Research progress of ZIC5 for tumor metastasis.

The zinc finger protein of the cerebellum (ZIC) family comprises five members (ZIC1-5), homologous with the odd-paired (OPA) gene in Drosophila melanogila. These transcription factors contain five Cys2His zinc finger domains, constituting one of the most abundant transcription factor families in human cells. ZIC proteins significantly contribute to transcriptional regulation and chromatin remodeling. As a member of the ZIC family, ZIC5 is essential for animal growth and development. Numerous studies have investigated the connection between ZIC proteins and cancer as well as tumor metastases in recent years. Many studies have found that within tumor tissues, the transcription and translation processes increase the expression of ZIC5 which is linked to tumor aggressiveness. This review aims to provide an objective summary of the impact of ZIC5 on tumor metastasis and consider the potential application of ZIC5 targets in both tumor therapy and the early detection of cancer.

Flexible, Wash-Resistant Human Mechanical Energy Harvesting and Storage System for Monitoring Human Movement.

The rapid development of personal portable electronic devices has brought an increasingly urgent need for flexible and portable power sources. Herein, a low-cost, wearable, efficient, sustainable energy harvesting and storage system for human motion detection has been developed, based on a supercapacitor (SC) and triboelectric nanogenerator (TENG). Carbon cloth (CC)-loaded ZnO/ZnS nanoarrays and a PVD-treated polyurethane conductive sponge are employed as positive and negative triboelectric friction layers, respectively. Besides, flexible and robust silicone rubber provides stable output performance and enables the TENG to harvest mechanical energy from human motion even under complex conditions. As a result, it shows excellent electrical output performance in terms of the open-circuit voltage, short-circuit current, and average power density, reaching 175 V, 12 µA, and 816.7 mW m-2, respectively. These outstanding performances enable the TENG to effectively charge an all-solid-state symmetrical SC (MnO2/LiMn2O4@CC//MnO2/LiMn2O4@CC) and subsequently store it as electrochemical energy for sustainable power supply. Because of the flexible all-texture-type structure of the entire system, it is capable of monitoring the human body's movement. This work has a promising future in random mechanical energy harvesting and storage, as well as human motion tracking.

Coexistence of tet(A) and blaKPC-2 in the ST11 hypervirulent tigecycline- and carbapenem-resistant Klebsiella pneumoniae isolated from a blood sample.

Carbapenem-resistant Klebsiella pneumoniae are distributed worldwide. This study aimed to characterize a hypervirulent tigecycline-resistant and carbapenem-resistant Klebsiella pneumoniae strain, XJ-K2, collected from a patient's blood. We tested antimicrobial susceptibility, virulence, and whole-genome sequencing (WGS) on strain XJ-K2. WGS data were used to identify virulence and resistance genes and to perform multilocus sequence typing (MLST) and phylogenetic analysis. Three novel plasmids, including a pLVPK-like virulence plasmid (pXJ-K2-p1) and two multiple resistance plasmids (pXJ-K2-KPC-2 and pXJ-K2-p3), were discovered in strain XJ-K2. The IncFII(pCRY) plasmid pXJ-K2-p3 carried the dfrA14, sul2, qnrS1, blaLAP-2, and tet(A) resistance genes. The IncFII(pHN7A8)/IncR plasmid pXJ-K2-KPC-2 also carried a range of resistance elements, containing rmtB, blaKPC-2, blaTEM-1, blaCTX-M-65, and fosA3. MLST analysis revealed that strain XJ-K2 belonged to sequence type 11 (ST11). Seven complete phage sequences and many virulence genes were found in strain XJ-K2. Meanwhile, antimicrobial susceptibility tests and G. mellonella larval infection models confirmed the extensively drug resistance (XDR) and hypervirulence of KJ-K2. To our knowledge, this is the first observation and description of the ST11 hypervirulent tigecycline- and carbapenem-resistant K. pneumoniae strain co-carrying blaKPC-2 and the tet(A) in a patient's blood in China. Further investigation is needed to understand the resistance and virulence mechanisms of this significant hypervirulent tigecycline- and carbapenem-resistant strain.

Contrast-enhanced Ultrasound Combined With Elastography for the Evaluation of Muscle-invasive Bladder Cancer in Rats.

