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Background: The occult onset and rapid progression of hepatocellular carcinoma (HCC) lead to an unsatisfactory overall survival (OS) rate. Established prognostic predictive models based on tumor-node-metastasis staging and predictive factors do not report satisfactory predictive efficacy. Arachidonic acid plays pivotal roles in biological processes including inflammation, regeneration, immune modulation, and tumorigenesis. We, therefore, constructed a prognostic predictive model based on seven genes linked to arachidonic acid metabolism, using samples of HCC patients from databases to analyze the genomic profiles. We also assessed the predictive stability of the constructed model., Methods: Sample data of 365 patients diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA, training set) and HCCDB18, GSE14520, and GSE76427 databases (validation sets). Patient samples were clustered using ConsensusClusterPlus analysis based on the expression levels of 12 genes involved in arachidonic acid metabolism that were significantly associated with HCC prognosis. Differentially expressed genes (DEGs) within different clusters were distinguished and compared using WebGestaltR. Immunohistochemistry (IHC) analysis was performed using a human HCC tissue microarray (TMA). Tumor immune microenvironment assessment was performed using ESTIMATE, ssGSEA, and TIDE., Results: Samples of patients with HCC were classified into three clusters, with significant differences in OS. Cluster 2 showed the best prognosis, whereas cluster 1 presented the worst. The three clusters showed significant differences in immune infiltration. We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis-related hub genes, making it a simplified prognostic model. TMA analysis for the seven target genes showed similar results of regression analyses. The high-risk group showed a significantly worse prognosis and reduced immunotherapy efficacy. Our model showed stable prognostic predictive efficacy., Conclusions: This seven-gene-based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

To fulfill the nutritional requirements of poultry, effective Zn supplementation is required due to Zn deficiency in basic feed. In this study, we investigated the effects of DMY-Zn (dihydromyricetin zinc chelate) on the growth performance, morphology, and biochemical indices; the expression of intestinal barrier-related genes; the intestinal microflora; and the cecum metabolome of Magang geese. A total of 300 14-day-old Magang geese (equal number of males and females) with an average body weight of 0.82 ± 0.08 kg were randomly divided into five groups and fed a basal diet; these groups were given DMY-Zn (low, medium, or high level of DMY-Zn with 30, 55, or 80 mg/kg Zn added to the basal diet) or ZnSO 4 (80 mg/kg Zn added) for 4 weeks. Our results revealed that DMY-Zn significantly impacts growth and biochemical indices and plays a significant role in regulating the intestinal barrier and microflora. DMY-Zn is involved in the upregulation of intestinal barrier gene (ZO1 and MUC2) expression, as well as upregulated Zn-related gene expression (ZIP5). On the other hand, a low concentration of DMY-Zn increased the ɑ diversity index and the abundance of Lactobacillus and Faecalibacterium. Additionally, a cecal metabolomics study showed that the main metabolic pathways affected by DMY-Zn were the pentose phosphate pathway, the biosynthesis of different alkaloids, and the metabolism of sphingolipids. In conclusion, DMY-Zn can reduce feed intake, increase the expression of intestinal barrier-related genes, help maintain the intestinal microflora balance, and increase the abundance of beneficial bacteria in the intestine to improve intestinal immunity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer with limited therapeutic options, and enhancing radiosensitivity remains a key challenge in improving treatment outcomes. Quercetin (Que) can inhibit the progression of hepatocellular carcinoma (HCC); however, its effect on HCC radiosensitivity remains unclear. This research investigates the role of Que in regulating HCC growth and radiosensitivity, aiming to provide a scientific foundation for enhancing the clinical efficacy of radiation therapy in HCC. The CCK-8 assay was used to determine the optimal treatment conditions for Que and X-rays. Changes in cell growth, cycle arrest, invasion, migration, the relative proportion of JC-1 red and green fluorescence (mitochondrial membrane potential), and the levels of ROS, MDA, SOD, and GSH-Px (oxidative stress) were assessed using flow cytometry, Transwell assays, JC-1 staining, Western blot, and ELISA, respectively, under Que, X-ray, and co-treatment conditions. The effect of miR-216a-3p knockdown on the action of Que was also explored, and the potential pathways by which Que regulates HCC growth and radiosensitivity were investigated in conjunction with in vivo subcutaneous transplantation tumor experiments. The in vitro treatment parameters for Que and X-rays were 100 µM and 4 Gy. Que combined with X-ray therapy enhanced HCC cell radiosensitivity, reduced proliferation, invasion, and migration, and promoted oxidative stress and apoptosis. Que was found to upregulate miR-216a-3p in HCC cells. Rescue experiments with miR-216a-3p knockdowns demonstrated that Que regulates HCC cell radiosensitivity via miR-216a-3p. In vivo research further showed that Que increased tumor sensitivity to X-rays by upregulating miR-216a-3p, thereby inhibiting HCC growth. In conclusion, Que has been shown to enhance HCC radiosensitization by upregulating miR-216a-3p and inhibiting HCC progression. Que may be a promising agent for increasing the radiosensitivity of HCC.

Prostate cancer (PCa) is one of the most common tumors affecting men all over the world. PCa has brought a huge health burden to men around the world, especially for elderly men, but its pathogenesis is unclear. In prostate cancer, epigenetic inheritance plays an important role in the development, progression, and metastasis of the disease. An important role in cancer invasion and metastasis is played by matrix metalloproteinases (MMPs), zinc-dependent proteases that break down extracellular matrix. We review two important forms of epigenetic modification and the role of matrix metalloproteinases in tumor regulation, both of which may be of significant value as novel biomarkers for early diagnosis and prognosis monitoring. The author considers that both mechanisms have promising therapeutic applications for therapeutic agent research in prostate cancer, but that efforts should be made to mitigate or eliminate the side effects of drug therapy in order to maximize quality of life of patients. The understanding of epigenetic modification, MMPs, and their inhibitors in the functional regulation of prostate cancer is gradually advancing, it will provide a new technical means for the prevention of prostate cancer, early diagnosis, androgen-independent prostate cancer treatment, and drug research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Zhejiang Shuren University. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the in vitro antioxidant activity of zinc ascorbate (AsA-Zn), its effects on the growth performance of and liver function in Magang geese under heat stress, and its potential mechanism. At AsA-Zn concentrations of 7.5, 15, 30, and 60 µmol/L, the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS· + ) radical scavenging rate increased significantly by 120.85%, 53.43%, 36.12%, and 0.99%, respectively, compared with that of ascorbic acid (AsA), indicating that AsA-Zn had better antioxidant performance in vitro. In this study, Magang geese were divided into a control group (basal diet, CON) and experimental groups, who received the basal diet supplemented with 400 mg/kg AsA or 30 (AsA-Zn30), 60 (AsA-Zn60), or 90 (AsA-Zn90) mg/kg AsA-Zn. AsA-Zn supplementation considerably reduced the feed-to-gain ratio, whereas both AsA and AsA-Zn significantly increased the thymus index. Moreover, AsA-Zn supplementation improved serum protein levels, lipid metabolism, liver function, and antioxidant capacity while reducing hepatocyte vacuolar degeneration. Furthermore, supplementation with AsA-Zn60 significantly increased the total antioxidant capacity, glutathione peroxidase activity, and superoxide dismutase activity and decreased the malondialdehyde content in the serum, liver, and hepatic mitochondria (P < 0.05), with more pronounced effects in the AsA-Zn60 group. Moreover, supplementation with ASA-Zn regulated the Nrf 2 signaling pathway and significantly increased the expression of genes encoding antioxidant-related factors in the liver. In conclusion, AsA-Zn has good antioxidant activity, and AsA-Zn supplementation may improve the antioxidant capacity of heat-stressed geese and promote their growth. Supplementation with 30 mg/kg AsA-Zn is recommended., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plant cells employ intricate defense mechanisms, including mRNA decay pathways, to counter viral infections. Among the RNA quality control (RQC) mechanisms, nonsense-mediated decay (NMD), no-go decay (NGD), and nonstop decay (NSD) pathways play critical roles in recognizing and cleaving aberrant mRNA molecules. Turnip crinkle virus (TCV) is a plant virus that triggers mRNA decay pathways, but it has also evolved strategies to evade this antiviral defense. In this study, we investigated the activation of mRNA decay during TCV infection and its impact on TCV RNA accumulation. We found that TCV infection induced the upregulation of essential mRNA decay factors, indicating their involvement in antiviral defense and the capsid protein (CP) of TCV, a well-characterized viral suppressor of RNA silencing (VSR), also compromised the mRNA decay-based antiviral defense by targeting AtXRN4. This interference with mRNA decay was supported by the observation that TCV CP stabilized a reporter transcript with a long 3' untranslated region (UTR). Moreover, TCV CP suppressed the decay of known NMD target transcripts, further emphasizing its ability to modulate host RNA control mechanisms. Importantly, TCV CP physically interacted with AtXRN4, providing insight into the mechanism of viral interference with mRNA decay. Overall, our findings reveal an alternative strategy employed by TCV, wherein the viral coat protein suppresses the mRNA decay pathway to facilitate viral infection., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

