Search

Aim: To compare the effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) with dipeptidyl peptidase-4 inhibitors (DPP4is) on major liver outcomes (MLO) in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: We included adult patients with T2D and MASLD, using metformin without specific liver conditions or surgeries, from the Merative MarketScan database. Patients initiating SGLT2is or DPP4is from 1 January 2014 to 31 December 2022 were identified. The primary outcome was time to MLO diagnosis. Overlap weighting balanced covariates, integrated with a Cox proportional hazards model for survival analysis., Results: Among 44 651 patients, 22 100 initiated SGLT2is, and 22 551 began DPP4is. After weighting, the incidence rate of MLO in the SGLT2i group was 3.8 per 1000 person-years, and it was 3.9 per 1000 person-years in the DPP4i group, resulting in an adjusted hazard ratio (aHR) of 0.82 (95% CI, 0.60-1.10). SGLT2i initiation was not associated with cirrhosis (aHR: 0.77; 95% CI, 0.55-1.06) or hepatocellular carcinoma (aHR: 0.99; 95% CI, 0.47-1.83) separately. Subgroup and sensitivity analyses did not yield significant results., Conclusions: In patients with T2D and MASLD, SGLT2is did not show a lower risk of MLO compared with DPP4is. Clinicians should consider the overall patient conditions and the additional benefits of SGLT2is to support the decision to switch from DPP4is., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3 -/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Clinical observation revealed an increase in metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence among adults and adolescents and young adults (AYA). However, its prevalence trend in specific subgroups and its characteristics are unclear., Approach and Results: This cross-sectional study included adults and AYA aged 20-79 and 12-19 years, respectively, from the National Health and Nutrition Examination Survey from 1999 to 2018. MASLD was defined as US Fatty Liver Index ≥30 in adults and alanine amino transaminase elevation and obesity in AYA. Joinpoint and logistic regression were used to evaluate the MASLD prevalence trend and its associated characteristics. MASLD was diagnosed in 17 156 892 of 51 109 914 (33.6%) adults and 1 705 586 of 29 278 666 AYA (5.8%). During the study period, MASLD prevalence significantly increased from 30.8% to 37.7% ( P  < 0.01) in adults and in subgroups of female participants, individuals aged 20-45 and 61-79 years, and non-Hispanic white individuals. Conversely, MASLD prevalence did not significantly change in AYA (from 5.1% to 5.2%, P  = 0.139), except in the subgroup of Mexican Americans (from 8.2% to 10.8%, P  = 0.01). Among adults, high MASLD prevalence was associated with male sex, Mexican American ethnicity, age >50 years, being unmarried, poverty income ratio <130, poor or fair health condition, obesity or overweight, and chronic conditions. Among AYA, high MASLD prevalence was associated with male sex, poverty income ratio <130, and education., Conclusion: Accordingly, we concluded that health care providers should prevent and treat conditions associated with MASLD by raising awareness of the increasing trend of MASLD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The ability to resolve the dynamic evolution of electrocatalytically induced processes with electrochemical liquid-phase electron microscopy (EM) is limited by the microcell configuration. Herein, a free-standing tri-layer graphene is integrated as a membrane and electrode material into the electrochemical chip and its suitability as a substrate electrode at the high cathodic potentials required for CO 2 electroreduction (CO 2 ER) is evaluated. The three-layer stacked graphene is transferred onto an in-house fabricated single-working electrode chip for use with bulk-like reference and counter electrodes to facilitate evaluation of its effectiveness. Electrochemical measurements show that the graphene working electrode exhibits a wider inert cathodic potential range than the conventional glassy carbon electrode while achieving good charge transfer properties for nanocatalytic redox reactions. Operando scanning electron microscopy studies clearly demonstrate the improvement in spatial resolution but reveal a synergistic effect of the electron beam and the applied potential that limits the stability time window of the graphene-based electrochemical chip. By optimizing the operating conditions, in situ monitoring of Cu nanocube degradation is achieved at the CO 2 ER potential of -1.1 V versus RHE. Thus, this improved microcell configuration allows EM observation of catalytic processes at potentials relevant to real systems., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

ConspectusThe value of operando and in situ characterization methodologies for understanding electrochemical systems under operation can be inferred from the upsurge of studies that have reported mechanistic insights into electrocatalytic processes based on such measurements. Despite the widespread availability of performing dynamic experiments nowadays, these techniques are in their infancy because the complexity of the experimental design and the collection and analysis of data remain challenging, effectively necessitating future developments. It is also due to their extensive use that a dedicated modus operandi for acquiring dynamic electrocatalytic information is imperative. In this Account, we focus on the work of our laboratory on electrochemical liquid-phase transmission electron microscopy (ec-LPTEM) to understand the transformation/activation of state-of-the-art nanocatalysts for the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and CO 2 electroreduction (CO 2 ER). We begin by describing the development of electrochemical microcells for TEM studies, highlighting the importance of tailoring the system to each electrochemical process to obtain reliable results. Starting with the anodic OER for alkaline electrolyzers, we demonstrate the capability of real-time monitoring of the electrowetting behavior of Co-based oxide catalysts and detail the fascinating insights gained into solid-liquid interfaces for the reversible surface reconstruction of the catalystic surfaces and their degradation processes. Importantly, in the case of the OER, we report the exceptional capacity of ec-LPTEM to probe gaseous products and therefore resolve solid-liquid-gas phenomena. Moving toward the cathodic ORR for fuel cells, we summarize studies that pertain to the evaluation of the degradation mechanisms of Pt nanoparticles and discuss the issues with performing real-time measurements on realistic catalyst layers that are composed of the carbon support, ionomer network, and Pt nanocatalysts. For the most cathodic CO 2 ER, we first discuss the challenges of spatiotemporal data collection in microcells under these negative potentials. We then show that control over the electrochemical stimuli is critical for determining the mechanism of restructuring/dissolution of Cu nanospheres, either for focusing on the first stages of the reaction or for start/stop operation studies. Finally, we close this Account with the possible evolution in the way we visualize electrochemical processes with ec-LPTEM and emphasize the need for studies that bridge the scales with the ultimate goal of fully evaluating the impact of the insights obtained from the in situ-monitored processes on the operability of electrocatalytic devices.

