Excessive M1 polarisation of synovial macrophages contributes substantially to the dysregulated immune environment that drives osteoarthritis (OA) progression, although the role of silent information regulator 1 (SIRT1) and its therapeutic relevance remain uncertain. We investigated whether quercetin protects against OA by modulating synovial macrophage polarisation and SIRT1-related signalling. SIRT1 expression and M1-associated markers were examined in synovial tissues from patients with OA. Myeloid-specific SIRT1-deficient mice were generated, and OA was induced by destabilisation of the medial meniscus (DMM). The animals received quercetin, either alone or together with the selective SIRT1 inhibitor EX527. In parallel, bone marrow-derived macrophages (BMDMs) were stimulated with lipopolysaccharide (LPS) to induce M1 polarisation before quercetin treatment. Molecular and cellular assays were used to evaluate macrophage polarisation and NF-κB p65 signalling. SIRT1 expression was markedly reduced in OA synovium and was lower in severe OA than in moderate OA, whereas M1 polarisation was enhanced. Myeloid-specific SIRT1 deficiency aggravated synovial inflammation, cartilage degradation, and subchondral bone remodelling. Quercetin increased SIRT1 activity, suppressed M1 polarisation, lowered pro-inflammatory cytokine and matrix metalloproteinase expression, and alleviated OA pathology. These protective effects were weakened by either pharmacological inhibition or genetic deletion of SIRT1. Collectively, the findings suggest that quercetin attenuates OA progression by regulating synovial macrophage polarisation through a mechanism that is at least partly dependent on SIRT1 and associated with modulation of NF-κB p65 signalling.

To construct a nomogram risk prediction model for osteoporotic vertebral compression fracture (OVCF) in postmenopausal osteoporosis (POP). A retrospective study was conducted on 326 POP patients from July 2023 to November 2024. The patients were randomly included into a training cohort of 228 cases and a validation cohort of 98 cases based on a 7:3 ratio; The training queue was assigned into a fracture group of 82 cases and a non fracture group of 146 cases. Risk factors were screened based on multiple logistic regression analysis. R software was used to construct nomogram prediction models. ROC curve, calibration curve, and clinical decision curve were performed to evaluate model discrimination, calibration, and practicality. For the non fracture group, the fracture group showed manifest increases in age, physical exercise time < 1 h/d, gastrointestinal diseases, uric acid, and type I collagen carboxy terminal peptide (β-CTX), and manifest decreases in bone mineral density (BMD) (T value), hemoglobin (Hb), and 5-hydroxyvitamin D [25-(OH)D] (P < 0.05). Increase in age, decrease in BMD (T value), physical exercise time < 1 h/d, presence of gastrointestinal diseases, increase in uric acid, increase in β-CTX, and decrease in 25-(OH)D were independent risk factors for OVCF in POP (P < 0.05). The calibration curves of the training queue and validation queue indicated a high degree of agreement between the predicted results of the model and the actual results, Hosmer-Lemeshow χ2 = 5.155, 4.490, P = 0.631, 0.810. The AUC of ROC curve was 0.974 and 0.909. In the decision curve analysis, the model demonstrated a net clinical benefit across threshold probability ranges of 0.05-0.97 in the training cohort and 0.02-0.99 in the validation cohort. The established nomogram prediction model can be used to reasonably evaluate the risk of OVCF in POP patients.

Osteoporosis (OP), characterized by reduced bone mass and microarchitectural deterioration, significantly impairs patient health and quality of life. Conventional therapies are often limited by long-term safety concerns and adverse effects. Recent studies suggest that extracellular vesicles (EVs) play a critical role in bone remodeling by promoting osteoblast differentiation and mineralization while inhibiting osteoclast activity, offering a potential therapeutic avenue for OP. In this study, we observed a significant reduction of Roseburia intestinalis (R.intestinalis), an anaerobic, gram-positive bacterium, in both OP patients and ovariectomized (OVX) model rats by 16S rRNA sequencing. We successfully isolated and characterized R.intestinalis-derived EVs (REVs), which were found to promote the differentiation and mineralization of human bone marrow mesenchymal stromal cells (hBMSCs) in vitro. Mechanistically, REVs were shown to enhance the production of histidylleucine, and the administration of histidylleucine alone was sufficient to promote hBMSCs differentiation and mineralization through the Akt/FOXO1 signaling pathway. Furthermore, both REVs and histidylleucine were effective in reversing gut microbiota dysbiosis and improving bone mineral density in vivo. These findings highlight the therapeutic potential REVs and their metabolite histidylleucine in OP treatment through modulation of the "gut-bone" axis, which providing insights into histidylleucine as a promising therapeutic agent for OP.

