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Qinqin Huang,1– 3 Yun Wang,1– 3 Xiaobao Wang,1 Zhenhua Xiang,1 Haixia Wang,1,2 Aiju Wang,1 Weiguo Liu,1 Yuming Gu1– 3 1Department of Traditional Chinese Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, 261042, People’s Republic of China; 2College of Traditional Chinese Medicine, Weifang Medical University, Weifang, 261000, People’s Republic of China; 3Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, 261042, People’s Republic of ChinaCorrespondence: Yuming Gu, Department of Traditional Chinese Medicine, Affiliated Hospital of Weifang Medical University, Weicheng District, Weifang City, Shandong Province, People’s Republic of China, Email guym@wfmc.edu.cnPurpose: The aim of this study is to evaluate the efficacy and safety of Snap Needles (SN) in the management of Postoperative Hemorrhoidal Pain (POHP).Patients and Methods: A systematic search was conducted in various databases, including EMBASE, Web of Science, PubMed, WanFang database, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and China Science and Technology Journal Database (VIP), spanning from their inception to August 2023, to identify relevant randomized controlled trials (RCTs) on SN for POHP. The primary outcome measure was the Visual Analog Scale (VAS), while secondary outcomes encompassed the Total Effective Rate (TER), Wound Healing Time (WHT), Pain Relief Time (PRT), Pain Disappearance Time (PDT), and Adverse Events (AEs). The Cochrane Risk of Bias Tool was employed to assess the quality of individual studies. A meta-analysis was conducted using RevMan 5.4.1 software.Results: The meta-analysis included 11 RCTs involving 1188 POHP patients, with an overall assessment of study quality ranging from very low to moderate. The findings revealed that the SN group exhibited significant improvements in

As a non-invasive optical imaging technique, optical coherence tomography (OCT) has proven promising for automatic fingerprint recognition system (AFRS) applications. Diverse approaches have been proposed for OCT-based fingerprint presentation attack detection (PAD). However, considering the complexity and variety of PA samples, it is extremely challenging to increase the generalization ability with the limited PA dataset. To solve the challenge, this paper presents a novel supervised learning-based PAD method, denoted as ISAPAD, which applies prior knowledge to guide network training and enhance the generalization ability. The proposed dual-branch architecture can not only learns global features from the OCT image, but also concentrate on layered structure feature which comes from the internal structure attention module (ISAM). The simple yet effective ISAM enables the proposed network to obtain layered segmentation features belonging only to Bonafide from noisy OCT volume data directly. Combined with effective training strategies and PAD score generation rules, ISAPAD obtains optimal PAD performance in limited training data. Domain generalization experiments and visualization analysis validate the effectiveness of the proposed method for OCT PAD., Comment: 12 pages, 14 figures

Purpose Hepatic echinococcosis is a parasitic disease. Ultrasound imaging is a crucially important tool for the diagnosis of this disease. Based on ultrasonic manifestations, hepatic echinococcosis can be classified into many subtypes. However, subtyping is nontrivial due to the challenges of complex sonographic textures and large intraclass and small interclass differences. The purpose of this study is to develop a computer-aided diagnosis system for hepatic echinococcosis based on ultrasound images. Methods We collected a multicenter ultrasound dataset containing 9112 images from 5028 patients who were diagnosed with hepatic echinococcosis (the largest cohort to date) and developed a two-stage multiresolution neural network for the automatic diagnosis of hepatic echinococcosis into nine subtypes, as suggested by the WHO. Our method was based on YOLO3 with two additional strategies to improve its performance: coarse grouping and multiresolution sampling. Considering that some subtypes are inherently very similar and difficult to differentiate; in the first stage, we detected and classified lesions into four coarse groups instead of making a direct classification into nine classes. In the second stage, we performed fine-grained classification within each coarse group. Multiple views with different resolutions were sampled from the detected lesions and were input into Darknet53. The softmax outputs for the multiresolution views were averaged to generate the final output. Results Both the proposed coarse grouping and multiresolution sampling strategies proved to be effective and improved the classification performance by a large margin compared with the setting without using the two strategies. Using fivefold cross-validation, our method achieved 87.1%, 86.2%, and 86.5% in the average recall, precision and F1-score, respectively, and outperformed other state-of-the-art methods remarkably. Conclusions The experimental results demonstrate the great promise of our method

Machining feature recognition is considered the key connecting technique to the integration of Computer-Aided Design (CAD) and Computer-Aided Process Planning (CAPP), and decision-making of the part processing scheme and the optimization of process route can effectively improve the processing efficiency and reduce the cost of product machining cost. At present, for the recognition of machining features in CAD models, there is a lack of a systematic method to consider process information (such as tolerance and roughness) and an effective process route optimization method to plan part processing procedures. Here we represent a novel model processing feature recognition method, and, on the basis of feature processing plan decision, realize the optimization of the process route. On the basis of a building model Attributed Adjacency Graph (AAG) based on model geometry, topology, and process information, we propose an AAG decomposition and reconstruction method based on Decomposed Base Surface (DBS) and Joint Base Surface (JBS) as well as the recognition of model machining features through Attributed Adjacency Matrix-based (AAM) feature matching. The feature machining scheme decision method based on fuzzy comprehensive evaluation is adopted, and the decision is realized by calculating the comprehensive evaluation index. Finally, the Machining Element Directed Graph (MEDGraph) is established based on the constraint relationship between Machining Elements (MEs). The improved topological sorting algorithm lists the topological sequences of all MEs. The evaluation function is constructed with the processing cost or efficiency as the optimization objective to obtain the optimal process route. Our research provides a new method for model machining feature recognition and process route optimization. Applications of the proposed approach are provided to validate the method by case study.