The rapid diagnosis of pathogenic infections plays a vital role in disease prevention, control, and public health safety. Recombinase-aided amplification (RAA) is an innovative isothermal nucleic acid amplification technology capable of fast DNA or RNA amplification at low temperatures. RAA offers advantages such as simplicity, speed, precision, energy efficiency, and convenient operation. This technology relies on four essential components: recombinase, single-stranded DNA-binding protein (SSB), DNA polymerase, and deoxyribonucleoside triphosphates, which collectively replace the laborious thermal cycling process of traditional polymerase chain reaction (PCR). In recent years, the CRISPR-Cas (clustered regularly interspaced short palindromic repeats-associated proteins) system, a groundbreaking genome engineering tool, has garnered widespread attention across biotechnology, agriculture, and medicine. Increasingly, researchers have integrated the recombinase polymerase amplification system (or RAA system) with CRISPR technology, enabling more convenient and intuitive determination of detection results. This integration has significantly expanded the application of RAA in pathogen detection. The step-by-step operation of these two systems has been successfully employed for molecular diagnosis of pathogenic microbes, while the single-tube one-step method holds promise for efficient pathogen detection. This paper provides a comprehensive review of RAA combined with CRISPR-Cas and its applications in pathogen detection, aiming to serve as a valuable reference for further research in related fields., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Zhu, Zhang, Ren, He, Zhou, Yin, Wang, Zhong, Wang, Xiao, Zhu, Yin and Yu.)

Objectives: To address gaps in health services for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB), a treatment cascade model was used to evaluate patient retention and attrition at each successive step required to achieve a successful treatment outcome., Methods: From 2015-2018, a four-step treatment cascade model was established in patients with confirmed MDR/RR-TB in southeast China. Step 1: diagnosis of MDR/RR-TB, step 2: Initiation of treatment, step 3: still under treatment at 6 month and step 4: cure or completion of MDR/RR-TB treatment, with each successive step including a gap that shows attrition of patients between steps. The retention and attrition of each step were graphed. Multi-variate logistic regression was carried out to further identify potential factors associated with the attrition., Results: In the treatment cascade consisting of 1752 MDR/RR-TB patients, the overall patient attrition rate was 55.8% (978/1752), with 28.0% (491/1752), 19.9% (251/1261), and 23.4% (236/1010) of patients attrition in the first, second, and third gap. Factors associated with MDR/RR-TB patients not initiating treatment included age ≥60 years (OR:2.875), and time for diagnosis ≥30 days (OR: 2.653). Patients who were diagnosed with MDR/RR-TB through rapid molecular test (OR: 0.517) and non-migrant residents of Zhejiang Province (OR: 0.273) both exhibited a lower likelihood of attrition during the treatment initiation phase. Meanwhile, old age (OR: 2.190) and non-resident migrants to the province were factors associated with not completing ≥ 6 months of treatment. Old age (OR: 3.883), retreatment (OR: 1.440), and time to diagnosis ≥30 days (OR: 1.626) were factors contributing to poor treatment outcomes., Conclusion: Several programmatic gaps were identified in the MDR/RR-TB treatment cascade. Future policies should provide more comprehensive support for vulnerable populations to improve the care quality at each step., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Highly efficient single-component full-color emitting Ca 6 Y 2 Na 2 (PO 4 ) 6 F 2 (CYNPF):Eu 2+ ,Tb 3+ ,Mn 2+ phosphors have been synthesized by a high-temperature solid-state reaction. Coupled with the Eu 2+ , Tb 3+ , and Mn 2+ emission bands centered at 455 nm, 547 nm, and 580 nm, color-tunable white light can be generated. The energy transfer (ET) process from Eu 2+ to Tb 3+ and Mn 2+ is attributed to the resonant dipole-dipole/dipole-dipole interaction mechanism with ultra-high ET efficiency (>90%). The emission color of the phosphors can be tuned from blue to yellowish green and orange with the corresponding CIE chromaticity coordinates of (0.1719, 0.1215), (0.2852, 0.4289), and (0.4752, 0.3903), respectively. Through controlling the concentration ratio of Tb 3+ and Mn 2+ ions, optimal white light emission can be obtained with CIE coordinates of (0.3381, 0.3353) excited at 365 nm, which is very close to the National Television Standards Committee white (0.330, 0.330). The thermal stability of the Eu 2+ , Tb 3+ , and Mn 2+ codoped CYNPF phosphors has been investigated systematically. A single-component white LED (wLED) device has been fabricated by combining the CYNPF:Eu 2+ ,Tb 3+ ,Mn 2+ phosphor with a 365 nm near-ultraviolet (n-UV) LED chip, which exhibits a high color rendering index ( R a = 80.2) along with a low color temperature of 5207 K and CIE coordinates of (0.3212, 0.3221). The results suggest that the phosphors can be used as a candidate material for single-component white phosphors for n-UV excited full-visible-spectrum wLEDs.

Multiview clustering has received great attention and numerous subspace clustering algorithms for multiview data have been presented. However, most of these algorithms do not effectively handle high-dimensional data and fail to exploit consistency for the number of the connected components in similarity matrices for different views. In this article, we propose a novel consistency-induced multiview subspace clustering (CiMSC) to tackle these issues, which is mainly composed of structural consistency (SC) and sample assignment consistency (SAC). To be specific, SC aims to learn a similarity matrix for each single view wherein the number of connected components equals to the cluster number of the dataset. SAC aims to minimize the discrepancy for the number of connected components in similarity matrices from different views based on the SAC assumption, that is, different views should produce the same number of connected components in similarity matrices. CiMSC also formulates cluster indicator matrices for different views, and shared similarity matrices simultaneously in an optimization framework. Since each column of similarity matrix can be used as a new representation of the data point, CiMSC can learn an effective subspace representation for the high-dimensional data, which is encoded into the latent representation by reconstruction in a nonlinear manner. We employ an alternating optimization scheme to solve the optimization problem. Experiments validate the advantage of CiMSC over 12 state-of-the-art multiview clustering approaches, for example, the accuracy of CiMSC is 98.06% on the BBCSport dataset.

