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The Ang-(1–7)/MasR axis is critically involved in treating several diseases; For example, Ang-(1–7) improves inflammatory response and neurological function after traumatic brain injury and inhibits post-inflammatory hypothermia. However, its function in traumatic brain injury (TBI) combined with seawater immersion hypothermia remains unclear. Here, we used a mice model of hypothermic TBI and a BV2 cell model of hypothermic inflammation to investigate whether the Ang-(1–7)/MasR axis is involved in ameliorating hypothermic TBI. Quantitative reverse transcription PCR, western blotting assay, and immunofluorescence assay were performed to confirm microglia polarization and cytokine regulation. Hematoxylin-eosin staining, Nissl staining, and immunohistochemical assay were conducted to assess the extent of hypothermic TBI-induced damage and the ameliorative effect of Ang-(1–7) in mice. An open field experiment and neurological function scoring with two approaches were used to assess the degree of recovery and prognosis in mice. After hypothermic TBI establishment in BV2 cells, the Ang-(1–7)/MasR axis induced phenotypic transformation of microglia from M1 to M2, inhibited IL-6 and IL-1β release, and upregulated IL-4 and IL-10 levels. After hypothermic TBI development in mice, intraperitoneally administered Ang-(1–7) attenuated histological damage and promoted neurological recovery. These findings suggest that hypothermia exacerbates TBI-induced damage and that the Ang-(1–7)/MasR axis can ameliorate hypothermic TBI and directly affect prognosis. [ABSTRACT FROM AUTHOR]

Sesquiterpene synthases (STPSs) catalyze carbocation‐driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation‐reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (−)‐cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (−)‐cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo‐electron microscopy‐derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure‐guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311‐S419‐C458]/[M311‐V419‐A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons. [ABSTRACT FROM AUTHOR]

Sesquiterpene synthases (STPSs) catalyze carbocation‐driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation‐reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (−)‐cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (−)‐cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo‐electron microscopy‐derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure‐guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311‐S419‐C458]/[M311‐V419‐A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results and Conclusions Implications With the rapid proliferation of online education, it is incumbent upon teachers to find ways to provide online students with science laboratory experiences. Existing research on online labs focuses heavily on computer‐supported inquiry learning environments, such as virtual laboratories and remote laboratories. There are limited studies on kitchen labs or home labs.This study investigated the effectiveness of home labs using lab kits from two perspectives: students' perceptions and experiences of labs conducted in a home environment, as well as whether home labs help with students' knowledge acquisition.This study employed lab quizzes to assess students' performance and lab reports to evaluate students' ability to interpret the lab results accurately in the authentic home lab contexts. Surveys and semi‐structured interviews were used to collect students' perceptions and experience data regarding these hands‐on experiments at home.We found that students' perceptions of home labs are similar to that of face‐to‐face labs, but they generally perceive home labs to be less complex. Students' performances on lab quizzes and lab reports indicate that the majority of them were able to apply the key scientific concepts to accurately interpret lab results in authentic home lab contexts. Students perceived that home labs provide flexibility and help in connecting learning to the real world. However, they also face challenges such as unexpected results and ambiguity during the process.Based on the key findings from this study and our reflections, four practice guidelines were provided for teaching hands‐on experiments online. [ABSTRACT FROM AUTHOR]

This article investigates the event-based distributed filtering design issue for interval type-2 (IT2) fuzzy systems over sensor networks under deception attacks. In sensor networks, while each sensor receives its measurement value, it can also sense neighbouring one's measurement based on the interconnected topology, thereby estimating system states. To reduce redundant transmission, a novel distributed dynamic event-triggered mechanism (DETM) is introduced to each sensor node. In particular, the proposed DETM contains an internal dynamic variable, which is a filtered version of the trigger event signal to increase the interval between two consecutive event triggers. Then, a new distributed filter error fuzzy system is well constructed under the consideration of DETM, networked-induced delay, and random deception attacks. To relax stability conditions, slack matrices with membership functions (MFs) information are used in the stability analysis. Furthermore, based on Lyapunov–Krasovskii functional approach, membership-functions-dependent sufficient criteria are obtained to ensure the established filter error fuzzy system is mean-square stability with H ∞ performance. Two examples are finally shown to demonstrate the effectiveness of the filtering method. [ABSTRACT FROM AUTHOR]

