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Nutricines, the nutritionally active substances in feed, play a vital role in enhancing immune function, antioxidant activity, and feed efficiency in dairy cows. Identifying nutricines in total mixed ration (TMR) provides insights into feed quality and their impact on dairy cow health. However, due to the structural diversity of nutricines, data mining using multivariate variable models faces challenges in exploring their relationships. To address this, this study established a hierarchical clustering and optimization factor strategy for 13 common flavonoid peaks detected using apparent data and HPLC-DAD. The establishment of the flavonoid fingerprint of TMR diet in dairy cows detected 13 common peaks, five of which were found using standard products: p-coumaric acid, sinapic acid, tricin, and diosmetin. In vitro fermentation results using different TMR samples in substrate fermentation indicated that the dry matter disappearance rate, NH3-N, acetate, propionate, butyrate, isovalerate, and valerate changes varied significantly (p < 0.05). In spectrum–activity relationship studies, P2, P6, P8, P9, P10, and P11 were all considered possible factors causing this effect. In the analysis of optimization factor strategy, the peak spectrum model of four fermentation parameters, i.e., pH, dry matter digestibility, NH3-N, and acetate, was constructed after optimization (p < 0.05), and the data model is listed in the main text. In structure–activity relationship studies, ferulic acid, isoferulic acid, methyl sinapic acid, methyl 4-hydroxycinnamate, and p-hydroxybenzalacetone may serve as candidate references for compound 10 and may play an important role in affecting the digestibility of dry matter in in vitro fermentation. These findings highlight the role of flavonoids in TMR feed as key factors in maintaining dairy cow health and differentiating nutritional value. This study proposes a novel method for future TMR diet formulation and quality evaluation, with potential implications for improving dairy cow health and performance. Further research is needed to validate these findings and elucidate the mechanisms underlying nutricine effects on dairy cow nutrition and health.

Dendrobium officinale polysaccharide (DOP), which serves as a prebiotic, exhibits a variety of biological activities, including hypoglycemic activities. However, the effects of DOP on diabetes prevention and its hypoglycemic mechanisms are still unclear. In this study, the effects of DOP treatment on the prediabetic mice model were studied and the mechanism was investigated. The results showed that 200 mg/kg/d of DOP reduced the relative risk of type 2 diabetes mellitus (T2DM) from prediabetes by 63.7%. Meanwhile, DOP decreased the level of LPS and inhibited the expression of TLR4 by regulating the composition of the gut microbiota, consequently relieving the inflammation and alleviating insulin resistance. In addition, DOP increased the abundance of SCFA (short chain fatty acid)-producing bacteria in the intestine, increased the levels of intestinal SCFAs, promoted the expression of short-chain fatty acid receptors FFAR2/FFAR3, and increased the secretion of the intestinal hormones GLP-1 and PYY, which helped to repair islet damage, suppress appetite, and improve insulin resistance. Our results suggested that DOP is a promising functional food supplement for the prevention of T2DM.

As a natural fermentation system, the rumen ecosystem of ruminants can efficiently degrade plant cellulose, indicating that the rumen microbiome offers an opportunity for anaerobic digestion to utilize biomass wastes containing cellulose. Knowledge of the response of the in situ microbial community to citrus pomace during anaerobic fermentation will help improve the current understanding of citrus biomass waste utilization.