Most plant viruses encode suppressors of RNA silencing (VSRs) to protect themselves from antiviral RNA silencing in host plants. The capsid protein (CP) of Turnip crinkle virus (TCV) is a well-characterized VSR, whereas SUPPRESSOR OF GENE SILENCING 3 (SGS3) is an important plant-encoded component of the RNA silencing pathways. Whether the VSR activity of TCV CP requires it to engage SGS3 in plant cells has yet to be investigated. Here, we report that TCV CP interacts with SGS3 of Arabidopsis in both yeast and plant cells. The interaction was identified with the yeast two-hybrid system, and corroborated with bimolecular fluorescence complementation and intracellular co-localization assays in Nicotiana benthamiana cells. While multiple partial TCV CP fragments could independently interact with SGS3, its hinge domain connecting the surface and protruding domains appears to be essential for this interaction. Conversely, SGS3 enlists its N-terminal domain and the XS rice gene X and SGS3 (XS) domain as the primary CP-interacting sites. Interestingly, SGS3 appears to stimulate TCV accumulation because viral RNA levels of a TCV mutant with low VSR activities decreased in the sgs3 knockout mutants, but increased in the SGS3-overexpressing transgenic plants. Transgenic Arabidopsis plants overexpressing TCV CP exhibited developmental abnormalities that resembled sgs3 knockout mutants and caused similar defects in the biogenesis of trans-acting small interfering RNAs. Our data suggest that TCV CP interacts with multiple RNA silencing pathway components that include SGS3, as well as previously reported DRB4 (dsRNA-binding protein 4) and AGO2 (ARGONAUTE protein 2), to achieve efficient suppression of RNA silencing-mediated antiviral defence., (© 2022 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Objective: To understand the trend of overall rifampicin resistance rates for tuberculosis in Zhejiang Province between 2015 and 2019., Methods: The basic demographic information of patients with tuberculosis who were screened for drug resistance in Zhejiang Province between January 1, 2015 and December 31, 2019 was collected through the national Tuberculosis Information Management System. The data were processed and analyzed using IBM SPSS 26.0 and GeoDa 1.14 software., Results: The total rifampicin resistance rate was 5.9% in 53,893 validated cases of drug resistance screening conducted in patients with pulmonary tuberculosis in Zhejiang Province during the study period. There was a decreasing trend in the rifampicin resistance rate in both initial and re-treated patients (P<0.001), but the rifampicin resistance rate was higher in re-treated TB patients than in TB patients receiving their initial treatment (11.4% vs 4.2%). The rate of drug resistance steadily decreased in all prefectures, and there was a significant upward trend in the use of the Xpert MTB/RIF rapid assay. An increasing trend was also identified in the rate of rifampicin and ofloxacin co-resistance (P<0.001)., Conclusion: The overall rate of rifampin resistance in patients with tuberculosis in Zhejiang Province in the past five years has shown a decreasing trend, but the rate of resistance to ofloxacin was high. Resistance testing to fluoroquinolones should be carried out as early as possible in patients whose diagnosis results indicate rifampin resistance, and more effective second-line treatment plans should be developed based on the results of this testing., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Ren et al.)

Natural killer T cells (NKTs) are an important part of the immune system. Since their discovery in the 1990s, researchers have gained deeper insights into the physiology and functions of these cells in many liver diseases. NKT cells are divided into two subsets, type I and type II. Type I NKT cells are also named iNKT cells as they express a semi-invariant T cell-receptor (TCR) α chain. As part of the innate immune system, hepatic iNKT cells interact with hepatocytes, macrophages (Kupffer cells), T cells, and dendritic cells through direct cell-to-cell contact and cytokine secretion, bridging the innate and adaptive immune systems. A better understanding of hepatic iNKT cells is necessary for finding new methods of treating liver disease including autoimmune liver diseases, alcoholic liver diseases (ALDs), non-alcoholic fatty liver diseases (NAFLDs), and liver tumors. Here we summarize how iNKT cells are activated, how they interact with other cells, and how they function in the presence of liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gu, Chu, Ma, Wang, Chen, Guan, Ren, Wu and Zhu.)

Healthcare workers (HCWs) are at a high risk for latent tuberculosis infection (LTBI) because of occupational exposure, and the attitudes and behaviors of frontline tuberculosis (TB)-related HCWs toward preventive treatment of LTBI in eastern China remain unknown. This study aimed to explore the attitudes and actual behaviors of TB-related HCWs toward TB preventive treatment (TPT) and to analyze the relevant factors influencing the attitudes of HCWs. A stratified random sample of 28 TB-designated hospitals was selected in Zhejiang Province, China. All TB-related HCWs in the selected hospitals were recruited to answer questionnaires and were tested for LTBI by the TB interferon gamma release assay. TPT use was assessed two years after the survey. Univariate analysis and binary logistic regression models were used to analyze the factors influencing the TPT intention of HCWs. A total of 318 TB-related HCWs were recruited from 28 TB-designated hospitals; 62.3% of them showed positive attitudes toward TPT, while the rest were reluctant to treat positive LTBI prophylactically. binary logistic regression analysis revealed that the factors influencing the attitudes of HCWs were mainly education level, household income, history of alcohol consumption, and workplace. The IGRA test found that 35.2% (112/318) of HCWs tested positive for LTBI. Most people refused treatment because of drug side effects, followed by the belief that treatment was ineffective, wanting to wait until the onset of the disease, and that it was too much trouble to take the medication. According to the results of a follow-up survey, only one of these HCWs underwent TPT, and the consistency rate of attitudes and behaviors was 36.6% (41/112). This study reveals different attitudes toward TPT among TB-associated HCWs in eastern China and a large gap between attitudes and actual action. The management of HCWs with LTBI still needs further strengthening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Ren, Liu, Peng, Chen, Chen and Jiang.)

Purpose: The aim of this study was to understand the resistance mechanism of ceftazidime/avibactam (CZA) in carbapenem-resistant Klebsiella pneumoniae under antibiotic selection pressure., Patients and Methods: Four CZA-resistant Klebsiella pneumoniae strains were isolated from two patients, and six CZA-resistant strains that were produced in vitro were screened from 25 carbapenem-resistant Klebsiella pneumoniae strains. The mechanisms of resistance to CZA of these strains were characterized by PCR and Sanger sequencing., Results: CZA-resistant Klebsiella pneumoniae with different resistance mechanisms (including upregulation of the expression of efflux pumps and KPC variants (KPC-14, KPC-44)) were isolated from the same patient (patient 1). In patient 2, the resistance mechanism of CZA-resistant Klebsiella pneumoniae was the mutation of KPC-2 to KPC-33. In addition, among the CZA-resistant Klebsiella pneumoniae that were produced in vitro, we found 3 new KPC variants: KPC-86 (D179G), KPC-87 (GT241A) and KPC-88 (G523T)., Conclusion: In this study, although the CZA-resistant bacteria originated from only two clinical patients, four different mechanisms of CZA resistance were detected. In the in vitro induction experiment, the mechanisms of resistance to CZA in strains from different patients were also different. The above result implies that the mechanisms of resistance to CZA are generally random and diverse. Therefore, elucidating the mechanism of resistance to CZA can provide a certain theoretical basis for the effective response of CZA-resistant strains and the selection of antibiotics., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Jiang et al.)

