High-normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: A real-world study.

OBJECTIVE: To investigate the association between serum unconjugated bilirubin (UCB) within normal limits and chronic kidney disease (CKD) in T2DM patients. METHOD: This cross-sectional, real-world study was performed in 8661 hospitalised T2DM patients. The subjects were stratified into quintiles based on serum UCB levels. The clinical characteristics and CKD prevalence were compared among the UCB quantile groups. The associations of serum UCB levels and quintiles with CKD were also analysed by binary logistic regression. RESULTS: After controlling for age, sex, and diabetes duration (DD), the CKD prevalence (20.4%, 12.2%, 10.6%, 8.3%, and 6.4% for the first, second, third, fourth, and fifth quintiles, respectively, p < 0.001 for trend) was significantly decreased across the serum UCB quintiles. The fully adjusted regression model showed negative associations of serum UCB levels (OR: 0.660, 95% CI: 0.585-0.744; p < 0.001 for trend) and quintiles (p < 0.001) with the presence of CKD. Compared with the subjects in the lowest UCB quintile, the risk of CKD decreased by 36.2%, 54.3%, 53.8%, and 62.1%, respectively, in those from the second to the highest UCB quintile. Additionally, C-reactive protein (CRP) levels were significantly higher in the subjects with CKD than in those without CKD (p < 0.001), and significantly decreased across the UCB quintiles (p < 0.001 for trend). CONCLUSIONS: Serum UCB levels within the normal range were significantly and negatively linked to CKD in T2DM patients. High-normal UCB may be an independent protective factor for CKD by its antioxidant and the following anti-inflammatory activities through its signalling activity, which was indicated by clearly decreased CRP levels across the UCB quintiles.

CHOP promotes coelomocyte apoptosis through p38-MAPK pathway in Vibrio splendidus-challenged sea cucumber Apostichopus japonicus.

CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) belongs to the C/EBP family of transcription factors that has been proven to regulate apoptosis in many vertebrate species. However, the functional role of CHOP in invertebrates is largely unknown. In this paper, the open reading frame of CHOP was cloned and characterized in the sea cucumber Apostichopus japonicus (AjCHOP). The deuced amino acid of AjCHOP shared a conserved RTP801_C domain from 63 to 171 aa. Phylogenetic analysis indicated that AjCHOP clustered with CHOPs from Lytechinus variegatus and Strongylocentrotus purpuratus. To confirm the immune function of AjCHOP, the time-course expression profiles of AjCHOP were investigated, and the findings revealed AjCHOP was significantly induced in coelomocytes at mRNA and protein levels after Vibro splendidus challenge. Furthermore, knockdown of AjCHOP in coelomocyes by siRNA transfection significantly decreased the apoptosis level induced by V. splendidus. Mechanically, AjCHOP-mediated apoptosis was dependent on the activation of p38-MAPK pathway but not JNK/ERK-MAPK. Overall, our results supported that V. splendidus triggers apoptosis among the coelomocytes, whereas AjCHOP mediates through the p38-MAPK pathway in A. japonicus.

Association of feeding patterns in infancy with later autism symptoms and neurodevelopment: a national multicentre survey.

BACKGROUND: We aimed to compare differences in infant feeding patterns (breastfeeding and complementary food supplementation) between children with the autism spectrum disorder (ASD) and typically developing (TD) children through a multicentre study. The relationship between these patterns and later core symptoms and neurodevelopment in children with ASD was also investigated. METHODS: We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms. RESULTS: Children with ASD had a shorter breastfeeding duration in infancy (8 (3-12) months vs. 10 (6-14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4-6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance. CONCLUSIONS: Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than TD children. These feeding patterns may be related to the symptoms and growth of children with ASD. The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms and that infants who have difficulty introducing complementary foods should be followed up for neurodevelopment. TRIAL REGISTRATION: The ethics committee of the Children's Hospital of Chongqing Medical University approved the study. Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194, registered on 23/03/2020).

Short-term daytime restricted feeding in rats with high salt impairs diurnal variation of Na+ excretion.

