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In this paper, we deal with the following chemotaxis-Stokes model with non-Newtonian filtration slow diffusion (namely, p > 2 ) { n t + u ⋅ ∇ n = ∇ ⋅ ( | ∇ n | p − 2 ∇ n ) − χ ∇ ⋅ ( n ∇ c ) , c t + u ⋅ ∇ c − Δ c = − c n , u t + ∇ π = Δ u + n ∇ φ , div u = 0 in a bounded domain Ω of R 3 with zero-flux boundary conditions and no-slip boundary condition. Similar to the study for the chemotaxis-Stokes system with porous medium diffusion, it is also a challenging problem to find an optimal p-value ( p ≥ 2 ) which ensures that the solution is global bounded. In particular, the closer the value of p is to 2, the more difficult the study becomes. In the present paper, we prove that global bounded weak solutions exist whenever p > p ⁎ ( ≈ 2.012 ) . It improved the result of [21] , [22] , in which, the authors established the global bounded solutions for p > 23 11 . Moreover, we also consider the large time behavior of solutions, and show that the weak solutions will converge to the spatially homogeneous steady state ( n ‾ 0 , 0 , 0 ) . Comparing with the chemotaxis-fluid system with porous medium diffusion, the present convergence of n is proved in the sense of L ∞ -norm, not only in L p -norm or weak-* topology.

Objective: Early lactate clearance was associated with mortality in sepsis patients, but needs further clarification whether it should be adjusted according to the age. Our study aimed to investigate the predictive value of early 6-hour lactate clearance rate with the mortality rate of septic shock patients according to age stratification.Methods and Results: This was a prospective, single center and observational study. A total of 261 patients with mean age of 69.5 years were enrolled. Male patients accounted for 61.6%, with a total mortality rate of 47.5%. The blood lactate levels (LAC1) of patients showed no significnat differences between Survival Group and Death Group (P=0.767) during ICU admission. However, after 6-hour treatment, the blood lactate levels of patients in Survival Group were significantly lower compared to Death Group (P65 years and ≤65 years was 0.778 and 0.845. AUC value of ROC curve for patients >80 years and ≤80 year old was 0.751 and 0.818. However, the lactate clearance rate showed no significant differences between Survival Group patients of different age (P= 0.5413 and P=0.338), respectively.Conclusion: In clinical practice, The blood lactate levels (LAC1) of patients showed no significnat differences between Survival Group and Death Group,but early 6-hour lactate clearance rate could be used to predict the mortality rate of patients with age stratification, with optimal accuracy.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA which has been identified to be involved in alternative non-homologous end joining (A-NHEJ) pathways by binding with PARP1 and LIG3 in myeloma cells. This study aims to explore the roles of MALAT1 in DNA repair processes in non-small cell lung cancer (NSCLC). The interactions between MALAT1 and proteins were identified by co-immunoprecipitation and RNA pulldown. The interactions between MALAT1 and microRNAs (miRNA) were predicted by bioinformatics tools and confirmed by luciferase assay and RNA pulldown. The DNA damages were quantified by comet assay. The cell viability was examined by MTT assay and the cell apoptosis was determined by flow cytometry. MALAT1 is identified to be involved in A-NHEJ pathway in NSCLC cells. However, in LIG3-null cells where A-NHEJ pathway is inactivated, targeting MALAT1 still increases DNA damages, suggesting that MALAT1 participates in other DNA repair pathways. Subsequently, MALAT1 is identified to bind with miR-146a and miR-216b, which directly target the 3′UTR of BRCA1. MALAT1 is confirmed to functions as a competing endogenous RNA (ceRNA) absorbing miR-146a and miR-216b, upregulating BRCA1 expression and protecting Homologous Recombination (HR) pathway in NSCLC cells. Finally, overexpression MALAT1 protects NSCLC cells from the cytotoxic effect of cisplatin. While, targeting MALAT1 in NSCLC cells induces DNA damages by repressing HR pathway and sensitizes NSCLC cells to cisplatin which had the potential for NSCLC treatment. MALAT1 is involved in HR pathway by protecting BRCA1 and targeting MALAT1 induces DNA damages in NSCLC.

