Hanchun Chen

Twist, the basic helix-loop-helix transcription factor, is involved in the process of epithelial to mesenchymal transitions (EMTs), which play an essential role in cancer metastasis. Overexpression of Twist or its promoter methylation is a common scenario in metastatic carcinomas. Twist is activated by a variety of signal transduction pathways, including Akt, signal transducer and activator of transcription 3, mitogen-activated protein kinase, Ras, and Wnt signaling. Activated Twist upregulates N-cadherin and downregulates E-cadherin, which are the hallmarks of EMT. Moreover, Twist plays an important role in some physiological processes involved in metastasis, like angiogenesis, invadopodia, extravasation, and chromosomal instability. Twist also protects cancer cells from apoptotic cell death. In addition, Twist is responsible for the stemness of cancer cells and the generation of drug resistance. Recently, targeting Twist has gained significant interests in cancer therapeutics. The inactivation of Twist by small RNA technology or chemotherapeutic approach has been proved successful. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified. Development of potential treatment strategies by targeting Twist has a great promise in cancer therapeutics.

The ACE2 gene is a receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) for COVID-19 (coronavirus disease 2019). To analyze the expression profiles and clinical significances for this gene in humans, RNA-seq data representing 27 different tissues were analyzed using NCBI; total RNA was extracted from different tissues of mouse and semi-quantitative reverse transcriptional-polymerase chain reaction (Q-RT-PCR) was carried out. Immunohistochemistry expression profiles in normal tissues and cancer tissues and TCGA survival analysis in renal and liver cancer were conducted. ACE2 was highly conserved in different species. In normal tissues, ACE2 expression distributions were organ-specific, mainly in the kidney, male testis and female breast, and cardiovascular and gastrointestinal systems. High level of expression in testis, cardiovascular and gastrointestinal system indicated that SARS-CoV-2 might not only attack the lungs, but also affect other organs, particularly the testes, thus it may severely damage male sexual development for younger male and lead to infertility in an adult male, if he contracted COVID-19. On the other side, high expression of ACE2 was correlated with increased survival rate in renal and liver cancer, indicating that ACE2 is a prognostic marker in both renal cancer and liver cancers. Thus, the ACE2 is a functional receptor for SARS-CoV-2 and has a potential anti-tumor role in cancer. Taken together, this study may not only provide potential clues for further medical pathogenesis of COVID-19 and male fertility, but also indicate the clinical significance of the role of the ACE2 gene in cancer.

Artificial photocatalytic energy conversion is considered as the most potential strategy for solving the increasingly serious energy crisis and environmental pollution problems by directly capturing solar energy. Therefore, high efficiency photocatalyst has drawn significant research attention in recent years. Due to the excellent electronic, optical, structural, and physicochemical performances, silver-based g-C3N4 have become promising photocatalysts. This review emphasizes the recent progresses and challenges on g-C3N4 decorated with silver for photocatalytic energy conversion. The extensive use of g-C3N4 decorated with silver in diverse photocatalytic reactions, including hydrogen evolution, pollutant degradation and carbon dioxide reduction, is also fully introduced. In addition, we propose the perspectives of g-C3N4 decorated with silver on photocatalytic applications. We hope that this review will shed some light on the photocatalytic energy conversion of g-C3N4 decorated with silver.

Although oxidation is the most common biological and energy producing reaction, oxidative stress is harmful to cell, because the products of oxidation such as free radicals and peroxides damage the cellular components, causing several diseases. Damage in DNA is responsible for cancer formation and progression. However, several enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase etc. act as antioxidants to influence oxidative stress. Polymorphisms in these enzymes are supposed to be associated with DNA damage and subsequently the individual's risk of cancer susceptibility. This review article aims to further elucidate the relationship between antioxidant enzymes and cancers by summarizing the findings of some of the important study concerning expression levels and genetic polymorphisms of antioxidant enzymes in cancer patients.

Resveratrol (RSV) is a natural polyphenol that is known as a powerful chemopreventive and chemotherapeutic anticancer molecule. This study focused on the effects of RSV on the activities and expression levels of antioxidant enzymes in the cancer cells. Prostate cancer PC-3 cells, hepatic cancer HepG2 cells, breast cancer MCF-7 cells and the non-cancerous HEK293T kidney epithelial cells were treated with a wide range of RSV concentrations (10-100 μM) for 24-72 h. Cell growth was estimated by trypan blue staining, activities of the antioxidant enzymes were measured spectrophotometrically, expression levels of the antioxidant enzymes were quantified by digitalizing the protein band intensities on Western blots, and the percentage of apoptotic cells was determined by flow cytometry. Treatment with a low concentration of RSV (25 μM) significantly increased superoxide dismutase (SOD) activity in PC-3, HepG2 and MCF-7 cells, but not in HEK293T cells. Catalase (CAT) activity was increased in HepG2 cells, but no effect was found on glutathione peroxidase (GPX) upon RSV treatment. RSV-induced SOD2 expression was observed in cancer cells, although the expression of SOD1, CAT and GPX1 was unaffected. Apoptosis increased upon RSV treatment of cancer cells, especially in PC-3 and HepG2 cells. Together, our data demonstrated that RSV inhibits cancer cell growth with minimal effects on non-cancerous cells. We postulate that the disproportional up-regulation of SOD, CAT and GPX expression and enzymatic activity in cancer cells results in the mitochondrial accumulation of H2O2, which in turn induces cancer cell apoptosis.

Thioflavin T (ThT), a water-soluble fluorescence probe and the conventional dye for the detection of amyloid fibrils has recently been demonstrated to recognize and bind nucleic acids. It induces the formation of G-quadruplex (G4) structure and appears as a sensor by emitting enhanced fluorescence. Incorporation of G-rich sequences in the nucleic acid amplification procedures assists the observation of the final products. In this manner, ThT with the "light-up" nature has emerged as a well-liked dye being devised in several biosensing applications. It offers sensitive and straightforward detection of biosubstrates including nucleic acids, proteins, small molecules as well as measurement of enzyme activities with the advantages of specificity, reduced background signal, and minimal cost. In this review, we aim to present a thorough overview of the ThT-based biosensing applications along with ThT/G-quadruplex complex formation and ThT-associated amplification techniques.

TRIM28 regulates its target genes at both transcriptional and posttranscriptional levels. Here we report that a TRIM28-TWIST1-EMT axis exists in breast cancer cells and TRIM28 promotes breast cancer metastasis by stabilizing TWIST1 and subsequently enhancing EMT. We find that TRIM28 is highly expressed in both cancer cell lines and advanced breast cancer tissues, and the levels of TRIM28 and TWIST1 are positively correlated with the aggressiveness of breast carcinomas. Overexpression and depletion of TRIM28 up- and down-regulates the protein, but not the mRNA levels of TWIST1, respectively, suggesting that TRIM28 upregulates TWIST1 post-transcriptionally. Overexpression of TRIM28 in breast cancer cell line promotes cell migration and invasion. Knockdown of TRIM28 reduces the protein level of TWIST1 with concurrent upregulation of E-cadherin and downregulation of N-cadherin and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull-down assays demonstrated that TRIM28 interacts with TWIST1 directly and this interaction is presumed to protect TWIST1 from degradation. Our study revealed a novel mechanism in breast cancer cells that TRIM28 enhances metastasis by stabilizing TWIST1, suggesting that targeting TRIM28 could be an efficacious strategy in breast cancer treatment.

Recently, microRNAs (miRNAs), a kind of small and non-coding RNA, can target the downstream molecules. Increasing evidence demonstrates that miRNAs meditate the onset and progression of a variety of tumors. In the present study, we carried out gene transfection, western blot, and reverse transcription PCR (RT-PCR) to explore the role of miR-22 in glioblastoma tissues and cell lines. Here, we verified that the expression of miR-22 was downregulated in glioblastoma tissues and cells rather than matched non-tumor tissues and normal human astrocyte (NHA) cells (p < 0.001). By contrast, SIRT1 messenger RNA (mRNA) and protein were upregulated in glioblastoma tissues and cells (p < 0.001). In vitro miR-22 mimics interfered with cell proliferation, migration, and invasion of U87 and U251 cells. Mechanically, the 3'-untranslated regions (3'-UTRs) of SIRT1 were a direct target of miR-22, leading to the decreased expression of SIRT1 protein in U87 and U251 cells. Meanwhile, miR-22 mimics also inhibited the expression of epidermal growth factor receptor (EGFR) and matrix metallopeptidase 9 (MMP9). In conclusion, miR-22 inhibited cell proliferation, migration, and invasion via targeting the 3'-UTR of SIRT1 in the progression of glioblastoma and miR-22-SIRT1 pathway can be recommended as a potential target for treatment of glioblastoma.

Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in carcinogenesis in different cancers, and hence is regarded as a promising anticancer molecule. Inhibition of epithelial to mesenchymal transition (EMT) regulators is an important approach in anticancer research. In this study, TQ was used to treat the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT-regulatory proteins and cancer metastasis. Our results showed that TQ has time-dependent and dose-dependent cytotoxic effects, and it also inhibits the migration and invasion processes in different cervical cancer cells. At the molecular level, TQ treatment inhibited the expression of Twist1, Zeb1 expression, and increased E-Cadherin expression. Luciferase reporter assay showed that TQ decreases the Twist1 and Zeb1 promoter activities respectively, indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also increased cellular apoptosis in some extent, but apoptotic genes/proteins we tested were not significant affected. We conclude that TQ inhibits the migration and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and Zeb1/E-Cadherin/EMT, among other signaling pathways.

Ochratoxin A (OTA) is one of the most common mycotoxins contaminating feed and foodstuffs. Therefore, a great deal of concern is associated with AFB1 toxicity. In this work, a fast and sensitive fluorescence aptamer biosensor has been proposed for the OTA assay. In the absence of OTA, the OTA aptamer can form a G-quadruplex structure with thioflavin T (ThT) dye, which results in increased fluorescence. After joining OTA, OTA aptamer combines with OTA and the G-quadruplex can be formed. Only faint fluorescence was finally observed when ThT weakly reacts with the quadruplex. Through this test method, the entire reaction and analysis process of OTA can be completed in 10 min. Under optimal experimental conditions (600 nM OTA-APT, 7 &mu;M ThT, and 3 min incubation time), this proposed assay has a good limit of detection (LOD) of 0.4 ng/mL and shows a good linear relationship within the range of 1.2⁻200 ng/mL under the best experimental conditions. This method has a high specificity for OTA relative to Ochratoxin B (23%) and Aflatoxin B₁ (13%). In addition, the quantitative determination of this method in real samples has been validated using a sample of red wine supplemented with a range of OTA concentrations (1.2 ng/mL, 12 ng/mL, and 40 ng/mL) with recoveries of 96.5% to 107%.

Although the early diagnosis of prostate cancer (PCa) enhances life expectancy with a 5-year survival rate of 100 %, metastasized-PCa is the fundamental reason for death by PCa, hence requires an advanced and target-directed treatment strategy. Metastasis is considered to be initiated with the epithelial-mesenchymal transition (EMT) event in which tumor cells change their epithelial characteristics into mesenchymal form and exacerbates the cancer progression. Herein, we investigated the effect and mechanism of resveratrol function in PCa cell proliferation and migration and reported that TNF-receptor associated factor 6 (TRAF6), an unconventional E3 ligase, is a key mediator of resveratrol function to inhibit PCa cell growth and proliferation and targeted for lysosomal degradation by resveratrol. MTT and cell counting demonstrated that resveratrol inhibited the viability and proliferation in DU145 and PC3 cells. Resveratrol (50 μM) mediated the degradation of TRAF6 which in turn facilitated repression of the NF-κB pathway. Also, wound healing and transwell migration assays and level of EMT-related proteins showed that resveratrol used TRAF6, at least in part to inhibit cell migration. Overexpression of TRAF6 augmented EMT in PCa by upregulating the expression of transcription factor SLUG. Moreover, TRAF6 overexpression was closely associated with EMT process through the NF-κB pathway. Our exploration exhibited that resveratrol may inhibit EMT through the TRAF6/NF-κB/SLUG axis. Altogether, this study represents that TRAF6 acts as an intermediary of resveratrol action to suppress PCa cell proliferation and migration, and concerns future attention to obtain as a therapeutic target for the treatment of PCa.