Background Osteosarcoma is a rare and aggressive bone malignancy, yet public awareness remains insufficient. As social media platforms have become key sources of health information, this study aims to evaluate the quality and reliability of osteosarcoma-related videos on these platforms. Methods This study collected 100 osteosarcoma-related videos from each platform, TikTok and Bilibili, based on their default ranking, resulting in 200 videos initially screened and 183 included after exclusions. Video characteristics were collected, including duration, likes, saves, comments, and shares. The Global Quality Scale (GQS) and Modified Discrimination Score (mDISCERN) were used to assess video quality and reliability. The completeness score (CS) was applied to evaluate five key aspects of the disease: etiology, clinical manifestations, diagnosis, treatment, and diagnosis. Finally, correlation analysis is carried out to explore the relationship among video features, audience engagement indicators, and video quality. Results A total of 183 osteosarcoma-related videos were included. Clinical manifestations, treatment, and diagnosis were the most frequently addressed topics, whereas etiology and prognosis received comparatively less attention. TikTok videos had a median GQS of 2(Q1 = 2.00, Q3 = 3.00), a median mDISCERN of 3 (Q1 = 2.00, Q3 = 4.00), and a median CS of 4 (Q1 = 2.00, Q3 = 4.00). In contrast, Bilibili videos demonstrated higher quality, with a median GQS of 3 (Q2 = 2.00, Q3 = 3.00), a median mDISCERN of 3 (Q1 = 3.00, Q3 = 4.00), and a median CS of 4 (Q1 = 3.00, Q3 = 6.00). Videos produced by healthcare professionals achieved significantly higher scores compared to those uploaded by non-professionals ( p < 0.01). Spearman correlation analysis revealed no significant association between video features and quality scores. Conclusion In conclusion, the overall quality and reliability of osteosarcoma-related videos on short video platforms were low. Videos uploaded by healthcare professionals and those on the Bilibili platform demonstrated relatively higher quality. These findings highlight the necessity of strengthening the regulation of health-related content on short video platforms and promoting greater involvement of healthcare professionals.

Purpose:BLM and RECQL4, key RecQ helicases and "genome guardians", maintain genomic stability. Their abnormal function/dysregulated expression is linked to tumorigenesis, but their roles in osteosarcoma (OS) remain unclear. Patients and Methods:Comprehensive bioinformatic analyses (multiple public databases) assess OS-related expression, gene networks, prognosis, targets, and drugs. Cellular experiments verified the effects of these compounds on 143B cell proliferation, migration, and invasion. Results:BLM and RECQL4 were significantly upregulated in OS tissues compared to normal tissues, correlating with a poor prognosis. Among the 153 patients with OS, 9% and 7% had altered BLM and RECQL4 expression, respectively. Abnormal methylation of BLM and RECQL4 may affect OS. BLM, RECQL4, and their altered neighboring genes (ANGs) form interaction networks that regulate tumor metabolism, proliferation, migration, and apoptosis. Their miRNA and kinase targets in OS were also identified. BLM and RECQL4 expression was negatively correlated with OS immune cell infiltration. In addition, anti-PD-1/CTLA-4/PD-L1 therapy, Sphingosine kinase 1 inhibitor II, and pilaralisib inhibited OS cell viability (by downregulating BLM or RECQL4) and the proliferation, migration, and invasion of 143B cells. Knockdown of BLM or RECQL4 suppressed the migration and invasion of 143B cells. Conclusion:BLM and RECQL4 are promising prognostic biomarkers and therapeutic targets for OS.

