Highly Reliable Van Der Waals Memory Boosted by a Single 2D Charge Trap Medium.

Charge trap materials that can store carriers efficiently and controllably are desired for memory applications. 2D materials are promising for highly compacted and reliable memory mainly due to their ease of constructing atomically uniform interfaces, however, remain unexplored as being charge trap media. Here it is discovered that 2D semiconducting PbI2 is an excellent charge trap material for nonvolatile memory and artificial synapses. It is simple to construct PbI2 -based charge trap devices since no complicated synthesis or additional defect manufacturing are required. As a demonstration, MoS2 /PbI2 device exhibits a large memory window of 120 V, fast write speed of 5 µs, high on-off ratio around 106 , multilevel memory of over 8 distinct states, high reliability with endurance up to 104 cycles and retention over 1.2 × 104 s. It is envisioned that PbI2 with ionic activity caused by the natively formed iodine vacancies is unique to combine with unlimited 2D materials for versatile van der Waals devices with high-integration and multifunctionality.

Evaluation the role of cuproptosis-related genes in the pathogenesis, diagnosis and molecular subtypes identification of atherosclerosis.

Background: At present, the pathogenesis of atherosclerosis has not been fully elucidated, and the diagnosis and treatment face great challenges. Cuproptosis is a novel cell death pattern that might be involved in the development of atherosclerosis. However, no research has reported the correlation between cuproptosis and atherosclerosis. Methods: The differential cuproptosis-related genes (CRGs) between atherosclerosis group and control group (A-CRGs) were discovered via differential expression analysis. The correlation analysis, PPI network analysis, GO, KEGG and GSEA analysis were performed to investigate the function of A-CRGs. The differences of biological function between atherosclerosis group and control group were investigated via immune infiltration analysis and GSVA. The LASSO regression, nomogram and machine learning models were constructed to predict atherosclerosis risk. The atherosclerosis molecular subtypes clusters were discovered via unsupervised cluster analysis. Subsequently, we used the above research methods to analyze the differential CRGs between clusters (M-CRGs) and evaluate the molecular subtypes identification performance of M-CRGs. Finally, we verified the diagnostic value for atherosclerosis and role in cuproptosis of these CRGs through the validation set and in vitro experiments. Results: Five A-CRGs were identified and they were mainly related to the biological function of copper ion metabolism and immune inflammatory response. The diagnostic models and nomogram of atherosclerosis based on 5 A-CRGs indicated that these genes had well diagnostic value. A total of two molecular subtypes clusters were obtained in the atherosclerosis group. There were many differences in biological functions between these two molecular subtypes clusters, such as mitochondrial outer membrane permeabilization and primary immunodeficiency. In addition, 3 M-CRGs were identified in the 2 clusters. Machine learning models and nomogram constructed based on M-CRGs showed that these genes had well molecular subtypes identification efficacy. In the end, the results of in vitro experiment and validation set confirmed the diagnostic value for atherosclerosis and role in cuproptosis of these genes. Conclusion: The cuproptosis may be a potential pathogenesis of atherosclerosis and CRGs may be promising markers for the diagnosis and molecular subtypes identification of atherosclerosis.

Research and practice of the BOPPPS teaching model based on the OBE concept in clinical basic laboratory experiment teaching.

"Clinical basic inspection technology" is one of the essential courses in the medical laboratory profession. Combining the characteristics of the discipline itself, the research and practice of the BOPPPS model based on the OBE concept in clinical basic laboratory experiment teaching are discussed, and the reform of in teaching objectives, teaching contents, and teaching design path is implemented. The "student-centered" teaching process is divided into six stages: before, during, and after class, and the teaching process is continuously improved to achieve the desired teaching effect. Results of the experiment teaching show that the model has improved students' active participation and developed their clinical thinking skills, and more than 95% of students are satisfied with this teaching model.

The association between the thyroid feedback quantile-based index and serum uric acid in U.S. adults.

