To address the technical challenge of balancing the stability and bioavailability of conventional iron supplements, this study developed a plant-based composite gel system in which Fe(II) served as both a nutritional factor and an ionic crosslinker. The results showed that the three-dimensional gel network was primarily maintained by hydrophobic interactions. Two-dimensional correlation analysis further indicated that Fe(II) may coordinate with the carboxyl groups of sodium alginate (SA) to form ionic bridges, triggering the dissociation and reconstruction of the hydrogen-bonding network, subsequently inducing soy protein isolate (SPI) conformational unfolding, thereby regulating gel network formation. At an Fe(II) concentration of 0.25%, the in-situ ionic crosslinking degree reached the optimum level, yielding a gel with a hardness of 55.72 ± 0.27 g, the highest storage modulus, and the most uniform pore distribution. The β-sheet content in the SPI secondary structure reached its maximum (38.40%), effectively retarding Fe(II) diffusion and gastrointestinal loss. Overall, this study elucidated the mechanism of Fe(II)-mediated in-situ ionic crosslinking and established the structure–function relationship among crosslinking degree, gel structure and Fe(II) controlled-release behavior. These findings provide a novel food-grade iron supplement for alleviating iron-deficiency anemia and expanding the application of plant protein-based composite gels in active mineral delivery.

Medulloblastoma (MB) is a common intracranial malignant tumor in children with a poor prognosis and high mortality rate. The lack of suitable models has hampered basic research and preclinical drug screening for MB. Three-dimensional (3D) bioprinting enables organoid construction that recapitulates primary tumors and supports high-throughput drug testing. Here, we report a novel silk fibroin (SF)-based ternary bioink optimized for 3D bioprinting and, for the first time, the fabrication of a 3D bioprinted MB organoid model along with its modular and detachable co-culture system. This ternary bioink exhibited high mechanical strength, demonstrating a significant enhancement in the extracellular matrix (ECM) stiffness while maintaining stable structural performance over 28 days in culture. Verification at the genetic and protein levels confirmed that key signal pathways, notably PI3K/AKT and Ras, were activated in the 3D MB organoid model. Consequently, tumor cells displayed enhanced malignant phenotypes, including proliferation, migration and invasion, alongside increased chemoresistance. Moreover, co-culture of MB organoids provides evidence for the critical role of vascular endothelial-tumor cell interactions in driving tumor drug resistance, offering a viable pathway to advance from simplified models to more physiologically complex systems. These phenotypic changes enable more accurate prediction of the in vivo therapeutic efficacy of anti-MB drug candidates. In summary, this study developed a set of long-term stable and flexibly configurable 3D bioprinted MB organoid models that address critical gaps in the existing preclinical systems, thereby enabling more reliable drug screening and pathological studies for MB.

ABSTRACT Natural drug‐food homology compounds have vast therapeutic potential, particularly for inflammatory bowel disease (IBD), but their poor water solubility, instability, and limited mucosal availability hinder their clinical translation. As a proof of principle, the natural polyphenol resveratrol (Res) was conjugated to a disulfide‐bridged carboxymethyl chitosan (CMCS) for inclusion in a negatively charged hydrogel (CMTR‐Gel). The CMTR‐Gel was stable, with a zeta potential of approximately −37 mV in the gastrointestinal environment, and significantly inhibited reactive oxygen species production and mitochondrial depolarization in RAW 264.7 cells under lipopolysaccharide‐induced stress. The orally administrated CMTR‐Gel preferentially adhered to inflamed mucosa for 24 h through electrostatic interactions between anionic CMCS and cationic transferrin. Because of its prolonged adhesion and precise Res release at inflamed mucosa, CMTR‐Gel achieved superior therapeutic efficacy compared to the first‐line drug sulfasalazine in colitis mice, and was especially efficacious for mucosal healing through its repair of tight junction integrity. The CMTR‐Gel represents a promising strategy for the application of natural drug‐food homology compounds in the management of IBD.