Summary: This article studies the memory‐based dynamic event‐triggered (MBDET) robust adaptive fuzzy control problem for a class of uncertain nonlinear MASs subject to Backlash‐Like Hysteresis. The considered MASs are modeled as a class of nonlinear leader‐following multiagent systems with multiple inputs for each subsystem, which can be used to model multiple multi‐rotor unmanned aerial vehicle (Multi‐UAV) attitude systems. In the framework of backstepping recursive design, the fuzzy approximation technology, the parameter estimation technology, and the first‐order filtering technology are integrated, and an effective fuzzy adaptive control method is proposed, which solves the problems of Backlash‐Like Hysteresis and external disturbances in the system while avoiding the "explosion of complexity". In order to relieve the communication pressure of Multi‐UAV attitude systems, a novel dynamic memory‐event‐triggered mechanism (DMETM) based on user‐set parameters is developed. Compared with the traditional event‐triggered mechanism, this DMETM has larger triggering time intervals, effectively reduces communication frequency, and has greater flexibility in balancing system performance and communication bandwidth resource constraints. The closed‐loop stability analysis scheme for Multi‐UAV attitude systems is presented by combining the backstepping recursive design technique and Lyapunov stability theory, which proves that closed‐loop stability and tracking performance can be ensured. Finally, the design method is successfully applied to show the effectiveness of the proposed method to solve the dynamic memory‐event‐triggered attitude control problem for nonlinear Multi‐UAVs. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2-mediated COVID-19 may cause sudden cardiac death (SCD). Factors contributing to this increased risk of potentially fatal arrhythmias include thrombosis, exaggerated immune response, and treatment with QT-prolonging drugs. However, the intrinsic arrhythmic potential of direct SARS-CoV-2 infection of the heart remains unknown. Objective: To assess the cellular and electrophysiological effects of direct SARS-CoV-2 infection of the heart using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Methods: hiPSC-CMs were transfected with recombinant SARS-CoV-2 spike protein (CoV-2 S) or CoV-2 S fused to a modified Emerald fluorescence protein (CoV-2 S-mEm). Cell morphology was visualized using immunofluorescence microscopy. Action potential duration (APD) and cellular arrhythmias were measured by whole cell patch-clamp. Calcium handling was assessed using the Fluo-4 Ca2+ indicator. Results: Transfection of hiPSC-CMs with CoV-2 S-mEm produced multinucleated giant cells (syncytia) displaying increased cellular capacitance (75±7 pF, n = 10 vs. 26±3 pF, n = 10; P<0.0001) consistent with increased cell size. The APD90 was prolonged significantly from 419±26 ms (n = 10) in untransfected hiPSC-CMs to 590±67 ms (n = 10; P<0.05) in CoV-2 S-mEm-transfected hiPSC-CMs. CoV-2 S-induced syncytia displayed delayed afterdepolarizations, erratic beating frequency, and calcium handling abnormalities including calcium sparks, large "tsunami"-like waves, and increased calcium transient amplitude. After furin protease inhibitor treatment or mutating the CoV-2 S furin cleavage site, cell-cell fusion was no longer evident and Ca2+ handling returned to normal. Conclusion: The SARS-CoV-2 spike protein can directly perturb both the cardiomyocyte's repolarization reserve and intracellular calcium handling that may confer the intrinsic, mechanistic substrate for the increased risk of SCD observed during this COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge. Although several clinical studies suggested that PLR is able to diagnose PE, there has been no systematic evaluation of the diagnostic utility. To examine the diagnostic accuracy and potential applicability of PLR in the detection of PE. Seven databases were searched using a combination of PLR and PE terms, and all potentially pertinent studies were systematically searched up to March 2023. All potentially relevant studies both prospective and retrospective were reviewed. To assess the diagnostic value of PLR for PE, pooled sensitivity (Sen), specificity (Spe), diagnostic odds ratio (DOR) and area under the summary receiver operating characteristic curve (SROC-AUC) were calculated. Thirteen studies were enrolled in the meta-analysis. In the second and third trimesters, the PLR suggested a diagnostic value for PE with a pooled Sen of 54.7% [95% confidence interval (CI) (51.7, 57.6)], Spe of 77.8% [95% CI (75.5, 80.0)], + LR of 2.457 [95% CI (1.897, 3.182)], -LR of 0.584 [95% CI (0.491, 0.695)], DOR of 4.434 [95% CI (3.071, 6.402)], the SROC-AUC of 0.7296 and the standard error (SE) of 0.0370. For the diagnosis of PE, PLR has a limited sensitivity but an acceptable specificity, and showed moderate accuracy. Further using complete blood count (CBC) indicators such as PLR alone or in combination to diagnose and predict PE could reduce healthcare costs and improve maternal and child prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Ginsenoside Rk1, a novel ginsenoside isolated from red ginseng, has anti-inflammatory and anti-tumor activities. This study was designed to elucidate the role of RK1 in an in vitro 1-methyl-4-phenylpyridinium (MPP+) cell model and an in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of Parkinson's disease (PD). Methods: The grasping test, pole-climbing test, and rotarod test were performed to measure the effects of RK1 on MPTP-induced motor disorders. The expression of tyrosine hydroxylase (TH) and IBA-1 were evaluated by western blotting. CCK-8 and flow cytometry assays were utilized to assess cell viability and apoptosis. Reactive oxygen species (ROS), Lactate dehydrogenase (LDH), and superoxide dismutase (SOD) were detected to analyze the effects of RK1 on oxidative stress. The levels of inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: The results showed that RK1 allayed motor deficit elicited by MPTP in a mouse model. RK1 administration augmented tyrosine hydroxylase (TH) expression in the brain striatum and substantia nigra (SN) of MPTP-treated mice. Moreover, RK1 pretreatment promoted viability and suppressed apoptosis in MPP+-induced PC-12 cells. Further, RK1 also attenuated MPP+-stimulated oxidative stress and inflammatory response in PC-12 cells. Besides, RK1 augmented the level of SIRT3, and SIRT3 deletion counteracted RK1-induced repression on MPP+-elicited apoptosis, oxidative stress, and inflammatory response in PC-12 cells via modulating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Conclusions: RK1 might exert neuroprotective effects against MPP+/MPTP-induced neurotoxicity via activating SIRT3-mediated Nrf2/HO-1 signaling. RK1 might be a promising candidate against PD. [ABSTRACT FROM AUTHOR]

This paper studies scheduling multiple sensors for jointly optimizing remote state estimation and wireless sensor network lifetime. Each sensor in the network sends its packet to the remote center for further estimation over wireless communication channels. Sensors in the network will inevitably run out of battery power due to transmission consumption and then reach the end of sensor network lifetime. This article focuses on the problem how to schedule multiple sensors minimizing the total remote estimation errors and simultaneously prolonging the sensor network lifetime. The problem is formulated as a special class of Markov decision process (MDP), stochastic shortest path (SSP) problem. Under this framework, we first derive a set of conditions to guarantee the optimality of structural policies in SSP. Subsequently, threshold structure of the optimal scheduling scheme is obtained by verifying the conditions. Moreover, two Value-of-Information-based multi-sensor scheduling algorithms and a linear-architecture-based learning algorithm are designed to tackle the curse of dimensionality and unknown channel statistics in large-scale sensor networks. Numerical simulations are given to validate effectiveness of our results. [ABSTRACT FROM AUTHOR]

