Is the voltage-gated sodium channel ß3 subunit (SCN3B) a biomarker for glioma?

Recent studies suggest a need for reliable biomarkers enhancing prognosis prediction and treatment strategies in cancer. Here, we performed a data analysis bearing on the expression of SCN3B, voltage-gated sodium channel (VGSC) ß3 subunit, as a possible candidate for the development of a glioma biomarker for the first time. This extends our previous review article that mentioned the potential of SCN3B as a prognostic biomarker for glioma survival, further examining its association with existing indicators and immune responses. We utilized clinical and genomic data from multiple glioma cohorts. These include the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We employed analytical techniques including time-dependent receiver operating characteristic (ROC) analysis, decision curves analysis (DCA), and correlation studies with immune checkpoint markers. Our findings indicate a differential SCN3B expression between glioma grades, and that this significantly correlates with patient survival, particularly in oligodendroglioma subtypes. The DCA curves suggested that the inclusion of SCN3B in the prognostic model would improve decision-making in these subtypes. Moreover, SCN3B expression positively correlated with the presence of key immune cells and negatively correlated with several immune checkpoint inhibitors. This suggests potential roles in modulating immune responses in glioma. Thus, SCN3B emerges as a promising potential prognostic biomarker for glioma, especially for oligodendroglioma. Its dual correlations with prognosis and immune regulation present a compelling case for further experimental and clinical investigations to establish its utility in enhancing glioma management strategies. These findings underscore the importance of integrating novel biomarkers with traditional prognostic models to refine treatment paradigms and improve patient outcomes.

Flexocatalysis Enhances Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) is long-standing suffered from elevated tumor interstitial fluid pressure (TIFP) and prevalent hypoxic microenvironment within the solid malignancies. Herein, sound-activated flexocatalysis is developed to overcome the dilemma of PDT through both enhancing tumor penetration of photosensitizers by reducing TIFP and establishing an oxygen-rich microenvironment. In detail, a Schottky junction is constructed by flexocatalyst MoSe2 nanoflowers and Pt. Subsequently, the Schottky junction is loaded with the photosensitizer indocyanine green (ICG) and encapsulated within tumor cytomembrane to constitute a bionic-flexocatalytic nanomedicine (MPI@M). After targeting the tumor, MPI@M orchestrates flexocatalytic water splitting in tumor interstitial fluid under acoustic stimulation to lower TIFP, which boosted the tumor penetration of ICG. Concurrently, the oxygen released from the flexocatalytic water splitting overcomes the limitation of hypoxia against PDT. Furthermore, superfluous singlet oxygen generated by PDT can induce mitochondrial dysfunction for further tumor cell apoptosis. After 60 min of flexocatalysis, both the 30% decrease of TIFP and the relieved tumor hypoxia are observed, significantly promoting the therapeutic effect of PDT. Consequently, MoSe2/Pt junction nanoflowers, with the excellent flexocatalytic performance, hold significant potential for future applications in biocatalytic cancer therapies.

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.

Identification of molecular targets of Hypericum perforatum in blood for major depressive disorder: a machine-learning pharmacological study.

