Upregulated CANT1 is correlated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: CANT1, as calcium-activated protein nucleotidase 1, is a kind of phosphatase. It is overexpressed in some tumors and related to poor prognosis, but few studies explore its function and carcinogenic mechanism in hepatocellular carcinoma (HCC). METHODS: The expression of CANT1 mRNA and protein was analyzed by the Cancer Genome Atlas (TCGA) database and immunohistochemistry(IHC) staining. The relationship between CANT1 expression and clinicopathology was evaluated by various public databases. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of CANT1 by the area under curve (AUC). Univariate, multivariate Cox regression and Kaplan-Meier curves were applied to evaluate the predictive value of CANT1 on the prognosis of HCC. Methsurv was used to analyze gene changes and DNA methylation, and its impact on prognosis. The enrichment analysis of DEGs associated with CANT1 revealed the biological process of CANT1 based on Gene Set Enrichment Analysis (GSEA). The relationship between immune cell infiltration level and CANT1 expression in HCC was investigated using the single-sample GSEA (ssGSEA) method and the Tumor Immune Estimation Resource (TIMER) database. Finally, the association between CANT1 and immune checkpoints and drug sensitivity was also analyzed. RESULTS: CANT1 was highly expressed in 22 cancers, including HCC, and CANT1 overexpression in HCC was confirmed by IHC. The expression of CANT1 was correlated with clinical features, such as histologic grade. Highly expressed CANT1 caused poor overall survival (OS) of HCC patients. Univariate and multivariate regression analysis suggested that CANT1 was an independent prognostic marker. Of the 31 DNA methylation at CpG sites, three CpG sites were associated with the prognosis of HCC. GSEA indicated that CANT1 was mainly involved in the cell cycle, DNA replication, and etc. Moreover, CANT1 expression was correlated with immune cell infiltration and independently associated with the prognosis of HCC patients. Finally, CANT1 expression was correlated with most immune checkpoints and drug sensitivity. CONCLUSION: CANT1 may be a latent oncogene of HCC, and associated with immune cells and immune checkpoints, which may assist in HCC treatment.

The m6A/m5C/m1A regulator genes signature reveals the prognosis and is related with immune microenvironment for hepatocellular carcinoma.

BACKGROUND: RNA methylation is a crucial in many biological functions, and its aberrant regulation is associated with cancer progression. N6-Methyladenosine (m6A), 5-Methylcytosine (m5C), N1-methyladenosine (m1A) are common modifications of RNA methylation. However, the effect of methylation of m6A/m5C/m1A in hepatocellular carcinoma (HCC) remains unclear. METHOD: The transcriptome datasets, clinic information, and mutational data of 48 m6A/m5C/m1A regulator genes were acquired from the TCGA database, and the prognostic hazard model was established by univariate and Least absolute shrinkage and selection operator (Lasso) regression. The multivariate regression was performed to determine whether the risk score was an independent prognostic indicator. Kaplan-Meier survival analysis and ROC curve analysis were used to evaluate the predictive ability of the risk model. Decision curve analysis（DCA）analysis was conducted to estimate the clinical utility of the risk model. We further analyzed the association between risk score and functional enrichment, tumor immune microenvironment, and somatic mutation. RESULT: The four-gene (YTHDF1, YBX1, TRMT10C, TRMT61A) risk signature was constructed. The high-risk group had shorter overall survival (OS) than the low-risk group. Univariate and multivariate regression analysis indicated that risk score was an independent prognostic indicator. Risk scores in male group, T3 + T4 group and Stage III + IV group were higher in female group, T1 + T2 group and stage I + II group. The AUC values for 1-, 2-, and 3-year OS in the TCGA dataset were 0.764, 0.693, and 0.689, respectively. DCA analysis showed that the risk score had a higher clinical net benefit in 1- and 2-year OS than other clinical features.The risk score was positively related to some immune cell infiltration and most immune checkpoints. CONCLUSION: We developed a novel m6A/m5C/m1A regulator genes' prognostic model, which could be applied as a latent prognostic tool for HCC and might guide the choice of immunotherapies.

