Comprehensiveness cuproptosis related genes study for prognosis and medication sensitiveness across cancers, and validation in prostate cancer.

Cuproptosis-related genes (CRGs) are important for tumor development. However, the functions of CRGs across cancers remain obscure. We performed a pan-cancer investigation to reveal the roles of CRGs across cancers. In an analysis of 26 cancers, 12 CRGs were differentially expressed, and those CRGs were found to have prognostic value across different cancer types. The expression of CRGs exhibited varied among tumors of 6 immune subtypes and were significantly correlated with the 16 sensitivities of drugs. The expression of CRGs were highly correlated with immunological subtype and tumor microenvironment (TME) of prostate cancer. We also established CRGs-related prognostic signatures that closely correlated with prognosis and drug sensitivity of prostate cancer patients. Single-cell RNA-seq revealed that several CRGs were enriched in the cancer cells. Finally, an in vitro experiment showed that elesclomol, a cuproptosis inducer, targets ferredoxin 1 and suppress cell viability in prostate cancer cells. In conclusion, we carried out a comprehensive investigation for determining CRGs in differential expression, prognosis, immunological subtype, TME, and cancer treatment sensitivity across 26 malignancies; and validated the results in prostate cancer. Our research improves pan-cancer knowledge of CRGs and identifies more effective immunotherapy strategies.

Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction.

Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis-benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 µg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH-DA staining suggested its anti-Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N-acetyl-cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti-Candida therapies.

Colorimetric detection of circulating tumor cells in breast cancer based on ladder-branch hybridization chain reaction and DFs/AuNCs nanozyme.

Breast cancer is the most common malignant tumor in women, which accounts for 6.9% of all cancer-related deaths. Early diagnosis is crucial for making the best clinical decision and improving the prognosis of patients. Circulating tumor cells (CTCs) have been regarded as significant tumor biomarkers. Herein, we designed a colorimetric biosensor for breast cancer CTCs quantification based on ladder-branch hybridization chain reaction (HCR) and DNA flowers/gold nanoclusters (DFs/AuNCs) nanozyme. With the assistance of complementary DNA labeled on magnetic beads (MBs), the cleavage products of RNA-cleaving DNAzymes (RCDs) could be rapidly captured, subsequently triggering ladder-branch HCR. In addition, the DFs/AuNCs nanozyme was applied for colorimetric analysis, which further improved the sensitivity for the detection of target CTCs. Benefiting from specific RCDs, ladder-branch HCR and DFs/AuNCs, we achieved a superior detection limit of 3 cells/mL as well as a broad linear range of 10 cells/mL to 104 cells/mL. Conclusively, this colorimetric biosensor achieved sensitively and selectively detection of breast cancer CTCs without the participation of enzymes at room temperature, which might provide new insight into the early detection of breast cancer.

Cell Membrane Camouflaged Biomimetic Nanoparticles as a Versatile Platform for Brain Diseases Treatment.

Although there are various advancements in biomedical in the past few decades, there are still challenges in the treatment of brain diseases. The main difficulties are the inability to deliver a therapeutic dose of the drug to the brain through the blood-brain barrier (BBB) and the serious side effects of the drug. Thus, it is essential to select biocompatible drug carriers and novel therapeutic tools to better enhance the effect of brain disease treatment. In recent years, biomimetic nanoparticles (BNPs) based on natural cell membranes, which have excellent biocompatibility and low immunogenicity, are widely used in the treatment of brain diseases to enable the drug to successfully cross the BBB and target brain lesions. BNPs can prolong the circulation time in vivo, are more conducive to drug aggregation in brain lesions. Cell membranes (CMs) from cancer cells (CCs), red blood cells (RBCs), white blood cells (WBCs), and so on are used as biomimetic coatings for nanoparticles (NPs) to achieve the ability to target, evade clearance, or stimulate the immune system. This review summarizes the application of different cell sources as BNPs coatings in the treatment of brain diseases and discusses the possibilities and challenges of clinical translation.