Ni- and Co-based catalysts with added Fe demonstrate promising activity in the oxygen evolution reaction (OER) during alkaline water electrolysis, with the presence of Fe in a certain quantity being crucial for their enhanced performance. The mode of incorporation, local placement, and structure of Fe ions in the host catalyst, as well as their direct/indirect contribution to enhancing the OER activity, remain under active investigation. Herein, the mechanism of Fe incorporation into a Co-based host was investigated using an in situ synthesized Co-Fe catalyst in an alkaline electrolyte containing Co 2+ and Fe 3+ . Fe was found to be uniformly incorporated, which occurs solely after the anodic deposition of the Co host structure and results in exceptional OER activity with an overpotential of 319 mV at 10 mA cm -2 and a Tafel slope of 28.3 mV dec -1 . Studies on the lattice structure, chemical oxidation states, and mass changes indicated that Fe is incorporated into the Co host structure by replacing the Co 3+ sites with Fe 3+ from the electrolyte. Operando Raman measurements revealed that the presence of doped Fe in the Co host structure reduces the transition potential of the in situ Co-Fe catalyst to the OER-active phase CoO 2 . The findings of our facile synthesis of highly active and stable Co-Fe particle catalysts provide a comprehensive understanding of the role of Fe in Co-based electrocatalysts, covering aspects that include the incorporation mode, local structure, placement, and mechanistic role in enhancing the OER activity.

Background and Aims: The purpose of this study is to examine patterns of utilization for antidiabetic medications among a nationally representative sample of the US population following the introduction of SGLT2 inhibitors in 2013., Methods: The study utilized National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2020 to identify adult patients with diabetes using antidiabetic medication. The proportion of patients with diabetes using different antidiabetic medications, including SGLT2 inhibitors, was plotted over time. To assess the statistical significance of the utilization trend of SGLT2 inhibitors and other oral antidiabetics, logistic regression models were employed., Results: A weighted total of 26,421,357 individuals included in our study were diagnosed with diabetes. Among these, 18,751,659 diabetes patients were identified as medication users, with 1,058,686 (5.7 %) of them taking SGLT2 inhibitors. Over the 7-year study period, the percentage of patients taking SGLT2 inhibitors increased 21-fold, from 0.4 % in 2013-2014 to 9.4 % in 2017-2020. Despite this substantial increase, the utilization of other second-line antidiabetic agents, such as sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and TZDs, remained relatively stable during the same period., Conclusions: SGLT2 inhibitor utilization has significantly increased among US diabetes patients; however, their rise has not substantially impacted the use of other second-line antidiabetic agents. Further research is needed to understand the social determinants and potential barriers affecting the broader adoption of these beneficial medications., Competing Interests: Declaration of competing interest Tsung-Hua Shen: none. Joel Farley: none., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States., Methods: Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients' 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use., Results: A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively)., Conclusions: Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Polypharmacy has become a major health issue for pregnant woman due to the increased trend of medication use during pregnancy. However, data on medication use in pregnancy are limited since pregnant women are rarely included in clinical trials. Our study aimed to investigate the trends of and characteristics associated with polypharmacy among pregnant women in the US. This study was conducted using data from The National Health and Nutrition Examination Survey in the US. Nine The National Health and Nutrition Examination Survey cycles between 1999 and 2016 were used to identify pregnant women aged 15 to 44 years. Polypharmacy was defined as more than 1 medication prescription used during pregnancy. Descriptive statistics were used to report the prevalence and trends of polypharmacy. Multivariable logistic regression models were used to evaluate characteristics associated with polypharmacy among US pregnant women. Among 3,350,983 US pregnant women, about 7.4% of them (247,525) experienced polypharmacy. The prevalence of polypharmacy increased from 2.8% (1999-2000) to 10.0% (2015-2016) (P < .01) over-the time period examined in this study. Pregnant women were less likely to have experienced polypharmacy than were nonpregnant women (7.4% vs 23.5%, P < .01). Levothyroxine and albuterol were 2 prescriptions commonly taken by pregnant women. Pregnant women who were non-Hispanic white (P < .05) or had asthma (P < .05) or diabetes (P < .01) were more likely to report polypharmacy. Regarding personal characteristics, women with a poor or fair self-reported general health condition (odds ratio: 5.12, 95% confidence interval: 1.23-21.34) and those with chronic conditions (odds ratio: 6.91, 95% confidence interval: 3.08-15.50) were found to be associated with polypharmacy. An increased trend of polypharmacy was found in the US from 1999 to 2016. Non-Hispanic white pregnant women with a poor health status and chronic diseases were at an increased risk of polypharmacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours. To detect acute responses to clinically relevant stimuli, we created mice expressing Rosa26-floxed-stop uracil phosphoribosyltransferase (Uprt) and inoculated 4-thiouracil (4-TU) to tag nascent RNA at selected time points. Cre-driven 4-TU-tagged RNA was isolated from intact kidneys and demonstrated that volume depletion and ischemia induced different genetic programs in collecting ducts and intercalated cells. Even lineage-related cell types expressed different genes in response to the 2 stressors. TU tagging also demonstrated the transient nature of the responses. Because we placed Uprt in the ubiquitously active Rosa26 locus, nascent RNAs from many cell types can be tagged in vivo and their roles interrogated under various conditions. In short, 4-TU labeling identifies stimulus-specific, cell-specific, and time-dependent acute responses that are otherwise difficult to detect with other technologies and are entirely obscured when sCr is the sole metric of kidney damage.

Sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor in lipogenesis and lipid metabolism, is critical for disease progression and associated with poor outcomes in prostate cancer (PCa) patients. However, the mechanism of SREBP-1 regulation in PCa remains elusive. Here, we report that SREBP-1 is transcriptionally regulated by microRNA-21 (miR-21) in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of SREBP-1, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in Pten/Trp53 double-null mouse embryonic fibroblasts (MEFs) and Pten/Trp53 double-null mutant mice. Strikingly, miR-21 loss significantly reduced cell proliferation and suppressed the prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, miR-21 inactivation decreased the levels of SREBP-1, FASN, and ACC in human PCa cells through downregulation of insulin receptor substrate 1 (IRS1)-mediated transcription and induction of cellular senescence. Conversely, miR-21 overexpression increased cell proliferation and migration; as well as the levels of IRS1, SREBP-1, FASN, and ACC in human PCa cells. Our findings reveal that miR-21 promotes PCa progression by activating the IRS1/SREBP-1 axis, and targeting miR-21/SREBP-1 signaling pathway can be a novel strategy for controlling PCa malignancy., (Copyright © 2021. Published by Elsevier B.V.)

The surface wettability of catalysts is typically controlled via surface treatments that promote catalytic performance. Here we report on potential-regulated hydrophobicity/hydrophilicity at cobalt-based oxide interfaces with an alkaline solution. The switchable wetting of single particles, directly related to their activity and stability towards the oxygen evolution reaction, was revealed by electrochemical liquid-phase transmission electron microscopy. Analysis of the movement of the liquid in real time revealed distinctive wettability behaviour associated with specific potential ranges. At low potentials, an overall reduction of the hydrophobicity of the oxides was probed. Upon reversible reconstruction towards the surface oxyhydroxide phase, electrowetting was found to cause a change in the interfacial capacitance. At high potentials, the evolution of molecular oxygen, confirmed by operando electron energy-loss spectroscopy, was accompanied by a globally thinner liquid layer. This work directly links the physical wetting with the chemical oxygen evolution reaction of single particles, providing fundamental insights into solid-liquid interfacial interactions of oxygen-evolving oxides., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Intercalation experiments on epitaxial graphene are attracting a lot of attention at present as a tool to further boost the electronic properties of 2D graphene. In this work, we studied the intercalation of Pb using buffer layers on 6H-SiC(0001) by means of electron diffraction, scanning tunneling microscopy, photoelectron spectroscopy and in situ surface transport. Large-area intercalation of a few Pb monolayers succeeded via surface defects. The intercalated Pb forms a characteristic striped phase and leads to formation of almost charge neutral graphene in proximity to a Pb layer. The Pb intercalated layer consists of 2 ML and shows a strong structural corrugation. The epitaxial heterostructure provides an extremely high conductivity of σ=100 mS/□. However, at low temperatures (70 K), we found a metal-insulator transition that we assign to the formation of minigaps in epitaxial graphene, possibly induced by a static distortion of graphene following the corrugation of the interface layer.

Background and Aim: Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population., Methods: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m 2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD., Results: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79)., Conclusion: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The optical characteristics of materials, such as their magnetooptical effects, birefringence, optical activities, linear and circular dichroism, are probed via the polarisation states of light transmitted through or reflected from the specimens. As such, the measurements of the polarisation states play an important role in many research disciplines. Experimentally, Stokes parameters provide a full description of the polarisation states of light. We report the implementation of a dual- photoelastic modulator based polarimeter in a light microscope, enabling the determination of Stokes parameters at each pixel. As a case study, polarimetric images of liquid crystal droplets of different internal structures are obtained, showing their distinct polarisation characteristics. We demonstrate that the prototype Stokes polarimetric microscope allows the quantitative determination of the polarisation characteristics of light at the object plane and enables the access of the information of full polarisation states as compared to a conventional cross polariser microscope. This work shows that Stokes polarimetric microscopy may find potential applications in a wide range of research fields., (© 2021. The Author(s).)

A ZnO/ZnCl 2 composite with stable 3D structural morphologies and long lasting superhydrophilicity was synthesized on the top surface of a nano porous anodic alumina (nanoPAA) substrate. The wettability of a nanoPAA-ZnO/ZnCl 2 was systematically characterized and the experimental data indicated that the water contact angle (WCA) of 0° could be achieved as well as maintained over 7 days and still remained at 4.36° after 50 days, and its 3D structural morphology had no clearly observable change during this period. The mechanism for the superhydrophilicity of the composites was interpreted in terms of the inherent hydrophilicity of ZnO/ZnCl 2 nanofilm, the three-dimensional structures of wrinkled nanoflakes, the nanogaps between neighbor nanoflakes, the difference of structual morphologies (i.e., size, shape, and upright posture of nanoflakes), and the measured True Volume of voids in the nanocomposite. The structural morphologies were mainly determined by the parameters such as the original concentration of precursor ZnCl 2 and the pore diameter of nanoPAA substrate. The study proposes a promising superhydrophilic nanomaterial and a cost-effective synthesis method, which will play a practical role in the fields of biomedical molecular sensors and micro/nanofluidic chips.