As a pre-clinical assessment, the present study aimed to investigate the safety and effectiveness of a novel valved pulmonary arterial conduit constructed entirely from biomaterials by transplanting it in the outflow tract of the right ventricle in sheep. Under extracorporeal circulation, the valved pulmonary arterial conduit was used to replace the pulmonary artery of sheep with a beating heart. The performance was assessed at 30, 90 and 180 days post-surgery. Hemodynamic and structural changes were evaluated, and safety was assessed after 180 postoperative days. The hemodynamic effect and biosafety of the implant were further evaluated by observing the changes in various pressure indicators of the heart, echocardiographic results, anatomical and pathological examination results, liver and kidney functions, routine blood tests, a blood coagulation test, and other test results following implantation of the purely biotic valved conduit. The conduit was successfully implanted in 12 sheep and no mortality occurred postoperatively. During the 180-day follow-up, there was no obvious stenosis or regurgitation of the right ventricular outflow tract and pulmonary valve after valved conduit implantation. The findings of autopsy, pathology and laboratory examinations were unremarkable. The implantation of this biosynthetic vascular graft into animals meets the safety and effectiveness requirements for clinical application. This pulmonary arterial conduit has potential clinical application for children with complex congenital heart disease who require pulmonary artery reconstruction to achieve a radical cure.

Developing low-cost and highly efficient catalysts toward the efficient oxygen evolution reaction (OER) is highly desirable for photoelectrochemical (PEC) water splitting. Herein, we demonstrated that N-incorporation could efficiently activate NiFeOx catalysts for significantly enhancing the oxygen evolution activity and stability of BiVO4 photoanodes, and the photocurrent density has been achieved up to 6.4 mA cm−2 at 1.23 V (vs. reversible hydrogen electrode (RHE), AM 1.5 G). Systematic studies indicate that the partial substitution of O sites in NiFeOx catalysts by low electronegative N atoms enriched the electron densities in both Fe and Ni sites. The electron-enriched Ni sites conversely donated electrons to V sites of BiVO4 for restraining V5+ dissolution and improving the PEC stability, while the enhanced hole-attracting ability of Fe sites significantly promotes the oxygen-evolution activity. This work provides a promising strategy for optimizing OER catalysts to construct highly efficient and stable PEC water splitting devices.

Disruption of the blood–brain barrier (BBB) has been considered as a major pathological change in stroke. eNOS/NO play a key role in maintain BBB function. Myricetin is one of the common flavones widely exists in food and fruit, show certain protective effect on the brain function. This experiment establishes oxygeneglucose deprivation and reoxygenation (OGD/R) brain cell model. The regulated effects of Myricetin on BBB function, eNOS/NO and eNOS uncoupling were evaluated. To investigate the molecular mechanism, Akt and Nrf2 inhibitor were also used. The result showed that Myricetin could significantly decreased the enhancement of endothelial permeability and inflammation in OGD/R model, in addition regulated eNOS/NO pathway. The regulate effect in endothelial permeability and eNOS activity by Myricetin were both decreased when combined with Akt inhibitor or Nrf2 inhibitor, and was abrogated when combined with Akt and Nrf2 inhibitor simultaneously. The regulated effect on eNOS uncoupling by Myricetin were abrogated when combined with Nrf2 inhibitor, but not with Akt inhibitor. In conclusion, Myricetin showed significant protect effect on ischemia/reperfusion-induced brain endothelial permeability, and related to simultaneously regulated Akt pathway and improvement of eNOS uncoupling through Nrf2 pathway. Keywords: Ischemia/reperfusion injury, eNOS/NO, eNOS uncoupling, Myricetin

Background Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte injury, which induced by metabolic disorder. Nowadays, there is still a lack of drugs for the treatment of DCM. Growth differentiation factor 11 (GDF11) is a novel member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in DCM remain largely unknown. Methods In this study, we sought to determine whether GDF11 could prevent DCM. The mouse model of diabetes was established by administering a high-fat diet and intraperitoneal injecting streptozotocin. After that, intramyocardial injection of an adeno-associated virus carrying GDF11 gene was used to achieve myocardium-specific overexpression. Results Our data showed that GDF11 overexpression remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression was observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were also eliminated by SIRT1 depletion. Conclusion Our results demonstrated for the first time that GDF11 protected against DCM by regulating SIRT1 signaling pathway, and GDF11 had the potential to become a novel target for reversing cardiac dysfunction in diabetic patients.

