Cancer-associated fibroblast-derived circFARP1 modulates non-small cell lung cancer invasion and metastasis through the circFARP1/miR-338-3p/SOX4 axis.

The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non-small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.

Identification and quantification of goat milk adulteration using mid-infrared spectroscopy and chemometrics.

The fraudulent adulteration of goat milk with cheaper and more available milk of other species such as cow milk is occurrence. The aims of the present study were to investigate the effect of goat milk adulteration with cow milk on the mid-infrared (MIR) spectrum and further evaluate the potential of MIR spectroscopy to identify and quantify the goat milk adulterated. Goat milk was adulterated with cow milk at 5 different levels including 10%, 20%, 30%, 40%, and 50%. Statistical analysis showed that the adulteration had significant effect on the majority of the spectral wavenumbers. Then, the spectrum was preprocessed with standard normal variate (SNV), multiplicative scattering correction (MSC), Savitzky-Golay smoothing (SG), SG plus SNV, and SG plus MSC, and partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLSR) were used to establish classification and regression models, respectively. PLS-DA models obtained good results with all the sensitivity and specificity over 0.96 in the cross-validation set. Regression models using raw spectrum obtained the best result, with coefficient of determination (R2), root mean square error (RMSE), and the ratio of performance to deviation (RPD) of cross-validation set were 0.98, 2.01, and 8.49, respectively. The results preliminarily indicate that the MIR spectroscopy is an effective technique to detect the goat milk adulteration with cow milk. In future, milk samples from different origins and different breeds of goats and cows should be collected, and more sophisticated adulteration at low levels should be further studied to explore the potential and effectiveness of milk mid-infrared spectroscopy and chemometrics.

Mechanisms of Lanthanum-mediated mitigation of salt stress in soybean (Glycine max L.).

Salinity is considered one of the abiotic stresses that have the greatest impact on soybean production worldwide. Lanthanum (La) is a rare earth element that can reduce adverse conditions on plant growth and productivity. However, the regulatory mechanism of La-mediated plant response to salt stress has been poorly studied, particularly in soybeans. Therefore, our study investigated the mechanisms of La-mediated salt stress alleviation from the perspectives of the antioxidant system, subcellular structure, and metabolomics responses. The results indicated that salt stress altered plant morphology and biomass, resulting in an increase in peroxidation, inhibition of photosynthesis, and damage to leaf structure. Exogenous La application effectively promoted the activity of superoxide dismutase (SOD) and peroxidase (POD), as well as the soluble protein content, while decreasing the Na+ content and Na+/K+ ratio in roots and leaves, and reducing oxidative damage. Moreover, transmission electron microscopy (TEM) demonstrated that La prevented the disintegration of chloroplasts. Fourier-transform infrared spectroscopy (FTIR) analysis further confirmed that La addition mitigated the decline in protein, carbohydrates, and pectin levels in the leaves. Lanthanum decreased the leaf flavonoid content and synthesis by inhibiting the content of key substances in the phenylalanine metabolism pathway during NaCl exposure. Collectively, our research indicates that La reduces cell damage by regulating the antioxidant system and secondary metabolite synthesis, which are important mechanisms for the adaptive response of soybean leaves, thereby improving the salt tolerance of soybeans.

Differential response of proline metabolism defense, Na+ absorption and deposition to salt stress in salt-tolerant and salt-sensitive rapeseed (Brassica napus L.) genotypes.

