RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

RhIII-promoted directed C-H N-heteroarylation of 2-pyridones.

A catalytic protocol for the Cp*RhIII-promoted C6-selective N-heteroarylation of 2-pyridones with N-heterocyclic boronates has been successfully developed utilizing a removable pyridine auxiliary. This system features high efficiency with mild conditions and also tolerates ortho- and meta-substituted pyridines, pyrazoles, pyrimidine, non-substituted quinolines, thiophene and furan well. The easy synthetic approach could potentially be applied to construct heterocyclic drug molecules bearing 2-pyridone-heteroaryl motifs.

Applications of triplex DNA nanostructures in sensor development.

Triplex DNA nanostructures are one of the most emerging and fascinating self-assembled nanostructures due to their unique nanoparticle-like organization and inherit characteristics. They have attracted numerous interests recently because of their versatile and powerful utility in diverse areas of science and technology, such as clinical or disease diagnosis and stimuli-based drug delivery. This review addresses particularly the utilization of DNA triplexes in the development of biosensors for detecting nucleic acid; strategies in sensing pH, protein activity, ions, or molecules. Finally, an outlook for potential applications of triplex DNA nanoswitches is provided.

The differential distributions of ASPM isoforms and their roles in Wnt signaling, cell cycle progression, and pancreatic cancer prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and treatment-resistant malignancy. The lack of pathway-informed biomarkers hampers the development of rational diagnostics or therapies. Recently, the protein abnormal spindle-like microcephaly-associated (ASPM) was identified as a novel Wnt and stemness regulator in PDAC, while the pathogenic roles of its protein isoforms remain unclarified. We developed novel isoform-specific antibodies and genetic knockdown (KD) of putative ASPM isoforms, whereby we uncovered that the levels of ASPM isoform 1 (iI) and ASPM-iII are variably upregulated in PDAC cells. ASPM isoforms show remarkably different subcellular locations; specifically, ASPM-iI is exclusively localized to the cortical cytoplasm of PDAC cells, while ASPM-iII is predominantly expressed in cell nuclei. Mechanistically, ASPM-iI co-localizes with disheveled-2 and active ß-catenin as well as the stemness marker aldehyde dehydrogenase-1 (ALDH-1), and its expression is indispensable for the Wnt activity, stemness, and the tumorigenicity of PDAC cells. By contrast, ASPM-iII selectively regulates the expression level of cyclin E and cell cycle progression in PDAC cells. The expression of ASPM-iI and ASPM-iII displays considerable intratumoral heterogeneity in PDAC tissues and only that of ASPM-iI was prognostically significant; it outperformed ALDH-1 staining and clinico-pathological variables in a multivariant analysis. Collectively, the distinct expression patterns and biological functions of ASPM isoforms may illuminate novel molecular mechanisms and prognosticators in PDAC and may pave the way for the development of therapies targeting this novel oncoprotein. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Comparison of two treatments on a covariate variable.

In clinical trials, the efficacy of treatment might be dependent on the value of a covariate variable. Therefore, it might be possible to detect the region over the covariate variable where the two treatments under investigation do not have significantly different efficacy or the region of superiority of one treatment. The non-significant region can be verified to be a confidence interval for the abscissa of the intersection point of two regression lines, and each of the complementary regions of the confidence interval corresponds to a region of superiority. In this study, we develop a method of constructing the confidence interval based on the concept of a generalized pivotal quantity, so as to perform the task of detecting the possible three regions for a clinical trial. Two real-world examples are given to illustrate the application of our proposed method, and a simulation study is conducted to evaluate its performance.

Effect of oil gauze silver dressings on diabetic foot ulcers in the elderly.