Human nasopharyngeal carcinoma (NPC) is a highly invasive cancer associated with proinflammation. Caspase-12 (Casp12), an inflammatory caspase, is implicated in the regulation of NF-κB-mediated cellular invasion via the modulation of the IκBα protein in NPC cells. However, the effect mechanisms of Casp12 need to be elucidated. NPC cells were transfected with the full length of human Casp12 cDNA (pC12) and the effect of human Casp12 (hCasp12) on the NF-κB activity was investigated. We found ectopic expression of hCasp12 increased the NF-κB activity accompanied by an increased p-IκBα expression and a decreased IκBα expression. Treatment of BMS, a specific IKK inhibitor, and pC12-transfected cells markedly decreased the NF-κB activity and ameliorated the expression level of IκBα reduced by hCasp12. Co-immunoprecipitation assays validated the physical interaction of hCasp12 with IKKα/β, but not with NEMO. Furthermore, the NF-κB activity of ΔCasp12-Q (a mutated catalytic of hCasp12) transfected cells was concentration-dependently induced, but lower than that of hCasp12-transfected cells. Importantly, the hCasp12-mediated NF-kB activity was enhanced by TNFα stimulation. That indicated a role of the catalytic motif of hCasp12 in the regulation of the NF-κB activity. This study indicated hCasp12 activated the NF-κB pathway through the activation of IKK in human NPC cells.

Background: The 12-lead electrocardiogram (ECG) has been adopted as an important component of preparticipation cardiovascular screening. However, there are still controversies in the screening and few studies with a large sample size have reported the results of ECGs of marathon runners. Therefore, the purpose of this study was to assess the prevalence of normal, borderline, and abnormal ECG changes in marathon runners., Methods: The 12-lead ECG data of 13,079 amateur marathon runners between the ages of 18 and 35 years were included for analysis. The prevalence of ECG abnormalities among different gender groups was compared with chi-square tests., Results: In terms of training-related changes, sinus bradycardia, sinus arrhythmia, and left ventricular high voltage were found in approximately 15, 5, and 3.28% of the participants, respectively. The incidence of right axis deviation in the marathon runners was 1.78%, which was slightly higher than the incidence of left axis deviation (0.88%). No more than 0.1% of the amateur marathon runners exhibited ST-segment depression, T wave inversion (TWI), premature ventricular contraction, pathologic Q waves, and prolonged QT interval., Conclusions: Training-related ECG changes, including sinus bradycardia, sinus arrhythmia, and left ventricular high voltage, were common in amateur marathon runners. Most abnormal ECG changes, including ST-segment depression, TWI, premature ventricular contraction, pathologic Q waves, and prolonged QT interval, were infrequently found in amateur marathon runners. The data also suggested Chinese amateur marathon runners may have a relatively lower prevalence of ECG abnormalities than black and white runners.

Size, morphology, and surface sites of electrocatalysts have a major impact on their performance. Understanding how, when, and why these parameters change under operating conditions is of importance for designing stable, active, and selective catalysts. Herein, we study the reconstruction of a Cu-based nanocatalysts during the startup phase of the electrochemical CO 2 reduction reaction by combining results from electrochemical in situ transmission electron microscopy with operando X-ray absorption spectroscopy. We reveal that dissolution followed by redeposition, rather than coalescence, is the mechanism responsible for the size increase and morphology change of the electrocatalyst. Furthermore, we point out the key role played by the formation of copper oxides in the process. Understanding of the underlying processes opens a pathway to rational design of Cu electro (re)deposited catalysts and to stability improvement for catalysts fabricated by other methods., (© 2020 Wiley-VCH GmbH.)

The incidence and mortality rates of colorectal cancer (CRC) have been high in recent years. Prevention and early detection are crucial for decreasing the death rate. Therefore, this study aims to characterize the alteration patterns of mothers against decapentaplegic homolog 3 ( SMAD3 ) in patients with CRC and its applications in early detection by using a genome-wide methylation array to identify an aberrant hypomethylation site in the intron position of the SMAD3 gene. Quantitative methylation-specific polymerase chain reaction showed that hypomethylated SMAD3 occurred in 91.4% (501/548) of Taiwanese CRC tissues and 66.6% of benign tubular adenoma polyps. In addition, SMAD3 hypomethylation was observed in 94.7% of patients with CRC from The Cancer Genome Atlas dataset. A decrease in circulating cell-free methylation SMAD3 was detected in 70% of CRC patients but in only 20% of healthy individuals. SMAD3 mRNA expression was low in 42.9% of Taiwanese CRC tumor tissues but high in 29.4% of tumors compared with paired adjacent normal tissues. Hypomethylated SMAD3 was found in cancers of the digestive system, such as liver cancer, gastric cancer, and colorectal cancer, but not in breast cancer, endometrial cancer, and lung cancer. In conclusion, SMAD3 hypomethylation is a potential diagnostic marker for CRC in Western and Asian populations.

Among the perovskites used to catalyze the oxygen evolution reaction (OER), Ba 0.5 Sr 0.5 Co 0.8 Fe 0.2 O 3-δ (BSCF) exhibits excellent activity which is thought to be related to dynamic reconstruction at the flexible perovskite surface due to accommodation of large amount of oxygen vacancies. By studying the local structure and chemistry of BSCF surfaces, in detail, via a range of transmission electron microscopy (TEM) methods, we show that the surfaces of the as-synthesized BSCF particles are Co/Fe rich, and remarkably, adopt a spinel-like structure with a reduced valence of Co ions. Post-mortem and identical location TEM analyses reveal that the Co/Fe spinel-like surface retains a stable chemical environment of the Co/Fe ions, although its structure weakens after electrochemical processing. Further, it is verified that prior to the onset of OER, the Co/Fe spinel-like surface promotes the formation of the highly active Co(Fe)OOH phase, which enhances the OER electrocatalytic properties of the underlying conductive BSCF perovskite. This study provides a detailed understanding of the fundamental transformations that oxide catalysts undergo during electrochemical processes and can aid in the development of novel oxide catalysts with enhanced activity.