In cloud manufacturing systems, the multi-granularity of service resource and design task models leads to the complexity of cloud service matching. In order to satisfy the preference of resource requesters for large-granularity service resources, we propose a multistage cloud-service matching strategy to solve the problem of matching tasks and resources with different granularity sizes. First, a multistage cloud-service matching framework is proposed, and the basic strategy of matching tasks with cloud services is planned. Then, the context-aware task-ontology modeling method is studied, and a context-related task-ontology model is established. Thirdly, a process-decomposition method of design tasks is studied, and the product development process with small granularity tasks is established. Fourthly, a matching strategy of ontology tasks and cloud services is studied, and the preliminary matching is accomplished. Finally, intelligent optimization is carried out, and the optimal cloud service composition is found with the optimal design period as the objective function. With the help of the preceding method, the service matching of maximizing the task granularity is realized on the premise of ensuring the matching success rate, which meets the preference of resource requesters for large-granularity service resources.

In order to prevent a roof fall accident of a coal mine roadway mining face, temporary support must be provided before the permanent support of the roadway. At present, the commonly used forepoling bar support has poor reliability and low efficiency, and other machine-mounted or self-moving temporary supports are also difficult to use widely due to the complex geological conditions and limited working space at the heading face. On the basis of the mechanical characteristics analysis and numerical simulation of the wall rock support system, we propose a temporary support scheme that can adapt to the uneven roof of the roadway and the complex geological conditions on site, and that can ensure the cooperative operation of multiple equipment on site. A self-moving temporary support (SmTS) is designed, and its mechanical characteristics are analyzed to meet the mechanical requirements of the wall rock support system on the mining face. The multiobjective optimization of the main beam structure based on response surface methodology (RSM) is carried out to eliminate the design redundancy on the premise of meeting the support requirements of the main beam. Our research provides a novel method and corresponding equipment for the temporary support of a mining face. Applications of the proposed approach in the 7900 mining area of a mine proves the effectiveness of the method and equipment.

Performance Monitor Unit (PMU) is a significant hardware module on the current processors, which counts the events launched by processor into a set of PMU counters. Ideally, the events triggered by instructions that are executed but the results are not successfully committed (transient execution) should not be recorded. However, in this study, we discover that some PMU events triggered by the transient execution instructions will actually be recorded by PMU. Based on this, we propose the PMUSpill attack, which enables attackers to maliciously leak the secret data that are loaded during transient executions. The biggest challenge is how to encode the secret data into PMU events. We construct an instruction gadget to solve this challenge, whose execution path that can be identified by PMU counters represents what values the secret data are. We successfully implement the PMUSpill attack to leak the secret data stored in Intel Software Guard Extensions (SGX) (a Trusted Execution Environment (TEE) in the Intel's processors) through real experiments. Besides, we locate the vulnerable PMU counters and their trigger instructions by iterating all the valid PMU counters and instructions. The experiment results demonstrate that there are up to 20 PMU counters available to implement the PMUSpill attack. We also provide some possible hardware and software-based countermeasures for addressing the PMUSpill attack, which can be utilized to enhance the security of processors in future.

Purpose Hepatic echinococcosis is a parasitic disease. Ultrasound imaging is a crucially important tool for the diagnosis of this disease. Based on ultrasonic manifestations, hepatic echinococcosis can be classified into many subtypes. However, subtyping is nontrivial due to the challenges of complex sonographic textures and large intraclass and small interclass differences. The purpose of this study is to develop a computer-aided diagnosis system for hepatic echinococcosis based on ultrasound images. Methods We collected a multicenter ultrasound dataset containing 9112 images from 5028 patients who were diagnosed with hepatic echinococcosis (the largest cohort to date) and developed a two-stage multiresolution neural network for the automatic diagnosis of hepatic echinococcosis into nine subtypes, as suggested by the WHO. Our method was based on YOLO3 with two additional strategies to improve its performance: coarse grouping and multiresolution sampling. Considering that some subtypes are inherently very similar and difficult to differentiate; in the first stage, we detected and classified lesions into four coarse groups instead of making a direct classification into nine classes. In the second stage, we performed fine-grained classification within each coarse group. Multiple views with different resolutions were sampled from the detected lesions and were input into Darknet53. The softmax outputs for the multiresolution views were averaged to generate the final output. Results Both the proposed coarse grouping and multiresolution sampling strategies proved to be effective and improved the classification performance by a large margin compared with the setting without using the two strategies. Using fivefold cross-validation, our method achieved 87.1%, 86.2%, and 86.5% in the average recall, precision and F1-score, respectively, and outperformed other state-of-the-art methods remarkably. Conclusions The experimental results demonstrate the great promise of our method

Session 1: Oral History and interview with Dr. Cecile Chu-Chin Sun, Professor Emerita, University of Pittsburgh. The interview focuses on her family history and education experience, especially the graduate study on Chinese-Western Comparative Literature. Session 1 also includes her teaching experience and courses design at University of Pittsburgh.

Session 2: Oral History and interview with Dr. Cecile Chu-Chin Sun, Professor Emerita, University of Pittsburgh. The interview focuses on her fields of Research: Classical Chinese Lyric Poetry and Aesthetics; Chinese-Western Comparative Literature and Poetics; Traditional Chinese Thought Systems (Confucianism, Daoism, Chan Buddhism).

Session 2: Oral History and interview with Dr. Cecile Chu-Chin Sun, Professor Emerita, University of Pittsburgh. The interview focuses on her fields of Research: Classical Chinese Lyric Poetry and Aesthetics; Chinese-Western Comparative Literature and Poetics; Traditional Chinese Thought Systems (Confucianism, Daoism, Chan Buddhism).

Session 1: Oral History and interview with Dr. Cecile Chu-Chin Sun, Professor Emerita, University of Pittsburgh. The interview focuses on her family history and education experience, especially the graduate study on Chinese-Western Comparative Literature. Session 1 also includes her teaching experience and courses design at University of Pittsburgh.