Acute ocular hypertension (AOH) is the most important characteristic of acute glaucoma, which can lead to retinal ganglion cell (RGC) death and permanent vision loss. So far, approved effective therapy is still lacking in acute glaucoma. PANoptosis (pyroptosis, apoptosis, and necroptosis), which consists of three key modes of programmed cell death—apoptosis, necroptosis, and pyroptosis—may contribute to AOH‐induced RGC death. Previous studies have demonstrated that melatonin (N‐acetyl‐5‐methoxytryptamine) exerts a neuroprotective effect in many retinal degenerative diseases. However, whether melatonin is anti‐PANoptotic and neuroprotective in the progression of acute glaucoma remains unclear. Thus, this study aimed to explore the role of melatonin in AOH retinas and its underlying mechanisms. The results showed that melatonin treatment attenuated the loss of ganglion cell complex thickness, retinal nerve fiber layer thickness, and RGC after AOH injury, and improved the amplitudes of a‐wave, b‐wave, and oscillatory potentials in the electroretinogram. Additionally, the number of terminal deoxynucleotidyl transferase dUTP nick‐end labeling‐positive cells was decreased, and the upregulation of cleaved caspase‐8, cleaved caspase‐3, Bax, and Bad and downregulation of Bcl‐2 and p‐Bad were inhibited after melatonin administration. Meanwhile, both the expression and activation of MLKL, RIP1, and RIP3, along with the number of PI‐positive cells, were reduced in melatonin‐treated mice, and p‐RIP3 was in both RGC and microglia/macrophage after AOH injury. Furthermore, melatonin reduced the expression of NLRP3, ASC, cleaved caspase‐1, gasdermin D (GSDMD), and cleaved GSDMD, and decreased the number of Iba1/interleukin‐1β‐positive cells. In conclusion, melatonin ameliorated retinal structure, prevented retinal dysfunction after AOH, and exerted a neuroprotective effect via inhibition of PANoptosis in AOH retinas. [ABSTRACT FROM AUTHOR]

To increase the efficiency of structural damage identification (SDI) methods and timeously and accurately detect initial structural damage, this research develops an SDI method based on a response surface method (RSM) and an imperialist competitive algorithm (ICA). At first, a Latin hypercube design method is used for experimental design and selection of sample points based on RSM. Then, a high-order response surface surrogate model for the target frequency response and stiffness reduction factor is established. Finally, analysis of variance is performed to assess the overall goodness-of-fit and prediction accuracy of the established model. Then the results obtained are combined with structural dynamic response data to construct objective functions; furthermore, the optimal solution of parameter vector in the objective function is solved based on the ICA. Then damage positioning and quantification can be achieved according to location and degree of change in each parameter; finally, the RSM-ICA-based SDI method proposed is applied to damage identification of high-dimensional damaged simply-supported beam models. To verify the effectiveness of the proposed method, the damage identification results are compared with the results obtained from traditional optimization algorithms. The results indicate that: average errors in the structural stiffness parameters and natural frequency that are identified by the proposed method are 6.104% and 0.134% respectively. The RSM-ICA-based SDI method can more accurately identify the location and degree of damages with more significantly increased identification efficiency and better precision compared to traditional algorithms. This approach provides a novel means of solving SDI problems. [ABSTRACT FROM AUTHOR]

In this article, the secure event-triggered control problem is investigated for multiagent systems (MASs) compromised by Denial-of-Service (DoS) attacks with multiple modes. With the rapid development of information technology, DoS attacks against communication topologies are more and more common in MASs with cyber-physical features. To actively reduce the influences caused by DoS attacks, a secure mode strategy is proposed to make agents switch into the secure mode when attacks occur. In this strategy, each agent accesses or terminates the secure mode with bounded time delays after DoS attacks begin or end. Based on the switched system theory, the secure mode strategy against DoS attacks is modeled as the asynchronous switching between agent models and topologies. Finally, we obtain the sufficient conditions on the frequency and duration of DoS attacks, under which the designed controller can guarantee the consensus of MASs. By practical examples, the MASs with the secure mode strategy are illustrated to have better attack-resistant effectiveness than the ones without the secure mode strategy. [ABSTRACT FROM AUTHOR]

As a new form of tourist accommodation, Airbnb has gained widespread popularity worldwide in Hong Kong. Considering the spatial heterogeneity and multiscale effects, this study employs the Multiscale Geographically Weighted Regression (MGWR) approach to reveal the impact of the built environment on Airbnb distribution in Hong Kong. The main findings are as follows: i) The density of hotels, cultural facilities, and tourist attractions, as well as the supply of residential land and open space (or recreational land), have a significant impact on the spatial distribution of Airbnb and vary according to geographic location; ii) At the local level, open spaces (or recreational land) present positively correlated with Airbnb density in mature tourism areas, yet this correlation reverses in certain localized communities; iii) Factors, such as location, traffic accessibility and caterings, may become less critical for Airbnb's location in highly developed cities like Hong Kong; iv) The density of cultural facilities has a global impact on Airbnb distribution, followed by hotel density, and the effect scale of residential land supply and open spaces (or recreational land) tend to be local. This empirical study can support precise and differentiated planning interventions and policy-making to promote a healthier development of the Airbnb market. • Exploring built environment factors that might have an impact on Airbnb distribution in Hong Kong. • Comparing to OLS, SLM and GWR, the MGWR model has the best analytical performance. • Justifying the factors affecting Airbnb distribution are spatially heterogeneous and act on different scales. • Planning intervention of Airbnb should be focused on the corresponding spatial scales and spatial differences. [ABSTRACT FROM AUTHOR]

This article introduces the evolution of themes and ideas related to the history, theory, and practice of learning analytics within the learning, design, and technology field through four eras. This review provides researchers with a fundamental understanding of the origin of learning analytics from a historical perspective and distinguishes learning analytics from educational data mining. This article also explores the relationship between theory and learning analytics, which provides some guidance for future related learning analytics research. Ethical concerns of learning analytics are also discussed in the hope of providing some guidance for practitioners and future research. [ABSTRACT FROM AUTHOR]

