To systematically evaluate the combined impact of water diversion projects on regional ecological-economic systems, this study uses the water diversion area of the Badi Reservoir in Danba County, Sichuan Province, as the research object and constructs a dynamic simulation model including water resource scheduling, ecological restoration, industrial development and policy intervention mechanisms on the basis of the system dynamics method. Focusing on core variables such as reservoir water storage, fish resources, and soil erosion intensity, four types of policy scenarios are set-the S0 baseline scenario, S1 ecological compensation enhancement scenario, S2 industrial structure synergy scenario and S3 economic synergy scenario-to simulate and analyze the regulatory effects of policy combinations on the evolutionary path of regional water-ecological-economic systems. The results show that (1) in the S0 scenario, the system's natural evolution capacity is limited, fish resources recover slowly, soil erosion persists, and the water diversion effect is not fully released; (2) although the S1 ecological compensation scenario effectively improves vegetation restoration and soil and water conservation by improving the compensation standard and suppresses the trend of soil erosion in the short term, the effect on fish resource recovery and industrial support is limited; (3) the S2 industrial synergy scenario indirectly improves ecosystem pressure while optimizing the employment structure of the tertiary industry, showing the adaptive path characteristics of medium-term industry-ecology coordination; and (4) the S3 economic synergy scenario has the best overall performance. While enhancing fishery output and improving the output value of primary industry and forestry, this scenario achieves systematic synergy by increasing reservoir water volume, restoring fish resources and alleviating soil erosion. The study shows that single policy interventions have difficulty simultaneously optimizing ecology and the economy. A composite "ecological compensation + industrial synergy + economic linkage" policy system should be built to dynamically adjust the rhythm of water resource scheduling and the industrial development structure and promote green transformation and high-quality development in the water diversion area.

Human activities and climate change have degraded coastal ecosystems by elevating nutrient concentrations, thereby exacerbating eutrophication in the coastal waters in the past decades. Increased nutrient levels lead to hypoxia, eutrophication, and frequent harmful algal blooms. However, current estuarine and marine assessments rely on Dissolved Inorganic Nitrogen (DIN) and Dissolved Inorganic Phosphorus (DIP), disconnecting them from land-based total nitrogen (TN) and total phosphorus (TP) indicator controls. To address this, we established site-specific TN and TP criteria based on salinity zonation to support integrated land-sea management. Using 9697 monitoring datasets (2012-2022), the study area was classified into four zones: tidal freshwater zone (salinity ≤2), low brackish mixed water area (2 < salinity ≤15), moderately brackish mixed water area (15 < salinity ≤25), and seawater area (salinity >25). Numeric nutrient criteria were derived using frequency distribution statistics and Classification and Regression Tree (CART) analyses to identify ecological response thresholds. The recommended TN criteria for the four respective zones were 1.80, 1.50, 0.50, and 0.40 mg/L, while TP criteria were 0.10, 0.06, 0.05, and 0.04 mg/L. Moreover, the derived reference values were compared and analyzed with those from other coastal waters, both domestically and internationally, to verify their rationality and applicability. Validation using independent data (2021-2024) indicated that TN-based assessment increased the compliance rate of "good quality" water compared to the traditional DIN criteria, effectively mitigating false negatives in water quality evaluation. These results demonstrate that the proposed criteria effectively bridge the gap between riverine discharge limits and marine quality objectives. This study provides a robust scientific foundation for the development of zoning-based nutrient management strategies, offering solutions for different ecological zones. It presents a systematic framework that integrates land-sea nutrient control, which can be applied to manage and mitigate eutrophication in complex estuarine and coastal environments.

