Surface Activity, Wettability, and Aggregation Behavior of Ecofriendly Fluorocarbon Surfactant Based on Double Perfluorinated Branched Short Chains.

This article reports the synthesis of a novel sulfonated fluorocarbon surfactant (SFDC) containing double C6 perfluorinated branched short chains and compares its surface properties with a similar structured compound (SFDC-L) in solutions. The critical micelle concentration (CMC) and the corresponding surface tension (γCMC) of SFDC aqueous solution are 9.77 × 10-3 mmol/L and 22.15 mN/m, respectively, indicating that SFDC has excellent surface properties. Besides, the addition of n-hexyltrimethylammonium bromide (HTAB) could further enhance the surface properties of SFDC. Meanwhile, the micellization, aggregation behavior, wettability, and adsorption at the air-water interface of SFDC and SFDC/HTAB mixture aqueous solutions are systematically investigated. Both SFDC and SFDC/HTAB show excellent wettability at low concentrations. The aggregation of SFDC and SFDC/HTAB mixtures in aqueous solution could be clearly seen as vesicles and rod-like micelles on TEM micrographs.

Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.

Risk Factors and Impact on Outcomes of Lung Cancer Patients Concurrent with Deep Vein Thrombosis.

PURPOSE: Many investigations on prognostic factors in lung cancer have been conducted; however, little is known regarding the outcomes of lung cancer cases complicated by deep vein thrombosis (DVT). This study aimed to determine the risk factors and impact on outcomes of lung cancer patients concurrent with DVT. METHODS: Lung cancer patients who underwent lower-extremity venous ultrasound were enrolled in this study. The patients were divided into a DVT group and a non-DVT group. Demographic information, clinical characteristics, and survival were analyzed by t-test, Wilcoxon test, chi-squared test, and logistic regression analysis. RESULTS: Of the 160 enrolled lung cancer patients, DVT was detected in 30 patients. Among the DVT group, adenocarcinoma was the most common histological type (27/30, 90.00%). Lung cancer complicated with DVT was associated with advanced stage, more severe myocardial injury, and a hypercoagulable state (P < .05). Differences in driver genes between the two groups were not significant. Radiologically, lung cancer patients with DVT were more likely to present with pericardial effusion and pleural effusion than patients without DVT (P < .05). Following multivariable logistic regression analysis, advanced stage (OR 5.368, [95%CI 1.871-18.165], P = .021), NT-proBNP >300 pg/ml (OR 5.575, [95%CI 1.733-3.722], P = .018), D-dimer >5 mg/L (OR 8.449, [95%CI 4.323-18.536], P = .004), CRP >12 mg/L (OR 6.687, [95%CI 1.967-13.617], P = .010), and serum CEA >25 ng/ml (OR 4.755, [95%CI 1.358-3.123], P = .029) were independent risk factors for adenocarcinoma complicated with DVT. Finally, survival analysis revealed that the occurrence of DVT resulted in a poorer prognosis despite anticoagulant therapy (P < .05). CONCLUSION: DVT is a potential complication in patients with lung adenocarcinoma and could represent a prognostic marker for unfavorable outcome. It is essential to screen for DVT in high-risk adenocarcinoma patients.

Long non-coding RNA FENDRR inhibits proliferation and invasion of hepatocellular carcinoma by down-regulating glypican-3 expression.

Long non-coding RNA FENDRR is implicated in progression of several cancers, but its exact role and mechanism in hepatocellular carcinoma (HCC) are largely unknown. In this study, we investigated the expression and biological roles of FENDRR in HCC tissues and cell lines. We found that the expression levels of FENDRR were significantly down-regulated in HCC tissues and cells. FENDRR overexpression could inhibit the growth of HCC cells in vitro and in vivo. Moreover, up-regulation of FENDRR suppressed the migration and invasion of HCC cells. Mechanistically, we demonstrated that FENDRR interacted directly with Glypican-3 (GPC3) promoter and methylated GPC3 promoter, which led to down-regulation of GPC3 expression. Ectopic expression of GPC3 ablated the inhibitory effects of FENDRR on HCC cell proliferation, migration and invasion. Taken together, we provided the first evidence for the inhibitory activity of FENDRR in HCC, which is causally linked to targeting GPC3 at the epigenetic level. Restoration of FENDRR may be a potential approach to prevent HCC progression and metastasis.