Abrupt drought-flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought-flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought-flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought-flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought-flood alteration stress, which are factors that leads to the rice grain yield reduction., (© 2018 Scandinavian Plant Physiology Society.)

The acute loss of kidney function has been diagnosed for many decades using the serum concentration of creatinine - a muscle metabolite that is an insensitive and non-specific marker of kidney function, but is now used for the very definition of acute kidney injury (AKI). Fortunately, myriad new tools have now been developed to better understand the relationship between acute tubular injury and elevation in serum creatinine (SCr). These tools include unbiased gene and protein expression analyses in kidney, urine and blood, the localization of specific gene transcripts in pathological biopsy samples by rapid in-situ RNA technology and single-cell RNA-sequencing analyses. However, this molecular approach to AKI has produced a series of unexpected problems, because the expression of specific kidney-derived molecules that are indicative of injury often do not correlate with SCr levels. This discrepancy between kidney injury markers and SCr level can be reconciled by the recognition that many separate subtypes of AKI exist, each with distinct patterning of molecular markers of tubular injury and SCr data. In this Review, we describe the weaknesses of isolated SCr-based diagnoses, the clinical and molecular subtyping of acute tubular injury, and the role of non-invasive biomarkers in clinical phenotyping. We propose a conceptual model that synthesizes molecular and physiological data along a time course spanning from acute cellular injury to organ failure.

Objective: The long non-coding RNA, FAM83H antisense RNA 1 (head to head) (FAM83H-AS1), has been reported to function as an oncogene in some types of cancer. However, the role of lncRNA FAM83H-AS1 in hepatocellular carcinoma (HCC) still remains unknown. The present work aims to explore the effect of lncRNA FAM83H-AS1 on cell proliferation and cell invasion in HCC., Patients and Methods: 66 pairs of HCC tissue samples and adjacent normal tissues were collected, and the expression level of lncRNA FAM83H-AS1 was detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis. Cell Counting Kit-8 (CCK-8) assay was performed to detect cell proliferation ability, and transwell assays were applied to observe the effect of lncRNA FAM83H-AS1 on cell migration and invasion. QRT-PCR and Western blot analysis was used to determine the mRNA and protein expression., Results: In the present study, our results confirmed that lncRNA FAM83H-AS1 expression was overexpressed in HCC tissues relative to the adjacent normal tissues. Furthermore, higher lncRNA FAM83H-AS1 expression significantly associated with tumor size and vascular invasion in patients with HCC. The Kaplan-Meier methods and log rank test demonstrated that increased lncRNA FAM83H-AS1 expression associated with shorter patient overall survival compared to lower lncRNA FAM83H-AS1 expression in patients with HCC. Moreover, function assays by CCK-8 cell proliferation and transwell cell migration and invasion assays showed that the knockdown of lncRNA FAM83H-AS1 significantly inhibited cell proliferation, migration, and invasion ability in HCC. Moreover, we found that the downregulating expression of lncRNA FAM83H-AS1 inhibited Wnt/β-catenin pathway by reducing β-catenin and WNT1 expression in HCC cells., Conclusions: Together, our results indicated that it plays an important role in HCC progression and may be a potential target for HCC treatment.

AlN thin films were epitaxially grown on a 4H-SiC substrate via atomic layer deposition (ALD) along with atomic layer annealing (ALA). By applying the layer-by-layer, in situ ALA treatment using helium/argon plasma in each ALD cycle, the as-deposited film gets crystallization energy from the plasma, which results in significant enhancement of the crystal quality to achieve a highly crystalline AlN epitaxial layer at a deposition temperature as low as 300 °C. In a nanoscale AlN epitaxial layer with a thickness of ∼30 nm, X-ray diffraction reveals a low full-width-at-half-maximum of the AlN (0002) peak of only 176.4 arcsec. Atomic force microscopy, high-resolution transmission electron microscopy, and Fourier diffractograms indicate a smooth surface and high-quality hetero-epitaxial growth of a nanoscale AlN layer on 4H-SiC. This research demonstrates the impact of the ALA treatment on the evolution of ALD techniques from conventional thin film deposition to low-temperature atomic layer epitaxy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

One of the key challenges in artificial photosynthesis is to design a photocatalyst that can bind and activate the CO 2 molecule with the smallest possible activation energy and produce selective hydrocarbon products. In this contribution, a combined experimental and computational study on Ni-nanocluster loaded black TiO 2 (Ni/TiO 2[Vo] ) with built-in dual active sites for selective photocatalytic CO 2 conversion is reported. The findings reveal that the synergistic effects of deliberately induced Ni nanoclusters and oxygen vacancies provide (1) energetically stable CO 2 binding sites with the lowest activation energy (0.08 eV), (2) highly reactive sites, (3) a fast electron transfer pathway, and (4) enhanced light harvesting by lowering the bandgap. The Ni/TiO 2[Vo] photocatalyst has demonstrated highly selective and enhanced photocatalytic activity of more than 18 times higher solar fuel production than the commercial TiO 2 (P-25). An insight into the mechanisms of interfacial charge transfer and product formation is explored., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Compositional abruptness of the interfaces is one of the important factors to determine the performance of Group IV semiconductor heterojunction (Si/Ge or Si/SiGe) nanowire devices. However, forming abrupt interfaces in the nanowires using the common vapor-liquid-solid (VLS) method is restricted because large solubility of Si and Ge in the Au eutectic liquid catalyst makes gradual composition change at the heterojunction after switching the gas phase components. According to the VLS growth mechanism, another possible approach to form an abrupt interface is making a change of the semiconductor concentration in the eutectic liquid before precipitation of the second phase. Here we show that the composition in AuSiGe eutectic liquid on SiGe nanowires of low Ge concentration (≤6%) can be altered by thermal oxidation at 700 °C. During the oxidation process, only Si is oxidized on the surface of the eutectic liquid, and the Ge/Si ratio in the eutectic liquid is increased. The subsequently precipitated SiGe step at the liquid/solid interface has a higher Ge concentration (∼20%), and a compositionally abrupt interface is produced in the nanowires. The growth mechanism of the heterojunction includes diffusion of Si and Ge atoms on nanowire surface into the AuSiGe eutectic liquid and step nucleation at the liquid/nanowire interface.