Osteoporosis is characterized by an imbalance between bone formation and resorption, and the dysregulated differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a central role. Our previous study identified Bhlhe22 as a key negative regulator of osteogenic differentiation; here, we further validate its role in osteoporotic BMSCs (OP-BMSCs) and investigate its therapeutic potential. Knocking down Bhlhe22 enhanced osteogenesis by upregulating key osteogenic markers (RUNX2, ALP, OPN) and suppressing the PI3K-Akt signaling pathway. To enable targeted delivery of siBhlhe22, we designed an aptamer-functionalized tetrahedral framework nucleic acid-based nanocarrier (Apt19S-tFNA-siBhlhe22, ATS). The ATS system exhibited well-defined nanostructure, excellent biocompatibility, and high cellular uptake efficiency in OP-BMSCs. In vitro, ATS-mediated Bhlhe22 knockdown significantly promoted osteogenic differentiation and matrix mineralization. This effect depended on the inhibition of PI3K-Akt signaling, as demonstrated by rescue experiments using the agonist Recilisib. Non-targeted metabolomics revealed that osteoporosis was associated with disruption of nucleotide and purine metabolism, which was effectively reversed by ATS treatment. Functional studies confirmed that intact purine metabolism, which was essential for ATP production and redox balance, was required for the pro-osteogenic effect of ATS. In an osteoporotic rat bone defect model, ATS delivered via GelMA hydrogel promoted bone regeneration. This was accompanied by in vivo suppression of PI3K-Akt signaling and upregulation of OCN and OPN. Our findings establish a novel gene therapy strategy that targets Bhlhe22 to simultaneously modulate pro-osteogenic signaling and metabolic reprogramming, offering a promising anabolic approach for osteoporosis treatment.

Thermal stability is a key factor in determining the phenomena of deep chlorophyll maxima (DCM) in stratified lakes, as it mediates the vertical balance between light and nutrients required by phytoplankton. While it is well established that lake stratification is sensitive to latitude gradients, the ways in which thermal stability modulates DCM characteristics (i.e., depth, thickness, and concentration) and nutrient–chlorophyll relationships across different latitude classifications remain unclear. In this study, data on thermocline depth, DCM feature, and water quality parameters were collected from 88 globally distributed stratified lakes. Our findings indicate that (1) higher-latitude lakes exhibit strong thermoclines, with light and nitrogen serving as the primary drivers of thermal stratification; (2) in high-latitude lakes, surface chlorophyll a concentrations are more tightly linked to total phosphorus than that at DCM depth in low-latitude lakes; and (3) structural equation modeling (SEM) results demonstrate that higher-latitude lakes form shallower and thinner DCM structures, where low light levels contribute to reduced peaks in algal biomass. These findings provide valuable insights for the management of stratified lakes facing the dual pressures of climate change and eutrophication.

Reservoir operations create complex environmental heterogeneity by altering hydrodynamic and nutrient regimes. However, their influence on the underlying processes governing phytoplankton community assembly remains inadequately understood. Here, we integrated long-term field monitoring data (2015-2023) with three-dimensional hydrodynamic-transport simulations to investigate how reservoir regulation drives phytoplankton succession and alters assembly processes in Zipingpu Reservoir, Sichuan, China. We observed a fundamental shift in the dominant phytoplankton group from Dinophyta (Peridiniopsis spp.) to green algae (Tetraselmis spp.), with the relative biomass of green algae surging from <10% to 96%. Reservoir operations reduced the water residence time (WRT) by 30% and increased the surface water total phosphorus (TP) concentration by approximately 170%, thereby significantly modulating key environmental filters. Concomitantly, the explanatory power (R2) of the neutral community model increased from 21.2% to 60.8%, and the modified stochasticity ratio increased from 43% to 52%. This quantitatively demonstrates a shift in community assembly from deterministic to stochastic dominance. Structural equation modeling further delineated a key pathway: operations → WRT → TP → phytoplankton. Our findings demonstrate that reservoir operations alter assembly mechanisms by alleviating phosphorus limitation, thereby weakening deterministic selection and enhancing stochastic processes. This study provides a mechanistic foundation for optimizing reservoir operations to manage phytoplankton communities.

Ubiquitin-specific protease 1 (USP1) regulates the DNA damage response (DDR) by deubiquitinating PCNA, and its inhibition potentiates PARP inhibitor efficacy, highlighting USP1 as a promising therapeutic target in triple-negative breast cancer (TNBC). Guided by USP1-UAF1 structural insights, we optimized the KSQ-4279 scaffold and identified 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one as a scaffold-hopping core for proof-of-concept exploration. Representative compound 57 exhibited nanomolar USP1-UAF1 inhibition, antiproliferative activity against MDA-MB-436 cells, favorable human liver microsomal stability, and 76% oral bioavailability in rats. In vitro assays and in vivo xenograft studies demonstrated synergistic antitumor activity between compound 57 and Olaparib, resulting in DNA damage and significantly enhanced tumor growth inhibition compared with Olaparib monotherapy. Transcriptomic analysis and Western blot results further supported enhanced suppression of tumor survival pathways. Collectively, this work establishes compound 57 as a scaffold-hopping, proof-of-concept USP1 inhibitor and provides in vivo validation for USP1-PARP inhibitor combination therapy in TNBC.

