Delayed Reproduction, Injury, and Regeneration of Testes in Out-of-Season Breeding of Largemouth Bass (Micropterus nigricans).

Out-of-season breeding is an effective method for addressing seasonal shortages of fry in aquaculture species such as largemouth bass (LMB) for year-round production. Off-season breeding of LMB can be achieved by subjecting breeding LMB to prolonged low-temperature conditions; however, this can alter reproductive rhythms, affecting the quality of their sperm and leading to a decrease in reproductive efficiency. Therefore, it is crucial to investigate issues such as the damage to the testes and the related mechanisms caused by low-temperature stress during out-of-season breeding. In this experiment, we assessed the changes in the testes during this time in LMB by comparing reproductive rhythms, testicular histomorphology, ultrastructure, antioxidant capacity and apoptosis. We synthesized measurements of LMB from three identically treated cement ponds and fish exposed to water temperatures of 13-16 °C to assess the changes in the testes. The results showed that (1) out-of-season reproduction delayed sperm production and promoted sperm redevelopment in LMB, various hormone levels have changed over time (e.g., LH, FSH, and T). (2) The head plasma membrane of LMB spermatozoa was separated, and the middle mitochondria were swollen. (3) The expression levels of antioxidant enzymes (cat, sod, and gpx) were upregulated, and oxidative stress occurred in LMB. (4) The expression levels of apoptosis genes (e.g., bax, bcl2, and caspase3) were upregulated, and apoptosis occurred in LMB due to off-season breeding. Moreover, important genes of the mitochondrial apoptosis pathway (bid, CYT-C) were upregulated, indicating that spermatozoan apoptosis in LMB was probably achieved through the mitochondrial apoptosis pathway. These results suggest the delays, damage, and regeneration of LMB testes. Our findings provide new insights into the molecular mechanisms that trigger changes in sperm quality during out-of-season breeding in fish.

Development of a Modular miRNA-Responsive Biosensor for Organ-Specific Evaluation of Liver Injury.

MicroRNAs (miRNAs) are increasingly being considered essential diagnostic biomarkers and therapeutic targets for multiple diseases. In recent years, researchers have emphasized the need to develop probes that can harness extracellular miRNAs as input signals for disease diagnostics. In this study, we introduce a novel miRNA-responsive biosensor (miR-RBS) designed to achieve highly sensitive and specific detection of miRNAs, with a particular focus on targeted organ-specific visualization. The miR-RBS employs a Y-structured triple-stranded DNA probe (Y-TSDP) that exhibits a fluorescence-quenched state under normal physiological conditions. The probe switches to an activated state with fluorescence signals in the presence of high miRNA concentrations, enabling rapid and accurate disease reporting. Moreover, the miR-RBS probe had a modular design, with a fluorescence-labeled strand equipped with a functional module that facilitates specific binding to organs that express high levels of the target receptors. This allowed the customization of miRNA detection and cell targeting using aptameric anchors. In a drug-induced liver injury model, the results demonstrate that the miR-RBS probe effectively visualized miR-122 levels, suggesting it has good potential for disease diagnosis and organ-specific imaging. Together, this innovative biosensor provides a versatile tool for the early detection and monitoring of diseases through miRNA-based biomarkers.

PCGF2 Acts as an Oncogenic Driver in Colon Cancer through the Upregulation of CENPE.