Soil salinization is a major abiotic factor threatening rapeseed yields and quality worldwide, yet the adaptive mechanisms underlying salt resistance in rapeseed are not clear. Therefore, this study aimed to explore the differences in growth potential, sodium (Na+) retention in different plant tissues, and transport patterns between salt-tolerant (HY9) and salt-sensitive (XY15) rapeseed genotypes, which cultivated in Hoagland's nutrient solution in either the with or without of 150 mM NaCl stress. The results showed that the inhibition of growth-related parameters of the XY15 genotype was higher than those of the HY9 in response to salt stress. The XY15 had lower photosynthesis, chloroplast disintegration, and pigment content but higher oxidative damage than the HY9. Under NaCl treatment, the proline content in the root of HY9 variety increased by 8.47-fold, surpassing XY15 (5.41-fold). Under salt stress, the HY9 maintained lower Na+ content, while higher K+ content and exhibited a relatively abundant K+/Na+ ratio in root and leaf. HY9 also had lower Na+ absorption, Na+ concentration in xylem sap, and Na+ transfer factor than XY15. Moreover, more Na+ contents were accumulated in the root cell wall of HY9 with higher pectin content and pectin methylesterase (PME) activity than XY15. Collectively, our results showed that salt-tolerant varieties absorbed lower Na+ and retained more Na+ in the root cell wall (carboxyl group in pectin) to avoid leaf salt toxicity and induced higher proline accumulation as a defense and antioxidant system, resulting in higher resistance to salt stress, which provides the theoretical basis for screening salt resistant cultivars.

Effects of Mixed Organic Acids and Essential Oils in Drinking Water on Growth Performance, Intestinal Digestive Capacity, and Immune Status in Broiler Chickens.

In order to evaluate the effects of acidifiers and essential oils in drinking water on growth, intestinal digestive capacity, and immune status in broilers, a total of 480, 1-day-old Arbore Acres broilers were randomly assigned to four treatments including normal tap water (Ctr) and tap water supplemented with acidifier I (ACI), acidifier I and essential oils (ACI+EO), and acidifier II (ACII). Both ACI+EO and ACII increased final body weight. The pH value of the crop and gizzards was reduced by ACI+EO, and ACII decreased the pH values of the proventriculus and gizzards (p < 0.05). Compared with control group, ACI, ACI+EO, ACII significantly enhanced lipase activity in jejunum but ACII decreased the level of serum total cholesterol and total triglyceride (p < 0.05). Compared with the control group, ACI+EO and ACII significantly increased the relative weight of the spleen, increased the level of serum IgA and IgM, and decreased E. coli in excreta, while ACII significantly decreased Salmonella in excreta (p <0.05). All treatments significantly increased Lactobacillus in excreta. In conclusion, ACI+EO improved immune status and ACII was effective in reducing Salmonella and promoting Lactobacillus, contributing to intestinal health.

Heterometallic Eu/Zn-MOF-based ratiometric sensing platform: Highly sensitive fluorescence / second-order scattering identification of tetracycline analogs and its molecular informatization applications.

The traditional preparation method of ratiometric probes faces challenges such as cumbersome preparation and low sensitivity. Thus, there is an urgent need to provide a simple method of preparing a highly sensitive ratiometric probe. Here, Eu3+-doped zinc-based organic framework (Eu/Zn-MOF) was prepared through hydrothermal method for the detection of tetracycline analogs (TCs). Under the same excitation conditions, the probe can simultaneously display valuable fluorescence and second-order scattering signals. The developed probe enabled specific identification and fast detection (1 min) of TCs, including tetracycline, oxytetracycline, doxycycline, and chlortetracycline. The linear detection ranges of tetracycline, oxytetracycline, doxycycline and chlortetracycline were respectively 100 nM - 200 µM, 100 nM - 200 µM, 98 nM - 195 µM, and 97 nM - 291 µM, and the corresponding detection limits were respectively 15.79 nM, 20.83 nM, 15.31 nM, and 28.30 nM. The developed sensor was successfully applied to detect TCs in real samples, and the recovery rate was from 92.54 % to 109.69 % and the relative standard deviation was from 0.04 % to 2.97 %. Moreover, the heterometallic Eu/Zn-MOF was designed as a ratiometric neuron for Boolean logic computing and information encryption based on the specific identification of TCs. As a proof of concept, molecular steganography was successfully employed to encode, store, and conceal information by transforming the specific identification patterns of Eu/Zn-MOF into binary strings. This study is anticipated to advance the application of metal-organic frameworks in logic detection and information security, and bridging the gap between molecular sensors and the realm of information.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis.