USP8 is a deubiquitinating enzyme in the family of ubiquitin-specific proteases (USPs) which can remove ubiquitin from the substrate and protect the substrate from degradation. The upregulated or mutated USP8 becomes hyperactivated and stabilizes numerous oncogenes or proto-oncogenes leading to cancer progression and survival by activating multiple signaling pathways. Moreover, USP8 inhibition is also important to overcome anticancer drug-resistant. This review is the first study to find, combine, analyze, and represent the multiple oncogenic signaling pathways with their downstream and upstream regulation activated or enhanced by USP8, which will help the researchers to find any therapeutic strategy for drug discovery by inhibiting or suppressing the multi-targeted USP8.

CTSL is expressed by cancerous tissues and encodes a lysosomal cysteine proteinase that regulates cancer progression and SARS-CoV-2 entry. Therefore, it is critical to predict the susceptibility of cancer patients for SARS-CoV-2 and evaluate the correlation between disease outcomes and the expression of CTSL in malignant cancer tissues. In the current study, we analyzed CTSL expression, mutation rate, survival and COVID-19 disease outcomes in cancer and normal tissues, using online databases. We also performed immunohistochemistry (IHC) to test CTSL expression and western blot to monitor its regulation by cordycepin (CD), and N6, N6-dimethyladenosine (m62A), respectively. We found that CTSL is conserved across different species, and highly expressed in both normal and cancer tissues from human, as compared to ACE2 or other proteinases/proteases. Additionally, the expression of CTSL protein was the highest in the lung tissue. We show that the mRNA expression of CTSL is 66.4-fold higher in normal lungs and 54.8-fold higher in cancer tissues, as compared to ACE2 mRNA expression in the respective tissues. Compared to other proteases/proteinases/convertases such as TMPRSS2 and FURIN, the expression of CTSL was higher in both normal lungs and lung cancer samples. All these data indicate that CTSL might play an important role in COVID-19 pathogenesis in normal and cancer tissues of the lungs. Additionally, the CTSL-002 isoform containing both the inhibitor_I29 and Peptidase_C1 domains was highly prevalent in all cancers, suggesting its potential role in tumor progression and SARS-CoV-2 entry in multiple types of cancers. Further analysis of the expression of CTSL mutant showed a correlation with FURIN and TMPRSS2, suggesting a potential role of CTSL mutations in modulating SARS-CoV-2 entry in cancers. Moreover, high expression of CTSL significantly correlated with a short overall survival (OS) in lung cancer and glioma. Thus, CTSL might play a major role in the susceptibility of lung cancer and glioma patients to SARS-CoV-2 uptake and COVID-19 severity. Furthermore, CD or m62A inhibited CTSL expression in the cancer cell lines A549, MDA-MB-231, and/or PC3 in a dose dependent manner. In conclusion, we show that CTSL is highly expressed in normal tissues and increased in most cancers, and CD or m62A could inhibit its expression, suggesting the therapeutic potential of targeting CTSL for cancer and COVID-19 treatment.

The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The association between DPP4 expression and survival in various tumor tissues was compared using GEPIA 2. The DNMIVD database was used to analyze the correlation between DPP4 expression and promoter methylation in various tumors. On the cBioPortal network, the frequency of <em>DPP4</em> DNA mutations in various cancers was analyzed. The correlation between DPP4 expression and immunomodulators was analyzed by TISIDB database. The inhibitory effects of cordycepin (CD), N6, N6‑dimethyladenosine (m⁶₂A) and adenosine (AD) on DPP4 in cancer cells were evaluated. DPP4 was mainly expressed in endocrine tissue, followed by gastrointestinal tract, female tissue (mainly in placenta), male tissue (mainly in prostate and seminal vesicle), proximal digestive tract, kidney, bladder, liver, gallbladder and respiratory system. In immune cells, DPP4 mRNA was mainly expressed in T cells, and its expression was upregulated in esophageal carcinoma, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma and thymoma. However, it was downregulated in breast invasive carcinoma, kidney chromophobe, lung squamous cell carcinoma and skin cutaneous melanoma. Thus, DPP4 is involved in viral invasion in most types of cancer. The expression of DPP4 could be inhibited by CD, m⁶₂A and AD in different tumor cells. Moreover, CD significantly inhibited the formation of GFP‑positive syncytial cells. <em>In vivo</em> experiments with AD injection further showed that AD significantly inhibited lymphocyte activating factor 3 expression. These drugs may have potential to treat COVID‑19 by targeting DPP4. Thus, DPP4 may be medically significant for SARS‑CoV‑2‑infected cancer patients, providing prospective novel targets and concepts for the creation of drugs against COVID‑19.

Hepatic copper determination is an important test for the diagnosis of Wilson's disease (WD). However, the method has not been standardized, the diagnostic accuracy has not been evaluated prospectively, and the optimal cut-off value remains controversial. Accordingly, we aimed to prospectively evaluate the diagnostic accuracy of hepatic copper content, as determined using the entire core of a liver biopsy sample. Patients for whom a liver biopsy was indicated were consecutively enrolled. Hepatic copper content was determined with atomic absorption spectroscopy. All assays were performed using careful quality control by a single technician. WD diagnosis was based on WD score or its combination with clinical follow-up results. A total of 3,350 consecutive patients underwent liver biopsy. Six hundred ninety-one patients, including 178 with WD, underwent two passes of liver biopsy with hepatic copper determination. Mean hepatic content in WD patients was 770.6 ± 393.2 μg/g dry weight (wt). Sensitivity, specificity, and positive and negative predictive values of hepatic copper content for WD diagnosis in the absence of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis at the cut-off value of 250 μg/g dry wt. were 94.4%, 96.8%, 91.8%, and 97.8%, respectively. The most useful cut-off value was 209 μg/g dry wt, with a sensitivity and specificity of 99.4% and 96.1%, respectively. A total of 23.3% of patients without WD and PBC had hepatic copper content >75 μg/g dry wt.A liver biopsy sample of more than 1 mg dry wt may reliably reflect hepatic copper content and should be used for hepatic copper determination. Hepatic copper determination is a very valid procedure for the diagnosis of WD, and the most useful cut-off value is 209 μg/g dry wt.

MicroRNA-34a (miR-34a), a tumor suppressor, has been reported to be dysregulated in various human cancers. MiR-34a is involves in certain epithelial-mesenchymal transition (EMT)-associated signal pathways to repress tumorigenesis, cancer progression, and metastasis. Due to the particularity of miR-34 family in tumor-associated EMT, the significance of miR-34a is being increasingly recognized. Competing endogenous RNA (ceRNA) is a novel concept involving mRNA, circular RNA, pseudogene transcript, and long noncoding RNA regulating each other's expressions using microRNA response elements to compete for the binding of microRNAs. Studies showed that miR-34a is efficient for cancer therapy. Here, we provide an overview of the function of miR-34a in tumor-associated EMT. ceRNA hypothesis plays an important role in miR-34a regulation in EMT, cancer progression, and metastasis. Its potential roles and challenges as a microRNA therapeutic candidate are discussed. As the negative effect on cancer progression, miR-34a should play crucial roles in clinical diagnosis and cancer therapy.

Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin's expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN-201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin's high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.

MicroRNA (miR)-125b has been shown to play a potential role in the development of glioma stem cells. However, the relationship between miRNA and glioma stem cells is still elusive. This study was designed to elucidate this potential relationship. We established a highly invasive glioma stem cell and progenitor (GSCP) cell line SU3. SU3 cell suspensions were injected into nude mice brains in situ, and the invasiveness of graft tumors was analyzed using hematoxylin and eosin staining as well as immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of miR-125b in SU3 and other cells. In vitro, SU3 cells expressed CD133 and nestin as well as differentiation markers glial fibrillary acidic protein (GFAP) and β-tubulin III, which were consistent with the characteristics of glioma stem cells. Scratch assays indicated that the migration ability of SU3 cells was stronger than that of U251 stem cells (U251s). In vivo, SU3 cells invaded into each part of the mouse brain from the caudate nucleus in a diffuse pattern and highly expressed invasive and proliferative cell markers matrix metalloprotease 2 (MMP2), MMP9, and Ki-67. Real-time PCR results revealed that the levels of miR-125b and MMP9 were significantly higher in SU3 and SU2, also a highly invasive GSCP cell line we established before, than in U251s. High expression of miR-125b both in newly established GSCPs, SU3, and long-term cultured GSCPs, SU2 suggests that miR-125b exhibits oncogene-like behavior. This behavior should be considered in further studies of miR-125b in cancer stem cells. Furthermore, MMP9, which plays a role in cancer stem cell invasion, may be a target gene of miR-125b.

Cervical cancer is one of the most common causes of cancer-related mortality in women in developing countries. Interferon (IFN)-α has been widely used in the treatment of various types of cancer, including cervical cancer, and IFN-stimulated gene 15 (ISG15), an ubiquitin-like protein, is upregulated by IFN-α treatment. The anti-virus and antitumor effects of ISG15 have been reported; however, its mechanism of action have not yet been fully elucidated. In this study, HeLa cells were used as a model system to investigate the roles of ISG15 in IFN-α-mediated cancer cell growth inhibition and induction of apoptosis. The results revealed that both p53 and p21 were upregulated in HeLa cells treated with IFN-α or in the HeLa cells overexpressing ISG15. In addition, the expression levels of ubiquitin-like modifier-activating enzyme 7 (UBA7, also known as UBE1L; ISG15 E1-activating enzyme), UBCH8 (ISG15 E2-conjugating enzyme) and HERC5 (ISG15 E3-ligase) were elevated in the HeLa cells treated with IFN-α. The levels of p53 in the HeLa cells were attenuated by transient transfection with small interfering RNA (siRNA) targeting ISG15 (ISG15-siRNA). Cell viability was inhibited by both IFN-α treatment and ISG15 overexpression. However, these effects were significantly diminished when p53 was knocked down, suggesting that the effects of inhibitory effects of ISG15 on HeLa cell growth and the induction of apoptosis were p53-dependent. Taken together, these results suggest the existence of the IFN-α/ISG15/p53 axis in cervical cancer cells and any strategies manipulating the levels of ISG15 may thus prove to be effective in the treatment of cervical cancer.

Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder.In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD.We found a novel heterozygous missense mutation, c.734T>C (p.L245P) in the PROM1 gene.Structurally, this mutation most likely impairs PROM1 protein stability, flexibility, and amino acid interaction network after changing the amino acid residue Leucine into Proline in the basic helix-loophelix leucine zipper domain.Molecular dynamic simulation and principal component analysis provide compelling evidence that this PROM1 mutation contributes to disease causativeness or susceptibility variants in patients with STGD4-like MD.Thus, this finding defines new approaches in genetic characterization, accurate diagnosis, and prevention of STGD4-like MD.

Herein, a turn-on fluorescence assay was introduced for alkaline phosphatase (ALP) detection based on ThT/G-quadruplex system. The basis of the method is that chelation of guanine bases at the binding sites by Ag+ blocks G-quadruplex formation and decreases the fluorescence intensity sharply. In the presence of ALP, ascorbic acid 2-phosphate (AAP) is hydrolyzed to form ascorbic acid (AA) which in turn reduces Ag+ to Ag0. As a result, the blockage ability of Ag+ is disrupted which augments the fluorescence intensity and relies on the concentration of ALP. Under the optimized parameters (500 nM DNA probe; 6 μM Ag+; 1 mM AAP; 30 min for Ag+ and DNA probe reaction time), fluorescence intensity correlates linear range between 1 and 100 U/L of ALP concentration with the detection limit of 0.503 U/L. In the inhibition assay, 50% of ALP inhibition is caused by Na3VO4 with a concentration of 0.254 mM. Furthermore, the assay was used to detect ALP activity in human serum samples in which the results were significant. Above all, the proposed strategy is potential, facile, and sensitive for analyzing ALP activity and screening ALP inhibitor.