OBJECTIVE: To compare the clinical efficacy and safety of oil gauze silver dressing and silver ions dressing on diabetic ulcers in elderly outpatients. METHODS: Twenty-two patients with Type-2 diabetic foot ulcers were included in the study conducted at Yantai Yuhuangding Hospital between April 2013 and April 2014. At the time of enrolment they were divided into the silver ions and oil gauze silver groups based on the order of admission. Dressings were changed twice weekly until the ulcer had healed. Clinical efficacy measures were healing outcomes and speed of healing. Adverse events were recorded. RESULTS: The silver ions and oil gauze silver groups were comparable at baseline (P>0.05). Before treatment, the fasting blood glucose (FBG) and two hour postprandial blood glucose (2h PBG) levels were 6.88±0.50 mmol /L and 15.55±2.47 mmol/L in the oil gauze silver group, and 6.93±0.41 mmol/L and 15.23±2.58 mmol/L in the silver ions group, respectively. After treatment, the FBG and 2h PBG levels were 6.82±0.32 mmol/L and 8.67±0.86 mmol/L in the oil gauze silver group, and 6.85±0.27 mmol/L and 8.83 ± 0.61 mmol/L in the silver ions group, respectively. The healing time of foot ulcers was 23.8±2.7 days in the silver ions group and 15.8±2.5 days in the oil gauze silver group (P<0.05). CONCLUSION: Oil gauze silver dressings for diabetic foot ulcers were associated with favorable clinical outcomes compared with silver ion dressings, especially with respect to ulcer healing speed.

A gene expression signature of epithelial tubulogenesis and a role for ASPM in pancreatic tumor progression.

BACKGROUND & AIMS: Many patients with pancreatic ductal adenocarcinoma (PDAC) develop recurrent or metastatic diseases after surgery, so it is important to identify those most likely to benefit from aggressive therapy. Disruption of tissue microarchitecture is an early step in pancreatic tumorigenesis and a parameter used in pathology grading of glandular tumors. We investigated whether changes in gene expression during pancreatic epithelial morphogenesis were associated with outcomes of patients with PDAC after surgery. METHODS: We generated architectures of human pancreatic duct epithelial cells in a 3-dimensional basement membrane matrix. We identified gene expression profiles of the cells during different stages of tubular morphogenesis (tubulogenesis) and of PANC-1 cells during spheroid formation. Differential expression of genes was confirmed by immunoblot analysis. We compared the gene expression profile associated with pancreatic epithelial tubulogenesis with that of PDAC samples from 27 patients, as well as with their outcomes after surgery. RESULTS: We identified a gene expression profile associated with tubulogenesis that resembled the profile of human pancreatic tissue with differentiated morphology and exocrine function. Patients with PDACs with this profile fared well after surgery. Based on this profile, we established a 6-28 gene tubulogenesis-specific signature that accurately determined the prognosis of independent cohorts of patients with PDAC (total n = 128; accuracy = 81.2%-95.0%). One gene, ASPM, was down-regulated during tubulogenesis but up-regulated in human PDAC cell lines and tumor samples; up-regulation correlated with patient outcomes (Cox regression P = .0028). Bioinformatic, genetic, biochemical, functional, and clinical correlative studies showed that ASPM promotes aggressiveness of PDAC by maintaining Wnt-ß-catenin signaling and stem cell features of PDAC cells. CONCLUSIONS: We identified a gene expression profile associated with pancreatic epithelial tubulogenesis and a tissue architecture-specific signature of PDAC cells that is associated with patient outcomes after surgery.

Molecular profiling of prostatic acinar morphogenesis identifies PDCD4 and KLF6 as tissue architecture-specific prognostic markers in prostate cancer.

Histopathological classification of human prostate cancer (PCA) relies on the morphological assessment of tissue specimens but has limited prognostic value. To address this deficiency, we performed comparative transcriptome analysis of human prostatic acini generated in a three-dimensional basement membrane that recapitulates the differentiated morphological characteristics and gene expression profile of a human prostate glandular epithelial tissue. We then applied an acinar morphogenesis-specific gene profile to two independent cohorts of patients with PCA (total n = 79) and found that those with tumors expressing this profile, which we designated acini-like tumors, had a significantly lower risk of postoperative relapse compared with those tumors with a lower correlation (hazard ratio, 0.078; log-rank test P = 0.009). Multivariate analyses showed superior prognostic prediction performance using this classification system compared with clinical criteria and Gleason scores. We prioritized the genes in this profile and identified programmed cell death protein 4 (PDCD4) and Kruppel-like factor 6 (KLF6) as critical regulators and surrogate markers of prostatic tissue architectures, which form a gene signature that robustly predicts clinical prognosis with a remarkable accuracy in several large series of PCA tumors (total n = 161; concordance index, 0.913 to 0.951). Thus, by exploiting the genomic program associated with prostate glandular differentiation, we identified acini-like PCA and related molecular markers that significantly enhance prognostic prediction of human PCA.