Raman chemical feature extraction for quality control of dairy products.

As a fast information acquisition technique, Raman spectroscopy can be used to control the quality of dairy products. Feature extraction is a necessary processing step to improve the efficiency of Raman spectral data. Principal component analysis is a traditional method that can effectively extract the features and reduce the dimension of spectral data. However, it is difficult to analyze the chemical information of the extracted feature, thus limiting its practical application. In this work, Raman spectral chemical feature extraction was carried out. The quality control of Dingxin dairy products (a famous dairy brand in China; purchased from Heilongjiang Zhaodong Tianlong Dairy Co. Ltd., Heilongjiang, China) was used as an example. Raman peak intensity, peak area, and peak ratio were extracted as chemical features and further investigated using Euclidean distance and the quality fluctuation control chart. The potential quality discrimination ability of the Raman feature extraction methods was demonstrated. The results showed that the Puzhen dairy products (purchased from Inner Mongolia Yinuo Halal Food Co. Ltd., Inner Mongolia, China) and Xueyuan dairy products (used as a control; purchased from Inner Mongolia Wulanchabu City Jining Xueyuan Dairy Co. Ltd., Inner Mongolia, China) could be distinguished from Dingxin dairy products when the Raman chemical features special peak intensity, peak area, and peak ratio were used, and their discriminatory ability increased in sequence. Hence, it was shown that Raman chemical feature extraction can achieve quality control and discriminant analysis of dairy products and that the spectral information is clear.

[Design of Electromagnetic Tracking System Using Rotating Magnetic Field Based on DSP].

This paper realized an electromagnetic tracking system based on electrically-controlled rotating magnetic field. A tracking system using the digital signal processor (DSP) as the control processing device was developed, including a controllable constant current source module, a magnetic field source module, a three-axis magnetic sensor and ADC interface circuit. The experimental results verified that each time the system could be stable positioning, average error of position was 0.282 cm, the average error of orientation was 0.696o, the positioning time was 1.572 s. Through calibration and further improvement of the hardware circuit, the performance of the system is expected to further improve.

Identification and Functional Profiling of Differentially Expressed Long Non-Coding RNAs in Nasal Mucosa with Allergic Rhinitis.

Long non-coding RNAs (lncRNAs) have been proved to play important roles in a variety of human immune diseases. However, their pathological effects on the development of allergic rhinitis (AR) have not been clearly understood. The aim of this study was to determine the expression profile of lncRNAs in nasal mucosa of AR patients by lncRNA microarray and to predict potential roles of specific lncRNAs in the pathogenic mechanisms of AR by analysis of lncRNA-mRNA co-expression network, Gene Ontology (GO) and pathway. The lncRNA microarray analysis showed that a total of 2,259 lncRNAs (1,033 up-regulated and 1,226 down-regulated) and 704 mRNAs (157 up-regulated and 547 down-regulated) were significantly differentially expressed in the nasal mucosa samples from 4 AR patients as compared to those from 4 non-allergic subjects (fold change > 2; P < 0.05). In addition, the lncRNA-mRNA co-expression network contained 143 network nodes including 76 lncRNAs and 67 mRNAs, in which 117 significant correlation pairs presented as positive, and 108 pairs presented as negative. The results from GO and pathway analysis indicated that the lncRNAs-coexpressed mRNAs were enriched in several biological processes and cellular signaling pathways related to AR development, such as positive regulation of interleukin-13 secretion, Fc epsilon RI signaling pathway and NF-kappa B signaling pathway. To summary, our study provides important information on the molecular mechanisms and biological functions of these AR-related lncRNAs, which could be utilized for developing novel therapeutic strategies for AR.

[Application of Raman Spectroscopy and Pattern Recognition Methods for Determining the Authenticity and Detecting the Adulteration of Milk Powder].