OBJECTIVES: By comparing with the control group, we evaluated the usefulness of contrast-enhanced ultrasound (CEUS) combined with elastography for the assessment of muscle invasion by bladder cancer (MIBC) in a Sprague-Dawley (SD) rat model. METHODS: In the experimental group, 40 SD rats developed in situ bladder cancer (BLCA) in response to N-methyl-N-nitrosourea treatment, whereas 40 SD rats were included in the control group for comparison. We compared PI, Emean , microvessel density (MVD), and collagen fiber content (CFC) between the two groups. In the experimental group, Bland-Altman test was used to assess the relationships between various parameters. The largest Youden value was used as the cut-off point, and binomial logistic regression analysis was performed to analyze the PI and Emean . Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic power of parameters, individually and in combination. RESULTS: The PI, Emean , MVD, and CFC were significantly lower in the control group than in the experimental group (P < .05). The PI, Emean , MVD, and CFC were significantly higher for MIBC than for non-muscle-invasive bladder cancer (P < .05). There were significant correlations between PI and MVD, and between Emean and CFC. The diagnostic efficiency analysis showed PI had the highest sensitivity, CFC had the highest specificity, and PI + Emean had the highest diagnostic efficacy. CONCLUSION: CEUS and elastography can distinguish lesions from normal tissue. PI, MVD, Emean , and CFC were useful for the detection of BLCA myometrial invasion. The comprehensive utilization of PI and Emean improved diagnostic accuracy and have clinical application.

Flexible Triboelectric Nanogenerators Based on Electrospun Poly(vinylidene fluoride) with MoS2/Carbon Nanotube Composite Nanofibers.

With the miniaturization of wearable smart devices, the demand for portable and sustainable power sources is increasing. Herein, a flexible and lightweight triboelectric nanogenerator (PMC-TENG) was fabricated with MoS2/carbon nanotube (MC)-doped PVDF as the friction substrate based on electrospinning for harvesting random body motion energy under complex mechanical deformations. The charge density on the friction surface of PVDF nanofibers was found to increase significantly as the introduced electron acceptor of the MC composite, and nylon as a clothing material for another friction layer simplifies the structure of the device. Upon optimization of the electrospinning preparation process, the output voltage of the prepared PMC-TENG can reach >300 V and the instantaneous power can reach 0.484 mW (∼6 cm × 6 cm). At the same time, the PMC-TENG remains stable over 3000 cycles and has the ability to charge a capacitor. The flexible device demonstrates an excellent capability of converting mechanical energy to electrical energy. Therefore, this study has good prospects for application in the field of power supply for portable electronic devices and others.

A unique porin meditates iron-selective transport through cyanobacterial outer membranes.

Cyanobacteria are globally important primary producers and nitrogen fixers with high iron demands. Low ambient dissolved iron concentrations in many aquatic environments mean that these organisms must maintain sufficient and selective transport of iron into the cell. However, the nature of iron transport pathways through the cyanobacterial outer membrane remains obscure. Here we present multiple lines of experimental evidence that collectively support the existence of a novel class of substrate-selective iron porin, Slr1908, in the outer membrane of the cyanobacterium Synechocystis sp. PCC 6803. Elemental composition analysis and short-term iron uptake assays with mutants in Slr1908 reveal that this protein is primarily involved in inorganic iron uptake and contributes less to the accumulation of other metals. Homologues of Slr1908 are widely distributed in both freshwater and marine cyanobacteria, most notably in unicellular marine diazotrophs. Complementary experiments with a homologue of Slr1908 in Synechococcus sp. PCC 7002 restored the phenotype of Synechocystis knockdown mutants, showing that this siderophore producing species also possesses a porin with a similar function in Fe transport. The involvement of a substrate-selective porins in iron uptake may allow cyanobacteria to tightly control iron flux into the cell, particularly in environments where iron concentrations fluctuate.

Chronic Psychological Stress Attenuates the Efficacy of anti-PD-L1 Immunotherapy for Bladder Cancer in Immunocompetent Mice.

We aimed to explore whether chronic psychological stress affects the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy in bladder cancer. The chronic unpredictable mild stress (CUMS) process was applied during the administration of anti-PD-L1 for subcutaneous tumors in mice. Tumor regression was obviously shown in anti-PD-L1 therapy groups, while this effect was notably attenuated by CUMS. Additionally, increased infiltration of regulatory T-cells, decreased amount of CD8+ lymphocytes, and reduced levels of tumor-associated cytokines in tumor sites were observed in mice treated with anti-PD-L1 under CUMS. Therefore, chronic psychological stress could weaken the potency of anti-PD-L1 immunotherapy for bladder cancer.