Cytopathological analysis of bronchoalveolar lavage fluid in patients with and without HIV infection.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) infection can lead to a broad spectrum of lung diseases, including infectious diseases and tumors. Recently, with the wide application of bronchoscopes and cytopathology of bronchoalveolar lavage fluid (BALF), the diagnostic efficiency of lung diseases has improved. The present study focuses on analyzing the cytopathologic characteristics of BALF in the diagnosis of HIV/AIDS-related lung disease and comparing the lung disease spectrum between HIV and HIV-uninfected patients. METHODS: BALF specimens were collected from 2211 patients. Using ThinPrep liquid-based technology, the cytologic smears were prepared by staining with Hematoxylin and Eosin (HE), Gomori's methenamine silver (GMS), and Periodic Acid Schiff (PAS), acid-fast and immunocytochemical (ICC) staining. Real-time PCR was used to detect cytomegalovirus (CMV) and Mycobacterium tuberculosis (M. tuberculosis) in the remaining BALF. PCR-reverse dot hybridization was used for mycobacterial species identification. RESULTS: From the 2211 BALF specimens, 1768 (79.96%) were specimens from HIV-infected patients, and 443 (20.04%) were speciments from HIV-uninfected patients. The HIV-infected patients with a median age of 38.5 ± 11.3 years were markedly younger than the HIV-uninfected patients (52.9 ± 14.9 years) (p < 0.01). We found that 1635 (92.5%) HIV-infected patients were males, showing a prominently higher proportion than those without HIV infection (71.1%) (p < 0.01). Meanwhile, 1045 specific lesions were found in 1768 HIV-infected patients (59.1%), including 1034 cases of infectious diseases and 11 neoplastic lesions, also exhibiting a distinctly higher proportion compared to the HIV-uninfected patients (12.2%) (p < 0.001). For the HIV-infected group, a distinctly higher proportion of single infection lesions (724/1768, 41%) was noted than the HIV-uninfected group (14/443, 3.2%) (p < 0.001). Among single infection lesions, the most common was Cytomegalovirus(CMV) infection (20.9%) for the HIV-infected group, followed by Pneumocystis jiroveci(PJ) (13.0%), Fungal (3.5%), and Mycobacterial infections (3.4%), of which M. tuberculosis infection accounted for 3.1%. Double infections (300/1768, 17.0%) and Triple infections (10/1768, 0.6%) were found only among the patients with HIV. The malignancies among HIV-infected patients included adenocarcinomas (0.22%), small cell carcinomas (0.2%), squamous cell carcinomas (0.1%), and diffuse large B-cell lymphoma (0.1%). HIV-infected patients exhibited a significantly lower incidence of neoplastic lesions (0.6% vs. 9.0%) than the HIV-uninfected patients (p < 0.001). CONCLUSIONS: There was a significant difference in the spectrum of lung diseases between HIV-infected and non-infected patients diagnosed by BALF cytopathology.

Analysis of the causes of cervical lymphadenopathy using fine-needle aspiration cytology combining cell block in Chinese patients with and without HIV infection.

BACKGROUND: Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block. METHODS: A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori's methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section. RESULTS: The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p < 0.01). Of all patients infected with HIV, 390 (86.1%) were males. This proportion was significantly higher than that of non-HIV-infected patients [65/136 (47.8%)] (p < 0.01). The major causes of cervical lymphadenopathy in HIV positive patients were mycobacterial infection (38.4%), reactive hyperplasia (28.9%), non-specific inflammation (19.9%), and malignant lesions (4.2%). In contrast, the most common causes in HIV negative patients were reactive hyperplasia (37.5%), malignancy (20.6%), non-specific inflammation (19.1%) and mycobacterial infection (12.5%). Opportunistic infections such as non-tuberculous mycobacteria (4.2%), cryptococcosis (1.5%), Talaromyces marneffei (1.5%) and other fungi (0.4%) were found only in HIV-infected individuals. Non-Hodgkin's lymphoma (2.4%) was the most common malignant lesion in patients with HIV infection, followed by Kaposi's sarcoma (0.9%) and metastatic squamous cell carcinomas (0.7%). However, the most common malignancy in non-HIV-infected patients was metastatic carcinomas (14%) including small cell carcinomas, adenocarcinomas, squamous cell carcinomas and hepatocellular carcinoma, which were noticeably greater than the HIV patients (p < 0.01). CONCLUSIONS: There were significantly different causes of cervical lymphadenopathy in HIV infected and non-HIV infected patients. FNAC was a useful diagnostic method for differential diagnosis of cervical lymphadenopathy.

Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS.