The authenticity and adulteration of dairy products are attracting broad attention in recent years. There is a need to develop rapid, simple and accurate analytical methods for the detection of authenticity and adulteration of dairy products. To discriminate between milk powder samples, Raman spectra of FIRMUS, Nestlé and Being Mate milk powder were collected. The nearest neighbor algorithm (NN)combined with the characteristic peaks were employed for the design of a model. On the basis of 10 cross validation, the average recognition rate was 99.56%. In order to achieve the analysis of the adulteration of milk powder, FIRMUS milk powder was mixed with Nestlé milk powder according to the mass ratio 0 :1, 1 : 3, 1 : 1, 3 : 1 and 1 : 0 to get five kinds of the adulterated milk powder samples. Then, fat was extracted from the adulterated milk powder samples. Raman spectra of the fat were collected, then two methods were employed for the design of models. One was the nearest neighbor algorithm combined with the characteristic peaks, another was the kernel principal component analysis (KPCA) combined with NN. On the basis of 10 cross validation, the average recognition rate reached 93.33% and 98.89%, the average operation time was 0.085 and 0.104 s. The results of this work showed that the nearest neighbor algorithm combined with the characteristic peaks can be applied for the determination of the authenticity of milk powder while Raman-KPCA-NN model can provide a simple, accurate and rapid method to investigate the adulteration of milk power.

Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models.

AIMS/HYPOTHESIS: 'Glucotoxicity' is a term used to convey the negative effect of hyperglycaemia on beta cell function; however, the underlying molecular mechanisms that impair insulin secretion and gene expression are poorly defined. Our objective was to define the role of transcription factor v-ets avian erythroblastosis virus E26 oncogene homologue 1 (Ets-1) in beta cell glucotoxicity. METHODS: Primary islets and Min6 cells were exposed to high glucose and Ets-1 expression was measured. Recombinant adenovirus and transgenic mice were used to upregulate Ets-1 expression in beta cells in vitro and in vivo, and insulin secretion was assessed. The binding activity of H3/H4 histone on the Ets-1 promoter, and that of forkhead box (FOX)A2, FOXO1 and Ets-1 on the Pdx-1 promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assay. RESULTS: High glucose induced upregulation of Ets-1 expression and hyperacetylation of histone H3 and H4 at the Ets-1 gene promoter in beta cells. Ets-1 overexpression dramatically suppressed insulin secretion and biosynthesis both in vivo and in vitro. Besides, Ets-1 overexpression increased the activity of FOXO1 but decreased that of FOXA2 binding to the pancreatic and duodenal homeobox 1 (PDX-1) homology region 2 (PH2), resulting in inhibition of Pdx-1 promoter activity and downregulation of PDX-1 expression and activity. In addition, high glucose promoted the interaction of Ets-1 and FOXO1, and the activity of Ets-1 binding to the Pdx-1 promoter. Importantly, PDX-1 overexpression reversed the defect in pancreatic beta cells induced by Ets-1 excess, while knockdown of Ets-1 prevented hyperglycaemia-induced dysfunction of pancreatic beta cells. CONCLUSIONS/INTERPRETATION: Our observations suggest that Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in type 2 diabetes.

Celastrol induces cell cycle arrest by MicroRNA-21-mTOR-mediated inhibition p27 protein degradation in gastric cancer.

OBJECTIVE: Celastrol has anti-cancer effects by increase of apoptosis of gastric cancer cells. However, its role in gastric cancer cell cycle is still unclear. The aim of this study was to investigate the effect and mechanism of celastrol on gastric cancer cell cycle. METHODS: The effects of celastrol on cell cycle in BGC-823 and MGC-803 cells were assayed via flow cytometry analysis. The expression of p27 and mTOR was detected by real-time PCR and western blot. The activity of mTOR and mTORC2 was measured by mTOR and mTORC2 kinase assays. miR-21 mimic was used to up-regulate miR-21 expression and mTOR expression plasmid was used to increase mTOR level in gastric cancer cells. RESULTS: Celastrol caused G2/M cell-cycle arrest that was accompanied by the down-regulation of miR-21 expression. In particular, miR-21 overexpression reversed cell cycle arrest effects of celastrol. Further study showed that celastrol increased levels of the p27 protein by inhibiting its degradation. miR-21 and mTOR signaling pathway was involved in the increase of p27 protein expression in BGC-823 and MGC-803 cells treated with celastrol. Significantly, miR-21 overexpression restored the decrease of mTOR activity in cells exposed celastrol. CONCLUSIONS: The effect of celastrol on cell cycle arrest of gastric cancer cells was due to an increase of p27 protein level via inhibiting miR-21-mTOR signaling pathway.

Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.

Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.

Recent advances in nanosized Mn-Zn ferrite magnetic fluid hyperthermia for cancer treatment.

This paper reviews the recent research and development of nanosized manganese zinc (Mn-Zn) ferrite magnetic fluid hyperthermia (MFH) for cancer treatment. Mn-Zn ferrite MFH, which has a targeted positioning function that only the temperature of tumor tissue with magnetic nanoparticles can rise, while normal tissue without magnetic nanoparticles is not subject to thermal damage, is a promising therapy for cancer. We introduce briefly the composition and properties of magnetic fluid, the concept of MFH, and features of Mn-Zn ferrite magnetic nanoparticles for MFH such as thermal bystander effect, universality, high specific absorption rate, the targeting effect of small size, uniformity of hyperthermia temperature, and automatic temperature control and constant temperature effect. Next, preparation methods of Mn-Zn ferrite magnetic fluid are discussed, and biocompatibility and biosecurity of Mn-Zn ferrite magnetic fluid are analyzed. Then the applications of nanosized Mn-Zn ferrite MFH in cancer are highlighted, including nanosized Mn-Zn ferrite MFH alone, nanosized Mn-Zn ferrite MFH combined with As2O3 chemotherapy, and nanosized Mn-Zn ferrite MFH combined with radiotherapy. Finally, the combination application of nanosized Mn-Zn ferrite MFH and gene-therapy is conceived, and the challenges and perspectives for the future of nanosized Mn-Zn ferrite MFH for oncotherapy are discussed.

Celastrol induces apoptosis of gastric cancer cells by miR-21 inhibiting PI3K/Akt-NF-κB signaling pathway.

OBJECTIVE: Celastrol, a plant triterpene, has anticancer effects by increase of apoptosis. In the present study, the mechanism of celastrol on gastric cancer cell apoptosis was examined. METHODS: The effect of celastrol on PI3K/Akt and the NF-κB signaling pathway was evaluated with Western blot and luciferase reporter assay. miR-21 expression was determined using real-time PCR. miR-21 inhibitor and miR-21 mimic were used to downregulate and upregulate miR-21 expression, respectively. RESULTS: It was identified that celastrol was capable of inducing apoptosis of gastric cancer cells, which was mediated via inhibiting the activation of PI3K/Akt and NF-κB. A strong activator of Akt, IGF-1 restored NF-κB activity in cells treated with celastrol. Celastrol could also significantly suppress miR-21 expression. Furthermore, miR-21 inhibitor could decrease phospho-Akt expression and NF-κB activity. Notably, upregulation of miR-21 expression can increase PI3K/Akt and NF-κB activity and decrease apoptosis of gastric cancer cells treated with celastrol, which could be reversed by PI3K inhibitor. CONCLUSIONS: Our data revealed that the effect of celastrol on apoptosis was due to miR-21 inhibiting the PI3K/Akt-dependent NF-κB pathway.

Neutrophil-to-lymphocyte ratio in colorectal tissue affects prognosis in patients with colorectal cancer.

The objective of this investigation was to analyse the correlation between the neutrophil-to-lymphocyte ratio (NLR) status in the immune microenvironment (IME) and the prognostic outcomes of patients who have undergone radical surgery for colorectal cancer (CRC). In light of the continued prevalence of CRC in China, this study utilised Kaplan-Meier and Cox regression analyses to assess the prognostic relevance of NLR status in IME among patients with CRC. Furthermore, cellular experiments, such as cell scratching, were conducted to elucidate the underlying mechanisms of NLR's impact on CRC. The NLR status in IME has been found to have a significant impact on the prognosis of patients with CRC. Patients who exhibit elevated intratumoural and extratumoural NLR are associated with a poor prognosis. Experimental evidence indicates that tumour-associated neutrophil (TAN) augments the migratory, invasive, and proliferative potential of HT-29, HCT-116 and LOVO colorectal cancer cells, while concurrently reducing their sensitivity to oxaliplatin. Conversely, lymphocytes have demonstrated cytotoxic effects on HT-29 cells. The NLR status in IME may serve as a prognostic biomarker for resectable CRC.

Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-κB activity.