Immunotherapy Strategy Targeting Programmed Cell Death Ligand 1 and CD73 with Macrophage-Derived Mimetic Nanovesicles to Treat Bladder Cancer.

Combination immunotherapy is a promising strategy to remove the inhibitory effect of the tumor microenvironment on immune effector cells, improving the efficacy of immune checkpoint inhibitor treatment in bladder cancer. However, it is challenging to deliver multiple drugs to the tumor tissue effectively and simultaneously to ensure optimal therapeutic effects. Macrophage-derived exosome-mimetic nanovesicles (EMVs) were designed and validated as a nanoplatform for coloading and delivery of the CD73 inhibitor (AB680) and the monoclonal antibody to programmed cell death ligand 1 (aPDL1). The tumor-targeting, biosafety, and therapeutic effects of these nanocomplexes (AB680@EMVs-aPDL1), as a combined immunotherapy strategy for bladder cancer, were assessed in vitro and in vivo. Our results indicate that the nanodrug system was highly stable, provided adequate biosafety, and enhanced tumor targeting in a mouse model of bladder cancer. Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted the activation and infiltration of cytotoxic T-lymphocytes, which helped to optimally suppress tumor growth and extend median survival in vivo. Therefore, using EMVs to deliver a combination of aPDL1 and the CD73 inhibitor may be a useful combined immunotherapy strategy for treating bladder cancer.

Potential Alterations of Functional Connectivity Analysis in the Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, but its pathogenesis remains unclear. As a kind of chronic pain which the patients suffered for more than 3 months, we investigated the influence on patients' brain functional connectivity in resting state. Methods: We recruited a cohort of 18 right-handed male patients with CP/CPPS and 21 healthy male right-handed age-matched controls. Their resting-state fMRI data and structural MRI data were preprocessed and processed by RESTPlus V1.22. To assess the integrity of the default mode network (DMN), we utilized the voxel-wised analysis that we set medial prefrontal cortex (mPFC) and posterior cingulate gyrus (PCC) as seed points to compare the global functional connectivity (FC) strength. Results: Compared with healthy control, the FC strength between left mPFC and posterior DMN decreased in the group of CP/CPPS (P < 0.05, GFR correction, voxel P < 0.01, cluster P < 0.05), and the FC strength between the left anterior cerebellar lobe and posterior DMN increased (P < 0.05, GFR correction, voxel P < 0.01, cluster P < 0.05). In the patient group, there was a positive correlation between the increased FC strength and the score of the Hospital Anxiety and Depression Scale (HADS) anxiety subscale (r = 0.5509, P = 0.0178) in the left anterior cerebellar lobe, a negative correlation between the decreased FC strength and the score of the National Institutes of Health Chronic Prostatitis Symptom Index (r = -0.6281, P = 0.0053) in the area of left mPFC, and a negative correlation between the decreased FC strength and the score of HADS anxiety subscale (r = -0.5252, P = 0.0252). Conclusion: Patients with CP/CPPS had alterations in brain function, which consisted of the default mode network's compromised integrity. These alterations might play a crucial role in the pathogenesis and development of CP/CPPS.

A Multi-Omics Study of Human Testis and Epididymis.

The human testis and epididymis play critical roles in male fertility, including the spermatogenesis process, sperm storage, and maturation. However, the unique functions of the two organs had not been systematically studied. Herein, we provide a systematic and comprehensive multi-omics study between testis and epididymis. RNA-Seq profiling detected and quantified 19,653 in the testis and 18,407 in the epididymis. Proteomic profiling resulted in the identification of a total of 11,024 and 10,386 proteins in the testis and epididymis, respectively, including 110 proteins that previously have been classified as MPs (missing proteins). Furthermore, Five MPs expressed in testis were validated by the MRM method. Subsequently, multi-omcis between testis and epididymis were performed, including biological functions and pathways of DEGs (Differentially Expressed Genes) in each group, revealing that those differences were related to spermatogenesis, male gamete generation, as well as reproduction. In conclusion, this study can help us find the expression regularity of missing protein and help related scientists understand the physiological functions of testis and epididymis more deeply.

