Characterization of a patient-derived variant of GPX4 for precision therapy.

Glutathione peroxidase 4 (GPX4), as the only enzyme in mammals capable of reducing esterified phospholipid hydroperoxides within a cellular context, protects cells from ferroptosis. We identified a homozygous point mutation in the GPX4 gene, resulting in an R152H coding mutation, in three patients with Sedaghatian-type spondylometaphyseal dysplasia. Using structure-based analyses and cell models, including patient fibroblasts, of this variant, we found that the missense variant destabilized a critical loop, which disrupted the active site and caused a substantial loss of enzymatic function. We also found that the R152H variant of GPX4 is less susceptible to degradation, revealing the degradation mechanism of the GPX4 protein. Proof-of-concept therapeutic treatments, which overcome the impaired R152H GPX4 activity, including selenium supplementation, selective antioxidants and a deuterated polyunsaturated fatty acid were identified. In addition to revealing a general approach to investigating rare genetic diseases, we demonstrate the biochemical foundations of therapeutic strategies targeting GPX4.

1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses. IMPORTANCE Multiple coronavirus pandemics have occurred over the last 2 decades. This has highlighted a need to be proactive in the development of therapeutics that can be readily deployed in the case of future coronavirus pandemics. We developed and validated a simplified cell-based assay for the identification of chemical inhibitors of 3CL proteases encoded by a wide range of coronaviruses. This assay is reporter free, does not require specialized biocontainment, and is optimized for performance in high-throughput screening. By testing reported 3CL protease inhibitors against a large collection of 3CL proteases with variable sequence similarity, we identified compounds with broad activity against 3CL proteases and uncovered structural insights into features that contribute to their broad activity. Furthermore, we demonstrated that this assay is suitable for identifying chemical inhibitors of proteases from families other than 3CL proteases.

FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation.

Ferroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2. We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc- or directly target the reducing enzyme GPX4, as do erastin and RSL3, respectively, nor does it deplete GPX4 protein, as does FIN56. Instead, FINO2 both indirectly inhibits GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation. These findings suggest that endoperoxides such as FINO2 can initiate a multipronged mechanism of ferroptosis.

Effects of local anesthetics on breast cancer cell viability and migration.

BACKGROUND: Breast cancer accounts for nearly a quarter of all cancers in women worldwide, and more than 90% of women diagnosed with breast cancer undergo mastectomy or breast-conserving surgery. Retrospective clinical studies have suggested that use of regional anesthesia leads to improved patient outcomes. Laboratory studies have reported that breast cancer cells are inhibited by some local anesthetics at millimolar concentration. Here, we present a comprehensive analysis of the effects of six common local anesthetics on two human breast cancer cell lines. We used concentrations ranging from those corresponding to plasma levels during regional block by local anesthetic (plasma concentration) to those corresponding to direct infiltration of local anesthetic. METHODS: Human breast cancer cell lines, MDA-MB-231 and MCF7, were incubated with each of six local anesthetics (lidocaine, mepivacaine, ropivacaine, bupivacaine, levobupivacaine, and chloroprocaine) (10 µM ~ 10 mM) for 6 to 72 h. Assays for cell viability, cytotoxicity, migration, and cell cycle were performed. RESULTS: High concentrations (> 1 mM) of local anesthetics applied to either MDA-MB-231 or MCF7 cells for 48 h significantly inhibited cell viability and induced cytotoxicity. At plasma concentrations (~ 10 µM) for 72 h, none of the local anesthetics affected cell viability or migration in either cell line. However, at 10 × plasma concentrations, 72-h exposure to bupivacaine, levobupivacaine or chloroprocaine inhibited the viability of MDA-MB-231 cells by > 40% (p < 0.001). Levobupivacaine also inhibited the viability of MCF7 cells by 50% (p < 0.001). None of the local anesthetics affected the viability of a non-cancerous breast cell line, MCF10A. MDA-MB-231 cell migration was inhibited by 10 × plasma concentrations of levobupivacaine, ropivacaine or chloroprocaine and MCF7 cell migration was inhibited by mepivacaine and levobupivacaine (p < 0.05). Cell cycle analysis showed that the local anesthetics arrest MDA-MB-231 cells in the S phase at both 1 × and 10 × plasma concentrations. CONCLUSIONS: Local anesthetics at high concentrations significantly inhibited breast cancer cell survival. At 10 × plasma concentrations, the effect of local anesthetics on cancer cell viability and migration depended on the exposure time, specific local anesthetic, specific measurement endpoint and specific cell line.