Using Pharmacokinetic-Pharmacodynamic Modeling to Study the Main Active Substances of the Anticancer Effect in Mice from Panax ginseng-Ophiopogon japonicus.

Ginseng Radix et Rhizoma Rubra (Panax ginseng C.A. Mey, Hongshen, in Chinese) and Ophiopogonis Radix (Ophiopogon japonicus (L.f) Ker-Gawl., Maidong, in Chinese) are traditional Chinese herbal pairs, which were clinically employed to enhance the immune system of cancer patients. This study employed the pharmacokinetic and pharmacodynamic (PK-PD) spectrum-effect association model to investigate the antitumor active substances of P. ginseng and O. japonicus (PG-OJ). The metabolic processes of 20 major bioactive components were analyzed using Ultra-Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (UPLC-MS/MS) in the lung tissue of tumor-bearing mice treated with PG-OJ. The ELISA method was employed to detect the levels of TGF-ß1, TNF-α, and IFN-γ in the lung tissue of mice at various time points, and to analyze their changes after drug administration. The results showed that all components presented a multiple peaks absorption pattern within 0.083 to 24 h post-drug administration. The tumor inhibition rate of tumor and repair rate of IFN-γ, TNF-α, and TGF-ß1 all increased, indicating a positive therapeutic effect of PG-OJ on A549 tumor-bearing mice. Finally, a PK-PD model based on the GBDT algorithm was developed for the first time to speculate that Methylophiopogonanone A, Methylophiopogonanone B, Ginsenoside Rb1, and Notoginsenoside R1 are the main active components in PG-OJ for lung cancer treatment.

Pretreatment with Daudi cells eliminates anti-CD47 monoclonal antibody interference in immunohematology testing.

BACKGROUND: Anti-CD47 monoclonal antibodies have increasing clinical applications in the treatment of cancer. However, anti-CD47 monoclonal antibodies interfere with immunohematology testing in patients who require blood transfusion. As the current approaches to removing any interferences have technical problems, new methods need to be developed to resolve anti-CD47 interference in immunohematology testing. MATERIALS AND METHODS: We evaluated the Daudi cell line for the adsorption of free anti-CD47 monoclonal antibodies from patients' plasma to facilitate immunohematology testing in patients treated with anti-CD47 monoclonal antibody. CD47 expression was identified on the Daudi cells using flow cytometry and confocal microscopy. Next, we tested the ability of intact Daudi cells mixed with simulating plasma and clinical samples to achieve efficient removal of interfering anti-CD47 monoclonal antibodies. The indirect antiglobulin test was used to verify whether interference from anti-CD47 monoclonal antibodies in plasma was eliminated and whether the detection of other irregular antibodies was affected. The effect of eliminating interference was also investigated in relation to the time that the Daudi cells were stored after having been fixed with paraformaldehyde. RESULTS: CD47 expression was higher on Daudi cells than on red blood cells. Analysis of the indirect antiglobulin test results revealed that anti-CD47 monoclonal antibody-treated patients' plasma absorbed by Daudi cells for 15 min at 37°C could completely prevent the interference of anti-CD47 monoclonal antibodies in immunohematology testing while the detection of the tested antibodies, including anti-D and anti-K, was unaffected. DISCUSSION: By decreasing the incubation time, we discovered that interferences in samples with agglutination strengths below 2+ could be eliminated after incubation for 5 min. Of importance, Daudi cells can be preserved with 4% paraformaldehyde for 14 days as short-term storage reagents. This is the first study in which Daudi cells were used to effectively resolve the interference of anti-CD47 monoclonal antibodies in pretransfusion tests.

Antifungal and anti-biofilm activities of patchouli alcohol against Candida albicans.