Lactococcus formosensis sp. nov., a lactic acid bacterium isolated from yan-tsai-shin (fermented broccoli stems).

A coccal-shaped organism, designated 516(T), was isolated from yan-tsai-shin (fermented broccoli stems), a traditional fermented food in Taiwan. 16S rRNA gene sequencing results showed that strain 516(T) had 98.9 % sequence similarity to that of the type strain Lactococcus garvieae NBRC 100934(T). Comparison of three housekeeping genes, rpoA, rpoB and pheS, revealed that strain 516(T) was well separated from Lactococcus garvieae NBRC 100934(T). DNA-DNA hybridization studies indicated that strain 516(T) had low DNA relatedness with Lactococcus garvieae NBRC 100934(T) (46.1 %). The DNA G+C content of strain 516(T) was 38.1 mol% and the major fatty acids were C16 : 0 (22.7 %), C19 : 0 cyclo ω8c (17.9 %) and summed feature 7 (29.0 %). Based on the evidence, strain 516(T) represents a novel species of the genus Lactococcus, for which the name Lactococcus formosensis sp. nov. is proposed. The type strain is 516(T) ( = NBRC 109475(T) = BCRC 80576(T)).

Undergraduate nursing education to address patients' concerns about sexual health: the perceived learning needs of senior traditional four-year and two-year recurrent education (rn-bsn) undergraduate nursing students in taiwan.

The aims of this study were to identify learning needs among traditional four-year and two-year recurrent education (RN-BSN) undergraduate nursing students in Taiwan with regard to patients' concerns about sexual health. A 24-item instrument (Learning Needs for Addressing Patients' Sexual Health Concerns) was used to collect data. Compared to RN-BSN undergraduate nursing students, traditional four-year undergraduate nursing students had more learning needs in the aspects of sexuality in health and illness (2.19 ± 0.66 vs. 1.80 ± 0.89, P = 0.005) and approaches to sexual health care (2.03 ± 0.72 vs. 1.76 ± 0.86, P = 0.033). After adjustment for other variables by the backward selection approach, those with experience in assessing patient's sexual functioning had fewer learning needs in sexuality in health and illness (ß = -0.375, P = 0.001), communication about patient's intimate relationships (ß = -0.242, P = 0.031), and approaches to sexual health care (ß = -0.288, P = 0.013); those who agreed that sexual health care was a nursing role also expressed greater needs to learn about these 3 aspects (all P < 0.01). Content related to sexuality in health and illness and approaches to sexual health care should be strengthened in the traditional undergraduate nursing curriculum in order to support sexual health related competence, build a positive attitude regarding sexual health care as a nursing role, and strengthen the experience of assessing patient's sexual functioning. A different, simplified program may be more suitable for those with clinical experience.

Enterocin T, a novel class IIa bacteriocin produced by Enterococcus sp. 812.

Enterococcus sp. 812, isolated from fresh broccoli, was previously found to produce a bacteriocin active against a number of Gram-positive bacteria, including Listeria monocytogenes. Bacteriocin activity decreased slightly after autoclaving (121 °C for 15 min), but was inactivated by protease K. Mass spectrometry analysis revealed the bacteriocin mass to be approximately 4,521.34 Da. N-terminal amino acid sequencing yielded a partial sequence, NH2-ATYYGNGVYXDKKKXWVEWGQA, by Edman degradation, which contained the consensus class IIa bacteriocin motif YGNGV in the N-terminal region. The obtained partial sequence showed high homology with some enterococcal bacteriocins; however, no identical peptide or protein was found. This peptide was therefore considered to be a novel bacteriocin produced by Enterococcus sp. 812 and was termed enterocin T.

Enterococcus saccharolyticus subsp. taiwanensis subsp. nov., isolated from broccoli.