BACKGROUND: Colon cancer (CC) is a highly prevalent malignancy that contributes significantly to global morbidity and mortality. The polycomb group ring finger 2 (PCGF2) has been identified as a relevant factor influencing the outcomes of CC. At the same time, the centromere-associated protein E (CENPE) is implicated in promoting carcinogenesis and adversely affecting the survival of tumor patients. The primary objective of this study was to elucidate the precise impact of PCGF2 on CC and unravel the underlying mechanisms associated with CENPE. METHODS: Human normal colon epithelial cells and CC cells were utilized to investigate the differential expression of PCGF2 and CENPE. CC cell line LOVO was exploited and transfected for PCGF2 regulation. Subsequently, cell viability and proliferation were assessed using the cell counting kit 8 (CCK-8) and colony forming assay. Cell viability and proliferation were assessed using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, while cell migration and invasion capabilities were determined using the transwell assay, and mRNA levels of cell cycle-related genes were measured for evaluating cell cycle activation. In addition, mice were used for in vivo experiments to investigate the progression of CC cells with different levels of PCGF2. Moreover, GSK-923295 was used to inhibit CENPE, followed by the evaluation of cell progression. RESULTS: PCGF2 and CENPE were upregulated in CC cell lines (p < 0.001), and upregulation/downregulation of PCGF2 led to the upregulation and downregulation of CENPE (p < 0.001). The upregulation/downregulation of PCGF2 led to an increase/decrease in viability, proliferation, migration, and invasion while suppressing/enhancing apoptosis in LOVO cells (p < 0.001), promoting cell progression. The tumor progression of LOVO cells with PCGF2 knockdown was slower (p < 0.001). The PCGF2-promoting LOVO cell progression was disrupted when CENPE was inhibited, presented by the reversely decreased viability, proliferation, migration, invasion, and cell cycle activation, and increased apoptosis (p < 0.001). CONCLUSION: PCGF2 promotes CC cell progression by upregulating CENPE, providing PCGF2 inhibition and CENPE inhibition as potential therapeutic targets for treating CC.

Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications.

Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs are critically involved in shaping the structure and function of the tumour microenvironment with numerous functions in regulating tumour behaviours, such as metastasis, invasion, and epithelial-mesenchymal transition (EMT). CAFs can interact extensively with cancer cells by producing extracellular vesicles (EVs), multiple secreted factors, and metabolites. Notably, CAF-derived EVs have been identified as critical mediators of cancer therapy resistance, and constitute novel therapy targets and biomarkers in cancer management. This review aimed to summarize the biological roles and detailed molecular mechanisms of CAF-derived EVs in mediating cancer resistance to chemotherapy, targeted therapy agents, radiotherapy, and immunotherapy. We also discussed the therapeutic potential of CAF-derived EVs as novel targets and clinical biomarkers in cancer clinical management, thereby providing a novel therapeutic strategy for enhancing cancer therapy efficacy and improving patient prognosis.

MCMV-infected maize attracts its insect vector Frankliniella occidentalis by inducing ß-myrcene.

Maize lethal necrosis is attributed to the accumulation of maize chlorotic mottle virus (MCMV), an invasive virus transmitted by insect vectors. The western flower thrips (WFT) can shift host to maize, thus promoting the spread of MCMV. However, our understanding of the characteristics and interactions involved in the transmission of MCMV is still limited. This study finds that non-viruliferous WFTs showed a 57.56% higher preference for MCMV-infected maize plants compared to healthy maize plants, while viruliferous WFTs showed a 53.70% higher preference for healthy maize plants compared to MCMV-infected maize plants. We also show for the first time that both adults and larvae of WFT could successfully acquire MCMV after 1 min of acquisition access period (AAP), and after 48 h of AAP, WFT could transmit MCMV in an inoculation access period of 1 h without a latent period. Both adults and larvae of WFT can transmit MCMV for up to 2 days. Furthermore, the decreasing number of viruliferous WFTs and transmission rates as time progressed, together with the transcriptomic evidence, collectively suggest that WFTs transmit MCMV in a semi-persistent method, a mode of transmission requiring minutes to several hours for acquisition access and having a retention time of several hours to a few days. Additionally, ß-myrcene can attract WFTs significantly and is detected in Nicotiana benthamiana plants transiently expressing MCMV CP (coat protein), which is consistent with results in MCMV-infected maize plants through the metabolomic profiling and the preference analyses of WFT. Therefore, this study demonstrates the indirect interaction between MCMV and WFT by inducing maize to synthesize ß-myrcene to attract insect vectors. The exploration of specific interactions between MCMV and WFT could help to expand the mechanism studies of virus-vector-host plant interaction and put forward a new insight for the combined control of MCMV and WFT through the manipulation of plant volatiles and key insect genes.

