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1.
Nanotechnology ; 35(27)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38569479

Herein, SnO2QDs (<10 nm) with small size instead of conventional nanoparticles was employed to modify ZnFe2O4to synthesize porous and heterogeneous SnO2/ZnFe2O4(ZFSQ) composites for gas sensing. By an immersion process combined with calcination treatment, the resultant porous ZFSQ composites with different contents of SnO2QDs were obtained, and their sensing properties were investigated. Compared with bare ZnFe2O4and SnO2QDs, porous ZFSQ composites based-sensors showed much improved sensor response to acetone. For contrast, the sensor performance of ZFSQ composites was also compared with that of ZnFe2O4sphere modified by SnO2nanoparticles with different size. The porous ZFSQ composite with 5 wt% SnO2QDs (ZFSQ-5) showed a better acetone sensing response than that of other ZFSQ composites, and it exhibited a high response value of 110-100 ppm of acetone and a low detection limit of 0.3 ppm at 240 °C. In addition to the rich heterojunctions and porous structure, the size effect of SnO2QDs was other indispensable reasons for the improved sensor performance. Finally, the ZFSQ-5 composite sensor was attempted to be applied for acetone sensing in exhaled breath, suggesting its great potential in monitoring acetone.

2.
Spine J ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38679078

BACKGROUND: Osteoporosis, a metabolic bone disorder, markedly elevates fracture risks, with vertebral compression fractures being predominant. Antiosteoporotic treatments for patients with osteoporotic vertebral compression fractures (OVCF) lessen both the occurrence of subsequent fractures and associated pain. Thus, diagnosing osteoporosis in OVCF patients is vital. PURPOSE: The aim of this study was to develop a predictive radiographic model using T1 sequence MRI images to accurately determine whether patients with lumbar spine compression fractures also have osteoporosis. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Patients over 45 years of age diagnosed with a fresh lumbar compression fracture. OUTCOME MEASURES: Diagnostic accuracy of the model (area under the ROC curve). METHODS: The study retrospectively collected clinical and imaging data (MRI and DEXA) from hospitalized lumbar compression fracture patients (L1-L4) aged 45 years or older between January 2021 and June 2023. Using the pyradiomics package in Python, features from the lumbar compression fracture vertebral region of interest (ROI) were extracted. Downscaling of the extracted features was performed using the Mann-Whitney U test and the least absolute shrinkage selection operator (LASSO) algorithm. Subsequently, six machine learning models (Naive Bayes, Support Vector Machine [SVM], Decision Tree, Random Forest, Extreme Gradient Boosting [XGBoost], and Light Gradient Boosting Machine [LightGBM]) were employed to train and validate these features in predicting osteoporosis comorbidity in OVCF patients. RESULTS: A total of 128 participants, 79 in the osteoporotic group and 49 in the non-osteoporotic group, met the study's inclusion and exclusion criteria. From the T1 sequence MRI images, 1906 imaging features were extracted in both groups. Utilizing the Mann-Whitney U test, 365 radiologic features were selected out of the initial 1,906. Ultimately, the lasso algorithm identified 14 significant radiological features. These features, incorporated into six conventional machine learning algorithms, demonstrated successful prediction of osteoporosis in the validation set. The NaiveBayes model yielded an area under the receiver operating characteristic curve (AUC) of 0.84, sensitivity of 0.87, specificity of 0.70, and accuracy of 0.81. CONCLUSIONS: A NaiveBayes machine learning algorithm can predict osteoporosis in OVCF patients using t1-sequence MRI images of lumbar compression fractures. This approach aims to obviate the necessity for further osteoporosis assessments, diminish patient exposure to radiation, and bolster the clinical care of patients with OVCF.