TMPRSS2 (OMIM: 602060) is a cellular protease involved in many physiological and pathological processes, and it facilitates entry of viruses such as SARS-CoV-2 into host cells. It is important to predict the prostate's susceptibility to SARS-CoV-2 infection in cancer patients and the disease outcome by assessing TMPRSS2 expression in cancer tissues. In this study, we conducted the expression profiles of the TMPRSS2 gene for COVID-19 in different normal tissues and PRAD (prostate adenocarcinoma) tumour tissues. TMPRSS2 is highly expressed in normal tissues including the small intestine, prostate, pancreas, salivary gland, colon, stomach, seminal vesicle and lung, and is increased in PRAD tissues, indicating that SARS-CoV-2 might attack not only the lungs and other normal organs, but also in PRAD cancer tissues. Hypomethylation of TMPRSS2 promoter may not be the mechanism for TMPRSS2 overexpression in PRAD tissues and PRAD pathogenesis. TMPRSS2 expresses eleven isoforms in PRAD tissues, with the TMPRSS2-001 isoform expressed highest and followed by TMPRSS2-201. Further isoform structures prediction showed that these two highly expressed isoforms have both SRCR_2 and Trypsin (Tryp_SPc) domains, which may be essential for TMPRSS2 functional roles for tumorigenesis and entry for SARS-CoV-2 in PRAD patients. Analyses of functional annotation and enrichment in TMPRSS2 showed that TMPRSS2 is mostly enriched in regulation of viral entry into host cells, protein processing and serine-type peptidase activity. TMPRSS2 is also associated with prostate gland cancer cell expression, different complex(es) formation, human influenza and carcinoma, pathways in prostate cancer, influenza A, and transcriptional misregulation in cancer. Altogether, even though high expression of TMPRSS2 may not be favourable for PRAD patient's survival, increased expression in these patients should play roles in susceptibility of the SARS-CoV-2 infection and clinical severity for COVID-19, highlighting the value of protective actions of PRAD cases by targeting or androgen-mediated therapeutic strategies in the COVID-19 pandemic.

The genetic polymorphisms of biotransformation phase I enzymes, cytochrome P450 (CYP1A1 and CYP2D6), and phase II enzymes, glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 204 healthy persons and 348 leukemia patients, who suffered from also acute lymphoblastic leukemia (ALL), acute nonlymphoblastic leukemia (ANLL) chronic myelogenous leukemia (CML), from the Han ethnic group in Changsha City of Hunan Province of China. Our results showed that the frequencies of polymorphisms of CYP1A1, CYP2D6 and GSTT1 among the groups including acute lymphoblastic leukemia, ANLL, chronic myelogenous leukemia and healthy control have no significant differences. The variation of GSTM1-null genotype alone correlated with the development of ANLL. The combined genotypes of GSTM1-null with GSTT1-null, or GSTM1-null with CYP1A1 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant and CYP2D6 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant, CYP2D6 heterozygous mutant and GSTT1-null were found in individuals with high risk of ANLL. All these findings suggest that GSTM1-null genotype alone or in coordination with the relevant genotypes of other metabolic enzymes might be susceptibility factors in the etiology of ANLL.

The chemopreventive effects of resveratrol (RSV) on prostate cancer have been well established; the androgen receptor (AR) plays pivotal roles in prostatic tumorigenesis. However, the exact underlying molecular mechanisms about the effects of RSV on AR have not been fully elucidated. A model system is needed to determine whether and how RSV represses AR transcriptional activity.The AR cDNA was first cloned into the retroviral vector pOZ-N and then integrated into the genome of AR-negative HeLa cells to generate the AR(+) cells. The constitutively expressed AR was characterized by monitoring hormone-stimulated nuclear translocation, DNA binding, and transcriptional activation, with the AR(-) cells serving as controls. AR(+) cells were treated with RSV, and both AR protein levels and AR transcriptional activity were measured simultaneously. Chromatin immunoprecipitation (ChIP) assays were used to detect the effects of RSV on the recruitment of AR to its cognate element (ARE).AR in the AR (+) stable cell line functions in a manner similar to that of endogenously expressed AR. Using this model system we clearly demonstrated that RSV represses AR transcriptional activity independently of any effects on AR protein levels. However, neither the hormone-mediated nucleus translocation nor the AR/ARE interaction was affected by RSV treatment.We demonstrated unambiguously that RSV regulates AR target gene expression, at least in part, by repressing AR transcriptional activity. Repressive effects of RSV on AR activity result from mechanisms other than the affects of AR nuclear translocation or DNA binding.

Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. In this study, the relationships between genetic polymorphisms of phase I metabolic enzymes including cytochrome P450 1A1 (CYP1A1), CYP2D6 and phase II metabolic enzymes such as glutathione S-transferase M1 (GSTM1) and GSTT1 and gastric carcinoma susceptibility were investigated. Genomic DNA was isolated from the peripheral blood of 129 healthy controls and 123 gastric carcinoma patients from Han ethnic group of Hunan Province located in Central South China. The genetic polymorphisms of the above mentioned enzymes were analyzed using PCR-RFLP techniques. There was no significant difference among the frequencies of CYP1A1 and/or CYP2D6 gene’s wild type, heterozygous or homozygous mutations between the gastric carcinoma group and control group. But the differences among the frequencies of GSTM1 and GSTT1 null genotype between the gastric carcinoma and control group were significant (both P < 0.05). Also there were significant differences in the frequencies of GSTM1 null in high/high–middle differentiated, middle differentiated, middle–low differentiated and low differentiated gastric tumor separately. GSTM1 null showed an increased risk in middle–low differentiated and low differentiated gastric carcinoma type, but GSTT1 null was not a risk factor for the four pathological types of gastric carcinoma mentioned above. We report here that the genotypes of CYP1A1 and CYP2D6 are not associated with gastric carcinoma risk; GSTM1 null, but not GSTT1 null inheritably increases risk of some pathological types of gastric carcinoma in Han ethnic population of Hunan Province.

Hexavalent chromium [Cr(VI)] and its compounds (e.g. chromates), which are extensively used in numerous industrial processes including leather tanning and steel manufacturing, are considered as priority pollutants. There is growing evidence supporting that Cr(VI) could be a human carcinogen that induces primary liver cancer after oral exposure, and this sheds light on the importance of the investigation of Cr(VI)-induced hepatotoxicity. Although it is known that mitochondria are major targets for heavy metals, the mechanisms of electron transfer chain (ETC) dysfunction involved in Cr(VI)-induced cytotoxicity are unclear.In the present study, by using mitochondrial respiratory chain complex (MRCC) I inhibitor rotenone (ROT) and its substrates glutamate/malate (Glu/Mal), MRCC III inhibitor antimycin A (AA) and its substrate coenzyme Q (CoQ), and the antioxidant Vitamin C (Vit C), we aimed to elucidate the role of mitochondrial ETC dysfunction in Cr(VI)-induced cytotoxicity.We found that Cr(VI) targeted and inhibited MRCC I and III to induce ETC dysfunction, which played an important role in Cr(VI)-induced cytotoxicity.Our current data provides novel important insight into the mechanisms of mitochondrial ETC dysfunction in Cr(VI)-induced cytotoxicity in the hepatocytes, and we will be poised to develop new methods in the prevention and treatment of liver diseases involving mitochondrial ETC dysfunction for the occupational exposure population.

Objective The aim of this study was to review the efficacy and safety of microvascular decompression (MVD) for idiopathic trigeminal neuralgia (ITN) in elderly patients older than 65 years. Methods From June 2006 to June 2011, a total of 59 elderly patients with ITN underwent MVD. We performed a retrospective study of the medical records and compared the outcome data with those from 164 patients younger than 64 years during the same period. Results The mean age of the elderly and younger patient groups was 72 and 55 years. The pain was completely relieved in 93.2% and partially relieved in another 5.1% of the elderly patient group after surgery. The mean follow-up period was 42 months (range, 16–75 mo). A total of 8.9% of the patients in the elderly patient group experienced recurrence. Headaches, nausea, and vomiting were more frequent complications. There were no mortalities and severe morbidities after surgery. Between the elderly and younger patient groups, no statistically significant differences existed in the outcomes. Conclusions Microvascular decompression is a safe and effective procedure for elderly patients with ITN. It is recommended that any patients with ITN should have the opportunity to choose MVD, unless their condition cannot tolerate general anesthesia.

Here we report a new approach for label-free colorimetric assay of T4 polynucleotide kinase/phosphatase (PNKP) activity based on G-quadruplex/hemin DNAzyme. In the presence of T4 PNKP, the DNA primer with a 3’-phosphate can be dephosphorylated into a 3’-hydroxyl and initiate a primer elongation reaction to open the hairpin probe, and leading to releasing the G-quartets. Under optimal conditions, the proposed method exhibited a considerable performance with a detection limit of 0.01 U/mL. Furthermore, the present assay can be used to study the potential T4 PNKP inhibitor screening, making it promise to be applied in the fields of drug discovery.

In this work, we developed a facile fluorescence method for quantitative detection of human serum albumin (HSA) based on the inhibition of poly(thymine) (poly T)-templated copper nanoparticles (CuNPs) in the presence of HSA. Under normal circumstances, poly T-templated CuNPs can display strong fluorescence with excitation/emission peaks at 340/610 nm. However, in the presence of HSA, it will absorb cupric ion, which will prevent the formation of CuNPs. As a result, the fluorescence intensity will become obviously lower in the presence of HSA. The analyte HSA concentration had a proportional linear relationship with the fluorescence intensity of CuNPs. The detection limit for HSA was 8.2 × 10−8 mol·L−1. Furthermore, it was also successfully employed to determine HSA in biological samples. Thus, this method has potential applications in point-of-care medical diagnosis and biomedical research.

The present work demonstrates a simple, rapid and label-free ATP detection method using a fluorescent aptasensor that is based on G-quadruplex formation. In the absence of ATP, the Thioflavin T (ThT) dye binds to the G-rich ATP aptamer and forms an ATP aptamer/ThT G-quadruplex complex, which results in high fluorescence intensity. Upon addition of ATP, the ATP aptamer/ThT complex will be replaced by the formation of an ATP aptamer/ATP complex. During this process, separation of the ThT dye from the ATP aptamer/ThT complex decreases the fluorescence intensity of the reaction mixture dramatically. This fluorescence aptasensor is highly sensitive and rapid, with a detection limit of 18 nM and a total reaction time of only 10 min. Furthermore, this method is cost-effective and simple, removing the requirement for labeling the detection reagents with a fluorophore-quencher pair.

Deubiquitinase (DUB)‐mediated cleavage of ubiquitin chain balances ubiquitination and deubiquitination for determining protein fate. USP7 is one of the best characterized DUBs and functionally important. Numerous proteins have been identified as potential substrates and binding partners of USP7; those play crucial roles in diverse array of cellular and biological processes including tumour suppression, cell cycle, DNA repair, chromatin remodelling, and epigenetic regulation. This review aims at summarizing the current knowledge of this wide association of USP7 with many cellular processes that enlightens the possibility of abnormal USP7 activity in promoting oncogenesis and the importance of identification of specific inhibitors.

Triple Negative Breast Cancer (TNBC) is considered as the most deadly subtype of breast cancer, because of heterogeneity, less treatment options and resistance to chemotherapy.To find out an efficient chemotherapeutic options, in this study we have investigated the combined therapy of 5-Fluorouracil (5-FU) and thymoquinone (TQ) against TNBC cell lines BT-549 and MDA-MB-231.We have tested 5-FU and TQ alone and in combination (5-FU + TQ) to observe the cellular growth, cell cycle and apoptosis status of BT-549 and MDA-MB-231 cells. Also we have measured the mRNA level expression of genes related to cell cycle and apoptosis.Experimental results suggest that both of 5-FU and TQ are effective in controlling cell growth, cell cycle and inducing apoptosis, but their combination is much more effective. 5-FU was found to be more effective in controlling cell growth, while TQ was found to be more effective in inducing apoptosis, but in both cases, their combination was most effective. TQ was found more effective in increasing and BAX/BCL-2 ratio, while 5-FU was more effective in inhibiting thymidylate synthase. They showed significant increasing effects on caspases and P53 and decreasing effect on CDK-2, where their combination was found most effective.Thus, TQ and 5-FU probably showed synergistic effect on both of cell cycle and apoptosis of tested TNBC cell lines. Our study reveals that TQ can synergise 5-FU action, and increase its anticancer efficiency against TNBC cells, which might be good choice in drug development for TNBC treatment.