Effect of Propofol on breast Cancer cell, the immune system, and patient outcome.

Breast cancer is the second leading cause of cancer death in women. Surgery is the first line of treatment for breast cancer. Retrospective clinical studies suggest that the type of anesthesia administered during oncological surgery may influence patient outcome. Propofol, the widely used intravenous anesthetic agent, may lead to better outcomes compared to volatile anesthetics. Here we review the literature on the effect of propofol in breast cancer cells, the immune system, pain management, and patient outcomes. Evidence from the study of breast cancer cell lines suggests that high concentrations of propofol have both anti-tumor and pro-tumor effects. Propofol and volatile anesthetics have different effects on the immune system. Propofol has also been shown to reduce the development and severity of acute and chronic pain following surgery. Although a retrospective study that included many types of cancer indicated that propofol increases the long-term survival of patients following surgery, the evidence for this in breast cancer is weak. It has been shown that Propofol combined with paravertebral block led to change of serum composition that affects the breast cancer cell behaviors and natural killer cell activity. Prospective studies are in progress and will be finished within 5 years. The existing evidence is not sufficient to warrant changes to current anesthetic management. Further research is needed to clarify the mechanisms by which propofol affects cancer cells and the immune system.

Changes in related circular RNAs following ERß knockdown and the relationship to rBMSC osteogenesis.

Recently, several studies have indicated that circular RNAs (circRNAs) play significant roles in various disease; however, little is known about the chronology of estrogen receptor beta (ERß) deficiency and altered circRNA expression, or their relationship with osteogenesis. Herein, we show through western-blot and quantitative real-time PCR assays, that when ERß is silenced, the expression of osteogenesis-related proteins and mRNAs were down-regulated. We then performed RNA-Seq to analyze differential circRNA expression between the control and ERß knockdown group. This analysis revealed that, 146 circRNAs were differentially expressed by fold-change≥2.0, p ≤ 0.05, and, among this group, 68 circRNAs were down-regulated, while 78 were up-regulated. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and PANTHER pathway analyses were performed to predict the function of these differentially expressed circRNAs. Finally, co-expressed targets gene, and circRNA-microRNA network were constructed for predicted miRNA sponges. This research suggested that ERß may through 2:27713879|27755789/2:240822115|240867796-miR-328-5p-mRNA axis to regulate osteogenic differentiation.

Flexocatalytic Reduction of Tumor Interstitial Fluid/Solid Pressure for Efficient Nanodrug Penetration.

The practical efficacy of nanomedicines for treating solid tumors is frequently low, predominantly due to the elevated interstitial pressure within such tumors that obstructs the penetration of nanomedicines. This increased interstitial pressure originates from both liquid and solid stresses related to an undeveloped vascular network and excessive fibroblast proliferation. To specifically resolve the penetration issues of nanomedicines for tumor treatment, this study introduces a holistic "dual-faceted" approach. A treatment platform predicated on the WS2/Pt Schottky heterojunction was adopted, and flexocatalysis technology was used to disintegrate tumor interstitial fluids, thus producing oxygen and reactive oxygen species and effectively mitigating the interstitial fluid pressure. The chemotherapeutic agent curcumin was incorporated to further suppress the activity of cancer-associated fibroblasts, minimize collagen deposition in the extracellular matrix, and alleviate solid stress. Nanomedicines achieve homologous targeting by enveloping the tumor cell membrane. It was found that this multidimensional strategy not only alleviated the high-pressure milieu of the tumor interstitium─which enhanced the efficiency of nanomedicine delivery─but also triggered tumor cell apoptosis via the generated reactive oxygen species and modulated the tumor microenvironment. This, in turn, amplified immune responses, substantially optimizing the therapeutic impacts of nanomedicines.

APR-246 increases tumor antigenicity independent of p53.

We previously reported that activation of p53 by APR-246 reprograms tumor-associated macrophages to overcome immune checkpoint blockade resistance. Here, we demonstrate that APR-246 and its active moiety, methylene quinuclidinone (MQ) can enhance the immunogenicity of tumor cells directly. MQ treatment of murine B16F10 melanoma cells promoted activation of melanoma-specific CD8+ T cells and increased the efficacy of a tumor cell vaccine using MQ-treated cells even when the B16F10 cells lacked p53. We then designed a novel combination of APR-246 with the TLR-4 agonist, monophosphoryl lipid A, and a CD40 agonist to further enhance these immunogenic effects and demonstrated a significant antitumor response. We propose that the immunogenic effect of MQ can be linked to its thiol-reactive alkylating ability as we observed similar immunogenic effects with the broad-spectrum cysteine-reactive compound, iodoacetamide. Our results thus indicate that combination of APR-246 with immunomodulatory agents may elicit effective antitumor immune response irrespective of the tumor's p53 mutation status.