The aim of this study is to develop a novel molybdenum oxide nanocomposite with good dispersion and targeting tumor cells and investigate their DOX delivery performance. Briefly, molybdenum oxide (MoOx) nanocomposite prepared by hydrothermal method were grafted with polyglycerol (MoOx-PG), followed by stepwise organic coupling with RGD peptide (MoOx-PG-RGD), and finally loaded with DOX. The physicochemical properties of MoOx-PG-RGD nanocomplexes were characterized by FTIR, SEM, XPS and TGA. The results showed that the grafted PG layer largely enhanced the dispersibility and biocompatibility of MoOx nanocomposite in physiological media. The obtained MoOx-PG-RGD/DOX exhibited drug-loading efficiency of 18.67 %. Drug release experiments indicated that MoOx-PG-RGD/DOX exhibited a faster release rate under acidic conditions in tumors. In addition, MTT cytotoxicity assay and cell uptake experiments indicated that MoOx-PG-RGD/DOX efficiently delivered DOX into targeted cells by integrin alpha v beta 3 receptor-mediated endocytosis, which leading to an enhanced therapeutic efficacy of DOX. These results suggested that MoOx-PG-RGD, as a novel anticancer drug delivery vector, had great potential for application in tumor therapy.

Predicting the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small molecules remains a major challenge in drug discovery. Here, we present MEGA-CL, a foundation graph neural network framework for universal molecular ADMET prediction. MEGA-CL integrates self-supervised contrastive learning with a multi-head external attention mechanism and an enhanced message-passing architecture, enabling simultaneous modeling of local chemical substructures and global inter-graph relationships while mitigating over-smoothing effects commonly observed in deep graph networks. Across 13 benchmark datasets and 21 downstream ADMET tasks, MEGA-CL consistently outperforms state-of-the-art baseline models. In particular, the framework demonstrates robust performance on challenging regression tasks, including clearance (CL) and steady-state volume of distribution (VDss), while maintaining strong generalization ability in independent external validation. Clinically relevant predictive accuracy was achieved, with more than 75% of predictions falling within a 3-fold error range. In an external evaluation on 18 novel compounds derived from recently approved FDA drugs, over 50% of human liver microsome clearance (HLMC) predictions were within a 2-fold error range. To further assess its practical applicability, MEGA-CL was prospectively evaluated on three preclinical drug candidates using in vitro hepatic microsomal metabolism assays and CYP450 inhibition assays guided by model predictions. The predicted HLMC values for all candidates were within 2.5-fold of the experimentally measured values, and 73.3% of CYP450 inhibition endpoints (11/15) were correctly classified. These results demonstrate the potential of MEGA-CL as a generalizable framework for accelerating in silico ADMET evaluation and early-stage drug candidate optimization.

Herein, a novel pyrrolo[2,3-b]pyridine-based glycogen synthase kinase 3 beta (GSK-3 beta) inhibitor, S01, was rationally designed and synthesised to target Alzheimer's disease (AD). S01 inhibited GSK-3 beta, with an IC50 of 0.35 +/- 0.06 nM, and had an acceptable kinase selectivity for 24 structurally similar kinases. Western blotting assays indicated that S01 efficiently increased the expression of p-GSK-3 beta-Ser9 and decreased p-tau-Ser396 levels in a dose-dependent manner. In vitro cell experiments, S01 showed low cytotoxicity to SH-SY5Y cells, significantly upregulated the expression of beta-catenin and neurogenesis-related biomarkers, and effectively promoted the outgrowth of differentiated neuronal neurites. Moreover, S01 substantially ameliorated dyskinesia in AlCl3-induced zebrafish AD models at a concentration of 0.12 mu M, which was more potent than Donepezil (8 mu M) under identical conditions. Acute toxicity experiments further confirmed the safety of S01 in vivo. Our findings suggested that S01 is a prospective GSK-3 beta inhibitor and can be tested as a candidate for treating AD.

Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.

The development of a fast and eco-friendly one-step synthesis method for constructing multifunctional hydrogels to eliminate postoperative residual tumor cells is highly required. In this work, Fe3+ ions were selected as inorganic cross-linkers to link gelatin (Gel) and protocatechuic acid (PA) for driving assembly process, and then to form gelatin-metal-polyphenol (GMP) hydrogel, Gel-Fe-PA. The in situ-formed metal-phenolic network nanoparticle (MPN NP) Fe-PA can effectively respond to NIR stimulation and then transform light energy into heat energy for inducing tumor cells apoptosis. Furthermore, damage-associated molecular patterns, including adenosine triphosphate (ATP), calreticulin (CRT) and high mobility group box-1 (HMGB1), will be released and captured by dendritic cells (DCs) to subsequently induce an immune response. In vivo local antitumor therapy results showed that the GMP hydrogel-mediated photothermal effect could effectively inhibit tumor tissue growth in the residual tumor bed. The distant tumor tissue growth could also be inhibited in a bilateral 4T1 tumor model. Considering there are so many types of reactions between polyphenols and metal ions, we believe this study provides a universal strategy for the in situ fabrication of an MPN NP-loaded hydrogel with advanced tumor photothermal-immunotherapy ability via a fast and eco-friendly one-step synthesis method.

Efficient cytosolic delivery of small interfering RNA (siRNA) remains a challenge in RNA therapeutics, particularly for oral administration. Identifying new cytosolic stimulus-responsive targets is thus crucial for optimizing siRNA delivery. Given the elevated intracellular arginase-1 (Arg1) levels in inflamed colonic mucosa, we developed lipid nanoparticles (siRNA-LANPs) derived from L-arginine-modified chitosan (ACS) for the cytosolic release of TNF-alpha-siRNA to treat ulcerative colitis (UC). The siRNA-LANPs exhibited superior Arg1-binding affinity compared to its substrate, L-arginine, enabling rapid Arg1-responsive release. Moreover, we found that siRNA-LANPs maintained nanoparticle stability, and 84.5 % of the loaded siRNA remained intact in simulated digestive fluids over 12 h. Following oral administration, siRNA-LANPs efficiently penetrated the mucus layer and preferentially accumulated in inflamed colonic tissue compared to healthy colon tissue. In DSS-induced colitis mice, siRNA-LANPs significantly reduced disease severity through TNF-alpha silencing, achieving greater therapeutic efficacy than sulfasalazine (a first-line UC treatment). The siRNA-LANPs exhibited superior TNF-alpha silencing compared to transfection reagent Lipo3000 and TNF-alpha biologic agent infliximab. The enhanced performance was attributed to multiple endocytic pathways, improved lysosomal escape capability (29.7 %), and Arg1-mediated cytoplasmic siRNA release. In summary, Arg1 seems to be a promising intracellular target for stimulus-responsive, oral siRNA delivery in UC treatment.

The development of potent glycogen synthase kinase-3 beta (GSK-3 beta) inhibitor has been increasingly recognized as the candidate treatment against the multifactorial pathogenic mechanism of Alzheimer's disease (AD). This study prepared various new pyrrolo[2,3-b]pyridine derivatives, evaluated the anti-AD activities and detected the security based on the structure-guided rational design. Our results indicated that many pyrrolo[2,3-b]pyridine derivatives had strong GSK-3 beta inhibitory activities, particularly compounds 41 , 46 and 54 , with the half maximal inhibitory concentrations (IC50) of 0.22, 0.26 and 0.24 nM, respectively, and each of them generally possessed GSK-3 beta selectivity over 24 structurally similar kinases. In addition, further targeting studies at the cellular level revealed that compound 41 increased GSK-3 beta phosphorylation at Ser9 site dose-dependently for inhibiting GSK3 beta activity, therefore inhibiting the hyperphosphorylation of tau protein by decreasing the p-tau-Ser396 abundance. Moreover, 41 up-regulated beta-catenin and neurogenesis-related markers (GAP43 and MAP-2), thereby promoting neurite outgrowth of neurons in SH-SY5Y cells. According to the in vitro cells assay, 41 showed the lower cytotoxicity to SH-SY5Y cells with a survival rate of over 70 % at the concentration of 100 mu M. In vivo efficacy and acute toxicity experiments showed that, 41 effectively ameliorated the dyskinesia in AlCl3-induced zebrafish AD models and exhibited its low-toxicity nature in C57BL/6 mice. Overall, the pyrrolo[2,3-b]pyridine derivative 41 could serve as a promising GSK-3 beta inhibitor for treating AD.