3.
PLoS One ; 19(3): e0298860, 2024.
Article En | MEDLINE | ID: mdl-38498431

BACKGROUND: Oxidative stress is a significant contributor to the development of various diseases, and the oxidative balance score (OBS) is a valuable tool for assessing the impact of dietary and lifestyle factors on oxidative stress in humans. Nevertheless, the precise relationship between OBS and thyroid function in adults remains elusive. METHODS: This cross-sectional study comprised 6222 adult participants drawn from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012. Employing weighted multivariable linear regression modeling, the study estimated the connection between OBS quartiles and thyroid functions. The causal relationship between OBS components and thyroid function was analyzed by Mendelian randomization (MR). RESULTS: We found a significant negative correlation between OBS and free thyroxine (FT4) and total thyroxine (TT4). Univariate and multivariate MR Analyses showed a causal relationship between BMI and FT4. Copper, smoking, and riboflavin showed a causal relationship with FT4 after moderation. CONCLUSION: We found that a lifestyle high in antioxidant exposure reduced FT4 and TT4 levels in the population. We suggest that BMI, Copper, and Riboflavin are important factors in the regulation of FT4 levels.


Copper , Mendelian Randomization Analysis , Adult , Humans , Nutrition Surveys , Cross-Sectional Studies , Thyroid Gland , Thyroxine , Oxidative Stress/genetics , Riboflavin , Thyrotropin
4.
Heliyon ; 10(3): e24798, 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38333878

Background and objectives: The purpose of this research was to develop and validate the first prognostic nomograms for 3-, 5-, and 10-year cancer-specific survival (CSS) and overall survival (OS) in patients diagnosed with locally advanced thyroid cancer (LATC) by evaluating independent predictors of prognosis in a population of LATC patients. Methods: Demographics, clinicopathologic characteristics, treatment, and follow-up of 2396 LATC patients in the surveillance, epidemiology, and end results database from 2004 to 2015 were retrospectively analyzed and compared with patients with LATC according to staging. We randomized all LATC patients into training and validation groups in a 7:3 ratio. Cox regression analyses helped us to derive independent prognostic factors for LATC patients. According to these results, we established and validated the first prognostic nomograms and risk stratification. Results: In our research, the clinical information of LATC patients was compared and significant differences were found in the relevant variables including CSS and OS (P < 0.05), with CSS of 82.0 % and 49.0 %, and OS of 70.6 % and 40.0 %, respectively. Cox regression analyses showed that age at diagnosis, tumor diameter, presence of DM, extrathyroidal extension sites, histological type, thyroidectomy scope, radiotherapy status, and chronological sequence of radiotherapy and surgery were observably correlated with CSS in LATC patients, and in addition to the above factors, gender, marital status, and chemotherapy status were also observably correlated with OS in LATC patients. The prognostic predictive power of the above factors is visualized by the Kaplan-Meier survival curve. The concordance index of nomograms for CSS and OS were 0.933, 0.925, and 0.926 (CSS), 0.918, 0.909, and 0.906 (OS), respectively, and the time-dependent receiver operating characteristic curve, area under curve, calibration curve and decision curve analysis curve indicate that the nomograms have good discriminatory ability, accuracy and clinical applicability in both the training and validation groups. Conclusions: In these findings, we drawed a conclusion that there were significant differences in clinical information between patients with T4a and T4b LATC, and we established and validated the first prognostic nomograms and risk stratification of CSS and OS for LATC patients at 3, 5, and 10 years, which will help clinicians to individualize their postoperative treatment and individualized follow-up.

5.
RSC Adv ; 14(9): 6048-6057, 2024 Feb 14.
Article En | MEDLINE | ID: mdl-38370456

Environmental protection mandates have spurred the widespread adoption of lead-free glass in electronic material adhesion. Glass powder, crucial for solar silver paste, notably affects the ohmic contact at the Ag-Si interface of crystalline silicon solar cells. This study examines how TeO2 content influences the high-temperature flowability and wettability of lead-free Bi2O3-TeO2-based glass powder, alongside the interplay between the glass's thermal properties and interface contact. Additionally, it investigates the Bi2O3-TeO2 ratio's impact on current transmission through the interfacial glass layer. Experimental results show that the synthesized glass powder exhibits superior high-temperature flowability and wettability, with a low contact resistance of 1.5 mΩ cm2 in silver paste applications. This study also proposes an optimal approach for enhancing current transmission through the interfacial glass layer. Consequently, this glass powder is highly valuable for c-Si solar cell silver paste applications, offering novel insights into improving current transmission efficiency.