In this paper, we consider the following system { u t = Δ u − χ ∇ ⋅ ( u ∇ ω ) , v t = d v Δ v − ξ ∇ ⋅ ( v ∇ ω ) , m t = d m Δ m + u − m , ω t = − ( γ 1 u + m ) ω , in two dimensional space with zero-flux boundary conditions. This model was proposed by Franssen et al. [7] to characterize the invasion and metastatic spread of cancer cells. We first establish the global existence of uniformly bounded global strong solutions. Then using the decay of ECM and the positivity of MDE, we further improve the regularity of obtained solutions, and achieve the uniform boundedness of solutions in the classical sense. Subsequently, we also prove the uniqueness of solutions. After that, we turn our attention to the large time behavior of solutions, and show that the global classical solution strongly converges to a semi-trivial steady state in the large time limit.

Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor Bmal1. A high-salt diet induces a phase shift in Bmal1 expression in the renal inner medulla that is dependent on endothelin type B (ETB) receptors. Furthermore, ETB receptor-mediated natriuresis is sex dependent. Therefore, experiments tested the hypothesis that collecting duct Bmal1 regulates blood pressure in a sex-dependent manner. We generated a mouse model that lacks Bmal1 expression in the collecting duct, where ETB receptor abundance is highest. Male, but not female, collecting duct Bmal1 knockout (CDBmal1KO) mice had significantly lower 24-h mean arterial pressure (MAP) than flox controls (105 ± 2 vs. 112 ± 3 mmHg for male mice and 106 ± 1 vs. 108 ± 1 mmHg for female mice, by telemetry). After 6 days on a high-salt (4% NaCl) diet, MAP remained significantly lower in male CDBmal1KO mice than in male flox control mice (107 ± 2 vs. 113 ± 1 mmHg), with no significant differences between genotypes in female mice (108 ± 2 vs. 109 ± 1 mmHg). ETB receptor blockade for another 6 days increased MAP similarly in both male and female CDBmal1KO and flox control mice. However, MAP remained lower in male CDBmal1KO mice than in male flox control mice (124 ± 2 vs. 130 ± 2 mmHg). No significant differences were observed between female CDBmal1KO and flox mice during ETB blockade (130 ± 2 vs. 127 ± 2 mmHg). There were no significant genotype differences in amplitude or phase of MAP in either sex. These data suggest that collecting duct Bmal1 has no role in circadian MAP but plays an important role in overall blood pressure in male, but not female, mice.

Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management.

Various routing protocols have been proposed for ad hoc networks such as the Internet of Things (IoT). Most of the routing protocols introduced for IoT are specific to applications and networks. In the current literature, it is essential to configure all the network nodes with a single proposed protocol. Moreover, it is also possible for a single IoT network to consist of different kinds of nodes. Two or more IoT networks can also be connected to create a bigger heterogeneous network. Such networks may need various routing protocols with some gateway nodes installed. The role of gateway nodes should not be limited to the interconnection of different nodes. In this paper, a multi-mode hybrid routing mechanism is proposed that can be installed on all or a limited number of nodes in a heterogenous IoT network. The nodes configured with the proposed protocols are termed smart nodes. These nodes can be used to connect multiple IoT networks into one. Furthermore, a game-theory-based model is proposed that is used for intercommunication among the smart nodes to gain optimal efficiency. Various performance matrices are assessed under different network scenarios. The simulation results show that the proposed mechanism outperforms in broader heterogeneous IoT networks with diverse nodes.