With the antibiotic crisis intensifies, the defense and treatment of pathogen infections in safe and effective fashion has become a critical issue. Herein, we report a novel and advanced type of sterilization agent designed via the functionalization DNA nanocarriers based on dihydromyricetin and CuO-loaded nanoparticles (DNA/DMY-CuO). Firstly, a pure dihydromyricetin (DMY) isolated from Ampelopsis grossedentata is used as a bridge to the stimulate the construction of DNA cross-linking networks by hydrogen bonding. Subsequently, a 3D spherical CuO-loaded nanocomposite (204.39 nm) is customized using the DNA/DMY network as a biological template through a simple coordination-assisted self-assembly method, which exhibits a high dispersibility, water-solubility and physiological stability. The reversible physical interactions in nanocarriers allows the selective separation and automatic release of CuO NPs from DNA/DMY-CuO in neutral and wound exudate environments, thereby extending the survival period of CuO NPs by nearly 24 h. Meanwhile, the nanocarriers system relied on the strong binding ability of DMY to the outer membrane of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) achieves controlled drug delivery onto the pathogen wall. The advanced antibacterial action of DNA/DMY-CuO also reflected in membrane destruction, cytoplasmic constituent leakages and ATP synthetic pathway cessation, thereby halting cytosolic metalloregulatory mechanisms and minimizing drug-resistant bacteria. In summary, such multi-functional CuO-loaded nanocomposite provides a water-dispersibility, controllable, low cytotoxicity and long-effective platform to address the ever-growing threats of bacterial infections., (Copyright © 2022. Published by Elsevier B.V.)

Background: Hypertension is rising as a major public health burden around the world. This study explored the association between single-nucleotide polymorphisms (SNPs) in the adenosine triphosphate (ATP)-Binding Cassette Subfamily A1 (ABCA1) gene and hypertension among Chinese Han adults., Method: A total of 2,296 Han Chinese in southeast China were recruited for this study. We collected medical reports, lifestyle details, and blood samples from individuals. The polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to detect the genotypes of these SNPs in the ABCA1 gene., Results: After adjusting some covariates, the additive and recessive models of the rs2472510 and rs2515614 were significantly associated with hypertension. The haplotypes TCTA (rs2297406-rs2472433-rs2472510-rs2515614) were associated with high SBP, and the haplotypes CCTA, TCTA, and TTTA were associated with high diastolic blood pressure (DBP)., Conclusion: The results of the relationship between the polymorphisms of rs2297406, rs2472433, rs2472510, and rs2515614 in ABCA1 and hypertension in southeastern China would provide a theoretical basis for genetic screening and disease prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Tong, Di, Zhang, Xu, Tan and Yang.)

Background: Hepatocellular carcinoma (HCC) is one of the most common diseases that threaten millions of lives annually. Evidence supports that bile acid (BA) affects HCC through inflammation, DNA damage, or other mechanisms., Methods: A total of 127 BA-associated genes were analyzed in HCC tumor and nontumor samples using The Cancer Genome Atlas data. Genes correlated to the prognosis of patients with HCC were identified using univariate and multivariate Cox regression analyses. Furthermore, a prediction model with identified genes was constructed to evaluate the risk of patients with HCC for prognosis., Results: Out of 26 genes with differential expressions between the HCC and nontumor samples, 19 and 7 genes showed upregulated and downregulated expressions, respectively. Three genes, NPC1, ABCC1, and SLC51B, were extrapolated to construct a prediction model for the prognosis of patients with HCC., Conclusion: The three-gene prediction model was more reliable than the pathological staging characters of the tumor for the prognosis and survival of patients with HCC. In addition, the upregulated genes facilitating the transport of BAs are associated with poor prognosis of patients with HCC, and genes of de novo synthesis of BAs benefit patients with HCC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Gang Wang et al.)

The recombination signal binding protein for immunoglobulin kappa J region (RBPJ) has a dual effect on Kaposi's sarcoma-associated herpesvirus (KSHV) replication. RBPJ interaction with replication and transcription activator (RTA) is essential for lytic replication, while the interaction with latency-associated nuclear antigen (LANA) facilitates latent infection. Furthermore, our previous study found that LANA decreased RBPJ through upregulating miRNA let-7a. However, it is unclear whether RTA regulates the expression of RBPJ. Here, we show RTA increases RBPJ by decreasing let-7a. During KSHV replication, the RBPJ expression level was positively correlated with the RTA expression level and negatively correlated with the LANA expression level. The let-7a expression level was inverse to RBPJ. Knockdown of RBPJ inhibited the self-activation of RTA promoter and LANA promoter and weakened LANA's inhibition of RTA promoter. Collectively, these findings indicate that RTA and LANA compete for let-7a/RBPJ signal to control the KSHV replication. Regulating the RBPJ expression level by RTA and LANA plays an important role during KSHV replication., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Di, Zheng, Zhang, Tong, Ren, Hong, Song, Chen, Tan and Yang.)

Objective: To inquiry about mechanism of miR-100-5p/CDC25A axis in breast carcinoma (BC), thus offering a new direction for BC targeted treatment., Methods: qRT-PCR was employed to explore miR-100-5p and CDC25A mRNA levels. Western blot was employed for detecting protein expression of CDC25A. Targeting relationship of miR-100-5p and CDC25A was verified by dual-luciferase assay. In vitro experiments were used for assessment of cell functions., Results: In BC tissue and cells, miR-100-5p was significantly lowly expressed ( P  < 0.05) while CDC25A was highly expressed. Besides, miR-100-5p downregulated CDC25A level. miR-100-5p had a marked influence on the prognosis of patients. The forced miR-100-5p expression hindered BC cell proliferation, migration and invasion, and facilitated cell apoptosis. Upregulated miR-100-5p weakened promotion of CDC25A on BC cell growth., Conclusion: Together, these findings unveiled that CDC25A may be a key target of miR-100-5p that mediated progression of BC cells. Hence, miR-100-5p overexpression or CDC25A suppression may contribute to BC diagnosis., Competing Interests: The authors declare there are no competing interests., (©2021 Li et al.)

Pancreatic cancer is a common malignant tumor with poor prognosis. Recently, cancer stem cells (CSCs) were identified in several solid tumors, including pancreatic cancer. Although accumulating evidence indicates that sirtuin 1 (SIRT1) exerts biological functions in various cancers, how it contributes to tumorigenesis and metastasis of pancreatic cancer, as well as its role in CSCs, is still poorly defined. Here we show that SIRT1 interacts with the Cullin 4B (CUL4B)-Ring E3 ligase (CRL4B) complex, which is responsible for H2AK119 monoubiquitination (H2AK119ub1), collaborating as a functional unit. Genome-wide analysis of SIRT1/CUL4B targets identified a cohort of genes, including GRHL3 and FOXO3, critically involved in cell differentiation, growth, and migration. Furthermore, we found that SIRT1 and CUL4B collectively promote the proliferation, autophagy, and invasion of pancreatic cancer cells. Remarkably, we demonstrate that SIRT1/CUL4B promotes CSC-like properties, including increased stemness marker expression and sphere formation. In vivo experiments implied that SIRT1 promoted established tumor xenograft growth, increased tumor-initiating capacity in NOD/SCID mice, and increased CSC frequency. Strikingly, SIRT1 and CUL4B expression is markedly upregulated in a variety of human cancers, including pancreatic cancer. Our data provide a molecular basis for the functional interplay between histone deacetylation and ubiquitination. The results also implicate the SIRT1/CRL4B complex in pancreatic cancer metastasis and stem cell properties, thus supporting SIRT1 as a promising potential target for cancer therapy development., (© 2021. The Author(s).)