OBJECTIVES: Previous studies have shown that there may be a positive correlation between serum uric acid levels and hyperthyroidism. However, the relationship between thyroid function and serum uric acid in healthy people is unclear. This study analyzed the relationship between impaired thyroid hormone sensitivity and serum uric acid levels, and presented them in quantitative form. RESEARCH DESIGN AND METHODS: This is a cross-sectional study of 4460 adults (male: 2300; female: 2160) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. Parameters representing central sensitivity to thyroid hormones were calculated as: thyroid feedback quantile-based index (TFQIFT4), thyroid stimulating hormone index (TSHI), and total thyroxine (T4) resistance index (TT4RI); Peripheral sensitivity to thyroid hormone was evaluated by FT3/FT4 ratio. In addition, we have innovated total triiodothyronine (T3) resistance index (TT3RI) and TFQIFT3 indexes based on FT3 and TSH. Multiple linear regression models were used to evaluate the correlation between thyroid resistance index and serum uric acid, and the results were presented graphically as smooth curve fittings. RESULTS: Higher levels of serum uric acid were associated with decreased sensitivity to thyroid hormones in euthyroid individuals. In conjunction with an increase in the thyroid hormone sensitivity index value, uric acid levels gradually increased as well. Furthermore, we found a segmented relationship between TT3RI and serum uric acid changes. The saturation and threshold analyses indicated that 18.85 was the turning point (logarithmic likelihood ratio test = 0.036). When TT3RI < 18.85, the relationship between serum uric acid and TT3RI was not significant [ß(95% CI) 0.47 (- 0.05, 1.00), P = 0.077], but when TT3RI > 18.85, there was a significant rise in serum uric acid with an increase in TT3RI [ß(95% CI) 3.94 (0.94, 6.95), P = 0.010]. A further finding of the interaction test was that impaired thyroid hormone sensitivity and uric acid changes vary among different age groups and BMI levels. CONCLUSIONS: Decreased sensitivity to thyroid hormones was associated with high levels of serum uric acid in people with normal thyroid function. The interaction test shows that different age groups and BMI groups impact the association between impaired thyroid hormone sensitivity and serum uric acid. Furthermore, smooth curve fitting revealed a segmental relationship between TT3RI and serum uric acid levels.

The effect of antibiotic prophylaxis on the incidence of surgical site infection after laparoscopic appendectomy for chronic appendicitis.

Background: The guidelinesthat specify whether antibiotic prophylaxis should be administered before laparoscopic clean-contaminated wound to prevent postoperative surgical site infection (SSI) need to be improved. Studies have shown that elective laparoscopic cholecystectomy with clean-contaminated wound does not require antibiotic prophylaxis. However, there are no studies on the effect of antibiotic prophylaxis on SSI after laparoscopic appendectomy for chronic appendicitis (LCA), which is a clean-contaminated wound. Methods: We conducted a single-center, double-blind, randomized controlled clinical trial. A total of 106 effective patients were randomly divided into the antibiotic group and saline group. Cefuroxime or clindamycin was administered intravenously in the antibiotic group (n = 52). Saline (0.9%) was administered intravenously in the saline group (n = 54). Interventions were administered as a single dose 30 min before surgery. Results: Among the 106 effective patients (median age, 37 years old [IQR, 25-45]; females, 77 [72.6%]), there were 6 cases (5.70%) of SSI: 3 cases (5.56%) in the saline group and 3 cases (5.70%) in the antibiotic group (OR = 1.00, [95% CI (0.20-5.4)], P = 0.96). There were no significant differences in the clinical outcomes of anal exhaust time, postoperative complications, and the symptom of primary abdominal pain between the two groups. Conclusion: For patients with chronic appendicitis undergoing laparoscopic appendectomy, preoperative intravenous antibiotic prophylaxis did not reduce the risk of SSI within 30 days of the surgery compared to the saline group. Trial registration: Registration number of China Clinical Trials Registration Center: ChiCTR2100048336.

Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges.