Night shift work increases risk of cardiovascular disease associated with an irregular eating schedule. Elevating this risk is the high level of salt intake observed in the typical Western diet. Renal Na+ excretion has a distinct diurnal pattern, independent of time of intake, yet the interactions between the time of intake and the amount of salt ingested are not clear. The hypothesis of the present study was that limiting food intake to the typically inactive period in addition to high-salt (HS) feeding will disrupt the diurnal rhythm of renal Na+ excretion. Male Sprague-Dawley rats were placed on either normal-salt (NS; 0.49% NaCl) or HS (4% NaCl) diets. Rats were housed in metabolic cages and allowed food ad libitum and then subjected to inactive period time-restricted feeding (iTRF) for 5 days. As expected, rats fed NS and allowed food ad libitum had a diurnal pattern of Na+ excretion. The diurnal pattern of Na+ excretion was not significantly different after 5 days of iTRF compared with ad libitum rats. In response to HS, the diurnal pattern of Na+ excretion was similar to NS-fed rats. However, this pattern was attenuated after 5 days of HS iTRF. The diurnal excretion pattern of urinary aldosterone was abolished in both NS iTRF and HS iTRF rats. These data support the hypothesis that HS intake combined with iTRF impairs circadian mechanisms associated with renal Na+ excretion.NEW & NOTEWORTHY Timing of food intake normally has little effect on the diurnal pattern of Na+ and water excretion. However, rats on a high-salt diet were unable to maintain this pattern, yet K+ excretion was more readily adjusted to match timing of intake. These data support the hypothesis that Na+ and water homeostasis are impacted by timing of high-salt diets.

Neurodevelopmental domain characteristics and their association with core symptoms in preschoolers with autism spectrum disorder in China: a nationwide multicenter study.

BACKGROUND: Autism spectrum disorder (ASD) is a group of clinically heterogenic neurodevelopmental disorders, with intellectual disability being one of its common comorbidities. No large-sample, multicenter study has focused on the neurodevelopmental aspect of preschoolers with ASD. This study investigated the neurodevelopmental characteristics of preschoolers with ASD in China and explored the association between them and the core symptoms. METHODS: We enrolled 1019 ASD preschoolers aged 2-7 years old from 13 cities around China between May 2018 and December 2019, and used the revised Children Neuropsychological and Behavior Scale (CNBS-R2016) to assess their neurodevelopment. Their autistic core behaviors were evaluated based on their Social Responsiveness Scale (SRS), Autism Behavior Checklist (ABC), Child Autism Rating Scale (CARS), and communication warning behavior (CWB) scores in the CNBS-R2016. RESULTS: Based on general developmental quotient (GQ) < 70, 68.4% of the preschoolers with ASD had a developmental delay (DD), rated mild in 32.7% of them. The highest DD rate (> 70%) was found in language and personal-social skills, followed by fine motor skills (68.9%). Gross motor skills had the lowest DD rate (34.0%). We found that fine motor, language, and personal-social developmental quotients (DQs) were significantly lower than gross motor skills in no DD (GQ > 70), mild DD (GQ 55-69), and moderate and below DD groups (GQ ≤ 54). Furthermore, the DQs for language and personal-social skills were significantly lower than for gross and fine motor skills in both DD groups. The ABC, SRS, CARS, and CWB scores in the no DD group were the lowest, moderate in the mild DD group, and highest in the moderate and below DD group. Besides, negative correlations were found between the DQs of the four domains and the ABC, SRS, CARS, and CWB scores, of which the language and personal-social skills DQs had the strongest correlations. CONCLUSIONS: Preschoolers with ASD had unbalanced neurodevelopment domain patterns and their neurodevelopmental levels were negatively correlated with the autism core symptoms. Hence, pediatricians should actively evaluate the neurodevelopment of children with ASD and conduct long-term follow-up during their early childhood to promote early diagnosis and develop personalized intervention plans. TRIAL REGISTRATION: ChiCTR2000031194 , registered on 03/23/2020.

Effect of medical researchers' creative performance on scientific misconduct: a moral psychology perspective.