6.
Nat Chem Biol ; 2024 Jan 08.
Article En | MEDLINE | ID: mdl-38191941

SLC15A4 is an endolysosome-resident transporter linked with autoinflammation and autoimmunity. Specifically, SLC15A4 is critical for Toll-like receptors (TLRs) 7-9 as well as nucleotide-binding oligomerization domain-containing protein (NOD) signaling in several immune cell subsets. Notably, SLC15A4 is essential for the development of systemic lupus erythematosus in murine models and is associated with autoimmune conditions in humans. Despite its therapeutic potential, the availability of quality chemical probes targeting SLC15A4 functions is limited. In this study, we used an integrated chemical proteomics approach to develop a suite of chemical tools, including first-in-class functional inhibitors, for SLC15A4. We demonstrate that these inhibitors suppress SLC15A4-mediated endolysosomal TLR and NOD functions in a variety of human and mouse immune cells; we provide evidence of their ability to suppress inflammation in vivo and in clinical settings; and we provide insights into their mechanism of action. Our findings establish SLC15A4 as a druggable target for the treatment of autoimmune and autoinflammatory conditions.

7.
Nat Chem Biol ; 2024 Jan 02.
Article En | MEDLINE | ID: mdl-38167919

Photoaffinity probes are routinely utilized to identify proteins that interact with small molecules. However, despite this common usage, resolving the specific sites of these interactions remains a challenge. Here we developed a chemoproteomic workflow to determine precise protein binding sites of photoaffinity probes in cells. Deconvolution of features unique to probe-modified peptides, such as their tendency to produce chimeric spectra, facilitated the development of predictive models to confidently determine labeled sites. This yielded an expansive map of small-molecule binding sites on endogenous proteins and enabled the integration with multiplexed quantitation, increasing the throughput and dimensionality of experiments. Finally, using structural information, we characterized diverse binding sites across the proteome, providing direct evidence of their tractability to small molecules. Together, our findings reveal new knowledge for the analysis of photoaffinity probes and provide a robust method for high-resolution mapping of reversible small-molecule interactions en masse in native systems.

8.
J Med Chem ; 67(3): 2083-2094, 2024 Feb 08.
Article En | MEDLINE | ID: mdl-38287228

Colorectal cancer remains the second leading cause of cancer-related mortalities worldwide. While artemisinin (ART), a key active compound from the traditional Chinese medicinal herb Artemisia annua, has been recognized for its antiproliferative activity against colon cancer cells, its underlying molecular underpinnings remain elusive. Whereas promiscuity of heme-dependent alkylating of macromolecules, mainly proteins, has been seen pivotal as a universal and primary mode of action of ART in cancer cells, accumulating evidence suggests the existence of unique targets and mechanisms of actions contingent on cell or tissue specificities. Here, we employed photoaffinity probes to identify the specific targets responsible for ART's anti-colon cancer actions. Upon validation, microsomal prostaglandins synthase-2 emerged as a specific and reversible target of ART in HCT116 colorectal cancer cells, whose inhibition resulted in reduced cellular prostaglandin E2 biosynthesis and cell growth. Our discovery opens new opportunities for pharmacological treatment of colon cancer.


Artemisinins , Colonic Neoplasms , Colorectal Neoplasms , Humans , Artemisinins/metabolism , Cyclooxygenase 2 , Colorectal Neoplasms/drug therapy , Prostaglandins
10.
Materials (Basel) ; 17(2)2024 Jan 17.
Article En | MEDLINE | ID: mdl-38255613