Characterization and validation of long noncoding RNAs as new candidates in prostate cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been proved to be an important regulator in gene expression. In almost all kinds of cancers, lncRNAs participated in the process of pathogenesis, invasion, and metastasis. Meanwhile, compared with the large amounts of patients, there is rare knowledge about the role of lncRNAs in prostate cancer (PCa). MATERIAL/METHOD: In this study, lncRNA expression profiles of prostate cancer were detected by Agilent microarray chip, 5 pairs of case and control specimens were involved in. Differentially expressed lncRNAs were screened out by volcano plot for constructing lncRNA-miRNA-mRNA central network. Then, the top ten up-regulated and down-regulated lncRNAs were validated by qRT-PCR in another 5 tumor specimens and 7 para-cancerous/benign contrasts. Furthermore, we searched for the survival curve of the top 10 upregulated and downregulated lncRNAs. RESULTS: A total of 817 differentially expressed lncRNAs were filtered out by the criteria of fold change (FC) and t-test p < 0.05. Among them, 422 were upregulated, whereas 395 were downregulated in PCa tissues. Gene ontology and KEGG pathway analyses showed that many lncRNAs were implicated in carcinogenesis. lnc-MYL2-4:1 (FC = 0.00141, p = 0.01909) and NR_125857 (FC = 59.27658, p = 0.00128) had the highest magnitude of change. The subsequent qPCR confirmed the expression of NR_125857 was in accordance with the clinical samples. High expression of PCA3, PCAT14 and AP001610.9 led to high hazard ratio while low expression of RP11-279F6.2 led to high hazard ratio. CONCLUSIONS: Our study detected a relatively novel complicated map of lncRNAs in PCa, which may have the potential to investigate for diagnosis, treatment and follow-up in PCa. Our study revealed the expression of NR_125857 in human PCa tissues was most up-regulated. Further studies are needed to investigate to figure out the mechanisms in PCa.

Coatomer subunit beta 2 (COPB2), identified by label-free quantitative proteomics, regulates cell proliferation and apoptosis in human prostate carcinoma cells.

Label-free quantitative proteomics has broad applications in the identification of differentially expressed proteins. Here, we applied this method to identify differentially expressed proteins (such as coatomer subunit beta 2 [COPB2]) and evaluated the functions and molecular mechanisms of these proteins in prostate cancer (PCA) cell proliferation. Proteins extracted from surgically resected PCA tissues and adjacent tissues of 3 patients were analyzed by label-free quantitative proteomics. The target protein was confirmed by bioinformatics and GEO dataset analyses. To investigate the role of the target protein in PCA, we used lentivirus-mediated small-interfering RNA (siRNA) to knockdown protein expression in the prostate carcinoma cell line, CWR22RV1 cells and assessed gene and protein expression by reverse transcription quantitative polymerase chain reaction and western blotting. CCK8 and colony formation assays were conducted to evaluate cell proliferation. Cell cycle distributions and apoptosis were assayed by flow cytometry. We selected the differentiation-related protein COPB2 as our target protein based on the results of label-free quantitative proteomics. High expression of COPB2 was found in PCA tissue and was related to poor overall survival based on a public dataset. Cell proliferation was significantly inhibited in COPB2-knockdown CWR22RV1 cells, as demonstrated by CCK8 and colony formation assays. Additionally, the apoptosis rate and percentage of cells in the G1 phase were increased in COPB2-knockdown cells compared with those in control cells. CDK2, CDK4, and cyclin D1 were downregulated, whereas p21 Waf1/Cip1 and p27 Kip1 were upregulated, affecting the cell cycle signaling pathway. COPB2 significantly promoted CWR22RV1 cell proliferation through the cell cycle signaling pathway. Thus, silencing of COPB2 may have therapeutic applications in PCA.

Outer Membrane Iron Uptake Pathways in the Model Cyanobacterium Synechocystis sp. Strain PCC 6803.