This article introduces an environmentally friendly and more economical method for preparing red selenium nanoparticles (Se-NPs) with high stability, good biocompatibility, and narrow size using yeast as a bio-reducing agent with high antioxidant, immune regulation, and low toxicity than inorganic and organic Se. The yeast-derived Se-NPs were characterized by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The results revealed spherical-shaped particles of Se-NPs with an average diameter of 71.14 ± 18.17 nm, an amorphous structure, and surface enhancement with an organic shell layer, that provide precise geometry and stability in the formation of bio-inert gray or black Se-NPs instead of red Se-NPs. Furthermore, the addition of 0.3-0.8 mg/kg Se-NPs in the feed significantly improved the health of mice. As Se-NPs stimulated the oxidative state of mice, it significantly increased the level of GSH-Px, SOD, and AOC, and decreased the level of MDA. The yeast-derived Se-NPs alleviated the immunosuppression induced by cyclophosphamide, whereas protected the liver, spleen, and kidney of mice, stimulated the humoral immune potential of the mice, and significantly increased the levels of I g M, IgA, and I g G. These results indicated that the yeast-derived Se-NPs, as a trace element feed additive, increased the defense of the animal against oxidative stress and infectious diseases and therefore Se-NPs can be used as a potential antibiotic substitute for animal husbandry., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of all incident esophageal cancers, with a 5-year survival rate of < 20%. Autophagy is of particular importance in cancers; however, the detailed regulatory mechanisms of oncogenic autophagy in ESCC have not been fully elucidated. In the present study, we address how splicing control of TSC2 is involved in mTOR-regulated oncogenic autophagy. Methods: Alternative splicing events controlled by DAZAP1 in ESCC cells were identified via RNAseq. Differential phosphorylation of short or long TSC2 splicing variants by AKT and their impacts on mTOR signaling were also examined. Results: We found that starvation-induced miR-10b could enhance autophagy via silencing DAZAP1, a key regulator of pre-mRNA alternative splicing. Intriguingly, we observed a large number of significantly changed alternative splicing events, especially exon skipping, upon RNAi of DAZAP1. TSC2 was verified as one of the crucial target genes of DAZAP1. Silencing of DAZAP1 led to the exclusion of TSC2 exon 26 (from Leu947 to Arg988), producing a short TSC2 isoform. The short TSC2 isoform cannot be phosphorylated at Ser981 by AKT, which resulted in continuous activation of TSC2 in ESCC. The active TSC2 inhibited mTOR via RHEB, leading to continually stimulated oncogenic autophagy of ESCC cells. Conclusions: Our data revealed an important physiological function of tumor suppressor DAZAP1 in autophagy regulation and highlighted the potential of controlling mRNA alternative splicing as an effective therapeutic application for cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications in premature infants. Since inflammation plays a crucial role in the pathogenesis of BPD, anti-inflammatory drugs, such as corticosteroids, have long been the focus of prevention research. In this meta-analysis, we aim to explore the long-term effects of the intratracheal administration of corticosteroids (IAC) in preventing BPD., Methods: EMBASE, MEDLINE, the Cochrane Library, Web of Science, CINAHL, Clinicaltrials.gov, the ISRCTN registry, and gray literature were searched to identify randomized controlled trials (RCTs) that evaluated the long-term effects of IAC for the prevention of BPD in premature infants., Results: Five RCTs (n = 1515) were eligible for further analysis. The meta-analysis revealed that the incidence of neurodevelopmental impairment (NDI) did not significantly differ between the IAC group and the control group (relative risk [RR] 0.9, 95% confidence interval [CI] 0.79 to 1.03, P = .14). There was no significant reduction in long-term mortality (RR, 1.13; 95% CI, 0.9 to 1.41; P = .3) or the incidence of rehospitalization (RR, 0.99; 95% CI, 0.89 to 1.09, P = .82). No significant differences were observed between the IAC group and the control group with regard to height, weight and head circumference at the age of 18 to 36 months of postmenstrual age (PMA) (mean difference [MD], 0.14; 95% CI, -0.26 to 0.54, P = .48)., Conclusions: Our study suggests that IAC in preterm infants does not have significant long-term benefits or adverse outcomes. However, before routine use, well-designed studies and studies involving large sample sizes are needed to confirm the pharmacokinetics and long-term effects of IAC., (© 2019 Wiley Periodicals, Inc.)

The long non-coding RNA (lncRNA) PCAT-1 resides in the chromosome 8q24 cancer-risk locus and acts as a vital oncogene during tumorigenesis and progression. However, how PCAT-1 is post-transcriptionally regulated, for example, by small ncRNAs, such as microRNAs (miRNAs) is largely unknown. Here, we report how miRNAs regulate PCAT-1 expression and also investigate the biological significance of this regulation in hepatocellular carcinoma (HCC). We found that miR-215, a P53-inducible miRNA, is a key regulator of PCAT-1 expression in HCC and identified an interaction between miR-215 and PCAT-1 in dual luciferase reporter gene assays. We also found that post-transcriptional silencing of PCAT-1 by miR-215 or PCAT-1 siRNAs significantly inhibited proliferation of HCC cells and, conversely, that inhibition of endogenous miR-215 up-regulated PCAT-1 expression and promoted cell viability. The tumor-suppressing role of miR-215 was further confirmed in an in vivo mouse HCC xenograft model. Of note, gene profiling assays suggested that the kinase CRK-like proto-oncogene, adaptor protein (CRKL), is a potential downstream target of the miR-215-PCAT-1 axis in HCC, and we demonstrated that CRKL silencing significantly suppresses cell proliferation. Taken together and considering the essential role of CRKL in cancer cells, we propose that the TP53-miR-215-PCAT-1-CRKL axis might represent an important regulatory pathway in HCC. In summary, our results highlight the involvement of several ncRNAs in HCC and thus provide critical insights into the molecular pathways operating in this malignancy., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

The aim of this study is to determine the accuracy rate of bronchopulmonary dysplasia (BPD) diagnosis and risk factors of short-term poor prognosis for premature infants. This study analyzed the clinical data of 81 premature infants (<32 weeks gestational age) with BPD, who were on oxygen therapy >28 days, and survived >36 weeks (corrected age). Outcome measures included treatments, conditions on the 28th day after birth, oxygen therapy conditions at the 36th week, occurrence of any serious complications during hospital stay. The major risk factors affecting prognosis were ventilation duration, duration of oxygen therapy, application of steroids, hypothyroidism and severity of BPD (all P<0.05). Interventions for complications (n=53) resulted in ceased inhalation of oxygen in 12 infants, improvement of symptoms in 26 infants, and were ineffective in 15 infants. BPD prognosis can be improved by shortening the duration of invasive ventilation and correcting thyroid function.

A complex reaction mechanism of oxidation of the anti-tubercular prodrug isoniazid (isonicotinic hydrazide, INH) by [IrCl 6 ] 2- as a model for redox processes of such drugs in biological systems has been studied in aqueous solution as a function of pH between 0 and 8.5. Similar experiments have been performed with its isomer nicotinic hydrazide (NH). All reactions are overall second-order, first-order in [IrCl 6 ] 2- and hydrazide, and the observed second-order rate constants k' have been determined as a function of pH. Spectrophotometric titrations indicate a stoichiometry of [Ir(iv)] : [hydrazide] = 4 : 1. HPLC analysis shows that the oxidation product of INH is isonicotinic acid. The derived reaction mechanism, based on rate law, time-resolved spectra and stoichiometry, involves parallel attacks by [IrCl 6 ] 2- on all four protolytic species of INH and NH as rate-determining steps, depending on pH. These steps are proposed to generate two types of hydrazyl free radicals. These radicals react further in three rapid consecutive processes, leading to the final oxidation products. Rate constants for the rate-determining steps have been determined for all protolytic species I-IV of INH and NH. They are used to calculate reactivity-pH diagrams. These diagrams demonstrate that for both systems, species IV is ca. 10 5 times more reactive in the redox process than the predominant species III at the physiological pH of 7.4. Thus, species IV will be the main reactant, in spite of the fact that its concentration at this pH is extremely low, a fact that has not been considered in previous work. The results indicate that pH changes might be an important factor in the activation process of INH in biological systems also, and that in such systems this process most likely is more complicated than previously assumed.