A coccal strain isolated from fresh broccoli was initially identified as Enterococcus saccharolyticus; however, molecular identification and phenotypic traits did not support this identification. DNA-DNA hybridization with the type strain of E. saccharolyticus (76.4 % relatedness), DNA G+C content (35.7 mol%), phylogenetic analysis based on 16S rRNA, pheS and rpoA gene sequences, rep-PCR fingerprinting and profiles of cellular fatty acids, whole-cell proteins and enzyme activities, together with carbohydrate metabolism characteristics, indicated that this strain is distinct and represents a novel subspecies, for which the name Enterococcus saccharolyticus subsp. taiwanensis subsp. nov. is proposed. The type strain is 812(T) ( = NBRC 109476(T) = BCRC 80575(T)). Furthermore, we present an emended description of Enterococcus saccharolyticus and proposal of Enterococcus saccharolyticus subsp. saccharolyticus subsp. nov. (type strain ATCC 43076(T) = CCUG 27643(T) = CCUG 33311(T) = CIP 103246(T) = DSM 20726(T) = JCM 8734(T) = LMG 11427(T) = NBRC 100493(T) = NCIMB 702594(T)).

Mortality in Emergency Department Sepsis score as a prognostic indicator in patients with pyogenic liver abscess.

OBJECTIVES: The purpose of this study was to explore the predictor index of mortality in patients with pyogenic liver abscess (PLA). METHODS: We performed a retrospective review that enrolled 431 patients 18 years and older hospitalized due to PLA between January 2005 and December 2010. Clinical characteristics, laboratory results, treatments, and outcomes retrieved from medical records were analyzed. Multiple logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The mean age of the 431 patients identified with PLA was 56.9 ± 15.0 years. The mean Mortality in Emergency Department Sepsis (MEDS) score on admission was 4.8 ± 4.1 (range, 0-17). During hospitalization, 94 patients (22%) required intensive care. Of the 431 patients, 63 died, yielding a 15% case fatality rate. Multivariate analysis revealed that higher MEDS scores on admission (P < .0001) and the presence of underlying malignancy (P = .006), multiple abscesses (P = .001), anaerobic infections (P < .0001), hyperbilirubinemia (P < .0001), and higher serum creatinine levels (P < .0001) were significantly associated with PLA mortality. The estimated area under the receiver operating characteristic curve for MEDS in predicting PLA mortality was 0.829 (95% confidence interval, 0.791-0.864; P < .0001). The optimal cutoff MEDS value of 7 or higher had a sensitivity of 76% sensitivity and a specificity of 81%, with a 10.7-fold PLA mortality risk (P < .0001) and a 26.2-fold intensive care unit admission risk (P < .0001). CONCLUSIONS: The MEDS scores on admission represent a significant prognostic indicator for patients with PLA.

Rapid Emergency Medicine Score as a main predictor of mortality in Vibrio vulnificus-related patients.

OBJECTIVES: Vibrio vulnificus causes potentially life-threatening and rapidly progressing infections. Therefore, the severity-of-illness assessment appears to be important for V vulnificus-infected patients at the time of admission. The aim of our study was to evaluate the performance of the severity-of-illness scoring model on admission in V vulnificus-infected patients. METHODS: One hundred seventy-one consecutive patients (mean age: 63.1 ± 12.3 years) with V vulnificus infection who were admitted to a teaching hospital between January 1999 and June 2010 were included in the study. Demographic and clinical characteristics, illness severity on admission, treatment, and outcomes were collected for each patient and extracted for analysis. Logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The mean Rapid Emergency Medicine Score (REMS) on admission was 6.5 ± 3.0 points. During hospitalization, 68 patients (40%) required intensive care. The overall case-fatality rate was 25%. In multivariate analysis, the presence of underlying liver disease (P = .002), hemorrhagic bullous lesions/necrotizing fasciitis (P = .012), and higher REMS values on admission (P < .0001) were associated with increased mortality risk; a time span <24 hours between arrival and surgical treatment was associated with a decreased mortality risk (P = .007). Additionally, the area under the receiver operating characteristic (ROC) curve for the REMS in predicting mortality risk was 0.895 (P < .0001). An optimal cut-off REMS ≥8 had a sensitivity of 81% and a specificity of 85%, with a 26.6-fold mortality risk (P < .0001) and a 12.5-fold intensive care unit admission risk (P < .0001). CONCLUSION: The REMS could provide clinicians with an effective adjunct risk stratification tool for V vulnificus-infected patients.

Nursing students' attitudes towards provision of sexual health care in clinical practice.