Prediction of (TiO2)x(Cu2O)y alloys for efficient photoelectrochemical water splitting.

The formation of (TiO(2))(x)(Cu(2)O)(y) solid-solutions is investigated using a global optimization evolutionary algorithm. First-principles calculations based on density functional theory are then used to gain insight into the electronic properties of these alloys. We find that: (i) Ti and Cu in (TiO(2))(x)(Cu(2)O)(y) alloys have similar local environments as in bulk TiO(2) and Cu(2)O except for (TiO(2))(Cu(2)O) which has some trigonal-planar Cu ions. (ii) The predicted optical band gaps are around 2.1 eV (590 nm), thus having much better performance in the absorption of visible light compared with both binary oxides. (iii) (TiO(2))(2)(Cu(2)O) has the lowest formation energy amongst all studied alloys and the positions of its band edges are found to be suitable for solar-driven water splitting applications.

Expression and potential immune involvement of cuproptosis in kidney renal clear cell carcinoma.

Cuproptosis is a newly identified programmed cell death pathway mediated by intracellular free copper. Cuproptosis genes were studied in this study for a better insight into the role of cuproptosis in cancers. The analysis identified kidney renal clear cell carcinoma (KIRC) as a cancer type most likely to be affected by cuproptosis. This study analyzed the multi-omic data to explore the cancer-noncancer expression pattern and potential immune involvement of the cuproptosis pathway in KIRC. This study clustered the TCGA KIRC samples based on the gene set of 12 cuproptosis genes to study the role of cuproptosis in the KIRC immune microenvironment and found the potential value of cuproptosis signature for immunotherapy prognosis. This study concluded that cuproptosis might affect KIRC and had potential application value in immune therapy. Hopefully, this study can contribute to the application of cuproptosis in the clinical therapy of KIRC.

A bioinformatic study of IGFBPs in glioma regarding their diagnostic, prognostic, and therapeutic prediction value.

BACKGROUND: It is essential to develop better biomarkers for diagnosis, prediction, and treating glioma patients to ensure successful clinical outcomes. The clinical application of Insulin-Like Growth Factor Binding Proteins (IGFBPs) for glioma is yet to be investigated. METHODS: Cohorts were obtained from TCGA, GTEx, CGGA, HPA, Oncomine, CancerSEA, TISCH, etc. The expressions, methylation, and survival association of IGFBPs were analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prognostic model. The correlation of IGFBPs and immune cells or immune molecules was analyzed. The effect of IGFBPs on immune therapy and chemotherapy was analyzed. The top 500 correlated genes of IGFBPs were enriched in GO terms. Correlations between IGFBPs and functional states in glioma single-cells and correlations between IGFBPs and chemokines in samples were analyzed. RESULTS: IGFBPs were overexpressed in glioma. Malignant cells were the major cell types that expressed IGFBPs. Higher-grade glioma had a higher expression of IGFBPs, which were associated with worse survival. A survival model of IGFBPs for glioma patients was trained and validated. A nomogram was generated. Generally, IGFBPs mRNA expression was negatively correlated with B cells and T cells. IGFBPs were associated with multiple immune molecules and drug sensitivity. CONCLUSION: IGFBPs were powerful diagnostic, prognostic, and therapeutic prediction biomarkers for glioma.

Pan-cancer genetic analysis of disulfidptosis-related gene set.

