A photoelectrochemical biosensor based on self-calibration platform of carbon-rich plasmonic probe with near-infrared driving signal amplification.

Exploring the photochemical (PEC) method induced by low-energy light source makes great significance to achieve high stability and accurate analysis. A sensing platform driven by near-infrared (NIR) light was designed by making the biochemically encoded carbon rich plasmonic hybrid (CPH) probe, the peptide@C-Mo2C. The inherent plasmonic effect of C-Mo2C CPH can directly absorb NIR light, thus starting effective electronic-hole pairs separation. Moreover, the photothermal effect of C-Mo2C CPH also promoted the reaction yield of photothermal catalyst reaction on sensing interface to assist the PEC signal amplification. In the presence of target trypsin, it cleaves the peptides, resulting in the release of peptide@C-Mo2C probe from interface, which leads to a relative decrease in PEC signal. More importantly, a self-calibration system consisting of two independent PEC test channels attempted to eliminate the influence of background signal and baseline drift. The test channel was used to specify the recognition target, while the blank channel was used as a reference. Therefore, the signal difference between two channels was recorded, so as to obtain results with less error and higher stability. In this NIR driven PEC sensor, the carbon rich probe with direct and efficient NIR light conversion promoted the sensitivity and a self-calibration system guaranteed the stability which provided innovative thoughts for developing ingenious PEC sensor.

Potential therapies targeting nuclear metabolic regulation in cancer.

The interplay between genetic alterations and metabolic dysregulation is increasingly recognized as a pivotal axis in cancer pathogenesis. Both elements are mutually reinforcing, thereby expediting the ontogeny and progression of malignant neoplasms. Intriguingly, recent findings have highlighted the translocation of metabolites and metabolic enzymes from the cytoplasm into the nuclear compartment, where they appear to be intimately associated with tumor cell proliferation. Despite these advancements, significant gaps persist in our understanding of their specific roles within the nuclear milieu, their modulatory effects on gene transcription and cellular proliferation, and the intricacies of their coordination with the genomic landscape. In this comprehensive review, we endeavor to elucidate the regulatory landscape of metabolic signaling within the nuclear domain, namely nuclear metabolic signaling involving metabolites and metabolic enzymes. We explore the roles and molecular mechanisms through which metabolic flux and enzymatic activity impact critical nuclear processes, including epigenetic modulation, DNA damage repair, and gene expression regulation. In conclusion, we underscore the paramount significance of nuclear metabolic signaling in cancer biology and enumerate potential therapeutic targets, associated pharmacological interventions, and implications for clinical applications. Importantly, these emergent findings not only augment our conceptual understanding of tumoral metabolism but also herald the potential for innovative therapeutic paradigms targeting the metabolism-genome transcriptional axis.

A gas-permeable, durable, and sensitive wearable strain sensor through thermal-radiation-promoted in situ welding.

A convenient strategy for fabricating a wearable sensor with favorable durability and sensitivity is reported. This approach exploits the reconstructed hydrogen bonds within the thermoplastic polyurethane (TPU) during the heating evaporation of metal to form robust welding of the fibers in the substrate. The sensor can steadily monitor pulse waves and facilitate real-time human-machine interaction.

Coiled-coil domain-containing 154 promotes colorectal cancer proliferation and metastasis via interacting with minichromosome maintenance complex component 2.

Coiled-Coil Domain-Containing (CCDC) is a large class of structural proteins containing left-handed supercoiled structure. The clinical value and the functional implication of CCDC in colorectal cancer (CRC) remain unknown. Based on the genetic, transcriptional, and clinical data from The Cancer Genome Atlas, five of thirty-six CCDC proteins were differentially expressed in the CRC and associated with the survival of patients with CRC. A CCDC-score model was established to evaluate the prognosis of patients. The potential function of Coiled-Coil Domain-Containing 154 (CCDC154) was investigated using bioinformatical methods, which unveiled that high expression of CCDC154 indicates poor survival for patients with CRC and correlates with low infiltration of CD8+ T cells and high infiltration of neutrophils, indicating that CCDC154 enhances tumor growth and metastasis. CCDC154 interacts with Minichromosome Maintenance Complex Component 2 (MCM2) protein and promotes malignant phenotype via MCM2. We validated the expression level and survival prediction value of CCDC154 in clinical samples, and analyzed its co-expression of MCM2, Ki-67 and p53. This work discloses the role of CCDC in clinical setting and CCDC154 functions in CRC.