BACKGROUND: Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide. Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy (PTCSL). AIM: To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation (PTOBF) technique guided by three-dimensional (3D) visualization. METHODS: This was a retrospective, single-center study analyzing, 140 patients who, between October 2016 and October 2023, underwent one-step PTCSL for hepatolithiasis. The patients were divided into two groups: The 3D-PTOBF group and the PTOBF group. Stone clearance on choledochoscopy, complications, and long-term clearance and recurrence rates were assessed. RESULTS: Age, total bilirubin, direct bilirubin, Child-Pugh class, and stone location were similar between the 2 groups, but there was a significant difference in bile duct strictures, with biliary strictures more common in the 3D-PTOBF group (P = 0.001). The median follow-up time was 55.0 (55.0, 512.0) days. The immediate stone clearance ratio (88.6% vs 27.1%, P = 0.000) and stricture resolution ratio (97.1% vs 78.6%, P = 0.001) in the 3D-PTOBF group were significantly greater than those in the PTOBF group. Postoperative complication (8.6% vs 41.4%, P = 0.000) and stone recurrence rates (7.1% vs 38.6%, P = 0.000) were significantly lower in the 3D-PTOBF group. CONCLUSION: Three-dimensional visualization helps make one-step PTCSL a safe, effective, and promising treatment for patients with complicated primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis. This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.

Adaptive fuzzy fixed-time bipartite consensus control for stochastic nonlinear multi-agent systems with performance constraints.

This paper investigates the fixed-time bipartite consensus control problem of stochastic nonlinear multi-agent systems (MASs) with performance constraints. A constraint scaling function is proposed to model the performance constraints with user-predefined steady-state accuracy and settling time without relying on the initial condition. Technically, the local synchronization error of each follower is mapped to a new error variable using the constraint scaling function and an error transformation function before being used to design the controller. To achieve fixed-time convergence of the local tracking error, a barrier function transforms the scaled synchronization error to a new variable to guarantee the prescribed performance. Then, an adaptive fuzzy fixed-time bipartite consensus controller is developed. The fuzzy logic system handles the uncertainties in the designing procedures, and one adaptive parameter needs to be estimated online. It is shown that the closed-loop system has practical fixed-time stability in probability, and the antagonistic network's consensus error evolves within user-predefined performance constraints. The simulation results evaluate the effectiveness of the developed control scheme.

The clinicopathologic significance of psammoma bodies in cytology specimens: A series of 78 cases.

BACKGROUND: Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies. METHODS: Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed. RESULTS: A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies. CONCLUSION: Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types.

Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.

Fusion of a rice endogenous N-methylpurine DNA glycosylase to a plant adenine base transition editor ABE8e enables A-to-K base editing in rice plants.

Engineering of a new type of plant base editor for simultaneous adenine transition and transversion within the editing window will greatly expand the scope and potential of base editing in directed evolution and crop improvement. Here, we isolated a rice endogenous hypoxanthine excision protein, N-methylpurine DNA glycosylase (OsMPG), and engineered two plant A-to-K (K = G or T) base editors, rAKBE01 and rAKBE02, for simultaneous adenine transition and transversion base editing in rice by fusing OsMPG or its mutant mOsMPG to a plant adenine transition base editor, ABE8e. We further coupled either OsMPG or mOsMPG with a transactivation factor VP64 to generate rAKBE03 and rAKBE04, respectively. Testing these four rAKBEs, at five endogenous loci in rice protoplasts, indicated that rAKBE03 and rAKBE04 enabled higher levels of A-to-G base transitions when compared to ABE8e and ABE8e-VP64. Furthermore, whereas rAKBE01 only enabled A-to-C/T editing at one endogenous locus, in comparison with rAKBE02 and rAKBE03, rAKBE04 could significantly improve the A-to-C/T base transversion efficiencies by up to 6.57- and 1.75-fold in the rice protoplasts, respectively. Moreover, although no stable lines with A-to-C transversion were induced by rAKBE01 and rAKBE04, rAKBE04 could enable simultaneous A-to-G and A-to-T transition and transversion base editing, at all the five target loci, with the efficiencies of A-to-G transition and A-to-T transversion editing ranging from 70.97 to 92.31% and 1.67 to 4.84% in rice stable lines, respectively. Together, these rAKBEs enable different portfolios of editing products and, thus, now expands the potential of base editing in diverse application scenario for crop improvement. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00138-8.