The Cordyceps mushrooms have a long history as medicinal fungi.In Traditional Chinese Medicine, Cordyceps have been used to treat several conditions including cancers for thousand of years.Extracts from both mycelium and fruiting bodies of C. sinensis, C. militaris and other Cordyceps species showed significant anticancer activities by various mechanisms such as, modulating immune system and inducing cell apoptosis.Some polysaccharide components and cordycepin (3'-deoxyadenosine) have been isolated from C. sinensis and C. militaris, which acted as potent anticancer components.This review article aims to further elucidate the importance of Cordyceps mushrooms by summarizing the findings of some of the important research works concerning possible mechanism of anticancer activity of this mushroom.

XinJiErKang (XJEK), a Chinese herbal formula, is identified as an effective preparation to treat coronary heart disease and myocarditis. The aim of the study is to investigate the anti-hypertensive effects of XJEK by oral administration and also to find out whether the drug has any role in oxidative stress and vascular endothelial function.Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) which reached a plateau after 4 weeks of surgery. Treatment of hypertensive rats (20 mmHg higher than basic systolic blood pressure) with XJEK (6, 12, 24 g/kg/day) and fosinopril (15 mg/kg/day) respectively by intragastric administration started 4 weeks after surgery and continued for 4 weeks. The sham-operated (Sh-Op) controls received drinking water. BP was monitored weekly using tail-cuff apparatus. At the end of 8 wk, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate of rise of left ventricular pressure (±dp/dtmax) were examined (PowerLab 8/30, AD Instruments, Australia). The myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes were investigated by hematoxylin and eosin (HE) and Van Gieson (VG) stain. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) content in serum, contents of hydroxyproline (Hyp) in the ventricular tissue were assayed by xanthin oxidase method, thiobarbituric acid (TBA) method, Griess method and alkaline hydrolysis method, respectively. Angiotensin II (Ang II) content in serum was detected by radioimmunoasssay method.XJEK therapy potently improved cardiac function, inhibited myocardial hypertrophy, improved cardiac pathology change, decreased the myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA), reduced the content of Hyp in the left ventricular tissue, inhibited the decrease of SOD activity and increase of MDA, Ang II content in serum. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting endothelial-dependent vasodilation of thoracic aortic rings and enhancing the NO activity in serum.These findings suggest that administration of XJEK possess protective effects against 2K1C induced hypertension and cardiac remodeling in rats, preserve NO activity and endothelial function.

Huwentoxin-IV (HWTX-IV, also named Mu-theraphotoxin-Hh2a) is a typical inhibitor cystine knot peptide isolated from the venom of Chinese tarantula Ornithoctonus huwena and is found to inhibit tetrodotoxin-sensitive (TTX-S) sodium channels from mammalian sensory neurons. This peptide binds to neurotoxin receptor site 4 located at the extracellular S3–S4 linker of domain II in neuronal sodium channels. However, the molecular surface of HWTX-IV interaction with sodium channels remains unknown. In this study, we synthesized HWTX-IV and three mutants (T28D, R29A and Q34D) and characterized their functions on TTX-S sodium channels from adult rat dorsal root ganglion (DRG) neurons. Analysis of liquid chromatography, mass spectrometry and circular dichroism spectrum indicated that all four synthetic peptides are properly folded. Synthetic HWTX-IV exhibited the same activity as native HWTX-IV, while three mutations reduced toxin binding affinities by 10–200 fold, indicating that the basic or vicinal polar residues Thr28, Arg29, and Gln34 in C-terminus might play critical roles in the interaction of HWTX-IV with TTX-S sodium channels.

This study aimed to investigate the effect of miR-423-5p on the sensitivity of glioma stem cells to apigenin and to explore the potential mechanism. Previous research indicated that apigenin can effectively inhibit the proliferation of many cancer cells, including glioma cells, though our data unexpectedly showed that apigenin had no effect on glioma stem cell apoptosis. As many studies have reported that malignant transformation and progression of glioma are due to glioma stem cells, an anti-glioma stem cell approach has become an important direction for glioma treatment. In this study, we found miR-423-5p to be overexpressed in glioma tissues and corresponding glioma stem cells. Downregulation of miR-423-5p repressed glioma stem cell growth but did not cause apoptosis. Based on the concept of "Pharmaco-miR," this study further demonstrated that the combination of miR-423-5p knockdown and apigenin had a notable additive effect on inhibiting proliferation and promoting apoptosis in glioma stem cells. Hoechst staining showed higher apoptosis rates and typical apoptotic morphological changes of the cell nucleus, and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocya-nine iodide) staining revealed reduced mitochondrial membrane potential. Further research demonstrated that the mechanism is associated with a shift in the Bax/Bcl-2 ratio, an increased cytochrome c level, Apaf-1 induction, and caspase-3 activation. In conclusion, this study indicates that downregulation of miR-423-5p enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.

Mutations are changes in the nucleotide sequence that derive from external factors or errors during cell division. They are the source of many diseases such as cancers, sickle cell anemia, hereditary diseases, etc. Their presence or absence is one of the best indicators in disease detection. Therefore, many DNA mutation detection methods were proposed to reduce the cost and improve the detection capability. Notably, biosensors and sequencing techniques have been improved tremendously by the creation of new devices and detection strategies. They were adapted to solve the numerous problems faced in mutation detection processes such as oligonucleotide length, low efficiency due to intermolecular effect, sample limitations, difficulty to detect SNPs in a dsDNA, low sensitivity, accuracy, etc. Herein, we review the recent and significant advances made in biosensors and sequencing technologies for the detection of mutations. We also discuss their advantages and limitations, as well as the challenges that remain and possible ways to overcome them.

Lung adenocarcinoma (ADC) is one of the major histological types of lung cancer. Genetic polymorphism in DNA repair genes and lung ADC susceptibility is well documented. In this case–control study, the association between the polymorphic sites of DNA repair genes XPD-751, XRCC1-399, and OGG1-326, and lung ADC susceptibility in ethnic Han Chinese population has been investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 82 lung ADC patients from the people of Hunan Province, China. Polymorphisms of the investigated genes were analyzed by using polymerase chain reaction–restriction fragment length polymorphism. There was no significant difference between the samples from lung ADC patients and healthy controls about the genotype frequencies of XPD-751, XRCC1-399, and OGG1-326 sites. However, multifactor dimensionality reduction analysis showed that the genetic polymorphisms of the three-loci models of DNA repair genes (XPD-751/XRCC1-399/OGG1-326) are associated with lung ADC. Thus, this study reveals that a three-order interaction among the polymorphic sites of XPD-751, XRCC1-399, and OGG1-326 is associated with lung ADC risk in the studied population, although polymorphism in individual gene was not associated.

N-type calcium channels play important roles in the control of neurotransmission release and transmission of pain signals to the central nervous system. Their selective inhibitors are believed to be potential drugs for treating chronic pain. In this study, a novel neurotoxin named Huwentoxin-XVI (HWTX-XVI) specific for N-type calcium channels was purified and characterized from the venom of Chinese tarantula Ornithoctonus huwena. HWTX-XVI is composed of 39 amino acid residues including six cysteines that constitute three disulfide bridges. HWTX-XVI could almost completely block the twitch response of rat vas deferens to low-frequency electrical stimulation. Electrophysiological assay indicated that HWTX-XVI specifically inhibited N-type calcium channels in rat dorsal root ganglion cells (IC50 ∼60 nM). The inhibitory effect of HWTX-XVI on N-type calcium channel currents was dose-dependent and similar to that of CTx-GVIA and CTx-MVIIA. However, the three peptides exhibited markedly different degrees of reversibility after block. The toxin had no effect on voltage-gated T-type calcium channels, potassium channels or sodium channels. Intraperitoneal injection of the toxin HWTX-XVI to rats elicited significant analgesic responses to formalin-induced inflammation pain. Toxin treatment also changed withdrawal latency in hot plate tests. Intriguingly, we found that intramuscular injection of the toxin reduced mechanical allodynia induced by incisional injury in Von Frey test. Thus, our findings suggest that the analgesic potency of HWTX-XVI and its greater reversibility could contribute to the design of a novel potential analgesic agent with high potency and low side effects.

Objectives The objectives of this work are to report the outcomes of our finding during microvascular decompression (MVD) for patients with recurrent trigeminal neuralgia (TN) and to introduce the sling retraction technique. Methods The authors performed a retrospective review of redo MVD for consecutive cases with recurrent TN after previous operation. Sling retraction techniques were used during the reoperation. Results Fifteen patients underwent redo MVD. During the second operation, arachnoid adhesion of the Teflon felt was confirmed at the trigeminal nerve in 10 cases, and neurovascular conflict was found in 4 cases. Symptoms were completely relieved in 14 patients (93.3%) and partially relieved in 1 patient (6.7%). The mean follow-up period was 38 months (range, 21–60 months), and no patient experienced recurrence. Conclusions Arachnoid adhesion of the Teflon felt and vascular compression to the nerve were main causes of recurrence. The sling retraction technique is still an effective and useful treatment for recurrent TN after MVD.

A label-free fluorescence assay has been developed for the detection of carcinoembryonic antigen based on dsDNA-templated copper nanoparticles.

The increasing incidence of prostate cancer (PCa) indicates an urgent need for the development of new effective drug therapy. There are limited options to treat the PCa, this study tried to determine a new therapy option for this acute cancer. Androgen-independent PCa cell lines PC3 and DU145 were treated with different melatonin concentrations (0.1~3.5 mM) for 1~3 days and assessed cell migration, cell invasion, cycle arrest in G0/G1 phase as well as apoptosis. We utilized RNA-seq technology to analyze the transcriptional misregulation pathways in DU145 prostate cancer cell line with melatonin (0.5 mM) treatment. Data revealed 20031 genes were up and down-regulated, there were 271 genes that differentially expressed: 97 up-regulated (P<0.05) and 174 down-regulated (P<0.05) genes. Furthermore, RNA-seq results manifested that the melatonin treatment led to a significant increase in the expression levels of HPGD, IL2Rβ, NGFR, however, IGFBP3 and IL6 (P <0.05) had decreased expression levels. The immunoblot assay revealed the expression of IL2Rβ and NGFR genes was up-regulated, qPCR confirmed the gene expression of HPGD and IL2RB were also up-regulated in Du145 cells. Consequently, we probed mechanisms that generate kinetic patterns of NF-κB-dependent gene expression in PCa cells responding to a NF-κB-activation, the significant results were indicated by the inhibition of the NF-kB pathway via IL2Rβ actions. Based on our investigation, it could be concluded that melatonin is a chemotherapeutic molecule against PCa and provides a new idea for clinical therapy of PCa.

A case-control study was conducted for analyzing the genetic polymorphisms of phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy subjects from Han ethnic group of Hunan Province located in Central South China. The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls. Genotypes of combining GSTP1 mutant/GSTM1(-) or GSTP1 mutant/GSTT1(-) led to high risk of lung cancer. Individuals carrying any two or all three of GSTM1(-), GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/-), GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/-) and GSTP1 wild genotypes. Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes. All these findings suggest that the genetic polymorphisms of phase II metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic group of Central South China.

A novel fluorescent probe for adenosine triphosphate (ATP) assay based on DNA ligation is proposed in this article. This approach uses a novel smart probe, T4 DNA ligase, and two short oligonucleotides. In the presence of ATP, the T4 DNA ligase catalyzes the ligation reaction and the ligation product restores the fluorescence of the smart probe. This method is very sensitive with a 0.5-nM limit of detection. Compared with current assay methods, the strategy is simpler, cheaper, and 40 times more sensitive.

Abstract Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer‐related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy‐related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next‐generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2 : c.7007G&gt;T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long‐term follow‐up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2 : c.7007G&gt;T (p.R2336L).