The opportunistic fungal pathogen Candida albicans could cause severe clinical outcomes which could be exacerbated by the scarcity of antifungals. The capacity of C. albicans to form biofilms on medical devices that are hard to eradicate, further deepen the need to develop antifungal agents. In this study, we, for the first time, showed that patchouli alcohol (PA) can inhibit the growth of multiple C. albicans strains, as well as four other Candida species, with MICs of 64 µg/mL and MFCs from 64 to 128 µg/mL. The biofilm formation and development, adhesion, yeast-to-hyphal transition and extracellular polysaccharide of C. albicans can be inhibited by PA in a concentration-dependent manner. Confocal microscopy analyses of cells treated with PA showed that PA can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. In C. elegans, PA did not influence the survival below 64 µg/mL. In this study PA demonstrated antifungal and antibiofilm activity against C. albicans and our results showed the potential of developing PA to fight Candida infections.

Research progress in cardiotoxicity of organophosphate esters.

Organophosphate esters (OPEs) have been extensively utilized worldwide as a substitution for brominated flame retardants. With an increased awareness of the need for environmental protection, the potential health risks and ecological hazards of OPEs have attracted widespread attention. As the dynamic organ of the circulatory system, the heart plays a significant role in maintaining normal life activities. Currently, there is a lack of systematic appraisal of the cardiotoxicity of OPEs. This article summarized the effects of OPEs on the morphological structure and physiological functions of the heart. It is found that these chemicals can lead to pericardial edema, abnormal looping, and thinning of atrioventricular walls in the heart, accompanied by alterations in heart rate, with toxic effects varying by the OPE type. These effects are primarily associated with the activation of endoplasmic reticulum stress response, the perturbation of cytoplasmic and intranuclear signal transduction pathways in cardiomyocytes. This paper provides a theoretical basis for further understanding of the toxic effects of OPEs and contributes to environmental protection and OPEs' ecological risk assessment.

Pancancer analysis of the correlations of HS6ST2 with prognosis, tumor immunity, and drug resistance.

HS6ST2 has ability to encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS and a crucial regulator of cell growth, differentiation, adhesion, and migration. Although mounting evidence supports a vital role for HS6ST2 in tumorigenesis of some cancers, no pan-cancer analysis of HS6ST2 has been reported. Therefore, we aimed to explore the prognostic value of HS6ST2 in 33 cancer types and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Lines Encyclopedia, Genotype Tissue Expression, and GSCA, we used a range of bioinformatics approaches to explore the potential carcinogenic role of HS6ST2, analysis of HS6ST2 and prognosis, DNA methylation, RNA methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and immune cell infiltration in different tumors. The results show that HS6ST2 was highly expressed in most cancers but lower in Breast invasive carcinoma, Kidney Chromophobe, Kidney renal clear cell carcinoma, Kidney renal papillary cell carcinoma, and Uterine Corpus Endometrial Carcinoma. Moreover, HS6ST2 is positively or negatively associated with prognosis in different cancers. HS6ST2 expression was not only associated with MSI in 5 cancer types and associated with TMB in 10 cancer types, and it's significantly correlated with DNA methylation in 13 types of cancer, but it's correlated with RNA methylation related genes in most cancer. HS6ST2 expression was correlated with immune cell infiltration, immune-related genes, tumor immune microenvironment, and drug resistance in various cancers. Eventually, HS6ST2 was validated in human lung adenocarcinoma tissues. Our study reveals that HS6ST2 can function as a prognostic marker in various malignant tumors because of its role in tumorigenesis and tumor immunity.

The role of autophagy in the treatment of type II diabetes and its complications: a review.

Type II diabetes mellitus (T2DM) is a chronic metabolic disease characterized by prolonged hyperglycemia and insulin resistance (IR). Its incidence is increasing annually, posing a significant threat to human life and health. Consequently, there is an urgent requirement to discover effective drugs and investigate the pathogenesis of T2DM. Autophagy plays a crucial role in maintaining normal islet structure. However, in a state of high glucose, autophagy is inhibited, resulting in impaired islet function, insulin resistance, and complications. Studies have shown that modulating autophagy through activation or inhibition can have a positive impact on the treatment of T2DM and its complications. However, it is important to note that the specific regulatory mechanisms vary depending on the target organ. This review explores the role of autophagy in the pathogenesis of T2DM, taking into account both genetic and external factors. It also provides a summary of reported chemical drugs and traditional Chinese medicine that target the autophagic pathway for the treatment of T2DM and its complications.

