Investigation into the role of H2-Ab1 in vascular remodeling in pulmonary arterial hypertension via Bioinformatics.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease of vascular remodeling characterized by persistent pulmonary arterial pressure elevation, which can lead to right heart failure and premature death. Given the complex pathogenesis and poor prognosis of PAH, the identification and investigation of biomarkers become increasingly critical for advancing further understanding of the disease. METHODS: PAH-related datasets, GSE49114, GSE180169 and GSE154959, were downloaded from the publicly available GEO database. By performing WGCNA on the GSE49114 dataset, a total of 906 PAH-related key module genes were screened out. By carrying out differential analysis on the GSE180169 dataset, a total of 576 differentially expressed genes were identified. Additionally, the GSE154959 single-cell sequencing dataset was also subjected to differential analysis, leading to the identification of 34 DEGs within endothelial cells. By taking intersection of the above three groups of DEGs, five PAH-related hub genes were screened out, namely Plvap, Cyp4b1, Foxf1, H2-Ab1, and H2-Eb1, among which H2-Ab1 was selected for subsequent experiments. RESULTS: A SuHx mouse model was prepared using the SU5416/hypoxia method, and the successful construction of the model was evaluated through Hematoxylin-Eosin staining, hemodynamic detection, fulton index, and Western Blot (WB). The results of WB and qRT-PCR demonstrated a significant upregulation of H2-Ab1 expression in SuHx mice. Consistent with the results of bioinformatics analysis, a time-dependent increase was observed in H2-Ab1 expression in hypoxia-treated mouse pulmonary artery endothelial cells (PAECs). To investigate whether H2-Ab1 affects the development and progression of PAH, we knocked down H2-Ab1 expression in PAECs, and found that its knockdown inhibited the viability, adhesion, migration, and angiogenesis, while concurrently promoted the apoptosis of PAECs. CONCLUSION: H2-Ab1 could regulate the proliferation, apoptosis, adhesion, migration, and angiogenesis of PAECs.

Comparative outcomes of video-assisted thoracoscopic surgery versus open surgery for bronchogenic cysts in adults: a retrospective cohort study.

Background: Open thoracotomy has been the traditional surgical approach for patients with bronchogenic cysts (BCs). This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic surgery (VATS) compared to open surgery for the treatment of BCs in adults. Methods: This single-institution, retrospective cohort study included 117 consecutive adult patients who underwent VATS (group A) or open surgery (group B) for BC resection between February 2019 and January 2023. Data regarding clinical history, operation duration, length of hospital stay, 30-day mortality, and recurrence during follow-up were collected and analyzed. Results: Of the total cohort, 103 (88.0%) patients underwent VATS, while 14 (12.0%) patients underwent open surgery. Patients' age in group B were much older than group A (P=0.014), and no significant differences in other demographic and baseline clinical characteristics were observed between the groups. The VATS group had shorter median operation duration (96 vs. 149.5 min, P<0.001) and shorter mean length of hospital stay (5.0±5.5 vs. 8.6±4.0 days, P<0.001). One death occurred in the open surgery group. During a median follow-up of 34 (interquartile range, 20.8-42.5) months, no instances of BC recurrence were observed in either group. Conclusions: Compared to open surgery, VATS is also a safe and efficacious approach for treating BCs in adults. What's more, VATS offered shorter operative times and hospital stays. Considering the minimally invasive, VATS may be a better choice in most patients with bronchial cysts.

Single atom nanozyme sensing platform for simultaneous rapid detection of multiple bisphenols.