Prostate cancer (PCa) is the most common cancer diagnosed and the second most common cause of cancer‐related death in men worldwide. The current androgen deprivation therapy for PCa cannot fully cure this disease. Moreover, androgen receptor gene amplification and mutation are associated with PCa to develop castration‐resistant prostate cancer (CRPC). This review focuses on the deubiquitinases (DUBs) involved in PCa development and progression. For PCa development and progression, several cellular pathways are regulated by specific DUBs which are also highlighted in here. The ubiquitin‐specific proteases (USPs), a family member of DUBs mostly involved in the regulation of cellular pathways for PCa development, and the ubiquitin C‐terminal hydrolases (UCHs), another family member of DUBs, are responsible for PCa metastasis. Small molecular inhibitors against DUBs can inhibit or reduce the level of specific DUBs through the regulation of cellular pathway to treat this disease. Some small molecular inhibitors are already identified against some of the DUBs, but very few of them are clinically proved in PCa. So, to find out other DUBs involving in the regulation of PCa‐related pathways and to develop more effective small molecule inhibitors with greater potency would be a great idea to target PCa cells for future therapeutics and drug development with or without the combination of other anticancer drugs. Significance of the study This review is targeting DUB proteins which are responsible for PCa induction, proliferation, and metastasis by highlighting their signalling pathway so that the readers can get information about other mechanisms for PCa besides androgen receptor pathway and helps to find other oncogenic DUBs involving in these signalling pathways. This review also hopes to find other oncogenic DUBs involving in PCa‐related signalling pathways or to find the DUBs that can regulate multiple oncogenic signalling pathways which might be a good target for PCa therapeutics. In addition, there are some small molecule inhibitors that can inhibit the oncogenic DUBs and thus able to control the oncogenic pathways which would be a novel strategy to treat CRPC by using DUB inhibitor combined with or without other anticancer drugs.

Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide. Interferon- α (IFN- α ) has been widely used in the treatment of HCC, but patients eventually develop resistance. ISG15 ubiquitin-like modifier (ISG15) is a ubiquitin-like protein transcriptionally regulated by IFN- α which shows antivirus and antitumor activities. However, the exact role of ISG15 is unknown. In the present study, we showed that IFN- α significantly induced ISG15 expression but failed to induce HepG2 cell apoptosis, whereas transient overexpression of ISG15 dramatically increased HepG2 cell apoptosis. ISG15 overexpression increased overall protein ubiquitination, which was not observed in cells with IFN- α -induced ISG15 expression, suggesting that IFN- α treatment not only induced the expression of ISG15 but also inhibited ISG15-mediated ubiquitination. The tumor suppressor p53 and p21 proteins are the key regulators of cell survival and death in response to stress signals such as DNA damage. We showed that p53 or p21 is only up regulated in HepG2 cells ectopically expressing ISG15, but not in the presence of IFN- α -induced ISG15. Our results suggest that ISG15 overexpression could be developed into a powerful gene-therapeutic tool for treating IFN- α -resistant HCC.

In this research, we investigated the allele frequencies and forensic parameters of 21 non-, CODIS short tandem repeat (STR) loci (D6S474, D12ATA63, D22S1045, D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433, D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435 and D5S2500) among 523 unrelated, Chinese Mongolians in the city of Tongliao, Horqin district, Inner Mongolia Autonomous Region.

Background: Fomitopsis officinalis (Vill. ex Fr. Bond. et Sing) is a medicinal mushroom, commonly called ‘Agarikon’; it has traditionally been used to treat cough and asthma in the Mongolian population. Objective: The objective of the study was to examine the significance of biological activity of F. officinalis and evaluation of the antioxidant activity and anticancer activity of six fractions of F. officinalis residues (Fo1-powder form dissolved in ethanol, Fo2-petroleum ether residue, Fo3-chloroformic, Fo4-ethylacetate, Fo5-buthanolic, and Fo6-waterethanolic) against hepatocellular carcinoma cells. Methods: We performed in vitro studies of cell proliferation and viability assay, annexin V-FITC/Propidium Iodide assay, and NF-kB signaling pathway by immunoblot analysis. Results: Our findings revealed that all six fractions/extracts have antioxidant activity, and somehow, they exert anticancerous effects against cancer cells. In cancerous cell lines (HepG2 and LO2), Fo3 chloroformic extract promoted the cancer cell apoptosis and cell viability, activated G2/M-phase cell cycle, and selectively induced NF-kB proteins, revealing as a novel antitumor extract. Conclusion: This study reports that Fo3-chloroformic extract is rich in antitumor activity, which was previously not investigated in cancer. To develop the impact of F. officinalis among natural products to treat/prevent oxidative stress disorders or cancers, further examinations of F. officinalis are needed to develop new natural drugs to treat cancer. However, this study assessed only one extract, Fo3-chloroformic, which has a significant impact against cancer cell lines.

Han is the largest of China's 56 ethnic groups and the most populous ethnic group in the world. The Luzhou region is located in southwest China, at the junction of three provinces. The unique historical factors contribute to the genetic polymorphism information. Short tandem repeats (STRs) are highly polymorphic, but the polymorphism of the Y chromosomal STRs (Y-STRs) loci in the Luzhou region is still unclear. It is of great significance to provide Y-STRs genetic data for the Han population from the Luzhou areas of southwest China. A total of 910 unrelated male individuals of the Han population from the Luzhou area were recruited, and 24 Y-STRs were analyzed. The population structure and phylogenetic relationships were compared with those of another 11 related Han populations. A total of 893 different haplotypes were achieved from 910 samples, of which 877 (98.21%) haplotypes were unique. Haplotype diversity and discrimination were 0.999956 and 0.981319, respectively. The lowest genetic diversity of DYS437 is 0.4321, and the highest genetic diversity of DYS385a/b is 0.9642. Pair-to-pair genetic distance and relative probability values indicate that Luzhou Han people are close to Sichuan Han people, Guangdong Han people, and Hunan Han people, which is consistent with geographical distribution, historical influence, and economic development. The 24 Y-STR markers of the southwest Luzhou Han population were highly polymorphic, which provided us with genetic polymorphism information and enriched the population genetic database. Therefore, it is of great value to our forensic applications and population genetics research.

Gliomas are one of the most common and most aggressive types of central nervous system tumor. Angiogenesis is an important basis for the growth of solid tumors, including gliomas, which is regulated by microRNAs (miRNAs). However, the mechanism remains unclear. Recently, it was demonstrated that miR‑24 was upregulated in gliomas, so the aim of the present study is to establish whether the dysregulation of miR‑24 in glioma cells promotes microvascular proliferation of endothelial cells (ECs), and to investigate the potential mechanism. miR‑24 was overexpressed or downregulated in U251 glioma cell line cells using miR‑24 mimics or inhibitors, respectively. Subsequently, the effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on cell viability, migration and angiogenesis of human umbilical vein ECs (HUVECs) were examined. The expression levels of vascular endothelial growth factor (VEGF) mRNA, basic fibroblast growth factor (bFGF) mRNA, epidermal growth factor (EGF) mRNA, transforming growth factor (TGF)‑β mRNA, matrix metalloproteinase (MMP)‑2 mRNA and MMP‑9 mRNA, and the mRNA and protein levels of VEGF and TGF‑β in miR‑24 mimic‑ or inhibitor‑transfected U251 cells were obtained by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The effects of conditional medium from miR‑24 mimic‑ or inhibitor‑transfected U251 cells on expression levels of VEGF mRNA, TGF‑β mRNA, MMP‑2 mRNA and MMP‑9 mRNA, and mRNA and protein expression levels of VEGF and TGF‑β, and intracellular AKT and β‑catenin signaling in HUVECs were also examined. The results indicated that the conditional medium from miR‑24 mimic‑transfected U251 cells exhibited significantly increased cell viability, cell migration and tube formation of HUVECs. By contrast, the conditional medium from miR‑24 inhibitor‑transfected U251 cells exhibited significantly decreased cell viability, cell migration and tube formation of HUVECs. Enforced expression of miR‑24 in U251 cells may promote the cell viability and angiogenesis of HUVECs. The mRNA expression levels of VEGF, bFGF, EGF, TGF‑β, MMP‑2 and MMP‑9 in U251 cells were significantly increased by miR‑24 mimics. Western blot detection confirmed the increased levels of VEGF and TGF‑β protein expression in U251 by miR‑24 mimics, and the decrease of VEGF and TGF‑β protein expression levels in U251 by miR‑24 inhibitors. The conditional medium from miR‑24 mimic‑transfected U251 cells increased the expression levels of the angiogenesis‑associated factors, including VEGF, TGF‑β, MMP‑2, and MMP‑9. By contrast, reduced expression of miR‑24 in U251 cells may downregulate the expression of those angiogenesis‑associated factors. Thus, miR‑24 in U251 cells may be important in the angiogenesis of HUVECs via VEGF and TGF‑β, and the intracellular signaling of AKT and β‑catenin may be involved in this process.

We have developed a new methodology for fluorescence turn-on detection of DNA methyltransferase (MTase) activity based on terminal deoxynucleotidyl transferase (TdT) using a thioflavin T probe. This method is highly selective and sensitive. The fluorescence intensity was direct proportion to Dam MTase concentration in the range from 0.1 to 8.0 U/mL with a detection limit of 0.1 U/mL. And because no labeling with a fluorophore-quencher pair was required, it is simple and low cost. We envision that our novel fluorescent detection method for Dam MTase activity could be applied as a useful tool in biomedical research.

Phosphorylation and dephosphorylation of DNA by polynucleotide kinase (PNK) has an important role in DNA damage repair, replication, and recombination. Traditionally, it is assayed by denaturing gel electrophoresis and autoradiography, which are tedious and not sensitive. We report on the development of a sensitive and simple method for PNK assay based on DNA ligation using a molecular beacon. Enzyme activity of PNK is measured down to a limit of 0.002 unit/ml. The method not only provides a universal platform for simultaneous monitoring of kinase and phosphatase activities, but also shows great potential in biological research, drug discovery, and clinical diagnostics.

BACKGROUND: PIK3CA gene encodes the p110 α catalytic subunit of the oncoprotein phosphatidylinositol 3-kinase (PI3 K) which regulates many biological processes such as cell proliferation, differentiation, migration and survival through the activation of various signaling pathways. OBJECTIVE: In t his study, we have investigated the possible somatic mutations in PIK3CA gene in invasive ductal breast carcinomas of Chinese women from Western China. METHODS: Genomic DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) tissue samples. The hotspot mutations in PIK3CA gene of exon 9 and exon 20 were studied by pyrosequencing. RESULTS: The sequencing identified two hotspot mutations in exon 20 of one cancer samples at p. H1047L (c. 3140A > T) and eight cancer sample at p. H1047R (c. 3140A > G). No mutation in exon 9 of PIK3CA gene was found in these breast cancer tissue samples. PIK3CA mutations showed surprising clinicopathological features in breast cancer patients, as incidence of lymph node invasiveness is increased in the patients with PIK3CA mutation. In addition, all the patients showed tumor size bigger than 3 cm in diameter. It is important that for early detection and early treatment for BC in developing countries or areas like Western China, and for people to provide popularization education using scientific knowledge in cancer fields. CONCLUSIONS: This study identified PIK3CA mutations in breast carcinoma patients of Western China that will enable a more rapid molecular diagnosis, and provide a stronger rationale evidence for development of precision therapeutic approaches as well as promising therapeutic targets for breast cancer treatment or patient management.

The evergreen shrub, Gardenia jasminoides Ellis var. grandiflora Nakai is one of the most popular garden-plants, with significant ornamental importance. Here, we have cloned improved random amplified polymorphic DNA (RAPD) derived fragments into T-vector, and developed sequence-characterized amplified region (SCAR) markers. These markers have been deposited in GenBank database with the accession numbers KP641310, KP641311, KP641312 and KP641313 respectively. The BLAST search of database confirmed the novelty of these markers. The four SCAR markers, namely ZZH11, ZZH31, ZZH41 and ZZH51 can specifically recognize the genetic materials of G. jasminoides from other plant species. Moreover, SCAR marker ZZH31 can be used to distinguish G. jasminoides Ellis var. grandiflora Nakai from other G. jasminoides on the market. Together, this study has developed four stably molecular SCAR markers by improved RAPD-derived DNA markers for the genetic identification and authentication, and for ecological conservation of medicinal and ornamental plant G. jasminoides.

Traditional methods of assaying polynucleotide kinase (PNK) activity are discontinuous, time-consuming, and laborious. Here we report a new quencher-free approach to real-time monitoring of PNK activity using a 2-aminopurine probe. When the 2-aminopurine probe was 5′-phosphorylated by PNK, it could be efficiently degraded by lambda exonuclease to release free 2-aminopurine molecules and generate a fluorescence signal. This method not only provides a universal approach to real-time monitoring of PNK activity, but also shows great potential for screening suitable inhibitor drugs for PNK.

