Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1α and ERK1/2 signaling pathways in bone regeneration.

Angiogenesis plays a crucial role in bone regeneration. Hypoxia is a driving force of angiogenesis at the initial stage of tissue repair. The hypoxic microenvironment could activate the hypoxia-inducible factor (HIF)-1α signaling pathway in cells, thereby enhancing the proliferation, migration and pro-angiogenic functions of stem cells. However, long-term chronic hypoxia could inhibit osteogenic differentiation and even lead to apoptosis. Therefore, shutdown of the HIF-1α signaling pathway and providing oxygen at later stage probably facilitate osteogenic differentiation and bone regeneration. Herein, an oxygen tension regulating hydrogel that sequentially activate and deactivate the HIF-1α signaling pathway were prepared in this study. Its effect and mechanism on stem cell differentiation were investigated both in vitro and in vivo. We proposed a gelatin-based hydrogel capable of sequentially delivering a hypoxic inducer (copper ions) and oxygen generator (calcium peroxide). The copper ions released from the hydrogels significantly enhanced cell viability and VEGF secretion of BMSCs via upregulating HIF-1α expression and facilitating its translocation into the nucleus. Additionally, calcium peroxide promoted alkaline phosphatase activity, osteopontin secretion, and calcium deposition through the activation of ERK1/2. Both Cu2+ and calcium peroxide demonstrated osteogenic promotion individually, while their synergistic effect within the hydrogels led to a superior osteogenic effect by potentially activating the HIF-1α and ERK1/2 signaling pathways.

Measured Regional Division Optimization for Acoustic Tomography Velocity Field Reconstruction in a Circular Area.

The acoustic tomography (AT) velocity field reconstruction technique has become a research hotspot in recent years due to its noninvasive nature, high accuracy, and real-time measurement advantages. However, most of the existing studies are limited to the reconstruction of the velocity field in a rectangular area, and there are very few studies on a circular area, mainly because the layout of acoustic transducers, selection of acoustic paths, and division of measured regions are more difficult in a circular area than in a rectangular area. Therefore, based on AT and using the reconstruction algorithm of the Markov function and singular value decomposition (MK-SVD), this paper proposes a measured regional division optimization algorithm for velocity field reconstruction in a circular area. First, an acoustic path distribution based on the multipath effect is designed to solve the problem of the limited emission angle of the acoustic transducer. On this basis, this paper proposes an adaptive optimization algorithm for measurement area division based on multiple sub-objectives. The steps are as follows: first, two optimization objectives, the condition number of coefficient matrix and the uniformity of acoustic path distribution, were designed. Then, the weights of each sub-objective are calculated using the coefficient of variation (CV). Finally, the measured regional division is optimized based on particle swarm optimization (PSO). The reconstruction effect of the algorithm and the anti-interference ability are verified through the reconstruction experiments of the model velocity field and the simulated velocity field.

Opportunities, challenges, and future directions of large language models, including ChatGPT in medical education: a systematic scoping review

BACKGROUND: ChatGPT is a large language model (LLM) based on artificial intelligence (AI) capable of responding in multiple languages and generating nuanced and highly complex responses. While ChatGPT holds promising applications in medical education, its limitations and potential risks cannot be ignored. METHODS: A scoping review was conducted for English articles discussing ChatGPT in the context of medical education published after 2022. A literature search was performed using PubMed/MEDLINE, Embase, and Web of Science databases, and information was extracted from the relevant studies that were ultimately included. RESULTS: ChatGPT exhibits various potential applications in medical education, such as providing personalized learning plans and materials, creating clinical practice simulation scenarios, and assisting in writing articles. However, challenges associated with academic integrity, data accuracy, and potential harm to learning were also highlighted in the literature. The paper emphasizes certain recommendations for using ChatGPT, including the establishment of guidelines. Based on the review, 3 key research areas were proposed: cultivating the ability of medical students to use ChatGPT correctly, integrating ChatGPT into teaching activities and processes, and proposing standards for the use of AI by medical students. CONCLUSION: ChatGPT has the potential to transform medical education, but careful consideration is required for its full integration. To harness the full potential of ChatGPT in medical education, attention should not only be given to the capabilities of AI but also to its impact on students and teachers.