Acute myocardial dysfunction in patients with sepsis is attributed to oxidative stress, inflammation, and cardiomyocyte loss; however, specific drugs for its prevention are still lacking. Tetrahydrocurcumin (THC) has been proven to contribute to the prevention of various cardiovascular diseases by decreasing oxidative stress and inflammation. This study was performed to investigate the functions and mechanism of action of THC in septic cardiomyopathy.After the oral administration of THC (120 mg/kg) for 5 consecutive days, a mouse model of sepsis was established via intraperitoneal lipopolysaccharide (LPS, 10 mg/kg) injection. Following this, cardiac function was assessed, pathological section staining was performed, and inflammatory markers were detected.Myocardial systolic function was severely compromised in parallel with the accumulation of reactive oxygen species and enhanced cardiomyocyte apoptosis in mice with sepsis. These adverse changes were markedly reversed in response to THC treatment in septic mice as well as in LPS-treated H9c2 cells. Mechanistically, THC inhibited the release of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, by upregulating mitogen-activated protein kinase phosphatase 1, to block the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK). Additionally, THC enhanced the levels of antioxidant proteins, including nuclear factor-erythroid 2-related factor 2, superoxide dismutase 2, and NAD(P)H quinone oxidoreductase 1, while decreasing gp91Our findings indicate that THC exhibited protective potential against septic cardiomyopathy by reducing oxidative stress and inflammation through the regulation of JNK/ERK signaling. The findings of this study provide a basis for the further evaluation of THC as a therapeutic agent against septic cardiomyopathy.

SARS‐CoV‐2, the virus responsible for the global coronavirus disease (COVID‐19) pandemic, attacks multiple organs of the human body by binding to angiotensin‐converting enzyme 2 (ACE2) to enter cells. More than 20 million people have already been infected by the virus. ACE2 is not only a functional receptor of COVID‐19 but also an important endogenous antagonist of the renin‐angiotensin system (RAS). A large number of studies have shown that ACE2 can reverse myocardial injury in various cardiovascular diseases (CVDs) as well as is exert anti‐inflammatory, antioxidant, anti‐apoptotic and anticardiomyocyte fibrosis effects by regulating transforming growth factor beta, mitogen‐activated protein kinases, calcium ions in cells and other major pathways. The ACE2/angiotensin‐(1‐7)/Mas receptor axis plays a decisive role in the cardiovascular system to combat the negative effects of the ACE/angiotensin II/angiotensin II type 1 receptor axis. However, the underlying mechanism of ACE2 in cardiac protection remains unclear. Some approaches for enhancing ACE2 expression in CVDs have been suggested, which may provide targets for the development of novel clinical therapies. In this review, we aimed to identify and summarize the role of ACE2 in CVDs.

Mitochondrial unfolding protein response (UPRmt) effectively resists the pathological cardiac hypertrophy and improves the mitochondrial function. However, the specific activation mechanism and drugs that can effectively activate UPRmt in the cardiac muscle are yet to be elucidated. The aim of this study was to determine the regulation role of UPRmt on preventing pathological cardiac hypertrophy by tetrahydrocurcumin (THC) and explore its underlying molecular mechanism. Male C57BL/6J wild-type (WT) mice were divided into a control group and subjected to sham treatment for 4 weeks, and a test group which was subjected to transverse aortic constriction (TAC) surgery. Animals in the control and test group were orally administered THC (50 mg/kg) for 4 weeks after TAC procedure; an equivalent amount of saline was orally administered in the control sham-treated group and the TAC group. Subsequently, oxidative stress and UPRmt markers were assessed in these mice, and cardiac hypertrophy, fibrosis, and cardiac function were tested. Small interfering RNA (siRNA) targeting proliferator-activated receptor-gamma coactivator (PGC)-1α and activating transcription factor 5 (ATF5) were used to determine the UPRmt activation mechanism. THC supplement partly upregulated UPRmt effectors and inhibited TAC-induced oxidative stress compared with TAC-operated WT mice, thereby substantially attenuating contractile dysfunction, cardiac hypertrophy, and fibrosis. Furthermore, PGC-1α knockdown blunted the UPRmt activation and the cardioprotective role of THC. The interaction between PGC-1α and ATF5 was tested in neonatal rat cardiac myocytes under normal conditions. The results showed that PGC-1α was an upstream effector of ATF5 and partly activated UPRmt. In vitro, phenylephrine- (PE-) induced cardiomyocyte hypertrophy caused ATF5 upregulating rather than downregulating corresponding to the downregulation of PGC-1α. The PGC-1α/ATF5 axis mediated the UPRmt activation and stress-resistance role of THC in vitro. Collectively, the present study provides the first evidence that PGC-1 and ATF5 can form a signaling axis to partly activate UPRmt that mediates the cardioprotective role of THC in pathological cardiac hypertrophy.

