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Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69–5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=

The mass production of grapevines, an agricultural waste, has imposed burdens on farmers and the environment. This study aims to address this issue by utilizing biochar derived from grapevines (GVC) in combination with polybutylene succinate (PBS) to develop an environmentally friendly bio-composite. To enhance the compatibility between GVC and PBS, maleic anhydride grafted PBS (MAPBS) was synthesized and incorporated into the bio-composite. Moreover, surface modification of GVC was conducted using a silane coupling agent to enhance its adhesion to the PBS matrix. The effects of GVC size, MAPBS content, and surface modification on the mechanical and thermal properties of PBS were investigated. The findings indicate that GVC sieved through a 200 mesh screen exhibited a better reinforcing effect compared to GVC sieved through a 120 mesh screen. The tensile test results indicated that the incorporation of 20 wt% GVC led to a reduction in the tensile strength of PBS. However, the introduction of silane-modified GVC resulted in a substantial enhancement of tensile strength, elevating it from 33.40 MPa to 40.16 MPa. Furthermore, when the composites contained both MAPBS and a lubrication agent, the tensile strength increased even further to 41.04 MPa. The thermal analysis results of the bio-composites revealed that the addition of GVC contributed to an increase in the char yield and heat resistance of PBS. Therefore, these GVC/PBS green bio-composites not only enhance the mechanical and thermal properties of PBS but also reuse the waste grapevines, and produce the high value-added green composites with carbon-storing and biodegradability characteristics.

Abstract Background Higher chemokine C-X-C motif ligand 5 (CXCL5) level was observed in type 2 diabetes mellitus (DM) patients; however, its role in diabetic vasculopathy was not clarified. This study aimed to explore the impacts and mechanistic insights of CXCL5 in neovasculogenesis and wound healing in DM. Methods Endothelial progenitor cells (EPCs) and human aortic endothelial cells (HAECs) were used in vitro. Streptozotocin-induced diabetic mice and Leprdb/JNarl mice were used as type 1 and type 2 DM models. Moreover, CXCL5 knockout mice were used to generate diabetic mice. Hindlimb ischemia surgery, aortic ring assays, matrigel plug assay, and wound healing assay were conducted. Results CXCL5 concentrations were increased in plasma and EPCs culture medium from type 2 DM patients. CXCL5 neutralizing antibody upregulated vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1) and promoted cell function in EPCs from type 2 DM patients and high glucose-treated EPCs from non-DM subjects as well as HAECs. CXCL5 directly up-regulated interleukin (IL)-1β/IL-6/tumor necrosis factor-α and down-regulated VEGF/SDF-1 via ERK/p65 activation through chemokine C-X-C motif receptor 2 (CXCR2). CXCL5 neutralizing antibody recovered the blood flow after hindlimb ischemia, increased circulating EPC number, and enhanced VEGF and SDF-1 expression in ischemic muscle. CXCL5 suppression promoted neovascularization and wound healing in different diabetic animal models. The above observation could also be seen in streptozotocin-induced CXCL5 knockout diabetic mice. Conclusions CXCL5 suppression could improve neovascularization and wound healing through CXCR2 in DM. CXCL5 may be regarded as a potential therapeutic target for vascular complications of DM.

Abstract Chemokines are key components in the pathology of chronic diseases. Chemokine CC motif ligand 7 (CCL7) is believed to be associated with cardiovascular disease, diabetes mellitus, and kidney disease. CCL7 may play a role in inflammatory events by attracting macrophages and monocytes to further amplify inflammatory processes and contribute to disease progression. However, CCL7-specific pathological signaling pathways need to be further confirmed in these chronic diseases. Given the multiple redundancy system among chemokines and their receptors, further experimental and clinical studies are needed to clarify whether direct CCL7 inhibition mechanisms could be a promising therapeutic approach to attenuating the development of cardiovascular disease, diabetes mellitus, and kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide and the prevalence of DKD has increased over recent decades. Inflammation is involved in the development and progression of DKD. In this study, we explored the potential role of macrophage inflammatory protein-1β (MIP-1β) in DKD. Clinical non-diabetic subjects and DKD patients with different levels of urine albumin-to-creatinine ratio (ACR) were enrolled in the study. Leprdb/db mice and MIP-1β knockout mice were also used as mouse models for DKD. We found that serum MIP-1β levels were elevated in the DKD patients, especially those with ACRs that were less than or equal to 300, suggesting that MIP-1β is activated in clinical DKD. The administration of anti-MIP-1β antibodies attenuated DKD severity in the Leprdb/db mice, which also showed reduced glomerular hypertrophy and podocyte injury, as well as decreased inflammation and fibrosis, suggesting that MIP-1β plays a role in the development of DKD. The MIP-1β knockout mice showed improved renal function and decreased renal glomerulosclerosis and fibrosis in DKD. Furthermore, podocytes from the MIP-1β knockout mice showed less high glucose-induced inflammation and fibrosis compared to those from wild-type mice. In conclusion, the inhibition or deletion of MIP-1β protected podocytes, modulated renal inflammation, and ameliorated experimental DKD, suggesting that novel anti-MIP-1β strategies could potentially be used to treat DKD.