BACKGROUND: Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Hypericum perforatum (HP) is a traditional herb that has been shown to have antidepressant effects, but its mechanism is unclear. This study aims to identify the molecular targets of HP for the treatment of MDD. METHODS: We performed differential analysis and weighted gene co-expression network analysis (WGCNA) with blood mRNA expression cohort of MDD and healthy control to identify DEGs and significant module genes (gene list 1). Three databases, CTD, DisGeNET, and GeneCards, were used to retrieve MDD-related gene intersections to obtain MDD-predicted targets (gene list 2). The validated targets were retrieved from the TCMSP database (gene list 3). Based on these three gene lists, 13 key pathways were identified. The PPI network was constructed by extracting the intersection of genes and HP-validated targets on all key pathways. Key therapeutic targets were obtained using MCODE and machine learning (LASSO, SVM-RFE). Clinical diagnostic assessments (Nomogram, Correlation, Intergroup expression), and gene set enrichment analysis (GSEA) were performed for the key targets. In addition, immune cell analysis was performed on the blood mRNA expression cohort of MDD to explore the association between the key targets and immune cells. Finally, molecular docking prediction was performed for the targets of HP active ingredients on MDD. RESULTS: Differential expression analysis and WGCNA module analysis yielded 933 potential targets for MDD. Three disease databases were intersected with 982 MDD-predicted targets. The TCMSP retrieved 275 valid targets for HP. Separate enrichment analysis intersected 13 key pathways. Five key targets (AKT1, MAPK1, MYC, EGF, HSP90AA1) were finally screened based on all enriched genes and HP valid targets. Combined with the signaling pathway and immune cell analysis suggested the effect of peripheral immunity on MDD and the important role of neutrophils in immune inflammation. Finally, the binding of HP active ingredients (quercetin, kaempferol, and luteolin) and all 5 key targets were predicted based on molecular docking. CONCLUSIONS: The active constituents of Hypericum perforatum can act on MDD and key targets and pathways of this action were identified.

Identification of the novel exhausted T cell CD8 + markers in breast cancer.

Cancer is one of the most concerning public health issues and breast cancer is one of the most common cancers in the world. The immune cells within the tumor microenvironment regulate cancer development. In this study, single immune cell data sets were used to identify marker gene sets for exhausted CD8 + T cells (CD8Tex) in breast cancer. Machine learning methods were used to cluster subtypes and establish the prognostic models with breast cancer bulk data using the gene sets to evaluate the impacts of CD8Tex. We analyzed breast cancer overexpressing and survival-associated marker genes and identified CD8Tex hub genes in the protein-protein-interaction network. The relevance of the hub genes for CD8 + T-cells in breast cancer was evaluated. The clinical associations of the hub genes were analyzed using bulk sequencing data and spatial sequencing data. The pan-cancer expression, survival, and immune association of the hub genes were analyzed. We identified biomarker gene sets for CD8Tex in breast cancer. CD8Tex-based subtyping systems and prognostic models performed well in the separation of patients with different immune relevance and survival. CRTAM, CLEC2D, and KLRB1 were identified as CD8Tex hub genes and were demonstrated to have potential clinical relevance and immune therapy impact. This study provides a unique view of the critical CD8Tex hub genes for cancer immune therapy.

Voltage-gated sodium channels in cancers.

Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from "non-excitable" tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers. Here, we review the expression patterns of all nine VGSC α-subunit genes (SCN1A-11A) and their four regulatory ß-subunit genes (SCN1B-4B). We reviewed data from the Cancer Genome Atlas (TCGA) database, complemented by an extensive search of the published papers. We summarized and reviewed previous independent studies and analyzed the VGSC genes in the TCGA database regarding the potential impact of VGSC on cancers. A comparison between evidence gathered from independent studies and data review was performed to scrutinize potential biases in prior research and provide insights into future research directions. The review supports the view that VGSCs play an important role in diagnostics as well as therapeutics of some cancer types, such as breast, colon, prostate, and lung cancer. This paper provides an overview of the current knowledge on voltage-gated sodium channels in cancer, as well as potential avenues for further research. While further research is required to fully understand the role of VGSCs in cancer, the potential of VGSCs for clinical diagnosis and treatment is promising.

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.

Chebulinic acid isolated from aqueous extracts of Terminalia chebula Retz inhibits Helicobacter pylori infection by potential binding to Cag A protein and regulating adhesion.