The oldest known highly conserved modification of RNA, N4-acetylcytidine, is widely distributed from archaea to eukaryotes and acts as a posttranscriptional chemical modification of RNA, contributing to the correct reading of specific nucleotide sequences during translation, stabilising mRNA and improving transcription efficiency. Yeast Kre33 and human NAT10, the only known authors of ac4C, modify tRNA with the help of the Tan1/THUMPD1 adapter to stabilise its structure. Currently, the mRNA for N4-acetylcytidine (ac4C), catalysed by NAT10 (N-acetyltransferase 10), has been implicated in a variety of human diseases, particularly cancer. This article reviews advances in the study of ac4C modification of RNA and the ac4C-related gene NAT10 in normal physiological cell development, cancer, premature disease and viral infection and discusses its therapeutic promise and future research challenges.

Xinkeshu for coronary heart disease complicated with anxiety or depression: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of coronary heart disease (CHD) complicated with anxiety or depression is increasing year by year. However, many anti-anxiety drugs or antidepressants have a certain degree of adverse reactions and are not easily accepted by patients. Xinkeshu (XKS), as a proprietary Chinese patent medicine with "psycho-cardiology" effect, is one of the commonly used drugs in the treatment of CHD complicated with anxiety or depression in China. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of XKS for CHD complicated with anxiety or depression. METHODS: Nine different electronic databases were independently searched to include randomized controlled trials (RCTs) of XKS for CHD complicated with anxiety or depression published from inception to February 2022, and the methodological quality was evaluated using the bias risk assessment tool from Cochrane Handbook 5.0 and the modified Jadad scale. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. The GRADE Profiler 3.6.1 and TSA 0.9.5.10 beta were adopted to evaluate the certainty and conclusiveness of the evidence. RESULTS: A total of 18 RCTs involving 1907 subjects were included. There were 956 subjects in the XKS group and 951 subjects in the control group. Baseline conditions were consistent and comparable between the groups. Compared with single-use western medicine (WM), XKS combined with WM significantly reduced scores of Hamilton Anxiety Scale (HAMA) [Mean difference (MD) = -7.60, 95% confidence interval (95% CI) (-10.37, -4.83), P < 0.000 01], Zung Self-rating Anxiety Scale (SAS) [MD = -10.05, 95% CI (-12.70, -7.41), P < 0.000 01], Hamilton Depression Scale (HAMD) [MD = -6.74, 95% CI (-11.58, -1.90), P = 0.006], and Zung Self-rating Depression Scale (SDS) [MD = -10.75, 95% CI (-17.05,-4.45), P = 0.000 8], as well as improved clinical effective rate [odds ratio (OR) = 4.24, 95% CI (2.47, 7.27), P < 0.000 01]. In terms of safety, 4 studies reported the adverse reactions in detail. The severity was mild and symptoms disappeared after treatment. CONCLUSION: Current evidence indicates that XKS may be effective and safe in the treatment of patients with CHD complicated with anxiety or depression. Since the quality of the literature included in this study was generally low, there is an urgent need for more RCTs with high quality, low bias risk and sufficient sample size to validate our conclusions.

Development and validation of a cardiovascular disease risk prediction model for patients with non-dialysis-dependent chronic kidney diseases based on the nomogram.

Introduction Most CKD patients experience cardiovascular issues before commencing renal replacement therapy. An accuracy prediction model is helpful for physicians to assess cardiovascular prognoses in each individual, and to provide insights on how to outline individualized lines of therapy. Method This study enrolled 1138 participants with non-dialysis-dependent chronic kidney disease (NDD-CKD). Following a proportion of 7:3, patients were randomly assigned to training and validation cohorts. The relevant predictors of cardiovascular events were screened using the least absolute shrinkage and selection operator (Lasso) regression. The area under the receiver operating characteristic curve (AUC) and the calibration curve with 1000 bootstraps resamples were used to assess the nomogram's performance. Tests on the discrimination of the prediction model used Kaplan-Meier (KM) curve. Results After screening all the predictors by lasso regression, the five remaining ones (albumin, estimated glomerular filtration rate, etiology of CKD, cardiovascular disease history, and age) were used to construct the prediction model. The AUC of 1-year, 2-year, and 3-year was 0.81 (95% CI = 0.75-0.87), 0.80 (95% CI = 0.75-0.86), and 0.80 (95% CI = 0.73-0.86), respectively. The calibration curve and the KM curve showed good prediction features, and the external validation also had a good prediction performance (AUC of 1-, 2-, and 3-years were 0.77, 0.84, and 0.82, respectively). Conclusion We successfully developed a novel nomogram that has decent prediction performance and can be used for assessing the probability of cardiovascular events in patients with NDD-CKD, displaying valuable potential for clinical application.