Polyphyllin I, a strong antifungal compound against Candida albicans.

This study was performed to explore the antifungal and antibiofilm effects of polyphyllin I (PPI) on Candida albicans. Microdilution assay was performed to determine the minimal inhibitory concentrations (MIC) of PPI against Candida species. Adhesion assay, hyphal growth assay, biofilm formation, and development were used to test the impacts of PPI on C. albicans virulence factors. Propidium iodide staining was performed to test whether the permeability of cell membrane was influenced by PPI. PPI showed significant antifungal activities against several Candida species, with MIC below or equal to 6.25 µM. PPI also inhibited the adhesion to polystyrene surfaces, hyphal growth, and biofilm formation. PPI significantly increased the permeability of C. albicans cell membrane. In sum, PPI can suppress the planktonic growth and biofilm of C. albicans and its mechanism involves the increased permeability of cell membrane.

Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma.

Lens epithelium-derived growth factor (LEDGF/p75) is a reader of epigenetic marks and a potential target for therapeutic intervention. Its involvement in human immunodeficiency virus (HIV) integration and the development of leukemia driven by MLL (also known as KMT2A) gene fusion make it an attractive candidate for drug development. However, exploration of LEDGF/p75 as an epigenetic reader of H3K36me3 in tumors is limited. Here, for the first time, we analyze the role of LEDGF/p75 in multiple cancers via multiple online databases and in vitro experiments. We used pancancer bulk sequencing data and online tools to analyze correlations of LEDGF/p75 with prognosis, genomic instability, DNA damage repair, prognostic alternative splicing, protein interactions, and tumor immunity. In summary, the present study identified that LEDGF/p75 may serve as a prognostic predictor for tumors such as adrenocortical carcinoma, kidney chromophobe, liver hepatocellular carcinoma, pancreatic adenocarcinoma, skin cutaneous melanoma, and clear cell renal cell carcinoma (ccRCC). In addition, in vitro experiments and gene microarray sequencing were performed to explore the function of LEDGF/p75 in ccRCC, providing new insights into the pathogenesis of the nonmutated SETD2 ccRCC subtype.

Hypocalcemic cataract secondary to idiopathic hypoparathyroidism in an adolescent.

Idiopathic hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia secondary to inadequate parathyroid hormone secretion. Hypocalcemia-related cataract is most often observed in patients with postoperative hypoparathyroidism, whereas primary hypoparathyroidism-related cataract is rare and displays slow progression. Cataract usually occurs in people aged 18 to 50 years. Here, we describe a 17-year-old boy with bilateral cataract and a history of hypocalcemic tetany who was diagnosed with idiopathic hypoparathyroidism. Phacoemulsification with implantation of a monofocal aspherical intraocular lens was performed in the right eye; 6 months later, it was performed in the left eye. Elevated phosphorus and diminished calcium were observed in blood and aqueous humor. A deep anterior chamber, relatively thin central corneal thickness, large white-to-white distance, and thin lens were also observed. During follow-up, neither eye displayed intraocular lens decentration; best-corrected visual acuity was 20/20 in both eyes. These findings suggest that ophthalmologists should be vigilant when hypocalcemic tetany and cataract are present, especially in adolescents and young adults.

Dehydrocostus lactone inhibits Candida albicans growth and biofilm formation.

Candida albicans infections are threatening public health but there are only several antifungal drugs available. This study was to assess the effects of dehydrocostus lactone (DL) on the Candida albicans growth and biofilms Microdilution assays revealed that DL inhibits a panel of standard Candida species, including C. albicans, as well as 9 C. albicans clinical isolates. The morphological transition of C. albicans in RPMI-1640 medium and the adhesion to polystyrene surfaces can also be decreased by DL treatment, as evidenced by microscopic, metabolic activity and colony forming unit (CFU) counting assays. The XTT assay and microscopy inspection demonstrated that DL can inhibit the biofilms of C. albicans. Confocal microscopy following propidium iodide (PI) staining and DCFH-DA staining after DL treatment revealed that DL can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. N-acetyl-cysteine could mitigate the inhibitory effects of DL on growth, morphological transition and biofilm formation, further confirming that ROS production induced by DL contributes to its antifungal and antibiofilm effects. This study showed that DL demonstrated antifungal and antibiofilm activity against C. albicans. The antifungal mechanisms may involve membrane damage and ROS overproduction. This study shows the potential of DL to fight Candida infections.