Ice, Cloud, and land Elevation Satellite-2 (ICESat-2), the first photon-counting laser altimetry satellite, is the most advanced on-orbit altimetry system in the world. The data obtained by it contain a large number of background photons, limited by sensitive photon detection system. In this study, a density-based adaptive method (DBAM) for photons detection of ground and canopy method is proposed, which is aimed at solving the problem of signal photons detection in vegetation areas. First, the photon density is homogenized according to the noise photon rate, to reduce the effect of uneven background noise. Then, the ground signal photons were extracted by the search ellipse adaptively changing direction and size along the slope direction to find the maximum density direction. The canopy signal photons were extracted again from the rest photons of the first step by using a vertical elliptical search area. At last of the DBAM, the photons between the ground and the canopy are extracted as vegetation signal photons. The effectiveness of DBAM is evaluated both quantitatively and qualitatively. The results show that the proposed method can effectively detect ground and canopy photons, with the Kappa coefficient of 0.88 and 0.91 of two selected datasets. Compared to the results of ATL08, DBAM can better adapt to the slope, the extracted ground photons have better continuity and can extract more accuracy vegetation photons. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris (AV) is a common dermatosis. For moderate to severe AV, isotretinoin is the first‐line treatment. Chemical peeling with supramolecular salicylic acid (SSA) was developed with water solubility and advanced skin penetration properties. In the present study, we investigated the efficacy and safety of oral low‐dose isotretinoin combined with 30% SSA chemical peeling. Methods: Thirty‐three moderate‐to‐severe acne patients were enrolled and received oral low‐dose (0.2–0.4 mg/kg/d) isotretinoin and were then randomly assigned to receive 30% SSA or not on each side of the face with 2‐week intervals for four sessions. Photos, the number of lesions, GAGS score, skin indices (melanin, erythema, pore, and texture), hydration, and transepidermal water loss (TEWL) were assessed at 0, 2, 4, 6, and 10 weeks. Side effects, efficacy, and satisfactory rates were recorded. Results: A total of 29 patients completed the study. Oral isotretinoin combined with SSA decreased response time compared to isotretinoin monotherapy, with significantly improved GAGS score, count of lesions, and efficacy (%) at 4–6 weeks. Skin indices of melanin, erythema, pore, and texture evaluated at week 10 were improved as well. Oral isotretinoin with or without SSA was effective by the lesion clearance; only SSA significantly improved the TEWL. All the side effects were temporary and tolerable, and no adverse effects were observed. Conclusion: Oral low‐dose isotretinoin combined with 30% SSA is safe and effective, which advanced the onset of action and improves lesion clearance. [ABSTRACT FROM AUTHOR]

Background: Online discussion is one of the commonly used tools to enhance students' interactions and engagements in online courses, but it is not clear how social presence in online discussions impacts students' learning and what kinds of interactions we should encourage. Social network analysis provides a new methodology to investigate how social interactions in online discussions influence learning. Objectives: The study aims to identify students' online discussion interaction patterns and investigate how they are related to students' learning performance in an asynchronous course. Methods: Students who enrolled in an asynchronous undergraduate course were invited to participate in this study. Participants' online discussion participation data were collected from six online discussions from an asynchronous online course. Data were analysed using social network analysis methods as well as correlation and regression analysis. Results and Conclusions: We found that statistically significant positive correlations existed between learning performance and out‐degree and closeness, respectively, which provided evidence to support that social interactions in online discussions have positive correlations with learning. We also found that out‐closeness contributes to students' learning performance. The results of the study imply that knowledge construction occurs mainly in the centre of the outgoing network. By interpreting this study's results with the social construction of knowledge model, we conclude that knowledge construction mainly happens in reading and commenting on others' posts by internalizing and integrating external useful information from others. Implications: While numerous studies have emphasized the importance of interactions in online discussions or collaborative learning, there are limited studies on what kind of interactions we should encourage and what role students play in knowledge construction. The results of this study provide evidence that knowledge construction happens when students are reading and commenting on others' posts, which includes a hidden process of integrating external useful information into their own understanding. Practical strategies are provided to encourage students to be expansive and actively reach out to other students. Lay Description: What is already known about this topic: Vygotsky's social development theory stresses the interaction of interpersonal, cultural‐historical, and individual factors as the key to human development.The interactions among students in asynchronous online discussions play an important role in higher phases of knowledge creation.Some studies have investigated the relationship between knowledge construction and centrality measurements of networks in asynchronous online discussions using social network analysis method, but the results are mixed. What this paper adds: This study investigated the interaction patterns at a deep level by using social network analysis techniques. The three main interaction patterns were found in six online discussions of one online asynchronous course over one semester.The interaction patterns of the networks of these online discussions indicate that the majority of students are not expansive enough; moreover, the network density, transitivity, and clustering coefficient are low.Using social network analysis, this study has found that out‐degree and closeness measurements of the online discussion networks are positively correlated with students' academic performance. This study also found that out‐closeness contributes to students' learning performance. The results of this study imply that outgoing networks play a more crucial role than incoming networks in students' learning performance. It appears that knowledge construction happens mainly in the centre of the outgoing network. Implications for practice and/or policy: Knowledge construction happens when students are reading and commenting on others' posts, which includes a hidden process of integrating external useful information into their own understanding. This process may externalize as reading and commenting on others' posts in online discussions.Expansively interacting with others in online discussions plays a vital role in knowledge construction. It may be beneficial to encourage more student interactions in online discussions, especially encouraging students to be expansive and actively reach out to other students. [ABSTRACT FROM AUTHOR]

This article concentrates on security issues of stochastic event‐based (SEB) sensor scheduling in cyber‐physical systems (CPSs). An SEB attack mechanism is proposed to compromise remote state estimation, in which the attacker can jam the feedback channel and inject false acknowledgments. Based on the Gaussian assumption, the minimum mean square error estimator under the SEB attack is obtained utilizing Bayes' theorem. In this article, the SEB attack stealthiness is composed of communication ratio invariance and anomaly detection invisibility with the forward channel. Furthermore, a double stealthy attack condition is given to complete persistent attacks from the perspective of the attacker. Aiming at maximizing average error covariances on the remote estimator, we design a generation algorithm of optimal SEB stealthy attack sequence and prove its optimality by rearrangement inequality and mathematical induction. Finally, the scalar and networked dc motor vector system simulations illustrate the corresponding theoretical results. [ABSTRACT FROM AUTHOR]