IntroductionThis study aimed to investigate the prevalence of developmental regression in children with Autism Spectrum Disorder (ASD) and to explore its relationship with disease severity.MethodsWe finally included 1,027 ASD children aged 2–5 years from 13 cities in China: 138 with regressive ASD and 889 with non-regressive ASD. The Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) were used to evaluate the core symptoms and developmental status of children in the two groups.ResultsAmong the 1,027 ASD children eventually included, 138 (13.44%) cases showed regressive behavior and the average regression occurring age was 24.00 (18.00–27.00) months. Among the regressive children, 105 cases (76.09%) had language regression, 79 cases (57.25%) had social regression, and 4 cases (2.90%) had motor regression. The total scores of ABC and the sub-score of sensory and stereotypic behavior (β = 5.122, 95% CI: 0.818, 9.426, P < 0.05; β = 1.104, 95% CI: 0.120, 2.089, P < 0.05; β = 1.388, 95% CI: 0.038, 2.737, P < 0.05), the SRS total scores and the sub-score of autistic mannerisms (β = 4.991, 95% CI: 0.494, 9.487, P < 0.05; β = 1.297, 95% CI: 0.140, 2.453, P < 0.05) of children in the regressive group were all higher than the non-regressive group. The total developmental quotient (DQ) of CNBS-R2016 and the DQ of gross motor, fine motor, adaptive behavior, language (β = −5.827, 95% CI: −11.529, −0.125, P < 0.05) and personal society in the regressive group were lower than the non-regressive group and the proportion of children with intelligent developmental impairment was higher the non-regressive group.ConclusionRegressive autism is mainly manifested as language and social regression. Children with regressive ASD have more severe core symptoms, lower neurodevelopmental level DQ, and more serious disease degree than children with non-regressive ASD, which requires further etiological examinations and more clinical attention.

Periodical road manhole cover measurement is extremely important to ensure road safety and reduce traffic disasters. This letter proposes an effective method for delineating road manhole covers from mobile laser scanning point cloud data. To improve processing efficiency, first, road surface points are segmented and rasterized into georeferenced intensity images. Then, object-oriented patches are generated through superpixel segmentation and further fed to a convolutional capsule network classifier for manhole cover detection. Finally, manhole covers are accurately delineated through a marked point process of disks. Quantitative evaluations on three data sets show that an average completeness, correctness, quality, and ${F} _{1}$ -measure of 0.965, 0.961, 0.929, and 0.963, respectively, are obtained. Comparative studies with three existing methods confirm that the proposed method performs superiorly in delineating manhole covers of varying conditions and on complex road surface environments.

This paper is concerned with the time periodic problem to a coupled chemotaxis-fluid model with porous medium diffusion \begin{document}$ \Delta n^m $\end{document} . The global existence of solutios for the initial and boundary value problem of this model have been studied by many authors, and in particular, the global solvability is established for \begin{document}$ m>\frac65 $\end{document} in dimension 3. Here, taking advantage of a double-level approximation scheme, we establish the existence of uniformly bounded time periodic solution for any \begin{document}$ m\ge \frac 65 $\end{document} and any large periodic source \begin{document}$ g(x, t) $\end{document} . In particular, the energy estimates techniques we used also applicable to the proof of global existence of the initial-boundary value problem, and one can supply the existence of global solutions for \begin{document}$ m = \frac65 $\end{document} by this method.

Purpose Travel companies are increasingly hosting online communities to extend their initiatives of customer relationship management and gain additional insight into their business. While the benefits to companies from hosting online communities are clear, another closely related issue has not been given comparative attention: Why do customers engage voluntarily in online travel communities? The purpose of this paper is to answer the question by developing and testing a conceptual model that exploring the influence of socialization interactions on customer engagement with the community. Design/methodology/approach Hypotheses were tested by applying structural equation modeling based on survey data collected from an online travel community (n=665). Findings The results supported the research hypotheses and demonstrated that socialization interactions (i.e. information and social exchange) in the online travel community are important catalysts for customer engagement. Originality/value The contribution of this study is twofold. First, from a theoretical perspective, it offers new insights into the conceptualization of customer engagement and its antecedents in the context of the online travel community. Second, from a pragmatic perspective, the conceptual model derived from this research aids practitioners in stimulating customer engagement from the perspective of socialization interactions.