BACKGROUND: Cytomegalovirus (CMV) is among the most common opportunistic infections identified in patients with HIV/AIDS. CMV often targets the colon in such patients. However, the role of regulatory T cells (Tregs) and Programmed death-1 (PD-1) in intestinal CMV infection is unclear. In this study, we evaluate the expression of programmed death -1 (PD-1) and its association with regulatory T cells (Tregs) in patients with HIV/AIDS having CMV colitis. METHODS: CMV was detected in the intestinal mucosal biopsy samples via nucleic acid in situ hybridization. PD-1, CD4, CD8, and Treg-specific marker as well as the winged-helix transcription factor and forkhead box P3 (FoxP3) were detected by immunohistochemical methods. RESULTS: Intestinal CMV diease was identified in 20 out of 195 patients with HIV/AIDS enrolled in our study. CMV was diagnosed microscopically by the presence of giant cell inclusion bodies in epithelial cells, histiocytes, and fibroblasts. Levels of immunoreactive PD-1 detected in mucosal biopsies from patients with HIV/AIDS having CMV colitis were significantly higher than CMV-negative control group (p = 0.023). FoxP3+ cells were detected in the CMV colitis group slight more than that in the control group. CD4+ T lymphocyte counts in the peripheral blood and intestinal mucosal biopsies from CMV colitis group were all notably decreased compared with those with control group (p < 0.001 for both). PD-1 had a significant negative correlation with CD4 counts in intestinal mucosa (p = 0.016). CD8+T lymphocyte counts in peripheral blood and intestinal mucosa were slightly lower than those in the control group, although the differences were not statistically significant. CONCLUSIONS: CMV colitis with HIV/AIDS is associated with significant changes in T lymphocyte populations. These findings may have important implications for disease pathogenesis and progression.

3D Printed Rotating Acentric Binary-Disk Electrode.

Rotating ring-disk electrode (RRDE) is a generator-collector electrochemical system widely used as an electroanalytical and kinetic device. However, RRDEs are costly and difficult to fabricate, particularly when the electrode material is fragile, small, and scarce. Taking advantage of readily available 3D printing technology an alternative generator-collector system was developed: rotating acentric binary-disk electrode (RABDE). RABDE consists of two close acentric disk electrodes arranged in a cylindrical matrix so that the line connecting their centers is perpendicular to radius of the device passing through the center of generator electrode. In contrast to RRDE that is based on radial flow velocity for mass transfer between the generator and the collector, RABDE mostly takes advantage of the larger tangential flow velocity. RABDE thus exhibits higher current densities than RRDE for a same rotation rate and evidences much better electroanalytical performances. These increased performances were tested and quantified using typical analytes: potassium ferricyanide system, copper ion system, and oxygen reduction reaction in alkaline solution.

Detection of 1,3-dihydroxyacetone by tris(2,2'-bipyridine)ruthenium(II) electrochemiluminescence.

1,3-Dihydroxyacetone, a common cosmetic material and food additive, has been successfully explored as an efficient electrochemiluminescence coreactant of Ru(bpy)32+ for the first time. It is about 25 times more effective than the well-known coreactant sodium oxalate. The high electrochemiluminescence efficiency allows sensitive detection of 1,3-dihydroxyacetone without any derivatization. The electrochemiluminescence method shows two linear electrochemiluminescence responses over the range of 5.0-500 µM and 500 µM-6.0 mM with a detection limit of 1.79 µM. The proposed method is at least two orders of magnitude more sensitive than other reported methods. Graphical abstract ECL intensity-potential profile of 1,3-dihydroxyacetone (DHA) and oxalate.

Tris(2,2'-bipyridyl)ruthenium(II) electrochemiluminescent determination of ethyl formate.

Ethyl formate is extensively used as food flavor, fungicide, and larvicide. It naturally exists in coffee, fruits, honey, brandy, and rum as well as dust clouds in an interstellar space of the Milky Way galaxy. Herein, its electrochemiluminescence (ECL) property has been firstly investigated. It shows intense ECL in reaction with Ru(bpy)32+ as luminophore, and thus a rapid and sensitive detection method for ethyl formate is proposed. Effects of pH, working potential, scan rate, and concentration of Ru(bpy)32+ were studied. ECL spectrum analysis was used to reveal the reaction mechanism. At the optimized experimental conditions, a linear relationship between ECL intensities and concentrations of ethyl formate is observed from 3.0 µM to 1.0 mM (R2 = 0.997). The limit of detection for ethyl formate is 0.7 µM (S/N = 3). The relative standard deviation with 1.0 mM concentration of ethyl formate for nine analyses is 2.7%. A 101.20-102.10% recovery was obtained in a real samples analysis. Graphical Abstract ᅟ.