Association of lower urinary tract symptoms and geriatric nutritional risk index in men: a cross-sectional study based on NHANES.

Background: Despite previous literature exploring the factors influencing lower urinary tract symptoms (LUTS), few studies have examined the relationship between nutritional status and LUTS. Objectives: The objective of this research was to evaluate the relationship between LUTS and Geriatric Nutritional Risk Index (GNRI) in middle-aged and older men. Methods: We included 2,607 men in the NHANES 2005-2006 and 2007-2008 cycles for cross-sectional analysis. We screened for LUTS based on four specific questions on the relevant questionnaire. We calculated GNRI according to the relevant calculation formula and included other covariates. Multivariate logistic analysis using GNRI as the principal independent variable and adjusting for other covariates were used to determine the association with LUTS, nocturia, and daytime LUTS. Results: According to the responses to the questionnaire, out of 2,607 eligible participants, 471 had LUTS, 906 had nocturia, and 819 had daytime LUTS. In the unadjusted regression model, LUTS (OR = 0.93, 95% CI = 0.91-0.96, p < 0.001), nocturia (OR = 0.90, 95% CI = 0.88-0.93, p < 0.001), and daytime LUTS (OR = 0.96, 95% CI = 0.94-0.99, p = 0.002) were significantly negatively associated with GNRI. After adjustment by adding covariates, LUTS (OR = 0.97,95% CI =0.94-0.99, p = 0.026) and nocturia (OR = 0.94, 95% CI =0.91-0.93, p < 0.001) were significantly negatively associated with GNRI. Conclusion: Low GNRI was associated with the development of LUTS. In the prevention and treatment of LUTS, urologists should consider the impact of nutritional status on LUTS, and interventions for nutritional status may prevent and improve LUTS.

Rock crack initiation triggered by energy digestion.

The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

Dynamical Symmetry-Reduction-Induced Giant Anharmonicity in IV-VI Compounds: Role of Cation Lone-Pair s Electrons.

The low thermal conductivity of group IV-VI semiconductors is often attributed to the soft phonons and giant anharmonicity observed in these materials. However, there is still no broad consensus on the fundamental origin of this giant anharmonic effect. Utilizing first-principles calculations and group symmetry analysis, we find that the cation lone-pairs s electrons in IV-VI materials cause a significant coupling between occupied cation s orbitals and unoccupied cation p orbitals due to the symmetry reduction when atoms vibrate away from their equilibrium positions under heating. This leads to an electronic energy gain, consequently flattening the potential energy surface and causing soft phonons and strong anharmonic effects. Our findings provide an intrinsic understanding of the low thermal conductivity in IV-VI compounds by connecting the anharmonicity with the dynamical electronic structures, and can also be extended to a large family of hybrid systems with lone-pair electrons, for promising thermoelectric applications and predictive designs.

Analysis of traditional Chinese medicine syndrome elements and clinical symptoms in prediabetes: A systematic review.