In situ vaccines have shown promise in cancer treatment but encounter obstacles such as limited tumor antigen release, immune-suppressive microenvironments, and insufficient antigen processing. To boost the effectiveness of in situ cancer vaccine, the rationally designed delivery technologies are urgently needed for improved immunotherapy. In the current study, NanoAlum based delivery system has been developed which could function for all the courses during the in situ vaccine formation, including immunogenic cancer death (ICD) induction, immunomodulator (R848) loading as well as carriers for autologous antigens. After intratumoral administration, the NanoAlum based delivery system would induce ICD upon near-infrared (NIR) heating for tumor-derived antigens release. The antigens would then be captured by NanoAlum therefore in situ cancer nanovaccine could be formed with the three moieties: autologous antigens by ICD, R848 as immunoadjuvant, and NanoAlum as delivery system. Under this paradigm, the NanoAlum based delivery system would optimize the efficacy of cancer vaccines by enhancing antigenicity, adjuvanticity, and modulation of immune suppression within the tumor microenvironment, thereby initiating a multistep cascade of antitumor responses. In vivo experiments demonstrated that NanoAlum based delivery system would generate complete eradication of primary tumors, potent abscopal effects on distant tumors and long-term immune response against cancer recurrence. More importantly, the safety of all the compositions within the vaccine has been proved by clinical trials, which makes it highly attractive for clinical translation. Overall, the attempt demonstrates the great potential of in situ cancer vaccine based on NanoAlum delivery system in boosting immunotherapy for cancer treatment.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) are notorious persistent organic pollutants (POPs) with proven toxicity to human and ecosystems. This review critically evaluates existing research, emphasizing knowledge gaps regarding PCDD/F emissions, environmental behavior, human exposure, and associated risks in China. The current emission inventory of PCDD/Fs in China remains highly uncertain, both in terms of total emissions and emission trends. Moreover, existing monitoring data primarily focus on areas near pollution sources, limiting comprehensive understanding of the overall spatiotemporal characteristics of PCDD/F pollution. To address this, we propose a novel approach that integrates the Multi-media Urban Mode (MUM) model with an atmospheric chemical transport model that includes a dual adsorption model to capture gas-particle partitioning of PCDD/Fs in the atmosphere. This coupled model can simulate the transport and fate of PCDD/Fs in multi-media environments with high spatiotemporal resolution, facilitating a nuanced understanding of the impacts of emissions, climate, urbanization and other factors on PCDD/F pollution. Additionally, dietary ingestion, particularly from animal-derived foods, is identified as the predominant source (up to 98%) of human exposure to PCDD/Fs. While the changes in dietary structure, population distribution, and age structure can influence human exposure to PCDD/Fs, their impacts have not yet been quantified. The proposed model lays the foundation for a systematic assessment of health risks from PCDD/F exposure through various pathways by further incorporating a food chain model. Overall, this review offers a comprehensive strategy for assessing PCDD/F pollution, encompassing the entire continuum from emissions to environmental impacts.