We consider the coupled chemotaxis-fluid model for periodic pattern formation on two- and three-dimensional domains with mixed nonhomogeneous boundary value conditions, and prove the existence of nontrivial time periodic solutions. It is worth noticing that this system admits more than one periodic solution. In fact, it is not difficult to verify that (0, c, 0, 0) is a time periodic solution. Our purpose is to obtain a time periodic solution with nonconstant bacterial density.

In this paper, we study the large time behavior of a chemotaxis model with nonlinear diffusion and consumption { u t = Δ u m − ∇ ⋅ ( u ∇ v ) + μ u ( 1 − u ) , v t − Δ v = − v u , where m > 1 . In a previous paper [5] , we have proved the existence and uniform boundedness of global weak solutions for any nonnegative initial data and any m > 1 . In this work, we show that the weak solutions strongly converge to ( 1 , 0 ) in the large time limit.

In this paper, we deal with the following coupled chemotaxis–haptotaxis system u t = Δ u m − χ ∇ ⋅ u ( 1 + u ) α ∇ v − ξ ∇ ⋅ u ( 1 + u ) β ∇ ω + μ u ( 1 − u − ω ) , v t = Δ v − v + u , ω t = − v ω in a bounded domain Ω of R 3 corresponding to zero-flux boundary conditions. We showed that for any m > 0 , the problem admits a global bounded weak solution. Subsequently, we also discussed the large time behavior of solutions for the fast diffusion case, and showed that when 0 m ≤ 1 , for appropriately large μ , for any initial datum, the solution ( u , v , ω ) goes to the steady state ( 1 , 1 , 0 ) as t → ∞ . The global existence result improved the work of Liu et al. (2016) in dimension 3, in which, the global existence is established for min { α , β } > 4 3 − m with m > 4 3 or m ≤ 1 .

In this paper, the existing quadrature element method (QEM) is extended to analyze the three-dimensional (3D) free vibration of multi-directional functionally graded material (FGM) parallelepipeds under general boundary conditions. The material properties vary continuously in multiple directions according to a power-law form. Formulations of the multi-directional FGM parallelepiped element are given. Since the element nodes do not coincide with the integration points, a different way is used to compute the strains at integration points to derive explicit element stiffness matrix. A number of case studies on multi-directional FGM square and rhombic thick plates with general boundary conditions and different power-law exponents have been conducted. The effect of power-law exponents and boundary conditions on the free vibration behavior of FGM plates is investigated. The natural frequencies are in excellent agreement with either existing results or data obtained by ABAQUS using fine meshes. It is demonstrated that the extended QEM is simple in formulations and capable of capturing the 3D vibration behavior of the multi-directional FGM plates with high precision. New results are presented and may be used as benchmark solutions for future researches.

We aimed to investigate the relationship between vitamin D status and core symptoms and neurodevelopmental levels in children with ASD with a multicenter survey.We enrolled 1321 ASD children and 1279 typically developing (TD) children aged 2-7 years from 13 cities in China. ASD symptoms were assessed with the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS), and neurodevelopmental levels were evaluated with the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016).Children with ASD had lower serum 25(OH)D levels than TD children. Serum 25(OH)D levels were negatively associated with CARS and communication warning behavior of CNBS-R2016 scores, and were not associated with the development quotients of ASD children. ASD Children were grouped based on the quartiles for 25(OH)D levels in the controls, and children in the first to third quartiles had higher SRS social communication and/or CARS and communication warning behavior of CNBS-R2016 scores than those in the fourth quartile.Serum 25(OH)D levels were primarily associated with core symptoms in children with ASD, and individuals with relatively lower 25(OH)D levels displayed worse autistic symptomatology. More research is needed to determine whether vitamin D supplements would be a useful treatment for ASD.