The design of a homogeneous sample plate to solve the sweet heating spot issues is the key step to expand the applicability of surface-assisted laser desorption/ionization mass spectrometry (SALDI MS). Herein, large-scale and highly oriented Langmuir-Blodgett (LB) films of uniform silver nanocrystals have been fabricated as a highly efficient and matrix-free sample plate for SALDI MS. Three individual silver nanocrystals (cubes, cuboctahedra and octahedra) assembled LB films have been applied as the sample plates for glucose detection by SALDI MS without an additional matrix. The results show that the signal intensity, background noise, signal-to-noise ratio and reproducibility have been significantly improved using LB films as the sample plate in comparison with commercial matrixes of CHCA and DHB. In particular, a relative signal of 5.7% was obtained for LB films of silver cuboctahedra. The significant improvement in the SALDI MS measurement could be attributed to the homogenous dissipation of laser irradiation energy to create a large area of the sweet heating spot on well-oriented silver cuboctahedra-based LB film. This ready-to-use sample plate has the potential for widespread commercial applications in SALDI MS.

Many family physicians still practice at an old age. Nevertheless, their practice patterns have scarcely been studied. To address this lack of research, the current study analyzed claims data for a total of 2,018,440 visits to 171 family physicians in 2011 sourced from Taiwan's National Health Insurance Research Database. Family physicians aged 65 years and over had fewer patients (mean: 2330, standard deviation (SD): 2019) and visits (mean: 9220, SD: 8600) than younger physicians had. Furthermore, the average age of the patients who visited physicians aged 65 years and over was 51.9 (SD: 21.5) years, significantly higher than that of patients who visited younger physicians. However, the proportions of visits for upper respiratory tract infections, hypertension, diabetes mellitus, and dyslipidemia did not differ significantly among different age groups of physicians. In the future, the manpower planning of physicians should take into consideration the age structure and work profile of physicians.

Metallic channel transistors have been proposed as the candidate for sub-10 nm technology node. However, the conductivity modulation in metallic channels can only be observed at low temperatures usually below 100 K. In this study, room-temperature field effect and modulation of the channel resistance was achieved in the metallic channel transistors, in which the oxygen-doped TiN ultrathin-body channels were prepared by the atomic layer delta doping and deposition (AL3D) with precise control of the channel thickness and electron concentration. The decrease of channel thickness leads to the reduction in electron concentration and the blue shift of absorption spectrum, which can be explained by the onset of quantum confinement effect. The increase of oxygen incorporation results in the increase of interband gap energy, also giving rise to the decrease in electron concentration and the blue shift of absorption spectrum. Because of the significant decrease in electron concentration, the screening effect was greatly suppressed in the metallic channel. Therefore, the channel modulation by the gate electric field was achieved at room temperature due to the quantum confinement and suppressed screening effect with the thickness down to 4.8 nm and the oxygen content up to 35% in the oxygen-doped TiN ultrathin-body channel.

One of the key motivations in producing 3D structures has always been the realization of metamaterials with effective constituent properties that can be tuned in all propagation directions at various frequencies. Here, we report the investigation of spatially oriented "Nanograter" structures with orientation-dependent responses over a wide spectrum by focused-ion-beam based patterning and folding of thin film nanostructures. Au nano units of different shapes, standing along specifically designated orientations, were fabricated. Experimental measurements and simulation results show that such structures offer an additional degree of freedom for adjusting optical properties with the angle of inclination, in additional to the size of the structures. The response frequency can be varied in a wide range (8 μm-14 μm) by the spatial orientation (0°-180°) of the structures, transforming the response from magnetic into electric coupling. This may open up prospects for the fabrication of 3D nanostructures as optical interconnects, focusing elements and logic elements, moving toward the realization of 3D optical circuits.

To determine whether adult kidney papillary label-retaining cells (pLRCs) are specialized precursors, we analyzed their transcription profile. Among genes overexpressed in pLRCs, we selected candidate genes to perform qPCR and immunodetection of their encoded proteins. We found that Zfyve27, which encodes protrudin, identified a subpopulation of pLRCs. With Zfyve27-CreERT2 transgenic and reporter mice we generated bitransgenic animals and performed cell-lineage analysis. Post tamoxifen, Zfyve27-CreERT2 marked cells preferentially located in the upper part of the papilla. These cells were low cycling and did not generate progeny even after long-term observation, thus they did not appear to contribute to kidney homeostasis. However, after kidney injury, but only if severe, they activated a program of proliferation, migration, and morphogenesis generating multiple and long tubular segments. Remarkably these regenerated tubules were located preferentially in the kidney medulla, indicating that repair of injury in the kidney is regionally specified. These results suggest that different parts of the kidney have different progenitor cell pools., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

A series of chiral tridentate Schiff-bases were prepared and used as ligands in the catalytic asymmetric Henry reaction. Under the optimal conditions, a variety of arylaldehydes were smoothly converted into corresponding adducts with high yields (up to 98%) and excellent enantioselectivities (up to 97% ee)., (© 2014 Wiley Periodicals, Inc.)