A method framework of automatic localization and quantitative segmentation for the cavum septum pellucidum complex and the cerebellar vermis in fetal brain ultrasound images.

Background: Early detection of central nervous system (CNS) anomalies in human embryos through prenatal screening is crucial for timely intervention and improved patient outcomes. Fetal brain mid-sagittal ultrasound images (FBMUIs) play a pivotal role as a diagnostic tool for detecting structural abnormalities. However, the automatic localization and quantitative segmentation of complex anatomical structures such as the corpus callosum-cavum septum pellucidum complex (CCC) and cerebellar vermis (CV) in FBMUIs present significant challenges. Methods: To address this issue, we propose an integrated framework that combines anatomical knowledge with computer vision techniques. Our framework comprises four steps: (I) generation of average templates for CCC and CV local images using a variational autoencoder (VAE); (II) localizing the CCC by using the "Initial Localization-Accurate Localization-Result Detection" strategy, followed by segmenting it based on morphological characteristics using the "Initial Contour Fitting-Contour Iteration" strategy; (III) applying a similar strategy as CCC localization and CV segmentation; and (IV) leveraging spatial and morphological characteristics to achieve accurate localization and segmentation. Results: Our CCC and CV localization and segmentation methods were validated by using 140 FBMUIs from various perspectives. The accuracy and effectiveness of our approach were demonstrated through data statistics and comparative analysis. Currently, clinical trials are being conducted on our method at Shengjing Hospital of China Medical University. Conclusions: Our proposed integrated framework presents a novel solution for the automatic localization and quantitative segmentation of the CCC and CV in FBMUIs. It shows promise for early diagnosis of CNS anomalies in human embryos, offering significant clinical implications.

Designing Multimodal Informative Sensing with an Exosome-Mediated Signal Coupling Transduction Strategy Based on a Single-Stimulus Multiresponse Recognition Interface.

Given that exosomes released from cancer cells carry various tumor-specific proteins on their surface, they have emerged as a source of biomarkers for cancer diagnosis. However, developing accurate and reliable assays to detect exosomes in the early stages of disease with low abundance and complex systems remains challenging. Here, the prepared PDIG film has the ability to sense multiple signals from a single stimulus, in which the presence of cobalt(II) chloride and deep eutectic solvents (DES) endows PDIG with thermochromic and thermosensitive properties. Concretely, the PDIG served as the recognition interface in series with a bipolar electrode (BPE) that exhibits a highly sensitive color and conductivity response to temperature stimuli triggered by the light-harvesting probe TiO2@CNOs introduced via proximity hybridization assay triggering a rolling circle amplification strategy, resulting in the output of colorimetric, photoacoustic, and electrochemiluminescent signals for the detection of colorectal cancer exosomes. This work is expected to provide a new direction for exploring the multisignal amplification strategy of BPE, broaden the application of BPE in biological analysis, and provide new insights for developing highly information-sensing elements to ensure the multimodal coupling for cancer-specific exosome detection.

Nickel nanoparticle decorated silicon carbide as a thermal filler in thermal conductive aramid nanofiber-based composite films for heat dissipation applications.