Plasma S-Klotho level affects the risk of hyperuricemia in the middle-aged and elderly people.

BACKGROUND: Soluble Klotho (S-Klotho) is an anti-aging protein mainly secreted by the kidneys. Hyperuricemia is prevalent among middle-aged and elderly individuals, which affects the development of various chronic diseases. However, there are relatively few studies investigating the association between plasma S-Klotho levels and hyperuricemia in middle-aged and elderly individuals. This study sought to clarify the relationship between S-Klotho and the risk of hyperuricemia in middle-aged and elderly people. METHODS: During 2007-2016, a total of 50,588 people participated in the National Health and Nutrition Examination Survey. Finally, 12,441 middle-aged and elderly people (aged 40-79) completed the soluble Klotho tests and had obtained complete data. S-Klotho was detected by ELISA kit, and the relationship between S-Klotho and hyperuricemia was assessed by multiple logistic regression. Hyperuricemia is defined as serum uric acid levels higher than or equal to 420 mmol/l in men and 360 mmol/l in women. RESULTS: In the middle-aged and elderly, plasma S-Klotho levels were negatively correlated with hyperuricemia, and there was a saturation effect. The inflection point of S-Klotho was 927.8 pg/ml (logarithmic likelihood ratio test = 0.002). When plasma S-Klotho < 927.8 pg/ml, the prevalence of hyperuricemia in middle-aged and elderly individuals with higher levels of S-Klotho decreased by 25.6% compared with those with low levels of S-Klotho [Q4 vs Q1, OR: 0.744, 95%CI: (0.634, 0.874), P < 0.001]; In different age groups, S-Klotho had a significantly greater effect on hyperuricemia in middle-aged people [age: 40-65 years, Q4 vs Q1, OR (95%CI): 0.69 (0.58, 0.82), P < 0.001; Age > 65 years: Q4 vs Q1, OR (95%CI): 0.72 (0.56, 0.92), P = 0.008)].When the level of S-Klotho was higher, the risk of hyperuricemia in men was lower than that in women [male: Q4 vs Q1, OR (95%CI): 0.67 (0.56, 0.81), P < 0.001; female: Q4 vs Q1 (95%CI):0.72 (0.58, 0.88), P < 0.001]. CONCLUSIONS: In middle-aged and elderly individuals, plasma S-Klotho levels were inversely correlated with hyperuricemia, with a saturation effect. Given the limitations of the research results, the underlying mechanism between S-Klotho and hyperuricemia should be further explored.

Double Signal Amplification Strategy for Dual-Analyte Fluorescent Aptasensors for Visualizing Cancer Biomarker Proteins.

The simultaneous analysis of diversified biomarkers with high sensitivity and in a point-of-care (POC) manner is of great significance for facile and early cancer diagnosis. Herein, we develop a target amplification-assisted ratiometric fluorescence assay (TARFA) platform integrating the dual-amplification strategy and colorimetric readout technology for sensitive and specific detection of two malignancy-associated biomarkers. Meanwhile, the NIR-excited alkaline-earth sulfide nanodots (ASNDs) with an ultrasmall (<10 nm) diameter and tunable emission wavelength are employed to replace commonly UV/visible light-excited fluorescent labels to minimize background interference from the sample matrix. Unique advantages of the ASNDs, together with superiority of consecutive signal amplification of enzymatic target recycling (ETR) and hybridization chain reaction (HCR), realize the pg/mL-range detection limit in specifically recognizing the vascular endothelial growth factor (VEGF) and soluble interleukin-6 receptors (sIL-6R). The combination detection of the dual analyte exhibits an improved sensitivity for cancer diagnosis. The addition of the target biomarkers leads to an increasingly ratiometric RGB signal, and quantification based on the ratio-dependent signal is more reliable rather than measuring the absolute RGB signals. Moreover, perceptible color transformation makes the TARFA platform competent for visual analysis of the target analytes as convenient as reading the pH indicator strip, and hue-based image analysis also improves the method with fine precision by quantitatively identifying the visual color. This work provides a new kind of NIR-excited aptasensing platform with a low detection limit, high throughput, and great portability, which also highlights the potential of the ASNDs in biomolecular fluorescent labeling.

