiotics in treating burn infections. However, the inadequacy of immune response or excessive inflammation both hinder effective bacterial clearance through immunotherapy, therefore necessitating a comprehensive approach that not only enhances immunotherapy against bacteria but also maintains immune homeostasis and promotes skin regeneration. Here, a membrane fusion-driven combination immunotherapy is reported that mobilizes macrophages to address abovementioned limitations. The core-shell structured membrane fusion-liposomes (MFL-Gal-Mal/Cur) can fuse their functional phospholipid shells with macrophages and bacteria, resulting in the remodeling of targets' surfaces with the galactose-maltotriose (Gal-Mal) moieties, and delivering their cores (curcumin-loaded mesoporous polydopamine, MPDA/Cur) into targets. The embedded Gal-Mal on membranes enhances macrophages' ability to phagocytize bacteria, as well as increases bacteria's sensitivity to immune cell-mediated killing. The intracellular MPDA/Cur evade lysosomal degradation, exerting antibacterial effects while also enhancing macrophage lysosomal bactericidal activity through autophagy promotion. This immunotherapy enhances macrophages' capacity to phagocytize (increase rate for S. aureus: 21%; E. coli: 29%) and eliminate intracellular bacteria (clearance rate for S. aureus: 98%; E. coli: 99%), without exacerbating inflammatory responses. The release of MFL-Gal-Mal/Cur from the polysaccharide composite hydrogel can alleviate pain and itching sensations in infected burns, while activating the regeneration of skin appendages.

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.

The antibiotic resistance of bacteria and the lack of efficient antibacterial agents result in significant worsening of microbial infection symptoms. To address this daunting issue, a multimodal antibacterial strategy that combines exogenous and endogenous stimulations is proposed. A novel two-dimensional heterojunction (termed MXP HJs) is developed by in situ growth of the metal-organic frameworks (MOFs) onto the MXene via the dielectric barrier discharge technique. Under light irradiation, MXP HJs exhibit excellent photocatalytic and photothermal performance to provide exogenous stimulation for killing bacteria. In addition, the MXP HJs promote electron transfer at the interfaces between the MXP HJs and bacteria, and this inhibits bacterial ribosomal pathways, resulting in endogenous antibacterial activity. Furthermore, MXP HJs can significantly promote wound healing through bacterial clearance, collagen deposition, and angiogenesis. Thus, this work lays the foundation for the development of a photocatalytic HJ platform that can be used in antibacterial applications for infectious wound repair.

In this project, we propose a highly effective photosensitizer that breaks through drug-resistant bacterial infections with zinc-doped carbon dots. By passing through the membrane of drug-resistant bacteria, the photosensitizers produce ROS in bacteria under the action of blue light to directly kill bacteria, so as to realize the antibacterial local treatment of drug-resistant bacteria. The experiment firstly uses an efficient one-step hydrothermal method to prepare zinc-doped red-light CDs as photosensitizers, in which zinc metal was doped to improve the optical properties of the CDs. Then we try first to use EDTA as a second-step attenuator for preparing CDs to obtain photosensitizers with high-efficiency and low toxicity. In vitro cytotoxicity tests, bacterial effect tests, and in vivo animal experiments have also demonstrated that this antibacterial method has great potential for clinical translation, with a bactericidal efficiency of up to 90%. More notably, we used this antibacterial regimen seven times repeatedly to simulate the bacterial resistance process, with a bactericidal efficiency of up to 90% every time. The result indicated that S. aureus did not develop resistance to our method, showing that our method has the potential to break through drug-resistant bacterial infections as an alternative to antibiotic candidates.

As a nano-material, carbon dots have been extensively studied and applied in many ways.

以超高效液相色谱建立参芪复方浸膏的指纹图谱,对其浸膏的质量控制进行研究.采用Opalshell C18(100 mm×4.6 mm,2.6μm)为色谱柱,含有0.1％甲酸的乙腈为流动相A,0.1％甲酸为流动相B,采用梯度洗脱分离并在波长254 nm处进行检测,获得参芪复方浸膏指纹图谱;采用LC-MS-MS法对色谱峰进行检测并分析裂解途径,获得20个共有峰的组分与结构信息;基于超高效液相指纹图谱对11个批次不同产地的参芪复方药材质量进行相似度分析、聚类分析和主成分分析.所测各批次样品指纹图谱与对照图谱的相似度较高,具有良好的相关性,表明不同批次间成分含量变化小,成品质量稳定.该方法重复性、精密度和稳定性良好,测得的指纹图谱可较好地反映出参芪复方浸膏中组分的分布,是评价本品及其药材质量的较好方法.