Bisphenol compounds (BPA, BPS, BPAF, etc.) are one class of the most important and widespread pollutants that poses severe threat to human health and the ecological environment. Because of the presence of multiple bisphenols in environmental and food samples, it is urgent and challenging to develop a rapid and cheap technique for simultaneously detecting BPA and its analogues. In this study, a series of M-N-C (M = Cu, Mg, Ni, Co, Fe, K) single-atom nanozymes (SAzymes) were created by simulating the structure of natural enzyme molecules, which were used as novel sensing platform for the fabrication of electrochemical sensors. Through systematic screening and characterization, it was interestingly discovered that the electrochemical sensor based on Cu-N-C SAzymes exhibited the best sensing performance for bisphenols among all SAzymes, which catalyzed not only BPA like tyrosinase, but also showed excellent catalytic capacity beyond tyrosinase (tyrosinase has no catalytic activity for BPS, BPAF, etc.), and achieved potential-resolved simultaneous rapid detection of BPA, BPS and BPAF. Further structure-activity relationship and catalytic mechanism characterizations of Cu-N-C SAzymes revealed that the presence of single atom Cu was predominantly in the form of Cu+ and Cu2+, which were anchored onto graphene nanosheet support through four coordination bonds with pyridinic N and pyrrolic N and acted as highly efficient active centers for electrocatalytic oxidation of bisphenols. The developed electrochemical sensing method exhibited excellent selectivity, sensitivity, and reliability for the rapid detection of multiple bisphenols in actual samples.

Cerium oxide /Co-Co Prussian blue analogue composite catalyst for enhanced peroxymonosulfate activation for effective removal of tetracycline hydrochloride from water.

In this paper, a novel CeO2/Co3[Co(CN)6]2 (CeO2/PBACo-Co) composite was prepared with co-precipitation and utilized to activate peroxymonosulfate (PMS) to eliminate tetracycline hydrochloride (TCH). Catalyst screening showed that the composite with a CeO2:PBACo-Co mass ratio of 1:5 (namely, 0.2-CeO2/PBACo-Co) had the best performance. The degradation efficiency of TCH in 0.2-CeO2/PBACo-Co/Oxone system was investigated. The experimental results illustrated that 98% of 50 mg/L TCH and 48.5% of TOC were degraded by 50 mg/L 0.2-CeO2/PBACo-Co and 400 mg/L Oxone within 120 min at 25 °C and initial pH 5.3. Recycling studies showed that the elimination rate of TCH can still achieve 85.8% after five cycles, suggesting that 0.2-CeO2/PBACo-Co composite processes good reusability. Trapping experiments and EPR tests revealed that the reaction system produced multiple active species (1O2, O2•-, SO4•-, and •OH). We proposed the catalytic mechanism of 0.2-CeO2/PBACo-Co for PMS activation, which mainly involves the promoted Co3+/Co2+ cycle by Ce3+ donated electrons. These results indicate that CeO2/PBACo-Co composite is an effective catalyst for wastewater remediation.

Single-cell analysis identifies critical regulators of spermatogonial development and differentiation in cattle-yak bulls.

Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

Oxygen vacancy based WO3/SnO2-x promote electrochemical H2O2 accumulation by two-electron water oxidation reaction and toxic uniform dimethylhydrazine degradation.

The key to constructing an anodic electro-Fenton system hinges on two pivotal criteria: enhancing the catalyst activity and selectivity in water oxidation reaction (WOR), while simultaneously inhibiting the decomposition of hydrogen peroxide (H2O2) which is on-site electrosynthesized at the anode. To address the issues, we synthesized novel WO3/SnO2-x electrocatalysts, enriched with oxygen vacancies, capitalize on the combined activity and selectivity advantages of both WO3 and SnO2-x for the two-electron pathway electrocatalytic production of H2O2. Moreover, the introduction of oxygen vacancies plays a critical role in impeding the decomposition of H2O2. This innovative design ensures that the Faraday efficiency and yield of H2O2 are maintained at over 80 %, with a noteworthy production rate of 0.2 mmol h-1 cm-2. We constructed a novel electro-Fenton system that operates using only H2O as its feedstock and applied it to treat highly toxic uniform dimethylhydrazine (UDMH) from rocket launch effluent. Our experiments revealed a substantial total organic carbon (TOC) removal, achieving approximately 90 % after 120 mins of treatment. Additionally, the toxicity of N-nitrosodimethylamine (NDMA), a byproduct of great concern, was shown to be effectively mitigated, as evidenced by acute toxicity evaluations using zebrafish embryos. The degradation mechanism of UDMH is predominantly characterized by the advanced oxidative action of H2O2 and hydroxyl radicals, as well as by complex electron transfer processes that warrant further investigation.

