Search

Background Sinonasal teratocarcinosarcoma (SNTCS) is a highly invasive malignant tumor most frequently found in the nasal cavity and paranasal sinuses. As a result, it can be confused with other sinonasal tumors. In addition, SNTCS progresses rapidly and often infiltrates other tissues or organs in the early phase, resulting in poor patient prognosis. The objective of this article was to report the case of a patient with SNTCS and discuss the management strategy. Furthermore, we conducted a literature review for SNTCS and summarized the findings from 107 cases. Case presentation: Here, we report a 47-year-old man diagnosed with SNTCS and treated with radiochemotherapy after an initial operation. After follow-up for 5 years, no tumor recurrence was observed. Conclusions As SNTCS progresses rapidly, early diagnosis and surgical treatment combined with radiochemotherapy can improve patient survival.

This study investigated the effect of sweet potato starch (SPS) and konjac glucomannan (KGM) on the textural, color, sensory, rheological properties, and microstructures of plant-based pork rinds. Plant-based gels were prepared using mixtures of soy protein isolate (SPI), soy oil, and NaHCO3 supplemented with different SPS and KGM concentrations. The texture profile analysis (TPA) results indicated that the hardness, cohesiveness, and chewiness of the samples improved significantly after appropriate SPS and KGM addition. The results obtained via a colorimeter showed no significant differences were found in lightness (L*) between the samples and natural pork rinds after adjusting the SPS and KGM concentrations. Furthermore, the rheological results showed that adding SPS and KGM increased both the storage modulus (G’) and loss modulus (G’’), indicating a firmer gel structure. The images obtained via scanning electron microscopy (SEM) showed that the SPS and KGM contributed to the formation of a more compact gel structure. A mathematical model allowed for a more objective sensory evaluation, with the 40% SPS samples and the 0.4% KGM samples being considered the most similar to natural pork rinds, which provided a comparable texture, appearance, and mouthfeel. This study proposed a possible schematic model for the gelling mechanism of plant-based pork rinds: the three-dimensional network structures of the samples may result from the interaction between SPS, SPI, and soybean oil, while the addition of KGM and NaHCO3 enabled a more stable gel structure.

Although China has enjoyed great economic growth in the past several years, environmental problems have not attracted enough attention, especially for the young Chinese population (Generation Z consumers). Based on the theory of planned behavior, this work aims to analyze the mediation role of product attributes, perceived consumer effectiveness (PCE), and environmental awareness in eco-label–informed purchase for Gen Z consumers in China. According to the result, it shows (a) eco-label–informed purchase could significantly increase two threads of PCE and product attributes, (b) those two threads intermediate the eco-labeling and environmental awareness positively, and (c) eventually lead to purchase behavior for Chinese Generation Z. For theoretical contribution, this article tries to have a more comprehensive investigation on green consumption, and to explore the theoretical relationship among product attributes, PCE, and environmental awareness in the context of Chinese Gen Z. Relevant managerial implications and practical guides are also discussed in this article.

This article presents a review of the theoretical and empirical studies of paradiplomacy produced to date, focusing on the literature on subnational diplomacy in China, specifically. It argues that the analytical frameworks of previous paradiplomacy studies lead their focus to be restricted to a very limited aspect of the phenomenon only. Moreover, previous studies focusing on the engagement of Chinese provinces in world politics mainly relied on the central-provincial frameworks and susceptible to a geographic bias. This article contributes to the existing literature in two ways: first, by improving the existing framework to better reflect the most essential dimensions of the international actorness of subnational actors and second, by expanding the geographical scope of the study of paradiplomacy to include more non-Western, centralized political system. It presents one of the first academic attempts to systematically review the existing literature regarding paradiplomatic theory and the paradiplomatic activities in China.

Though religion-informed charitable behavior has gained much academic attention recently, there is an ambiguous relationship between individual donation intention and Buddhist determinants. Drawing on the theories of reasoned action and product semantics, this study tries to examine the effects of product design with Buddhist symbols on individual charitable donation behavior and the underlying mechanism. Some studies have argued for the positive effects of religious symbols on people’s behavioral reactions; however, limited prior research has addressed the impact of a touchable product, such as a donation box, on people’s charitable donation intentions from the perspective of Buddhism. The current study statistically shows that donation boxes with Buddhist symbols could significantly improve people’s charitable donation intention through two sequential mediators, namely, their perceived religiosity and product attitude. The study provides both theoretical contributions and practical implications for future research.