BACKGROUND: Celastrol, a plant triterpene, is known to play important role in inhibiting proliferation and inducing apoptosis of gastric cancer cells. In the present study, the mechanism of celastrol on gastric cancer cells apoptosis was examined. METHODS: We assessed effect of celastrol on NF-κB signaling pathway in gastric cancer cells using western blot and luciferase reporter assay. The real-time PCR was used to evaluate the effect of celastrol on miR-146a expression, and miR-146a mimic to evaluate whether over-expression of miR-146a can affect NF-κB activity. Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor. RESULTS: Celastrol decreased gastric cancer cells viability in a dose-dependent. Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity. Furthermore, Celastrol could increase miR-146a expression and up-regulation of miR-146a expression could suppress NF-κB activity. More important, down-regulation of miR-146a expression can reverse the effect of celastrol on NF-κB activity and apoptosis in gastric cancer cells. CONCLUSIONS: In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

Expression and Clinical Significance of TIGIT in Primary Breast Cancer.

Purpose: The roles of T cell immunoreceptor with Ig and ITIM domains (TIGIT) in the diagnosis of primary breast cancer (PBC) are still unclear. This study was designed to investigate the expression of TIGIT in PBC patients, with an aim to analyze its diagnostic value in PBC. Patients and Methods: We first explore the expression of TIGIT in cancer patients based on TCGA database, and then we analyzed its correlation with clinicopathological features. Afterwards, we compared the protein and mRNA expressions of TIGIT in two BC cell lines (MCF-7 and MDA-MB-231) and normal breast epithelial cell line (MCF-10A). Subsequently, 56 PBC female patients admitted to the Taizhou People's Hospital from October 2018 to June 2021 were included in this study. Flow cytometry was used to detect TIGIT level on peripheral blood CD3+ T cells of PBC patients and healthy controls. TIGIT expression in PBC tissues was detected by immunohistochemistry (IHC) and immunofluorescence staining. Results: TCGA database showed that compared with adjacent tissues, TIGIT was significantly upregulated in tumor tissues. High TIGIT expression was positively correlated with tumor stage and negatively correlated with recurrence free survival (RFS) and overall survival (OS). TIGIT level in BC cell lines, peripheral blood and tumor tissues of PBC patients was significantly higher than that of control (P < 0.05). TIGIT level was correlated with age (P < 0.05), rather than tumor size, pathological type, lymph node metastasis, ER, PR, HER-2, and P53. ROC curve showed that the optimal critical value of peripheral blood TIGIT for BC screening was 23.38%. Postoperative TIGIT level in peripheral blood was significantly decreased compared to the preoperative TIGIT level (P < 0.05). Conclusion: TIGIT was upregulated in PBC and was correlated with age. It may be a potential target for the diagnosis and immunotherapy of PBC.

A demonstration based on multi-omics transcriptome sequencing data revealed disulfidptosis heterogeneity within the tumor microenvironment of esophageal squamous cell carcinoma.

BACKGROUND: It is of great concern to identify prognostic signatures for the prediction and prediction of esophageal squamous cell carcinoma (ESCC), which is the lethal pathological type of malignancy. METHOD: Bulk RNA sequencing and scRNA-seq data were retrieved from GSE53624, GSE53622, and GSE188900. Disulfidptosis-related differentially expressed genes (DEGs) were identified between disulfidptosis-high score and disulfidptosis-low score groups. Functional annotation of DEGs were analyzed by Gene Ontology (GO). Consistent clustering and co-expression modules were analyzed, and then constructed a risk score model via multivariate Cox regression analysis. Immune infiltration and immunotherapy response analyses were conducted based on risk score. qRT-PCR, colony formation assay, and flow cytometry analysis were conducted in KYSE-150 and TE-1 cell lines. RESULTS: Seven genes (CD96, CXCL13, IL2RG, LY96, TPK1, ACAP1, and SOX17) were selected as marker genes. CD96 and SOX17 are independent prognostic signatures for ESCC patients, with a significant correlation with infiltrated immune cells. ESCC patients had worse response to nivolumab in the high-risk group. Through cellular experiments, we found that CD96 expression was associated with apoptosis and cell cycle ESCC cells. CONCLUSION: In a word, the risk score based on disulfidptosis is associated with prognosis and the immune microenvironment, which may direct immunotherapy of ESCC. The key gene of risk score, namely CD96, plays a role in proliferation and apoptosis in ESCC. We offer an insight into the exploration of the genomic etiology of ESCC for its clinical management.

NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway.

BACKGROUND: NAT10 (N-acetyltransferase 10) is a newly identified novel acetyltransferase. Abnormal expression of NAT10 is associated with several human disorders, including cancer, autoimmune diseases, and cardiovascular disease. This study aimed to investigate the role of NAT10 in promoting lung cancer malignant progression through the NF-κB (nuclear factor κB) signaling pathway. METHODS: Cells lines BEAS-2B, NCI-H524, A549, PC-9, NCI-H23, and NCI-H258 were cultured for identification. Western blotting and PCR assays determined gene expression within the sample cells. Cellular functionality was assayed using CCK8 (Cell Counting Kit-8), Dual-Luciferase Reporter, and Colony formating. RESULTS: The PCR assay and Western blotting showed a significant elevation of NAT10 levels within tumor tissues compared to paraneoplastic tissues (p < 0.05). Specifically, NAT10 only affected the expression and content of RelA/p65 in lung cancer. Analysis from the TCGA (The Cancer Genome Atlas) database indicated that elevated expression levels of NAT10 in tumors can be a good prognostic indicator for lung cancer patients. The CCK8 assay showed that the knockdown of NAT10 significantly suppressed the A549 cells' progression rate (p < 0.05). The colony formation assays further confirmed that the overexpression of NAT10 significantly increased the generation of clones in the NCI-H524 cells (p < 0.05). The proliferation rate influenced by the overexpression of NAT10 was inhibited by blocking the NF-κB signaling pathway (p < 0.05). Dual-luciferase reporter gene assay results revealed NAT10's potential in promoting the NF-κB signaling pathway's activity in lung cancer. Immunohistochemical staining underscored a strong link between NAT10 protein expression and the NF-κB signaling pathway in lung cancer tissues. CONCLUSIONS: NAT10's expression is significantly upregulated in tumor tissues, supported by PCR results. NAT10 plays a role in the development and proliferation of lung cancer cells and can activate the NF-κB signaling pathway in lung cancer. Hence, NAT10's regulation of the NF-κB signaling pathway is critical in the malignant proliferation of lung cancer.

Potential application of Klotho as a prognostic biomarker for patients with diabetic kidney disease: a meta-analysis of clinical studies.

Background: Diabetic kidney disease (DKD) is a serious diabetic complication and the performance of serum Klotho in DKD's prognostic evaluation is controversial. Objective: To assess the association of serum Klotho with adverse kidney and non-kidney clinical outcomes in patients with DKD. Design: Clinical studies regarding the relationship of serum Klotho with DKD were included. Study quality was assessed using the Newcastle-Ottawa scale. Subgroup and sensitive analyses were performed to search for the source of heterogeneity. Data sources and methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane library databases up to 27 September 2022. The associations of Klotho with albuminuria, such as the urinary albumin creatinine ratio (UACR), kidney outcomes such as persistent albuminuria, estimated glomerular filtration rate decline, and non-kidney outcomes such as diabetic retinopathy, cardiovascular morbidity, and mortality, were evaluated. The indicators, such as the correlation coefficient (r), odds ratio (OR), relative risk, and hazard ratio, were retrieved or calculated from the eligible studies. Results: In all, 17 studies involving 5682 participants fulfilled the inclusion criteria and were included in this meta-analysis. There was no significant association of serum Klotho with UACR in DKD patients [summary r, -0.28 (-0.55, 0.04)] with high heterogeneity. By contrast, a strong association was observed regarding serum Klotho with kidney outcomes [pooled OR, 1.60 (1.15, 2.23)], non-kidney outcomes [pooled OR, 2.78 (2.11, 3.66)], or combined kidney and non-kidney outcomes [pooled OR, 1.96 (1.45, 2.65)] with moderate heterogeneity. Subgroup analysis indicated that age, study design, and the estimated glomerular filtration rate may be the sources of heterogeneity. Conclusion: A decreased serum Klotho level is possibly associated with an increased risk of developing kidney and non-kidney clinical outcomes in DKD patients; thus, Klotho may be a possible biomarker to predict DKD clinical outcomes. Additional studies are needed to clarify and validate Klotho's prognostic value.