Several algorithms for nuclear power plant (NPP) break event detection, isolation, localization, and size estimation are proposed. A break event can be promptly detected and isolated after its occurrence by simultaneously monitoring changes in the sensing readings and by employing an interquartile range-based isolation scheme. By considering the multi-sensor data block of a break to be rank-one, it can be located as the position whose lead field vector is most orthogonal to the noise subspace of that data block using the Multiple Signal Classification (MUSIC) algorithm. Owing to the flexibility of deep neural networks in selecting the best regression model for the available data, we can estimate the break size using multiple-sensor recordings of the break regardless of the sensor types. The efficacy of the proposed algorithms was evaluated using the data generated by Maanshan NPP simulator. The experimental results demonstrated that the MUSIC method could distinguish two near breaks. However, if the two breaks were close and of small sizes, the MUSIC method might wrongly locate them. The break sizes estimated by the proposed deep learning model were close to their actual values, but relative errors of more than 8% were seen while estimating small breaks’ sizes.

Management education, continuously evolving since the 1990s, recognizes the need to develop proficient management professional's adept at strategic decision-making. The present research delves into the effectiveness of a management course for first-year students at a chosen School of Management, underlining its paramount importance in ensuring student retention and bolstering departmental stability. The purpose of this research is to evaluate the effectiveness of traditional physical and online learning methods in a management course for first-year students at a university in Taiwan, focusing on students' satisfaction with their learning performance. The study aims to compare the educational efficacy of these two instructional modes and analyze the variations in student performance and satisfaction. The methodology involved a longitudinal design with data collection from first-year students in 2022 (online learning) and 2023 (physical learning). The research employed pre-test and post-test evaluations, regression analysis, and Importance Performance Analysis (IPA) to assess the impact of course units on students' learning satisfaction. This study employed regression analysis to determine the influence of enhancing "Management Basis" and "Management Operations" on satisfaction. The results revealed that online learning outperformed physical learning in terms of overall student satisfaction, particularly in understanding "Management Basis" and "Management Operations." However, physical learning demonstrated higher improvements in student scores and satisfaction, particularly in areas requiring detailed explanations and hands-on engagement, such as "Control Tools.". The novelty of this research lies in its comparative approach to evaluating two distinct learning environments during a critical period marked by the COVID-19 pandemic. The findings offer valuable insights into how different teaching modalities impact student satisfaction and learning outcomes, providing guidance for educators to refine instructional strategies to enhance student learning efficacy across different formats. The study underscores the importance of adapting teaching methods to suit the specific demands of online and physical learning environments.

Reactive oxygen species (ROS) and oxidative stress are associated with the progression of diabetic nephropathy (DN). Hydralazine is an antihypertensive agent and may act as a xanthine oxidase (XO) inhibitor to reduce uric acid levels in a mouse renal injury model. This study aimed to investigate the potential mechanisms of hydralazine in experimental DN. Streptozotocin-induced diabetic mice were fed a high-fat diet to generate DN. Human renal proximal tubular epithelial cells were used in vitro. Nitrendipine and allopurinol which can reduce blood pressure or XO activity levels, were used as two positive controls. Hydralazine downregulated NF-κB/p38 signaling pathways and reduced TNF-α/IL-6 expressions in high glucose-stimulated renal proximal tubular epithelial cells. Hydralazine reduced in vitro ROS production via XO inhibition and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated heme oxygenase (HO)-1 activation. Furthermore, hydralazine reduced high glucose-induced apoptosis by downregulating PARP/caspase-3 signaling. Hydralazine and allopurinol but not nitrendipine reduced serum uric acid levels and systemic inflammation. Hydralazine and allopurinol treatment improved renal function with decreased urinary albumin-to-creatinine ratios, glomerular hypertrophy, glomerulosclerosis, and fibrosis in the kidney of DN mice. While both hydralazine and allopurinol downregulated XO and NADPH oxidase expression, only hydralazine upregulated Nrf2/HO-1 renal expression, suggesting the additional effects of hydralazine independent of XO/ NADPH oxidase inhibition. In conclusion, hydralazine protected renal proximal tubular epithelial cells against the insults of high glucose and prevented renal damage via XO/NADPH oxidase inhibition and Nrf-2/HO-1 activation, suggesting the comprehensive antioxidation and anti-inflammation mechanisms for the management of DN.