Driven by advanced voice interaction technology, the voice-user interface (VUI) has gained popularity in recent years. VUI has been integrated into various devices in the context of the smart home system. In comparison with traditional interaction methods, VUI provides multiple benefits. VUI allows for hands-free and eyes-free interaction. It also enables users to perform multiple tasks while interacting. Moreover, as VUI is highly similar to a natural conversation in daily lives, it is intuitive to learn. The advantages provided by VUI are particularly beneficial to older adults, who suffer from decreases in physical and cognitive abilities, which hinder their interaction with electronic devices through traditional methods. However, the factors that influence older adults’ adoption of VUI remain unknown. This study addresses this research gap by proposing a conceptual model. On the basis of the technology adoption model (TAM) and the senior technology adoption model (STAM), this study considers the characteristic of VUI and the characteristic of older adults through incorporating the construct of trust and aging-related characteristics (i.e., perceived physical conditions, mobile self-efficacy, technology anxiety, self-actualization). A survey was designed and conducted. A total of 420 Chinese older adults participated in this survey, and they were current or potential users of VUI. Through structural equation modeling, data were analyzed. Results showed a good fit with the proposed conceptual model. Path analysis revealed that three factors determine Chinese older adults’ adoption of VUI: perceived usefulness, perceived ease of use, and trust. Aging-related characteristics also influence older adults’ adoption of VUI, but they are mediated by perceived usefulness, perceived ease of use, and trust. Specifically, mobile self-efficacy is demonstrated to positively influence trust and perceived ease of use but negatively influence perceived usefulness. Self-actualization exhibits positive influences on perceived usefulness and perceived ease of use. Technology anxiety only exerts influence on perceived ease of use in a marginal way. No significant influences of perceived physical conditions were found. This study extends the TAM and STAM by incorporating additional variables to explain Chinese older adults’ adoption of VUI. These results also provide valuable implications for developing suitable VUI for older adults as well as planning actionable communication strategies for promoting VUI among Chinese older adults.

As one of the most promising biodegradable material, poly(lactic acid) (PLA) is widely used for 3D printing bone scaffolds. However, the inflammation resulted by the intermediate product (lactic acid) of PLA degradation and poor cell affinity still pose a challenge. Blending PLA with o-carboxymethyl chitosan (CMC) is a proven method to achieve a better cell affinity and mechanical behavior material. This study applied a molecular dynamics simulation combining experimental method to investigate the micro-structures and mechanical properties of PLA/CMC composites. Composites were prepared by fused mixing process and extruded into filaments for FDM printing. Results show that the addition of CMC largely reduces the fractional free volume and the molecular chain motion capability, and results a higher density and better hydrophilic system. Interestingly, the tensile modulus increases as the concentration of CMC increases, indicating the introduction of CMC could enhance the stiffness of PLA. While, the tensile strength first increases and then decreases with the increase of CMC content, and 8PLA/2CMC owns the largest tensile strength. Finally, the root reason for these phenomena was found to be attributed to the stronger intermolecular interaction of CMC, the stronger interaction would result the aggregation behavior of CMC. Keywords: Polylactic acid, o-Carboxymethyl chitosan, Fused deposition modeling, Mechanical properties, Molecular simulation

The hydrogen evolution reaction is a promising route to produce clean hydrogen fuel; however, its efficient electrolytic generation relies on expensive platinum. Here, the authors show how modulating electron density in a metal sulfide, NiCo2S4, boosts hydrogen desorption to achieve high catalytic activity.