3D ultrasound (US) has become prevalent due to its rich spatial and diagnostic information not contained in 2D US. Moreover, 3D US can contain multiple standard planes (SPs) in one shot. Thus, automatically localizing SPs in 3D US has the potential to improve user-independence and scanning-efficiency. However, manual SP localization in 3D US is challenging because of the low image quality, huge search space and large anatomical variability. In this work, we propose a novel multi-agent reinforcement learning (MARL) framework to simultaneously localize multiple SPs in 3D US. Our contribution is four-fold. First, our proposed method is general and it can accurately localize multiple SPs in different challenging US datasets. Second, we equip the MARL system with a recurrent neural network (RNN) based collaborative module, which can strengthen the communication among agents and learn the spatial relationship among planes effectively. Third, we explore to adopt the neural architecture search (NAS) to automatically design the network architecture of both the agents and the collaborative module. Last, we believe we are the first to realize automatic SP localization in pelvic US volumes, and note that our approach can handle both normal and abnormal uterus cases. Extensively validated on two challenging datasets of the uterus and fetal brain, our proposed method achieves the average localization accuracy of 7.03 degrees/1.59mm and 9.75 degrees/1.19mm. Experimental results show that our light-weight MARL model has higher accuracy than state-of-the-art methods., Comment: Accepted by Medical Image Analysis (10 figures, 8 tabels)

To reduce uploading bandwidth and address privacy concerns, deep learning at the network edge has been an emerging topic. Typically, edge devices collaboratively train a shared model using real-time generated data through the Parameter Server framework. Although all the edge devices can share the computing workloads, the distributed training processes over edge networks are still time-consuming due to the parameters and gradients transmission procedures between parameter servers and edge devices. Focusing on accelerating distributed Convolutional Neural Networks (CNNs) training at the network edge, we present DynaComm, a novel scheduler that dynamically decomposes each transmission procedure into several segments to achieve optimal layer-wise communications and computations overlapping during run-time. Through experiments, we verify that DynaComm manages to achieve optimal layer-wise scheduling for all cases compared to competing strategies while the model accuracy remains untouched., Comment: 16 pages, 12 figures. IEEE Journal on Selected Areas in Communications

Knowledge of the evolutionary processes which govern pathogen recognition is critical to understanding durable disease resistance. We determined how Phytophthora infestans effector PiAVR2 is recognised by evolutionarily distinct resistance proteins R2 and Rpi-mcq1. We employed yeast two-hybrid, co-immunoprecipitation, virus-induced gene silencing, transient overexpression, and phosphatase activity assays to investigate the contributions of BSL phosphatases to R2- and Rpi-mcq1-mediated hypersensitive response (R2 HR and Rpi-mcq1 HR, respectively). Silencing PiAVR2 target BSL1 compromises R2 HR. Rpi-mcq1 HR is compromised only when BSL2 and BSL3 are silenced. BSL1 overexpression increases R2 HR and compromises Rpi-mcq1. However, overexpression of BSL2 or BSL3 enhances Rpi-mcq1 and compromises R2 HR. Okadaic acid, which inhibits BSL phosphatase activity, suppresses both recognition events. Moreover, expression of a BSL1 phosphatase-dead (PD) mutant suppresses R2 HR, whereas BSL2-PD and BSL3-PD mutants suppress Rpi-mcq1 HR. R2 interacts with BSL1 in the presence of PiAVR2, but not with BSL2 and BSL3, whereas no interactions were detected between Rpi-mcq1 and BSLs. Thus, BSL1 activity and association with R2 determine recognition of PiAVR2 by R2, whereas BSL2 and BSL3 mediate Rpi-mcq1 perception of PiAVR2. R2 and Rpi-mcq1 utilise distinct mechanisms to detect PiAVR2 based on association with different BSLs, highlighting central roles of these effector targets for both disease and disease resistance.

Mo Yi,1 Di Jiang,2 Yuanmin Jia,1 Wei Xu,3 Haixia Wang,1 Yizhang Li,1 Zeyi Zhang,1 Jingjing Wang,1 Ou Chen1 1School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Department of Psychology, Shanghai Normal University, Shanghai, 200234, People’s Republic of ChinaCorrespondence: Ou ChenSchool of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, 44# Wenhua xi Road, Lixia District, Jinan City, Shandong Province, People’s Republic of ChinaTel +86 53188382000Email chenou@sdu.edu.cnPurpose: Caregivers of COPD patients experience various caregiving burden, which is related to their quality of life. We aimed to explicitly explore whether social support and negative coping styles play the chain mediating roles in the relationship between the caregiving burden of caregivers of COPD patients and their health-related quality of life.Methods: We conducted a multicenter cross-sectional survey in four hospitals using a convenience sample. Participants who met the inclusion criteria completed five relevant scales, including a sociodemographic scale. One-way ANOVA and Pearson’s method were used to analyze the data accordingly, and chain mediated effect values were estimated by bootstrap method to determine whether the model holds.Results: Among the 201 caregivers who participated in this study, the mean age was 55.94 years, most of them were female (61.2%), the mean caregiving burden score was 52.39 ± 14.65, and the quality of life score was 37.97 ± 3.55. Among them, age, gender, education, relationship with the patient, and the number of chronic diseases were the main factors affecting the quality of life score of the caregivers. According to Pearson results, there was a negative correlation between quality of life and caregiving burden, and negative coping styles. The model

Session 1: Oral History and interview with Dr. Cecile Chu-Chin Sun, Professor Emerita, University of Pittsburgh. The interview focuses on her family history and education experience, especially the graduate study on Chinese-Western Comparative Literature. Session 1 also includes her teaching experience and courses design at University of Pittsburgh.

Session 2: Oral History and interview with Dr. Cecile Chu-Chin Sun, Professor Emerita, University of Pittsburgh. The interview focuses on her fields of Research: Classical Chinese Lyric Poetry and Aesthetics; Chinese-Western Comparative Literature and Poetics; Traditional Chinese Thought Systems (Confucianism, Daoism, Chan Buddhism).