BackgroundCardiac rehabilitation (CR) is recommended for patients with acute heart failure (HF). However, the results of outcome studies and meta-analyses on CR in post-acute care are varied. We aimed to assess the medium- to long-term impact of CR and ascertain the predictors of successful CR.MethodsIn this propensity score-matched retrospective cohort study, records of consecutive patients who survived acute HF (left ventricular ejection fraction

Chronic inflammation in diabetes mellitus (DM) is the leading cause of non-healing wounds. Chemokine CC motif ligand 4 (CCL4) is enhanced in the circulation and in the wounds of DM patients. This study aimed to investigate the effect of endogenous CCL4 inhibition on diabetic wound healing. Endothelial progenitor cells (EPCs) and human dermal microvascular endothelial cells (HDMECs) were used. Mice were injected with streptozotocin to generate hyperglycemia. An enhanced CCL4 level as well as decreased tube formation and migration abilities were observed in high-glucose-treated HDMECs and in EPCs from type 2 DM patients. CCL4 inhibition by siRNA restored the damaged cell function by upregulating the Akt/endothelial nitric oxide synthase/vascular endothelial growth factor/stromal cell-derived factor-1α pathways. Wild-type diabetic mice had delayed wound repair, whereas the CCL4-knockout diabetic mice showed an accelerated rate of wound closure. In a Matrigel plug assay, CCL4-knockout diabetic mice showed higher blood vessel and hemoglobin levels. Higher CD31 and Ki67 expression in the wound area and Matrigel plugs was detected in the CCL4-knockout diabetic mice. CCL4-knockout mice had upregulated angiogenic factors and downregulated inflammatory factors. This study might provide the theoretical basis for CCL4 inhibition as a therapeutic option for clinical diabetic wound treatment.

The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.

This study examined the effectiveness of Memrise application in motivating American middle school students to learn Chinese as a foreign language (CFL). Participants (N = 27) in the study were middle school students enrolled in CFL courses in an urban public middle school in the Midwestern region of the United States. During the study, the experimental group used the Memrise application while the control group used the traditional paper-made flashcards to learn new Chinese characters. Results of the mixed-design ANOVA indicated that there was no significant (p > 0.05) difference in the scores between students in the experimental and control groups on Chinese characters acquisition. However, the Group main effect was significant (p < 0.001), indicating that the students in the experimental group had stronger motivation in learning CFL than those in the control group. It is suggested that further research should include a larger sample size and other types of CFL learning applications.

The present study aimed to examine the barriers faced by Taiwanese university English as a foreign language (EFL) instructors when incorporating mobile-assisted language learning (MALL) into their teaching, and to explore how these barriers are influenced by the instructors' background characteristics. To assess the variables, a survey questionnaire was developed and administered to a sample of 350 university instructors. Additionally, interviews were conducted with a subset of instructors to complement and clarify the quantitative data. The findings indicated that university EFL instructors encountered moderate barriers when integrating MALL into their teaching practices. Furthermore, the study identified significant differences in the barriers experienced based on the amount of time instructors dedicated to MALL on a daily basis. Both quantitative and qualitative data highlighted the importance of time as a critical factor for successful MALL integration. As a recommendation, it is advised that university administrators consider reducing instructors' workload to facilitate the seamless integration of MALL.

Purpose: Podcasting is a new mobile technology application for language learning. Drawing upon the stimulus-organism-response model and the interest driven creator (IDC) theory from e-learning, this study aims to develop and test an integrative conceptual framework. This study investigates contextual and environmental stimuli effects (content richness [CR], self-directed learning [SDL] and situational interest [SI]) from a podcast English learning context on learners' experience states (cognitive absorption [CA], pleasure [PL] and arousal [AR]) and their subsequent responses (continuance learning intention [CLI]). Design/methodology/approach: Using 416 valid responses from five universities located in North Taiwan, data analysis is performed using a structural equation model. Findings: The results show that most of the interest factor stimuli (CR, SDL and SI) have significant impacts on learners' experiences (CA, PL and AR), which in turn affect their CLI. Practical implications: The findings provide useful insights for English show podcasters and operators to invest in establishing learners' interest factor and stimulating experiences to improve their CLI. Originality/value: This paper contributes to a better understanding of students who use contextual factors of podcast English learning and how these factors influence their CLI via a framework of stimulus-organism-response and the IDC theory.