In order to study the mechanical behavior and energy absorption characteristics of a metal circular tube with axial pre-compression under axial impact load. The finite element analysis was carried out based on Abaqus. A circular tube whoseR/t value is 15 was studied. At the same time,considering the influence of the initial geometric imperfections,the initial geometric deformation caused by pre-loading and boundary conditions,the corresponding control group was established in the finite element simulation. The simulation results are concluded as follows:（ 1） The deformation mode of the fixed end simply supported is more complex than the clamped case. Energy absorption characteristics and the corresponding deformation modes have a great relationship. When the asymmetric fold is more,the energy absorption characteristic becomes worse.（ 2） Initial geometric imperfections can induce circular tubes to produce non-axisymmetric folds,while the axial pre-compression tube is less sensitive to initial geometric imperfections,and the smaller pre-loading can counteract the effects of initial geometric imperfections.

Erasure codes, such as Reed-Solomon (RS) codes and local reconstruction codes (LRCs), are being increasingly adopted in distributed storage systems since they offer lower redundancy than data replication. While these codes significantly save storage space, they can incur large I/O overhead and network traffic in reconstructing unavailable data. Most existing storage systems use replication for hot data and an erasure code for warm and cold data, thereby achieving a good tradeoff between storage overhead and recovery performance. However, these storage systems do not take the access characteristics of data into account and tend to use only an erasure code, which hinders the possibility of reducing storage overhead and recovery cost. In this paper, we propose a new adaptive coding selection method that instead uses multiple LRCs for warm data. The LRCs are selected based on the access characteristics of the data. Each time a file is accessed, we assume that each of the involved data blocks is unavailable, in turn. It is necessary to calculate the I/O cost to recover unavailable blocks for different LRCs. The sum of the I/O costs for each LRC is calculated, and the LRC with the minimal I/O cost is selected for warm data. For cold data, we use an RS code that is optimized for storage overhead to reduce the storage burden. Our method is implemented on the top of the Hadoop distributed file system. Evaluations show that it reduces the storage overhead by up to 5% and the reconstruction traffic by up to 22%.

Based on the high-performance computing global virtual data space system, a wide-area collaborative scheduling system for big data processing applications was designed and implemented.This system can address the issue of how big data processing applications unified use wide-area storage and computing resources.And it can collaborative schedule of application data and computing tasks based on the computing characteristics of the application and data layout through collaborative scheduling, load balancing scheduling, data locality scheduling strategies.By unified scheduling of application data and computing tasks in the wide-area environment, it can coordinate the utilization of wide-area computing and storage resources, and effectively improve the running performance of big data processing applications.The actual test results in the national high-performance computing environment show that the scheduling method proposed can support big data processing applications effectively, and the running efficiency of typical applications such as wide-area target collaborative recognition and molecular docking can be increased by 3~4 times.

Tree peony (Paeonia suffruticosa Andr.), a species native to China, is one of the most important ornamental and medicinal plants. Like other tree species in temperate and boreal zones, the dormancy-activity transition of floral buds is critical for blooming time and fruit production. However, floral buds contain high levels of secondary metabolites, making the isolation of high quality RNA difficult. To obtain a method suitable for extracting RNA from floral buds of tree peony, we evaluated five different methods, including the cetyltrimethylammonium bromide (CTAB) and Sodium dodecyl sulfate (SDS)-based methods, a modified SDS-TRNzol protocol, and two commercial kits (TRNzol and Qiagen RNeasy Plant Mini Kit). The modified SDS-TRNzol method was capable of efficiently removing polyphenols and other metabolites in floral buds. The isolated RNA was of high purity and integrity, as demonstrated by the the A260/280 ratio of approximately 2.0, and RIN values of more than 9.0. Gel electrophoresis analysis indicated that the extracted RNA had clear 28S and 18S ribosomal RNA bands without DNA contamination. The RNA isolated by this protocol was successfully used for downstream manipulations, such as RT-PCR, RACE, and real-time PCR. Together, the modified SDS-TRNzol protocol is an easy, efficient, and highly reproducible method for RNA isolation from floral buds rich in secondary metabolites.

Tourists’ experiential perceptions and specific behaviors are of importance to facilitate geographers’ and planners’ understanding of landscape surroundings. In addition, the potentially significant role of online user generated content (UGC) in tourism landscape research has only received limited attention, especially in the era of artificial intelligence. The motivation of the present study is to understand international tourists’ online reviews of Mt. Huangshan in China. Through a state-of-the-art natural language processing network (BERT) analyzing posted reviews across international tourists, our results facilitate relevant landscape development and design decisions. Second, the proposed analytic method can be an exemplified model to inspire relevant landscape planners and decision-makers to conduct future researches. Through the clustering results, several key topics are revealed, including international tourists’ perceptual image of Mt. Huangshan, tour route planning, and negative experience of staying.

