Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b.

During vertebrate early embryogenesis, the ventral development is directed by the ventral-to-dorsal activity gradient of the bone morphogenetic protein (BMP) signaling. As secreted ligands, the extracellular traffic of BMP has been extensively studied. However, it remains poorly understood that how BMP ligands are secreted from BMP-producing cells. In this work, we show the dominant role of Marcksb controlling the secretory process of Bmp2b via interaction with Hsp70 in vivo. We firstly carefully characterized the role of Marcksb in promoting BMP signaling during dorsoventral axis formation through knockdown approach. We then showed that Marcksb cell autonomously regulates the trafficking of Bmp2b from producing cell to the extracellular space and both the total and the extracellular Bmp2b was decreased in Marcksb-deficient embryos. However, neither the zygotic mutant of marcksb (Zmarcksb) nor the maternal zygotic mutant of marcksb (MZmarcksb) showed any defects of dorsalization. In contrast, the MZmarcksb embryos even showed increased BMP signaling activity as measured by expression of BMP targets, phosphorylated Smad1/5/9 levels and imaging of Bmp2b, suggesting that a phenomenon of "genetic over-compensation" arose. Finally, we revealed that the over-compensation effects of BMP signaling in MZmarcksb was achieved through a sequential up-regulation of MARCKS-family members Marcksa, Marcksl1a and Marcksl1b, and MARCKS-interacting protein Hsp70.3. We concluded that the Marcksb modulates BMP signaling through regulating the secretory pathway of Bmp2b.

Porcine epidemic diarrhea virus nsp4 induces pro-inflammatory cytokine and chemokine expression inhibiting viral replication in vitro.

Porcine epidemic diarrhea virus (PEDV) causes severe economic loss in the pig industry each year. To better understand the relationship between cytokines and PEDV replication, in this study, pro-inflammatory cytokine and chemokine expression profiles in Vero cells infected with PEDV were analyzed. Real-time quantitative PCR assay indicated that IL-1α, IL-1ß, TNF-α, CCL2, CCL5 and CXCL8 expression levels were significantly upregulated. Moreover, overexpression and siRNA silencing assays showed that overexpression of IL-1α, IL-1ß, TNF-α, CCL2, CCL5 and CXCL8 could significantly inhibit PEDV replication, while silencing of IL-1α, IL-1ß, TNF-α, CCL2, CCL5 and CXCL8 could significantly promote PEDV replication. Finally, a dual-luciferase reporter assay showed that nsp4 contributed to the expression of IL-1α, IL-1ß, TNF-α, CCL2, CCL5 and CXCL8 via the NF-κB pathway. Together, these data determined that PEDV nsp4 could upregulate pro-inflammatory cytokine and chemokine expression, inhibiting viral replication in vitro. These results provided novel insights for understanding the roles of cytokines in PEDV replication.

Acute and subchronic toxicity studies of seabuckthorn (Hippophae rhamnoides L.) oil in rodents.

Seabuckthorn (Hippophae rhamnoides L.) has been traditionally used as medicine and nutritional supplement for a long period of time. However, information on the systemic toxicity and safety evaluation of seabuckthorn and its extracts is still scarce. The purpose of this study was to evaluate the potential toxicity of seabuckthorn oil by an acute oral toxicity study in mice and a 90-day repeated oral toxicity study in rats. No mortality or signs of toxicity was observed in mice treated with 20 mL/kg body weight seabuckthorn oil in the acute toxicity study. In the subchronic toxicity study, 80 Sprague-Dawley rats (10 animals per sex per treatment group) were administrated with 10, 5, 2.5 and 0 (control) mL/kg body weight of seabuckthorn oil daily for 90 days by gavage. There were no signs of toxicity and treatment-related changes in rats treated with seabuckthorn oil on mortality, body and organ weights, food consumption, blood biochemistry and hematology, gross necropsy and histopathological examinations. Based on the finding of this study, the maximum tolerated dose of seabuckthorn oil was >20 mL/kg for mice for acute toxicity study, and the no-observed-adverse-effect level was 10 mL/kg body weight for both male and female rats for 90-day toxicity study.

Safety assessment of xylan by a 90-day feeding study in rats.

Xylans are present naturally in various plants and have important uses in nutrition, food, novel material and biotechnology; however, to date, data regarding their systemic toxicity and safety evaluation is still limited. This study investigated the potential toxicity of xylan from sugarcane bagasse by a subchronic toxicity study in rats. A total of 80 male and female rats were fed with diets containing 10%, 5%, 2.5% and 0% (control) xylan for 90 days. A toxicological assessment was performed including mortality, body and organ weights, food consumption, blood biochemistry, hematology, urinalysis, gross necropsy and histopathological examinations. There were no signs of toxicity and treatment-related changes in rats treated with xylan. The no-observed-adverse-effect levels (NOAEL) of xylan were 9.0 g kg-1 bw for males and 10.6 g kg-1 bw for females of rats under this experimental condition, respectively.