La transcription des symboles et des caractères spéciaux utilisés dans la version originale de ce résumé n’a pas été possible en raison de limitations techniques. La version correcte de ce résumé peut être lue en PDF.Avec la détérioration du climat mondial et la pénurie croissante de ressources pétrolières, l'exploration de sources d'énergie propres, renouvelables et durables est devenue la priorité absolue. On s'attend à ce que les piles à combustible à éthanol direct (DEFC) deviennent un combustible alternatif pour leurs applications potentielles en tant que sources d'énergie portables, car l'éthanol possède une haute densité d'énergie, une faible toxicité et peut-être produit à partir de la biomasse, ce qui en fait un combustible vert. Néanmoins, la commercialisation des DEFC est entravée par la faible sélectivité de la génération de CO2 et la lente cinétique à l'anode. Il est très important de développer un catalyseur anodique avec une activité, une stabilité et une efficacité d'oxydation élevées. Cette thèse débute par l'étude de l'effet de l'épaisseur de la couche de Rh (liée au nombre d'impulsions laser Nlp) sur la morphologie, la taille des particules et l'électrooxydation du CO. Afin d'améliorer l'efficacité de l'électrooxydation de l'éthanol, du SnO2 est ajouté comme support. Une série d'électrocatalyseurs Pt/SnO2, Rhx/Pt et Rhx/Pt/SnO2 sur du papier carbone déposé couche par couche fabriquée en PLD sont étudiés pour l'électrooxydation du CO ainsi que de l'éthanol. Les résultats révèlent le rôle du promoteur du dioxyde d'étain et du rhodium dans l'amélioration de l'activité électrocatalytique envers la réaction d'oxydation de l'éthanol (ROE). Il concerne en particulier l'effet de la quantité de Rh (Nlp, Rh). On constate que le catalyseur ternaire Rh5/Pt/SnO2 (Nlp, Rh=5000) présente les meilleures performances, tandis que le catalyseur Rh50/Pt/SnO2 est le plus mauvais. En outre, un accent particulier est mis sur l'influence du substrat pour améliorer la sur

Konosirus punctatus is an important economic fish in the Northwest Pacific Ocean, especially along the coast of China, and an important substitute in the marine ecosystem. The aim of this study is to quantify the variation of sagittal shapes to discriminate the K. punctatus stocks between China coasts (Wei Hai, Yan Tai, Zhou Shan, Wen Zhou, Dong Ying, Hai Kou and Qing Dao) and Aomori (Am) in Japan by comparing the sagittal morphometric features. The sagitta variation of eight K. punctatus stocks was examined using nine shape indices (Roundness, Circularity, Form-factor, Rectangularity, Ellipticity, Radius ratio, Feret ratio, Aspect ratio and Surface density). Multiple comparisons on shape indices showed that three shape indices (Roundness, Feret ratio and Surface density) have significant differences between nine stocks. The comprehensive judgment accuracy rate is 54.5%. Based on the Fourier coefficient eight Fourier parameters can fit the shape of sagittal. The comprehensive judgment accuracy rate is 56.1%. The results showed that the otolith morphology was not significantly different between seven China stocks, while the China stocks showed a large sagittal morphological difference from the Japanese stock. It could be related to environmental factors and geographical conditions in various sea areas.

Haixia Wang, Chenxiao Bai, Mo Yi, Yuanmin Jia, Yizhang Li, Di Jiang, Ou Chen School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaCorrespondence: Ou ChenSchool of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaTel +8615990991181Email chenou@sdu.edu.cnBackground: Although metabolic syndrome is awell-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial.Objective: The aim of this study was to explore the associations of metabolic syndrome and its components with incident asthma in Chinese adults.Methods: We conducted an open cohort study of participants who were asthma-free at baseline (n=42,304) in the Shandong multi-center health check-up longitudinal study from 2004 to 2015. Participants aged ≥ 20 years and had regular physical examination (once ayear) more than three times during follow-up.Results: Ninety subjects (38 women and 52 men) developed incident asthma over 12 years of follow-up. Our study suggested that metabolic syndrome itself was not significantly associated with incident asthma in either women or men (P> 0.050). Interestingly, we found that overweight and/or obesity was arisk factor for incident asthma among women but not men in the Cox proportional hazards model after adjusting covariates (adjusted incidence rate ratio (IRR)= 2.940, 95% confidence interval (CI): 1.467– 5.894, P=0.002). The result was consistent with the Poisson regression model (hazard ratio (HR)= 2.241, 95% CI: 1.135– 4.988, P=0.026). After stratifying according to overweight and/or obesity, we found that female subjects with overweight and obesity were associated with the occurrence of incident asthma (P< 0.050). However, we did not find this result among men. Conclusion: Metabolic syndrome was not significantly associated with incident a

Haixia Wang, Yuanmin Jia, Mo Yi, Yizhang Li, Ou Chen School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaCorrespondence: Ou ChenSchool of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaTel +86 15990991181Email chenou@sdu.edu.cnBackground: Several cross-sectional studies have suggested an association between SUA and asthma. However, few studies have investigated this relationship longitudinally. Although SUA is an independent risk factor for chronic kidney disease and cardiovascular diseases, its contribution to incident asthma remains uncertain.Objective: To determine whether a high SUA was a risk factor for adult incident asthma.Methods: By using health care data from the Shandong multicenter health check-up, 76,369 participants, aged 20 to 79 years, were identified who had an SUA determination with a mean follow-up period of 3.73± 2.21 years. Multivariate modeling employed Cox proportional hazards models to verify the association between SUA and incident asthma by adjusting age, BMI, smoking habits, drinking habits, and asthma-like diseases.Results: A total of 51,389 individuals were included in the analysis. Cut-off values of SUA able to discriminate asthma status were identified by means of maximally selected rank statistics in the whole participants (≥ 376.80umol/L), women (≥ 314.45umol/L), and men (≥ 376.80umol/L). Multivariate Cox regression analyses adjusted for covariates (age, body mass index (BMI), smoking habit, drinking habit, and asthma-like disease) identified an independent association between SUA and incident asthma in the whole participants (hazard ratio (HR) 2.92, 95% confidence intervals (CI), 1.76– 4.48, P=0.00) and men (HR 3.02, 95% CI 1.70– 5.39, P=0.00), but not in women.Conclusion: The results of the current study confirmed that high SUA was a

Researchers determined that National Parks were Americans destination of choice over the Summer of 2020. This is no surprise as consumers feel more comfortable in isolated spaces opposed to heavily populated areas due to the COVID-19 pandemic. Short term rentals, campgrounds, and RVs all saw an uptick in usage throughout the summer months.