The liver plays a central role that influences cardiovascular disease outcomes through regulation of glucose and lipid metabolism. It is recognized that the local liver molecular clock regulates some liver-derived metabolites. However, it is unknown whether the liver clock may impact cardiovascular function. Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue surrounding blood vessels. Importantly, cross talk between the endothelium and PVAT via vasoactive factors is critical for vascular function. Therefore, we designed studies to test the hypothesis that cardiovascular function, including PVAT function, is impaired in mice with liver-specific circadian clock disruption. Bmal1 is a core circadian clock gene, thus studies were undertaken in male hepatocyte-specific Bmal1 knockout (HBK) mice and littermate controls (i.e., flox mice). HBK mice showed significantly elevated plasma levels of β-hydroxybutyrate, nonesterified fatty acids/free fatty acids, triglycerides, and insulin-like growth factor 1 compared with flox mice. Thoracic aorta PVAT in HBK mice had increased mRNA expression of several key regulatory and metabolic genes, Ppargc1a, Pparg, Adipoq, Lpl, and Ucp1, suggesting altered PVAT energy metabolism and thermogenesis. Sensitivity to acetylcholine-induced vasorelaxation was significantly decreased in the aortae of HBK mice with PVAT attached compared with aortae of HBK mice with PVAT removed, however, aortic vasorelaxation in flox mice showed no differences with or without attached PVAT. HBK mice had a significantly lower systolic blood pressure during the inactive period of the day. These new findings establish a novel role of the liver circadian clock in regulating PVAT metabolic gene expression and PVAT-mediated aortic vascular function.

Power grid is becoming more and more smart and complex. It is necessary for us to measure, monitor and manage smart devices in power grid. In case of fault, the power grid equipment will suffer serious damage and cause great economic losses. A Cloud-based Wide-area Measurement System approach is proposed for fault detection in this paper. Fault detection using cloud-based WAMS can be divided into two main parts: Edging detection and Cloud detection. In edging devices, we try to find out the suspected local faults in power grid. In Cloud, we try to probe global faults by analysis of global features collected from edges.

Recent evidence indicates a crucial role for G protein-coupled estrogen receptor 1 (GPER1) in the maintenance of cardiovascular and kidney health in females. The current study tested whether GPER1 activation ameliorates hypertension and kidney damage in female Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. Adult female rats were implanted with telemetry transmitters for monitoring blood pressure and osmotic minipumps releasing G1 (selective GPER1 agonist, 400 μg/kg/day ip) or vehicle. Two weeks after pump implantation, rats were shifted from a normal-salt (NS) diet (0.4% NaCl) to a matched HS diet (4.0% NaCl) for 2 wk. Twenty-four hour urine samples were collected during both diet periods and urinary markers of kidney injury were assessed. Histological assessment of kidney injury was conducted after the 2-wk HS diet period. Compared with values during the NS diet, 24-h mean arterial pressure markedly increased in response to HS, reaching similar values in vehicle-treated and G1-treated rats. HS also significantly increased urinary excretion of protein, albumin, nephrin (podocyte damage marker), and KIM-1 (proximal tubule injury marker) in vehicle-treated rats. Importantly, G1 treatment prevented the HS-induced proteinuria, albuminuria, and increase in KIM-1 excretion but not nephrinuria. Histological analysis revealed that HS-induced glomerular damage did not differ between groups. However, G1 treatment preserved proximal tubule brush-border integrity in HS-fed rats. Collectively, our data suggest that GPER1 activation protects against HS-induced proteinuria and albuminuria in female Dahl SS rats by preserving proximal tubule brush-border integrity in a blood pressure-independent manner.

In this paper, we study the time periodic problem to a three-dimensional chemotaxis-Stokes model with porous medium diffusion Δ n m and inhomogeneous mixed boundary conditions. By using a double-level approximation method and some iterative techniques, we obtain the existence and time-space uniform boundedness of weak time periodic solutions for any m > 1. Moreover, we improve the regularity for [Formula: see text] and show that the obtained periodic solutions are, in fact, strong periodic solutions.