Background Laboratory studies demonstrate glucose‐insulin‐potassium ( GIK ) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin‐glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double‐blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass , GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KC l) or placebo treatment was administered intravenously at 1 mL /kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in‐hospital major adverse cardiac events including all‐cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate‐1 and protein kinase B in the hearts of GIK ‐treated patients. Systemic blood lactate was also reduced in GIK ‐treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in‐hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK . Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT 01516138.

Mitochondrial unfolding protein response (UPRmt) effectively resists the pathological cardiac hypertrophy and improves the mitochondrial function. However, the specific activation mechanism and drugs that can effectively activate UPRmt in the cardiac muscle are yet to be elucidated. The aim of this study was to determine the regulation role of UPRmt on preventing pathological cardiac hypertrophy by tetrahydrocurcumin (THC) and explore its underlying molecular mechanism. Male C57BL/6J wild-type (WT) mice were divided into a control group and subjected to sham treatment for 4 weeks, and a test group which was subjected to transverse aortic constriction (TAC) surgery. Animals in the control and test group were orally administered THC (50 mg/kg) for 4 weeks after TAC procedure; an equivalent amount of saline was orally administered in the control sham-treated group and the TAC group. Subsequently, oxidative stress and UPRmt markers were assessed in these mice, and cardiac hypertrophy, fibrosis, and cardiac function were tested. Small interfering RNA (siRNA) targeting proliferator-activated receptor-gamma coactivator (PGC)-1α and activating transcription factor 5 (ATF5) were used to determine the UPRmt activation mechanism. THC supplement partly upregulated UPRmt effectors and inhibited TAC-induced oxidative stress compared with TAC-operated WT mice, thereby substantially attenuating contractile dysfunction, cardiac hypertrophy, and fibrosis. Furthermore, PGC-1α knockdown blunted the UPRmt activation and the cardioprotective role of THC. The interaction between PGC-1α and ATF5 was tested in neonatal rat cardiac myocytes under normal conditions. The results showed that PGC-1α was an upstream effector of ATF5 and partly activated UPRmt. In vitro, phenylephrine- (PE-) induced cardiomyocyte hypertrophy caused ATF5 upregulating rather than downregulating corresponding to the downregulation of PGC-1α. The PGC-1α/ATF5 axis mediated the UPRmt activation and stress-resistance role of THC in vitro. Collectively, the present study provides the first evidence that PGC-1 and ATF5 can form a signaling axis to partly activate UPRmt that mediates the cardioprotective role of THC in pathological cardiac hypertrophy.