Aramid nanofibers (ANFs) have shown potential applications in the fields of nanocomposite reinforcement, battery separators, thermal insulation and flexible electronics. However, the inherent low thermal conductivity limits the application of ANFs, currently, to ensure long lifetime in electronics. In this work, new nickel (Ni) nanoparticles were employed to decorate the silicon carbide (SiC) filler by a rapid and non-polluting method, in which nickel acetate tetrahydrate (Ni(CH3COO)2·4H2O) and SiC were mixed and heated under an inert atmosphere. The composites as thermal fillers were applied to prepare an aramid nanofiber (ANF)-based composite film. Our results showed that the decoration of SiC by an appropriate amount of Ni nanoparticles played an important role in improving the thermal conductivity, hydrophobicity, thermal stability, and puncture resistance of the ANF composite film. After adjusting the balling time at 10 h, the optimized content of 10 mol% Ni nanoparticles improved the thermal conductivity to 0.502 W m-1 K-1, 298.4% higher than that of the original ANF film. Moreover, increasing the content of thermal fillers to 30 wt% realized a high thermal conductivity of 0.937 W m-1 K-1, which is 643.7% higher than that of the pristine ANF film. Moreover, the compatibility between thermal fillers and ANFs and thermal stability were improved for the ANF-composite films. The effective heat transfer function of our composite films was further confirmed using a LED lamp and thermoelectric device. In addition, the obtained composite films show certain mechanical properties and better hydrophobicity; these results exhibit their great potential applications in electronic devices.

Two-phase dual-signal-readout immunosensing platform based on multifunctional carbon nano-onions for ovarian cancer biomarker detection.

In order to detect early tumor markers and gain valuable time for treatment, there is an urgent need to develop a fast, cheap, and ultrasensitive multi-reading sensing platform. Herein, a solid/liquid two-phase dual-output biosensor was explored based on a sensitized sonochemiluminescence (SCL) strategy and a multifunctional carbon nano-onion (CNO) probe. It is clear that ultrasonic radiation caused the formation of hydroxyl radicals (˙OH), triggering the SCL signal of the emitter lucigenin (Luc2+). Meanwhile, titanium carbide nanodots and ethanol were used to enhance the SCL signal, and an astonishingly linear enhancement of the SCL intensity was produced with increasing ethanol concentration. More importantly, the CNOs, with their excellent photothermal properties and adsorption capacity, can output both the temperature signal and an enhanced SCL strength from the solid-liquid phase. Through inter-calibration of the signals from the two-phases, this biosensor shows excellent analytical performance for the detection of the ovarian cancer biomarker, human epididymis-specific protein 4, from 10-5 to 10 ng mL-1 with a low detection limit of 3.3 fg mL-1. This work not only provides a novel two-phase signal-output mode that broadens the scope of multiperformance joint applications of CNOs, but also enriches the quantitative detection of point-of-care testing.

A pressure-colorimetric multimode system with photothermal activated multiple rolling signal amplification for ovarian cancer biomarker detection.

Utilizing the photothermal effect to activate enzyme activity, realize signal conversion and amplification show promising prospects in biosensing. Herein, a pressure-colorimetric multi-mode bio-sensor was proposed through the multiple rolling signal amplification strategy of photothermal control. Under NIR light radiation, the Nb2C MXene labeled photothermal probe caused notable temperature elevation on a multi-functional signal conversion paper (MSCP), leading to decomposition of thermal responsive element and in-situ formation of Nb2C MXene/Ag-Sx hybrid. The generation of Nb2C MXene/Ag-Sx hybrid accompanied with valid color change from pale yellow to dark brown on MSCP. Moreover, the Ag-Sx as a signal amplification element enhanced the NIR light absorption to further improve the photothermal effect of Nb2C MXene/Ag-Sx thereby induce cyclic in situ production of Nb2C MXene/Ag-Sx hybrid with rolling enhanced photothermal effect. Subsequently, the continuously enhanced photothermal effect rolling activated catalase-like activity of Nb2C MXene/Ag-Sx, which accelerated the decomposition of H2O2 and promoted the pressure elevation. Therefore, the rolling-enhanced photothermal effect and rolling activated catalase-like activity of Nb2C MXene/Ag-Sx considerately amplified the pressure and color change. Making full use of multi-signal readout conversion and rolling signal amplification, accurate results can be obtained in a short time, whether in the laboratory or in the patient's homes.