Background: Terminalia chebula Retz, known as the King of Tibet, is considered a functional food in China, celebrated for its antioxidant, immune-modulating, antibacterial, and anti-inflammatory properties. Chebulinic acid, derived from aqueous extracts of Terminalia chebula Retz, is known for its anti-inflammatory properties. However, its potential as an anti-Helicobacter pylori (HP) agent has not been fully explored. Methods: Herein, we extracted the main compound from Terminalia chebula Retz using a semi-preparative liquid chromatography (LC) system and identified compound 5 as chebulinic acid through Ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). To evaluate its role, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, scanning electron microscope (SEM) imaging, inhibiting kinetics curves, urea fast test, cell counting kit-8 (CCK-8) assay, western blot analysis, griess reagent system, and molecular docking. Results: Our results showed that chebulinic acid effectively inhibited the growth of the HP strain ATCC 700392, damaged the HP structure, and exhibited selective antimicrobial activity without affecting normal epithelial cells GES-1. Importantly, it suppressed the expression of Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Molecular docking analysis predicted a strong affinity (-9.7 kcal/mol) between chebulinic acid and Cag A protein. Conclusion: Overall, our findings suggest that chebulinic acid acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, which is a critical step in HP infection. It also suppresses the Cag A protein. These results highlight the potential of chebulinic acid against HP infections.

Helicobacter pylori infection facilitates cell migration and potentially impact clinical outcomes in gastric cancer.

Gastric cancer is a significant health concern worldwide. Helicobacter pylori (HP) infection is associated with gastric cancer risk, but differences between HP-infected and HP-free gastric cancer have not been studied sufficiently. The objective of this study was to investigate the effects of HP infection on the viability and migration of gastric cancer cells and identify potential underlying genetic mechanisms as well as their clinical relevance. Cell counting kit-8, lactate dehydrogenase, wound healing, and transwell assay were applied in the infection model of multiple clones of HP and multiple gastric cancer cell lines. Genes related to HP infection were identified using bioinformatics analysis and subsequently validated using real-time quantitative PCR. The association of these genes with immunity and drug sensitivity of gastric cancer was analyzed. Results showed that HP has no significant impact on viability but increases the migration of gastric cancer cells. We identified 1405 HP-upregulated genes, with their enriched terms relating to cell migration, drug, and immunity. Among these genes, the 82 genes associated with survival showed a significant impact on gastric cancer in consensus clustering and LASSO prognostic model. The top 10 hub HP-associated genes were further identified, and 7 of them were validated in HP-infected cells using real-time quantitative PCR, including ERBB4, DNER, BRINP2, KCTD16, MAPK4, THPO, and VSTM2L. The overexpression experiment showed that KCTD16 medicated the effect of HP on gastric cancer migration. Our findings suggest that HP infection may enhance the migratory potential of gastric cancer cells and these genes might be associated with immunity and drug sensitivity of gastric cancer. In human subjects with gastric cancer, HP presence in tumors may affect migration, immunity, and drug sensitivity.

Near-infrared-II photocharging nanozyme for enhanced tumor immunotherapy.

In tumor therapy, copper (Cu)-based nanozymes with peroxidase-like activity play a crucial role in converting hydrogen peroxide into hydroxyl radicals (OH). This process induces immunogenic cell death, which in turn activates the body's immune response, enhancing the efficacy of tumor immunotherapy. Nonetheless, the efficiency of this reaction is curtailed due to the oxidation of Cu(I) to Cu(II), leading to the self-depletion of the nanozyme's activity and an insufficient yield of OH for effective immunotherapeutic activation. To surmount this challenge, our research introduces a photocharging self-doped semiconductor nanozyme, copper sulfide (Cu9S8). The photocharging effect enables the nanozyme to convert internal Cu(II) back to Cu(I) through charge transfer induced by near-infrared (NIR)-II photothermal energy, thereby effectively maintaining the enzyme-like activity of the nanozyme. Additionally, Cu9S8 is enhanced with a calcium sulfide (CaS) coating. This coating reacts in the acidic microenvironment of tumors to generate hydrogen sulfide (H2S) gas, which in turn suppresses the catalase activity inherent in tumor cells, ensuring a plentiful supply of H2O2 for the nanozyme's operation. This dual strategy of amplifying enzyme-like activity and substrate availability culminates in the generation of ample OH within tumor cells, leading to significant immunogenic cell death and thereby realizing potent immunotherapy.

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.