Dyregulation of autophagy is implicated in human cancers and the mechanism details remains largely unclear. Herein we report the regulatory role of miR-638 in autophagy of esophageal squamous cell carcinoma (ESCC) and breast cancer cells. We found that miR-638 overexpression promotes starvation- and rapamycin-induced autophagy. In ESCC and breast cancer cells, miR-638 acts as an oncogene and promotes cell proliferation, migration, as well as invasion in vitro and in vivo. In accordance with this, we observed significantly higher miR-638 expression in ESCC and breast cancer tissues compared to normal tissues. To further elucidate regulatory mechanisms of miR-638 in autophagy, we performed a computational nomination of its target genes through intersecting the results of multiple prediction algorithms. DACT3, a key regulator of Wnt/β-catenin signaling, was predicted to be regulated by miR-638 by all programs and confirmed by experimental results. Depletion of DACT3 phenocopied effects of miR-638 overexpression, demonstrating its importance in autophagy. These results elucidate that the miR-638-DACT3 axis might be an important molecular pathway in controlling autophagy and tumorigenesis. Our data in clinical tissue samples highlight miR-638 and DACT3 as histological marker for cancer detection and their potentially therapeutic implications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Long noncoding RNA (lncRNA) MALAT1 acts as an essential oncogene lncRNA (onco-lncRNA) in the development of ESCC. Down-regulation of onco-lncRNA MALAT1 mediated by microRNA-101 (miR-101) and microRNA-217 (miR-217) has been proved to effectively suppress ESCC. In this study, poly(glycidyl methacrylate)-based star-like polycations with flanking folic acid (FA) ligands and rich hydrophilic hydroxyl groups (denoted as s-PGEA-FA) were proposed as efficient nanovectors to deliver miR-101 and miR-217 for silencing onco-lncRNA MALAT1 in different ESCC cells. The inhibition of ESCC by s-PGEA-FA/miRNA nanocomplexes would be achieved via subsequently targeting onco-lncRNA MALAT1 in ESCC cells. To evaluate the ESCC tumor-suppressing efficacy mediated by s-PGEA-FA/miRNA nanocomplexes, a series of assays were carried out, including gene transfection, cell proliferation, cell migration, and cell invasion. The results revealed that s-PGEA-FA-mediated miR-101 and miR-217 delivery effectively inhibited ESCC development, indicating the s-PGEA-FA nanovector was promising for future ESCC therapy.

Given a natural image from the single sensor, the key task is to properly reconstruct the full color image. This paper presents an effectively demosaicking algorithm based on fully directional estimation using Bayer color filter array pattern. The proposed method smoothly keeps access to current reconstruction implementations, and outperforms the horizontal and vertical estimating approaches in terms of the perceptual quality. To analyze the target of existing methods, the proposed algorithm use the multiscale gradients in single green channels as the diagonal information for the auxiliary interpolation. Furthermore, two group of weights (one is from the horizontal and vertical directions, another is from the diagonal and anti-diagonal directions) are built. Combinational weight is better suited for representing neighbor information. Another contribution is to better use the prior result. While calculating the same type of color difference, we divide all the color difference values into two interleaved parts. Estimated value in the first part will guide the subsequent color difference in the second part. It less brings the artifact of the interpolation procedure. Experimental results show that this adaptive algorithm is efficient both in the objective and subjective output measures.

Unlabelled: Nucleic acid-based gene therapy is a promising treatment option to cure numerous intractable diseases. For non-viral gene carriers, low-molecular-weight polymeric vectors generally demonstrate poor transfection performance, but benefit their final removals from the body. Recently, it was reported that aminated poly(glycidyl methacrylate) (PGMA) is one potential gene vector. Based on ethylenediamine (ED)-functionalized low-molecular-weight PGMA (denoted by PGED), a flexible strategy was herein proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with friendly crosslinking reagents for highly efficient nucleic acid delivery. α-Lipoic acid (LA), one natural antioxidant in human body, was readily introduced into ED-functionalized PGMA and crosslinked to produce cationic PGED-NGs with plentiful reducible lipoyl groups. PGED-NGs could effectively complex plasmid DNA (pDNA) and short interfering RNA (siRNA). Compared with pristine PGED, PGED-NGs exhibited much better performance of pDNA transfection. PGED-NGs also could efficiently transport MALAT1 siRNA (siR-M) into hepatoma cells and significantly suppressed the cancer cell proliferation and migration. The present work indicated that reducible cationic nanogels involving LA crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems., Statement of Significance: Recently, the design of new types of high-performance nanoparticles is of great significance in delivering therapeutics. Nucleic acid-based therapy is a promising treatment option to cure numerous intractable diseases. A facile and straightforward strategy to fabricate safe nucleic acid delivery nanovectors is highly desirable. In this work, based on ethylenediamine-functionalized low-molecular-weight poly(glycidyl methacrylate), a flexible strategy was proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with α-Lipoic acid, one friendly crosslinking reagent, for highly efficient nucleic acid delivery. Such PGED-NGs possess plentiful reducible lipoyl groups, effectively encapsulated pDNA and siRNA and exhibited excellent abilities of nucleic acid delivery. The present work indicated that reducible cationic nanogels involving α-lipoic acid crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Genome-wide association studies (GWASs) have provided many insights into cancer genetics. However, the molecular mechanisms of many susceptibility SNPs defined by GWASs in cancer heritability and in promoting cancer risk remain elusive. New research strategies, including functional evaluations, are warranted to systematically explore truly causal genetic variants. In this study, we developed an integrative functional genomics methodology to identify cancer susceptibility SNPs in transcription factor-binding sites across the whole genome. Employing integration of functional genomic data from c-Myc cistromics, 1000 Genomes, and the TRANSFAC matrix, we successfully annotated 12 SNPs present in the c-Myc cistrome with properties consistent with modulating c-Myc binding affinity in hepatocellular carcinoma (HCC). After genotyping these 12 SNPs in 1,806 HBV-related HCC case subjects and 1,708 control subjects, we identified a HCC susceptibility SNP, rs157224G>T, in Chinese populations (T allele: odds ratio = 1.64, 95% confidence interval = 1.32-2.02; p = 5.2 × 10(-6)). This polymorphism leads to HCC predisposition through modifying c-Myc-mediated transcriptional regulation of EPB41, with the risk rs157224T allele showing significantly decreased gene expression. Based on cell proliferation, wound healing, and transwell assays as well as the mouse xenograft model, we identify EPB41 as a HCC susceptibility gene in vitro and in vivo. Consistent with this notion, we note that EPB41 expression is significantly decreased in HCC tissue specimens, especially in portal vein metastasis or intrahepatic metastasis, compared to normal tissues. Our results highlight the involvement of regulatory genetic variants in HCC and provide pathogenic insights of this malignancy via a genome-wide approach., (Copyright © 2016 American Society of Human Genetics. All rights reserved.)