Three novel antioxidant peptides MHW, YHW and FHW were designed by the analysis of 3D-QSAR. Two accurate CoMFA (Q2 = 0.886 and R2 = 0.988) and CoMSIA (Q2 = 0.737 and R2 = 0.955) models were established. The FTC assay showed that activities of the new peptides on lipid peroxidation is significantly better than that of the template molecule LHW. The results of erythrocyte hemolysis assay demonstrated that MHW, YHW and FHW significantly inhibited AAPH-induced erythrocyte hemolysis by scavenging free radicals at the cellular level. It caused the restoration of intracellular antioxidant enzyme (GSH, CAT and SOD) activities at an acceptable pace and the silencing of intracellular MDA formation. Furthermore, MTT toxicity assay showed that the novel antioxidant peptides had good biocompatibility and no cytotoxicity. Molecular docking and molecular dynamics simulations were used to investigate the molecular mechanism. The results showed that Ser363, Arg380, Asn414 and Arg415 residues played key roles in the antioxidant activity of MHW, YHW and FHW. And they mainly binded to the important residues of Keap1 protein stably by electrostatic force, van der Waals force, H-bonds and hydrophobic interactions, which can better fit the Kelch pocket structural domain of Keap1. Therefore, MHW, YHW and FHW had strong potential to interfere with Keap1-Nrf2 interaction and promoted the enzymatic expression of Nrf2-ARE downstream target pathway.

The recent remarkable success of mesoporous silica nanoparticle (MSN) technology has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. However, as an anti-tumor drug delivery system, traditional MSN is prone to clearance by the host immune system, resulting in suboptimal pharmacokinetics and inadequate drug concentrations in tumors. The emergence of biomimetic drug delivery systems has effectively addressed these challenges. In this study, we aimed to develop a biomimetic drug delivery system based on MSN to achieve both immune evasion and tumor targeting. To this end, we coated folic acid-modified mesoporous silica (FMSN) cores with lipid-hybridized macrophage membranes (HEs) through co-extrusion, yielding FMSN@HEs. Initially, we demonstrated effective retention of key proteins Integrin α4 and Integrin β1 in the HEs, leading to significantly reduced clearance of FMSN@HEs by phagocytes in vitro. CCK-8 experiments validated the ability of CUR-FMSN@HEs to effectively inhibit the proliferation of tumor cells. In tumor-bearing mice, FMSN@HEs exhibited stronger tumor targeting and penetration abilities compared to MSN without HEs. The immune escape and tumor-targeting properties of the FMSN@HEs suggest that they could be used as novel bionic drug carriers, potentially providing more options for antitumor therapy.

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG(O)) was developed to achieve cancer ozone therapy (O3-T) based on intracellular Criegee's reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG(O)) was prepared as a chemotherapeutic agent for local O3-T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG(O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O3-T could directly destroy tumor cells via intracellular Criegee's reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical's production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG(O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O3-T, especially for postoperative skin diseases.

Iron (Fe)-based nanoparticles (NPs) have attracted considerable attention in nanomedicine research due to their enhancement effects in magnetic resonance imaging (MRI) and cancer therapy. Although zero-valent Fe (Fe(0)) can serve as an active catalyst to decompose H2O2 into reactive oxygen species (ROS), its activity is compromised in physiological conditions due to its susceptibility to oxidation. Here it is reported that a 9 nm FeAu alloy NP system can efficiently stabilize Fe(0) in neutral pH solution, but release Fe(0) in tumor-bearing environment, catalyzing H2O2 decomposition to ROS. Although Fe3O4 NPs and Au NPs are well-known for their biocompatible, FeAu NPs effectively eliminate cancer cells at an IC50 as low as 15 mu g mL-1 Fe. Further proteomics analysis reveals that FeAu NPs can concomitantly induce both ferroptosis and pyroptosis. Additional near-infrared (NIR) irradiation further increases cell death and promotes maturation of dendritic cells within tumor-draining lymph nodes and infiltration of helper T cells and cytotoxic T lymphocytes within tumor sites, resulting in significant reduction in tumor growth and metastasis. The studies demonstrate a great potential of FeAu NPs as a stable Fe(0) reservoir for pH/NIR controlled Fe(0) release and further for ferroptosis and pyroptosis co-mediated tumor immunotherapy. FeAu alloy nanoparticles are designed as zero-valent iron reservoirs with pH and near-infrared laser-dependent iron release behavior. While Fe3O4 and Au are generally considered to be biocompatible, the FeAu alloy nanoparticles cause a synergistic combination of ferroptosis and pyroptosis, which are further enhanced upon laser irradiation for efficient tumor immunotherapy. image