Optical and Acoustic Synergetic Sensing Platform Enabled by a Pyrene-Based Conjugated Polymer Self-Circulating Amplified System for Lung Cancer Detection.

A stable and reusable electrochemiluminescent (ECL) signal amplification strategy was proposed through a pyrene-based conjugated polymer (Py-CP) triggered self-circulating enhancement system. Specifically, the delocalized conjugated π-electrons of Py-CPs made it an excellent coreactant to arouse the initial ECL signal improvement of Ru(phen)32+, but the subsequent signal reduction was attributed to the consumption of Py-CPs, in which this stage was called the signal sensitization evoking phase (SSEP). Then, the maximum use of ECL luminescence of Ru(phen)32+ produced in the SSEP was made to irradiate the photosensitizer Py-CPs for in situ producing numerous ·OH, and a stronger and more stable ECL response stage defined as the signal sensitization stabilize phase was reached. Encouragingly, the incorporation of Nb2C MXene quantum dots with an exceptional physicochemical property not only foreshortens the SSEP for quickly acquiring a stable ECL signal but also introduces the photoacoustic (PA) transduce mechanism for achieving dual-signal outputting. Ultimately, the portable and miniaturized ECL-PA synergetic sensing platform based on the closed-bipolar electrode realized sensitive let-7a detection in a wide linear range from 10-9 to 10-2 nM with a low detection limit of 3.3 × 10-10 nM and also demonstrated good selectivity, excellent stability, and high reliability. The successful application of an innovative signal transduction mechanism and dexterous coupling modality will provide new insights for advancing the development of flexible analytical devices.

The casein-derived peptide YFYPEL alleviates intestinal epithelial cell dysfunction associated with NEC by regulating the PI3K/AKT signaling pathway.

Necrotizing enterocolitis (NEC) is a life-threatening risk to the health of neonates, but thus far, there is no very effective treatment. Although many studies have confirmed the therapeutic role of peptides in diseases, the effect of peptides in NEC remains poorly understood. This study investigated the role of casein-derived peptide YFYPEL in NEC cells and animal models. We synthesized YFYPEL and analysed its protective effects on NEC both in vitro and in vivo. YFYPEL integration in the intestine increased rat survival and clinical conditions, lowered the incidence of NEC, alleviated bowel inflammation, and enhanced intestinal cell migration. Furthermore, YFYPEL significantly decreased interleukin 6 expression and increased intestinal epithelial cell migration. Moreover, YFYPEL alleviated intestinal epithelial cell dysfunction through the PI3K/AKT pathway, as demonstrated by western blotting and bioinformatics analysis. A selective PI3K activator reversed the protective effect of YFYPEL on lipopolysaccharide-stimulated intestinal epithelial cells. Our study showed that YFYPEL reduced inflammatory cytokine expression and enhanced migration by regulating the PI3K/AKT pathway. The use of YFYPEL may thus develop into a novel modality in NEC treatment.

Diagnostic and economic value of carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4 in gastrointestinal cancers.

BACKGROUND: The diagnostic and economic value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale. AIM: To reassess the diagnostic and economic value of the three tumor biomarkers. METHODS: A retrospective analysis of all 32857 subjects who underwent CEA, CA19-9, CA72-4, gastroscopy and colonoscopy from October 2006 to May 2018 was conducted. Then, we assessed the discrimination and clinical usefulness. Total cost, cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes (gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive). RESULTS: The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer (CRC), while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers (GICs). Regarding early diagnosis, only CEA could be used for early CRC. The combination of biomarkers didn't greatly increase the area under the curve. The economic indicators of CEA were superior to those of CA19-9, CA72-4 and any combination. At the threshold of 1.8 µg/L to 10.4 µg/L, all four indicators of CEA were lower than those in the scheme that conducted gas-trointestinal endoscopy only. Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable. CONCLUSION: CEA had qualified diagnostic value for CRC and superior economic value for GICs, especially for elderly health checkup subjects. CA72-4 was not suitable as a diagnostic biomarker.