α-Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC-dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system.

Shape manipulation of nanowires is highly desirable in the construction of nanostructures, in producing free-standing interconnect bridges and as a building block of more complex functional structures. By introducing asymmetry in growth parameters, which may result in compositional or microstructural non-uniformity in the nanowires, thermal annealing can be used to induce shape modification of free-standing nanowires. We demonstrate that such manipulation is readily achieved using vertically grown Pt-Ga-C composite nanowires fabricated by focused-ion-beam induced chemical vapor deposition. Even and controllable bending of the nanowires has been observed after a rapid thermal annealing in a N2 atmosphere. The mechanisms of the shape modification have been examined. This approach has been used to form electrical contacts to freestanding nano-objects as well as nano-'cages' for the purpose of securing ZnO tubs. These results suggest that thermally induced bending of nanowires may have potential applications in constructing three-dimensional nanodevices or complex structures for the immobilization of particles and large molecules.

We have investigated the magneto-optical properties of highly ordered Co-Pt alloy nanowire arrays embedded in anodic aluminum oxide templates. The magnetic field-dependent Stokes parameters, Faraday rotation angle and ellipticity were investigated by an in-house magneto-optical measurement system. The extracted hysteresis loops are broadly consistent with magnetic hysteresis loops obtained from the vibrating sample magnetometer. The maximum Faraday rotation angle and ellipticity of these samples were examined as a function of nanowire composition. With an increase of platinum content from 9 at.% to 86 at.% in the as-deposited nanowire arrays, the maximum Faraday rotation angle per length decreases linearly from 1.39 x 10(3) degrees/cm to 1.58 x 10(2) degrees/cm. The maximum ellipticity shows a similar behavior with the composition. These linear relationships suggest a dilution model for the magnetic moment in the alloy nanowires. Our results indicate that magneto-optical measurements comprise an effective and sensitive method for monitoring the behavior of AAO-based magnetic nanowire arrays.

Stokes parameters fully characterize the polarization state of light in an experimentally accessible manner. Photoelastic modulator (PEM) based Stokes polarimetry offers a very high sensitivity which is particularly suitable for the investigation of the magneto-optical properties of nanostructured magnetic materials. In this paper, we shall describe a robust methodology recently developed by us that utilizes a dual PEM setup. As an example of its application, we report on the magneto-optical characteristics of focused Ga ion beam patterned Fe films. We have investigated Ga ion irradiation of single-layer polycrystalline Fe films deposited on Si3N4 substrates, which allows us to study the effects of ion implantation with minimum added complications. Complemented by structural and other characterization techniques, the absolute measurement of magneto-optical effects through the determination of Stokes parameters has enabled us to effectively separate the various contributions from film thinning due to sputtering, structural modifications and compositional changes caused by Ga incorporation. A comparison is also made between the magneto-optical behavior of patterned thin films and that of anodic aluminum oxide embedded magnetic nanowire arrays.

Cre-loxp mediated conditional knockout strategy has played critical roles for revealing functions of many genes essential for development, as well as the causal relationships between gene mutations and diseases in the postnatal adult mice. One key factor of this strategy is the availability of mice with tissue- or cell type-specific Cre expression. However, the success of the traditional molecular cloning approach to generate mice with tissue specific Cre expression often depends on luck. Here we provide a better alternative by using bacterial artificial chromosome (BAC)-based recombineering to insert iCreERT2 cDNA at the ATG start of the Upk2 gene. The BAC-based transgenic mice express the inducible Cre specifically in the urothelium as demonstrated by mRNA expression and staining for LacZ expression after crossing with a Rosa26 reporter mouse. Taking into consideration the size of the gene of interest and neighboring genes included in a BAC, this method should be widely applicable for generation of mice with tissue specific gene expression or deletions in a more specific manner than previously reported.

The magneto-optical properties of Ni nanowire arrays embedded in anodic aluminum oxide templates are studied, for a selection of photon energies, as a function of their diameter and length for the first time. This was achieved by the determination of Stokes parameters of the transmitted light. The magneto-optical response is found to differ considerably from that of the bulk material. At all photon energies studied, a linear association of the Faraday rotation angle with nanowire length has been observed; moreover, a proportional relationship between rotation angle per unit length and nanowire diameter has also been also observed, consistent with our earlier work on Fe and Co nanowires. The relationship between the Faraday rotation angle per unit length with different nanowire diameters and photon energy has been found to exhibit clear spectroscopic structure.