Integrating Tertiary Lymphoid Structure-Associated Genes into Computational Models to Evaluate Prognostication and Immune Infiltration in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor response to all therapeutic modalities and dismal prognosis. The presence of tertiary lymphoid structures (TLSs) in various solid cancers is of crucial prognostic significance, highlighting the intricate interplay between the tumor microenvironment and immune cells aggregation. However, the extent to which TLS and immune status affect PDAC prognosis remains incompletely understood. Here, we sought to unveil the unique properties of TLS in PDAC by leveraging both single-cell and bulk transcriptomics, and culminating in a risk model that predicts clinical outcomes. We used TLS score based on 12 genes (CCL2, CCL3, CCL4, CCL5, CCL8, CCL18, CCL19, CCL21, CXCL9, CXCL10, CXCL11 and CXCL13) and 9 genes (PTGDS, RBP5, EIF1AY, CETP, SKAP1, LAT, CCR6, CD1D and CD79B) signature, respectively, and examined their distribution in cell clusters of single-cell data from PDAC samples. The markers involved in these clusters were selected to develop a prognostic model using The Cancer Genome Atlas Program (TCGA) database as the training cohort and Gene Expression Omnibus (GEO) database as the validation cohort. Further we compared the immune infiltration, drug sensitivity, enriched and differentially expressed genes between the high-risk and low-risk groups in our model. Therefore, we established a risk model that has significant implications for the prognostic assessment of PADC patients with remarkable differences in immune infiltration and chemo-sensitivity between the low-risk and high-risk groups. And this paradigm established by TLS-related cell marker genes provides a prognostic prediction and a panel of novel therapeutic targets for exploring potential immunotherapy.

Construction of an oxidative phosphorylation-related gene signature for predicting prognosis and identifying immune infiltration in osteosarcoma.

BACKGROUND: Osteosarcoma is a prevalent malignant tumor that originates from mesenchymal tissue. It typically affects children and adolescents. Although it is known that the growth of osteosarcoma relies on oxidative phosphorylation for energy production, limited attention has been paid to exploring the potential of oxidative phosphorylation-related genes in predicting the prognosis of individuals suffering from osteosarcoma. METHODS: All the data were retrieved from the UCSC Xena and GEO (GENE EXPRESSION OMNIBUS). Identification of the oxidative phosphorylation genes linked to the prognosis of individuals with osteosarcoma was done by means of univariate COX and LASSO regression analyses. Following that, patients were categorized into a high-risk group and a low-risk group as per the risk score determined by the identified oxidative phosphorylation genes. Furthermore, a comparison was made in terms of the survival and immune infiltration between both groups, and the prognostic model was established. RESULTS: Five oxidative phosphorylation genes (ATP6V0D1, LHPP, COX6A2, MTHFD2, NDUFB9) associated with the prognosis of individuals with osteosarcoma were identified and the risk prognostic models were constructed. In the current research, the analysis of the ROC curves indicated a superior predictive accuracy exhibited by the risk model. The prognosis was adversely affected by immune infiltration in the high-risk group in comparison with the low-risk group. The function of the oxidative phosphorylation-related prognostic gene set was verified by GO and KEGG analysis. Furthermore, the link between oxidative phosphorylation-related genes and osteosarcoma immune infiltration was examined by GSEA analysis. CONCLUSIONS: In this study, a prognostic model that demonstrated good predictive performance was constructed. Additionally, this study highlighted a correlation between oxidative phosphorylation-related genes and immune infiltration.

Constructing core-shell structured Co3O4-MnWO4 composite photoelectrode with superior PEC water purification performance.

Semiconductor photoelectrocatalytic (PEC) technology is one of the most effective methods for removing organic pollutants from wastewater in advanced oxidation processes(AOPs). The selection of suitable semiconductor materials as photoanodes is a crucial factor for achieving superior PEC performance. Here, a core-shell structured Co3O4-MnWO4 architecture is created by enveloping MnWO4 nanoparticles onto the surface of Co3O4 nanowires through a two-step hydrothermal process. The optimized Co3O4-MnWO4-5 photoelectrode showed superior PEC degradation efficiency for KN-R (∼91.2% in 2 h) and durable stability (the accelerated lifetime reached ∼9100 s at a current density of 50 mA cm-2). Three actual wastewaters were also collected to verify the practical applicability of the photoelectrode.The energy consumption was measured at 4.48 kWhm-3, with a COD removal efficiency of 83% and a decolorization rate of 98%. These results demonstrate the excellent performance and promising application of the photoelectrode. The enhancement of PEC performance for the core-shell structured Co3O4-MnWO4 architecture can be attributed to the suitable energy band structure of the Co3O4-MnWO4 composite, higher OEP, larger electrochemical active surface area, accelerated transport of interface carriers, and lower charge transfer resistance. The energy band structure of the Co3O4-MnWO4 composite showed a strong redox ability to induce electrons/holes (e-/h+), which enhances the generation of intermediate active species (hydroxyl radical ·OH and superoxide radicals ·O2-). Therefore, the rationally designed core-shell structured Co3O4-MnWO4 architecture exhibited excellent practical applicability in the degradation of organic pollutants.