Hydrochemical processes and inorganic nitrogen sources of shallow groundwater in the Sanjiang Plain, northeast China.

This study investigates the chemical characteristics, formation, and sources of inorganic nitrogen (IN) of shallow groundwater across the Sanjiang Plain, aiming to enhance drinking water safety management and pollution control. A total of 167 groundwater and 27 surface water samples were collected for constituents and isotopes (H2 and O18). The hydrogeochemical characteristics showed that the major type is HCO3- Ca·Mg, with low total dissolved solids and a neutral to weak alkaline nature. Rock weathering processes govern the hydrochemical composition of groundwater. Hydrogen and oxygen stable isotopes analyses revealed that precipitation serves as the main water source. In alluvial areas, oxidative conditions lead to the enrichment of NO3-N concentrations, with sewage, manure, and fertilizers being the primary IN sources. In lacustrine areas, intensive rice cultivation results in reductive conditions and strong denitrification processes, causing the loss of NO3-N and leaving NH4-N as the dominant IN form. Organic matter mineralization is likely a more significant contributor to NH4-N concentrations than ammonium fertilizers. These findings provide valuable information for further research on natural sources and groundwater pollution in areas with similar hydrogeological conditions. PRACTITIONER POINTS: Rock weathering processes govern the hydrochemical composition of groundwater, and precipitation serves as the main water source. In alluvial areas, oxidative conditions lead to the enrichment of NO3-N. In lacustrine areas, intensive rice cultivation results in reductive conditions and strong denitrification processes. Organic matter mineralization is likely a more significant contributor to NH4-N concentrations than ammonium fertilizers. These findings provide references for water management and information for further research on natural sources and groundwater pollution in areas with similar hydrogeological conditions.

A new dual-thickness semi-transparent beamstop for small-angle X-ray scattering.

An innovative dual-thickness semi-transparent beamstop designed to enhance the performance of small-angle X-ray scattering (SAXS) experiments is introduced. This design integrates two absorbers of differing thicknesses side by side into a single attenuator, known as a beamstop. Instead of completely stopping the direct beam, it attenuates it, allowing the SAXS detector to measure the transmitted beam through the sample. This approach achieves true synchronization in measuring both scattered and transmitted signals and effectively eliminates higher-order harmonic contributions when determining the transmission light intensity through the sample. This facilitates and optimizes signal detection and background subtraction. This contribution details the theoretical basis and practical implementation of this solution at the SAXS station on the 1W2A beamline at the Beijing Synchrotron Radiation Facility. It also anticipates its application at other SAXS stations, including that at the forthcoming High Energy Photon Source, providing an effective solution for high-precision SAXS experiments.

Protocol for in vivo nucleic acid delivery utilizing the rolling microneedle electrode array.

Electroporation temporarily enhances cell membrane permeability and promotes the absorption of external molecules. We have developed a device termed the rolling microneedle electrode array (RoMEA) that combines a densely arranged microneedle array of electrodes with rolling structures. Use RoMEA to create uniform skin micropores for efficient, low-damage transfection of nucleic acids over extended areas of the body. We describe in detail the design, fabrication, and assembly of the device and the application of in vivo electroporation of nucleic acids. For complete details on the use and execution of this protocol, please refer to Tongren Yang et al. 1.

Gabapentinoids-Related Delirium Adverse Events: A Real-World Study from 2004 to 2022 Based on FAERS.