Oomycetes such as the potato blight pathogen Phytophthora infestans deliver RXLR effectors into plant cells to manipulate host processes and promote disease. Knowledge of where they localize inside host cells is important in understanding their function. Fifty-two P. infestans RXLR effectors (PiRXLRs) up-regulated during early stages of infection were expressed as fluorescent protein (FP) fusions inside cells of the model host Nicotiana benthamiana. FP-PiRXLR fusions were predominantly nucleo-cytoplasmic, nuclear, or plasma membrane-associated. Some also localized to the endoplasmic reticulum, mitochondria, peroxisomes, or microtubules, suggesting diverse sites of subcellular activity. Seven of the 25 PiRXLRs examined during infection accumulated at sites of haustorium penetration, probably due to co-localization with host target processes; Pi16663 (Avr1), for example, localized to Sec5-associated mobile bodies which showed perihaustorial accumulation. Forty-five FP-RXLR fusions enhanced pathogen leaf colonization when expressed in Nicotiana benthamiana, revealing that their presence was beneficial to infection. Co-expression of PiRXLRs that target and suppress different immune pathways resulted in an additive enhancement of colonization, indicating the potential to study effector combinations using transient expression assays. We provide a broad platform of high confidence P. infestans effector candidates from which to investigate the mechanisms, singly and in combination, by which this pathogen causes disease.

It was recently shown that mouse fibroblasts could be reprogrammed into cells of a cardiac fate by forced expression of multiple transcription factors and microRNAs. For ultimate application of such a reprogramming strategy for cell-based therapy or in vivo cardiac regeneration, reducing or eliminating the genetic manipulations by small molecules would be highly desirable. Here, we report the identification of a defined small-molecule cocktail that enables the highly efficient conversion of mouse fibroblasts into cardiac cells with only one transcription factor, Oct4, without any evidence of entrance into the pluripotent state. Small-molecule-induced cardiomyocytes spontaneously contract and exhibit a ventricular phenotype. Furthermore, these induced cardiomyocytes pass through a cardiac progenitor stage. This study lays the foundation for future pharmacological reprogramming approaches and provides a small-molecule condition for investigation of the mechanisms underlying the cardiac reprogramming process.

It was recently shown that mouse fibroblasts could be reprogrammed into cells of a cardiac fate by forced expression of multiple transcription factors and microRNAs. For ultimate application of such a reprogramming strategy for cell-based therapy or in vivo cardiac regeneration, reducing or eliminating the genetic manipulations by small molecules would be highly desirable. Here, we report the identification of a defined small-molecule cocktail that enables the highly efficient conversion of mouse fibroblasts into cardiac cells with only one transcription factor, Oct4, without any evidence of entrance into the pluripotent state. Small-molecule-induced cardiomyocytes spontaneously contract and exhibit a ventricular phenotype. Furthermore, these induced cardiomyocytes pass through a cardiac progenitor stage. This study lays the foundation for future pharmacological reprogramming approaches and provides a small-molecule condition for investigation of the mechanisms underlying the cardiac reprogramming process.

The purpose of this study is to examine the changes in the understanding of learners of Chinese as a Foreign language (CFL) of certain Chinese metaphorical expressions (e.g. color phrases). By implementing conceptual metaphor theory as a way to connect language and culture in CFL instruction, the present study examines how instructional interventions can be used to raise students’ conceptual awareness of certain metaphorical expressions and their communicative intent in a lower level Chinese language classes. The research questions are: 1) What are the initial interpretations of certain color phrases by students from different linguistic and cultural backgrounds? 2) How, if at all, do students’ explanations of color phrases with metaphorical meanings change from pre-test to post-test? 3) Can students make use of the knowledge that they gained from instruction to interpret novel metaphoric expressions using the color metaphors that they have learned? The findings demonstrated that the students were able to interpret the color metaphors in a culturally appropriate way and applied their knowledge of three Chinese colors to metaphoric expressions that they had not encountered before. The findings also revealed that intentional instruction is needed for raising students’ metaphorical awareness to better understand metaphorical meanings in the target language and culture. The pedagogical implications raises the issue of the need to balance instruction on language and instruction on conceptual metaphors. This study is beneficial to the foreign language education field for several reasons. First, instruction on metaphoric interpretations will encourage the students to use metaphors to communicate meaning in a foreign language, and facilitate their comprehension of cultural meanings of the texts in the target language. Because Chinese is a less commonly-taught language, this study furthers our understanding of Chinese color metaphors, a new research area that has not been fu

The purpose of this study is to examine the changes in the understanding of learners of Chinese as a Foreign language (CFL) of certain Chinese metaphorical expressions (e.g. color phrases). By implementing conceptual metaphor theory as a way to connect language and culture in CFL instruction, the present study examines how instructional interventions can be used to raise students’ conceptual awareness of certain metaphorical expressions and their communicative intent in a lower level Chinese language classes. The research questions are: 1) What are the initial interpretations of certain color phrases by students from different linguistic and cultural backgrounds? 2) How, if at all, do students’ explanations of color phrases with metaphorical meanings change from pre-test to post-test? 3) Can students make use of the knowledge that they gained from instruction to interpret novel metaphoric expressions using the color metaphors that they have learned? The findings demonstrated that the students were able to interpret the color metaphors in a culturally appropriate way and applied their knowledge of three Chinese colors to metaphoric expressions that they had not encountered before. The findings also revealed that intentional instruction is needed for raising students’ metaphorical awareness to better understand metaphorical meanings in the target language and culture. The pedagogical implications raises the issue of the need to balance instruction on language and instruction on conceptual metaphors. This study is beneficial to the foreign language education field for several reasons. First, instruction on metaphoric interpretations will encourage the students to use metaphors to communicate meaning in a foreign language, and facilitate their comprehension of cultural meanings of the texts in the target language. Because Chinese is a less commonly-taught language, this study furthers our understanding of Chinese color metaphors, a new research area that has not been fu