Photoredox-catalyzed trifluoromethylation of 2H-indazoles using TT-CF3+OTf- in ionic liquids.

A protocol for metal and oxidant free photoredox catalyzed trifluoromethylation of 2H-indazoles was developed by using Eosin Y as the photocatalyst and recoverable ionic liquids as the solvents. A series of trifluoromethylated products were obtained in moderate to good yields in this protocol under mild conditions. The reaction proceeded via a free-radical mechanism with a broad substrate range, excellent regioselectivity, and good functional group tolerance. Furthermore, the utility of this protocol was demonstrated by the synthesis of a highly selective ligand for estrogen receptor beta (ERß) and the drug granisetron. The protocol provides a mild and environmentally friendly solution for trifluoromethylation reaction.

Association of traditional Chinese medicine body constitution and cold syndrome with leukocyte mitochondrial functions: An observational study.

Body constitution in traditional Chinese medicine (TCM) refers to the holistic and relatively durable state of an individual, based on the qi and blood assessment, and TCM syndrome is defined as the theoretical abstraction of disease-symptom profiles. The biological basis as related to mitochondria, which produce most of the cellular energy, has not been well studied. This study aimed to elucidate the association of mitochondrial function with TCM body constitution and cold syndrome. Body constitution and cold syndrome in TCM were assessed using the Constitution in Chinese Medicine Questionnaire (CCMQ). The mitochondrial function of peripheral leukocytes was evaluated based on oxygen consumption rate (OCR) and enzyme activity; OCR reflects mitochondrial activity and the capacity to produce adenosine triphosphate (ATP). Cellular adenosine nucleotides and malondialdehyde levels were determined using high-performance liquid chromatography to assess the potential bioenergetic mechanisms. A total of 283 adults participated in this study. Leukocytes from subjects with a balanced constitution had higher OCRs than those with unbalanced constitutions. Yang deficiency and cold syndrome also demonstrated lower energy metabolism, as indicated by reduced basal metabolic rate and cellular levels of ATP and malondialdehyde. Decreased mitochondrial enzyme activity has been observed in individuals with the cold syndrome. Unbalanced body constitutions in TCM impair mitochondrial function in leukocytes, which may contribute to the high disease susceptibility. Cold syndrome is characterized by reduced mitochondrial mass, which may explain its symptoms of low-energy metabolism and cold intolerance.

Upregulation of LRRC8A by m5C modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer.

Cervical cancer (CC) is one of the most common gynecological malignancies with poor prognosis for advanced CC patients. LRRC8A is a volume-regulated anion channel protein involved in cellular homeostasis, but its role in CC remains largely unknown. In this study, we found that LRRC8A is elevated in CC and associated with poor prognosis. LRRC8A maintains cell survivals under the hypotonic condition, and promotes tumorigenesis through apoptosis suppression in vitro and in vivo. Notably, LRRC8A is upregulated by NSUN2-mediated m5C modification. m5C modified-LRRC8A mRNA is bound by the RNA binding protein YBX1 followed by the increased RNA stability. Moreover, loss of NSUN2 suppresses the proliferation and metastasis of CC cells, and NSUN2 expression is positively correlated with LRRC8A expression in CC. Altogether, our study demonstrates that the NSUN2-m5C-LRRC8A axis is crucial and would be a potential therapeutic target for CC.

Interaction between glycolysis‒cholesterol synthesis axis and tumor microenvironment reveal that gamma-glutamyl hydrolase suppresses glycolysis in colon cancer.