Purpose: This study comprehensively describes and evaluates the correlation between gabapentinoids and all types of delirium. Methods: We used AERSMine to select all adverse reaction data from 2004 Q1 to the 2022 Q4 in the FDA Adverse Event Reporting System (FAERS) database, and delirium events reported by gabapentinoids drugs were included in this study. Collected and analyzed the clinical details of these reports. We have developed four models. Among the four models, reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to evaluate the potential association between and delirium. We undertook a subgroup analysis for the age and sex cohorts. Results: A total of 2950 reports of gabapentinoids-related delirium was collected. Excluding cases with a history of delirium (Model 2), opioid drugs (Model 3), and other adverse events related to gabapentinoids drugs (Model 4), pain cases with gabapentin drugs as the main suspected drug were selected. In model 1, the reporting rates of delirium at the delirium and delirium tremens levels were higher in the gabapentinoids group than in the non-gabapentinoids group (ROR 1.09(1.05,1.13); ROR 1.54(1.16,2.04)). In model 2.3 the delira and the delirium level were higher in the gabapentinoids group (ROR 1.42(1.29,1.56), ROR 1.44(1.31,1.59); ROR 1.43(1.30,1.58), ROR 1.46(1.33,1.61)). There is no difference in delirium levels in Model 4. Delirium levels were higher in the gabapentinoids group than in the non-gabapentinoids group in ≥65 years old. The delirium and deliria levels were higher in the male group than in the female group. Conclusion: The delirium adverse reactions of the gabapentinoids group were significantly higher than those of non-gabapentinoids group in the first three models. However, with the removal of confounding factors, there was no significant difference in this type of adverse reaction in Model 4. In elderly and male patients, the incidence of delirium with gabapentinoids was significantly increased.

Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression.

The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti-HBc compound-colchicine, an alkaloid compound-that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Chromosome-level genome assembly of the invasive pest Pseudococcus jackbeardsleyi (Hemiptera: Pseudococcidae).

Among over 2,000 species of mealybugs (Hemiptera: Pseudococcidae), only 13 genomes have been published so far, seriously limiting the researches on the phylogeny and adaptive evolution of this group. The continuous publication of mealybug genomes will significantly facilitate our exploration of the biological characteristics, detrimental attributes, and control strategies of the Pseudococcidae family. Jack Beardsley mealybug (Pseudococcus jackbeardsleyi) as one of the hazardous invasive pests, it could cause enormous losses to the fruit and vegetable industries worldwide. Herein, we combined Nanopore long-read, short-read Illumina and Hi-C sequencing, generating a high-quality chromosome-level genome assembly of P. jackbeardsleyi. The genome size was determined to be 334.818 Mb, which was assembled into 5 linkage groups with a N50 of 67.233 Mb. The BUSCO analysis demonstrated the completeness of the genome assembly and annotation are 95.7% and 92.8%, respectively. The developed high-quality genome will serve as an asset for delving into the genetic mechanisms underlying the invasiveness of P. jackbeardsleyi, thereby offering a crucial theoretical foundation for the prevention and management of Pseudococcidae pests.

Cross-talk between oxidative stress and lipid metabolism regulators reveals molecular clusters and immunological characterization in polycystic ovarian syndrome.

BACKGROUND: Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS. METHODS: Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model. RESULTS: 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968-1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses. CONCLUSION: A novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.

The Growth and Shape Evolution of Indium Nanoplates Studied by In Situ Liquid Cell TEM.

Understanding the growth mechanisms of nanomaterials is crucial for effectively controlling their morphology which may affect their properties. Here, the growth process of indium nanoplates is studied using in situ liquid cell transmission electron microscopy. Quantitative analysis shows that the growth of indium nanoplate is limited by surface reaction. Besides, the growth process has two stages, which is different from that of other metal nanoplates reported previously. At the first stage, indium particles transform gradually from face-centered cubic to body-centered tetragonal (bct) structure as the seeds grow. At the second stage, the seeds grow faster than at the first stage and form indium triangular nanoplates. Indium triangular nanoplates have a bct structure with {011}-twin, which is found to form through kinetic reactions. In addition, the shape evolution of truncated triangle nanoplate with multiple twin planes is studied. The growth rate of truncated edge changes with the varied number of re-entrant grooves. The present work provides valuable insights into the growth mechanism of metal nanoplates with low-symmetric structure and the role of twin planes in the shape evolution of plate-like metal nanomaterials.