This article studies the event-based adaptive practical fixed-time decentralized control problem for a class of large-scale uncertain nonlinear systems subject to non-affine nonlinear faults. By fusing the techniques of fixed-time control and command filter, the problems such as singular-value and computational explosion in fixed-time control based on backstepping design framework are solved. Based on the fuzzy approximation theory and Butterworth low-pass filter (BLPF) technique, the non-affine nonlinear fault terms are processed and fault-tolerant controllers are designed to realize fault compensation. In order to relieve the communication the pressure between system components, a novel switching event-triggering mechanism (SETM) based on user-set threshold parameters is proposed. This switching threshold design the scheme combines the advantages of the traditional fixed threshold and relative threshold design strategies, providing greater flexibility in balancing system performance and network constraints. By combining the practical fixed-time stability criterion with the Lyapunov stability theory, it is demonstrated that both the tracking performance and the closed-loop stability can be ensured in a fixed-time. Finally, two simulation examples are given to verify the effectiveness of the proposed fixed-time switching event-triggered control (SETC) scheme. [ABSTRACT FROM AUTHOR]

Melatonin is involved in exerting protective effects in aged-related and neurodegenerative diseases through a silent information regulator type 1 (SIRT1)-dependent pathway. However, little was known about the impact of melatonin on retinal ganglion cell (RGC) senescence and apoptosis following optic nerve crush (ONC). Thus, this study aimed to examine the effects of melatonin on RGC senescence and apoptosis after ONC and investigate the involvement of SIRT1 in this process. To study this, an ONC model was established. EX-527, an inhibitor of SIRT1, was injected intraperitoneally into mice. And melatonin was administrated abdominally into mice after ONC every day. Hematoxylin & eosin staining, retina flat-mounts and optical coherence tomography were used to evaluate the loss of retina cells/neurons. Pattern electroretinogram (p-ERG) was performed to evaluate the function of RGCs. Immunofluorescence and western blot were used to evaluate protein expression. SA-β-gal staining was employed to detect senescent cells. The results demonstrated that melatonin partially rescued the expression of SIRT1 in RGC 3 days after ONC. Additionally, melatonin administration partly rescued the decreased RGC number and ganglion cell complex thickness observed 14 days after ONC. Melatonin also suppressed ONC-induced senescence and apoptosis index. Furthermore, p-ERG showed that melatonin improved the amplitude of P50, N95 and N95/P50 following ONC. Importantly, the protective effects of melatonin were reversed when EX-527 was administered. In summary, this study revealed that melatonin attenuated RGC senescence and apoptosis through a SIRT1-dependent pathway after ONC. These findings provide valuable insights for the treatment of RGC senescence and apoptosis. [Display omitted] • Melatonin rescued the expression of SIRT1 in RGC after ONC. • Melatonin alleviated ONC-induced RGC senescence and apoptosis. • EX-527, an inhibitor of SIRT1, could suppress the neuroprotective effects of melatonin. • Melatonin exerted its neuroprotective effects through a SIRT1-dependent pathway after ONC. • These findings may offer a valuable insight into the therapeutic potential of melatonin for RGC senescence and apoptosis. [ABSTRACT FROM AUTHOR]

A new arc-consistent viscous-spring artificial boundary (ACVAB) was proposed by changing a traditional flat artificial boundary based on the theory of viscous-spring artificial boundaries. Through examples, the concept underpinning the establishment and specific setting of the boundary in the finite element software were described. Through comparison with other commonly used artificial boundaries in an example for near-field wave analysis using the two-dimensional (2D) half-space model, the reliability of the ACVAB was verified. Furthermore, the ACVAB was used in the numerical analysis of the effects of an earthquake on underground structures. The results were compared with the shaking table test results on underground structures. On this basis, the applicability of the ACVAB to a numerical model of seismic response of underground structures was evaluated. The results show that the boundary is superior to common viscous-spring boundaries in terms of accuracy and stability, and therefore, it can be used to evaluate radiation damping effects of seismic response of underground structures and is easier to use. [ABSTRACT FROM AUTHOR]

Summary: In this article, the memory‐based dynamic event‐triggered controller design issue is investigated for networked interval type‐2 (IT2) fuzzy systems under non‐periodic denial‐of‐service (DoS) attacks. For saving limited network bandwidth, a novel memory‐based dynamic event‐triggered mechanism (DETM) is proposed to schedule data communication. Unlike existing event‐triggered generators, the developed memory‐based DETM can utilize a series of newly released signals and further save network resources by introducing interval dynamic variables. Moreover, to improve design flexibility, an IT2 fuzzy controller with freely selectable fuzzy rule number and premise membership functions (MFs) is synthesized. Then, a new switched time‐delay system with imperfectly matched MFs is established under the consideration of memory‐based DETM and DoS attacks simultaneously. Besides, based on the property of MFs, the boundary information of membership grades and slack matrices are introduced in the stability analysis. Furthermore, by using a piecewise Lyapunov–Krasovskii method, membership‐functions‐dependent criteria are deduced to ensure the asymptotic stability of built fuzzy switched systems. Finally, the effectiveness of proposed control strategies is demonstrated by simulation examples. [ABSTRACT FROM AUTHOR]

This article is concentrated on the stabilization problem of inertial memristive neural networks (IMNNs) with time-varying delay. Here, removing the reduced order method, the stabilization of delayed IMNNs is directly studied under the framework of the second-order system. To decrease control cost, the aperiodically intermittent control strategy is adopted. This strategy implies that work time (with control input) alternates with rest time (without control input), and every work or rest width may be different. By constructing a suitable Lyapunov functional, some algebraic criteria are achieved to guarantee the stabilization of the considered system. Note that the obtained control gains are often larger than practical needs due to the conservatism deriving from inevitable inequality scaling. For further saving control resources, an intermittent adaptive control strategy is applied to stabilize the delayed IMNNs. Finally, a numerical example is exhibited to confirm the availability of the developed theoretical outcomes. [ABSTRACT FROM AUTHOR]