The wide-area high-performance computing environment is the core information infrastructure to support technology innovation, economic development, and national defense.However, heterogeneous storage resources are geographically distributed in wide-area high-performance computing environments, resulting in the barriers between applications and data.The requirements of unified data management and efficient data access cannot be met.A method of establishing virtual data space and a data access optimization method was presented, and a global virtual data space (GVDS) for wide-area high-performance computing environments to satisfy the requirements was implemented.GVDS aggregates geographically distributed and heterogeneous storage resources, creating a unified virtual data space to provide unified and efficient data access.Sharing and collaborative processing of geographically distributed data were achieved in widearea environments.The experimental results indicate that compared with the state-of-the-art wide-area storage system in the field of high-performance computing, such as OneData and GFFS, GVDS has similar functions and improves the read bandwidth significantly.

Contemporarily, almost all the global IT giants have aimed at the smart home industry and made an active strategic business layout. As the early-stage and entry-level product of the voice-enabled smart home industry, the smart speakers have been going through rapid development and rising fierce market competition globally in recent years. China, one of the most populous and largest markets in the world, has tremendous business potential in the smart home industry. The market sales of smart speakers in China have gone through rapid growth in the past three years. However, the market penetration rate of related smart home devices and equipment still stays extremely low and far from mass adoption. Moreover, the market sales of smart speakers have also entered a significant slowdown and adjustment period since 2020. Chinese consumers have moved from early impulsive consumption to a rational consumption phase about this early-stage smart home product. Trust in the marketing field is considered an indispensable component of all business transactions, which plays a crucial role in adopting new technologies. This study explores the influencing factors of Chinese users’ perceived trust in the voice-enabled smart home systems, uses structural equation modeling (SEM) to analyze the interaction mechanism between different variables, and establishes a perceived trust model through 475 valid samples. The model includes six variables: system quality, familiarity, subjective norm, technology optimism, perceived enjoyment, and perceived trust. The result shows that system quality is the essential influence factor that impacts all other variables and could significantly affect the perceived trust. Perceived enjoyment is the most direct influence variable affected by system quality, subjective norm, and technology optimism, and it positively affects the perceived trust in the end. The subjective norm is one of the most distinguishing variables for Chinese users, since China has a collectivist consumption culture. People always expect their behavior to meet social expectations and standards to avoid criticism and acquire social integration. Therefore, policy guidance, authoritative opinions, and people with important reference roles will significantly affect consumers’ perceived trust and purchase intention. Familiarity and technology optimism are important influential factors that will have an indirect impact on the perceived trust. The related results of this study can help designers, practitioners, and researchers of the smart home industry produce products and services with higher perceived trust to improve consumers’ adoption and acceptance so that the market penetration rate of related products and enterprises could be increased, and the maturity and development of the voice-enabled smart home industry could be promoted.

BACKGROUND: The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited. METHODS: This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated. RESULTS: Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced. CONCLUSIONS: Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors. IMPACT: We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors.

Although the utilization of mobile technologies has recently emerged in various educational settings, limited research has focused on cognitive load detection in the pen-based learning process. This research conducted two experimental studies to investigate what and how multimodal data can be used to measure and classify learners' real-time cognitive load. The results found that it was a promising method to predict learners' cognitive load by analysing their handwriting, touch gestural and eye-tracking data individually and conjunctively. The machine learning approach used in this research achieved a prediction accuracy of 0.86 area under the receiver operating characteristic curve (AUC) and 0.85/0.86 sensitivity/specificity by only using handwriting data, 0.93 AUC and 0.93/0.94 sensitivity/specificity by only using touch gestural data, and 0.94 AUC and 0.94/0.95 sensitivity/specificity by using both the touch gestural and eye-tracking data. The results can contribute to the optimization of cognitive load and the development of adaptive learning systems for pen-based mobile learning.