AIMS AND OBJECTIVES: To investigate nursing students' attitudes towards providing sexual health care in clinical practice and to identify associated factors. BACKGROUND: Sexual health care is an important component of holistic health care. Nurses' personal sexual knowledge and attitudes are shown to influence provision of sexual health care. DESIGN: This is a descriptive, cross-sectional study. METHODS: We selected 146 senior nursing students by convenience sampling from nursing schools in two medical universities in central Taiwan. Data were collected using the Nursing Attitudes on Sexual Health Care scale developed based on the 'Permission/Limited Information/Specific Suggestions/Intensive Therapy' model. Higher scores indicated more positive attitudes. RESULTS: Participants' mean age was 22.15 years. Mean total Nursing Attitudes on Sexual Health Care scores ranged from 45-75 (61.40 ± 10.17). Nursing students' most positive attitudes towards Permission/Limited Information/Specific Suggestions/Intensive Therapy sexual healthcare interventions were at the Permission level, and least positive attitudes were at levels of Specific Suggestion and Intensive Therapy. The top three positive items were as follows: accept patients' expression of sexual concerns, initiate discussions and encourage patients to talk. Male nursing students had negative attitudes towards sexual healthcare interventions, which became more positive as age increased, especially at the Limited Information level. CONCLUSIONS: Nursing students had different attitudes towards different levels of sexual health care in the Permission/Limited Information/Specific Suggestions/Intensive Therapy model. Attitudes were associated with age and gender. The Nursing Attitudes on Sexual Health Care scale is useful and reliable for identifying nurses' attitudes towards providing sexual health care. RELEVANCE TO CLINICAL PRACTICE: The Permission/Limited Information/Specific Suggestions/Intensive Therapy-based Nursing Attitudes on Sexual Health Care scale helps to identify nurses' attitudes. A better understanding of nurses' attitudes towards provisional sexual health care will provide information needed to develop appropriate education programmes to improve delivery of sexual health care.

Intervention effect of encouraging mental and programmed nursing of patients in interventional operating room on their compliance and bad moods.

BACKGROUND: Patients' lack of correct understanding of cardiovascular disease and interventional therapy is often accompanied by varying degrees of fear, depression and anxiety. Negative emotion will affect the hemodynamic fluctuation of patients undergoing interventional surgery, which is not conducive to the smooth and safe operation of interventional surgery. Therefore, it is very important to implement effective nursing intervention in the operating room. AIM: To explore the intervention effect of motivational psychological nursing combined with programmed nursing on compliance and bad mood of patients in interventional operating room. METHODS: A total of 98 patients in the interventional operating room of our hospital from October 2019 to March 2021 were randomly divided into study group (n = 49) and control group (n = 49). The control group took routine nursing. However, the study group took motivational psychological nursing combined with procedural nursing on the basis of the control group. Statistics were made on rehabilitation compliance, Positive and Negative Affect Schedule of bad mood, Simplified Coping Styles Questionnaire score of coping style and satisfaction of intervention between the two groups before and after intervention. RESULTS: The rehabilitation compliance of the study group (95.92%) was higher than that of the control group (81.63%) (P < 0.05). After intervention, the scores of upset, fear, irritability, tension and fear in the study group were respectively, which were lower than those in the control group (P < 0.05). After intervention, the score of positive coping in the study group was higher than that in the control group. However, the score of negative coping in the study group was lower than that in the control group (P < 0.05). The intervention satisfaction of the study group (93.88%) was higher than that of the control group (79.59%) (P < 0.05). CONCLUSION: The intervention of motivational psychological nursing combined with procedural nursing can improve the rehabilitation compliance, and alleviate the bad mood. In addition, it can change their coping style to the disease, and the patients are more satisfied with the nursing work.

Revisiting with a relative-density calibration approach the determination of growth rates of microorganisms by use of optical density data from liquid cultures.

To solve the problems of measuring the growth rates of microorganisms from optical density (OD)-growth time plots, we used relative-density (RD) plots. The relationship of OD and RD was built from the diluted grown cultures. This method was satisfactorily applied to study the growth of Escherichia coli and the cyanobacterium Anabaena spiroides.

Relationship Between Metabolic Syndrome Severity and Kidney Function as Related to Gender: A Population-Based Longitudinal Study.