The Madden–Julian Oscillation (MJO) phase 7 has been recognized as a driver for Northern Hemisphere (NH) sudden stratospheric warmings (SSWs) in the literature recently. However, uncertainties remain on the exact relationship between MJO phase 3 and the stratospheric polar vortex. Here, we re‐examined and compared the observed evolution of the MJO before the two types of NH extreme stratospheric polar vortex events (i.e. strong vortex (SV) events and weak vortex (WV) events) in this study. Our analysis reveals that MJO phase 3 (7) is the dominant intraseasonal variability mode in about 2 weeks before onset of the SV (WV) events, suggesting these two phases are closely linked to variation in the intensity of the stratospheric polar vortex. MJO phase 3 (7) leads to a strengthened (weakened) polar vortex due to the suppressed (enhanced) wave‐number 1 wave activity in the extratropical stratosphere resulting from destructive (constructive) interference between the negative (positive) Pacific–North American (PNA)‐like pattern induced by MJO phase 3 (7) and the background field. Note that the time‐scales for the peak responses of wave activity in the extratropical stratosphere to MJO phases 3 and 7 are around 2 weeks and 1 week, respectively. Thus, within 2 weeks, MJO phase 3 (7) can be treated as the precursor to the strengthened (weakened) polar vortex. [ABSTRACT FROM AUTHOR]

Purpose: The magnetic compression technique (MCT) is a new surgical method that has been used for gastrointestinal anastomosis, choledochojejunostomy, and intestinal anastomosis, but there are no reports on its use for esophagogastric anastomosis. This study aimed to investigate the feasibility of using MCT to fashion esophagogastric anastomoses in rabbits. Methods: Twenty rabbits were randomized into an MCT group (study group, n = 10) and a hand-sewn group (control group, n = 10). The magnetic compression anastomosis device used in this study was made of neodymium iron boron (NdFeB) and possessed parent (PMR) and daughter (DMR) magnetic rings. To fashion the anastomosis, the PMR and DMR were inserted into the lower esophagus and gastric fundus, respectively. The coupled magnets automatically compressed the sandwiched tissues and were expelled once the anastomosis was installed. The two groups were further compared in terms of the anastomosis construction time, survival rate, and postoperative complications. One month after the anastomosis was installed, the burst pressure and gross appearance of the anastomoses were evaluated. Results: The anastomosis construction time in the study group was significantly shorter than that in the control group (10.50 ± 1.58 min vs. 18.60 ± 2.22 min; P < 0.05), and the magnetic rings were defecated out in 10.70 ± 3.49 days. The incidence of anastomotic blockage in both the study and control groups did not differ significantly (0%, 0/10 vs. 20%, 2/10; P > 0.05). Anastomotic leakage was not found in either of the groups, and the anastomoses burst pressures were similar in the two groups. However, the magnetically compressed anastomoses in the study group had a relatively smoother gross appearance than the hand-sewn anastomoses. Conclusion: The magnetic compression anastomosis device is a safe and feasible tool for fashioning esophagogastric anastomoses in this animal model. [ABSTRACT FROM AUTHOR]

Construction project cost prediction is an important function in construction-related fields; it can provide an important basis for project feasibility study and design scheme comparison and selection, and its accuracy will directly affect the investment decision of the project. The successful realization of construction cost prediction can bring great convenience to the control and management of construction cost. The purpose of this paper is to study a fast, accurate, convenient, deducible, and rational construction project cost prediction method, to provide a basis for the cost management of the whole life cycle of the project. Therefore, this paper uses particle swarm optimization algorithm to improve BP neural network and proposes a novel construction project cost prediction algorithm based on particle swarm optimization-guided BP neural network. Aiming at the defects of BP neural network updating weights and thresholds with the gradient descent method, this paper uses the advantages of particle swarm optimization in the field of parameter optimization to optimize BP neural network with PSO algorithm. The structure of BP neural network weights and the threshold of each neuron in the coding, through intelligent search for each particle, find the most suitable weights and thresholds, so that the BP neural network has faster convergence speed, better generalization ability, and higher prediction precision. Simulation results also show that the proposed algorithm is competitive enough. [ABSTRACT FROM AUTHOR]

This paper investigates the problems of decentralized adaptive neural network (NN) secure control for a class of nonstrict-feedback nonlinear interconnected large-scale systems (NILSs) under denial-of-service (DoS) attacks. The considered systems contain not only unknown interconnected terms but also general nonlinear functions that are not required to be globally Lipschitz, in contrast to most of the existing results in the area. When the system subject to the DoS attack, the sampled data can neither be sent by the sensors nor received by the actuators due to the appearance of DoS in the sensor-to-controller (S-C) and the controller-to-actuator (C-A) communication channels. The data packets sent from the sensors are blocked and the traditional backstepping technology cannot be adopted. In order to solve this difficulty, a novel dynamic gain observer is constructed, which can obtain the desired states from the NILSs under DoS attacks. Considering the energy limitation of attackers, two reasonable Assumptions of DoS attack intensity are given. The stability is proven based on the Lyapunov stability theory (LST) and the improved average dwell time (ADT) method. The proposed controller guarantees that all signals in closed-loop systems are bounded, while the tracking error signals converge to a small residual set. Finally, two simulation examples are provided to illustrate the effectiveness of the proposed control method. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides‐Zinc (QDTP‐Zn) complex. The present study investigated the protective effects of QDTP‐Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP‐Zn (0.2 and 0.4 g kg−1 day−1).QDTP‐Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP‐Zn also regulated colon tissue injury by upregulating ZO‐1 and occludin protein expression, at the same time as downregulating tumor necrosis factor‐α and interleukin‐6β levels. Furthermore, QDTP‐Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short‐chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid.In summary, QDTP‐Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP‐Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This article studies the problem of event‐triggered consensus for linear multiagent systems. Leaderless and leader‐following cases are considered here. By adopting adaptive technology and utilizing the relationship between parameters, novel fully distributed control schemes are proposed. Both the control updates and the communication consumption between agents can be declined under the designed hybrid event‐triggered controller. Meanwhile, different from some existing event‐based control schemes, the projection operator is avoided so that the developed controllers use only local signal, which relies on neither the minimum nonzero eigenvalue of the Laplacian matrix nor the total number of agents. The designed control schemes can ensure that leaderless and leader‐following consensus to be achieved asymptotically, and Zeno behavior is excluded by presenting a hybrid event‐triggered mechanism. Simulation examples are provided to demonstrate the effectiveness of the presented control protocols. [ABSTRACT FROM AUTHOR]