Recent studies have shown that STAT3 negatively regulates the proliferation of muscle satellite cells (MuSCs) and injury-induced muscle regeneration. These studies have been largely based on STAT3 inhibitors, which may produce off-target effects and are not cell type-specific in vivo. Here, we examine the role of STAT3 in MuSCs using two different mouse models: a MuSC-specific Stat3 knockout line and a Stat3 (MuSC-specific)/dystrophin (Dmd) double knockout (dKO) line. Stat3−/− MuSCs from both mutant lines were defective in proliferation. Moreover, in both mutant strains, the MuSC pool shrank, and regeneration was compromised after injury, with defects more pronounced in dKO mice along with severe muscle inflammation and fibrosis. We analyzed the transcriptomes of MuSCs from dKO and Dmd−/− control mice and identified multiple STAT3 target genes, including Pax7. Collectively, our work reveals a critical role of STAT3 in adult MuSCs that regulates their self-renewal during injury-induced muscle regeneration. © 2016 The Author(s)

Recent studies have shown that STAT3 negatively regulates the proliferation of muscle satellite cells (MuSCs) and injury-induced muscle regeneration. These studies have been largely based on STAT3 inhibitors, which may produce off-target effects and are not cell type-specific in vivo. Here, we examine the role of STAT3 in MuSCs using two different mouse models: a MuSC-specific Stat3 knockout line and a Stat3 (MuSC-specific)/dystrophin (Dmd) double knockout (dKO) line. Stat3−/− MuSCs from both mutant lines were defective in proliferation. Moreover, in both mutant strains, the MuSC pool shrank, and regeneration was compromised after injury, with defects more pronounced in dKO mice along with severe muscle inflammation and fibrosis. We analyzed the transcriptomes of MuSCs from dKO and Dmd−/− control mice and identified multiple STAT3 target genes, including Pax7. Collectively, our work reveals a critical role of STAT3 in adult MuSCs that regulates their self-renewal during injury-induced muscle regeneration. © 2016 The Author(s)

Recent studies have shown that STAT3 negatively regulates the proliferation of muscle satellite cells (MuSCs) and injury-induced muscle regeneration. These studies have been largely based on STAT3 inhibitors, which may produce off-target effects and are not cell type-specific in vivo. Here, we examine the role of STAT3 in MuSCs using two different mouse models: a MuSC-specific Stat3 knockout line and a Stat3 (MuSC-specific)/dystrophin (Dmd) double knockout (dKO) line. Stat3−/− MuSCs from both mutant lines were defective in proliferation. Moreover, in both mutant strains, the MuSC pool shrank, and regeneration was compromised after injury, with defects more pronounced in dKO mice along with severe muscle inflammation and fibrosis. We analyzed the transcriptomes of MuSCs from dKO and Dmd−/− control mice and identified multiple STAT3 target genes, including Pax7. Collectively, our work reveals a critical role of STAT3 in adult MuSCs that regulates their self-renewal during injury-induced muscle regeneration. © 2016 The Author(s)

The rapid development of multi-core system and increase of data-intensive application in recent years call for larger main memory. Traditional DRAM memory can increase its capacity by reducing the feature size of storage cell. Now further scaling of DRAM faces great challenge, and the frequent refresh operations of DRAM can bring a lot of energy consumption. As an emerging technology, Phase Change Memory (PCM) is promising to be used as main memory. It draws wide attention due to the advantages of low power consumption, high density and nonvolatility, while it incurs finite endurance and relatively long write latency. To handle the problem of write, optimizing the cache replacement policy to protect dirty cache block is an efficient way. In this paper, we construct a systematically multilevel structure, and based on it propose a novel cache replacement policy called MAC. MAC can effectively reduce write traffic to PCM memory with low hardware overhead. We conduct simulation experiments on GEM5 to evaluate the performances of MAC and other related works. The results show that MAC performs best in reducing the amount of writes (averagely 25.12%) without increasing the program execution time.

A four-degree-of-freedom model of disc brake with friction and contact loss nonlinearities is developed to investigate the mechanism and dynamic characteristics of brake squeal. The nonlinear equations of motion are presented, and Coulomb and Stribeck friction models are applied and compared in the analysis. The effects of key parameters on system stability are investigated based on the linear equations around the equilibrium point using the complex eigenvalue analysis method. Mode-coupling motion is found to be one significant mechanism to initiate the system instability and lead to brake squeal, and is exceptionally reliant on the parameter configurations of brake system. Numerical solutions of the nonlinear equations of motion are obtained to examine the dynamic behaviors and find the routes to squeal of the brake system with nonlinearities. Results demonstrate that the tangential stiffness of the pad and the rotating velocity of the disc play important roles on the occurrence of stick-slip vibration resulting from the falling characteristic of friction coefficient, and contact loss nonlinearity may make system become unstable even for constant friction coefficient. The separation between the brake pad and disc is dependent on the ratio of normal stiffness of pad/disc and contact stiffness. Strong nonlinear items of the brake system may lead to complicated quasi-periodic and chaotic motions, resulting in squeal problem.