Zn2SnO4@Ti ceramic film anode preparation by microarc oxidation for 2e- WOR degradation of unsymmetrical dimethylhydrazine (UDMH).

The main challenge facing the anodic electro-Fenton through the 2e- water oxidation reaction (WOR) for toxics degradation lies in the electrode's stability, because the anodic oxygen evolution (OER) generated O2 will inevitably exfoliate the electro-active components loaded on the electrode substrate. To address this point, two aspects need attention: 1) Identifying a catalyst that exhibits both excellent electrocatalytic activity and selectivity can improve the faradaic efficiency of hydrogen peroxide (H2O2); 2) Employing novel methods for fabricating highly stable electrodes, where active sites can be firmly coated. Consequently, this study utilized microarc oxidation (MAO) to prepare a ceramic film electrode Zn2SnO4@Ti at 300 V. Zn2SnO4 acts as an WOR electrocatalyst and further improved the generation of H2O2 for treating real wastewater containing Unsymmetrical Dimethylhydrazine (UDMH). From the perspective of characterization of electrode structure, Zn2SnO4@Ti forms a stable active coating, the electrochemical yield of H2O2 is high up to 78.4 µmol h-1 cm-2, and the selectivity of H2O2 is over 80% at 3.3 V vs. RHE, which can be fully applied to scenarios where it is inconvenient to transport H2O2 and need in-situ safe production. Additionally, the prepared electrodes exhibit significant stability, suitable for various applications, providing insightful preparation strategies and experiences for constructing highly stable anodes.

Small Channels Assembled by Multilayer ZIF-8 in Nanocomposite Membranes for Filtration of Ofloxacin in Water.

Metal-organic framework (MOF)-based hybrid membranes still face many unsolved difficulties in the field of liquid separation, with a reliable production technique standing out, in particular, for the water-stable MOF membranes. In this study, zeolitic imidazolate framework-8 (ZIF-8) with acceptable water stability, favorable polymer affinity, and high selectivity was meticulously grafted on commercial poly(vinylidene fluoride) (PVDF) via substrate carboxylation-assisted etching and then overlaid onto PVDF to fabricate a novel hybrid membrane by a layer-by-layer self-assembly method. The optimal membrane manufacturing conditions, including assembly time (10 min), Hmim/Zn2+ molar ratio (8:1), and optimal layer number (three layers), were thoroughly investigated for cutting-off ofloxacin in water filtration. Under low pressure, a nanofiltration scale permeability of about 199.2 L m-2 h-1 MPa-1 and 97.9% rejection of ofloxacin were obtained in bench-scale tests based on the synergistic effect of the Donnan effect and steric hindrance. More significantly, the resulting hybrid membrane demonstrated excellent hydrophilicity, high antifouling, and mechanical and repeatability performances, suggesting promising application possibilities in real-world wastewater filtering settings.

Transcriptomics and metabolomics of blood, urine and ovarian follicular fluid of yak at induced estrus stage.

To gain a deeper understanding of the metabolic differences within and outside the body, as well as changes in transcription levels following estrus in yaks, we conducted transcriptome and metabolome analyses on female yaks in both estrus and non-estrus states. The metabolome analysis identified 114, 13, and 91 distinct metabolites in urine, blood, and follicular fluid, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted an enrichment of pathways related to amino acid and lipid metabolism across all three body fluids. Our transcriptome analysis revealed 122 differentially expressed genes within microRNA (miRNA) and 640 within long non-coding RNA (lncRNA). Functional enrichment analysis of lncRNA and miRNA indicated their involvement in cell signaling, disease resistance, and immunity pathways. We constructed a regulatory network composed of 10 lncRNAs, 4 miRNAs, and 30 mRNAs, based on the targeted regulation relationships of the differentially expressed genes. In conclusion, the accumulation of metabolites such as amino acids, steroids, and organic acids, along with the expression changes of key genes like miR-129 during yak estrus, provide initial insights into the estrus mechanism in yaks.