Radiotherapy is an important treatment for cervical cancer, but the efficacy of radiotherapy is often reduced in clinical practice owing to high frequency and high dose radiation leading to radiotherapy resistance. The development of efficient and low-toxicity radiotherapy sensitizers to reduce radiation dose is an effective strategy. Therefore, based on the existing radiotherapy sensitizers responding to radiophysical sensitization radiotherapy, we propose to design radiotherapy sensitizers with enzyme-mimicking and dual physical-chemical sensitization properties. In this work, we constructed Ru-Se complexes with cytochrome P450 enzyme-mimicking properties. On the one hand, the high concentration of ROS in tumor cells, along with the complexes, catalyzed the oxidation of intracellular active substances, breaking the redox balance of the cells and chemically sensitizing radiotherapy; on the other hand, the high atomic numbers of ruthenium and selenium responded to X-rays and physically sensitized radiotherapy. Experimental results demonstrated that the Ru-Se complexes can efficiently mimic cytochrome P450 enzyme activity and simultaneously respond to radiation dual sensitization radiotherapy, causing the expression of intracellular DNA damage response proteins. Thus, inhibition of repair protein expression overcomes radiotherapy resistance. This work provides a new idea for the development of efficient radiation sensitizers in the future.

Introduction: Osteoporosis, a critical public health challenge, is marked by skeletal deformities and heightened fracture risk. Steleophaga plancyi (Boleny) (SP), a component of traditional Chinese medicine, is known to enhance bone health, but the molecular mechanisms behind its osteoprotective effects are not well understood. Methods: We isolated extracellular vesicle (EV)-like particles from SP (SP-EVLP) using differential velocity centrifugation and investigated their effects on human bone marrow stromal cells (hBMSCs) in vitro. We utilized CCK-8, Alkaline phosphatase (ALP) and alizarin red staining (ARS), RNA-seq, bioinformatics, immunofluorescence, and Western blot to elucidate the osteoprotective role and mechanisms of SP-EVLP. The therapeutic potential of SP-EVLP was evaluated in an ovariectomized (OVX) rat model, a standard model for osteoporosis, by encapsulating them in enteric-coated capsules. Results: SP-EVLP were successfully isolated and characterized, and they were shown to be effectively internalized by hBMSCs, enhancing osteogenic differentiation. In the OVX rat model, SP-EVLP encapsulated in enteric-coated capsules significantly increased bone mass, indicating a robust osteoprotective effect. Further mechanistic studies revealed that SP-EVLP promotes osteoblast proliferation by activating melatonin-induced autophagy, a pathway that may improve osteoporotic conditions. Conclusion: Our results establish SP-EVLP as a promising therapeutic candidate for osteoporosis. The activation of melatonininduced autophagy by SP-EVLP suggests a molecular mechanism for its osteoprotective effects, opening new possibilities for osteoporosis treatment development.

Introduction:Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo.Methods:DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry.Results:Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis.Conclusion:Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.

Pancreatic cancer is an aggressive malignancy with a dismal prognosis, and the underlying molecular mechanisms remain only partially understood. This study aimed to clarify the role of microRNA-21-5p (miR-21-5p) in pancreatic cancer progression and to investigate the associated mechanisms. We found that miR-21-5p was significantly elevated in pancreatic cancer tissues, and its high expression correlated with poorer patients’ prognosis. Functional assays revealed that miR-21-5p enhanced the proliferation, migration, and invasive capabilities of pancreatic cancer cells. Through bioinformatics analysis and experimental validation, we discovered ATP-binding cassette transporter D2 (ABCD2) as a novel direct target gene of miR-21-5p. ABCD2 expression was significantly downregulated in pancreatic cancer tissues, and its low expression was associated with reduced patient survival. Mechanistically, miR-21-5p inhibited ABCD2 transcription and translation by directly targeting its 3'UTR, a process facilitated by exosome delivery. Importantly, overexpression of ABCD2 effectively reversed the pro-oncogenic effects of miR-21-5p. Our findings establish the critical role of the miR-21-5p/ABCD2 axis in pancreatic cancer progression and highlight the tumor-suppressive function of ABCD2. ABCD2 may represent a promising therapeutic target and a potential site for the diagnosis and treatment of pancreatic cancer.