Pyridoxal 5'-phosphate assay based on lucigenin chemiluminescence.

The authors describe the first chemiluminescence (CL) based method for determination of pyridoxal 5'-phosphate (PLP). PLP is found to generate intense CL with lucigenin higher than that of the conventional lucigenin-H2O2 system by a factor of about 9.0. This new finding is used to be in a detection method for PLP via flow injection analysis (FIA). Response is linear in the 50 nM to 200 µM PLP concentration range with a correlation coefficient of 0.998, and the detection limit (at an S/N of 3) is 6.9 nM. The assay is highly selective over various amino acids, vitamins, sugars, coenzymes and metal ions cofactors. It exhibits advantages over the commonly employed HPLC methods in that it is rapid, more economic, eco-friendly and high throughput FIA detection of PLP without the need for toxic derivatization reagents, organic solvents, and HPLC instrumentation. The method was successfully applied to the determination of PLP in (spiked) human blood samples with recoveries in the range from 96.2-101.6% with % RSD < 4.0. The new system is also employed to determine lucigenin in the linear range of 0.3 to 100.0 µM with a correlation coefficient of 0.994 and the limit of detection is 0.04 µM. Graphical abstract Schematic of the chemiluminescent assay for pyridoxal 5'-phosphate (PLP). Lucigenin-PLP demonstrates 9-fold stronger chemiluminescence intensity than the lucigenin-H2O2 system. The detection limit of PLP is 6.9 nM. The method can detect PLP in human serum with good recoveries.

Stainless Steel Electrode for Sensitive Luminol Electrochemiluminescent Detection of H2O2, Glucose, and Glucose Oxidase Activity.

Electrogenerated chemiluminescence (ECL) application of stainless steel, a robust and cost-effective material, has been developed for the first time. Type 304 stainless steel electrode shows appealing ECL performance in the luminol-H2O2 system. It enables the detection of H2O2 with a linear range from 1 to 1000 nM and a limit of detection of 0.456 nM [signal-to-noise ratio (S/N) = 3]. The ECL method based on type 304 stainless steel electrode is more sensitive, more cost-effective, and much simpler than other ECL methods reported before. Because the stainless steel electrode has excellent performance for H2O2 detection and H2O2 participates in many important enzymatic reactions, applications of stainless steel electrode-based ECL for detection of enzyme activities and enzyme substrates were further investigated by use of glucose oxidase (GODx) and glucose as representative enzyme and substrate. The concentrations of glucose and the activity of GODx were directly proportional to ECL intensities over a range of 0.1-1000 µM and 0.001-0.7 units/mL with limits of detection of 0.076 µM and 0.00087 unit/mL (S/N = 3), respectively. This method was successfully used for determining glucose in honey. Because of their remarkable performance and user-friendly features, stainless steel electrodes hold great promise in various electroanalytical applications, such as biosensing, disposable sensors, and wearable sensors.

Ultrasensitive Glutathione Detection Based on Lucigenin Cathodic Electrochemiluminescence in the Presence of MnO2 Nanosheets.

Glutathione (GSH) is a crucial antioxidant produced endogenously and plays key roles in biological systems. It is vitally important to design simple, selective, and sensitive methods to sense GSH and monitor changes of GSH concentration. In this work, the cathodic electrochemiluminescence (ECL) of lucigenin in the presence of MnO2 nanosheets at a glassy carbon electrode was utilized for GSH detection. GSH can reduce MnO2 nanosheets into Mn(2+) which can obviously inhibit the ECL of lucigenin. The ECL inhibition efficiencies increase linearly with the concentrations of glutathione in the range of 10 to 2000 nM. The detection limit for GSH measurement is 3.7 nM. This proposed method is highly sensitive, selective, simple, fast, and cost-effective. Moreover, this approach can detect GSH in human serum samples with excellent recoveries, which indicates its promising application under physiological conditions.

Increasing Electrochemiluminescence Intensity of a Wireless Electrode Array Chip by Thousands of Times Using a Diode for Sensitive Visual Detection by a Digital Camera.