The plant species Lycium, commonly known as box‑thorn, is a genus of flowering plants of the Solanaceae family. It is commonly used in Traditional Chinese Medicine (TCM) for its fruits. As there are numerous different species Lycium, the present study, aimed to analyze the genetic diversity and similarities between some of these species. For this purpose, samples from 16 Lycium species were collected, and cluster dendrograms were created using random amplified microsatellite polymorphism (RAMP)‑PCR and inter‑simple sequence repeat (ISSR) markers. A total of 1,249 bands were produced, where each random amplified polymorphic DNA (RAPD) primer had 2‑9 valuable bands with an average of 6, of which 89.05% bands were polymorphic by RAMP‑PCR. Genetic distances were observed among different cultivars or species, which had a similarity coefficient (SC) index of 0.37‑0.98. Similar to RAMP‑PCR, ISSR analysis of the Lycium DNA samples yielded an SC index of 0.36‑0.98. ISSR markers produced 956 bands with average of 5.9 bands per ISSR primer, and 88.28% of the bands were polymorphic. The SC index between sample 2 and sample 16 was found to be 0.72 by both RAMP‑PCR and ISSR, which clustered together, which indicated that these two cultivars have good genetic association, in spite of their vast geographic distance. On the whole, the present study performed a genetic analysis of different Lycium species, which may prove to be useful for the conservation of the genetic diversity of different Lycium species/cultivars, as well as of other plant species.

Reactive oxygen species are involved in the etiology and progress of many kinds of diseases such as cancer, cardiovascular diseases, inflammatory and neurodegenerative disorders. Epidemiological studies reported that fruits, vegetables, and wines containing a high percentage of phenolics and flavonoids showed a positive impact in treating inflammatory diseases, reducing cancer risk, and increasing life expectancy.Some Mongolian medicinal plants were studied for their antioxidant activity and anticancer effects.Selected Mongolian medicinal plant extracts were examined for their antioxidant activity by the DPPH-radical scavenging assay, the content of phenolics and flavonoids by Folin-Ciocalteu and the Dowd method, respectively, and anti-cancer activities in human hepatoma cell line HepG2 cells by MTT assay.Methanol extract from Hippophae rhamnoides L. leaf and ethanol extract from Artemisia macrocephala Jacq. ex Bess. showed the highest efficiency to scavenge free radicals. Ethanol extracts from Hippophae rhamnoides L. grain and Paeonio anomala L. leaf showed the highest total phenolics content, whereas Hippophae rhamnoides L. fruit methanol extract and ethanol extract from Caragana leucophloea pojark. mentioned the highest flavonoids content. The Artemisia macrocephala Jacq. ex Bess seed wallet and Paeonia anomala L. seed wallet showed the most potent antiproliferative effects against human liver cancer HepG2 cell line. Gnetin-H compound was isolated from the Paeonio anomala L. seed wallet extract, and its molecular structure was determined by 1H and 13C NMR spectrum and IR spectroscopy methods.The screening study on anti-oxidative effects of 21 extracts from 15 Mongolian medicinal plants showed anti-oxidative activities and was rich in phenolics and flavonoids. Among these, methanol extract of the Hippophae rhamnoides L. leaf showed a better anti-oxidative effect than the ethanol extract. Artemisia macrocephala Jacq. ex Bess and Paeonia anomala L. seed wallet mentioned the best anti-cancer effects. Gnetin-H, methyl gallate, ethylgallate were the major components in the extract from the Paeonio anomala L. seed wallet. Finally, the molecular structure of gnetin-H was determined by NMR and IR spectroscopy. Further investigation, especially in vivo antioxidant activity, is needed to justify the use of a natural source of antioxidants to prevent the progression of diseases such as cancer.

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.

We have developed a new methodology for label-free highly sensitive telomerase activity assay using chemiluminescence imaging. This method can detect the telomerase activity from as little as 10 cultured cancer cells without PCR. Furthermore, telomerase inhibition is shown, demonstrating the potential for screening of telomerase inhibitors as anticancer drug agents.

In this paper, a robot arm is designed and set on the top of the wheeled robot, which can recognize the numbers or signs and push the buttons. There is a micro-camera set on the tip of the robot arm for the image processing and pattern recognition. Then, the inverse kinematics is used to calculate the angle of each link of the robot arm to press the desired button correctly. Integrating the techniques of image processing, pattern recognition, and motion control, the robot is implemented to achieve the elevator-button pushing task.

The multiple-code (MC) and multicode-keying (MK) schemes were recently proposed to support multirate multimedia services in asynchronous optical code-division multiple-access (O-CDMA) systems. A user in the MC scheme simultaneously conveys multiple codewords to represent the transmission of multiple data bits of 1. While the MK scheme only transmits one codeword at a time, each codeword represents a symbol (of multiple data bits of 0 and 1). In this paper, a hybrid multirate asynchronous O-CDMA system model that comprises the conventional single-rate scheme and these two multirate schemes is studied. The bit error probability (BEP), spectral efficiency (SE), and throughput of the proposed hybrid system are formulated. The conditions and combinations of simultaneous users from these three schemes that can optimize the system&#x2019;s BEP, SE, and throughput are investigated. Finally, the new analytical models are validated with numerical examples and computer simulations.

To cope with the memory wall of von-Neumann computing architecture, the in-memory-computing (IMC) architecture has been proposed. The IMC architecture embeds logic into the memory array to reduce the data transfer between the processor and memory. This paper proposes a configurable 8T SRAM which can provide the functions of ternary content address memory, left shift, and right shift in addition to the storage function. The method only needs to modify the peripheral circuitry of an 8 T SRAM. The Hspice simulator is used to verify configurable 8T SRAM using TSMC 0.18μm CMOS technology.

Although uveal melanoma (UM) at the early stage is controllable to some extent, it inevitably ultimately leads to death due to its metastasis. At present, the difficulty is that there is no way to effectively tackle the metastasis. It is hypothesized that these will be treated by target molecules, but the recognized target molecule has not yet been found. In this study, the target molecule was explored through proteomics.Transgenic enhanced green fluorescent protein (EGFP) inbred nude mice, which spontaneously display a tumor microenvironment (TME), were used as model animal carriers. The UM cell line 92.1 was inoculated into the brain ventricle stimulating metastatic growth of UM, and a graft re-cultured Next, the UM cell line 92.1-A was obtained through monoclonal amplification, and a differential proteomics database, between 92.1 and ectopic 92.1-A, was established. Finally, bioinformatics methodologies were adopted to optimize key regulatory proteins, and in vivo and in vitro functional verification and targeted drug screening were performed.Cells and tissues displaying green fluorescence in animal models were determined as TME characteristics provided by hosts. The data of various biological phenotypes detected proved that 92.1-A were more malignant than 92.1. Besides this malignancy, the key protein p62 (SQSTM1), selected from 5267 quantifiable differential proteomics databases, was a multifunctional autophagy linker protein, and its expression could be suppressed by chloroquine and dacarbazine. Inhibition of p62 could reduce the malignancy degree of 92.1-A.As the carriers of human UM orthotopic and ectopic xenotransplantation, transgenic EGFP inbred nude mice clearly display the characteristics of TME. In addition, the p62 protein optimized by the proteomics is the key protein that increases the malignancy of 92.1 cells, which therefore provides a basis for further exploration of target molecule therapy for refractory metastatic UM.

Ubiquitin-specific protease 8 (USP8) has been recently reported to be involved in tumorigenesis. Prostate cancer (PCa) is the most diagnosed malignancy among men, but USP8's role in PCa is not yet investigated comprehensively. Therefore, the PCa cell lines DU145 and PC3 were transfected with USP8 siRNA or overexpressing vector together with or without docetaxel. The silencing USP8 and docetaxel treatment reduced cell viability and migration and promoted apoptosis. In contrast, USP8 knockdown was found to enhance docetaxel antitumor activity. In contrast, increased cell viability and migration were noticed upon USP8 overexpression, thereby decreasing apoptosis and suppressing docetaxel antitumor activity. Notably, although EGFR, PI3K, and NF-kB were found to be increased in both USP8 overexpression and docetaxel treatment, it significantly attenuated the effects in USP8 silencing followed by with or without docetaxel. Although EGFR silencing decreased PI3K and NF-kB activation, overexpression of USP8 was shown to counteract SiEGFR's effects on NF-kB signaling by increasing PI3K expression. Our findings revealed that USP8 plays an oncogenic role in PCa and can suppress docetaxel activity. Additionally, as EGFR/PI3K/NF-kB was previously reported to develop docetaxel resistance, the combination treatment of USP8 knockdown with docetaxel might be a potential PCa therapeutic.

Alkaline phosphatase (ALP) is a metalloenzyme, the level of which is clinically significant as an abnormality of ALP activity results in several diseases. In the present study, we introduced a MnO2 nanosheet-based assay for ALP detection employing the adsorption and reduction characteristics of G-rich DNA probes and ascorbic acid (AA), respectively. Ascorbic acid 2-phosphate (AAP) was utilized to act as a substrate for ALP which hydrolyzes AAP generating AA. In the absence of ALP, MnO2 nanosheets adsorb the DNA probe destructing the G-quadruplex formation and showing no fluorescence emission. On the contrary, being present in the reaction mixture ALP hydrolyzes AAP yielding AA, then the AA reduce the MnO2 nanosheets into Mn2+, hence, the probe is free to react with a dye, thioflavin T (ThT), and synthesizes ThT/G-quadruplex to spark high fluorescence intensity. Therefore, under optimized conditions (250 nM DNA probe, 8 μM ThT, 96 μg/mL MnO2 nanosheets, and 1 mM AAP) the sensitive and selective measurement of ALP activity can be achieved through the change of fluorescence intensity, with a linear range and a limit of detection of 0.1–5 U/L and 0.045 U/L. Our assay exhibited its potential to assess the ALP inhibitor when in an inhibition assay Na3VO4 inhibited ALP with an IC50 value of 0.137 mM and also was validated in clinical samples.

The proportion of the super-aged population (at the age of 80 or above) in patients with chronic subdural hematoma (CSDH) and the incidence of CSDH of the population have been increasing. Since it is widely accepted that YL-1 needle is effective in CSDH treatment, this paper aimed to probe into the efficacy of YL-1 needle in minimally invasive surgery for super-aged (at the age of 80-90) CSDH patients.A retrospective analysis on the clinical information of 17 super-aged CSDH patients having received the YL-1 needle puncture treatment provided by the hospital from May 2012 to December 2016 was performed. At the same time, another 19 CSDH patients (ages 60-79) who were hospitalized during the same period were randomly selected to form a control group. The same surgical treatment was provided for both groups to observe and compare the treatment efficacy.The patients of both groups were cured and discharged. Among the super-aged patients, there was 1 patient with postoperative hematoma recurrence, 1 patient with pneumocephalus, and 1 patient with wound infection; among the aged patients, 1 reported postoperative recurrence and 2 had pneumocephalus; The average length of stay of the super-aged group was 9.235 ± 2.948 days while that of the aged group was 7.316 ± 3.660 days, which showed no statistical difference.The YL-1 needle puncture treatment is safe and efficacious for both the super-aged and the aged CSDH patients.

The aim of the present study was to explore the clinical effects, including the prevention of complications, of the treatment of chronic subdural hematoma with double needle aspiration.The clinical data of 31 patients with chronic subdural hematoma treated by double YL-1 needle double skull drilling and 31 controls treated by traditional drilling and drainage were analyzed retrospectively.In the YL-1 needle group, only 1 patient was with hematoma recurrence, 1 patient was with intracranial pneumocephalus, and the remaining patients who were followed up for 3 months achieved a clinical cure. In the traditional drilling and drainage group, 13 patients were with hematoma recurrence within 3 months after the operation and 7 patients were with postoperative intracranial pneumocephalus.The method of double YL-1 needle is better than the traditional drilling and drainage method for the treatment of chronic subdural hematoma because it reduces the postoperative recurrence rate and complications.