Carbon dots (CDS) have been proved to be a type of ideal biological imaging probe. They have the advantages of spontaneous fluorescence, anti-photobleaching, good biocompatibility and easy surface decoration, and are receiving special attention from researchers. The early imaging diagnosis of tumors has always been a practical means of clinical diagnosis. Finding an efficient and low-toxicity tumor probe is the continuous goal of tumor clinical diagnosis and treatment. Therefore, this article uses the modifiable properties of the surface structure of carbon dots, and at the same time, uses the characteristics of tumors with high expression of folate receptors (FR) that can specifically take up folic acid (FA) to construct folic acid carbon dot conjugates (FA–CDs) to achieve targeted tumor uptake. Firstly, CCK8 toxicity tests proved that FA–DCCDs had good biocompatibility and were almost non-toxic. Further, confocal cell imaging experiments, microplate quantitative experiments and flow cytometry experiments proved that FA–CDs were selective and more easily absorbed by tumor cells with high expression of folate receptors, and bare carbon dots could be absorbed into cells without selectivity. Through in vivo experiments, the law of injection of bare CDs into the body was explored, which proved that they had no obvious accumulation and had high distribution in the liver and kidneys. FA–CDs was applied to the targeted imaging of a mouse tumor model in vivo for the first time, which proved again that the carbon point coupled with folic acid had selectivity for tumor cells with high expression of FR receptors, which provided a basis for tumor drug research and early clinical diagnosis of tumors.

针对肿瘤血管抑制剂DX1002的含量测定,构建一种基于新型纳米碳点材料(CDs)的特异性荧光定量方法.以柠檬酸和尿素为原料,热解法制得碳点(CACCDs),经TEM、IR、UV/Vis、Flu等方法对其进行结构表征.内滤光效应下碳点荧光可被DX1002特异性定量猝灭,CACCDs浓度为250?μg/mL时,于λex/λem=400/530处测定猝灭前后的荧光差值(ΔF).结果表明,DX1002浓度在2.5～75?μg/mL范围内与ΔF具良好线性关系(r2=0.9988),检出限为1.16?μg/mL,平均加标回收率为101.7％(RSD=2.08％),常见细胞阳离子、微量金属离子、糖类、氨基酸等潜在共存物质及有关物质对测定无干扰,DX1002含量测定的结果(101.3％±1.33％)与HPLC法测定结果(99.4％±1.19％)基本吻合(P>0.05),但较HPLC分析时间快约75倍.该方法快速、灵敏、特异性强,可为建立DX1002高通量特异性体内分析方法提供体外定量的依据.

In many plant species nonzygotic embryos can develop from diploid somatic cells grown in tissue culture. Extracellular glycoproteins have been identified that can rescue arrested somatic embryos. One of these glycoproteins may be part of a mechanism that controls the expansion of plant cells.

该文建立大鼠血浆中DX1002的浓度的UPLC-MS/MS法,研究DX1002在大鼠体内的药代动力学特性及其生物利用度.DX1002分别经口给药和静脉给药100 mg/kg后,分别于设定的时间点采血,制备出的血浆通过预处理后采用UPLC-MS/MS法测定,色谱条件为UPLC C18为色谱柱(50 mm×2.10 mm,1.7μm),流量:0.5 mL/min,流动相A相为0.1％甲酸,B相为0.1％甲酸乙腈,采用梯度洗脱;质谱条件为ESI源的MRM检测模式;检测到的血药浓度采用Analyst软件计算药代动力学参数.结果DX1002在1.0～2000 ng/mL内线性良好(r2≥0.9979),精密度、准确度均满足测定需要.口服条件大鼠下平均Cmax分别为35597.0 ng/mL,平均AUC0～24 h为47291.5 h·ng/mL,平均t1/2为2.42 h,平均Tmax为0.235 h;经静脉给药后,雌雄大鼠的平均AUC0～24 h为174043.5 h·ng/mL,平均t1/2为4.26 h.同等剂量下大鼠口服给药的平均绝对生物利用度为27.29％.最后,所建方法是大鼠体内DX1002药代动力学研究的较好方法.