Objective: Most patients with osteosarcoma (OS) have an extremely poor prognosis. The primary purpose of this investigation was to explore the biological effect of Lnc-CLSTN2-1:1 on OS and the potential processes involved. Materials and procedures: We selected differentially overexpressed Lnc-CLSTN2-1:1 from our laboratory's existing RNA sequence analysis data (fibroblast osteoblast (hFOB 1.19) and three osteosarcoma cell lines (HOS, MG63, and U2OS) as the research object. Next, we detected Lnc-CLSTN2-1:1 in the osteosarcoma HOS cell line and fibroblast cells using qRT-PCR. We evaluated cell proliferation ability using EdU incorporation test, CCK-8 test, and cell clone formation; cell invasion and migration were assessed using the Transwell test, while flow cytometry examined cell cycle, apoptosis, and reactive oxygen species (ROS); Subsequently, the activity changes of selenase (GPx) glutathione peroxidase and (TrxR) thioredoxin reductase were detected. In addition, changes in related proteins were analyzed through Western blotting. Results: The expression of Lnc-CLSTN2-1:1 in osteosarcoma cells was significantly increased. The proliferation, invasion, and migration of osteosarcoma cells were significantly inhibited by knockdown of the expression of Lnc-CLSTN2-1:1, and the cell cycle-related signaling pathway PI3K/AKT/GSK-3β/cycinD1 was also inhibited. However, insulin-like growth factor-1 (igf-1) could reverse this process. In addition, we examined the activity of two selenophenases (TrxR and GPx) and the changes of ROS before and after Lnc-CLSTN2-1:1 knockdown. The results showed that both TrxR and GPx activities were reduced after Lnc-CLSTN2-1:1 knockdown, resulting in the inhibition of antioxidant stress levels, while intracellular ROS levels were high, which eventually caused killing effects on tumor cells due to the imbalance between oxidative stress and antioxidant stress. Conclusion: Our results showed that Lnc-CLSTN2-1:1 enhanced anti-oxidative stress TrxR and GPx selenoprotein activities through the PI3K/AKT signaling pathway while counteracting the loss of reactive oxygen species ROS produced by mitochondria to osteosarcoma cells, which protected osteosarcoma cells and thus promoted the proliferation and metastatic ability of OS.

Diabetic wound is one of the most common and serious complications of diabetes, which is characterized by abnormal number and quality of wound repair related cells. Previous studies have shown that human endothelial progenitor cells derived exosomes (EPCs-EXO) can promote diabetic wound healing through modulating vascular endothelial cell function. The purpose of this study was to investigate the biological effects and molecular mechanisms of EPCs-EXO on diabetic wound healing. The regulation of EPCs-EXO on human immortalized epidermal cell line HaCaT in high glucose (HG) environment was evaluated. Our data showed that EPCs-EXO promoted the proliferation, migration, while inhibited apoptosis of HaCaTs challenged by HG via elevating miR-182-5p expression level in vitro. Skin wound healing was significantly enhanced by EPCs-EXO in diabetic mice. Moreover, bioinformatics analyses and luciferase reporter assay indicated that exosomal miR-182-5p was bound to PPARG 3' UTR sequence and inhibited the expression of PPARG. Collectively, our findings provided a new role of EPCs-EXO in the clinical treatment of diabetic skin wounds. Diabetic wound is one of the most common and serious complications of diabetes, which is characterized by abnormal number and quality of wound repair related cells. Previous studies have shown that human endothelial progenitor cells derived exosomes (EPCs-EXO) can promote diabetic wound healing through modulating vascular endothelial cell function. The purpose of this study was to investigate the biological effects and molecular mechanisms of EPCs-EXO on diabetic wound healing. The regulation of EPCs-EXO on human immortalized epidermal cell line HaCaT in high glucose (HG) environment was evaluated. Our data showed that EPCs-EXO promoted the proliferation, migration, while inhibited apoptosis of HaCaTs challenged by HG via elevating miR-182-5p expression level in vitro. Skin wound healing was significantly enhanced by EPCs-EXO in diabetic mice. Moreover, bioinformatics analyses and luciferase reporter assay indicated that exosomal miR-182-5p was bound to PPARG 3' UTR sequence and inhibited the expression of PPARG. Collectively, our findings provided a new role of EPCs-EXO in the clinical treatment of diabetic skin wounds.