BACKGROUND: In recent years, some researchers have engaged in scientific misconduct such as fabrication, falsification, and plagiarism to achieve higher research performance. Considering their detrimental effects on individuals' health status (e.g., patients, etc.) and extensive financial costs levied upon healthcare systems, such wrongdoings have even more salience in medical sciences. However, there has been little discussion on the possible influence of medical researchers' existing creative performance on scientific misconduct, and the moral psychological mechanisms underlying those effects are still poorly understood. METHODS: We build a moderated mediation model to test how medical researchers' creative performance affects their scientific misconduct and explore the role of moral licensing and moral identity in this process. Based on situational experiments and projection techniques, 287 medical researchers in China participated in a survey. RESULTS: Medical researchers' creative performance positively relates to scientific misconduct, and moral licensing plays a mediating role in the relationship between them. In addition, moral identity has a negative moderating effect on the mediating effect of moral licensing on creative performance and scientific misconduct. CONCLUSION: Moral licensing plays a fully mediating role in the relationship between creative performance and scientific misconduct. And moral identity negatively moderates the indirect effect of creative performance on scientific misconduct through moral licensing. The findings provide theoretical and practical implications for the prevention of medical researchers' scientific misconduct.

Early life exposure to triclosan from antimicrobial daily necessities may increase the potential risk of autism spectrum disorder: A multicenter study in China.

BACKGROUND: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders with unclear etiologies. Our recent work indicated that maternal exposure to triclosan (TCS) significantly increased the autistic-like behavior in rats, possibly through disrupting neuronal retinoic acid signaling. Although environmental endocrine disruptors (EEDs) have been associated with autism in humans, the relationship between TCS, one of the EEDs found in antibacterial daily necessities, and autism has received little attention. OBJECTIVE: The aims of this multicenter study were to evaluate TCS concentrations in typically developing (TD) children and ASD children, and to determine the relationship between TCS levels and the core symptoms of ASD children. METHODS: A total of 1345 children with ASD and 1183 TD children were enrolled from 13 cities in China. Ages ranged between 2 and 7 years. A questionnaire was used to investigate the maternal use of antibacterial daily necessities (UADN) during pregnancy. The core symptoms of ASD were evaluated using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Response Scale (SRS), and the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). The TCS concentration was measured using LC-MS/MS. RESULTS: Maternal UADN during pregnancy may be an unrecognized potential environmental risk factor for ASD (OR=1.267, P = 0.023). Maternal UADN during pregnancy strongly correlated with TCS levels in the offspring (Adjusted ß = 0.277, P < 0.001). TCS concentration was higher in ASD children (P = 0.005), and positively correlated with ABC (Sensory subscales: P = 0.03; Social self-help subscales: P = 0.011) and SRS scale scores (Social awareness subscales: P = 0.045; Social communication subscales: P = 0.001; Autism behavior mannerisms subscales: P = 0.006; SRS total score: P = 0.003) in ASD children. This association was more pronounced in boys than in girls. CONCLUSION: To our knowledge, this is the first case-control study to examine the correlation between TCS and ASD. Our results suggest that maternal UADN during pregnancy may be a potential risk of ASD in offspring. Further detection of TCS levels showed that maternal UADN during pregnancy may be associated with excessive TCS exposure. In addition, the level of TCS in children with ASD is higher than TD children. The higher levels of TCS in children with ASD may be significantly associated with more pronounced core symptoms, and this association was more significant in male children with ASD.

Activation of G protein-coupled estrogen receptor 1 ameliorates proximal tubular injury and proteinuria in Dahl salt-sensitive female rats.

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.

Liver circadian clock disruption alters perivascular adipose tissue gene expression and aortic function in mice.

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 ß-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.

Sleep problems in children with autism spectrum disorder: a multicenter survey.