Whole-genome resequencing of major populations revealed domestication-related genes in yaks.

BACKGROUND: The yak is a symbol of the Qinghai-Tibet Plateau and provides important basic resources for human life on the plateau. Domestic yaks have been subjected to strong artificial selection and environmental pressures over the long-term. Understanding the molecular mechanisms of phenotypic differences in yak populations can reveal key functional genes involved in the domestication process and improve genetic breeding. MATERIAL AND METHOD: Here, we re-sequenced 80 yaks (Maiwa, Yushu, and Huanhu populations) to identify single-nucleotide polymorphisms (SNPs) as genetic variants. After filtering and quality control, remaining SNPs were kept to identify the genome-wide regions of selective sweeps associated with domestic traits. The four methods (π, XPEHH, iHS, and XP-nSL) were used to detect the population genetic separation. RESULTS: By comparing the differences in the population stratification, linkage disequilibrium decay rate, and characteristic selective sweep signals, we identified 203 putative selective regions of domestic traits, 45 of which were mapped to 27 known genes. They were clustered into 4 major GO biological process terms. All known genes were associated with seven major domestication traits, such as dwarfism (ANKRD28), milk (HECW1, HECW2, and OSBPL2), meat (SPATA5 and GRHL2), fertility (BTBD11 and ARFIP1), adaptation (NCKAP5, ANTXR1, LAMA5, OSBPL2, AOC2, and RYR2), growth (GRHL2, GRID2, SMARCAL1, and EPHB2), and the immune system (INPP5D and ADCYAP1R1). CONCLUSIONS: We provided there is an obvious genetic different among domestic progress in these three yak populations. Our findings improve the understanding of the major genetic switches and domestic processes among yak populations.

Unlocking a Type-II CoO@BiVO4 Heterostructure for Wastewater Purification.

Developing a semiconductor-based heterostructure photoanode is crucial in improving the photoelectrocatalytic (PEC) efficiency for degrading refractory organic pollutants. Nevertheless, the PEC performance of the photoanodes is usually restricted by electron/hole pair recombination, oxygen evolution, and slow electron transfer. Herein, a novel CoO@BiVO4 nanowire array film (Ti/CoO@BiVO4) with n-type semiconductor characteristics was prepared via a straightforward hydrothermal method. The optimized Ti/CoO@BiVO4 electrode exhibited excellent PEC decolorization efficiency of active brilliant blue KN-R (∼92.8%) and long-term stability, outperforming recent reports. The insight reason for enhancing the PEC degradation efficiency of the Ti/CoO@BiVO4 electrodes can be attributed to the large electrochemical active area, low charge transfer resistance, and negative flat band potential. The formation of a type-II heterostructure was investigated between CoO and BiVO4 further to promote the generation and separation efficiency of electron/hole pairs, indicating that the optimized Ti/CoO@BiVO4 electrode has the potential for the water PEC degradation ability and superior service life.

Comprehensive analysis of risk factors for surgical site infections following thoracoscopic radical resection in patients with lung cancer.