Early impoundment creates highly non-stationary hydrothermal conditions in tributary bays, making broad seasonal ecological operations too coarse to effectively support fish migration. However, indicator-based approaches that translate hydrothermal dynamics into ecologically interpretable migration accessibility and operation timing remain limited. Here, we developed a hydrothermal migration connectivity framework to identify migration windows and ecological operation windows in Heishui Bay, a tributary bay of Baihetan Reservoir. Multivariate change point detection was used to divide the early impoundment period into distinct hydrothermal regimes, and a CE-QUAL-W2 model calibrated and evaluated against observed water levels and vertical temperature profiles was used to reconstruct backwater intrusion, circulation, and thermal stratification. Species-specific thermal and hydraulic requirements were translated into corresponding migration-supporting corridor states, including thermal corridors, velocity corridors, and composite corridors. To characterize corridor performance, we quantified occurrence timing, persistence, continuity, and fragmentation, and further evaluated corridor quality using composite connectivity and corridor fragmentation indicators. The results showed that the early impoundment period was divided into five hydrothermally distinct regimes. Backwater intrusion length varied from approximately 22 to 30 km and was jointly controlled by water level fluctuation, the mainstream to tributary discharge ratio, and thermally induced density structure. Composite corridor connectivity was highly transient: the first through-going composite corridor appeared on 2 March but lasted only 1 day, while a second brief through-going event occurred on 16 May. In addition, indicator-based corridor quality analysis further identified 2–9 March as a low-fragmentation interval forming the core of the primary ecological operation window, with a weaker secondary window in mid-May. These findings show that ecological operations in tributary bays should be refined beyond broad breeding-season schedules to reflect species-specific and process-dependent connectivity dynamics. The proposed framework provides a basis for translating hydrothermal variability into operation relevant timing in newly impounded tributary bay systems.

This study systematically evaluates the regulatory effects of multi-reservoir water diversion on ecological risk thresholds in the upper Yangtze River. Taking multiple reservoirs in the upper basin as the research object, a system dynamics model was developed to simulate reservoir operation, water level regulation, ecological water diversion, and diversion capacity enhancement. Key indicators included upstream ecological risk thresholds, ecohydrological risk levels, habitat ecological risk levels, and water environment ecological risk levels. Five scenarios were designed: S0 (baseline), S1 (enhanced ecological compensation), S2 (industrial coordination and optimization), S3 (economic synergy promotion), and S4 (comprehensive regulation and optimization). These scenarios were used to assess the combined effects of different diversion strategies on ecological risk control. Results indicate the following: (1) All scenarios reduce ecological risks to some extent, but the degree of effectiveness differs. (2) The overall ranking is S4 > S1 > S3 > S2 > S0, demonstrating that comprehensive regulation optimization is most effective in mitigating ecohydrological risks, improving habitat quality, and enhancing water environment security. (3) S1 is particularly effective in reducing ecohydrological risks and is suitable as an emergency safeguard during dry seasons, though less effective than S4 in habitat and water quality improvements. (4) S3 supports economic–ecological synergy but remains less effective than S1 and S4. (5) S2 primarily enhances industrial–ecological coordination with limited contribution to overall risk control. (6) S0 yields minimal improvement under existing operational conditions, failing to meet ecosystem safety thresholds. Overall, the findings highlight that in multi-reservoir joint diversion contexts, a composite strategy centered on comprehensive regulation optimization, supplemented by ecological compensation and economic synergy, should be prioritized to achieve systematic ecological risk reduction and ensure long-term watershed ecological security.