Both a wireless electrochemiluminescence (ECL) electrode microarray chip and the dramatic increase in ECL by embedding a diode in an electromagnetic receiver coil have been first reported. The newly designed device consists of a chip and a transmitter. The chip has an electromagnetic receiver coil, a mini-diode, and a gold electrode array. The mini-diode can rectify alternating current into direct current and thus enhance ECL intensities by 18 thousand times, enabling a sensitive visual detection using common cameras or smart phones as low cost detectors. The detection limit of hydrogen peroxide using a digital camera is comparable to that using photomultiplier tube (PMT)-based detectors. Coupled with a PMT-based detector, the device can detect luminol with higher sensitivity with linear ranges from 10 nM to 1 mM. Because of the advantages including high sensitivity, high throughput, low cost, high portability, and simplicity, it is promising in point of care testing, drug screening, and high throughput analysis.

Sensitive and selective colorimetric detection of Hg(2+) by a Hg(2+) induced dual signal amplification strategy based on cascade-type catalytic reactions.

A simple and fast colorimetric method is developed for the sensitive and selective detection of Hg(2+) based on a dual signal amplification strategy: in situ Hg(2+) induced catalytic synthesis of oxidase-like AuHg nanoparticles and subsequent catalytic oxidation of TMB by AuHg nanoparticles.

Electrogenerated chemiluminescence of tris(2,2'-bipyridine)ruthenium(II) using N-(3-aminopropyl)diethanolamine as coreactant.

Coreactant plays a critical role for the application of electrochemiluminescence (ECL). Herein, N-(3-aminopropyl)diethanolamine (APDEA) has been explored as a potential coreactant for enhancing tris(2,2'-bipyridyl)ruthenium(II) ECL. It is much more effective than tripropylamine at gold and platinum electrodes although it has one primary amine group besides a tertiary amine group. The presence of primary amine group and hydroxyl groups in APDEA promotes the oxidation rates of amine and thus remarkably increases ECL intensity. The ECL intensities of the Ru(bpy)3 (2+)/APDEA system are approximately 10 and 36 times stronger than that of Ru(bpy)3 (2+)/tripropylamine system and about 1.6 and 1.14 times stronger than that of Ru(bpy)3 (2+)/N-butyldiethanolamine system at Au and Pt electrodes, respectively. The ECL intensity of the Ru(bpy)3 (2+)/APDEA system is 2.42 times stronger than that of Ru(bpy)3 (2+)/N-butyldiethanolamine at glassy carbon electrodes.

N-Hydroxysuccinimide as an effective chemiluminescence coreactant for highly selective and sensitive detection.

The development of novel coreactants for chemiluminescence is very important to improve performance and widen its applications without using any other catalyst. N-Hydroxysuccinimide (NHS), a highly popular amine-reactive, activating, or protecting reagent in biochemical applications and organic synthesis, has been explored as an efficient and stable chemiluminescence coreactant for the first time. The chemiluminescence intensity of the newly developed luminol-NHS system is about 22 times higher than that of the traditional luminol-H2O2 system. Chemiluminescence of this system is dramatically enhanced by Co2+. This new chemiluminescence system is then applied for the highly selective and ultrasensitive detection of Co2+ with limit of detection (0.01 nM) better than those of several conventional analytical methods. This system also enables the efficient detection of luminol (LOD = 7 pM) and NHS (LOD = 3.0 µM) with excellent sensitivity. This chemiluminescence method was then also utilized to detect Co2+ in tap water and blue silica gel with excellent recoveries in the range 99.20-103.07 %. This novel chemiluminescence system has several advantages, including simple, cost-effective, highly sensitive, selective, and wide linear range. We expect that this chemiluminescence system will be a promising candidate for chemical and biological sensing. Graphical Abstract Comparison of CL peak intensities of classical luminol-H2O2 CL system and newly developed luminol-NHS CL system.

[Pathology of hepatic iron deposition in hemochromatosis].