Cyanobacteria are foundational drivers of global nutrient cycling, with high intracellular iron (Fe) requirements. Fe is found at extremely low concentrations in aquatic systems, however, and the ways in which cyanobacteria take up Fe are largely unknown, especially the initial step in Fe transport across the outer membrane. Here, we identified one TonB protein and four TonB-dependent transporters (TBDTs) of the energy-requiring Fe acquisition system and six porins of the passive diffusion Fe uptake system in the model cyanobacterium Synechocystis sp. strain PCC 6803. The results experimentally demonstrated that TBDTs not only participated in organic ferri-siderophore uptake but also in inorganic free Fe (Fe') acquisition. 55Fe uptake rate measurements showed that a TBDT quadruple mutant acquired Fe at a lower rate than the wild type and lost nearly all ability to take up ferri-siderophores, indicating that TBDTs are critical for siderophore uptake. However, the mutant retained the ability to take up Fe' at 42% of the wild-type Fe' uptake rate, suggesting additional pathways of Fe' acquisition besides TBDTs, likely by porins. Mutations in four of the six porin-encoding genes produced a low-Fe-sensitive phenotype, while a mutation in all six genes was lethal to cell survival. These diverse outer membrane Fe uptake pathways reflect cyanobacterial evolution and adaptation under a range of Fe regimes across aquatic systems.IMPORTANCE Cyanobacteria are globally important primary producers and contribute about 25% of global CO2 fixation. Low Fe bioavailability in surface waters is thought to limit the primary productivity in as much as 40% of the global ocean. The Fe acquisition strategies that cyanobacteria have evolved to overcome Fe deficiency remain poorly characterized. We experimentally characterized the key players and the cooperative work mode of two Fe uptake pathways, including an active uptake pathway and a passive diffusion pathway in the model cyanobacterium Synechocystis sp. PCC 6803. Our finding proved that cyanobacteria use ferri-siderophore transporters to take up Fe', and they shed light on the adaptive mechanisms of cyanobacteria to cope with widespread Fe deficiency across aquatic environments.

The role of drug-induced sleep endoscopy: predicting and guiding upper airway surgery for adult OSA patients.

PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder that can be corrected with upper airway surgery. Prior to surgery, drug-induced sleep endoscopy (DISE) is routinely used to evaluate obstruction sites and severity. Evidence suggests that the findings of DISE may relate to the final surgical outcome. Therefore, we evaluated the ability of drug-induced sleep endoscopy to predict the final effect of upper airway surgery and potentially to guide surgical treatment decision-making. METHODS: A retrospective analysis was conducted on 85 adult patients with OSA (50 men with mean apnea-hypopnea index [AHI] 30 ± 15 events/h) who underwent DISE followed by tonsillectomy, uvulopalatopharyngoplasty (UPPP), or a combination of the two. Surgery outcome was evaluated at follow-up by polysomnography. Success response to surgery was defined as a postoperative value of the AHI< 20 events/h and more than 50% postoperative reduction of AHI. RESULTS: Of the 85 patients evaluated, 48 (53%) were responders. DISE revealed significant differences between the two groups. Specifically, complete circumferential collapse at the velum and complete anterior-posterior collapse at the tongue base occurred at higher frequencies in nonresponders. In contrast, the presence of grade 3-4 tonsillar hypertrophy and anterior-posterior mild/partial collapse at the velum were positively associated with responders. CONCLUSIONS: Our results suggest that DISE may help predict the final outcome of tonsillectomy, UPPP, or a combination of the two in adult patients with OSA. The use of DISE shows potential to guide treatment decisions for individual patients with OSA.

Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

TFPI-2 expression is decreased in bladder cancer and is related to apoptosis.

PURPOSE: This study aimed to study the role of TFPI-2 in bladder cancer and its relation with apoptosis. METHODS: Immunohistochemical (IHC) staining of TFPI- 2 and TUNEL were applied. By semiquantitative analysis of the IHC data, we compared the TFPI-2 expression with clinicopathological parameters of 24 bladder cancer samples. TUNEL assay was used to study the apoptotic level of bladder cancer cells. Also, quantitative PCR and Western blot were used to confirm IHC results. RESULTS: The expression of TFPI-2 decreased with progression of bladder cancer grade (p<0.001) and tumor stage (p<0.001). Also, TFPI-2 expression was not significantly decreased in smaller and single tumors (p=0.536 and p=0.378, respectively). Increased TFPI-2 expression was significantly correlated with increased apoptosis (p<0.001). Lower TFPI-2 was also correlated with lower Ki67 index but not with TP53 positivity (p=0.003 and p=0.195, respectively). Expression of TFPI-2 detected by IHC was consistent with that detected by Western blotting and PCR. CONCLUSION: TFPI-2 expression was decreased in bladder cancer. TFPI-2 expression was decreased with progression in tumor grade and stage and was correlated to decreased apoptosis. Our findings indicated that TFPI-2 could be a marker of bladder cancer and enhancement of TFPI-2 could combat bladder cancer.