Silver powder, as the primary component of solar silver paste, significantly influences various aspects of the paste's performance, including printing, sintering, and conductivity. This study reveals that, beyond the shape and size of the silver powders, their microstructure is a critical factor influencing the performance of both silver powders and silver pastes in solar cell applications. The growth process leads to the formation of either polycrystalline aggregated silver powder or crystal growth silver powder. Analyzing the performance characteristics of these different microstructures provides guidance for selecting silver powders for silver pastes at different sintering temperatures. Polycrystalline aggregated silver powder exhibits higher sintering activity, with a sintering initiation temperature around 450 °C. The resulting silver paste, sintered at 750 °C, demonstrates a low sheet resistance of 2.92 mΩ/sq and high adhesion of 2.13 N. This silver powder is suitable for formulating silver pastes with lower sintering temperatures. The solar cell electrode grid lines have a high aspect ratio of 0.37, showing poor uniformity. However, due to the high sintering activity of the silver powder, the glass layer dissolves and deposits more silver, resulting in excellent conductivity, a low contact resistance of the silver electrode, a low series resistance of the solar cell of 1.23 mΩ, and a high photoelectric conversion efficiency of 23.16%. Crystal growth silver powder exhibits the highest tap density of 5.52 g/cm3. The corresponding silver paste shows improved densification upon sintering, especially at 840 °C, yielding a sheet resistance of 2.56 mΩ/sq and adhesion of 3.05 N. This silver powder is suitable for formulating silver pastes with higher sintering temperatures. The solar cell electrode grid lines are uniform with the highest aspect ratio of 0.40, resulting in a smaller shading area, a high fill factor of 81.59%, and a slightly higher photoelectric conversion efficiency of 23.17% compared to the polycrystalline aggregated silver powder.

11.
Mol Neurobiol ; 61(1): 294-307, 2024 Jan.
Article En | MEDLINE | ID: mdl-37605094

This study investigated the impact of low-dose lipopolysaccharide (LPS) on spinal cord injury (SCI) and the potential molecular mechanism. Rats were randomly assigned to four groups: Sham, SCI, SCI + LPS, and SCI + LPS + agomir. Allen's weight-drop method was used to establish an in vivo SCI model. The Basso Bcattie Bresnahan rating scale was employed to monitor locomotor function. An in vitro SCI model was constructed by subjecting PC12 cells to oxygen and glucose deprivation/ reoxygenation (OGD/R). Enzyme-linked immunosorbent assay (ELISA) was applied for the determination interleukin (IL)-1ß and IL-6. The dual luciferase reporter assay was used to validate the targeting of microRNA (miR)-429 with PI3K. Immunohistochemical staining was used to assess the expression of PI3K, phosphorylated AKT and Nrf2 proteins. The Nrf2-downstream anti-oxidative stress proteins, OH-1 and NQO1, were detected by western blot assay. MiR-429 expression was detected by fluorescence in situ hybridization and real-time quantitative reverse transcription PCR. In vitro, low-dose LPS decreased miR-429 expression, activated PI3K/AKT/Nrf2, inhibited oxidative stress and inflammation, and attenuated SCI. MiR-429 was found to target and negatively regulate PI3K. Inhibition of miR-429 suppressed low-dose LPS-mediated oxidative stress and inflammation via activation of the PI3K/AKT/Nrf2 pathway. In vivo, miR-429 was detectable in neurons. Inhibition of miR-429 blocked low-dose LPS-mediated oxidative stress and inflammation via activation of the PI3K/AKT/Nrf2 pathway. Overall, low-dose LPS was found to alleviate SCI-induced neuronal oxidative stress and inflammatory response by down-regulating miR-429 to activate the PI3K/AKT/Nrf2 pathway.


MicroRNAs , Spinal Cord Injuries , Animals , Rats , Apoptosis/genetics , In Situ Hybridization, Fluorescence , Inflammation/metabolism , Lipopolysaccharides/pharmacology , MicroRNAs/genetics , MicroRNAs/metabolism , Neurons/metabolism , NF-E2-Related Factor 2/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Spinal Cord Injuries/metabolism
13.
BMC Cardiovasc Disord ; 23(1): 485, 2023 10 04.
Article En | MEDLINE | ID: mdl-37794366