Chloroplast genome data of five Amygdalus species: Clarifying genome structure and phylogenetic relationships.

Amygdalus species have considerable ecological and economic value, however, the phylogenetic relationships among Amygdalus remain controversy. In this study, we sequenced and assembled the chloroplast (cp) genomes of five Amygdalus species: Prunus communis, P. mongolica, P. pedunculata, P. triloba, and P. mira. We then conducted comparative genomic analyses and constructed their phylogenetic relationships. The genome length ranged from 157,870 to 158,451 bp, and 131 genes were annotated (86 protein-coding genes, 37 tRNAs, and 8 rRNAs). Additionally, 49-57 simple sequence repeats were detected, with most in the large single-copy region and with AT base preferences. Comparative genomic analyses revealed high similarities in structure, order, and gene content. However, we identified four highly divergent sequences: trnR-UCU-atpA, nbdhC-trnV-UAC, ycf4-cemA, and rpl32-trnL-UAG. The phylogenomic relationship analysis suggested that the Amygdalus species were grouped together, in which P. pedunculata, P. triloba, and Prunus tangutica were categorized into a branch, P. mongolica and Prunus davidiana were clustered a branch. This study provides an improved understanding of the genetic relationships among the Amygdalus and provides a basis for the development and utilization of Amygdalus resources.

Dual-Band All-Optical Logic Gates by Coherent Absorption in an Amorphous Silicon Graphene Metasurface.

The dual-band polarization-independent all-optical logic gate by coherent absorption effect in an amorphous silicon (a-Si) graphene metasurface is investigated theoretically and numerically. Taking the substrate effect into consideration, the coherent perfect absorption condition of the a-Si graphene metasurface is derived on the basis of the Cartesian multipole method. The coherent nearly perfect absorption of the a-Si graphene metasurface is realized by the interference of multipole moments and the interband transition of monolayer graphene, achieving peak values of 91% and 92% at 894.5 nm and 991.5 nm, respectively. The polarization independence of the coherent absorption is revealed due to the center symmetry of the structure of the a-Si graphene metasurface. The dual-band polarization-independent all-optical XOR and OR logic gates are implemented at 894.5 nm and 991.5 nm by the a-Si graphene metasurface based on the coherent nearly perfect absorption, which has the opportunity to be utilized in all-optical computing, all-optical data processing, and future all-optical networks.

The underlying mechanisms of DNA methylation in high salt memory in hypertensive vascular disease.

This study demonstrates the effect and DNA methylation-related mechanisms of a high-salt diet and salt memory-induced hypertension and vasculopathy. Thirty Sprague Dawley rats were randomly divided into a control (CON) group (n = 6) and a modeling group (n = 24). A 12% NaCl solution (1 mL/100 g) was intragastrically administered for 60 consecutive days for modeling. An increase in blood pressure up to 140 mmHg was considered successful modeling. Twelve of fifteen successfully modeled rats were randomly selected and divided into a High Salt Diet (HSD) group and a High Salt Memory (HSM) group (n = 6). Rats in HSD group were intragastrically administered a 12% NaCl solution, while rats in HSM group were administered a 3% NaCl solution twice a day for 30 days. At the end of the intervention, blood pressure and the serum levels of ET-1, NO, TNF-α and IL-1ß were measured. RRBS-heavy sulfite sequencing technology was selected for DNA methylation analysis. The systolic blood pressure of rats in the HSD group and HSM group was significantly higher than that in the CON group. Compared with those in the CON group, the serum levels of ET-1 in the HSM group and the serum levels of NO in the HSD group and HSM group were significantly increased. The methylation level of the CON group was lower than that of the HSD group and the HSM group, and there was no significant difference between the HSD group and the HSM group. The methylation level of Myoz3 was downregulated in the HSD group and HSM group. The methylation level of Fgd3 were upregulated in HSD group and downregulated in the HSM group. The methylation levels of AC095693.1, Adamts3, PDGFA and PDGFRα were downregulated in the HSD group and upregulated in the HSM group. According to the GO database, the differentially methylated genes were significantly enriched in the coordination of cell function, genetic development, and RNA transcription. There were three main metabolic pathways that were enriched in the differentially expressed genes between the groups: the PI3K-Akt signaling pathway, MAPK signaling pathway, and Hippo signaling pathway. Excessive salt intake may cause hypertension and vascular damage, and this damage may continue after the reduction of salt intake. Therefore, salt memory phenomenon exists, and this memory effect may be correlated with the levels of DNA methylation.