Xiaowu Wang,1,* Bo Xu,1,* Hongliang Liang,1 Shuyun Jiang,1 Hongmei Tan,1 Xinrong Wang,1 Xia Wang,2 Shiqiang Yu,1 Jincheng Liu1 1Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China; 2Department of Health Statistics, Faculty of Preventive Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China *These authors contributed equally to this work Purpose: Oral warfarin anticoagulation is a long-term treatment that is required after heart valve replacement. This treatment can prevent serious complications, such as embolism, thereby increasing patients’ postoperative survival rates and quality of life. Patients treated with artificial mechanical heart valve replacement were followed up over the phone at different times after the procedure, which is an effective method for preventing accidents related to postoperative oral warfarin anticoagulation. Our goal was to determine a method for providing theoretical guidance to patients on oral warfarin anticoagulation following heart valve replacement. Patients and methods: The participants of this study were patients who received artificial mechanical heart valve replacements and were followed up for 2 years after the procedure. Patient adherence to medical advice was calculated, and the distribution characteristics of adherence to prescribed timing, prescribed dose, and regular clinical follow-up among patients of both sexes and of different ages, regions, and educational levels attained were compared. Results: Univariate and multifactorial logistic regression analyses were used to evaluate the factors influencing adherence. Our analyses showed that adherence to oral warfarin anticoagulation in patients after heart valve replacement is influenced by sex, age, residential location, and educational attainment. The medication habits of patients can be evaluated accordingly via phone follow-up. As such, dose adjustment recommendations can be provided, significantly increasing the adherence to oral warfarin anticoagulation in patients after heart valve replacement. Conclusion: Adherence to oral warfarin anticoagulation among patients after heart valve replacement is affected by sex, age, type of residence, and educational level, as well as adherence to clinical follow-up over the phone. The follow-up sessions help establish good doctor–patient communication, which is critical for timely medication guidance, thus shortening medication administration delays and decreasing the overall length of therapy. Keywords: warfarin, artificial mechanical heart valve replacement, AMHVR, telephone follow-up, adherence, distribution characteristics

Objectives The aim of this study was to evaluate the safety and feasibility of total arch repair with open placement of a novel double-branched stent graft for acute Type A aortic dissection (TAAD). Methods We retrospectively analysed the effect of the double-branched stent graft for total aortic arch placement with acute TAAD from December 2013 to February 2015. The effectiveness of the open placement of the double-branched stent graft was estimated by complete thrombus obliteration of the false lumen surrounding it on computed tomography angiography. Follow-up was performed at 6 months postoperatively and annually thereafter. Results The double-branched stent graft was successfully placed into the true lumen of the descending aorta, aortic arch, left subclavian artery and left common carotid artery through the delivery system in 21 patients with acute TAAD. The mean cardiopulmonary bypass time was 210.2 ± 32.4 min, the mean aortic cross-clamp time was 94.9 ± 18.0 min, and the selective cerebral perfusion and deep hypothermia cardiopulmonary arrest time was 27.0 ± 10.4 min. The in-hospital mortality rate was 4.8%. The mean follow-up duration was 38.2 ± 12.5 months. No severe complications related to the surgery or residual dissection occurred during the follow-up. All survivors resumed normal activities. Conclusions The novel double-branched stent graft is proved to be safe and effective for total arch repair with acute TAAD in this study. It would be a new selective method for total arch repair in patients with acute TAAD. Clinical registration number Research on pathogenic risk factors or characteristic features and clinical treatment of aortic dissection in Chinese Population (20120216-4).

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9–CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9’s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis.

The non-deterministic nature of multi-threaded workloads running on multi-core platforms often leads to notable performance variability from run to run. Such variability makes experimental results prone to misinterpretations or misguided claims. To deal with such variability, statistical inference methods are usually used to summarize the experimental results with certain confidence levels by running the experiments or measurements a large number of times. However, such statistical results are often too vague or too simplistic. They are not sufficient to help users understand the causes of such variability, and allow more in-depth analysis on the results or reproduce the results for validation during design space exploration. To allow better analyzability and reproducibility, we propose a framework to tackle such variability, called VarCatcher. The key to VarCatcher is to characterize a parallel execution using Parallel Characteristics Vector (PCV). A clustering-based approach is then used to group runs with similar execution characteristics that can later be used to analyze results in-depth, to customize different evaluation strategies, reproduce the result for variability, to determine the impact of features, or to assist performance diagnosis. We have built a prototype of VarCatcher that includes a user-level toolset for runtime monitoring and measurements using the Intel Processor Trace feature on commodity Intel processors as well as an architecture extension with very low runtime overheads (around 3 and 0.01 percent accordingly). Several case studies confirm that VarCatcher enables several appealing features such as in-depth result analysis, customized evaluation strategies, and reproducibility.