BACKGROUND: Electrocardiographic markers, as surrogates for sympathetic excitotoxicity, are widely predictive of cardiovascular adverse events, but whether these markers can predict postsurgical sepsis (SS) is unclear. METHODS: We retrospectively analyzed patients who underwent abdominal surgery from March 2013 to May 2023. We collected basic data, comorbidities, blood samples, echocardiology, electrocardiogram, and surgical data, as well as short-term outcome. The primary endpoints were postsurgical SS, in which logistic regression analyses can identify independent risk factors. The optimal cut-off value predictive postsurgical SS both P wave and PR interval were calculated in the receiver operating characteristic curve (ROC). RESULTS: A total of 1988 subjects were analyzed, and the incidence of postsurgical SS was 3.8%. The mean age at enrollment was 68.6 ± 7.1 years, and 53.2% of the participants were men. In the ROC analysis, the areas under the curve (AUC) for P wave and PR interval predictive postsurgical SS were 0.615 (95%CI, 0.548-0.683; p = 0.001) and 0.618 (95%CI, 0.554-0.682; p = 0.001), respectively. The P wave and PR interval predicted postoperative sepsis with optimal discrimination of 103 and 157 ms, with a sensitivity of 0.744 and 0.419, and a specificity of 0.427 and 0.760. P-wave less than 103 ms or PR interval less than 157 ms associated with a 2.06 or 2.33 fold increase occurred risk postsurgical SS. CONCLUSIONS: Shorter P-wave and PR intervals were both independently associated with postsurgical SS. These preoperative electrophysiological markers could have potential useful for early recognition of postoperative SS.


Sepsis , Male , Humans , Aged , Female , Prognosis , Retrospective Studies , Sepsis/diagnosis , Sepsis/epidemiology , Electrocardiography , Risk Factors , Postoperative Complications/diagnosis , Postoperative Complications/etiology , ROC Curve
14.
PeerJ ; 11: e15919, 2023.
Article En | MEDLINE | ID: mdl-37663283

Background: Spinal cord injury (SCI) is a neurological disease associated with a high disability rate. Low-dose lipopolysaccharide (LPS) has been reported to activate cross-immune tolerance and alleviate the effects of various traumatic stimuli. The present study aimed to explore the effect of LPS on SCI and the potential molecular mechanism. Methods: Male Sprague-Dawley (SD) rats were used to established an in vivo SCI model and were intraperitoneally injected with lentivirus particles encoding a MALAT1 small interfering RNA (siRNA) on day 10 prior to SCI and with 0.2 mg/kg LPS 72 h prior to SCI. Basso, Beattie, and Bresnahan (BBB) scoring; HE staining; and TUNEL assay were used to assess neurological function and pathophysiological changes. Western blot and immunohistochemistry (IHC) were used to detect cell autophagy and Nrf2 nuclear translocation. PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to establish an in vitro SCI model. In vitro SCI model cells were pretreated with LPS and transfected with siMALAT1 or MALAT1 overexpression plasmid aimed at knocking down MALAT1 or overexpressing MALAT1. The cell counting kit-8 (CCK-8) assay was used to measure the toxicity of LPS towards PC12 cells. Flow cytometry and immunofluorescence analysis were performed to investigate cell apoptosis and Nrf2 nuclear translocation. Results: SCI rats preconditioned with low-dose LPS had higher BBB scores, reduced SCI injury, increased MALAT1 expression and activated autophagy and Nrf2 nuclear translocation in the in vivo SCI model. In the in vitro SCI model, low-dose LPS treatment suppressed the apoptotic ratio of PC12 cells, increased MALAT1 expression, activated autophagy, and promoted Nrf2 nuclear translocation. Silencing MALAT1 exacerbated OGD/R injury in vitro and weakened the protective effect of low-dose LPS. Overexpression of MALAT1 inhibits OGD/R-induced apoptosis by inducing autophagy and promoting Nrf2 nuclear translocation. This was also been confirmed in animal experiments, silencing MALAT1 blocked the promotion of Nrf2 by low-dose LPS and the alleviated of SCI apoptosis. Conclusions: Low-dose LPS exhibited a protective role on SCI by activating autophagy and suppressing nerve cell apoptosis via the lncRNA MALAT1/Nrf2 axis.