This paper considers an energy‐constrained sensor power allocation problem for remote estimation under Denial‐of‐Service attack. Due to power constraints, the sensor needs to make a decision on how much power it should employ to optimise the state estimation performance under Denial‐of‐Servic attacks without using real‐time acknowledgment information. Different from the existing works concerning non‐zero power value with discrete values or one power value, the authors consider the multilevel continuous‐valued energy allocation policy containing zero power value in this work. By analysing the effects on performance index under different energy allocation policies, an optimal off‐line power scheduling policy with non‐decreasing structure is derived. To obtain the optimal power scheduling sequences, the authors formulate the problem as non‐linear programming after analysing the probability distribution of the estimation error covariance matrix. Moreover, the two power values energy allocation policy is investigated as a special case. At last, simulation examples are presented to verify the effectiveness of their theoretical results. [ABSTRACT FROM AUTHOR]

This paper focuses on the observer‐based resilient event‐triggered security control issue for networked T‐S fuzzy‐model‐based systems suffered from energy‐limited Denial‐of‐Service (DoS) attacks. Firstly, a novel resilient adaptive event‐triggered mechanism (AETM) is designed to deal with the packet losses problem induced by energy‐limited DoS attacks. Specifically, the resilient AETM threshold is adaptively updated based on the latest available packages. Secondly, according to Lyapunov theory, membership‐function‐dependent stabilisation criterions are obtained to ensure the control systems are stable with H∞ performance. Besides, the mismatched premise variables between model and controller are considered, and a slack matrix with the membership functions information is introduced to relax stability conditions. Then, the relationship between allowable duration of DoS attack and resilient AETM parameter is clarified. An algorithm is also presented to derive the resilient AETM parameter and observer‐based controller gains simultaneously. Finally, two examples are provided to demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

From the security of multi-agent systems (MASs), this paper investigates false-data injection attacks that cooperatively compromise communication links to stealthily destabilize the leader-following control process. Different from centralized systems, the communication coupling of MASs enables attackers to have more complex adverse influences. In view of this, we focus on how attacks perform ripple effect by spreading their influences to the agents receiving no compromised communication data. First of all, the existence of cooperative false-data injection (CFDI) attacks is studied based on the spectral radius of system matrices. Further, we explore attack ripple effect from the relations between impaired agents and attack targets against communication links. Therefore, with the geometric and algebraic properties of edge-to-node incidence matrices, a necessary and sufficient condition of minimum attack targets is developed. On this basis, the protection targets of communication data are qualitatively analyzed to resist CFDI attacks in MASs. The numerical simulations conducted on a group of two-link planar robots illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

As a typical class of Cyber-Physical Systems (CPSs), microgrids (MGs) are susceptible to malicious cyber attacks and disturbances that can compromise their security and reliability. To address this issue, an event-triggered distributed resilient control method is proposed in this paper to mitigate the impacts of disturbances, FDI and DoS attacks on MGs. The proposed approach employs a piecewise control strategy and utilizes adaptive method to achieve the secondary control objective of MGs. In order to conserve computing and communication resources, an event-triggered mechanism is adopted and its parameter selection is associated with attacks. This design ensures system stability while also eliminating Zeno behavior. By applying Lyapunov stability theory, it can be proven that the algorithm proposed in this paper is capable of achieving the desired control objective. Finally, the effectiveness and superiority of the developed method are demonstrated through simulation examples. • We propose a control algorithm to solve the problems caused by simultaneous disturbances, FDI, and DoS attacks on MGs. • The employed adaptive control tackles unknown-upper-bound FDI attacks and disturbances on any number of DGs. • To ensure system stability, an attack-related event-triggered mechanism is employed in this study. [ABSTRACT FROM AUTHOR]

Polysaccharides (TCMPs) derived from traditional Chinese medicines (TCMs), such as Ganoderma lucidum , Astragalus membranaceus , Lycium barbarum , and Panax ginseng , are considered to be the main active constituents in TCMs. However, the significant pharmacological effects of orally administered TCMPs do not align well with their poor pharmacokinetics. This article aims to review the literature published mainly from 2010 to 2022, focusing on the relationship between pharmacokinetics and pharmacological effects. It has been found that unabsorbed TCMPs can exert local pharmacological effects in the gut, including anti-inflammation, anti-oxidation, regulation of intestinal flora, modulation of intestinal immunity, and maintenance of intestinal barrier integrity. Unabsorbed TCMPs can also produce systemic pharmacological effects, such as anti-tumor activity and immune system modulation, by regulating intestinal flora and immunity. Conversely, some TCMPs can be absorbed and distributed to various tissues, especially the liver, where they exhibit tissue-protecting effects against inflammation and oxidative stress-induced damage and improve glucose and lipid metabolism. In future studies, it is important to improve quality control and experimental design. Furthermore, research on enhancing the oral bioavailability of TCMPs, exploring the activity of TCMP metabolites, investigating pharmacokinetic interactions between TCMPs and oral drugs, and developing oral drug delivery systems using TCMPs holds great significance. [Display omitted] [ABSTRACT FROM AUTHOR]