The idea of multiple differentiation capacity of glioma stem cells and progentior cells (GSCPs) has been accepted by most of the researchers, but the effect of local environment on the differentiation of GSCPs is unclear. GSCPs SU2 and CM-Dil-stained C6 cells (C6-Dil) were injected into the brain of GFP transgenic nude mice. The xenografts were sectioned. Morphological changes of tumor cells that resided in the choroid plexus, molecular markers expression, and the relationship between the original tumor cells and host cells were studied carefully. The tumorigenicity rate was 40/40 (100%) in all of the inoculated nude mice. Cell morphology and molecular expression of neoplasm settled in the choroid plexus showed that choroidcarcinoma derived from GSCPs was developed. These results showed that GSCPs may have the multiple differentiation capacity, which can be induced by the local environment of host brain as NSCs, and cell fusion may play an important role in the transformation.

An area-efficient CTDSM for sensor applications is presented. The proposed capacitively-coupled CTDSM combines the functions of precision amplifier and DSM to achieve hardware efficiency. The 1-bit quantizer with FIR-DAC improves the linearity without using DEM in multi-bit architectures or large-size analog filters. The proposed currentsplitting OTA saves the capacitor area in the first integrator stage. Fabricated in a 0.18-μm CMOS, this chip draws 70 μA (?) from a 1.8-V supply, and achieves 12-bit resolution under 2-kHz bandwidth at ±40-mV input range. The circuit area is only 0.2 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .

The mutations in patients with X-linked retinitis pigmentosa (xlRP) have not been well described in the Chinese population. In the present study, a five-generation Chinese retinitis pigmentosa (RP) family was recruited; targeted next-generation sequencing (TGS) was used to identify causative genes and Sanger sequencing for co-segregation. RNA-seq data analysis and revere transcriptional-polymerase chain reaction (RT-PCR) were applied to investigate gene expression patterns of RP GTPase regulator (RPGR) in human and Rpgr in mouse. A novel, hemizygous, deleterious and missense variant: c.G644A (p.G215E) in the RPGR gene (NM_000328.2) exon 7 of X-chromosome was identified in the proband, which was co-segregated with the clinical phenotypes in this family. RNA-seq data showed that RPGR is ubiquitously expressed in 27 human tissues with testis in highest, but no eye tissues data. Then the expressions for Rpgr mRNA in mice including eye tissues were conducted and showed that Rpgr transcript is ubiquitously expressed very highly in retina and testis, and highly in other eye tissues including lens, sclera, and cornea; and expressed highly in the six different developmental times of retinal tissue. Ubiquitous expression in different tissues from eye and very high expression in the retina indicated that RPGR plays a vital role in eye functions, particularly in retina. In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum. These findings facilitate better understanding of the molecular pathogenesis of this disease; provide new insights for genetic counseling and healthcare.

This study was performed to investigate the method of cranioplasty in patients with abnormal bone window pressure after decompressive craniectomy.We performed a retrospective analysis for 25 cases after decompressive craniectomy in patients with abnormal flap pressure of clinical data.Flap pressure increased in 15 cases, including 6 cases of hydrocephalus, 5 cases of contralateral subdural effusion, 2 cases of subdural effusion bone window, 2 cases of bone window cystic encephalomalacia communicating with the ventricle; Flap pressure decreased in 10 cases, including 6 cases of hydrocephalus after ventriculoperitoneal shunt, and 4 cases of low intracranial pressure. ALL of patients were treated by appropriate measures to make the operation smoothly.Our data suggest that after analysis of the factors for abnormal bone window flap pressure by decompressive craniectomy and symptomatic treatment, the difficulty of operation and operative complications can be reduced.

Mutations of the β-catenin gene are common in various cancer types. MicroRNA (miR)-24 suppresses gene expression during the cell cycle. However, the effects of miR-24 on the cell viability and autophagy of glioma cells, and how these biological processes are regulated by β-catenin are largely unclear. The current study aimed to investigate the role of β-catenin in regulating the effects of miR-24 on the cell viability and autophagy of glioma cells. The expression levels of microtubule-associated proteins 1A/1B light chain 3B (LC3B) and Beclin1 were detected by immunohistochemistry and western blotting. Glioma C6 cells were transfected with miR-24 mimics, miR-24 inhibitors and negative control miRNAs. C6 cells transfected with miR-24 mimics or negative control miRNAs were treated with the β-catenin inhibitor, XAV-939. An MTT assay was utilized to evaluate the viability of C6 cells. The expression of miR-24 and mRNA expression of autophagy related 4a cysteine peptidase (ATG4A) were detected by quantitative polymerase chain reaction analysis. The protein expression of LC3B and Beclin1 decreased significantly in glioma tissue and glioma C6 cells compared with normal brain tissue. Compared with the negative control group, C6 cells transfected with miR-24 mimics exhibited significantly higher cell viability at 24 and 48 h, and those transfected with miR-24 inhibitors exhibited significantly lower cell viability at 48 h. XAV-939 decreased the stimulatory effects of miR-24 mimics on the viability of C6 cells. The expression of miR-24 significantly decreased and ATG4A mRNA significantly increased in C6 cells transfected with XAV-939 compared with those transfected with the negative control miRNA. XAV-939 attenuated the miR-24-induced decrease of the protein expression of LC3B and Beclin1, and decreased the stimulatory effects of miR-24 mimics on cell viability. In addition, XAV-939 attenuated the miR-24-induced decrease of autophagy marker expression by attenuating miR-24 expression and increasing ATG4A mRNA expression in glioma C6 cells. To the best of our knowledge, the present study is the first to demonstrate whether β-catenin regulates the intracellular effects of miR-24 on the viability and autophagy of glioma cells. The results also provide some mechanistic basis to the pharmaceutical targeting of WNT signaling in high grade glial tumors.

Background: Interferon-alpha (IFN-α) is the traditional therapeutic agent for chronic myeloid leukemia (CML). The molecular mechanism of IFN-α efficacy in the treatment of CML is not fully clear. Objectives: To identify the peptides and/or proteins that bind to the proteins specifically expressed on the surface of IFN-α-sensitive CML cells by using a phage display library. Design/methods: IFN-α-sensitive KT-1/A3 cells were used as the target, and IFN-α-resistant subline KT-1/A3R was used as absorber for phage display biopanning. The positive phage clones were identified by enzyme-linked immunosorbent assay and flow cytometry. The peptides were deduced from their DNA sequences. Results: Multiple clones showed high binding efficiency to KT-1/A3 cells compared with that of the other leukemia cells. One of the peptides, KLWVIPQ, has a partial amino acid sequence homology with the C-terminal domain of E3 ubiquitin-protein ligase. Conclusions: This study presents the identification of specific heptapeptides that bind to IFN-α-sensitive KT-1/A3 cells. The cancer-selective ligands provide novel strategies for early and differential diagnoses, as well as potential targeted drug delivery.

Erratum to: Mol. Cells DOI/10.1007/s10059-013-2259-z This paper was initially published in the journal, Mol. Cells 35, 219–225. But there were some errors in the text. They should be corrected as follows. In the first line of the left column on page 223, “Fig. 2A” should be changed to “Fig. 2B”. In the fourteenth line of the left column on page 223, “Fig. 2B” should be changed to “Fig. 2A”. In the thirty-eighth line of the left column on page 223, “Fig. 2A” should be changed to “Fig. 2B”.

Creating an affordable, sensitive, and highly selective assay for mutation discrimination in cancer patients has become imperative in personalized medicine and early molecular diagnosis. In this work, we proposed a sensitive and affordable colorimetric assay for single nucleotide mutation (SNM) detection combining PCR, GQ-RCA and G-quadruplex/hemin DNAzyme complex formation. By using DNA sample, a PCR was first performed to produce a sufficient among of ssDNA along with lambda exonuclease digestion capability and a 5′-end phosphorylated primer. The ssDNA was then hybridized with a padlock probe (PLP) DNA, which can discriminate a single base mismatch. A successful ligation was followed by an RCA event to generate an abundance of G-quadruplex (GQ-RCA) which was then transformed into a DNAzyme (G-quadruplex/hemin complex) by the addition of hemin. The color change from colorless 3,3’,5,5’-tetramethylbenzidine (TMB) into colored oxTMB when hydrogen peroxide (H2O2) was added indicated the presence of a mutation. The assay had a limit of detection (LOD) of 180 pM and an LOD for visual detection of 10 pM. Mutations in samples from breast cancer patients were successfully detected with an accuracy of 100% when compared to Sanger sequencing results. The method is easily applicable even in resource poor setting regions given that it doesn’t require any sophisticated or expensive instrument, the signal readout is detectable simply by naked eyes. Our assay might be a useful tool for genetic analysis and clinical molecular diagnosis for breast cancer risk assessment and early detection. In addition, by simply constructing the corresponding PCR primers and padlock probe DNAs, the assay can be used to identify other mutation-related diseases.

Simultaneous degradation and detoxification in the pharmaceuticals and personal care products (PPCPs) removal process is significant for water treatment. In this study, a type I heterojunction, sodium niobate nanocubes decorated graphitic carbon nitride (NbNC/g-C3N4), was fabricated to achieve efficient photocatalytic degradation and detoxification of ciprofloxacin (CIP) under simulated solar light. NaNbO3 nanocubes were in-situ transformed from Na2Nb2O6•H2O via thermal dehydration at the interface of g-C3N4. The hybridized NbNC/g-C3N4 showed a high conduction band (CB) level of -1.68 eV, leading to efficient transfer of photogenerated electron to O2 to produce primary reactive species, •O2-. Mulliken population analysis of built-in electric field intensity indicates 0.37 e– transfers from NaNbO3 to g-C3N4 in NbNC/g-C3N4. NbNC/g-C3N4 offered 3.3- and 2.3-fold of CIP degradation rate constant (k1 = 0.173 min-1) compared with pristine g-C3N4 and NaNbO3, respectively. Degradation CIP mainly proceeded as defluorination and ring-opening on piperazine moiety of after •O2- attack.

Simultaneous degradation and detoxification in the pharmaceuticals and personal care products (PPCPs) removal process is significant for water treatment. In this study, a type I heterojunction, sodium niobate nanocubes decorated graphitic carbon nitride (NbNC/g-C3N4), was fabricated to achieve efficient photocatalytic degradation and detoxification of ciprofloxacin (CIP) under simulated solar light. NaNbO3 nanocubes were in-situ transformed from Na2Nb2O6•H2O via thermal dehydration at the interface of g-C3N4. The hybridized NbNC/g-C3N4 showed a high conduction band (CB) level of -1.68 eV, leading to efficient transfer of photogenerated electron to O2 to produce primary reactive species, •O2-. Density functional theory (DFT) calculation on density of state indicates C 2p and Nb 3d contribute to the CB, and 0.37 e– transfers from NaNbO3 to g-C3N4 in NbNC/g-C3N4 based on the Mulliken population analysis of built-in electric field intensity. NbNC/g-C3N4 offered 3.3- and 2.3-fold of CIP degradation rate constant (k1 = 0.173 min-1) compared with pristine g-C3N4 and NaNbO3, respectively. In addition, N24, N19 and C5 in CIP with high Fukui index are reactive sites for electrophilic attack by •O2-, resulting in defluorination and ring-opening on piperazine moiety of the dominant degradation pathways. Intermediates/products identification integrated with computational toxicity evaluation further indicated the great detoxification effect during CIP degradation in the photocatalysis system.

暴发性肝豆状核变性(FWD)是其中的一种少见而严重的临床类型,病情凶险,预后极差,如不进行肝移植,病死率几乎为100%.我们最近采用内科综合治疗方法成功地抢救1例FWD患者,对其进行了病理、基因突变检查,现将结果报道如下。

Using the phage display biopanning technique, we have previously identified a heptapeptide KLWVIPQ which specifically binds to the surface of the IFN-α-sensitive but not the IFN-α-resistant CML cells. The effects of this heptapeptide on the IFN-α-sensitive CML cells were investigated in the present study. IFN-α-sensitive KT-1/A3 and IFN-α-resistant KT-1/A3R CML cells were transfected by pEGFP-KLWVIPQ expression vector and/or induced by IFN-α. WST-1 cell proliferation assay, flow cytometry, and western blotting were performed to determine the effects of this heptapeptide and/or IFN-α on CML cells. The viability of the KT-1/A3 cells was inhibited and apoptosis was induced by either expression of the heptapeptide KLWVIPQ or IFN-α treatment with concurrent upregulation of P53 and downregulation of P210(bcr/abl). However, these effects were not observed in the IFN-α-resistant KT-1/A3R cells. These results suggest that the heptapeptide KLWVIPQ shares a similar mechanism with IFN-α in the regulation of CML cell growth and apoptosis, implying that the heptapeptide KLWVIPQ could be a novel target to go further into mechanisms of IFN-α sensitivity and/or resistance in CML.