Nowadays, with the rapid development of information technologies (e.g. web 2.0, cloud computing and virtual reality) and manufacturing technologies (e.g. additive manufacturing), users become more actively involved in the product development stage to create personalized products with higher efficiency. This emerging manufacturing paradigm is known as mass personalization, of which user experience (e.g. emotional factors and product utility), co-creation (e.g. user participation), and product change (e.g. modular design) are regarded as three key characteristics. In previous studies, researchers often treat each characteristic separately with an illustrative example to demonstrate its significant effect respectively. They, however, cannot fully reflect the product development process for mass personalization, and may cause inconsistency in implementing the existing methods into real cases. To fill the gap, this work proposes a three-model based (i.e. physical model, cyber model and user experience model) generic framework for conducting user experience based product development for mass personalization. A case study of a personalized smart wearable product development is described, of which the three key characteristics are considered collectively. It can also be seen as a typical case integrating the frontier techniques to enable mass personalization. The authors hope this work can provide some useful guidance to product designers and engineer-to-order companies.

Through the synergies of advanced IT technologies in sensor network and hardware infrastructure, both industrial and consumer products are evolving rapidly to carry more smart features. To sharpen competitive edge in global market, manufacturers today ought to enable their customers to personalize their products to meet diversifying customer needs (CNs). However, the increasing complexity of smart product is dramatically expanding the design space due to over-loaded smart features, which results in significant challenges in the personalization of smart products. Typically, manufacturers operating in a configure-to-order (CTO) manner would adopt a mass customization strategy and implement it with a product configuration system (also known as product configurator). The user experience (UX) of personalizing products by conducting product configuration is crucial for encouraging customer retention and loyalty. This project studied the product personalization process for smart products by observing a group of customers conducting a series of product configuration tasks in several types of product configurators we developed for different platforms (web-based and Virtual Reality (VR) based version). By analyzing mental and physical reaction of the customer, a more systematic understanding of user preference has been attained. The proposed VR-based approach for realizing customer-centric product personalization has been proved to be valid and should be a valuable reference in the future development of the product configuration system.

Bacillus pumilus is one of the most characterized microorganisms that are used for high-level production of select industrial enzymes. A novel B. pumilus SCU11 strain possessing high alkaline protease activity was obtained in our previous work. The culture supernatant of this strain showed efficient dehairing capability with minimal collagen damage, indicating promising potential applications in the leather industry. In this study, the strain's extracellular proteome was identified by LC-MS/MS-based shotgun proteomic analysis, and their related secretory pathways were characterized by BLAST searches. A total of 513 proteins, including 100 actual secreted and 413 intracellular proteins, were detected in the extracellular proteome. The functions of these secreted proteins were elucidated and four complete secretory systems (Sec, Tat, Com, and ABC transporter) were proposed for B. pumilus. These data provide B. pumilus a comprehensive extracellular proteome profile, which is a valuable theoretical and applicative basis for future genetic modifications and development of industrial enzymes.