Effect of Liuzijue exercise in different periods on circadian rhythm of blood pressure in patients with essential hypertension: A randomized trial.

BACKGROUND: Exercising at different times of the day is a widely employed strategy for treating essential hypertension, aimed at enhancing the circadian rhythm of blood pressure. This study aimed to investigate the effects of Liuzijue exercise in the morning and afternoon on the circadian rhythm of blood pressure in patients with essential hypertension. METHODS: This clinical randomized trial recruited 36 patients. They were randomly divided into 3 groups: morning exercise, afternoon exercise, and waiting treatment group. Randomization was performed at a ratio of 1:1:1, ensuring an equal distribution of participants among the 3 groups. Based on maintaining routine work and rest and continuing the original drug treatment, the exercise performed Liuzijue exercise for 12 weeks. The exercise time was 9:00 to 10:00 in the morning exercise group and 14:00 to 15:00 in the afternoon exercise group. The waiting treatment group did not perform any form of fitness exercise. The subjects in the 3 groups were monitored by 24-hour ambulatory blood pressure on the day before and after the first day. RESULTS: After the 12-week Liuzijue exercise intervention, mean systolic blood pressure during the night significantly decreased in the morning exercise group (P < .01). In contrast, the waiting group experienced substantial increases in 24-hour mean systolic blood pressure (24hSBP), 24-hour mean diastolic blood pressure (24hDBP), mean systolic blood pressure during the daytime (dSBP), and mean diastolic blood pressure during the daytime (dDBP) (P < .01). Further analysis showed that the morning exercise group had significantly lower 24hSBP, 24hDBP, dSBP, dDBP, and mean systolic blood pressure during the night than the waiting group (P < .05). Additionally, the morning exercise group had lower 24hSBP and dSBP levels than the afternoon exercise group (P < .05). In contrast, the afternoon exercise group had lower 24hDBP and dDBP than the waiting treatment group (P < .05). CONCLUSIONS: The 12-week Liuzijue exercise in the morning regimen demonstrated superior efficacy in reducing 24-hour ambulatory blood pressure levels among patients with essential hypertension. Moreover, it facilitates the transition of non-dipper blood pressure patterns to dippers, thereby rectifying aberrant circadian rhythms.

A randomized, double-blinded, placebo-controlled clinical trial of duloxetine hydrochloride enteric-coated tablets in the treatment of refractory chronic cough.

INTRODUCTION: Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough. METHODS AND ANALYSIS: This is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test. DISCUSSION: This study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition. TRIAL REGISTRATION: Our study was registered in the Chinese Clinical Trials Register ( www.chictr.org.cn/ ) (ChiCTR2000037429) in 28/08/2020.

DeePMD-kit v2: A software package for deep potential models.

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.

A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro.

Osteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-b-P(C7-co-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-b-P(C7-co-CA) micelle was investigated. mPEG-b-P(C7-co-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-b-P(C7-co-CA) micelles could regulate the cell cycle and inhibit the proliferation of 143B cells, which was demonstrated by flow cytometry analysis, CCK-8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) staining. The wound-healing assay and transwell assay showed that mPEG-b-P(C7-co-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-b-P(C7-co-CA) micelles downregulated the levels of proliferation and apoptosis-related proteins and affected osteosarcoma migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). In addition, mPEG-b-P(C7-co-CA) micelles can also inhibit the transcriptional activity of the PI3K/Akt signaling pathway. Therefore, these findings provide new evidence for the pharmacological effects of mPEG-b-P(C7-co-CA) micelles.

Scoping review update on somatic symptom disorder that includes additional Chinese data.