Our preliminary studies indicated that KX-01 inhibits tubulin polymerization in a reversible and concentration-dependent manner, resulting in dramatically low toxicity across various solid and liquid tumor types. However, KX-01 has not yet been approved as an anticancer agent due to its insufficient efficacy, and research on its derivatives remains limited. To improve its antitumor activity and investigate the structure-activity relationships (SARs), sixty-seven KX-01 analogs were designed and synthesized based on the KX-01-tubulin cocrystal structure. Among them, compound 8h exhibited the most potent antiproliferative activity, with IC50 values of 3.5 ± 0.6, 2.4 ± 0.2, 15.7 ± 3.1, 22.1 ± 1.9, and 7.3 ± 1.1 nM against HCT116, HeLa, A2780S, A2780T, and HT29 cells, respectively, indicating its potential to overcome multidrug resistance. Replacing the endocyclic nitrogen atom in the pyridine ring of KX-01 with an exocyclic fluorine atom directly results in the loss of Src inhibitory activity. The cocrystal of 8h-tubulin complex revealed that it simultaneously occupies the colchicine site in β-tubulin and a cavity in α-tubulin. In the HT29 xenograft model, orally administered 8h (5 mg/kg, once daily) showed marginally superior in vivo antitumor efficacy than KX-01.

The concomitant inhibition of PI3Kδ and bromodomain and extra-terminal (BET) that exerts a synergistic effect on the B-cell receptor signaling pathway provides a new strategy for the treatment of aggressive diffuse large B-cell lymphoma (DLBCL). Herein, a merged pharmacophore strategy was utilized to discover a series of thieno[3,2-d]pyrimidine derivatives as the first-in-class bifunctional PI3Kδ-BET inhibitors. Through optimization, a highly potent compound (10b) was identified to possess excellent and balanced activities against PI3Kδ [inhibitory concentration (IC50) = 112 ± 8 nM] and BRD4-BD1 (IC50 = 19 ± 1 nM) and exhibited strong antiproliferative activities in DLBCL cells. Notably, this compound demonstrated good PI3Kδ selectivity over other kinases with minimal cytotoxicity in normal cells. Moreover, 10b has a good oral pharmacokinetic profile in mice and achieves outstanding antitumor activity in the SU-DHL-6 xenograft model. Taken together, these results indicate that targeting PI3Kδ and BET with a bifunctional inhibitor is a promising strategy to treat DLBCL.

Our preliminary studies indicate that cevipabulin concurrently binds to both the vinca site and the gatorbulin site, and promotes tubulin degradation. To improve its antiproliferative activity and investigate the structure-activity relationships (SARs), thirty-eight cevipabulin derivatives were designed and synthesized based on the cevipabulin-tubulin cocrystal structure. Among them, compound 8g exerted optimal antiproliferative activity, with IC50 values ranging from 0.016 to 0.035 μM against three tested tumor cell lines. The cocrystal structure of the 8g-tubulin complex revealed that it simultaneously occupies both the vinca site and the gatorbulin site, while maintaining a binding mode similar to that of cevipabulin. Furthermore, 8g promoted αβ-tubulin degradation and displayed good oral bioavailability. In an HT29 xenograft model, oral administration of 8g at doses of 20 and 40 mg/kg every 3 days resulted in potent in vivo antitumor activity, with tumor growth inhibition (TGI) rates of 41.0 % and 49.5 %, respectively. Moreover, 8g exhibited significantly reduced toxicity and fewer adverse effects compared to cevipabulin, supporting its potential as a promising therapeutic agent for cancer treatment.

Advanced glycation end products (AGEs) are the key pathological factors linking hyperglycemia and diabetic bone disorder. The excessive accumulation of AGEs in diabetic patients weakens the bone matrix's structural stability while simultaneously impairing the ability of bone marrow mesenchymal stem cells (BMSCs) to differentiate into bone-forming cells by inducing pyroptosis, ultimately resulting in bone loss and elevated fracture risk. Resveratrol (Rsv), a natural polyphenolic compound derived from plants, is demonstrated to facilitate osteogenic differentiation and mineralization of BMSCs while inhibiting pyroptosis. However, its therapeutic effect is limited by poor water solubility and rapid metabolic degradation in vivo. Tetrahedral framework nucleic acids (tFNAs) exhibit remarkable biocompatibility, high cellular uptake efficiency, and enhanced stability, making them ideal drug carriers. In this study, a novel nanoconstruct termed tFNAs/Rsv is constructed by integrating Rsv with tFNAs. It significantly improves osteogenic potential of BMSCs in the AGEs-rich environment, suppresses actuation of pyroptotic pathway, and promotes bone regeneration in osteoporotic animal models. This method offers a prospective strategy for the management of diabetic skeletal complications.