Surgical site infections (SSIs) post-thoracoscopic radical resection in lung cancer patients pose significant clinical challenges. This study aims to comprehensively identify the independent risk factors that influence the occurrence of SSIs following thoracoscopic radical resection for lung cancer. The study employed a retrospective analysis of 130 patients who underwent thoracoscopic radical resection for lung cancer. Inclusion and exclusion criteria were clearly defined, and ethical approvals were obtained. Patients were monitored for SSIs via clinical and biochemical markers, with data comprehensively gathered from electronic health records. Statistical analysis was rigorously conducted using SPSS v27.0, with methodologies including t-tests, Chi-square tests and logistic regression. The study aimed to identify independent risk factors for SSIs and incorporated a multidimensional assessment approach to provide robust, clinically relevant findings. Univariate analysis revealed surgical duration ≥3 h, non-usage of antibiotics, presence of diabetes and elevated levels of C-reactive protein (CRP) and procalcitonin (PCT) as significant correlates for SSIs. Multivariate analysis substantiated these factors as independent risk variables: surgery duration (odds ratio [OR] = 9.698, p < 0.05), presence of diabetes (OR = 6.89, p < 0.05), elevated CRP (OR = 7.306, p < 0.05) and elevated PCT (OR = 6.838, p < 0.05). Conversely, antibiotic administration served as a protective factor (OR = 0.572, p < 0.05). Surgical duration of 3 h or more, diabetes and elevated levels of CRP and PCT significantly heighten the risk for SSIs after thoracoscopic radical resection in lung cancer patients. Perioperative antibiotic administration acts as a protective factor. Clinicians should implement tailored preventative strategies to mitigate these identified risks.

Identification of topoisomerase 2A as a novel bone metastasis-related gene in liver hepatocellular carcinoma.

BACKGROUND: Bone is the second most frequent site of metastasis for Liver hepatocellular carcinoma (LIHC), which leads to an extremely poor prognosis. Identifying novel biomarkers and therapeutic targets for LIHC patients with bone metastasis is urgently needed. METHODS: In this study, we used multiple databases for comprehensive bioinformatics analysis, including TCGA, GEO, ICGC, GTEx, TISIDB, and TIMER, to identify key genes related to bone metastasis of LIHC. Clinical tissues and tissue microarray were adopted to assess the expression of TOP2A through qRT-PCR and immunohistochemistry analyses in LIHC. Gene enrichment analysis, DNA methylation, gene mutation, prognosis, and tumor immunity associated with TOP2A in LIHC were investigated. In vitro and in vivo experiments were performed to explore the functional role of TOP2A in LIHC bone metastasis. RESULTS: We identified that TOP2A was involved in LIHC bone metastasis. Clinically, TOP2A was highly expressed in LIHC tumoral specimens, with the highest level in the bone metastasis lesions. TOP2A was an independent prognostic factor that higher expression of TOP2A was markedly associated with poorer prognosis in LIHC. Moreover, the abnormal expression of TOP2A might be related to DNA hypomethylation, often accompanied by TP53 mutation, immune escape and immunotherapy failure. Enrichment analysis and validation experiments unveiled that TOP2A stimulated the Hippo-YAP signaling pathway in LIHC. Functional assays confirmed that TOP2A could promote bone-specific metastatic potential and tumor-induced osteolysis in LIHC. CONCLUSIONS: These findings unveil that TOP2A might be a novel prognostic biomarker and therapeutic target for LIHC bone metastasis.

A1BG-AS1 promotes the biological functions of osteosarcoma cells via regulating the microRNA-148a-3p/USP22 axis and stabilizing the expression of SIRT1 through deubiquitinase function.

BACKGROUND: The study aims to explore the role of A1BG antisense RNA 1 (A1BG-AS1), microRNA (miR)-148a-3p and ubiquitin-specific protease 22 (USP22) on osteosarcoma (OS) cell growth. RESEARCH DESIGN & METHODS: A1BG-AS1, miR-148a-3p, USP22, and silent information regulator 2 homolog 1 (SIRT1) levels in OS tissues and cells were determined. The effects of A1BG-AS1, miR-148a-3p, and USP22 on the biological functions of OS cells were examined by functional assays. In vivo assay was conducted to observe the effect of A1BG-AS1 on OS growth in vitro. The relationship of A1BG-AS1, miR-148a-3p, and USP22 was analyzed by bioinformatics analysis, RNA-fluorescence in situ hybridization, luciferase activity, and RNA binding protein immunoprecipitation assays. The relation between USP22 and SIRT1 was evaluated by immunoprecipitation. RESULTS: A1BG-AS1 and USP22 were highly expressed, and miR-148a-3p was lowly expressed in OS tissues and cells. Down-regulation of A1BG-AS1 and USP22 or up-regulation of miR-148a-3p impaired the malignant behaviors of OS cells. A1BG-AS1 sponged miR-148a-3p, and miR-148a-3p targeted USP22, thereby inhibiting USP22 expression. Up-regulating USP22 reversed the A1BG-AS1 suppression-induced phenotypic inhibition of OS cells. USP22 affected the biological functions of OS cells by deubiquitinating SIRT1. CONCLUSION: A1BG-AS1 facilitates the biological functions of OS cells via mediating the miR-148a-3p/USP22 axis.