Somatic symptom disorder (SSD) is a new diagnosis introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is expected to solve the diagnostic difficulties of patients with medically unexplained symptoms. Based on the previous work, this review aims to comprehensively synthesise updated evidence related to SSD from recent years in English publications and, more extensively, from data published in Chinese language journals. The scoping review update was based on an earlier scoping review and included Chinese language publication data from China National Knowledge Internet (CNKI), WANFANG and WEIPU between January 2013 and May 2022 and data from PubMed, PsycINFO, and Cochrane Library between June 2020 and May 2022. Initially, 2 984 articles were identified, of which 63 full texts were included for analysis. In China, SSD is mainly applied in scientific research, but it also shows good predictive validity and clinical application potential. The mean frequency of SSD was 4.5% in the general population, 25.2% in the primary care population and 33.5% in diverse specialised care settings. Biological factors, such as brain region changes and heart rate variability, are associated with the onset of SSD. Psychological impairment related to somatic symptoms is the best predictor of prognosis. While adolescent SSD was significantly associated with family function, SSD overall is associated with an increased dysfunction of cognition and emotion, decreased quality of life, and high comorbidity with anxiety and depressive disorders. Further research is needed on suicide risk and cultural and gender-related issues. Updating the data of Chinese language studies, our research enriches the evidence-based findings related to the topics addressed in the text sections of the SSD chapter of DSM-5. However, research gaps remain about SSD reliability, population-based prevalence, suicide risk, and cultural and gender-related issues.

Tibial plateau fracture and RNA sequencing with osteogenesis imperfecta: a case report.

Osteogenesis imperfecta (OI) is a hereditary skeletal dysplasia with an incidence of approximately 1:15,000 to 20,000. OI is usually caused by the mutation of COL1A1 and COL1A2, which would encode the α-chain of type I collagen. OI is clinically characterized by decreased bone mass, increased risk of bone fragility, blue sclerae, and dentinogenesis. Case presentation: A 29-year-old male patient was diagnosed with right tibial plateau fracture caused by slight violence. Physical examination revealed the following: height, 140 cm; weight, 70 kg; body mass index (BMI), 35.71 kg/m2; blue sclera and barrel chest were observed. X-ray examination showed left convex deformity of the thoracic vertebrae with reduced thoracic volume. Laboratory examinations revealed a decrease in both vitamin D and blood calcium levels. Bone mineral density (BMD) was lower than the normal range. After the preoperative preparation was completed, the open reduction and internal fixation of the right tibial plateau fracture were performed. Meanwhile, whole blood samples of this OI patient and the normal control were collected for RNA transcriptome sequencing. The RNA sequence analysis revealed that there were 513 differentially expressed genes (DEGs) between this OI patient and the normal control. KEGG-enriched signaling pathways were significantly enriched in extracellular matrix (ECM)-receptor interactions. Conclusion: In this case, DEGs between this OI patient and the normal control were identified by RNA transcriptome sequencing. Moreover, the possible pathogenesis of OI was also explored, which may provide new evidence for the treatment of OI.

Topology of vibrational modes predicts plastic events in glasses.

The plastic deformation of crystalline materials can be understood by considering their structural defects such as disclinations and dislocations. Although also glasses are solids, their structure resembles closely the one of a liquid and hence the concept of structural defects becomes ill-defined. As a consequence it is very challenging to rationalize on a microscopic level the mechanical properties of glasses close to the yielding point and to relate plastic events to structural properties. Here we investigate the topological characteristics of the eigenvector field of the vibrational excitations of a two-dimensional glass model, notably the geometric arrangement of the topological defects as a function of vibrational frequency. We find that if the system is subjected to a quasistatic shear, the location of the resulting plastic events correlate strongly with the topological defects that have a negative charge. Our results provide thus a direct link between the structure of glasses prior their deformation and the plastic events during deformation.

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/ß-Catenin Signaling Pathway.

In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, ß-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, ß-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/ß-catenin signaling pathway.

An injectable liposome-anchored teriparatide incorporated gallic acid-grafted gelatin hydrogel for osteoarthritis treatment.

Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1-34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1-34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1ß-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.

Rapid Evaluation of Lung Adenocarcinoma Progression by Detecting Plasma Extracellular Vesicles with Lateral Flow Immunoassays.