The TP63 gene, a member of the TP53 tumor suppressor gene family, can be expressed as at least six isoforms due to alternative promoter use and alternative splicing. The lack of p63 isoform-specific antibodies has limited the analysis of the biological significance of p63. We report a novel set of well-defined antibodies to examine p63 isoforms in mouse and human urothelium during embryogenesis and tumor progression, respectively. We provide evidence that basal and intermediate urothelial cells express p63 isoforms, with the TAp63 variant the first to be detected during development, whereas umbrella cells are characterized by a p63-negative phenotype. Notably, we report that p63-null mice develop a bladder with an abnormal urothelium, constituted by a single layer of cells that express uroplakin II and low molecular weight cytokeratins, consistent with an umbrella cell phenotype. Finally, analysis of 202 human bladder carcinomas revealed a new categorization of invasive tumors into basal-like (positive for ΔNp63 and high molecular weight cytokeratins and negative for low molecular weight cytokeratins) versus luminal-like (negative for ΔNp63 and high molecular weight cytokeratins and positive for low molecular weight cytokeratins) phenotypes, with ΔNp63 expression associated with an aggressive clinical course and poor prognosis. This study highlights the relevance of p63 isoforms in both urothelial development and bladder carcinoma progression, with ΔNp63 acting as an oncogene in certain invasive bladder tumors., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Genome wide association studies (GWAS) are an important approach to understanding the genetic mechanisms behind human diseases. Single nucleotide polymorphisms (SNPs) are the predominant markers used in genome wide association studies, and the ability to predict which SNPs are likely to be functional is important for both a priori and a posteriori analyses of GWA studies. This article describes the design, implementation and evaluation of a family of systems for the purpose of identifying SNPs that may cause a change in phenotypic outcomes. The methods described in this article characterize the feasibility of combinations of logical and probabilistic inference with federated data integration for both point and regional SNP annotation and analysis. Evaluations of the methods demonstrate the overall strong predictive value of logical, and logical with probabilistic, inference applied to the domain of SNP annotation.

Many common and chronic diseases are influenced at some level by genetic variation. Research done in population genetics, specifically in the area of single nucleotide polymorphisms (SNPs) is critical to understanding human genetic variation. A key element in assessing role of a given SNP is determining if the variation is likely to result in change in function. The SNP Integration Tool (SNPit) is a comprehensive tool that integrates diverse, existing predictors of SNP functionality, providing the user with information for improved association study analysis. To evaluate the SNPit system, we developed an alternative gold standard to measure accuracy using sensitivity and specificity. The results of our evaluation demonstrated that our alternative gold standard produced encouraging results.

Genome wide association studies can potentially identify the genetic causes behind the majority of human diseases. With the advent of more advanced genotyping techniques, there is now an explosion of data gathered on single nucleotide polymorphisms (SNPs). The need exists for an integrated system that can provide up-to-date functional annotation information on SNPs. We have developed the SNP Integration Tool (SNPit) system to address this need. Built upon a federated data integration system, SNPit provides current information on a comprehensive list of SNP data sources. Additional logical inference analysis was included through an inference engine plug in. The SNPit web servlet is available online for use. SNPit allows users to go to one source for up-to-date information on the functional annotation of SNPs. A tool that can help to integrate and analyze the potential functional significance of SNPs is important for understanding the results from genome wide association studies.

Although bladder cancer represents a serious health problem worldwide, relevant mouse models for investigating disease progression or therapeutic targets have been lacking. We show that combined deletion of p53 and Pten in bladder epithelium leads to invasive cancer in a novel mouse model. Inactivation of p53 and PTEN promotes tumorigenesis in human bladder cells and is correlated with poor survival in human tumors. Furthermore, the synergistic effects of p53 and Pten deletion are mediated by deregulation of mammalian target of rapamycin (mTOR) signaling, consistent with the ability of rapamycin to block bladder tumorigenesis in preclinical studies. Our integrated analyses of mouse and human bladder cancer provide a rationale for investigating mTOR inhibition for treatment of patients with invasive disease.

High areal density CoPt alloy nanowire arrays have been fabricated in anodic aluminum oxide templates by AC electrodeposition. We demonstrate that the AC electrodeposition time in this technique is a very important parameter for the microstructure and magnetic properties of the nanowire arrays. It is found that the mean length of the nanowire arrays, for given electrodeposition conditions, may reach a maximum value at a certain electrodeposition time. As nanowire arrays reach their maximum length, magnetic switching jump in hysteresis loops is observed and it becomes more remarkable with further increasing the deposition time. The corresponding origins of these properties are discussed.

In order to investigate the reliability of detecting HPV DNA in cervical smears, we compared the performance of nested MY/GP PCR and FDA approved-Hybrid Capture II (HCII) using clinical cervical scrapings from 40 patients. It was found that PCR was more sensitive (81.8%) in comparison to HCII (36.4%) in detecting HPV although specificity of HCII was much higher (96.6%) than PCR (58.6%). The Negative Predictive Value (NPV) of both the techniques were quite similar but Positive Predictive Value (PPV) of HCII was much higher (80.0%) compared to PCR (42.9%). While the HCII method showed good specificity for HPV detection, its lack of sensitivity as compared to PCR may be a drawback for diagnostic use.

Human papillomavirus (HPV) is well known as an etiological factor for the development of anogenital carcinomas. The aim of our study was to compare the performance of USFDA approved Hybrid II (HCII) Assay and recently introduced DR. HPV Chip Kit for the detection of HPV DNA in clinical cervical scrapings from 40 patients. HPV DNA testing was performed using the automated HCII Assay system and DR. HPV Chip Kit. Taking cytological results as gold standard, it was found that HCII was more sensitive (36.4%) than DR. HPV Chip Kit (18.2%) although specificity was 100% with the latter method. In addition, both these molecular methods had comparable negative and positive predictive values. It was concluded that both HCII and DR. HPV Chip Kit have comparable specificity. However, sensitivity for detection of HPV in clinical samples with HCII is almost double as compared to DR. HPV Chip Kit.

PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis, and tumor suppression. PML has been found to be essential for the formation of the NBs, as these structures do not form in Pml null cells, although PML add back fully rescues their formation. However, the basis for such a structural role of PML is unknown. We demonstrate that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation. We demonstrate that the PML RING domain is critical for PML SUMOylation and PML-NB formation. We propose a model for PML-NB formation whereby PML SUMOylation and noncovalent binding of PML to SUMOylated PML through the SUMO binding motif constitutes the nucleation event for subsequent recruitment of SUMOylated proteins and/or proteins containing SUMO binding motifs to the PML NBs.