ABSTRACT Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM) – bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM) – to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids, alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models, without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement towards addressing the unmet medical need for improved therapies targeting this challenging disease.

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer mortality among women worldwide. A large number of patients experience recurrence and BC-associated mortality following adjuvant chemotherapy. The present study aimed to determine the most suitable pathological subtype of BC to benefit from intensive dose-dense (DD) chemotherapy. A total of four electronic databases were searched from inception up to March 10, 2023. Randomized controlled trials (RCTs) and retrospective studies comparing DD chemotherapy with standard chemotherapy in patients with BC were included. Pairwise random effects and network meta-analyses were performed to summarize efficacy and safety outcomes. A total of 27 original studies including 27,580 patients with BC were included. In terms of efficacy, the present study evaluated overall survival, disease-free survival, event-free survival, recurrence-free survival, pathological complete response and objective remission rate. Significant differences were identified in overall, hormone receptor+ (HR+) and HR- subgroups. Furthermore, from the network analysis, the HR+ and Her2- subgroups had the highest ranking, and these findings suggested that HR+/Her2- patients with BC should adhere to a treatment strategy including intensive DD chemotherapy, which is also characterized by an acceptable safety profile. In conclusion, patients with HR+ and Her2- BC were revealed to be the most suitable pathological type and are most likely to benefit from intense DD chemotherapy. The present study was registered with PROSPERO, CRD2022420351567.

Considering the application requirements for modern biomedicine,research into novel biomaterials with unusual functions is highly desired.As an alternative,liquid metals(LMs),a nontraditional family of metal materials,have piqued the interest of biomedical researchers and made significant advances in biomed-ical areas,owing to their shape transformability,self-healing capability,excellent electrical,and thermal conductivities.In particular,many functionalized strategies for the preparation and modification of LMs or LMs-based composites to achieve extended biomedical applications have been investigated in recent years.These findings provided inspiring while constructive reference for the fabrication and engineering of novel LMs-based composites.Herein,in this topic review,we elaborate on the recent advances of LMs-based functional materials,with particular focuses on the synthesis,modification,and bio-applications,especially in antitumor therapy,antibacterial,contrast agent for imaging,bone repair,electronic skin sen-sor,and nerve connection agent.Further on,the current challenges and future prospects of LMs-based composites are carefully discussed.

This study evaluated the subacute toxicity and toxicokinetics of a potential anti-cancer drug candidate, pterostilbene, in rats. Animals were orally administered at two repeated doses of 200 and 500 mg/kg for 28 days. No mortality was observed during the 28 days of continuous administration of pterostilbene. Body weight and food consumption in each group increased steadily, while no significant difference was found. Liver weight in the 500 mg/kg female, but not male group increased with mild cytoplasmic vacuoles observed in histopathological study. Toxicokinetics was assessed by measuring plasma concentrations of pterostilbene on the first and 28th day of administration using UPLC-MS/MS. Toxicokinetic parameters showed that AUC(0-)(t) significantly increased in all animals, while the increase in females was greater than males. System exposure of pterostilbene appeared to be linear within the administrated dose range. In conclusion, our findings suggested a minimal subacute toxicity profile of pterostilbene, which could strongly support further development of this compound as a novel anti-cancer agent.