Background: Metabolic reprogramming is a feature of cancer. However, colon cancer subtypes based on the glycolysis‒cholesterol synthesis axis have not been identified, and little is known about connections between metabolic features and the tumor microenvironment. Methods: Data for 430 colon cancer cases were extracted from The Cancer Genome Atlas, including transcriptome data, clinical information, and survival outcomes. Glycolysis and cholesterol synthesis-related gene sets were obtained from the Molecular Signatures Database for a gene set variation analysis. The relationship between the genomic landscape and immune landscape were investigated among four metabolic subtypes. Hub genes were determined. The clinical significance of candidate hub gene was evaluated in 264 clinical samples and potential functions were validated in vitro and in vivo. Results: Colon cancer cases were clustered into four metabolic subtypes: quiescent, glycolytic, cholesterogenic, and mixed. The metabolic subtypes differed with respect to the immune score, stromal score, and estimate score using the ESTIMATE algorithm, cancer-immunity cycle, immunomodulator signatures, and signatures of immunotherapy responses. Patients in the cholesterogenic group had better survival outcomes than those for other subtypes, especially glycolytic. The glycolytic subtype was related to unfavorable clinical characteristics, including high mutation rates in TTN, APC, and TP53, high mutation burden, vascular invasion, right colon cancer, and low-frequency microsatellite instability. GGH, CACNG4, MME, SLC30A2, CKMT2, SYN3, and SLC22A31 were identified as differentially expressed both in glycolytic-cholesterogenic subgroups as well as between colon cancers and healthy samples, and were involved in glycolysis‒cholesterol synthesis. GGH was upregulated in colon cancer; its high expression was correlated with CD4+ T cell infiltration and longer overall survival and it was identified as a favorable independent prognostic factor. The overexpression of GGH in colon cancer-derived cell lines (SW48 and SW480) inhibited PKM, GLUT1, and LDHA expression and decreased the extracellular lactate content and intracellular ATP level. The opposite effects were obtained by GGH silencing. The phenotype associated with GGH was also validated in a xenograft nude mouse model. Conclusions: Our results provide insight into the connection between metabolism and the tumor microenvironment in colon cancer and provides preliminary evidence for the role of GGH, providing a basis for subsequent studies.

Modular and Noncontact Wireless Detection Platform for Ovarian Cancer Markers: Electrochemiluminescent and Photoacoustic Dual-Signal Output Based on Multiresponse Carbon Nano-Onions.

An electrochemiluminescent (ECL)-photoacoustic (PA) dual-signal output biosensor based on the modular optimization and wireless nature of a bipolar electrode (BPE) was constructed. To further simplify the detection process, the BPE structure was designed as three separate units: anode ECL collection, cathode catalytic amplification, and intermediate functional sensing units. Specifically, the anode unit was placed with Eosin Yellow, a cheap and effective ECL reagent, and the cathode unit was a laser-induced polyoxometalate-graphene electrode, which was helpful to enhance the anode ECL signal. The intermediate functional sensing unit consisted of a temperature-sensitive conductive film. Further, using a carbon nano-onion nanocomposite with excellent absorption performance in the near-infrared region as a signal tag not only leads to changes in the electrical conductivity of the film through heat transfer and thus affects the ECL signal but also produces a strong PA response. With this design, PA and ECL signals can be output simultaneously. This work not only realizes multiple modularization processes in the design of sensors but also implements the diversification of signal output modes, which will enrich the joint research field of ECL detection technology and other new detection methods.

Molecular Characteristics of T Cell-Mediated Tumor Killing in Hepatocellular Carcinoma.

Background: Although checkpoint blockade is a promising approach for the treatment of hepatocellular carcinoma (HCC), subsets of patients expected to show a response have not been established. As T cell-mediated tumor killing (TTK) is the fundamental principle of immune checkpoint inhibitor therapy, we established subtypes based on genes related to the sensitivity to TKK and evaluated their prognostic value for HCC immunotherapies. Methods: Genes regulating the sensitivity of tumor cells to T cell-mediated killing (referred to as GSTTKs) showing differential expression in HCC and correlations with prognosis were identified by high-throughput screening assays. Unsupervised clustering was applied to classify patients with HCC into subtypes based on the GSTTKs. The tumor microenvironment, metabolic properties, and genetic variation were compared among the subgroups. A scoring algorithm based on the prognostic GSTTKs, referred to as the TCscore, was developed, and its clinical and predictive value for the response to immunotherapy were evaluated. Results: In total, 18 out of 641 GSTTKs simultaneously showed differential expression in HCC and were correlated with prognosis. Based on the 18 GSTTKs, patients were clustered into two subgroups, which reflected distinct TTK patterns in HCC. Tumor-infiltrating immune cells, immune-related gene expression, glycolipid metabolism, somatic mutations, and signaling pathways differed between the two subgroups. The TCscore effectively distinguished between populations with different responses to chemotherapeutics or immunotherapy and overall survival. Conclusions: TTK patterns played a nonnegligible role in formation of TME diversity and metabolic complexity. Evaluating the TTK patterns of individual tumor will contribute to enhancing our cognition of TME characterization, reflects differences in the functionality of T cells in HCC and guiding more effective therapy strategies.