C1q-tumor necrosis factor-related protein-3 (CTRP3) is an adipokine, which exerts protective function in ischemic or diabetic heart injury. However, the role of CTRP3 in cardiac hypertrophy remains unclear. The aim of this study was to investigate the pharmacological effects of CTRP3 on pathological cardiac hypertrophy induced by hypertension. Male C57BL/6 J wild-type (WT) mice, Ctrp3 knockout mice, and mice infected with lentivirus overexpressing mouse Ctrp3 underwent sham surgery or transverse aortic constriction (TAC) surgery. After 4 weeks, cardiac hypertrophy, fibrosis, and cardiac function were examined. Compared with WT mice, Ctrp3 deficiency substantially impaired contractile dysfunction, exacerbated the enlargement of cardiomyocytes and myocardial fibrosis, and reprogramed the expression of pathological genes after TAC. Conversely, CTRP3 overexpression played a role in restoring the left ventricular cardiac contractile function, alleviating cardiac hypertrophy and fibrosis, and inhibiting the expression of hypertrophic and fibrotic signaling in mice after TAC. Furthermore, CTRP3 regulated the expression of the p38/CREB pathway and of the primary modulating factors of the endoplasmic reticulum stress, i.e., GRP78 and the downstream molecules eukaryotic translation inhibition factor 2 submit α, C/EBP homologous protein, and inositol-requiring enzyme-1. Further, inhibition of p38 MAPK by SB203580 blunted the ER stress intensified by Ctrp3 deficiency. In vitro, CTRP3 protected neonatal rat cardiac myocytes against phenylephrine-induced cardiomyocyte hypertrophy. We conclude that CTRP3 protects the host against pathological cardiac remodeling and left ventricular dysfunction induced by pressure overload largely by inhibiting the p38/CREB pathway and alleviating p38-induced ER stress.

Detecting concurrency bugs, such as data race, atomicity violation and order violation, is a cumbersome task for programmers. This situation is further being exacerbated due to the increasing number of cores in a single machine and the prevalence of threaded programming models. Unfortunately, many existing software-based approaches usually incur high runtime overhead or accuracy loss, while most hardware-based proposals usually focus on a specific type of bugs and thus are inflexible to detect a variety of concurrency bugs. In this paper, we propose Hydra, an approach that leverages massive parallelism and programmability of fused CPU-GPU architectures to simultaneously detect multiple concurrency bugs in threaded software, including data race, atomicity violation and order violation. Hydra extends contemporary fused CPU and GPU by introducing two modules: 1) a trace collecting module (TCM) that instruments and collects program behavior on CPU; 2) a trace preprocessing module (TPM) that processes and then transfers the traces to GPU for bug detection. Furthermore, Hydra exploits three optimizations to improve speed and accuracy, which includes: 1). using the bloom filter to filter out unnecessary traces; 2). avoiding eviction of shared traces; 3). comparing only last-write traces for shared data with the happens-before relation. Hydra incurs small hardware complexity and requires no changes to internal critical-path processor components such as cache and its coherence protocol, and is with about 1.1 percent hardware overhead under a 32-core configuration. Experimental results show that Hydra only introduces about 0.18 percent overhead on average for detecting one type of bugs and 0.46 percent overhead for simultaneously detecting multiple bugs, yet with the similar detectability of a heavyweight software bug detector (e.g., Helgrind).

Objective This study aimed to evaluate the safety and feasibility of total endovascular repair of the aortic arch using a novel designed stent-graft system (Yanger stent-graft system; Lifetech Scientific, Shenzhen, China) in vitro and in a canine model. Methods The Yanger stent-graft system is composed of a main stent-graft, branched stent-graft, and a delivery system. In an in vitro aortic arch simulation test bench, the system was tested, and the success rate of stent-graft releasing, anchoring, and positioning was recorded and analyzed. Meanwhile, in vivo implantation of the Yanger stent-graft system was carried out in 16 healthy adult crossbreed dogs. The feasibility of using these stent-grafts was evaluated with aortography, multislice computed tomography, and autopsy 6 months after the procedure. Results All stent-graft releasing and positioning were successful for in vitro test. In the canine model, the Yanger stent-graft system was placed successfully in the aortic arch in all 14 dogs with the exception of 2 mortalities. All dogs survived for at least 3 months with normal physiologic signs. Aortography, multislice computed tomography, and animal necropsy revealed good fixation in all cases. The ascending aorta, descending aorta, brachiocephalic trunk, and left subclavian artery were all covered without endoleak. There was no significant obstruction or stenosis in brachiocephalic branches at the 6-month follow-up. Conclusions Total endovascular repair of aortic arch with the novel designed Yanger stent-graft system is safe and feasible in preclinical studies. With a better understanding of preclinical knowledge, patient selection criteria and first-in-human studies will be addressed.