OBJECTIVE: To identify the type of iron deposition and describe its amount, distribution and associated lesions, in order to support an etiologic diagnosis for hemochromatosis. METHODS: Hematoxylineosin (HE) stain, reticular fiber stain, Masson's stain and Perl's iron stain were used to assess liver biopsies from 31 patients with hemochromatosis. The Ishak scoring system and Deugnier scoring system were used to assess the histological change in liver and to semi-quantify the excess of hepatic iron. Genetic testing results were received from a portion of the patients and used in analysis. RESULTS: One patient had hereditary (-HFE) hemochromatosis complicated with Gilbert's syndrome, for which the pattern of iron deposition was similar to that of the four patients with Gilbert's syndrome. Iron accumulation appeared as fine granules predominating at the biliary pole of cells and was distributed throughout the lobule with a decreasing gradient spanning from the periportal to centrolobular areas. Mild chronic inflammation was found to be commonly associated with low stage fibrosis.One patient had HFE hemochromatosis complicated with hepatitis B virus infection, and the pattern of iron deposition resembled that in the eight patients with viral hepatitis, wherein the deposition was mainly in the sinusoidal cells and/or portal macrophages. Histological grading and fibrosis staging differed among patients. The five patients with blood disordered showed iron accumulation mainly in the periportal hepatocytes, but mesenchymal iron deposits were also present. The grade of inflammation, as well as of fibrosis,was mild. The five patients with alcoholic disease and the five patients with drug-induced hepatitis showed hepatic iron deposition in swollen or ballooned hepatocytes. The two patients with excessive iron supply showed iron deposition localized within the parenchymal and mesenchymal cells. CONCLUSION: Etiologic diagnosis of hemochromatosis relies on both the type of iron deposition and the nature of associated lesions. Liver biopsy is necessary for both diagnosis and prognosis.

DNA damage in peripheral blood lymphocytes from patients with OSAHS.

PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by intermittent hypoxia during sleep time, followed by oxidative stress. Hypoxia-induced oxidative stress can lead to DNA damage, which is related to chromosome aberrations and micronuclei. The purpose of this study is to investigate the level of DNA damage in peripheral blood of patients with OSAHS. METHODS: Thirty patients with OSAHS diagnosed by polysomnography and 28 healthy volunteers were assessed by the Epworth sleepiness scale. The levels of DNA damage were investigated through the cytokinesis-blocked micronucleus assay. RESULTS: In the group of patients with OSAHS, the mean frequency of binucleated cells with micronuclei were significantly higher than that in the control group (P<0.01), and the frequency of micronuclei among the patients in mild, moderate, and severe stages differed significantly (P<0.05). The mean frequency of nucleoplasmic bridge in OSAHS group was also higher than that in the control group (P<0.05). Nasal continuous positive airway pressure treatment decreased the frequencies of binucleated cells with micronuclei, nucleoplasmic bridge, and nuclear buds. CONCLUSIONS: Oxidative DNA damage increased in peripheral blood lymphocytes of OSAHS patients. It may be related to oxidative stress induced by intermittent hypoxia and may be involved in the pathogenesis of cardiovascular and other target organ injuries.

Comprehensive Pan-Cancer Analysis of KIF18A as a Marker for Prognosis and Immunity.

KIF18A belongs to the Kinesin family, which participates in the occurrence and progression of tumors. However, few pan-cancer analyses have been performed on KIF18A to date. We used multiple public databases such as TIMER, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA) to explore KIF18A mRNA expression in 33 tumors. We performed immunohistochemistry on liver cancer and pancreatic cancer tissues and corresponding normal tissues to examine the expression of KIF18A protein. Univariate Cox regression and Kaplan-Meier survival analysis were applied to detect the effect of KIF18A on overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of patients with these tumors. Subsequently, we explored KIF18A gene alterations in different tumor tissues using cBioPortal. The relationship between KIF18A and clinical characteristics, tumor microenvironment (TME), immune regulatory genes, immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs), DNA methylation, RNA methylation, and drug sensitivity was applied for further study using the R language. Gene Set Enrichment Analysis (GSEA) was utilized to explore the molecular mechanism of KIF18A. Bioinformatic analysis and immunohistochemical experiments confirmed that KIF18A was up-regulated in 27 tumors and was correlated with the T stage, N stage, pathological stage, histological grade, and Ki-67 index in many cancers. The overexpression of KIF18A had poor OS, DSS, and PFI in adrenocortical carcinoma (ACC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower-grade glioma (LGG), liver cancer (LIHC), lung adenocarcinoma (LUAD), and pancreatic cancer (PAAD). Univariate and multivariate regression analysis confirmed KIF18A as an independent prognostic factor for LIHC and PAAD. The mutation frequency of KIF18A is the highest in endometrial cancer. KIF18A expression levels were positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, MMRs, DNA methylation, RNA methylation, and drug sensitivity in certain cancers. In addition, we discovered that KIF18A participated in the cell cycle at the single-cell level and GSEA analysis for most cancers. These findings suggested that KIF18A could be regarded as a latent prognostic marker and a new target for cancer immunological therapy.