As an emerging artificial intelligence system, social robot could socially communicate and interact with human beings. Although this area is attracting more and more attention, limited research has tried to systematically summarize potential features that could improve facial anthropomorphic trustworthiness for social robot. Based on the literature from human facial perception, product, and robot face evaluation, this paper systematically reviews, evaluates, and summarizes static facial features, dynamic features, their combinations, and related emotional expressions, shedding light on further exploration of facial anthropomorphic trustworthiness for social robot design.

Smart homes, as one of the most prosperous industries of the Internet of Things, have tremendous potential in helping the elderly aging in place and dealing with the global aging society challenges. This study takes the needs of future elderly in China as a starting point and proposes that the core requirement of the aging group is “connectivity”, smart homes for older adults should assist them with connectivity establishment both physically and psychologically to improve their quality of life and help them live an independent, safe, and happy life in their older stage. The article defines the types of elderly connectivity needs as two main types and eight sub-connectivity, and further puts forward thirty smart home subsystems and their implementation elements. Moreover, the research applies the Kano model and questionnaire survey to provide the empirical proof of those thirty smart home subsystems based on the analysis of 371 questionnaire responses. Last but not least, we construct a five-layer architecture and abstract four principles on the connectivity building of a smart home for future Chinese elders. The research explores the possibility of building a wide range of connectivity and all-around happiness smart home environment for future elderly, which provides significant insights and an important reference for both the smart home industry and the pension industry.

With the gradual deepening of environmental problems and the increase in consumer awareness of environmental protection, many enterprises have already begun to pay attention to green supply chain management. However, the price of green products is higher than that of nongreen products, which is an enormous challenge for many small- or medium-sized enterprises. To study the pricing and coordination of green supply chains under capital constraints, a model consisting of a manufacturer and a capital-constrained retailer is established; the manufacturer invests in green products and provides a deferred payment contract. Setting the situation without capital constraints as a benchmark, this study explores the impact of the retailer’s capital constraints on the manufacturer’s product greenness design; an interesting result shows that deferred payment can help encourage the retailer to order more products and improve the profit of the manufacturer and the efficiency of the entire supply chain as well as the product’s greenness level simultaneously. However, the profit of the retailer will be hurt by the deferred payment contract. Therefore, to guarantee the profit of the entire channel and to make the two agents obtain a win-win outcome, a new two-way revenue-sharing contract is designed to coordinate the green supply chain.

BackgroundDBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide‐induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether DBZ could attenuate atherosclerosis at early and advanced stages. Methods and ResultsThe effects of DBZ on the development of atherosclerosis were studied using apolipoprotein E–deficient (apoE−/−) mice. For early treatment, 5‐week‐old apoE−/− mice were fed a Western diet and treated daily by oral gavage with or without DBZ or atorvastatin for 10 weeks. For advanced treatment, 5‐week‐old apoE−/− mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then they were randomly divided into 4 groups and subjected to the treatment of vehicle, 20 mg/kg per day DBZ, 40 mg/kg per day DBZ, or 10 mg/kg per day atorvastatin for the subsequent 10 weeks. We showed that early treatment of apoE−/− mice with DBZ markedly reduced atherosclerotic lesion formation by inhibiting inflammation and decreasing macrophage infiltration into the vessel wall. Treatment with DBZ also attenuated the progression of preestablished diet‐induced atherosclerotic plaques in apoE−/− mice. In addition, we showed that DBZ may affect LXR (liver X receptor) function and that treatment of macrophages with DBZ suppressed lipopolysaccharide‐stimulated cell migration and oxidized low‐density lipoprotein–induced foam cell formation. ConclusionsDBZ potentially has antiatherosclerotic effects that involve the inhibition of inflammation, macrophage migration, leukocyte adhesion, and foam cell formation. These results suggest that DBZ may be used as a therapeutic agent for the prevention and treatment of atherosclerosis.