RNA, Long Noncoding , Spinal Cord Injuries , Male , Animals , Rats , Rats, Sprague-Dawley , RNA, Long Noncoding/genetics , Lipopolysaccharides/pharmacology , NF-E2-Related Factor 2/genetics , Spinal Cord Injuries/genetics , Apoptosis/genetics , Autophagy/genetics , Glucose
15.
Nature ; 622(7983): 507-513, 2023 Oct.
Article En | MEDLINE | ID: mdl-37730997

Marine-derived cyclic imine toxins, portimine A and portimine B, have attracted attention because of their chemical structure and notable anti-cancer therapeutic potential1-4. However, access to large quantities of these toxins is currently not feasible, and the molecular mechanism underlying their potent activity remains unknown until now. To address this, a scalable and concise synthesis of portimines is presented, which benefits from the logic used in the two-phase terpenoid synthesis5,6 along with other tactics such as exploiting ring-chain tautomerization and skeletal reorganization to minimize protecting group chemistry through self-protection. Notably, this total synthesis enabled a structural reassignment of portimine B and an in-depth functional evaluation of portimine A, revealing that it induces apoptosis selectively in human cancer cell lines with high potency and is efficacious in vivo in tumour-clearance models. Finally, practical access to the portimines and their analogues simplified the development of photoaffinity analogues, which were used in chemical proteomic experiments to identify a primary target of portimine A as the 60S ribosomal export protein NMD3.


Antineoplastic Agents , Chemistry Techniques, Synthetic , Imines , Spiro Compounds , Humans , Apoptosis/drug effects , Cell Line, Tumor , Imines/chemical synthesis , Imines/chemistry , Imines/pharmacology , Neoplasms/drug therapy , Proteomics , Ribosomes/metabolism , RNA-Binding Proteins/metabolism , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , Spiro Compounds/pharmacology , Structure-Activity Relationship , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
16.
Orthop Surg ; 15(10): 2515-2522, 2023 Oct.
Article En | MEDLINE | ID: mdl-37537414

OBJECTIVE: Displacement of bone cement following percutaneous vertebral augmentation for Kümmell disease (KD) presents a significant concern, resulting in increasing back pain and compromising daily activities. Unfortunately, current literature does not yet establish a validated and minimally invasive surgical intervention for this issue. This study aims to investigate the effects of a novel hollow pedicle screw combined with kyphoplasty (HPS-KP) in preventing bone cement displacement following simply percutaneous kyphoplasty for the management of KD. METHODS: A total of 22 patients (six males, 16 females, averagely aged 77.18 ± 7.63 years) with KD without neurological deficits treated by HPS-KP at the hospital between March 2021 and June 2022 were hereby selected, among which, there were three stage I KD cases, 12 stage II KD cases, and seven stage III KD cases according to Li's classification. Bone mineral density (BMD), spinal X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) were examined before the operation. The operation time, intraoperative blood loss, and postoperative complications were all recorded. The follow-up focused on visual analog scale (VAS) score, Oswestry dysfunction index (ODI), anterior vertebral height (AVH), middle vertebral height (MVH), posterior vertebral height (PVH), wedge-shape affected vertebral Cobb angle (WCA), and bisegmental Cobb angle (BCA). One-way analysis of variance (ANOVA) followed by Bonferroni post-hoc test was employed for performing multiple comparisons in the present study. RESULTS: All patients having received the operation successfully were followed up for more than 8 months (ranging from 8 to 18 months). The operation time, intraoperative blood loss, and BMD (T-score) were 39.09 ± 5.64 min, 14.09 ± 3.98 ml, and - 3.30 ± 0.90 g/cm3 , respectively. Statistically significant differences were observed in the VAS score, ODI, AVH, MVH, and WCA (All p < 0.05), but there was no statistically significant difference in PVH and BCA at different time points (All p > 0.05). During follow-up, five patients suffered from bone cement leakage, and one presented an adjacent vertebral fracture and no bone cement displacement. CONCLUSION: HPS-KP could be safe and effective in the treatment of KD without neurological deficits, effectively relieving the symptoms of patients, restoring partial vertebral height, and preventing the occurrence of bone cement displacement.