Pathophysiology and Clinical Management of Autoimmune Encephalitis-Associated Seizures.

Seizures are a very common manifestation of autoimmune encephalitis (AE), ranging from 33% to 100% depending on the antigen, most often accompanied by other clinical features such as behavioral changes, movement disorders, memory deficits, autoimmune disturbances, and altered levels of consciousness. Unusual seizure frequency, resistance to antiepileptic treatment, and often, definitive response to immunotherapy emphasize the importance for neurologists to consider the probable etiology of immune disorders. Studies on pathogenic mechanisms of autoantibodies have improved the understanding of different pathophysiologies and clinical characteristics of different AE groups. In encephalitis with antibodies to neuronal extracellular antigens, autoantibodies play a direct role in disease pathogenesis. They have access to target antigens and can potentially alter the structure and function of antigens but induce relatively little neuronal death. Prompt immunotherapy is usually very effective, and long-term antiepileptic treatment may not be needed. In contrast, in encephalitis with antibodies against intracellular antigens, autoantibodies may not be directly pathogenic but serve as tumor markers. These autoantibodies cannot reach intracellular target antigens and are considered to result from a T-cell-mediated immune response against antigens released by apoptotic tumor cells, which contain nerve tissue or express neuronal proteins. Neuronal loss is frequently described and predominantly induced through cytotoxic T-cell mechanisms. They often exhibit an inadequate response to immunotherapy and require early tumor treatment. Long-term antiepileptic treatment is usually needed. In conclusion, each neural autoantibody can specifically precipitate seizures. Early proper management of these cases may help prevent neurological deterioration and manage the occurrence of seizures. Consequently, confirmation of the presence of neuronal autoantibodies is strongly recommended even in patients with confirmed AE, as they are not only essential in achieving a good outcome but also may provide evidence for underlying neoplasia.

Polysaccharides, Next Potential Agent for the Treatment of Epilepsy?

Epilepsy is a chronic neurological disorder. Current pharmacological therapies for epilepsy have limited efficacy that result in refractory epilepsy (RE). Owing to the limitations of conventional therapies, it is needed to develop new anti-epileptic drugs. The beneficial effects of polysaccharides from Chinese medicines, such as Lycium barbarum polysaccharides (COP) and Ganoderma lucidum polysaccharides (GLP), for treatment of epilepsy include regulation of inflammatory factors, neurotransmitters, ion channels, and antioxidant reactions. Especially, polysaccharides could be digested by intestinal microbial flora, referred as "intestinal brain organ" or "adult's second brain", may be the target for treatment of epilepsy. Actually, polysaccharides can effectively improve the type and quantity of intestinal flora such as bifidobacteria and lactic acid bacteria and achieve the purpose of treating epilepsy. Therefore, polysaccharides are hypothesized and discussed as potential agent for treatment of epilepsy.

Immune Infiltration and Clinical Outcome of Super-Enhancer-Associated lncRNAs in Stomach Adenocarcinoma.

Super-enhancers (SEs) comprise large clusters of enhancers that highly enhance gene expression. Long non-coding RNAs (lncRNAs) tend to be dysregulated in cases of stomach adenocarcinoma (STAD) and are vital for balancing tumor immunity. However, whether SE-associated lncRNAs play a role in the immune infiltration of STAD remains unknown. In the present study, we identified SE-associated lncRNAs in the H3K27ac ChIP-seq datasets from 11 tumor tissues and two cell lines. We found that the significantly dysregulated SE-associated lncRNAs were strongly correlated with immune cell infiltration through the application of six algorithms (ImmuncellAI, CIBERSORT, EPIC, quantiSeq, TIMER, and xCELL), as well as immunomodulators and chemokines. We found that the expression of SE-associated lncRNA TM4SF1-AS1 was negatively correlated with the proportion of CD8+ T cells present in STAD. TM4SF1-AS1 suppresses T cell-mediated immune killing function and predicts immune response to anti-PD1 therapy. ChIP-seq, Hi-C and luciferase assay results verified that TM4SF1-AS1 was regulated by its super-enhancer. RNA-seq data showed that TM4SF1-AS1 is involved in immune and cancer-related processes or pathways. In conclusion, SE-associated lncRNAs are involved in the tumor immune microenvironment and act as indicators of clinical outcomes in STAD. This study highlights the importance of SE-associated lncRNAs in the immune regulation of STAD.