Establishment of a new molecular subtyping and prognostic signature with m6A/m5C/m1A/m7G regulatory genes for hepatocellular carcinoma.

Background: RNA modification, including m6A, m5C, m1A, and m7G, participated in tumor progress. Therefore, the purpose of the present study was to explore the role of m6A/m5C/m1A/m7G regulatory genes in the prognosis and tumor microenvironment (TME) for hepatocellular carcinoma (HCC). Methods: 71 m6A/m5C/m1A/m7G regulatory genes expression for HCC was detected, differentially expressed genes were screened, and molecular forms were classified by unsupervised consensus clustering. Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) analysis were applied to establish a prognostic signature. Time-dependent receiver operating characteristic (ROC) curves were evaluated for clinical effectiveness and accuracy of the prognostic hazard model. In cluster subtypes and risk models, the differences in prognosis, immune cell infiltration, immune checkpoint, immunotherapy, and drug sensitivity between different subtypes were evaluated. Results: HCC patients were classified into two clusters (cluster 1 and cluster 2) according to the expression of 71 m6A/m5C/m1A/m7G regulatory genes. Cluster 1 had a poor prognosis and different immune cell infiltration. Cluster 1 had higher immune checkpoint expression and TIDE score than cluster 2. Subsequently, we construct a five-gene prognostic model of m6A/m5C/m1A/m7G regulatory genes (YTHDF2, YTHDF1,YBX1, TRMT61A, TRMT10C). The Kaplan-Meier and ROC curve analysis showed that the prognostic signature exhibited good predictability. The risk score was considered an independent poor prognostic index. The high-risk group had higher immune checkpoint expression and higher TIDE scores. 5-Fluorouracil, docetaxel, doxorubicin, etoposide, gemcitabine, paclitaxel, sorafenib, and vinblastine were more suitable for high-risk patients. ECM receptor interaction, cell cycle, and Leishmania infection were enriched in the high-risk group. Conclusion: The clustering subgroups and prognostic model of m6A/m5C/m1A/m7G regulatory genes were linked with bad prognosis and TME for HCC, and had the potential to be a novel tool to evaluate the outcomes of HCC patients.

Strong Photocurrent Response of Selenoarsenates With Different Transition Metal Complexes as Structure-Directing Agents.

Four selenoarsenates with different transition-metal complexes [Co(tren)2H]AsSe4 [tren = tris(2-aminoethyl)amine] (1); [Ni2(dien)4](As2Se5) (dien = diethylenetriamine) (2); [Zn(tren)]2(As2Se5) (3) and [Mn(tren)]2(As2Se5) (4) were solvothermally synthesized in a mixed solvent of organic amine and alcohol solution. The compounds 1-4 have pyramidal/tetrahedral structures (AsSe3/AsSe4), and contain transition metal (Co2+, Ni2+, Zn2+ and Mn2+) complex that form distinct zero-dimensional (0-D) clusters. Arsenic atoms form a tetrahedron in compounds 1 and 2; 1 consists of discrete tetrahedral (AsSe4) and transition metal complex [Co(tren)2]2+; 2 is composed of an anion [As2Se5]4- cluster and transition metal complex [Ni(dien)2]2+. In compounds 3 and 4, arsenic atom forms a pyramidal AsSe3 and the two pyramidal AsSe3 share a corner connection to form a dimer [As2Se5]4-; 3 is characterized as a cluster consisting of two unsaturated [Zn(tren)]2+ caiton linked by a dimer (As2Se5)4- linkage; in 4, unsaturated [Mn(tren)]2+ caiton is linked to two trigonal-bipyramidal [Mn(tren)]Se via dimer (As2Se5)4- to form [Mn(tren)]4[As4Se10] cluster. To our knowledge, [Zn(tren)]2(As2Se5) (3) is the first zinc selenoarsenate containing the (As2Se5)4- anion type. Furthermore, the Mn2+ ions adopt a trigonal-biyramidal (five-coordinate) and octahedral (six-coordinate) environment. Adding K2CO3/Cs2CO3 to the synthesis system is necessary and may act as a mineralizer. Several properties of compounds 1-4 have been characterized in our studies, in particular their strong photocurrent response characteristics under visible light irradiation.