BACKGROUND: A recent study has identified a novel programmed cell death pathway, termed disulfidptosis, which is based on disulfide proteins. This discovery provides new insight into the mechanisms of cell death and may have implications for therapeutic strategies targeting cell death pathways. This study aimed to evaluate the pan-cancer genomics and clinical association of disulfidptosis and disulfidptosis-related cell death genes, including SLC7A11, INF2, CD2AP, PDLIM1, ACTN4, MYH9, MYH10, IQGAP1, FLNA, FLNB, TLN1, MYL6, ACTB, DSTN, and CAPZB. METHODS: Using multi-omics profiling data, this study provides a comprehensive and systematic characterization of disulfidptosis genes across more than 9000 samples of over 30 types of cancer. RESULTS: FLNA and FLNB were the two most frequently mutated disulfidptosis cell death genes in cancer. UCEC and SKCM were the two cancer types that have the highest mutation rates while the mutation of ACTN4 was associated with worse survival of CESC and ESCA. Breast cancer was potentially affected by disulfidptosis because its subtypes are different in disulfidptosis gene expression. Similarly, KIRC might also be associated with disulfidptosis. Additionally, the association of disulfidptosis-related cell death genes with survival was analyzed, with MESO and LGG as the top cancer types with survival associated with disulfidptosis cell death genes. The correlation between CNV and survival across multiple cancer types found that UCEC, KIRP, LGG, and KIRC were the top cancer types where the CNV level was associated with survival. There was a negative correlation between expression and methylation for most of the genes and there was only a slight correlation between methylation levels and survival of cancer in LGG. About half of the disulfidptosis-related cell death proteins were associated with the activation of EMT. Disulfidptosis genes were correlated to immune cell infiltration levels in cancers. Multiple compounds were identified as potential drugs that might be affected by disulfidptosis-related cell death for future study. CONCLUSION: Disulfidptosis cell death genes are potentially involved in many cancer types and can be developed as candidates for cancer diagnosis, prognosis, and therapeutic biomarkers.

MAPK signaling pathway-based glioma subtypes, machine-learning risk model, and key hub proteins identification.

An early diagnosis and precise prognosis are critical for the treatment of glioma. The mitogen­activated protein kinase (MAPK) signaling pathway potentially affects glioma, but the exploration of the clinical values of the pathway remains lacking. We accessed data from TCGA, GTEx, CGGA, etc. Up-regulated MAPK signaling pathway genes in glioma were identified and used to cluster the glioma subtypes using consensus clustering. The subtype differences in survival, cancer stemness, and the immune microenvironment were analyzed. A prognostic model was trained with the identified genes using the LASSO method and was validated with three external cohorts. The correlations between the risk model and cancer-associated signatures in cancer were analyzed. Key hub genes of the gene set were identified by hub gene analysis and survival analysis. 47% of the MAPK signaling pathway genes were overexpressed in glioma. Subtypes based on these genes were distinguished in survival, cancer stemness, and the immune microenvironment. A risk model was calculated with high confidence in the prediction of overall survival and was correlated with multiple cancer-associated signatures. 12 hub genes were identified and 8 of them were associated with survival. The MAPK signaling pathway was overexpressed in glioma with prognostic value.

Research on Response Parameters and Classification Identification Method of Concrete Vibration Process.

The vibration process applied to fresh concrete is an important link in the construction process, but the lack of effective monitoring and evaluation methods results in the quality of the vibration process being difficult to control and, therefore, the structural quality of the resulting concrete structures difficult to guarantee. In this paper, according to the sensitivity of internal vibrators to vibration acceleration changes under different vibration media, the vibration signals of vibrators in air, concrete mixtures, and reinforced concrete mixtures were collected experimentally. Based on a deep learning algorithm for load recognition of rotating machinery, a multi-scale convolution neural network combined with a self-attention feature fusion mechanism (SE-MCNN) was proposed for medium attribute recognition of concrete vibrators. The model can accurately classify and identify vibrator vibration signals under different working conditions with a recognition accuracy of up to 97%. According to the classification results of the model, the continuous working times of vibrators in different media can be further statistically divided, which provides a new method for accurate quantitative evaluation of the quality of the concrete vibration process.

Exploring the mechanism underlying hyperuricemia using comprehensive research on multi-omics.

Hyperuricemia involves multiple complex metabolisms, but no study has conducted a comprehensive analysis using human blood and urine metabolomics for hyperuricemia. Serum and urine samples from 10 patients with hyperuricemia and 5 controls were collected and analyzed by the UHPLC-MS/MS. Differential metabolites were identified and used in the enrichment analysis where we collected hyperuricemia target genes. Hyperuricemia kidney differential expressed genes (DEGs) were identified using RNA-sequencing data from the hyperuricemia mouse model induced by the potassium oxonate. A Mendelian randomization analysis of the association between caffeine-containing drinks and gout risk was conducted. An intersection analysis between hyperuricemia target genes and hyperuricemia kidney DEGs was conducted and the resulting genes were used for network analysis using the STRING. 227 differential metabolites were identified as differential metabolites and were enriched in 7 KEGG pathways, among which "Caffeine metabolism" was the top. The Mendelian randomization analysis revealed a significant association between tea or coffee intake and gout risk. There were 2173 genes that were identified as hyperuricemia kidney DEGs from mouse data. The intersection analysis identified 51 genes for the hyperuricemia regulation network. A hyperuricemia regulation protein network in the kidney was constructed. This study suggested a potential association between caffeine and hyperuricemia and constructed a hyperuricemia regulation network for future reference.