NIR-to-Vis Handheld Platforms for Detecting miRNA Level and Mutation Based on Sub-10 nm Sulfide Nanodots and HCR Amplification.

Sub-10 nm monodisperse alkaline-earth sulfide nanodots (ASNDs) with bright near-infrared (NIR)-excitation fluorescence and adjustable emission wavelength were prepared by a thermal decomposition method for the first time. The ASNDs exhibited high NIR-to-vis conversion efficiency and served as multicolor fluorescent labels in the proposed miR-224 assay. Targeted detection of the miR-224 level and single-nucleotide variation in miR-224 was carried out on a smartphone-based platform using a hybridization chain reaction (HCR) amplification strategy. In the presence of miR-224, the ASND-labeled HCR probes self-assembled on the surface of the diagnosis kits, generating strong fluorescent signals linearly proportional to miR-224 contents in the range of 10-2000 fM. Significantly, mutations in miR-224 led to the variation in the fluorescence intensity ratio in RGB channels. Simultaneously, evident changes of fluorescent brightness and color were easily visualized by the naked eye, which enabled on-site discrimination of miR-224 with different mutant loci. This work provides a novel preparation approach for ultrasmall NIR excitation sulfide nanodots and reveals the potential of the as-synthesized ASNDs in point-of-care (POC) nucleic acid testing. Further, it may provide a handheld platform for miRNA single-nucleotide polymorphism analysis.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer.

About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40 Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for C/C, 44.7% for C/G and 41.1% for G/G. The average tumor regression rate after 40 Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of C/C genotype was 44.6% ± 0.170, which was higher than that of genotype C/G and G/G (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F = 3.169 p = 0.045). The higher tumor regression rate in patients with C/C genotype suggested that G allele was a protective factor against radiation therapy. Using the median tumor regression rate of 34%, we divided the entire cohort into two groups, and found that the frequency distribution of PARP-1 gene rs3219073 had significant difference between these two groups (p < 0.05). These results showed that PARP-1 gene polymorphism may affect patient radiation sensitivity and predict the efficacy of radiotherapy. It therefore presents an opportunity for developing new therapeutic targets to improve radiotherapy outcome.

Integrated signaling system under endoplasmic reticulum stress in eukaryotic microorganisms.

The endoplasmic reticulum (ER) is a multifunctional organelle, which is crucial for correct folding and assembly of secretory and transmembrane proteins. Perturbations of ER function can cause ER stress. ER stress can activate the unfolded protein response (UPR) to cope with the accumulation of misfolded proteins and protein toxicity. UPR is a coordination system that regulates transcription and translation, leading to the recovery of ER homeostasis or cell death. However, cells have an integrated signaling system to cope with ER stress, which helps cells to restore and balance their ER function. The main components of this system are ER-associated degradation (ERAD), autophagy, hypoxia signaling, and mitochondrial biogenesis. If the balance cannot be restored, the imbalance will lead to cell death or apoptosis, or even to a series of diseases. In this review, a series of activities to restore the homeostasis of cells during ER stress are discussed. KEY POINTS: • Endoplasmic reticulum (ER) plays a key role in the biological process of cells. • Perturbations of ER function can cause ER stress, including the ER overload response (EOR), sterol-regulated cascade reaction, and the UPR. • Cells have an integrated signaling system (ERAD, autophagy, hypoxia signaling, and mitochondrial biogenesis) to cope with the adverse impact caused by ER stress.

Long Noncoding RNA OIP5-AS1 Promotes the Disease Progression in Nasopharyngeal Carcinoma by Targeting miR-203.