Immune profiling of premalignant lesions in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS), is a rare autosomal dominant hereditary disease characterized by an elevated risk of various cancers. Serine/Threonine Kinase 11 (STK11) gene is a major tumor suppressor crucial for immune evasion with and beyond tumorigenic cells. It has garnered increasing attention in the realm of oncology treatment, particularly in the context of immunotherapy development. OBJECTIVE: This study aimed to assess the suitability of polyps obtained from individuals with PJS, resulting from germline STK11 deficiency, for immunotherapy. Additionally, we seek to identify potential shared mechanisms related to immune evasion between PJS polyps and cancers. To achieve this, we examined PJS polyps alongside familial adenomatous polyposis (FAP) and sporadic polyps. METHODS: Polyps were compared among themselves and with either the paracancerous tissues or colon cancers. Pathological and gene expression profiling approaches were employed to characterize infiltrating immune cells and assess the expression of immune checkpoint genes. RESULTS: Our findings revealed that PJS polyps exhibited a closer resemblance to cancer tissues than other polyps in terms of their immune microenvironment. Notably, PJS polyps displayed heightened expression of the immune checkpoint gene CD80 and an accumulation of myeloid cells, particularly myeloid-derived suppressor cells (MDSCs). CONCLUSION: The findings suggest an immunobiological foundation for the increased cancer susceptibility in PJS patients, paving the way for potential immune therapy applications in this population. Furthermore, utilizing PJS as a model may facilitate the exploration of immune evasion mechanisms, benefiting both PJS and cancer patients.

Nanomaterials for bone metastasis.

Bone metastasis, a prevalent occurrence in primary malignant tumors, is often associated with a grim prognosis. The bone microenvironment comprises various coexisting cell types, working together in a coordinated manner. This dynamic microenvironment plays a pivotal role in the initiation and progression of bone metastases. While cancer therapies have made advancements, the available options for addressing bone metastases remain insufficient. The advent of nanotechnology has ushered in a new era for managing and preventing bone metastases because of the physicochemical and adaptable advantages of nanoplatforms. In this review, we make an introduction of the underlying mechanisms and the current clinical therapies of bone metastases, highlighting the advances of intelligent nanosystems that can stimulate vascular regeneration, promote bone regeneration, eliminate tumor cells, minimize bone damage, and expedite bone healing. The innovation surrounding bone-targeting nanoplatforms presents a fresh approach to the theranostics of bone metastases.

A Nomogram to Predict Intracranial Hypertension in Moderate Traumatic Brain Injury Patients.

OBJECTIVE: Patients with moderate traumatic brain injury (mTBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which mTBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in mTBI patients. METHODS: Baseline data collected on admission of 296 mTBI patients with Glasgow Coma Scale (GCS) score of 9-11 was collected and analyzed. Multivariable logistic regression modeling with backward stepwise elimination was used to develop a prediction model for IHT. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. Finally, the prediction model was validated in a separate cohort of 122 patients from 3 hospitals. RESULTS: Four independent prognostic factors for IHT were identified: GCS score, Marshall head computed tomography score, injury severity score, and location of contusion. The C-statistic of the prediction model in internal validation was 84.30% (95% CI: 0.794-0.892). The area under the curve for the prediction model in external validation was 82.80% (95% CI: 0.747-0.909). CONCLUSIONS: A prediction model based on baseline parameters was found to be highly sensitive in distinguishing mTBI patients with GCS score of 9-11 who would suffer IHT. The high discriminative ability of the prediction model supports its use in identifying mTBI patients with GCS score of 9-11 who need ICP-lowering therapy or invasive ICP monitoring.

Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration.

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

SPP1 could be an immunological and prognostic biomarker: From pan-cancer comprehensive analysis to osteosarcoma validation.

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan-cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan-Meier survival analyses to analyze overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.