The Potential Effect of General Anesthetics in Cancer Surgery: Meta-Analysis of Postoperative Metastasis and Inflammatory Cytokines.

Metastasis or recurrence following curative surgery is the main indicator of tumor progress and is the main cause of patient death. For more than three decades, the potential for general anesthesia to affect cancer outcomes has been a subject of concern with considerable research interest. Here, we conducted this systematic review and meta-analysis to summarize the effect of inhalational anesthesia (IHNA) vs. propofol-based total intravenous anesthesia (TIVA) on metastasis and recurrence after cancer surgery from clinical and pre-clinical studies. The relative risk for metastasis/recurrence in TIVA is 0.61 (95% confidence interval (95% CI) 0.46 to 0.82, p = 0.0009) compared to IHNA. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery, thus we analyzed inflammatory cytokines levels after surgery under IHNA or TIVA. Based on pooled analysis, a lower IL-6 level was noticed in TIVA in comparison to IHNA (standardized mean difference (SMD) = 0.77, 95% CI = 0.097 to 1.44, I2 = 92%, p = 0.02) but not TNF-α or IL-10. Preclinical animal model studies show that inhalational anesthetics increase the risk of breast cancer metastasis compared to propofol. In conclusion, the current evidence suggests intravenous anesthetic propofol is associated with less metastasis/recurrence and lower postoperative IL-6 level over inhaled anesthetics in the oncological surgery. We urge more well-designed clinical and preclinical studies in this field.

Si3AlP: a new promising material for solar cell absorber.

First-principles calculations were performed to study the structural and optoelectronic properties of the newly synthesized nonisovalent and lattice-matched (Si(2))(0.6)(AlP)(0.4) alloy (Watkins, T.; et al. J. Am. Chem. Soc.2011, 133, 16212). We found that the most stable structure of Si(3)AlP is a superlattice along the [111] direction with separated AlP and Si layers, which has a similar optical absorption spectrum to silicon. The ordered C1c1-Si(3)AlP is found to be the most stable one among all structures with a basic unit of one P atom surrounded by three Si atoms and one Al atom, in agreement with experimental suggestions. We predict that C1c1-Si(3)AlP has good optical properties, i.e., it has a larger fundamental band gap and a smaller direct band gap than Si; thus, it has much higher absorption in the visible light region. The calculated properties of Si(3)AlP suggest that it is a promising candidate for improving the performance of the existing Si-based solar cells. The understanding on the stability and band structure engineering obtained in this study is general and can be applied for future study of other nonisovalent and lattice-matched semiconductor alloys.

Pan-cancer profiles of the cuproptosis gene set.

A recent study has revealed a novel cell death pathway, called "cuproptosis", a programmed cell death based on copper. A total of 12 genes were involved in the cuproptosis pathway, including 7 pro-cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, and PDHB) genes, 3 anti-cuproptosis genes (MTF1, GLS, and CDKN2A), and 2 key copper transporters ATP7B and SLC31A1. The insight into these cuproptosis genes in cancer is necessary to understand cuproptosis-related tumorigenesis and to develop the cuproptosis pathway as a potential therapeutic target for clinical cancer treatment. By mining multi-omic profiling data, we performed a comprehensive and systematic characterization of the cuproptosis of these 12 genes across more than 9000 samples of 33 types of cancer. This letter not only revealed diverse mechanisms of the gene expression regulations of the cuproptosis gene set in cancer but also analyzed the potential associations between cuproptosis and other common cancer pathways, providing an overall picture of cuproptosis in cancer for future reference. This study comprehensively clarified the genomic pan-cancer profiles of the cuproptosis gene set regarding the SNV, CNV, methylation, mRNA expression, pathway cross-talk, and miRNA regulations across 33 solid tumors. Our findings revealed that genomic alterations and miRNA-mRNA network-mediated ectopic expression of cuproptosis genes were involved in the activation of other cancer-related pathways and also identified KIRC as a potential cancer type that might be affected by cuproptosis. We think, as the rase of the cuproptosis cancer research, these in-time profiles will provide a genetic overview and useful information for future studies on the cuproptosis in cancers.