Dehydrogenases are a class of oxidoreductases that catalyze a wide variety of oxidative reactions in living organisms to maintain the redox homeostasis. Developing materials with dehydrogenase activity to break the homeostasis for the treatment of diseases with immortal proliferative properties has broad application prospects. Here, we use porphyrin ligands with good biocompatibility, and Co metal centers with high catalytic activity to jointly construct various dimensional Co porphyrin nano-coordination frameworks, and mimicking their catalytic performance of dehydrogenase activity. The results show that the one-dimensional nanoframeworks have the best dehydrogenase-like catalytic oxidation efficiency. At the same time, the cobalt porphyrin nanoframeworks with dehydrogenase-like activity inhibit cancer proliferation effectively.

Two-dimensional materials have excellent performance in energy catalysis and biomedicine due to their unique advantages in surface and interfacial properties. Taking into account the unique advantages of the surface interface and catalysis of two-dimensional materials, it is a very feasible way to construct two-dimensional materials with clear atomic structure to break the redox balance in tumor cells, so as to achieve efficient anti-tumor effects. Based on this, we selected the porphyrin ligands that widely exist in nature, equipped with iron metal active centers, and constructed a two-dimensional iron porphyrin nanozyme with a clear atomic structure, which simulated the redox activity of cytochrome P450 enzymes. The experimental results show that by carrying a rotatable pyridine group on the porphyrin ring, the iron porphyrin monomers can be effectively connected and expanded into a two-dimensional iron porphyrin microstructure. Enough iron centers are exposed on the surface of two-dimensional iron porphyrins as catalytic sites. In the presence of oxidants, two-dimensional iron porphyrins can efficiently catalyze the oxidation of small organic molecules, and have good P450-like enzymatic activity. At the same time, the two-dimensional iron porphyrin nanomaterial was used for anti-tumor, and it was found that it has an efficient ability to inhibit tumor proliferation, which may be due to the catalytic oxidation of various organic small molecules in tumor cells by the high concentration of hydrogen peroxide in tumor cells. At the same time, we found that the two-dimensional iron porphyrin nanozyme may have a good drug loading capacity due to the many exposed iron sites on its surface, which provides a possible option for drug loading to achieve combined high-efficiency tumor therapy.

Glucocorticoid (GC)‐induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation‐regulating activity, is employed to construct cysteine‐decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL‐Cys@SeNPs) and D‐Cys@SeNPs, the L‐Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)‐induced osteoblasts cells apoptosis. Intracellular L‐Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex‐induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β‐catenin pathway. Consistently, L‐Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex‐exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se‐based drug design through chirality control engineering.

Osteosarcoma is prone to metastasis and has a low long-term survival rate. The drug treatment of osteosarcoma, side effects of treatment drugs, and prognosis of patients with lung metastasis continue to present significant challenges, and the efficacy of drugs used in the treatment of osteosarcoma remains low. The development of new therapeutic drugs is urgently needed. In this study, we successfully isolated Pinctada martensii mucilage exosome-like nanovesicles (PMMENs). Our findings demonstrated that PMMENs inhibited the viability and proliferation of 143B cells, induced apoptosis, and inhibited cell proliferation by suppressing the activation of the ERK1/2 and Wnt signaling pathways. Furthermore, PMMENs inhibited cell migration and invasion by downregulating N-cadherin, vimentin, and matrix metalloprotease-2 protein expression levels. Transcriptomic and metabolomic analyses revealed that differential genes were co-enriched with differential metabolites in cancer signaling pathways. These results suggest that PMMENs may exert anti-tumor activity by targeting the ERK1/2 and Wnt signaling pathways. Moreover, tumor xenograft model experiments showed that PMMENs can inhibit the growth of osteosarcoma in mice. Thus, PMMENs may be a potential anti-osteosarcoma drug.