Wenhao Shi,1–3 Jinliang Wang,4,5 Yan Lin,4,5 Jianhui Geng,4,5 Haixia Wang,4,5 Yueqin Gong,4,5 Huaxu Liu,1,4,5 Furen Zhang1–4 1Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, 2Shandong Provincial Key Lab for Dermatovenereology, 3School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 4Shandong Provincial Hospital for Skin Diseases, Shandong University, 5Shandong Provincial Medical Center for Dermatovenereology, Jinan, Shandong, People’s Republic of China Background: Currently, 595 nm pulsed dye laser (PDL) therapy is offered as one of the effective treatments of port wine stains (PWSs). However, the efficacy of PDL differs in different populations.Objective: The purpose of the study was to investigate the efficacy, and related factors, of 595 nm PDL in the treatment of PWSs in Chinese patients with skin type III to IV. Methods: A total of 848 cases that were treated with PDL were enrolled and analyzed in this study. An independent dermatologist evaluated these lesions according to the before and after photographs.Results: The response rate (RR) of all the 848 PWS patients was 69.9%, within which the cure rate was 6.3%. The patients aged ≤1 year had the highest RR (93.9%), whereas those treated after age 50 reacted the worst (RR =25%). We analyzed the anatomical distribution of the lesion and found that the temporal region had the highest lesion clearance (RR =75.3%), while the extremities had the lowest clearance (RR =44.5%). Compared with the patients whose lesion size was larger than 80 cm2, the patients with small lesion size, of 0–20 cm2, had better clinical effect (RR =73.8% vs 53.2%). The reactions of the patients with hyperplastic lesion were worse than those with red patches (RR =36.4% vs 71.7%). As well, increasing treatment numbers could achieve higher clearance rates (P=0.005).Conclusion: The PDL had a relative

A four-degree-of-freedom model of disc brake with friction and contact loss nonlinearities is developed to investigate the mechanism and dynamic characteristics of brake squeal. The nonlinear equations of motion are presented, and Coulomb and Stribeck friction models are applied and compared in the analysis. The effects of key parameters on system stability are investigated based on the linear equations around the equilibrium point using the complex eigenvalue analysis method. Mode-coupling motion is found to be one significant mechanism to initiate the system instability and lead to brake squeal, and is exceptionally reliant on the parameter configurations of brake system. Numerical solutions of the nonlinear equations of motion are obtained to examine the dynamic behaviors and find the routes to squeal of the brake system with nonlinearities. Results demonstrate that the tangential stiffness of the pad and the rotating velocity of the disc play important roles on the occurrence of stick-slip vibration resulting from the falling characteristic of friction coefficient, and contact loss nonlinearity may make system become unstable even for constant friction coefficient. The separation between the brake pad and disc is dependent on the ratio of normal stiffness of pad/disc and contact stiffness. Strong nonlinear items of the brake system may lead to complicated quasi-periodic and chaotic motions, resulting in squeal problem.

High pressure torsion (HPT) is an important process for producing ultrafine grained materials, and while numerous experimental investigations of HPT have been carried out, most concentrated on microstructure, texture, or the mechanical properties of the processed materials, while few work has been carried out by using FEM because of extreme mesh distortion during deformation. In this paper, a FEM model of HPT with a mapping solution method of Abaqus has been established and used to investigate the plastic deformation of HPT process, the stress and equivalent strain distribution and evolution along the radius and axial directions were presented, inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation could be anticipated if the strain applied reached a high enough level. The FEM results agreed quite well with the experimental results. A FEM model with mapping solution method of Abaqus was established and used to investigate the plastic deformation, the stress and equivalent strain distribution and evolution of the HPT process. Inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation along the whole sample could be anticipated if the strain applied reached a high enough level.

High pressure torsion (HPT) is an important process for producing ultrafine grained materials, and while numerous experimental investigations of HPT have been carried out, most concentrated on microstructure, texture, or the mechanical properties of the processed materials, while few work has been carried out by using FEM because of extreme mesh distortion during deformation. In this paper, a FEM model of HPT with a mapping solution method of Abaqus has been established and used to investigate the plastic deformation of HPT process, the stress and equivalent strain distribution and evolution along the radius and axial directions were presented, inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation could be anticipated if the strain applied reached a high enough level. The FEM results agreed quite well with the experimental results. A FEM model with mapping solution method of Abaqus was established and used to investigate the plastic deformation, the stress and equivalent strain distribution and evolution of the HPT process. Inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation along the whole sample could be anticipated if the strain applied reached a high enough level.

High pressure torsion (HPT) is an important process for producing ultrafine grained materials, and while numerous experimental investigations of HPT have been carried out, most concentrated on microstructure, texture, or the mechanical properties of the processed materials, while few work has been carried out by using FEM because of extreme mesh distortion during deformation. In this paper, a FEM model of HPT with a mapping solution method of Abaqus has been established and used to investigate the plastic deformation of HPT process, the stress and equivalent strain distribution and evolution along the radius and axial directions were presented, inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation could be anticipated if the strain applied reached a high enough level. The FEM results agreed quite well with the experimental results. A FEM model with mapping solution method of Abaqus was established and used to investigate the plastic deformation, the stress and equivalent strain distribution and evolution of the HPT process. Inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation along the whole sample could be anticipated if the strain applied reached a high enough level.

High pressure torsion (HPT) is an important process for producing ultrafine grained materials, and while numerous experimental investigations of HPT have been carried out, most concentrated on microstructure, texture, or the mechanical properties of the processed materials, while few work has been carried out by using FEM because of extreme mesh distortion during deformation. In this paper, a FEM model of HPT with a mapping solution method of Abaqus has been established and used to investigate the plastic deformation of HPT process, the stress and equivalent strain distribution and evolution along the radius and axial directions were presented, inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation could be anticipated if the strain applied reached a high enough level. The FEM results agreed quite well with the experimental results. A FEM model with mapping solution method of Abaqus was established and used to investigate the plastic deformation, the stress and equivalent strain distribution and evolution of the HPT process. Inhomogeneous deformation was observed along the radius and axial directions and a homogenous deformation along the whole sample could be anticipated if the strain applied reached a high enough level.

Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to cystic fibrosis, but the regulation of CFTR is not fully understood. Here, we identified the intermediate filament protein keratin K18 (K18) as a CFTR-binding protein by various approaches. We mapped a highly conserved "hydrophobic patch" ((FLVI1416)-F-1413) in the CFTR C-terminus, known to determine plasmalemmal CFTR stability, as the K18-binding site. On the other hand, the C-terminal tail of K18 was found to be a critical determinant for binding CFTR. Overexpression of K18 in cells robustly increased the surface expression of wild-type CFTR, whereas depletion of K18 through RNA interference specifically diminished it. K18 binding increased the surface expression of CFTR by accelerating its apical recycling rate without altering CFTR biosynthesis, maturation, or internalization. Importantly, CFTR surface expression was markedly reduced in duodenal and gallbladder epithelia of K18(-/-) mice. Taken together, our results suggest that K18 increases the cell surface expression of CFTR by interacting with the CFTR C-terminal hydrophobic patch. These findings offer novel insights into the regulation of CFTR and suggest that K18 and its dimerization partner, K8, may be modifier genes in cystic fibrosis.

p38 mitogen-activated protein kinase (MAPK) is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways.

Studying how invasive species respond to environmental stress at the molecular level can help us assess their impact and predict their range expansion. Development of markers of genetic polymorphism can help us reconstruct their invasive route. However, to conduct such studies requires the presence of substantial amount of genomic resources. This study aimed to generate and characterize genomic resources using high throughput transcriptome sequencing for Pomacea canaliculata, a nonmodel gastropod indigenous to Argentina that has invaded Asia, Hawaii and southern United States. De novo assembly of the transcriptome resulted in 128 436 unigenes with an average length of 419 bp (range: 1508556 bp). Many of the unigenes (2439) contained transposable elements, showing the existence of a source of genetic variability in response to stressful conditions. A total of 3196 microsatellites were detected in the transcriptome; among 20 of the randomly tested microsatellites, 10 were validated to exhibit polymorphism. A total of 15 412 single-nucleotide polymorphisms (SNPs) were detected in the ORFs. LC-MS/MS analysis of the proteome of juveniles revealed 878 proteins, of which many are stress related. This study has demonstrated the great potential of high throughput DNA sequencing for rapid development of genomic resources for a nonmodel organism. Such resources can facilitate various molecular ecological studies, such as stress physiology and range expansion.

Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to cystic fibrosis, but the regulation of CFTR is not fully understood. Here, we identified the intermediate filament protein keratin K18 (K18) as a CFTR-binding protein by various approaches. We mapped a highly conserved "hydrophobic patch" ((FLVI1416)-F-1413) in the CFTR C-terminus, known to determine plasmalemmal CFTR stability, as the K18-binding site. On the other hand, the C-terminal tail of K18 was found to be a critical determinant for binding CFTR. Overexpression of K18 in cells robustly increased the surface expression of wild-type CFTR, whereas depletion of K18 through RNA interference specifically diminished it. K18 binding increased the surface expression of CFTR by accelerating its apical recycling rate without altering CFTR biosynthesis, maturation, or internalization. Importantly, CFTR surface expression was markedly reduced in duodenal and gallbladder epithelia of K18(-/-) mice. Taken together, our results suggest that K18 increases the cell surface expression of CFTR by interacting with the CFTR C-terminal hydrophobic patch. These findings offer novel insights into the regulation of CFTR and suggest that K18 and its dimerization partner, K8, may be modifier genes in cystic fibrosis.

p38 mitogen-activated protein kinase (MAPK) is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways.

The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by the expression of a few transcription factors has attracted enormous interest in biomedical research and the field of regenerative medicine. iPSCs nearly identically resemble embryonic stem cells (ESCs) and can give rise to all cell types in the body, and thus have opened new opportunities for personalized regenerative medicine and new ways of modeling human diseases. Although some studies have raised concerns about genomic stability and epigenetic memory in the resulting cells, better understanding and control of the reprogramming process should enable enhanced efficiency and higher fidelity in reprogramming. Therefore, small molecules regulating reprogramming mechanisms are valuable tools to probe the process of reprogramming and harness cell fate transitions for various applications.

p38 mitogen-activated protein kinase (MAPK) is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways.

Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to cystic fibrosis, but the regulation of CFTR is not fully understood. Here, we identified the intermediate filament protein keratin K18 (K18) as a CFTR-binding protein by various approaches. We mapped a highly conserved "hydrophobic patch" ((FLVI1416)-F-1413) in the CFTR C-terminus, known to determine plasmalemmal CFTR stability, as the K18-binding site. On the other hand, the C-terminal tail of K18 was found to be a critical determinant for binding CFTR. Overexpression of K18 in cells robustly increased the surface expression of wild-type CFTR, whereas depletion of K18 through RNA interference specifically diminished it. K18 binding increased the surface expression of CFTR by accelerating its apical recycling rate without altering CFTR biosynthesis, maturation, or internalization. Importantly, CFTR surface expression was markedly reduced in duodenal and gallbladder epithelia of K18(-/-) mice. Taken together, our results suggest that K18 increases the cell surface expression of CFTR by interacting with the CFTR C-terminal hydrophobic patch. These findings offer novel insights into the regulation of CFTR and suggest that K18 and its dimerization partner, K8, may be modifier genes in cystic fibrosis.

Studying how invasive species respond to environmental stress at the molecular level can help us assess their impact and predict their range expansion. Development of markers of genetic polymorphism can help us reconstruct their invasive route. However, to conduct such studies requires the presence of substantial amount of genomic resources. This study aimed to generate and characterize genomic resources using high throughput transcriptome sequencing for Pomacea canaliculata, a nonmodel gastropod indigenous to Argentina that has invaded Asia, Hawaii and southern United States. De novo assembly of the transcriptome resulted in 128 436 unigenes with an average length of 419 bp (range: 1508556 bp). Many of the unigenes (2439) contained transposable elements, showing the existence of a source of genetic variability in response to stressful conditions. A total of 3196 microsatellites were detected in the transcriptome; among 20 of the randomly tested microsatellites, 10 were validated to exhibit polymorphism. A total of 15 412 single-nucleotide polymorphisms (SNPs) were detected in the ORFs. LC-MS/MS analysis of the proteome of juveniles revealed 878 proteins, of which many are stress related. This study has demonstrated the great potential of high throughput DNA sequencing for rapid development of genomic resources for a nonmodel organism. Such resources can facilitate various molecular ecological studies, such as stress physiology and range expansion.

Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.

Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.