With the rapid development of socioeconomics and the continuous advancement of urbanization, water environment issues in plain river networks have become increasingly prominent. Accurate and reliable water quality (WQ) predictions are a prerequisite for water pollution warning and management. Data-driven modeling offers a promising approach for WQ prediction in plain river networks. However, existing data-driven models suffer from inadequate capture of spatiotemporal (ST) dependencies and misalignment between direct prediction strategy assumptions with actual data characteristics, limiting prediction accuracy. To address these limitations, this study proposes a spatiotemporal graph neural network (ST-GNN) that integrates four core modules. Experiments were performed within the Chengdu Plain river network, with performance comparisons against five baseline models. Results suggest that ST-GNN achieves rapid and accurate WQ prediction for both short-term and long-term, reducing prediction errors (MAE, RMSE, MAPE) by up to 46.62%, 37.68%, and 45.67%, respectively. Findings from the ablation experiments and autocorrelation analysis further confirm the positive contribution of the core modules in capturing ST dependencies and eliminating data autocorrelation. This study establishes a novel data-driven model for WQ prediction in plain river networks, supporting early warning and pollution control while providing insights for water environment research.

This study uses high-frequency monitoring across a river-barrier lake-reservoir continuum in the upper Minjiang River, southwestern China, to quantify the spatiotemporal dynamics and drivers of aquatic CO2 partial pressure (pCO(2)) and to identify the dominant controls under contrasting lotic and lentic conditions. River reaches were CO2-supersaturated throughout the year, with higher pCO(2) in the wet season (mean 521 ppm) than in the dry season (421 ppm), indicating persistent CO2 evasion to the atmosphere. In contrast, the downstream canyon-type reservoir showed a pronounced seasonal reversal. During the wet season, surface-water pCO(2) averaged 395 ppm, about 24% lower than that of the river and below atmospheric levels (similar to 419 ppm); more than 55% of observations were undersaturated, with minima as low as 141-185 ppm, indicating temporary CO2-sink behavior. In the dry season, mean pCO(2) increased to 563 ppm, exceeding both riverine and atmospheric levels and returning the reservoir to a CO2 source. The reservoir pCO(2) variability was governed by the interaction of hydrology and metabolism: rising water levels and longer residence times likely enhanced CO2 accumulation from the decomposition of inundated organic matter, while warm temperatures, high light and monsoon-driven nutrient inputs promoted phytoplankton growth that removed dissolved CO2 and elevated dissolved oxygen, producing temporary sink behavior. In the river, short residence time and strong turbulence limited in-stream biological regulation, and pCO(2) variability was mainly driven by catchment-scale carbon inputs along the elevation gradient. Overall, our results demonstrate that dam construction and impoundment can substantially modify carbon cycling in high-mountain rivers. Under specific conditions (warm water, sufficient nutrients, high algal biomass), lentic environments may strengthen photosynthetic CO2 uptake and temporarily transform typical riverine CO2 sources into sinks, with important implications for carbon-budget assessments and reservoir management in mountainous basins.

Bone Morphogenetic Protein-2 (BMP-2) is a key growth factor for inducing osteogenic differentiation and promoting bone remodeling. However, the exogenous application of delivery systems for BMP-2 has been hampered by various postoperative complications, poor stability and high price. Hence, in situ enrichment of endogenous BMP-2 is promising. The discovery of a small molecule BMP-2 binding peptide (BBP) that binds specifically to BMP-2 with high affinity lays the foundation for the construction of bioactive materials that capture endogenous BMP-2. In contrast, conventional enrichment strategies have low binding efficiency due to steric hindrance caused by the disordered arrangement of BBPs. Tetrahedral framework nucleic acid (tFNA) exhibits good editability and unique three-dimensional spatial structure that enables topological control of multivalent ligands in spatial distribution. The BBPs are further designed to be stably modified on tFNA (BBPs-tFNA) via click chemistry of the azide-alkyne addition to achieve the orderly arrangement of BBPs in spatial organization, to improve the binding efficiency of BMP-2. Therefore, in this study, BBPs-tFNA is modified on biocompatible hyaluronic acid methacryloyl (HAMA) to construct the functionalized bioactive composite hydrogel scaffolds, with the aim of achieving precise and efficient capture of endogenous BMP-2, stimulating osteogenic differentiation and promoting in situ osteogenesis for bone defect repair.