Faith-based programs have been long regarded as influential social approaches to form positive attitudes to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) within the last few decades. However, recent scholars argue that religions serve a double role in supporting HIV-infected people. Moreover, relevant evidence is mainly collected from studies among participants of the Western religious traditions, such as Christianity. This study applies the theory of the attitude formation model to examine Buddhist factors impacting discriminatory attitudes towards HIV/AIDS and the causal path to positive behavior intention. To investigate its underlying mechanism, Buddhist elements, as an important antecedent, were introduced in the advertisement against HIV/AIDS-related discrimination to influence people’s attitudinal reaction. Results show that Buddhist advertising could significantly increase perceived religiosity and compassion. Then, both perceived religiosity and compassion jointly increase anti-prejudical attitudes towards HIV-infected people and have a positive impact on interaction intention at the end.

Buddhist aesthetics, as a profound intrinsic value of pleasure, has continually attracted scholars to shed light on its influential effects. Its aesthetic nature, however, has drawn on the laws of profound Buddhist thoughts, which is challenging for empiricists to generate evidence for. Though some individual components or factors deriving from Buddhist aesthetics have been developed and exploited in previous studies, a holistic construct of Buddhist aesthetics remains ambiguous and lacks a pragmatically useable measure. This study fills this gap by creating a Buddhist aesthetics scale. A total of fifteen items have been found valid and reliable to measure three determinants, namely, value, acumen, and response. This scale can be used in further empirical studies in designing objects aiming to elicit the unique Buddhist aesthetic experience. Moreover, it can be utilized in measuring Buddhist aesthetics as a determinant in relevant practices, such as religious psychotherapy, cognitive engineering, and business.

Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS), radial strain rate (RSR) and longitudinal strain (LS), showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E', an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS), E/A and E'/A' at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy.

Regular exercise can protect the heart against external stimuli, but the mechanism is not well understood. We determined the role of adenosine monophosphate-activated protein kinase (AMPK) in regulating swimming exercise-mediated cardiac protection against β-adrenergic receptor overstimulation with isoproterenol (ISO) in mice. Ten-week-old AMPKα2+/+ and AMPKα2-knockout (AMPKα2-/-) littermates were subjected to 4 weeks of swimming training (50 min daily, 6 days a week) or housed under sedentary conditions. The mice received daily subcutaneous injection of ISO (5 mg/kg/d), a nonselective β-adrenergic receptor agonist, during the last 2 weeks of swimming training. Swimming training alleviated ISO-induced cardiac fibrosis in AMPKα2+/+ mice but not AMPKα2-/- mice. Swimming training activated cardiac AMPK in AMPKα2+/+ mice. Furthermore, swimming training attenuated ISO-induced production of reactive oxygen species (ROS) and expression of NADPH oxidase and promoted the expression of antioxidant enzymes in AMPKα2+/+ mice but not AMPKα2-/- mice. In conclusion, swimming training attenuates ISO-induced cardiac fibrosis by inhibiting the NADPH oxidase-ROS pathway mediated by AMPK activation. Our findings provide a new mechanism for the cardioprotective effects of exercise.

Aggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a PRS for the risk of recurrence score weighted on proliferation (ROR-P), an established prognostic signature. Using 2363 breast cancers with tumor gene expression data and single nucleotide polymorphism (SNP) genotypes, we examined the associations between ROR-P and known breast cancer susceptibility SNPs using linear regression models. We constructed PRSs based on varying p-value thresholds and selected the optimal PRS based on model r2 in 5-fold cross-validation. We then used Cox proportional hazards regression to test the ROR-P PRS's association with breast cancer-specific survival in two independent cohorts totaling 10,196 breast cancers and 785 events. In meta-analysis of these cohorts, higher ROR-P PRS was associated with worse survival, HR per SD = 1.13 (95% CI 1.06-1.21, p = 4.0 × 10-4). The ROR-P PRS had a similar magnitude of effect on survival as a comparator PRS for estrogen receptor (ER)-negative versus positive cancer risk (PRSER-/ER+). Furthermore, its effect was minimally attenuated when adjusted for PRSER-/ER+, suggesting that the ROR-P PRS provides additional prognostic information beyond ER status. In summary, we used integrated analysis of germline SNP and tumor gene expression data to construct a PRS associated with aggressive tumor biology and worse survival. These findings could potentially enhance risk stratification for breast cancer screening and prevention.