Timing of food intake has become a critical factor in determining overall cardiometabolic health. We hypothesized that timing of food intake entrains circadian rhythms of blood pressure (BP) and renal excretion in mice. Male C57BL/6J mice were fed ad libitum or reverse feeding (RF) where food was available at all times of day or only available during the 12-h lights-on period, respectively. Mice eating ad libitum had a significantly higher mean arterial pressure (MAP) during lights-off compared to lights-on (113 ± 2 mmHg vs 100 ± 2 mmHg, respectively; P 0.05); however, RF induced a diurnal rhythm of MAP (79 ± 3 mmHg vs 95 ± 2 mmHg, lights-off vs lights-on phase; P, Graphical Abstract Graphical Abstract

Loss of endothelin (ET) control of Na + reabsorption results in salt-sensitive hypertension. Diet-induced obesity such as via high fat (HF) diet can produce salt-sensitive hypertension. The goal of this study was to determine if obesity produced by HF diet impairs the renal ET system. Male SD rats were fed either HF (45 Kcal% fat) or normal fat (10 Kcal% fat, NF) diet at 6 weeks of age and for 8 weeks duration. Telemetry transmitters were implanted for systolic blood pressure (SBP) and activity monitoring. During the last 2 weeks of the diet, HF and NF rats were sub-divided into 2 groups to receive an additional high salt (4% NaCl, HS) diet or continue on normal salt (0.3% NaCl, NS) diet. Urine was collected and food and water intakes monitored in 12-hr increments the final 2 days. All groups maintained a diurnal BP pattern. However, rats on HF had significantly higher SBP compared to NF (146 ± 1 vs 138 ± 2 mmHg during the active period, p=0.003, n= 12/group). 12-hr urine volume or Na + excretion values were similar between groups. However, urinary ET-1, a measure of intrarenal ET-1 production, was significantly lower in the HF compared to NF controls (0.92 ± 0.15 vs 1.52 ± 0.09 pg/12hrs, p= 0.0007, n= 12/group). Relative mRNA expression of ET-1 in the renal cortex collected at ZT12 was significantly lower in the HF vs. NF (0.8 ± 0.1 vs 1.3 ± 0.2, p= 0.008, n= 6/group). A similar reduction of ET-1 mRNA was observed in the OM of HF rats. However, there was no change in ET-1 mRNA in the IM of HF rats compared to NF (0.8 ± 0.1 vs 1.0 ± 0.2, p= 0.28, n= 8/group). HS diet led to a further increase in SBP in HF vs the HF/NS group (152 ± 2 vs 147 ± 1 mmHg, p=0.04, n= 8/group) while addition of HS to the NF group showed no significant increase in SBP (145 ± 2 vs 140 ± 3 mmHg, p=0.37 n= 6/group). The NF/HS group had a significant increase in active-time ET-1 excretion compared to NF/NS (4.0 ± 0.4 vs 1.5 ± 0.2 pg/12hrs, p

Early life stress (ELS) is an independent risk factor for the development of cardiovascular disease in adulthood in both humans and rodent models. Maternal separation and early weaning (MSEW), a model of ELS, produces mice with an increased risk of cardiovascular dysfunction in adulthood, despite resting blood pressures (BP), heart rates (HR), and body weights comparable to normally reared controls. Autonomic regulation of HR and BP is an important component of the homeostatic response to stress but has not been investigated in MSEW mice. We hypothesized that exposure to MSEW impairs autonomic function at baseline and in response to an acute psychosocial stressor in adult male mice. C57Bl/6J litters were randomly assigned to MSEW or normally reared control conditions. MSEW litters were separated from dams for 4 h on postnatal days (PDs) 2-5, 8 h on PDs 6-16, and weaned at PD 17. Control litters were undisturbed until weaning at PD 21. At 9 weeks old, telemeters were implanted in MSEW (n=16) and control mice (n=12). During cage switch stress (CSS), mice were moved to a soiled, unfamiliar cage for 4 h. HR, systolic BP (SBP), diastolic BP (DBP), and activity (monitored by telemetry) were similar between control and MSEW mice at baseline and during CSS (p>0.05, 2-way ANOVA). Spectral analysis of HR, SBP, and DBP indicated that HR variability (HRV) total power was lower in MSEW mice during the 12 h inactive period compared to controls (18.9±1.1 ms 2 vs. 27.5±3.1 ms 2 ; p=0.0033, 2-way ANOVA) at baseline. HRV low frequency (LF) power was also lower during the 12 h inactive period in MSEW mice (4.2±0.4 ms 2 vs.6.6±0.9 ms 2 ; p=0.009). At baseline, 12 h and 24 h DBP variability LF/high frequency (HF) ratio, normalized LF, and normalized HF power were lower in the MSEW group (p