Periostin Mediates TGF-ß-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells.

BACKGROUND: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-ß. TGF-ß could upregulate periostin expression in some cells, and both TGF-ß and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-ß-induced EMT in prostate cancer cells. METHODS: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. RESULTS: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3ß, which could be inhibited using a PI3K inhibitor. Additionally, TGF-ß increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-ß-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. CONCLUSION: Our findings indicate that periostin is an important mediator of TGF-ß-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

Immobilization of ALA-Zn(II) Coordination Polymer Pro-photosensitizers on Magnetite Colloidal Supraparticles for Target Photodynamic Therapy of Bladder Cancer.

5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn(II) coordination polymers as shells (Fe3O4@ALA-Zn(II) ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn(II) ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe3O4@ALA-Zn(II) microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe3O4@ALA-Zn(II) shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent.

Fast imputation using medium or low-coverage sequence data.

BACKGROUND: Accurate genotype imputation can greatly reduce costs and increase benefits by combining whole-genome sequence data of varying read depth and array genotypes of varying densities. For large populations, an efficient strategy chooses the two haplotypes most likely to form each genotype and updates posterior allele probabilities from prior probabilities within those two haplotypes as each individual's sequence is processed. Directly using allele read counts can improve imputation accuracy and reduce computation compared with calling or computing genotype probabilities first and then imputing. RESULTS: A new algorithm was implemented in findhap (version 4) software and tested using simulated bovine and actual human sequence data with different combinations of reference population size, sequence read depth and error rate. Read depths of ≥ 8× may be desired for direct investigation of sequenced individuals, but for a given total cost, sequencing more individuals at read depths of 2× to 4× gave more accurate imputation from array genotypes. Imputation accuracy improved further if reference individuals had both low-coverage sequence and high-density (HD) microarray data, and remained high even with a read error rate of 16%. With read depths of ≤4×, findhap (version 4) had higher accuracy than Beagle (version 4); computing time was up to 400 times faster with findhap than with Beagle. For 10,000 sequenced individuals plus 250 with HD array genotypes to test imputation, findhap used 7 hours, 10 processors and 50 GB of memory for 1 million loci on one chromosome. Computing times increased in proportion to population size but less than proportional to number of variants. CONCLUSIONS: Simultaneous genotype calling from low-coverage sequence data and imputation from array genotypes of various densities is done very efficiently within findhap by updating allele probabilities within the two haplotypes for each individual. Accuracy of genotype calling and imputation were high with both simulated bovine and actual human genomes reduced to low-coverage sequence and HD microarray data. More efficient imputation allows geneticists to locate and test effects of more DNA variants from more individuals and to include those in future prediction and selection.

Human epidermal growth factor receptor 2: a significant indicator for predicting progression in non-muscle-invasive bladder cancer especially in high-risk groups.

PURPOSE: Current pathological and clinical parameters provide important prognostic information. However, they are still limitations for predicting the true malignant potential of a specific cancer. The aim of this study was to validate the predicting role of HER-2 expression and demonstrated that combination of the high-risk factors with HER-2 expression is more valuable for determining which non-muscle-invasive bladder cancer (NMIBC) is more aggressive. MATERIALS AND METHODS: In total, 238 patients treated by transurethral resection of the bladder tumor were histopathologically confirmed to be NMIBC. Two experienced uropathologists re-reviewed the slides. HER-2 expression was evaluated by immunohistochemistry and scored for intensity and area of staining. The association of HER-2 staining with tumor recurrence and progression was evaluated by univariate and multivariate analyses and Kaplan-Meier survival curves. RESULTS: In multivariable analyses, HER-2 expression was an independent risk factor for predicting tumor progression (HR 2.64, p = 0.024). Combining the EORTC risk scores with HER-2 expression status led to more accurate prediction of progression, especially in patients with intermediate- and high-risk EORTC scores (p < 0.0001, log-rank test). CONCLUSIONS: HER-2 positivity is prognostic for predicting progression to muscle invasion in NMIBC. Combination of the high-risk factors with HER-2 expression is more valuable for determining which NMIBC is more aggressive.