This paper investigates the security state estimation issue facing replay attacks in confidential cyber–physical systems. Smart sensor equipped with a power harvester transmits critical measurements to the remote estimator over wireless networks, in which the transmission modes include encrypted and normal. In order to complete the persistent threats, the adversary launches multi-stage discontinuous replay attacks to compromise the estimation process. In virtue of the designed label detection scheme, we transform attack detection into encryption scheduling optimization under the constraint of sensor energy harvesting and acquire a rigorous relationship between detection probability, attack duration, and encryption ratio. Different from most existing studies only focusing on attack detection, the localization of replay interval measured by detection immediacy is also analyzed. Subsequently, the optimal periodic encryption scheduling strategy is given to maximally determine the attack interval by adopting an optimization-based approach. Further, a complete algorithm of replay attack detection, isolation, and recovery (RADIR) is designed to minimize deterioration from multi-stage attacks, which can guarantee the estimated performance of the system as much as possible. Finally, the unmanned ground vehicle system is applied to validate the theoretical results, where the dataset of replay attacks is obtained by capturing the normal operation data of a moving vehicle. Also, we compare the optimal encryption strategy designed in this paper with general centralized and random scheduling strategies. [ABSTRACT FROM AUTHOR]

Summary: This article studies the static output feedback (SOF) secure control issue for cyber‐physical systems against replay attacks. The fundamental purpose focuses on how to stabilize the closed‐loop system regardless of whether the replay attacks occur. First, a detection scheme is presented that can find the behavior of the adversary and recognize which sensor suffers from the attacks. Then, the SOF controller is designed and the adverse influence induced by the replay attacks can be eliminated through the detection information. Thereafter, a sufficient condition has been established which guarantees the closed‐loop system is stable and satisfies a prescribed H∞ performance. Finally, simulation results verify the effectiveness and superiority of the presented design and detection scheme. [ABSTRACT FROM AUTHOR]

Caveolin-3 (Cav-3) is an essential scaffolding protein for caveolae formation in cardiomyocytes and targets multiple long QT syndrome (LQTS)-associated ion channels. Mutations in CAV3 have caused an LQT3-like accentuation in late sodium current, I Na (Nav1.5). Here, we characterize a novel CAV3-V37L variant and determine whether it is the substrate for the patient's LQTS. The proband was a 39-year-old female with drug-induced, sudden cardiac arrest (SCA) with profound QT prolongation (QTc > 600 ms). Genetic testing revealed a rare CAV3-V37L variant of uncertain significance (VUS). Whole-cell patch clamp technique was used to measure I Ks , I Kr , I Na , and I Ca, L currents co-expressed with either CAV3-WT or CAV3-V37L in TSA201 cells and to measure the action potential duration (APD) in control human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) overexpressed with CAV3-WT or CAV3-V37L. CAV3-V37L did not affect Nav1.5 late current. Instead, CAV3-V37L resulted in 1) I Ca, L with slower inactivation, a 1.5 fold increase in peak I Ca, L current density and a 1.1 fold increase in I Ca, L persistent current, 2) dramatically reduced I Ks peak current density by 74.9%, 3) significantly reduced I Kr peak current density by 31.1%, and 4) significantly prolonged the APD in hiPSC-CMs. These functional validation assays enabled the promotion of CAV3-V37L from VUS status to a likely pathogenic variant. Although Nav1.5 was spared, this monogenetic insult precipitated an oligo-proteomic impact with a concomitant gain-of-function of I Ca, L and loss-of-function of both I Ks and I Kr culminating in a marked prolongation of the cardiomyocyte's action potential duration. • Cav3-V37L did not increase Nav1.5 (SCN5A) late current. • CAV3-V37L increased I Ca, L inactivation tau, peak, and persistent current. • CAV3-V37L dramatically reduced the I Ks current and reduced I Kr peak current. • CAV3-V37L reduced intensity of CAV3 on the membrane and co-localization with Cav1.2 channel. • CAV3-V37L prolonged APD50 and APD90 when overexpressed in control hiPSC-CMs. [ABSTRACT FROM AUTHOR]

Summary: In this article, an adaptive fuzzy output feedback control method is presented for nonlinear time‐delay systems with time‐varying full state constraints and input saturation. To overcome the problem of time‐varying constraints, the integral barrier Lyapunov functions (IBLFs) integrating with dynamic surface control (DSC) are applied for the first time to keep the state from violating constraints. The effects of unknown time delays can be removed by using designed Lyapunov‐Krasovskii functions (LKFs). An auxiliary design system is introduced to solve the problem of input saturation. The unknown nonlinear functions are approximated by the fuzzy logic systems (FLS), and the unmeasured states are estimated by a designed fuzzy observer. The novel controller can guarantee that all signals remain semiglobally uniformly ultimately bounded and satisfactory tracking performance is achieved. Finally, two simulation examples illustrate the effectiveness of the presented control methods. [ABSTRACT FROM AUTHOR]

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)-induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription-quantitative PCR results indicated that inhibition of miR-125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR-125a abrogated this effect. Furthermore, dual-luciferase reporter assay results identified that 3-hydroxy-3-methyglutaryl-coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR-125a. Moreover, HMGCR knockdown, similarly to miR-125a overexpression, suppressed HG-induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin-induced diabetes mellitus, it was demonstrated that miR-125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG-induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR-125a mimic. Therefore, the present results suggest that decreased miR-125a expression contributed to HG-induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR-125a-mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis. [ABSTRACT FROM AUTHOR]

This paper investigates the security of cyber-physical systems (CPSs) in the presence of periodic denial-of-service (DoS) attacks with energy harvester. The objective is designing periodic DoS attacks to maximize the attack performance on estimation error. For the jammer equipped with an energy harvester, two scenarios are studied: the energy harvester collects constant or time-varying energy during every period. For the first scenario, we present the optimal periodic attack strategy by dealing with the Markov decision process. For the second scenario, we offer an algorithm to obtain the optimal attack strategy, which is an improved strategy search method adopted to solve the optimization problems. The numerical results are presented to illustrate the effectiveness of proposed methods. [ABSTRACT FROM AUTHOR]