Histone deacetylase (HDAC) enzymes regulate transcription through epigenetic modification of chromatin structure, but their specific functions in the kidney remain elusive. We discovered that the human kidney expresses class I HDACs. Kidney medulla-specific inhibition of class I HDACs in the rat during high-salt feeding results in hypertension, polyuria, hypokalemia, and nitric oxide deficiency. Three new inducible murine models were used to determine that HDAC1 and HDAC2 in the kidney epithelium are necessary for maintaining epithelial integrity and maintaining fluid-electrolyte balance during increased dietary sodium intake. Moreover, single-nucleus RNA-sequencing determined that epithelial HDAC1 and HDAC2 are necessary for expression of many sodium or water transporters and channels. In performing a systematic review and meta-analysis of serious adverse events associated with clinical HDAC inhibitor use, we found that HDAC inhibitors increased the odds ratio of experiencing fluid-electrolyte disorders, such as hypokalemia. This study provides insight on the mechanisms of potential serious adverse events with HDAC inhibitors, which may be fatal to critically ill patients. In conclusion, kidney tubular HDACs provide a link between the environment, such as consumption of high-salt diets, and regulation of homeostatic mechanisms to remain in fluid-electrolyte balance., Kidney histone deacetylase activity is necessary for maintaining fluid-electrolyte balance during environmental insults such as a high sodium diet.

Baroreflex function is an integral component maintaining consistent blood pressure. Hypertension is often associated with baroreflex dysfunction, and environmental risk factors such as high salt diet exacerbate hypertension in subjects with baroreflex dysfunction. However, the interactions between high salt diet, baroreflex dysfunction, and hypertension are incompletely understood. The endothelin system is another potent mediator of blood pressure control especially in response to a high salt diet. We hypothesized that the endothelin B (ET(B)) receptor activation on adrenergic nerves decreases baroreflex sensitivity. We utilized male ET(B) receptor deficient (ET(B)-def) rats that express functional ET(B) receptors only on adrenergic nerves and transgenic (TG) controls to evaluate baroreflex function during normal (0.49% NaCl) and high (4.0% NaCl) salt diets. In conscious rats equipped with telemetry, ET(B)-def rats had an increased lability of systolic blood pressure (SBP) compared to TG controls as indicated by higher standard deviation (SD) of SBP under both normal (10.2±0.6 vs. 12.4±0.9 mmHg, respectively, p=0.0001) and high (11.7±0.6 vs. 16.1±1.0 mmHg, p=0.0001) salt diets. In anesthetized preparations, ET(B)-def rats displayed reduced heart rate (p genotype=0.0167) and renal sympathetic nerve (p genotype=0.0022) baroreflex sensitivity. We then gave male Sprague-Dawley rats the selective ET(B) receptor antagonist, A-192621 (10 mg/kg/day), to block ET(B) receptors. Following ET(B) receptor antagonism, even though SBP increased (131±7 before vs. 152±8 mmHg after, p