This paper aims to explore the narrative expression skill of design students through manipulating image structure. Moreover, narrative expression is the skill of interpreting design with narrative. The study is a classroom experiment conducted naturally, and the experimental data is obtained and analysed by quantitative analysis. We found differences in students' narrative tendencies and richness in overall narrative expression. The teaching and training of design narrative can effectively help students familiarise themselves with the design process and personal skill integration and encourage students to pay attention to the design of elements and content. This will improve students' design competencies under skills different from technology. The paper concludes that students must improve and integrate design competencies through practical methods under other narrative tendencies. Furthermore, the lecturer can explore and adjust design teaching through design narrative training to strengthen or balance students' design performance competency.

Atherosclerosis is an arterial inflammatory disease. The circulating level of the C-C chemokine ligand (CCL4) is increased in atherosclerotic patients. This study aimed to investigate whether CCL4 inhibition could retard the progression of atherosclerosis. In ApoE knockout mice, CCL4 antibody treatment reduced circulating interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels and improved lipid profiles accompanied with upregulation of the liver X receptor. CCL4 inhibition reduced the atheroma areas and modified the progression of atheroma plaques, which consisted of a thicker fibrous cap with a reduced macrophage content and lower matrix metalloproteinase-2 and -9 expressions, suggesting the stabilization of atheroma plaques. Human coronary endothelial cells (HCAECs) and macrophages were stimulated with TNF-α or oxidized LDL (ox-LDL). The induced expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were attenuated by the CCL4 antibody or CCL4 si-RNA. CCL4 inhibition reduced the adhesiveness of HCAECs, which is an early sign of atherogenesis. CCL4 blockade reduced the activity of metalloproteinase-2 and -9 and the production of TNF-α and IL-6 in stimulated macrophages. The effects of CCL4 inhibition on down-regulating adhesion and inflammation proteins were obtained through the nuclear factor kappa B (NFκB) signaling pathway. The direct inhibition of CCL4 stabilized atheroma and reduced endothelial and macrophage activation. CCL4 may be a novel therapeutic target for modulating atherosclerosis.

In this research, the authors analyze the addition of bacterial producer of biological cement on sandy soil to increase its stability. Pseudomonas sp was injected into the soil to produce urease enzyme, which converts urea that reacted with water become ammonium and carbonate, causing calcite precipitation. Soil stability can be improved by the production of pore-filling materials and particle-binding materials through the calcite precipitation process. The aim of these applications is to improve the mechanical properties of soil that it will be more suitable for construction or environmental purposes. After bacterial inoculation, the experiment with variation of bacterial content concluded the best way to increase soil stability is inject 15% bacteria relative to total weight of soil. Highest permeability reduction is 73,73% and highest shear strength increation for cohesion is 6,84 with friction angle 44,46°. California Bearing Ratio test with 10 of hits generated that the treatment soil can proved a significant penetration stress changed. From Environmental Scanning Electron Microscopy test results of the inoculation sand test images and surface scan, the formed exopolysaccharide attached to the wall of the sand soil particles which expected will fill, patch, and close the pores between the sandy soil particles.

The purpose of this study was to research about supplementation of different concentrations of the substrate on the degradation rate of xenobiotic and to determine the optimal concentrations of the auxiliary substrates that are most beneficial of xenobiotic degradation rate. 2,4-dichlorophenol acid (2,4-D) was used representative xenobiotic organic compounds, while peptone and sugar used for auxiliary substrates. The activated sludge was completely break down 100 mg/l of 2,4-D for three consecutive times. The different concentrations between biogenic substracts of sucrose and peptone were fed separately or combined into the medium containing 200 mg/l of 2,4-D and 140 mg SS/l of activated sludge. The results showed that sugar and peptone could affect 2,4-D degradation rate to several different degree at different concentrations. In separate supplementation, 2,4-D degradation completed within 25 hours, 40 mg/l sugar and 150 mg/l peptone concentrations were found to be the optimal concentrations. In combined case, 2,4-D was consumed totally within 20 hours and the optimal concentration of the combined sugar and peptone concentrations were 40 and 150 mg/l, respectively.