The purpose of this study was to explore the relationship between the metabolic syndrome severity Z-score and kidney function by gender. We also examined the estimated glomerular filtration rate in relation to other known risk factors. The study used was a population-based prospective longitudinal research design. A total of 4,838 participants (2,683 females and 2,155 males) included individuals aged >30 years who were undergoing a health examination from 2006 to 2014 in Pingzhen City, Taiwan. In the initial generalized estimated equation model analysis, which included the covariates of age of first visit, period between the first and current visit, and metabolic syndrome severity Z-score, the results indicated that the interaction between age and metabolic syndrome severity Z-score is significantly related to the estimated glomerular filtration rate for males (p = .040). For females, the interaction between age and metabolic syndrome severity Z-score was not significant, but a higher metabolic syndrome severity Z-score was significantly associated with lower estimated glomerular filtration rate (p = .001). After controlling for the confounders, unhealthy behaviors, and comorbidities, the metabolic syndrome severity Z-score was still a negative predictor of estimated glomerular filtration rate in both the male (p = .005) and female (p = .023) models.

Effects of Heart Rate Variability Biofeedback in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

BACKGROUND: Autonomic dysfunction, cognitive impairment, and psychological distress are associated with poorer prognosis in patients with acute ischemic stroke (AIS). Heart rate variability (HRV) biofeedback (BF) improves autonomic dysfunction, cognitive impairment, and psychological distress in other patient populations, but its effect in patients with AIS is still unclear. OBJECTIVE: This study investigated the effects of an HRVBF intervention on autonomic function, cognitive impairment, and psychological distress in patients with AIS. METHOD: In this randomized, controlled, single-blind trial, patients with AIS were randomly assigned to the experimental or control group. The experimental group received four HRVBF training sessions. The control group received usual care. Repeated measures of HRV, mini-mental status examination (MMSE), and Hospital Anxiety and Depression Scales (HADS) were collected prior to and at 1 and 3 months postintervention. RESULTS: A total of 35 patients completed the study (19 experimental, 16 control). HRV and HADS significantly improved in the experimental group (p < .001) but not in the control group. Likewise, only the experimental group showed significant improvements in HRV, MMSE, and HADS over time (p < .05). CONCLUSION: HRVBF is a promising intervention for improving autonomic function, cognitive impairment, and psychological distress in patients with AIS. More studies of HRVBF interventions are needed to further optimize the effects of HRVBF on autonomic, cognitive, and psychological function in patients with AIS.

ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-ß-catenin signaling.

Recurrent and hormone-refractory prostate cancer (PCA) exhibits aggressive behaviors while current therapeutic approaches show little effect of prolonging the survival of patients with PCA. Thus, a deeper understanding of the patho-molecular mechanisms underlying the disease progression in PCA is crucial to identify novel diagnostic and/or therapeutic targets to improve the outcome of patients. Recent evidence suggests that activation of Wnt signaling in cancer stem cells (CSCs) contributes to cancer progression in malignant tumors. Here, we report that a novel Wnt co-activator ASPM (abnormal spindle-like microcephaly associated) maintains the prostate CSC subpopulation by augmenting the Wnt-ß-catenin signaling in PCA. ASPM expression is incrementally upregulated in primary and metastatic PCA, implicating its potential role in PCA progression. Consistently, downregulation of ASPM expression pronouncedly attenuated the proliferation, colony formation, and the invasive behavior of PCA cells, and dramatically reduced the number of ALDH+ CSCs and inhibited cancer stemness and tumorigenicity. Mechanistically, ASPM interacts with disheveled-3 (Dvl-3), a cardinal upstream regulator of canonical Wnt signaling, and inhibits its proteasome-dependent degradation, thereby increasing its protein stability and enabling the Wnt-induced ß-catenin transcriptional activity in PCA cells. In keeping with the role of ASPM as a CSC-regulator, ASPM co-localizes with ALDH in PCA tissues and its expression exhibits high intra-tumoral heterogeneity. The proportion of high-ASPM-expressing cells in the tumor inversely correlates with the relapse-free survival of PCA patients. Collectively, our data points to ASPM as a novel oncoprotein and an essential regulator of Wnt signaling and cancer stemness in PCA, which has important clinical and therapeutic significance.