RNA 5-Methylcytosine Regulators Contribute to Metabolism Heterogeneity and Predict Prognosis in Ovarian Cancer.

5-Methylcytosine (m5C) is an abundant and highly conserved modification in RNAs. The dysregulation of RNA m5C methylation has been reported in cancers, but the regulatory network in ovarian cancer of RNA m5C methylation-related genes and its implication in metabolic regulation remain largely unexplored. In this study, RNA-sequencing data and clinical information of 374 ovarian cancer patients were downloaded from The Cancer Genome Atlas database, and a total of 14 RNA m5C regulators were included. Through unsupervised consensus clustering, two clusters with different m5C modification patterns were identified with distinct survivals. According to enrichment analyses, glycosaminoglycan and collagen metabolism-related pathways were specifically activated in cluster 1, whereas fatty acid metabolism-related pathways were enriched in cluster 2, which had better overall survival (OS). Besides the metabolism heterogeneity, the higher sensitivity to platinum and paclitaxel in cluster 2 can further explain the improved OS. Ultimately, a least absolute shrinkage and selection operator prediction model formed by ALYREF, NOP2, and TET2 toward OS was constructed. In conclusion, distinct m5C modification pattern exhibited metabolism heterogeneity, different chemotherapy sensitivity, and consequently survival difference, providing evidence for risk stratification.

An integrated bioinformatic investigation of mitochondrial solute carrier family 25 (SLC25) in colon cancer followed by preliminary validation of member 5 (SLC25A5) in tumorigenesis.

Solute carrier family 25 (SLC25) encodes transport proteins at the inner mitochondrial membrane and functions as carriers for metabolites. Although SLC25 genetic variants correlate with human metabolic diseases, their roles in colon cancer remain unknown. Cases of colon cancer were retrieved from The Cancer Genome Atlas, and the transcriptionally differentially expressed members (DEMs) of SLC25 were identified. DNA level alterations, clinicopathological characteristics, and clinical survival were also investigated. A risk score model based on the DEMs was constructed to further evaluate their prognostic values in a clinical setting. The results were preliminarily validated using bioinformatic analysis of datasets from the Gene Expression Omnibus, immunohistochemical evaluations in clinical specimens, and functional experiments in colon cancer-derived cell lines. Thirty-seven DEMs were identified among 53 members of SLC25. Eight of 37 DEMs were introduced into a risk score model using integrated LASSO regression and multivariate Cox regression. Validated by GSE395282 and GSE175356, DEMs with high-risk scores were associated with the phenotypes of increasing tumor immune infiltration and decreasing glycolysis and apoptosis contents. SLC25A5 was downregulated in cancer, and its upregulation was related to better overall survival in patients from public datasets and in clinical cases. High SLC25A5 expression was an independent prognostic factor for 79 patients after surgical treatment. A negative correlation between CD8 and SLC25A5 was determined in specimens from 106 patients with advanced colon cancer. SLC25A5 attenuated cell proliferation, upregulated the expression of programmed cell death-related signatures, and exerted its biological function by inhibiting the MAPK signaling pathway. Our study reveals that mitochondrial SLC25 has prognostic value in patients with colon cancer. The bioinformatic analyses by following verification in situ and in vitro provide direction for further functional and mechanistic studies on the identified member of SLC25.