BACKGROUND: Prediabetes mellitus (PDM) and impaired glucose regulation precedes diabetes and serve as early warning signals. A 2018 Chinese epidemiological survey reported prediabetes at 25.5% prevalence and type 2 diabetes at 10.8%, respectively. Untreated carries one-third of the risk of diabetes progression. This study aimed to understand traditional Chinese medicine syndromes in PDM to guide clinical practice and diabetes prevention. METHODS: We systematically searched the Chinese and English literature in PubMed, EMBASE, Sinomed, CNKI, VIP, Wanfang until March 31, 2023. We manually explored the Chinese prediabetes literature, trial registrations, and references, adhering to predefined criteria. The results were independently summarized by 2 researchers. Statistical analysis was performed using EXCEL, IBM SPSS 27.0, and IBM SPSS Modeler 18.0, with data mining techniques including association and cluster analysis. RESULTS: Analysis of 23 clinical trials (8943 patients) identified phlegm dampness syndrome as predominant, with qi deficiency, dampness, and phlegm as the principal pathogenic elements. Spleen syndrome elements dominated, with a priori correlation analysis favoring spleen dampness. The prevalent PDM clinical symptoms include amnesia, mental fatigue, limb fatigue, dizziness, and lumbar discomfort. CONCLUSION: Prediabetes is strongly associated with spleen dampness, highlighting its role. Common traditional Chinese medicine syndrome elements include qi deficiency, phlegm, and dampness. Clinical diagnosis and treatment should prioritize syndrome differentiation and emphasize spleen-focused approaches. Although limited research exists on prediabetes syndromes, further exploration of PDM and spleen dampness is crucial.

Tissue-engineered mesenchymal stem cell constructs alleviate tendinopathy by suppressing vascularization.

Tendinopathy leads to low-grade tissue inflammation and chronic damage, which progresses due to pathological imbalance in angiogenesis. Reducing early pathological vascularization may be a new approach in helping to regenerate tendon tissue. Conventional stem cell therapy and tissue engineering scaffolds have not been highly effective at treating tendinopathy. In this study, tissue engineered stem cells (TSCs) generated using human umbilical cord mesenchymal stem cells (hUC-MSCs) were combined with microcarrier scaffolds to limit excessive vascularization in tendinopathy. By preventing VEGF receptor activation through their paracrine function, TSCs reduced in vitro angiogenesis and the proliferation of vascular endothelial cells. TSCs also decreased the inflammatory expression of tenocytes while promoting their anabolic and tenogenic characteristics. Furthermore, local injection of TSCs into rats with collagenase-induced tendinopathy substantially reduced early inflammation and vascularization. Mechanistically, transcriptome sequencing revealed that TSCs could reduce the progression of pathological angiogenesis in tendon tissue, attributed to Rap1-mediated vascular inhibition. TSCs may serve as a novel and practical approach for suppressing tendon vascularization, and provide a promising therapeutic agent for early-stage clinical tendinopathy.

Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model.

Previous studies have reported the correlation between gut microbiota (GM), GM-derived metabolites, and various intestinal and extra-intestinal cancers. However, limited studies have investigated the correlation between GM, GM-derived metabolites, and osteosarcoma (OS). This study successfully established a female BALB/c nude mouse model of OS. Mice (n = 14) were divided into the following two groups (n = 7/group): OS group named OG, injected with Saos-2 OS cells; normal control group named NCG, injected with Matrigel. The GM composition and metabolites were characterized using 16S rDNA sequencing and untargeted metabolomics, respectively. Bioinformatics analysis revealed that amino acid metabolism was dysregulated in OS. The abundances of bone metabolism-related genera Alloprevotella, Rikenellaceae_RC9_gut_group, and Muribaculum were correlated with amino acid metabolism, especially histidine metabolism. These findings suggest the correlation between GM, GM-derived metabolites, and OS pathogenesis. Clinical significance: The currently used standard therapeutic strategies for OS, including surgery, chemotherapy, and radiation, are not efficacious. The findings of this study provided novel insights for developing therapeutic, diagnostic, and prognostic strategies for OS.