Osteoporosis (OP) is the most common bone disorder worldwide, especially in postmenopausal women. However, many OP drugs are not suitable for long term use due to major adverse effects. Therefore, there is an urgent need to identify more effective and safe therapeutic drugs. Pueraria lobata has been reported to promote osteoblast growth in bone regeneration, but the exact mechanisms still need further exploration. The current study found that Pueraria lobata-derived exosome-like nanovesicles (PELNs) promoting primary human bone mesenchymal stem cells (hBMSCs) differentiation and mineralization both in vitro and in ovariectomized (OVX)-induced osteoporotic rats. Interestingly, the relative abundance of harmful strains significantly decreased in the intestine of the osteoporosis SD rat model administrated PELNs via the regulation of trimethylamine-N-oxide (TMAO), a metabolite of gut microbiota. Moreover, RNA sequencing revealed that the osteogenic activity of PELNs is revealed to autophagy signaling. In vitro and in vivo experiments also showed that the treatment with PELNs promoted the differentiation and function of hBMSCs by elevating autophagy via the degradation of TMAO. Collectively, PELNs demonstrate promise as a therapeutic approach for OP, with TMAO emerging as a potential target of OP treatment.

Radiotherapy is widely used clinically, but the toxic and side effects of nonselective killing of high-energy radiation limit its application. Finding biocompatible materials to assemble radiotherapy sensitizers and studying their sensitization patterns are of great significance for the clinical application. Here, biocompatible zinc porphyrin was chosen as sub-unit to construct various dimensional coordination frameworks. By employing top-down approach, suitable nanoframeworks with various dimensional zinc porphyrin were synthesized as radiosensitizers. The experimental data showed that high-dimensional zinc porphyrin nanoframeworks exhibit higher X-ray response performance.

Facilely synthesized nanoradiosensitizers with well-controlled structure and multifunctionality are greatly desired to address the challenges of cancer radiotherapy. In this work, a universal method is developed for synthesizing chalcogen-based TeSe nano-heterojunctions (NHJs) with rod-, spindle-, or dumbbell-like morphologies by engineering the surfactant and added selenite. Interestingly, dumbbell-shaped TeSe NHJs (TeSe NDs) as chaperone exhibit better radio-sensitizing activities than the other two nanostructural shapes. Meanwhile, TeSe NDs can serve as cytotoxic chemodrugs that degrade to highly toxic metabolites in acidic environment and deplete GSH within tumor to facilitate radiotherapy. More importantly, the combination of TeSe NDs with radiotherapy significantly decreases regulatory T cells and M2-phenotype tumor-associated macrophage infiltrations within tumors to reshape the immunosuppressive microenvironment and induce robust T lymphocytes-mediated antitumor immunity, resulting in great abscopal effects on combating distant tumor progression. This study provides a universal method for preparing NHJ with well-controlled structure and developing nanoradiosensitizers to overcome the clinical challenges of cancer radiotherapy.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and teenagers and is characterized by high malignant potential, rapid disease progression and high disability and mortality rates. Recently, noncoding RNAs (ncRNAs) have attracted the attention of many scholars due to their major regulatory roles in gene expression. Among them, lncRNA PVT1 and circPVT1 encoded by the PVT1 gene have been the focus of many studies; they are upregulated in OS, and abundant evidence indicates that lncRNA PVT1 and circPVT1 play key roles in the occurrence and development of OS. This review summarizes the mechanisms of action of lncRNA PVT1 and circPVT1 in regulating apoptosis, proliferation, glycolysis, invasion, migration and epithelial-mesenchymal transition (EMT) in OS and discusses their clinical applications in diagnosis, prognosis determination and drug resistance treatment, with the aim of helping researchers better understand the regulatory roles of lncRNA PVT1 and circPVT1 in OS progression and providing a theoretical basis for the development of early screening and accurate targeted treatment strategies and prognostic biomarkers for OS based on lncRNA PVT1 and circPVT1.

骨肉瘤是一种青少年常见的原发性骨肿瘤 [1].据统计,在我国,骨肉瘤发病率约为 3 / 100 万,而在 15～ 19 岁青春期患者中发病率可达 11 / 100 万 [2],且有逐年上升趋势,是青少年癌症死亡的主要原因.由于缺乏特异性诊断标志物及检测指标,约 85％的患者首诊时即出现难以察觉的微小转移 [3-4].近几十年来,以外科手术为基础联合化疗的综合治疗策略已成为骨肉瘤的标准治疗模式,患者的 5 年生存率从 70％提升至 82％ [5].