The reductions of Pt(iv) anticancer prodrugs [Pt(dach)Cl4] (ormaplatin/tetraplatin), cis-[Pt(NH3)2Cl4], and cis,cis,trans-[Pt(NH3)2Cl2Br2] by the several dominant reductants in human plasma have been characterized kinetically in this work, including l-ascorbic acid (Asc), l-glutathione (GSH), l-cysteine (Cys), dl-homocysteine (Hcy), and a dipeptide Gly-Cys. All the reductions follow an overall second-order kinetics, being first-order each in [Pt(iv)] and in the [reductant]. A general reactivity trend of Asc < Hcy < Cys-Gly < GSH < Cys is clearly revealed for the reductions of [Pt(dach)Cl4] and [Pt(NH3)2Cl4] at 37.0 °C and pH 7.40. Analysis of the observed second-order rate constants k' implies that these Pt(iv) prodrugs have a very short lifetime (less than a minute) in human plasma and can hardly enter into cells before reduction and that Asc might not play a dominant role in the reduction process among the reductants. The reductions of [Pt(dach)Cl4] and [Pt(NH3)2Cl4] by Asc have been studied in a wide pH range, and a reaction mechanism has been proposed involving parallel reductions of the Pt(iv) complexes by the Asc protolytic species. Moreover, a halide-bridged (inner-sphere) electron transfer mode for the rate-determining steps is discussed in detail; several lines of evidence strongly bolster this type of electron transfer. Furthermore, the observed activation parameters corresponding to k' have been measured around pH 7.40. Analysis of the established k'-pH profiles indicates that k' is a composite of at least three parameters in the pH range of 5.74-7.40 and the measured activation parameters in this range do not correspond to a single rate-determining step. Consequently, the isokinetic relationship reported previously using the measured ΔH(‡) and ΔS(‡) in the above pH range might be an artifact since the relationship is not justified anymore when our new data are added.

The chromosome 5p15.33 TERT-CLPTM1L region has been identified by genome-wide association studies as a susceptibility locus of multiple malignancies. However, the involvement of this locus in esophageal squamous cell carcinoma (ESCC) development is still largely unclear. We fine-mapped the TERT-CLPTM1L region through genotyping 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. After analyzing 2098 ESCC patients and frequency-matched 2150 unaffected controls, we found that rs2853691, rs2736100 and rs451360 genetic polymorphisms are significantly associated with ESCC risk in Chinese (all P<0.05). Reporter gene assays indicated that the ESCC susceptibility SNP rs2736100 locating in a potential TERT intronic promoter has a genotype-specific effect on TERT expression. Similarly, the CLPTM1L rs451360 SNP also showed allelic impacts on gene expression. After measuring TERT and CLPTM1L expression in sixty-six pairs of esophageal cancer and normal tissues, we observed that the rs2736100 G risk allele carriers showed elevated oncogene TERT expression. Also, subjects with the rs451360 protective T allele had much lower oncogene CLPTM1L expression than those with G allele in tissue specimens. Results of these analyses underline the complexity of genetic regulation of telomere biology and further support the important role of telomerase in carcinogenesis. Our data also support the involvement of CLPTM1L in ESCC susceptibility.

As a well-known oncogene, B cell lymphoma-2 (BCL-2) can promote cancer cell survival through preventing their apoptosis. Several functional BCL-2 single nucleotide polymorphisms (SNPs), such as rs2279115, rs1801018, and rs1564483, have been identified and might contribute to cancer susceptibility. However, the involvement of these SNPs in small cell lung cancer (SCLC) was still unclear. As a result, we investigated associations between these three genetic variants and SCLC risk in a case-control design. Genotypes were determined in two independent case-control sets consisted of 520 SCLC patients and 1040 controls from two medical centers. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated utilizing unconditional logistic regression. We found that only BCL-2 rs2279115 genetic variant significantly contributed to decreased SCLC risk in Chinese Han populations, with the rs2279115 A allele as the protective allele. Stratified analyses of association between BCL2 rs2279115 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk of the limited stage SCLC but not the extensive stage disease. Our results indicate that the BCL-2 rs2279115 genetic variant was associated with SCLC risk in Chinese populations and support the hypothesis that SNPs in regulatory regions of oncogenes might contribute to cancer susceptibility.

treRNA is a long non-coding RNA (lncRNA) involved in cancer progression. In this study, we show that miR-190a can silence treRNA post-transcriptionally. Suppression of treRNA by miR-190a led to significant changes of mesenchymal-epithelial transition markers and impaired migration and invasion capability of hepatoma cells. TCGA data indicated that miR-190a exhibited lower expression in hepatoma tissues, especially from patients with vascular tumor invasion, compared to normal tissues. Our results reveal the involvement of miR-190a-treRNA axis in hepatoma progression and shed light on lncRNA-based cancer therapies for hepatoma patients at high risk of metastasis., (Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

5S rRNA plays an important part in ribosome biology and is over-expression in multiple cancers. In this study, we found that 5S rRNA is a direct target of miR-150 and miR-383 in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-150 and miR-383 inhibited ESCC cell proliferation in vitro and in vivo. Moreover, 5S rRNA silencing by miR-150 and miR-383 might intensify rpL11-c-Myc interaction, which attenuated role of c-Myc as an oncogenic transcriptional factor and dysregulation of multiple c-Myc target genes. Taken together, our results highlight the involvement of miRNAs in ribosomal regulation during tumorigenesis., (Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

As a well-known DNA repair gene, RAD52 plays an essential role in homologous recombination repair of double strand break, maintenance of genomic stability and prevention of cell malignant transformation. Previous genome-wide association studies (GWASs) have identified common genetic variants at 12p13.33 RAD52 locus associated with lung cancer risk in Caucasians. However, little or nothing has been known about the RAD52 single nucleotide polymorphisms (SNPs) in small cell lung cancer (SCLC) in the Chinese population. As a result, we examined the association between six RAD52 SNPs (rs10849605, rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and SCLC susceptibility in Chinese. After 520 SCLC cases and 1040 controls in two independent case-control sets were genotyped, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with SCLC risk among six RAD52 SNPs genotyped. The odds of having the rs7963551 CA genotype in SCLC patients was 0.38 (95% CI = 0.24-0.62, P = 1.1×10(-4)) compared with the CC genotype. Stratified analyses of association between rs7963551 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk among smokers but not nonsmokers. Our results demonstrated that the functional RAD52 rs7963551 SNP contributes to susceptibility to developing SCLC in the Chinese population.

L-Selenomethionine (SeMet), the predominant form of selenium acquired from the diet by humans, has been used as a supplement, and exhibit some important functions like cancer prevention and antioxidative defense. Its interactions with Pt(II) anticancer drugs have been characterized, but its redox reactions with platinum(IV) anticancer prodrugs have not been exploited. In this work, the oxidation of SeMet by Pt(IV) anticancer model compounds trans-[PtX2(CN)4](2-) (X = Cl, Br) was characterized. A stopped-flow spectrometer was used to record the rapid scan spectra and to follow the reaction kinetics over a wide pH range. An overall second-order rate law was derived: -d[Pt(IV)]/dt = k'[Pt(IV)][SeMet], where k' pertains to the observed second-order rate constants. The k'-pH profiles showed that k' increased only about 6 times even though the solution pH was varied from 0.25 to 10.5. The redox stoichiometry was determined as Δ[Pt(IV)]/Δ[SeMet] = 1 : (1.07 ± 0.07), suggesting that SeMet was oxidized to selenomethionine selenoxide. The selenoxide together with its hydrated form was identified explicitly by high resolution mass spectral analysis. A reaction mechanism was proposed which encompassed three parallel rate-determining steps relying on the protolytic species of SeMet. Rate constants of the rate-determining steps were obtained from the simulations of the k'-pH profiles. Activation parameters were determined for the reactions of the zwitterionic form of SeMet with the Pt(IV) complexes. A bridged electron transfer process is delineated in the rate-determining steps and several lines of evidence support the bridged electron transfer mode. Strikingly, reduction of [PtX2(CN)4](2-) by SeMet is 3.7 × 10(3)-5.7 × 10(4) times faster than that by L-methionine. Some potential biological consequences resulting from the strikingly fast reduction are discussed.