BACKGROUND: High prevalence of sleep problems have been reported in children with Autism Spectrum Disorder (ASD). This study aims to investigate the sleep conditions of ASD children in China, and explore the relationship between the common sleep problems and core symptoms and developmental levels. METHODS: Using a cross-sectional design, we included 2 to 7-year-old children from 13 cities in China: 1310 with ASD and 1158 with typically-developing (TD) children. The neurodevelopmental level was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). ASD were diagnosed with DSM-5 and Child Autism Rating Scale (CARS). the Social Responsiveness Scale (SRS), the Autism Behavior Checklist (ABC) and the communication warning behavior sub-scale in CNBS-R2016 valued autism behaviors. The children' s sleep habits questionnaire (CSHQ) assessed sleep conditions. RESULTS: The prevalence of sleep disorders in ASD children was significantly higher than that in TD (67.4% vs. 51%, p < 0.01), and among them the four dimensions with the highest prevalence of sleep problems were bedtime resistance (25.6%), sleep anxiety (22.7%), sleep onset delay (17.9%) and daytime sleepiness (14.7%). ASD children with sleep onset delay or sleep anxiety had higher ABC, SRS scores and higher scores on communication warning behavior with sleep anxiety, with daytime sleepiness had higher ABC, SRS and CARS scores, and with bedtime resistance had higher SRS total scores. Differences in the neurodevelopmental level were not significant. CONCLUSION: Children with ASD have a higher prevalence of sleep problems. Bedtime resistance, anxiety, sleep onset delay and daytime sleepiness may be related to the core symptoms, but not be related to the developmental level in ASD children. In the clinic, sleep assessment should be included in the routine of ASD visits, and during the intervention, sleep hygiene education is as important as the treatment of biological factors. TRIAL REGISTRATION: The study was approved by the ethics committee of the Children's Hospital of Chongqing Medical University, Approval Number: (2018) IRB (STUDY) NO. 121, and registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000031194 ).

[Association between serum trace elements and core symptoms in children with autism spectrum disorder: a national multicenter survey].

OBJECTIVE: To study the association of serum levels of trace elements with core symptoms in children with autism spectrum disorder (ASD). METHODS: From September 2018 to September 2019, an investigation was performed for 1 020 children with ASD and 1 038 healthy children matched for age and sex in the outpatient service of grade A tertiary hospitals and special education institutions in 13 cities of China. Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood Autism Rating Scale (CARS) were used to assess the core symptoms of the children with ASD. The inductively coupled plasma mass spectrometry was used to measure serum levels of trace elements magnesium, iron, copper, and zinc. RESULTS: The children with ASD had significantly lower serum levels of magnesium, copper, and zinc than the healthy children (P < 0.05). The children with severe ASD had significantly lower serum levels of magnesium and zinc than those with mild-to-moderate ASD (P < 0.05). The results of partial correlation analysis showed that serum magnesium level was negatively correlated with the total score of ABC and the score of communication (r=-0.318 and -0.282 respectively; P 0.001), and serum zinc level was negatively correlated with the total score of ABC and the scores of communication and somatic movement (r=-0.221, -0.270, and -0.207 respectively; P < 0.001). CONCLUSIONS: The serum levels of magnesium and zinc may be associated with core symptoms in children with ASD, which requires further studies. The nutritional status of trace elements should be monitored for children with ASD in clinical practice.

Loss of circadian gene Bmal1 in the collecting duct lowers blood pressure in male, but not female, mice.

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.

High dietary sodium causes dyssynchrony of the renal molecular clock in rats.

Speed JS, Hyndman KA, Roth K, Heimlich JB, Kasztan M, Fox BM, Johnston JG, Becker BK, Jin C, Gamble KL, Young ME, Pollock JS, Pollock DM. High dietary sodium causes dyssynchrony of the renal molecular clock in rats. Am J Physiol Renal Physiol 314: F89-F98, 2018. First published September 27, 2017; doi:10.1152/ajprenal.00028.2017.-Dyssynchrony of circadian rhythms is associated with various disorders, including cardiovascular and metabolic diseases. The cell autonomous molecular clock maintains circadian control; however, environmental factors that may cause circadian dyssynchrony either within or between organ systems are poorly understood. Our laboratory recently reported that the endothelin (ET-1) B (ETB) receptor functions to facilitate Na+ excretion in a time of day-dependent manner. Therefore, the present study was designed to determine whether high salt (HS) intake leads to circadian dyssynchrony within the kidney and whether the renal endothelin system contributes to control of the renal molecular clock. We observed that HS feeding led to region-specific alterations in circadian clock components within the kidney. For instance, HS caused a significant 5.5-h phase delay in the peak expression of Bmal1 and suppressed Cry1 and Per2 expression in the renal inner medulla, but not the renal cortex, of control rats. The phase delay in Bmal1 expression appears to be mediated by ET-1 because this phenomenon was not observed in the ETB-deficient rat. In cultured inner medullary collecting duct cells, ET-1 suppressed Bmal1 mRNA expression. Furthermore, Bmal1 knockdown in these cells reduced epithelial Na+ channel expression. These data reveal that HS feeding leads to intrarenal circadian dyssynchrony mediated, in part, through activation of ETB receptors within the renal inner medulla.

Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats.

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.

An Improved Two-Layer Authentication Scheme for Wireless Body Area Networks.

Wireless body area networks (WBANs) comprises a number of sensor nodes and the portable mobile device such as smartphone. It is used to monitor the physical condition and provide a reliable healthcare system. Utilizing the wireless communication network, sensor nodes collect the physiological data of one patient to the portable mobile device and the latter analyzes and transmits them to the application providers. Therefore, the personal data confidentiality and user privacy are cores of WBANs. Recently, Shen et al. presented a multi-layer authentication protocol for WBANs, which is lightweight and much easier to implement. However, we observe that their authentication between sensor nodes and the portable mobile device could ensure the forward security property only when the sensor nodes are changed (add or delete). When the sensor nodes are constant, the security property is not satisfied. Meanwhile, the authentication between the portable mobile device and application provider is prone to mutual impersonation attack, so the critical goal of mutual authentication can not be achieved. In this paper, an improved two-layer authentication scheme is proposed to remove the flaws. The analysis shows that our method is more secure and could withstand various attacks.

Provably Secure Heterogeneous Access Control Scheme for Wireless Body Area Network.

Wireless body area network (WBAN) provides a medium through which physiological information could be harvested and transmitted to application provider (AP) in real time. Integrating WBAN in a heterogeneous Internet of Things (IoT) ecosystem would enable an AP to monitor patients from anywhere and at anytime. However, the IoT roadmap of interconnected 'Things' is still faced with many challenges. One of the challenges in healthcare is security and privacy of streamed medical data from heterogeneously networked devices. In this paper, we first propose a heterogeneous signcryption scheme where a sender is in a certificateless cryptographic (CLC) environment while a receiver is in identity-based cryptographic (IBC) environment. We then use this scheme to design a heterogeneous access control protocol. Formal security proof for indistinguishability against adaptive chosen ciphertext attack and unforgeability against adaptive chosen message attack in random oracle model is presented. In comparison with some of the existing access control schemes, our scheme has lower computation and communication cost.

Attenuated recovery of contractile function in aging hearts following global ischemia/reperfusion: Role of extracellular HSP27 and TLR4.

BACKGROUND: While cardiac functional recovery is attenuated in the elderly following cardiac surgery with obligatory global myocardial ischemia/reperfusion (I/R), the underlying mechanism remains incompletely understood. We observed previously that human and mouse myocardium releases heat shock protein (HSP) 27 during global I/R. Extracellular HSP27 induces myocardial inflammatory response and plays a role in post-ischemic cardiac dysfunction in adult mouse hearts. OBJECTIVE: This study was to determine the role of extracellular HSP27 and Toll-like receptor 4 (TLR4) in the attenuated functional recovery in aging mouse hearts following global I/R. METHODS AND RESULTS: Hearts isolated from aging (18-24 months) and adult (4-6 months) mice were subjected to ex vivo global I/R. Augmented release of HSP27 in aging hearts is associated with greater production of cytokines (TNF-α and IL-1ß) and worse functional recovery. Anti-HSP27 suppressed the inflammatory response and markedly improved functional recovery in aging hearts. Perfusion of recombinant HSP27 to aging hearts resulted in greater cytokine production and more severe contractile depression in comparison to adult hearts. TLR4 deficiency abolished cytokine production and functional injury in aging hearts exposed to recombinant HSP27. Interestingly, aging hearts had higher TLR4 protein levels and displayed enhanced TLR4-mediated NF-κB activation following HSP27 stimulation or I/R. CONCLUSION: Extracellular HSP27 and TLR4 jointly enhance the inflammatory response and hamper functional recovery following I/R in aging hearts. The enhanced inflammatory response to global I/R and attenuated post-ischemic functional recovery in aging hearts is due, at least in part, to augmented myocardial release of HSP27 and elevated myocardial TLR4 levels.

Renal denervation attenuates hypertension but not salt sensitivity in ETB receptor-deficient rats.