Extracellular vesicles (EVs) have been widely used in liquid biopsy to diagnose and monitor cancers. However, since samples containing EVs are usually body fluids with complex components, the cumbersome separation steps for EVs during detection limit the clinical application and promotion of EV detection methods. In this study, a dyad lateral flow immunoassay (LFIA) strip for EV detection, containing CD9-CD81 and EpCAM-CD81, was developed to detect universal EVs and tumor-derived EVs, respectively. The dyad LFIA strip can directly detect trace plasma samples and effectively distinguish the cancerous sample from healthy plasma. The limit of detection for detecting universal EVs was 2.4 × 105 mL-1. The whole immunoassay can be performed in 15 min and only consumes 0.2 µL of plasma for one test. To improve the suitability of a dyad LFIA strip in complex scenarios, a smartphone-based photographic method was developed, which provided a consistency of 96.07% to a specialized fluorescence LFIA strip analyzer. In further clinical testing, EV-LFIA discriminated lung cancer patient groups (n = 25) from healthy controls (n = 22) with 100% sensitivity and 94.74% specificity at the best cutoff. The detection of EpCAM-CD81 tumor EVs (TEVs) in lung cancer plasma revealed the differences in TEVs in individuals, which reflected the different treatment effects. TEV-LFIA results were compared with CT scan findings (n = 30). The vast majority of patients with increased TEV-LFIA detection intensity had lung masses that enlarged or remained unchanged in size, which reported no response to treatment. In other words, patients who reported no response (n = 22) had a high TEV level compared with patients who reported a response to treatment (n = 8). Taken together, the developed dyad LFIA strip provides a simple and rapid platform to characterize EVs to monitor lung cancer therapy outcomes.

Corrigendum to 'Teriparatide ameliorates articular cartilage degradation and aberrant subchondral bone remodeling in DMM mice' [J. Orthop. Transl.] 38 (2023) 241-255].

[This corrects the article DOI: 10.1016/j.jot.2022.10.015.].

Hybrid Auxiliary Field Quantum Monte Carlo for Molecular Systems.

We propose a quantum Monte Carlo approach to solve the many-body Schrödinger equation for the electronic ground state. The method combines optimization from variational Monte Carlo and propagation from auxiliary field quantum Monte Carlo in a way that significantly alleviates the sign problem. In application to molecular systems, we obtain highly accurate results for configurations dominated by either dynamic or static electronic correlation.

Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC.

Background: Copper is an indispensable mineral element involved in many physiological metabolic processes. Cuproptosis is associated with a variety of cancer such as hepatocellular carcinoma (HCC). The objective of this study was to examine the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of HCC. Methods: The differentially expressed genes (DEGs) between high and low CRGs expression groups in HCC samples were identified, and further were analyzed for functional enrichment analysis. Then, CRGs signature of HCC was constructed and analyzed utilizing LASSO and univariate and multivariate Cox regression analysis. Prognostic values of CRGs signature were evaluated by Kaplan-Meier analysis, independent prognostic analysis and nomograph. The expression of prognostic CRGs was verified by Real-time quantitative PCR (RT-qPCR) in HCC cell lines. In addition, the relationships between prognostic CRGs expression and the immune infiltration, tumor microenvironment, antitumor drugs response and m6A modifications were further explored using a series of algorithms in HCC. Finally, ceRNA regulatory network based on prognostic CRGs was constructed. Results: The DEGs between high and low CRG expression groups in HCC were mainly enriched in focal adhesion and extracellular matrix organization. Besides, we constructed a prognostic model that consists of CDKN2A, DLAT, DLST, GLS, and PDHA1 CRGs for predicting the survival likelihood of HCC patients. And the elevated expression of these five prognostic CRGs was substantially in HCC cell lines and associated with poor prognosis. Moreover, immune score and m6A gene expression were higher in the high CRG expression group of HCC patients. Furthermore, prognostic CRGs have higher mutation rates in HCC, and are significantly correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, and anti-tumor drug sensitivity. Then, eight lncRNA-miRNA-mRNA regulatory axes that affected the progression of HCC were predicted. Conclusion: This study demonstrated that the CRGs signature could effectively evaluate prognosis, tumor immune microenvironment, immunotherapy response and predict lncRNA-miRNA-mRNA regulatory axes in HCC. These findings extend our knowledge of cuproptosis in HCC and may inform novel therapeutic strategies for HCC.

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma.

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated. Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed. Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established. Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.