Endonasal transphenoidal approach by neuroendoscopy has its own advantage, such as direct access, invasive, better visualization of the anterior communicating artery aneurysm and so on. The study is to provide anatomical knowledge for anterior communicating artery aneurysm surgery by endonasal transphenoidal approach with neuroendoscopy. Take 10 skull base specimens, observe and measure the anatomical structures around anterior communicating artery. Take 10 cadaveric heads, simulate the anterior communicating artery aneurysm surgery with neuroendoscopy by endonasal transphenoidal approach. Find the natural opening of sphenoid sinus, then open the skull base, expand bone window in anterior skull base. After that, cut off the dura, find the optic nerve, optic chiasm, cisterna lamina terminalis, anterior cerebral artery, a portion of frontal lobe, anterior communicating artery complex and its important branches, such as heubner artery, hypothalamic artery, orbitofrontal artery and so on. Lift up anterior communicating artery complex and seperate arachnoid in cisterna lamina terminalis, the lamina terminalis is exposed. Block bilateral A1 of anterior cerebral artery with aneurysm clip, the anterior communicating artery complex and its important branches are in view, so we can clip anterior communicating artery aneurysm safely. Anterior communicating artery aneurysm surgery can be finished with neuroendoscopy by endonasal transphenoidal approach. The vital structures can be clearly observed with neuroendoscopy. The rhombus anatomic region formed by bilateral olfactory nerve and optic nerve is a safe surgical area. According to the calculation, the safe surgical area is about 161.48 ± 12.78 mm2. Measure the distance between the important anatomic structures in the rhombus anatomic region. By means of SPSS 17 Statistical analysis software, the measuring distance is expressed with (x ± S)mm. The anterior communicating aneurysm surgery by endonasal transphenoidal approach with neuroendoscopy has its own advantage, such as direct access, minimally invasive, less bleeding, light pain, quick recovery, better visualization of the anterior communicating artery aneurysm and so on. This operation approach needs further study and exploration to clinical application, in order to become a mature approach of anterior communicating artery aneurysm surgery.

Potential conflict of interest: Nothing to report. We sincerely appreciate the comments and questions raised by Sintusek and Dhawan regarding our article.1 Based on our findings, we recommended that an entire core of liver biopsy sample with more than 1 mg dry weight should be used for hepatic copper determination. However, the coefficient of variation (CV) of the hepatic copper measurement was not significantly different between subgroups classified by dry weight of the liver, although there was a trend. Sintusek and Dhawan questioned the rationality of our recommendation and present data showing that estimation of liver copper is reliable in children with Wilson's disease (WD) even when the liver biopsy sample size is less than 1 mg. The copper concentration in the liver of a normal human newborn contains roughly 6‐8 times that of an adult, and this concentration falls to the adult value, approximately 30 µg/g of dry tissue, within 6 months and varies little throughout life.2 However, the amount of liver copper in WD patients after birth does not fall to the normal range, but gradually increases because of the WD gene mutation. Therefore, if the liver copper concentration in an untreated WD patient is not elevated, the most likely cause is laboratory error, including sampling error and/or measurement error. It is well accepted that the distribution of copper in the liver is inhomogeneous and that the accuracy of liver copper measurement is improved with an adequately sized specimen.3 The tissue obtained with biopsy needle is only 1.0∼3.5 mg dry weight. In clinical practice, liver copper content is usually determined with a part of a needle biopsy specimen. This practice may occasionally result in a false result. Indeed, nondiagnostic hepatic copper levels in patients with confirmed WD have been reported by many investigators in the past two to three decades. Among 28 patients with genetically confirmed WD, as reported by Sintusek and Dhawan, liver copper concentration was below 250 µg/g dry weight in 8 patients. These data demonstrate that estimation of liver copper is not reliable using their method. In our study, we observed a trend where larger liver biopsy specimens resulted in smaller CV of the copper measurement. Although the P value was not less than that required for statistical significance, we believe that the size of the liver biopsy specimen has important influence on the precise determination of the copper content, based on “Do not reject null hypothesis” rather than “Accept null hypothesis.” More important, the sensitivity of hepatic copper level for the diagnosis of WD at the conventional cut‐off value of 250 µg/g dry weight was as high as 94.4% with our method. Although not a head‐to‐head comparison, the sensitivity of our method was higher than that reported by Ferenci et al., which determined sensitivity using part of a needle biopsy specimen (83.3%).4

Great excitement surrounded the initial discovery of the Philadelphia chromosome translocation and the molecular rearrangement of the abl protooncogene which is generated by this translocation in chronic myelogenous leukemia (CML). In this review, we will discuss how molecular analysis of the biological abnormalities generated in the CML cells by this molecular rearrangement can be applied to new directions in therapy for this disease.

To identify 14 bacteria by sequencing the 16S rRNA gene and establish the basis for clinical application in the future.DNA samples of the 14 bacteria were extracted. The 16S rRNA genes were amplified by PCR and sequenced with common primers. The sequences of the 16S rRNA genes were aligned by online software Blastn in nucleotide database. The bacteria were identified according to the homology of their 16S rRNA genes.Twelve bacteria were classified to species, the other 2 bacteria were classified to genus.16S rRNA gene sequence analysis is useful in identifying pathogenic bacteria.

Based on the distribution of genetic polymorphisms regarding phase I metabolic enzyme cytochrome P450 1A1 (CYP1A1) and phase II metabolic enzymes glutathione S-transferase GSTM1 and GSTT1 genotypes in acute leukemia patients and health controls among general population of Hunan in China, this study was to explore the relationship between these gene polymorphisms and the susceptibility to acute leukemia.Using case-control methodology, we studied 204 healthy controls and 232 patients with acute leukemia, of which 112 patients were suffering acute lymphoblastic leukemia (ALL) and 120 with acute non-lymphoblastic leukemia (ANLL). The frequencies of the genotypes were detected by PCR and PCR-RFLP techniques.The variation frequencies of CYP1A1 gene (Msp I polymorphisms, site 3801T-C variation) in ALL and ANLL groups were 74.1% and 70.8% respectively which were higher than 63.3% appeared in the healthy controls. However, the differences between patients (ALL or ANLL) and healthy controls were not statistically significant (P > 0.05 for both). The null genotype of GSTM1 (GSTM1 -/-) in ALL group was 60.7%, which was not significantly different from the controls (55.4%). However, GSTM1 -/- genotype in ANLL group was 68.3%, significantly different from the controls (P < 0.05). The null genotypes among GSTT1 (GSTT1 -/-) in ALL, ANLL and control group were 50.9%, 55.0% and 49.0% but their differences were not statistically significant (P > 0.05). The incidences of GSTM1 -/- and GSTT1 -/- combined genotype in ALL, ANLL and control group were 33.0%, 40.0% and 27.5%, of which the difference between ANLL group and control group was statistically significant (P < 0.05) and CYP1A1 gene heterozygous mutation type or homozygous mutation type combined with GSTM1 -/- and GSTT1 -/- increased the risk of ANLL (OR value 1.890, 95% CI: 1.084-3.295).These results indicated that both the variation of CYP1A1 gene or GSTT1 -/- genotype alone might not be associated with the susceptibility of acute leukemia while GSTM1 -/- genotype alone or combined with GSTT1 -/- or the 3801 T-C variation of CYP1A1 gene were correlated with ANLL. These findings suggest that GSTM1 - / - genotype alone or in combination with other defective genotypes might serve as risk factors to the etiology of ANLL.

Objective:To optimize the solubility of indirubin in water,and study the inhibitory effect of indirubin on K562 cells(Chronic myeloid leukemia cell line) and its mechanism.Methods:With dimethyl sulfoxide(DMSO) as double solvent,the effects of indirubin on the proliferation activity of K562 cells in vitro were investigated by MTT assay and flow cytometry.Results:Compared with negative control group,indirubin was not effective to inhibit the proliferation activity of K562 cells with final concentration 10 mg.L-1.Conclusion:Indirubin didn't effectively inhibit K562 cell viability through its direct action on the leukemia cells,which suggested that the secondary metabolite of indirubin might be involved in the mechanism of this effect.

Objective To study the correlations between genetic polymorphisms of cytochrome P450 CYP1A1 and CYP2D6 and leukemia predisposition through investigating the frequency distributions of genetic polymorphisms ofCYP1A1 andCYP2D6 in leukemia patients and healthy controls in the population of Hunan Province in China.Methods The frequencies of polymorphic genotypes ofCYP1A1 andCYP2D6 were detected by PCR and PCR-RFLP technologies.Results Frequencies of the wild(W/W),the heterozygous mutation(W/M) and the homozygous mutation(M/M) types of bothCYP1A1 andCYP2D6 genes showed no significant differences among the patients with acute lymphoblastic leukemia(ALL),acute non-lymphoblastic leukemia(ANLL) or chronic myelogenous leukemia(CML) and healthy controls.The individuals with W/M or M/M genotypes ofCYP1A1 orCYP2D6 didn't show increased leukemia risk over their wild type counterparts.However,the frequency ofCYP1A1 W/M genotype combined withCYP2D6 W/M genotype of ANLL group was higher than that of the controlgroup.Conclusion The polymorphic variation ofCYP1A1 alone or ofCYP2D6 alone does not affect the susceptibility to leukemia.However,heterozygous mutation ofCYP1A1 gene combined with that ofCYP2D6 gene increases the risk of ANLL.

Unfortunately, as for the second institute name of first author Baixu Zhou, "Department of Gynecology and Obstetrics, Guangzhou Women and Children's Hospital, Guangzhou, Guangdong, China", should be "Department of Gynecology and Obstetrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China".

Abstract Regulation of gene expression by TRIM28 is not only by transcriptional repression but also by post-translational regulation. Here we report that TRIM28 promotes breast cancer cell metastasis through TRIM28-TWIST1-EMT pathway. We find that TRIM28 is highly expressed in metastatic cancer cell lines and advanced breast cancer tissues. The expression of TRIM28 and TWIST1 is positively correlated with most of the invasive breast carcinomas. Notably, we find that overexpression of TRIM28 upregulates TWIST1 protein, whereas TRIM28 depletion downregulates TWIST1 protein, indicating that TWIST1 upregulation likely occurs at post-transcriptional level, not at transcriptional level. Overexpression of TRIM28 in BT549 breast cancer cell line promotes cell migration and invasion functionally; conversely, knockdown of TRIM28 reduces TWIST1 protein level, up-regulates E-cadherin and down-regulates N-cadherin, and consequently inhibits cell migration and invasion. Furthermore, Immunoprecipitation and GST pull down reveal that TRIM28 interacts with TWIST1 directly, thereby preventing from proteasomal degradation. Moreover, TWIST1 degradation rate is reduced after cycloheximide blocking protein synthesis through the depletion of TRIM28 in BT549 cells. Taken together, our findings suggest that TRIM28 functionally stabilizes TWIST1 protein, reveals a novel mechanism, and provides an effective therapeutic strategy to target TRIM28 in breast cancer treatments. Citation Format: Chunli Wei, Jingliang Cheng, Hanchun Chen, Dianzheng Zhang, Junjiang Fu. Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1674.

Two multirate techniques, so-called the multiple-code (MC) and multicode-keying (MK) schemes, were recently proposed to support multimedia services with different bit rates in asynchronous optical code-division multiple-access (O-CDMA) systems. In the MC scheme, a user maps multiple data bit 1s to multiple code matrices and transmits them at the same time. In the MK scheme, a user only transmits one of its assigned codewords at a time, and each codeword represents a symbol of multiple data bits. In terms of error probability, the performances of these multirate schemes were also analyzed. Spectral efficiency (SE) is another figure-of-merit useful for comparing O-CDMA schemes. In this paper, the performances and SEs of the multirate MC and MK schemes are formulated and the conditions of which scheme offers a better SE are investigated with formal proofs. Numerical examples are given to validate the analyses.