Hypertension is a prevalent pathology that increases risk for numerous cardiovascular diseases. Because the etiology of hypertension varies across patients, specific and effective therapeutic approaches are needed. The role of renal sympathetic nerves is established in numerous forms of hypertension, but their contribution to salt sensitivity and interaction with factors such as endothelin-1 are poorly understood. Rats deficient of functional ETB receptors (ETB-def) on all tissues except sympathetic nerves are hypertensive and exhibit salt-sensitive increases in blood pressure. We hypothesized that renal sympathetic nerves contribute to hypertension and salt sensitivity in ETB-def rats. The hypothesis was tested through bilateral renal sympathetic nerve denervation and measuring blood pressure during normal salt (0.49% NaCl) and high-salt (4.0% NaCl) diets. Denervation reduced mean arterial pressure in ETB-def rats compared with sham-operated controls by 12 ± 3 (SE) mmHg; however, denervation did not affect the increase in blood pressure after 2 wk of high-salt diet (+19 ± 3 vs. +16 ± 3 mmHg relative to normal salt diet; denervated vs. sham, respectively). Denervation reduced cardiac sympathetic-to-parasympathetic tone [low frequency-high frequency (LF/HF)] during normal salt diet and vasomotor LF/HF tone during high-salt diet in ETB-def rats. We conclude that the renal sympathetic nerves contribute to the hypertension but not to salt sensitivity of ETB-def rats.

Molecular cloning and functional characterization of theta class glutathione S-transferase from Apostichopus japonicus.

Glutathione S-transferases (GSTs) are the superfamily of multifunctional detoxification isoenzymes and play crucial roles in innate immunity. In the present study, a theta class GST homology was identified from A. japonicus (designated as AjGST-θ) by RACE approaches. The full-length cDNA of AjGST-θ was of 1013 bp encoded a cytosolic protein of 231 amino acids residues. Structural analysis revealed that AjGST-θ processed the characteristic N-terminal GSH-binding site (G-site) and the C-terminal hydrophobic substrate binding site (H-site). Multiple sequence alignment and phylogenetic analysis together supported that AjGST-θ belonged to a new member of theta class GST protein subfamily. Spatial expression analysis revealed that AjGST-θ was ubiquitously expressed in all examined tissues with the larger magnitude in intestine. The Vibrio splendidus challenge in vivo and LPS stimulation in vitro could both significantly up-regulate the mRNA expression of AjGST-θ when compared with control group. The recombinant protein was expressed in Escherichia coli and the purified AjGST-θ showed high activity with GST substrate. Meantime, disc diffusion assay showed that recombinant AjGST-θ protein could markedly improve bacterial growth under Cumene hydroperoxide exposure. More importantly, the recombinant AjGST-θ could effectively prevent primary coelomocytes apoptosis after LPS exposure. Our present findings suggested that AjGST-θ might play significantly roles in the modulation of immune response and protect cells from pathogens infection in A. japonicus.

miR-92a regulates coelomocytes apoptosis in sea cucumber Apostichopus japonicus via targeting Aj14-3-3ζ in vivo.

miR-92a, a well-documented oncogene, was previously found to be differentially expressed in diseased sea cucumber Apostichopus japonicus by high-throughput sequencing. In this study, we identified Aj14-3-3ζ as a novel target of miR-92a in this species and investigated their regulatory roles in vivo. The negative expression profiles between miR-92a and Aj14-3-3ζ protein were detected in both LPS-exposed primary coelomocytes and Vibrio splendidus-challenged sea cucumbers. Over-expression of miR-92a by injection of miR-92a agomir significantly depressed the mRNA and protein expression of Aj14-3-3ζ and promoted coelomocytes apoptosis with 5.04-fold increase in vivo, which was consistent with those from siRNA-mediated Aj14-3-3ζ knockdown assay. In contrast, miR-92a antagomir significantly elevated the mRNA and protein expression of Aj14-3-3ζ and decreased coelomocytes apoptosis. Taken together, our result confirmed that miR-92a is involved in apoptotic signaling pathway regulation perhaps via targeting Aj14-3-3ζ in sea cucumbers, which will enhance our understanding of miR-92a regulatory roles in sea cucumber pathogenesis.