A pan-cancer analysis of DDR1 in prognostic signature and tumor immunity, drug resistance.

Disk-like domain receptor 1 (DDR1) is a crucial regulator of pro-inflammatory mediators and matrix-degrading enzymes. Although mounting evidence supports a vital role for DDR1 in the tumorigenesis of some cancers, no pan-cancer analysis of DDR1 has been reported. Therefore, we aimed to explore the prognostic value of DDR1 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of DDR1 in multiple cancers. We found that DDR1 was expressed at high levels in most cancers. DDR1 expression was positively or negatively associated with prognosis in different cancers. DDR1 expression was significantly associated with DNA methylation in 8 cancers, while there was a correlation between DDR1 expression and RNA methylation-related genes and mismatch repair gene in most cancers. Furthermore, DDR1 expression was significantly associated with microsatellite instability in 6 cancers and tumor mutation burden in 11 cancers. In addition, DDR1 expression was also significantly correlated with immune cell infiltration, tumor microenvironment, immune-related genes, and drug resistance in various cancers. In conclusion, DDR1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

Cyasterone inhibits IL-1ß-mediated apoptosis and inflammation via the NF-κB and MAPK signaling pathways in rat chondrocytes and ameliorates osteoarthritisin vivo.

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1ß and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1ß in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.

The clinical effect of modified slow Mohs circular skin biopsy on penoscrotal extramammary Paget's disease.

OBJECTIVE: Determining the tumor margin is the main problem in penoscrotal extramammary Paget's disease (PEMPD) surgery. This study aimed to explore the role of modified slow Mohs circular skin biopsy in determining the tumor margin in patients with PEMPD before operation. METHODS: Thirty-six PEMPD patients were divided into the control group and the observation group according to the simple randomization method. The control group, which consisted of 16 patients, underwent wide local excision, and the observation group, which consisted of 20 patients, underwent a modified slow Mohs circular skin biopsy to determine the tumor margin before surgery. The duration of surgery, number of frozen sections, satisfaction with the appearance of the skin, tumor recurrence rate, and incidence of functional sequelae were statistically analyzed. RESULTS: The number of frozen sections, duration of surgery, incidence of functional sequelae, and tumor recurrence rate in the observation group were lower than in the control group. The satisfaction with the appearance of the skin was higher in the observation group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Modified slow Mohs circular skin biopsy can determine the tumor margin before surgery and reduce the number of frozen sections, tumor recurrence rate, and the incidence of functional sequelae. It also increases the postoperative satisfaction of patients.

The combination of ginger and zinc supplement could improve lead-induced reproductive dysfunction by inhibiting apoptosis mediated by oxidative damage and inflammation.

Due to the growing industry and industrialization of many urban communities, one of the dangers that threaten human life is long-term exposure to heavy metals such as lead. Lead contamination can have a detrimental effect on fertility. On the other hand, the combination of ginger and zinc supplements can be a powerful sexual enhancer. Despite extensive studies on the effect of ginger and zinc on reproduction, the effects of the combination of ginger and zinc supplement on lead-induced reproductive dysfunction are not fully understood. Sixty-four adult male rats were allocated into control, lead acetate (10 mg/kg), ginger (250 mg/kg), ginger-lead group, zinc (120 mg/kg) group, zinc-lead group, ginger-zinc group and ginger-zinc-lead group. The drugs were administrated by gavage for 4 weeks. The concentration of LH, FSH, testosterone, TNF-α, IL-1ß, antioxidant enzyme activity, MDA, spermatogenesis, and sperm parameters were measured. The expression of NF-kB, Nrf2, Bcl2, BAX, and Cas-3 was evaluated. The histopathological assessment was also detected. Lead significantly could induce inflammation, apoptosis, and oxidative damage in testis tissue, and decrease hormonal levels, spermatogenesis, and sperm parameters compared to the control group (p < 0.05). While in reverse manner ginger, zinc, and their combination significantly improved all of them compared to the lead group (p < 0.05). These results were also supported by histological findings. It can be concluded that ginger, zinc, and their combination could prevent lead-induced reproductive dysfunction by inhibiting apoptosis mediated by oxidative damage and inflammation and improve reproductive performance.