Nasopharyngeal carcinoma (NPC) is a kind of malignancy generated from the nasopharyngeal epithelium. Recently, long noncoding RNA (lncRNA) has been shown to be involved in the regulation of many signaling pathways and is closely associated with carcinogenesis and tumor progression. However, the precise role of lncRNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in NPC is not well understood. Here, we find that OIP5-AS1 is overexpressed in NPC patient specimens and NPC cell lines. Further investigations reveal that knockdown of OIP5-AS1 significantly inhibits the proliferation, migration, and invasion and accelerates the apoptosis of NPC cells in vitro. Consistent with these findings, NPC progression is significantly slowed in mice when OIP5-AS1 is knocked down. Interestingly, there is a functional link between OIP5-AS1 and microRNA-203 (miR-203), a tumor suppressor, in NPC cells. In conclusion, our data demonstrate that OIP5-AS1 plays an important role in the development and progression of NPC by targeting miR-203 and therefore provide a promising target for the treatment of NPC.

Z-Guggulsterone Induces Apoptosis in Gastric Cancer Cells through the Intrinsic Mitochondria-Dependent Pathway.

BACKGROUND: To study the effects of z-guggulsterone on gastric cancer cell apoptosis and the mechanism related. MATERIALS AND METHODS: Human gastric tumor SGC-7901 cells and GES-1 normal epithelial cells were treated with z-guggulsterone (0-75 µM) for 24 h. MTT assay was applied to evaluate cell proliferation. Flow cytometry and Hoechst staining were used to assess cell apoptosis. Western blotting was applied to evaluate FXR, small heterodimer partner (SHP), Bcl-2, and Bax protein expression. ELISA was applied to gain the levels of active caspase-3 and the contents of TNF-α, TGF-ß1, and VEGF. RESULTS: The expression levels of FXR and SHP were higher in tumor cells than in normal epithelial cells. Inhibition of FXR signaling with z-guggulsterone dose-dependently inhibited SGC-7901 cell proliferation and promoted SGC-7901 cell apoptosis. Bcl-2 protein expression was significantly decreased, and active caspase-3 and Bax protein expression was increased in SGC-7901 cells incubated with z-guggulsterone. The content of TNF-α was significantly increased, and the contents of VEGF and TGF-ß1 were decreased in SGC-7901 cells incubated with z-guggulsterone. CONCLUSIONS: Inhibition of FXR signaling with z-guggulsterone induced anticancer effects in SGC-7901 cells by decreasing cell proliferation and promoting apoptosis. Z-guggulsterone induced cell apoptosis through the mitochondria-dependent pathway.

Characterization of the Relationship Between the Expression of Aspartate ß-Hydroxylase and the Pathological Characteristics of Breast Cancer.

BACKGROUND This study aimed to investigate the relationship between the expression of aspartate b-hydroxylase (ASPH) and the molecular mechanisms of ASPH-related genes in breast cancer (BC). MATERIAL AND METHODS ASPH expression was determined by immunohistochemistry and western blot analysis in samples of BC tissues and adjacent normal tissues. ASPH mRNA expression data and their clinical significance in BC were retrieved from the Oncomine and GEPIA datasets. Enrichment analysis of genes coexpressed with ASPH and annotation of potential pathways were performed with Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis. Hub genes were shown in an ASPH coexpression gene-interaction network. The expression of the hub genes associated with patient survival were analyzed to determine the role of ASPH in the progression of BC. RESULTS ASPH levels were overexpressed in BC and correlated with cancer type, lymph node involvement, and TNM stage. Conversely, ASPH levels did not correlate with patient age, invasive carcinoma types, or molecular subtypes. Enrichment analysis showed the involvement of multiple pathways, including lipid metabolism and oxidation-reduction processes. Six hub genes, PPARG, LEP, PLIN1, AGPAT2, CAV1, and PNPLA2, were related to ASPH expression and had functional roles in the occurrence and progression of BC. CONCLUSIONS ASPH may be involved in the development of BC and may have utility as a prognostic biomarker in BC. The coexpression of ASPH-associated genes may also be beneficial in improving BC prognosis.