18.
Toxicol Mech Methods ; 33(9): 781-795, 2023 Nov.
Article En | MEDLINE | ID: mdl-37488941

BACKGROUND: This study identified and verified the characteristic differentially expressed ferroptosis-related genes (CDEFRGs) in osteosarcoma (OS). METHODS: We extracted ferroptosis-related genes (FRGs), identified differentially expressed FRGs (DEFRGs) in OS, and conducted correlation analysis between DEFRGs. Next, we conducted GO and KEGG analyses to explore the biological functions and pathways of DEFRGs. Furthermore, we used LASSO and SVM-RFE algorithms to screen CDEFRGs, and evaluated its accuracy in diagnosing OS through ROC curves. Then, we demonstrated the molecular function and pathway enrichment of CDEFRGs through GSEA analysis. In addition, we evaluated the differences in immune cell infiltration between OS and NC groups, as well as the correlation between CDEFRGs expressions and immune cell infiltrations. Finally, the expression of CDEFRGs was verified through qRT-PCR, western blotting, and immunohistochemistry experiments. RESULTS: We identified 51 DEFRGs and the expression relationship between them. GO and KEGG analysis revealed their key functions and important pathways. Based on four CDEFRGs (PEX3, CPEB1, NOX1, and ALOX5), we built the OS diagnostic model, and verified its accuracy. GSEA analysis further revealed the important functions and pathways of CDEFRGs. In addition, there were differences in immune cell infiltration between OS group and NC group, and CDEFRGs showed significant correlation with certain infiltrating immune cells. Finally, we validated the differential expression levels of four CDEFRGs through external experiments. CONCLUSIONS: This study has shed light on the molecular pathological mechanism of OS and has offered novel perspectives for the early diagnosis and immune-targeted therapy of OS patients.


Bone Neoplasms , Ferroptosis , Osteosarcoma , Humans , Ferroptosis/genetics , Osteosarcoma/genetics , Algorithms , Computational Biology , Bone Neoplasms/genetics
20.
Front Immunol ; 14: 1012999, 2023.
Article En | MEDLINE | ID: mdl-37180139

Background: The spindle and kinetochore associated (SKA) complex, which plays important roles in proper chromosome segregation during mitosis by maintaining the stabilization of kinetochore-spindle microtubule attachment during mitosis, has recently been reported to exert regulatory effects on the initiation and progression of various human cancer types. Nevertheless, the prognostic significance and immune infiltration of the SKA family across cancers have not been well elucidated. Methods: Using data from three large public datasets, including The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, a novel scoring system (termed the SKA score) was developed to quantify the SKA family level across cancers. We then evaluated the prognostic impact of the SKA score on survival and assessed the effect of the SKA score on immunotherapy at the pan-cancer level using multiomics bioinformatic analyses. The correlation of the SKA score and the tumor microenvironment (TME) was also explored in depth. Potential small molecular compounds and chemotherapeutic agents were assessed by CTRP and GDSC analyses. Immunohistochemistry was performed to verify the expression of the SKA family genes. Results: Our results demonstrated a close correlation between the SKA score and tumor development and prognosis in multiple cancers. The SKA score was positively related to cell cycle pathways and DNA replication across cancers, such as E2F targets, the G2M checkpoint, MYC targets V1/V2, mitotic spindles and DNA repair. Additionally, the SKA score was negatively related to the infiltration of various immune cells with antitumor effects in the TME. In addition, the potential value of the SKA score was identified to predict immunotherapy response for melanoma and bladder cancer. We also demonstrated a correlation between SKA1/2/3 and the response to drug treatment across cancers and the promising potential of the SKA complex and its genes as therapeutic targets in cancer. Immunohistochemistry demonstrated that the expression differences of SKA1/2/3 were significant between the breast cancer group and the paracancerous group. Conclusion: The SKA score plays a critical role in 33 cancer types and is highly related to tumor prognosis. Patients with elevated SKA scores have a clear immunosuppressive TME. The SKA score may serve as a predictor for patients receiving anti-PD-1/L1 therapy.


Kinetochores , Neoplasms , Humans , Kinetochores/metabolism , Microtubule-Associated Proteins/metabolism , Microtubules/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Prognosis , Neoplasms/genetics , Neoplasms/metabolism , Tumor Microenvironment/genetics
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