Alkyl-Substituted N,S-Embedded Heterocycloarenes with a Planar Aromatic Configuration for Hosting Fullerenes and Organic Field-Effect Transistors.

Cycloarenes and heterocycloarenes display unique physical structures and hold great potential as organic semiconductors. However, the synthesis of (hetero)cycloarenes remains a big challenge, and there are limited reports on their applications. Herein, a series of nitrogen- and sulfur-codoped cycloarenes NS-Octulene-n (n = 2, 3, 4) with branched alkyl substituents containing linear spacer groups from C2 to C4 have been conveniently synthesized. Compared with their isoelectronic analogues Octulene and S-Octulene, both having a saddle-shaped configuration, the coincorporation of two nitrogen atoms and two sulfur atoms leads to a fully coplanar aromatic backbone structure. Each of these three planar heterocycloarenes acts as a supramolecular host for encapsulation of both fullerenes C60 and C70 with a stronger donor-acceptor interaction for the complexation between the heterocycloarene and C70 due to the unique molecular geometry and defined cavity. Meanwhile, the electron-rich nitrogen atoms also slightly increase the energies of both highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in this series of planar heterocycloarenes, indicating that they can be used as p-type semiconductors. Most importantly, benefitting from the planar π-conjugated backbone structure accompanied by excellent crystallinity and ordered molecular packing, as well as upon the engineering of the alkyl chain branching position, thin-film field-effect transistors of NS-Octulene-3 with moderate alkyl branching point exhibit the maximum hole mobility of 0.86 cm2 V-1 s-1, which is the highest for (hetero)cycloarene-based organic semiconductors. This study will shed new light on designing novel high-performance macrocyclic polycyclic aromatic hydrocarbon (PAH) semiconductors.

Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: A pan-cancer analysis.

Ferredoxin 1 (FDX1) functions by transferring electrons from NADPH to mitochondrial cytochrome P450 via the ferredoxin reductase and is the key regulator in copper-dependent cell death. Although mounting evidence supports a vital role for FDX1 in tumorigenesis of some cancers, no pan-cancer analysis of FDX1 has been reported. Therefore, we aimed to explore the prognostic value of FDX1 in pan-cancer and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, Human Protein Atlas, and Gene Set Cancer Analysis, we used a range of bioinformatics approaches to explore the potential carcinogenic role of FDX1, including analyzing the relationship between FDX1 expression and prognosis, DNA methylation, RNA methylation-related genes, mismatch repair (MMR) gene, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), immune-related genes, and drug sensitivity in different tumors. The results show that FDX1 was lowly expressed in most cancers but higher in glioblastoma multiforme, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Moreover, FDX1 expression was positively or negatively associated with prognosis in different cancers. FDX1 expression was significantly associated with DNA methylation in 6 cancers, while there was a correlation between FDX1 expression and RNA methylation-related genes and MMR gene in most cancers. Furthermore, FDX1 expression was significantly associated with MSI in 8 cancers and TMB in 10 cancers. In addition, FDX1 expression was also significantly correlated with immune cell infiltration, immune-related genes, TME, and drug resistance in various cancers. An experiment in vitro showed FDX1 is downregulated by elesclomol, resulting in inhibiting cell viability of bladder cancer, clear cell renal cell carcinoma, and prostate cancer cells. Our study reveals that FDX1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.