Though it is not easy for Western learners to master, the Chinese language has gain its popularity in the United States in recent years. Modern digital instructional technologies can address some of the issues in learning difficulties of the language. This study examined the effects of Quizlet-based learning activities on the attitudes, beliefs, and confidence of urban American high school students (N = 56) in learning Chinese as a second language. Results of the mixed-design ANOVA indicated that students in the experimental group reported a significantly (p < 0.05) more positive attitude toward learning Chinese as a second language than the control group. Though both groups expressed less confidence in their ability in reading, listening, speaking, and learning Chines vocabularies, the experimental group lost lesser degree of confidence in those areas. It is concluded that these Quizlet-based learning activities had a significantly positive effect on students' beliefs and confidence in learning Chinese. Future studies should include a larger sample size that covers each grade level of the high school as well as using other gamification-oriented learning tools to compare their effectiveness on students' confidence in learning Chinese.

BACKGROUND: Therapeutic antibodies targeting the IGF1R have shown diverse efficacy and safety signals in oncology clinical trials. The success of these agents as future human therapeutics depends on understanding the specific mechanisms by which these antibodies target IGF1R signaling. METHODOLOGY/PRINCIPAL FINDINGS: A panel of well-characterized assays was used to investigate the mechanisms by which ganitumab, a fully human anti-IGF1R antibody undergoing clinical testing, inhibits IGF1R activity. Epitope mapping using IGF1R subdomains localized the ganitumab binding site to the L2 domain. Binding of ganitumab inhibited the high-affinity interaction of IGF-1 and IGF-2 required to activate IGF1R in cells engineered for IGF1R hypersensitivity and in human cancer cell lines, resulting in complete blockade of ligand-induced cellular proliferation. Inhibition of IGF1R activity by ganitumab did not depend on endosomal sequestration, since efficient ligand blockade was obtained without evidence of receptor internalization and degradation. Clinically relevant concentrations of ganitumab also inhibited the activation of hybrid receptors by IGF-1 and IGF-2. Ganitumab was not an agonist of homodimeric IGF1R or hybrid receptors in MCF-7 and COLO 205 cells, but low-level IGF1R activation was detected in cells engineered for IGF1R hypersensitivity. This activation seems biologically irrelevant since ganitumab completely inhibited ligand-driven proliferation. The in vivo efficacy profile of ganitumab was equivalent or better than CR and FnIII-1 domain-specific antibodies, alone or in combination with irinotecan. CR domain-specific antibodies only blocked IGF-1 binding to IGF1R but were more potent than ganitumab at inducing homodimer and hybrid receptor downregulation in vitro, however this difference was less obvious in vivo. No inhibition of hybrid receptors was observed with the FnIII-1 domain antibodies, which were relatively strong homodimer and hybrid agonists. CONCLUSIONS/SIGNIFICANCE: The safety and efficacy profile of ganitumab and other anti-IGF1R antibodies may be explained by the distinct molecular mechanisms by which they inhibit receptor signaling.

This study investigated behavioral and cortical mechanisms for short-term postural training with error amplification (EA) feedback in the elderly. Thirty-six elderly subjects (65.7 ± 2.2 years) were grouped (control and EA, n = 18) for training in stabilometer balance under visual guidance. During the training session (8 training rounds of 60 s in Day 2), the EA group received visual feedback that magnified errors to twice the real size, whereas the control group received visual feedback that displayed real errors. Scalp EEG and kinematic data of the stabilometer plate and ankle joint were recorded in the pre-test (Day 1) and post-test (Day 3). The EA group (-46.5 ± 4.7%) exhibited greater post-training error reduction than that of the control group (-27.1 ± 4.0%)(p = 0.020), together with a greater decline in kinematic coupling between the stabilometer plate and ankle joint (EA: -26.6 ± 4.8%, control: 2.3 ± 8.6%, p = 0.023). In contrast to the control group, the EA group manifested greater reductions in mean phase-lag index (PLI) connectivity in the theta (4-7 Hz)(p = 0.011) and alpha (8-12 Hz) (p = 0.027) bands. Only the EA group showed post-training declines in the mean PLI in the theta and alpha bands. Minimal spanning tree analysis revealed that EA-based training led to increases in the diameter (p = 0.002) and average eccentricity (p = 0.004) of the theta band for enhanced performance monitoring and reduction in the leaf fraction (p = 0.030) of the alpha band for postural response with enhanced automaticity. In conclusion, short-term EA training optimizes balance skill, favoring multi-segment coordination for the elderly, which is linked to more sophisticated error monitoring with less attentive control over the stabilometer stance.