Construction and validation of a novel cuproptosis-mitochondrion prognostic model related with tumor immunity in osteosarcoma.

BACKGROUND: The purpose of this study was to develop a new prognostic model for osteosarcoma based on cuproptosis-mitochondrion genes. MATERIALS AND METHODS: The data of osteosarcoma were obtained from TARGET database. By using Cox regression and LASSO regression analysis, a novel risk score was constructed based on cuproptosis-mitochondrion genes. Kaplan-Meier, ROC curve and independent prognostic analyses were performed to validate the risk score in GSE21257 dataset. Then, a predictive nomogram was constructed and further validated by calibration plot, C-index and ROC curve. Based on the risk score, all patients were divided into high-risk and low-risk group. GO and KEGG enrichment, immune correlation and drug sensitivity analyses were performed between groups. Real-time quantitative PCR verified the expression of cuproptosis-mitochondrion prognostic model genes in osteosarcoma. And we explored the function of FDX1 in osteosarcoma by western blotting, CCK8, colony formation assay, wound healing assay and transwell assays. RESULTS: A total of six cuproptosis-mitochondrion genes (FDX1, COX11, MFN2, TOMM20, NDUFB9 and ATP6V1E1) were identified. A novel risk score and associated prognostic nomogram were constructed with high clinical application value. Strong differences in function enrichment and tumor immune microenvironment were shown between groups. Besides, the correlation of cuproptosis-mitochondrion genes and drug sensitivity were revealed to search for potential therapeutic target. The expression of FDX1, COX11, MFN2, TOMM20 and NDUFB9 at mRNA level was elevated in osteosarcoma cells compared with normal osteoblast hFOB1.19. The mRNA expression level of ATP6V1E1 was decreased in osteosarcoma. Compared with hFOB1.19, western blotting revealed that the expression of FDX1 was significantly elevated in osteosarcoma cells. Functional experiments indicated that FDX1 mainly promoted the migration of osteosarcoma rather than proliferation. CONCLUSIONS: We developed a novel prognostic model of osteosarcoma based on cuproptosis-mitochondrion genes, which provided great guidance in survival prediction and individualized treatment decision making for patients with osteosarcoma.

Anoikis-Related Gene Signature for Prognostication of Pancreatic Adenocarcinoma: A Multi-Omics Exploration and Verification Study.

Anoikis, a form of apoptosis that occurs due to detachment of cells from the extracellular matrix, has been linked to the development of cancer in several studies. However, its role in pancreatic cancer remains incompletely understood. In this study, we utilized univariate Cox regression and LASSO regression analyses to establish a prognostic model for pancreatic adenocarcinoma based on anoikis-related genes in the TCGA database. Additionally, we performed univariate and multifactorial Cox analyses of protein expression results for TCGA pancreatic adenocarcinoma. We further explored the difference in immune infiltration between the high-risk and low-risk groups and verified the expression of the screened genes using quantitative real-time PCR (qRT-PCR). Our findings indicate that numerous anoikis-related genes are linked to pancreatic adenocarcinoma prognosis. We identified seven prognostic genes (MET, DYNLL2, CDK1, TNFSF10, PIP5K1C, MSLN, GKN1) and validated that their related proteins, such as EGFR and MMP2, have a significant impact on the prognosis of pancreatic adenocarcinoma. Based on clustering analyses of the seven prognostic genes, patients could be classified into three distinct categories, for which somatic mutations varied significantly across the groups. High-risk and low-risk groups also exhibited significant differences in immune infiltration. All genes were found to be highly expressed in pancreatic cancer cell lines (ASPC-1, CFPAC-1) as compared to a normal pancreatic cell line (HPDE). Based on the seven anoikis-related genes, we formulated a robust prognostic model with high predictive accuracy. We also identified the significant impact of KRAS, P53, and CDKN2A mutations on the prognosis of this fatal disease. Therefore, our study highlights the crucial role of anoikis in the development of the pancreatic adenocarcinoma tumor microenvironment.