Background The novel estrogen receptor, G‐protein–coupled estrogen receptor ( GPER ), is responsible for rapid estrogen signaling. GPER activation elicits cardiovascular and nephroprotective effects against salt‐induced complications, yet there is no direct evidence for GPER control of renal Na + handling. We hypothesized that GPER activation in the renal medulla facilitates Na + excretion. Methods and Results Herein, we show that infusion of the GPER agonist, G1, to the renal medulla increased Na + excretion in female Sprague Dawley rats, but not male rats. We found that GPER mRNA expression and protein abundance were markedly higher in outer medullary tissues from females relative to males. Blockade of GPER in the renal medulla attenuated Na + excretion in females. Given that medullary endothelin 1 is a well‐established natriuretic factor that is regulated by sex and sex steroids, we hypothesized that GPER activation promotes natriuresis via an endothelin 1–dependent pathway. To test this mechanism, we determined the effect of medullary infusion of G1 after blockade of endothelin receptors. Dual endothelin receptor subtype A and endothelin receptor subtype B antagonism attenuated G1‐induced natriuresis in females. Unlike males, female mice with genetic deletion of GPER had reduced endothelin 1, endothelin receptor subtype A, and endothelin receptor subtype B mRNA expression compared with wild‐type controls. More important, we found that systemic GPER activation ameliorates the increase in mean arterial pressure induced by ovariectomy. Conclusions Our data uncover a novel role for renal medullary GPER in promoting Na + excretion via an endothelin 1–dependent pathway in female rats, but not in males. These results highlight GPER as a potential therapeutic target for salt‐sensitive hypertension in postmenopausal women.

Electronic health record (EHR) has recorded the process of occurrence, development, and treatment of diseases. So it has high medical value. Owing to the private and sensitive nature of medical data for patients, the data sharing and privacy preservation are critical issues in EHR. Blockchain technology may be a promising solution for the problems above since it holds the features of decentralization and tamper resistance. In the paper, we propose a medical data sharing and protection scheme based on the hospital's private blockchain to improve the electronic health system of the hospital. Firstly, the scheme can satisfy various security properties such as decentralization, openness, and tamper resistance. A reliable mechanism is created for the doctors to store medical data or access the historical data of patients while meeting privacy preservation. Furthermore, a symptoms-matching mechanism is given between patients. It allows patients who get the same symptoms to conduct mutual authentication and create a session key for their future communication about the illness. The proposed scheme is implemented by using PBC and OpenSSL libraries. Finally, the security and performance evaluation of the proposed scheme is given.

Deniable authenticated encryption (DAE) is a cryptographic primitive that supports data confidentiality with deniable authentication in an efficient manner. The DAE plays a significant role in location-based service systems for privacy protection. In this paper, we construct a certificateless DAE (CLDAE) scheme. The CLDAE is based on certificateless cryptosystems (CLCs), which avoids the need to manage public key certificates in public key infrastructure (PKI)-based cryptosystems and key escrow problems in identity-based cryptosystems (IBCs). Our design utilizes hybrid methods: tag-key encapsulation mechanism (TKEM) and data encapsulation mechanism (DEM). This technique is more suitable for location-based applications. We show how to construct a CLDAE scheme utilizing a certificateless deniable authenticated tag-KEM (CLDATK) and a DEM. We also design a CLDATK scheme and provide formal security proof using the random oracle model (ROM). We conduct a comprehensive performance analysis, which shows that CLDAE is highly efficient in terms of communication overhead. We also provide an application of the CLDAE for a location-based service (LBS) system.

The diurnal rhythms of sodium handling and blood pressure are thought to be regulated by clock genes, such as Bmal1. However, little is known about the regulation of these factors by Bmal1, especially in rats. Using a novel whole-body Bmal1 knockout rat model ( Bmal1 − /− ), we hypothesized that time of day regulation of sodium excretion is dependent on Bmal1. Using telemetry to continuously record mean arterial pressure, we observed that male and female Bmal1 −/− rats had significantly reduced mean arterial pressure over the course of 24 hours compared with littermate controls. The circadian mean arterial pressure pattern remained intact in both sexes of Bmal1 −/− rats, which is in contrast to the Bmal1 −/− mouse model. Male Bmal1 −/− rats had no significant difference in baseline sodium excretion between 12-hour active and inactive periods, indicating a lack of diurnal control independent of maintained mean arterial pressure rhythms. Female Bmal1 −/− rats, however, had significantly greater sodium excretion during the active versus inactive period similar to controls. Thus, we observed a clear dissociation between circadian blood pressure and control of sodium excretion that is sex dependent. These findings are consistent with a more robust ability of females to maintain control of sodium excretion, and furthermore, demonstrate a novel role for Bmal1 in control of diurnal blood pressure independent of sodium excretion.