Background: Iturin A is a potential lipopeptide antibiotic produced by Bacillus subtilis. Optimization of iturin A yield by adding various concentrations of asparagine (Asn), glutamic acid (Glu) and proline (Pro) during the fed-batch fermentation process was studied using an artificial neural network-genetic algorithm (ANN-GA) and uniform design (UD). Here, ANN-GA based on the UD data was used for the first time to analyze the fed-batch fermentation process. The ANN-GA and UD methodologies were compared based on their fitting ability, prediction and generalization capacity and sensitivity analysis., Results: The ANN model based on the UD data performed well on minimal statistical designed experimental number and the optimum iturin A yield was 13364.5 ± 271.3 U/mL compared with a yield of 9929.0 ± 280.9 U/mL for the control (batch fermentation without adding the amino acids). The root-mean-square-error for the ANN model with the training set and test set was 4.84 and 273.58 respectively, which was more than two times better than that for the UD model (32.21 and 483.12). The correlation coefficient for the ANN model with training and test sets was 100% and 92.62%, respectively (compared with 99.86% and 78.58% for UD). The error% for ANN with the training and test sets was 0.093 and 2.19 respectively (compared with 0.26 and 4.15 for UD). The sensitivity analysis of both methods showed the comparable results. The predictive error of the optimal iturin A yield for ANN-GA and UD was 0.8% and 2.17%, respectively., Conclusions: The satisfactory fitting and predicting accuracy of ANN indicated that ANN worked well with the UD data. Through ANN-GA, the iturin A yield was significantly increased by 34.6%. The fitness, prediction, and generalization capacities of the ANN model were better than those of the UD model. Further, although UD could get the insight information between variables directly, ANN was also demonstrated to be efficient in the sensitivity analysis. The results of these comparisons indicated that ANN could be a better alternative way for fermentation optimization with limited number of experiments.

Hepatitis C virus (HCV) core protein has long been considered an attractive candidate for inclusion in a protective vaccine. However, this protein may hamper the development of systemic immune responses because of its immune suppressive properties. We previously reported that immune responses to HCV core protein could be efficiently induced by attenuated Salmonella carrying the HCV core protein, but not the HCV core DNA vaccine. To optimize the combination of the core protein and envelope protein 2 (E2) into a vaccine formulation to induce cellular immune responses and neutralizing antibodies, we constructed a plasmid containing two expression cassettes. One expression cassette was included to regulate the expression of HCV core protein by an inducible in vivo-activated Salmonella promoter, the other was included to regulate the expression of HCV E2 protein by the cytomegalovirus enhancer/promoter. Oral immunization of BALB/c mice with the attenuated Salmonella strain SL7207 carrying this plasmid efficiently induced HCV core and E2-specific cellular immune responses and antibodies. IgG purified from immunized mice could neutralize the infectivity of HCV pseudoparticles (HCVpp) of both the autologous Con 1 isolate and the heterologous H77 isolate, and cell culture produced HCV (HCVcc) of Con1-JFH1 chimera. These results indicated that this vaccine strategy can effectively deliver core and E2 protein to the immune system and provide a promising approach for the development of prophylactic and therapeutic vaccines against HCV infection., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the feasibility of induction of neutralization antibodies against hepatitis C virus (HCV) infection by HCV envelope 2 protein (E2) DNA vaccines immunization., Methods: Two kinds of expression plasmids of HCV envelope 2 protein, plasmid pCI-1b661 Delta encoding hydrophobic carboxyl terminal truncated E2 and pCI-1b661 Delta encoding E2 with deletion of hypervariable region 1 (HVR1) and carboxyl terminal, were constructed and respectively transfeted 293T cells, and truncated E2 protein in whole cell lysate and supernatant of 293T cells were analyzed by Western blot. After BALB/c mouse were intramuscularly immunized by the plasmids, sera antibodies against HVR1 were detected by ELISA and the neutralization activity of the antibodies were assayed with HCV pseudotype particle (HCVpp)., Results: Both plasmids could express secretary truncated E2 protein. All the mice immunized with plasmid pCI-1b661 produced HVR1 antibodies,while no HVR1 antibodies were detected in pCI-1b661 Delta immunized mice. The sera neutralization percentages against HCVpp in pCI1lb661 Delta and pCI-lb661 Delta immunized mice were (78.5 +/- 13.8)% and (38.7 +/- 6.5)%, respectively (P <0.01). Sera neutralization activity against HCVpp was positive correlated with the level of HVR1 antibodies in pCI-1b661 immunized mice (r = 0.967, P<0.01)., Conclusion: DNA vaccines expressing truncated E2 protein could induce neutralization antibodies against HCV, and neutralization antibodies mainly was consisted of the antibodies against HVR1.

HCV infection is often associated with B-cell regulatory control disturbance and delayed appearance of neutralizing antibodies. CD81 is a cellular receptor for HCV and can bind to HCV envelope protein 2 (E2). CD81 also participates to form a B cell costimulatory complex. To investigate whether HCV influences B cell activation and immune function through E2 -CD81 engagement, here, human Burkitt's lymphoma cell line Raji cells and primary human B lymphocytes (PHB) were treated with HCV E2 protein and cell culture produced HCV particles (HCVcc), and then the related cell phenotypes were assayed. The results showed that both E2 and HCVcc triggered phosphorylation of IκBα, enhanced the expression of anti-apoptosis Bcl-2 family proteins, and protected Raji cells and PHB cells from Fas-mediated death. In addition, both E2 protein and HCVcc increased the expression of costimulatory molecules CD80, CD86 and CD81 itself, and decreased the expression of complement receptor CD21. The effects were dependent on E2-CD81 interaction on the cell surface, since CD81-silenced Raji cells did not respond to both treatments; and an E2 mutant that lose the CD81 binding activity, could not trigger the responses of both Raji cells and PHB cells. The effects were not associated with HCV replication in cells, for HCV pseudoparticle (HCVpp) and HCVcc failed to infect Raji cells. Hence, E2-CD81 engagement may contribute to HCV-associated B cell lymphoproliferative disorders and insufficient neutralizing antibody production.

Two new sesquiterpene lactones, 1beta-sulfate-5alpha, 6betaH-eudesma-3-en-12, 6alpha-olide (1) and 1beta-(p-hydroxyphenyl acetyl)-15-O-beta-D-glucopyranosyl-5alpha, 6betaH-eudesma-3-en-12, 6alpha-olide (2) were isolated from Sonchus arvensis L. (Asteraceae), together with eight known compounds. Their structures were elucidated through spectroscopic and chemical methods. They were evaluated for antibacterial activity. Among them, compounds 1 and 7 exhibited antibacterial activity against oral pathogen Streptococcus mutans ATCC 25175 with MIC values of 15.6 and 62.5 microg/ml, respectively., (Copyright 2010 Elsevier B.V. All rights reserved.)

This paper studied the resistant physiology of three mangrove species, Sonneratia caseolaris, Aegiceras corniculaturn and Bruguiera gymnorrhiza in a subsurface flow-constructed wetland sewage treatment system under freshwater condition. The results showed that in a year period, the superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities of three mangrove species increased gradually and maintained at a high level, the proline content reached the maximum from July to September, while the plasma membrane permeability did not show any obvious change. In comparing with those grown in the Futian Nature Reserve of Shenzhen, three mangrove species in the test sewage treatment system had lower SOD, POD and CAT activities and higher proline content, while no significant difference was observed in the malondialdehyde (MDA) content and plasma membrane permeability. It was suggested that three mangrove species could adapt to the subsurface flow-constructed wetland sewage treatment system under freshwater condition.