Upon the activation of inflammasomes, inflammatory caspases cleave and activate gasdermin D (GSDMD), leading to pore formation that causes cell membrane rupture and amplifies downstream inflammatory responses. Dysregulated inflammasome activation and pyroptosis signaling pathways are implicated in numerous inflammatory diseases. In our work, a set of novel thiazole amide compounds with inhibitory activity against NLRP3 inflammasome-induced pyroptosis was identified. Of all the compounds tested, compound 21 demonstrated the most potent anti-pyroptotic effects. It suppressed GSDMD cleavage and decreased IL-1β and lactate dehydrogenase (LDH) release in a concentration-dependent manner. Compound 21 bound to NLRP3 protein and increased the thermal stability of NLRP3 concentration-dependently. The molecular docking and dynamics simulations revealed that compound 21 binds to the NLRP3 protein's active site, suppressing inflammasome activation. Further investigations showed that compound 21 also partially blocked upstream NF-κB signaling and downstream GSDMD N-terminal domain (GSDMD-NT) oligomerization, which explains its broad inhibitory effects on pyroptosis driven by multiple inflammasomes. Overall, this study presents a promising thiazole amide compound with inhibitory activity against inflammasome activation and subsequent pyroptosis, warranting further exploration.

Inflammation is a protective response by the body aimed at maintaining tissue homeostasis by eliminating pathogenic microbial infection, irritants, or tissue damage. However, dysregulated inflammation is pathological and involved in various diseases such as metabolic disorders, cancer, and neurodegenerative diseases. In this study, multicomponent reaction, an efficient tool for the synthesis of complex compounds with potential biological activities, was employed to synthesize twenty 3,4-dihydro-pyrazine[1,2-b]indazole-1(2H)-one derivatives and two 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one analogues. We next identified compounds 6e and 6r as potential inhibitors for NLRP3 inflammasome-driven pyroptosis through activity-based screening and investigated their potential binding modes with the NLRP3 protein via molecular docking. Further studies on anti-inflammatory activity showed that compounds 6e and 6r also significantly inhibited LPS-induced NO release, among which compound 6e had better anti-inflammatory activity, with an IC50 of 8.55 ± 0.32 μM in inhibiting NO release. Additionally, qPCR analysis indicated that compound 6e notably suppressed the gene transcription of the pro-inflammatory cytokine IL-6. In conclusion, this study identifies compound 6e, featuring a novel 3,4-dihydro-pyrazine[1,2-b]indazole-1(2H)-one scaffold, as a promising hit compound with inhibitory activity against pyroptosis and key inflammatory mediators. These findings highlight this chemotype as a valuable starting point for the development of a new class of anti-inflammatory agents. This work describes a novel 3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one compound 6e with promising anti-inflammatory activity.

Precise delivery of pharmaceuticals administered to bone marrow for various bone diseases is challenging, given the bone marrow-blood barrier (MBB). Bone marrow stromal cells (BMSCs) derived from bone marrow can naturally infiltrate the MBB and home to bone tissue. Here, biomimetic nanovesicles (namely mNVs) engineered with the extracted cell membrane from BMSCs are reported for homing delivery of different core nanomedicines to bone marrow. The cargo-loaded mNVs exhibited excellent bone targeting in crossing natural barriers is demonstrated to augment drug concentrations in bone marrow, and the bio-function of mNVs is verified in typical models of chronic metabolic bone disease and metastatic carcinoma. In the induced osteoporosis model, engineered mNVs deliver the nanocore of teriparatide-loaded poly(lactic-co-glycolic acid), forming a sustained-release system of teriparatide, which can significantly slow bone loss, maintain bone mass, and alleviate osteoporosis indicators. In osseous and systematic metastatic breast carcinoma models, the mNVs are employed to deliver DNA tetrahedron embedded doxorubicin and efficiently inhibit tumor progression and osteolytic lesions. This work suggests that high-efficiency bone marrow delivery of medications can be camouflaged by the cell membrane derived from BMSCs, initiating a new platform for bone targeting drug delivery for developing more effective therapeutics for bone diseases.