Pterostilbene (PT), an analog of resveratrol, exerts a potent anti-inflammatory effect. However, the protective effects of PT against inflammation in endothelial cells have not been elucidated. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of endothelial cell inflammation. In this study, we explored the effect of PT on the tumor necrosis factor-α (TNF-α)-induced inflammatory response in human umbilical vein endothelial cells (HUVECs) and elaborated the role of ERS in this process. TNF-α treatment significantly upregulated the levels of inflammation-related molecules in cell culture media, increased the adhesion of monocytes to HUVECs, and enhanced the expression of the MMP9 and ICAM proteins in HUVECs. Additionally, TNF-α potently increased ERS-related protein levels, such as GRP78 and p-eIF2α. However, PT treatment reversed the increased production of inflammatory cytokines and the adhesion of monocytes to HUVECs, as well as reduced the TNF-α-induced effects exerted by ERS-related molecules. Furthermore, thapsigargin (THA), an ERS inducer, attenuated the protective effect of PT against TNF-α-induced inflammation and ERS in HUVECs. Additionally, the downregulation of ERS signaling using siRNA targeting eIF2α and IRE1 not only inhibited ERS-related molecules but also simulated the therapeutic effects of PT on TNF-α-induced inflammation. In summary, PT treatment potently attenuates inflammation in vascular endothelial cells, which at least partly depends on the reduction of ERS.

Cloud manufacturing (CMfg) promotes a dynamic distributed manufacturing environment by connecting the service providers and manages them in a centralized way. Due to the distinct production capabilities, the service providers tend to be delegated services of different granularities. Meanwhile, users of different types may be after services of different granularities. A traditional aggregate production planning method is often incapable of dealing with type of problems. For this reason, a multi-level aggregate service planning (MASP) methodology is proposed. The MASP service hierarchy is presented, which integrates the services of different granularities into a layered structure. Based on this structure, one of data mining technologies named time series is introduced to provide dynamic forecast for each layer. In this way, MASP can not only deal with the services of multi-granularity, but also meet the requirements of all related service providers irrespective of their manufacturing capabilities. A case study has been carried out, showing how MASP can be applied in a CMfg environment. The results of the prediction are considered reliable as the order of magnitude of the production for each service layer is much greater than that of the corresponding mean forecast error.

Sharing Economy promotes Shared Manufacturing (SharedMfg) that allows self-organized individuals to get involved in manufacturing activities through peer-to-peer (P2P) collaborations. It extends the scope and depth of resources sharing and enables society-based manufacturing integration. SharedMfg is complex and is still in its infancy. It demands encouraging research to clarify the concept and understand the key operations. In this paper, the SharedMfg is analysed along with two significant manufacturing evolutional trends, (i.e., Servitization and Industry 4.0). Based on this, to reduce the complexities in operations, the concept and definition of SharedMfg are presented on the basis of a service hierarchy that includes Product-Service System, Configuration-Service System and Resource-Service System. At the same time, this paper looks SharedMfg as an independent socialization manufacturing mode (e.g. compared with Cloud Manufacturing), and also, the benefit in contributing to the integration of the manufacturing and service sectors is revealed. However, apart from the complexity, high-degree dynamics and uncertainties related to service operations challenge the application of SharedMfg as well. To meet both requirements, based on the construction of a three-dimensional SharedMfg Service (SMS) modelling framework, a hybrid integration and interoperable SharedMfg architecture is proposed to ensure the provision of SMS in efficiency and effectiveness. Furthermore, a dynamic SMS scheduling method in support of the technologies of Complex Network Analysis is presented. A case study associated with the networked fabrication of an assistive glove is applied by implementing a prototype system to validate the proposed frameworks and methods. Finally, an experiment for evaluating the efficiency of service matching is carried out to prove the SharedMfg that can provide better performance than Cloud Manufacturing and Social Manufacturing.