Safety assessment of powdered Cistanche deserticola Y. C. Ma by a 90-day feeding test in Sprague-Dawley rats.

Cistanche deserticola (C. deserticola), a holoparasitic plant widely distributed in arid or semi-arid areas in Eurasia and North Africa, has been used as an important tonic in traditional Eastern medicine for centuries. However, little information on the systemic toxicity and safety evaluation of it is available. The purpose of this study was to investigate the potential toxicity of powdered C. deserticola as a novel food ingredient by use of a subchronic toxicity study in Sprague-Dawley (SD) rats. A total of 80 male and female rats were fed with diets containing 8, 4, 2 and 0% (control) powdered C. deserticola for 90 days. A toxicological assessment was performed including mortality, body and organ weight, food consumption, blood biochemistry, hematology, gross necropsy and histopathological examinations. There were no signs of toxicity and treatment-related changes in rats treated with powdered C. deserticola. The no-observed-adverse-effect level (NOAEL) of powdered C. deserticola was 7.8 g kg-1 body weight for males and 8.0 g kg-1 body weight for females of rats under the experimental conditions of this study.

Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure.

The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg-1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO3 up to 1 mg kg-1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO3 treated rats. However, the comparisons between AgNPs and AgNO3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017.

Effect of Cadmium on Cellular Ultrastructure in Mouse Ovary.

This study aimed at analyzing the cytotoxicity and pathological effects of cadmium on the ovary. Our studies revealed that cadmium was deposited in the mouse ovary after 8 d cadmium injection in vivo. Also, the increase in the rate of body weight was slowed, while the gonadosomatic index was reduced in the CdCl2 group, compared with the control group. Meanwhile, cadmium affected the maturation of follicles, the degradation of corpus luteum, the arrangement of follicles and corpus luteum, and increased the number of atresia follicles. Besides, under the electron microscope, chromatin margination, karopyknosis, swelling of mature cisternae of Golgi apparatus, mitochondrial cristae disappearance, and swelling of the rough endoplasmic reticulum can be observed in the CdCl2 group mice. Collectively, our findings elucidated the morphological mechanism that the exposure of cadmium changed the ultrastructure of cells in ovary tissues.

Bilateral subconjunctival haemorrhage in spinal cord injury: a case report.

Neurogenic lower urinary tract dysfunction is a common symptom after spinal cord injury. Here, the case of a 45-year-old male patient who was treated with indwelling urinary catheter during spinal surgery for a fall fracture injury of the T12 thoracic vertebra, associated with decreased muscle strength of both lower extremities, is described. During hospitalization in the rehabilitation department, conventional anticoagulation therapy was administered, and the urinary catheter was removed with the patient urinating by increasing abdominal pressure. At 8 days following urinary catheter removal, the patient was found to have a slight subconjunctival haemorrhage of the left eye, which gradually developed into massive subconjunctival haemorrhage in both eyes. After re-indwelling the urinary catheter, the bilateral subconjunctival haemorrhage gradually improved. No abnormal indicators were found during re-examination of coagulation function and platelet count, and the results of ophthalmological examination were normal. For patients with neurogenic bladder dysfunction associated with spinal cord injury, the risk of bleeding during the anticoagulation period should be carefully assessed to eliminate possible underlying bleeding risk factors (including past medical history and appropriate use of anticoagulant drugs) when considering spontaneous urination through the mode of abdominal pressure.

Efficient biodegradation of tris-(2-chloroisopropyl) phosphate by a novel strain Amycolatopsis sp. FT-1: Process optimization, mechanism studies and toxicity changes.

In this study, a newly isolated strain Amycolatopsis sp. FT-1 was confirmed to be an efficient tris-(2-chloroisopropyl) phosphate (TCPP) degrader. The maximum degradation efficiency of 100 % was achieved when glucose concentration was 6.0 g/L, TCPP concentration was 1.1 mg/L, pH was 6.3 and temperature was 35 °C. Proteome analysis indicated that TCPP was transformed into diester, monoester and ketone product through hydrolysis by phosphoesterase and oxidation mediated by proteins involved in bio-Fenton reaction. The increased expression of proteins serving as organic hydroperoxides scavenger and two subunits of xanthine dehydrogenase enabled Amycolatopsis sp. FT-1 to defend against TCPP-induced oxidative damage. Meanwhile, proteins involved in the resistance to proteotoxic stress were found to be up-regulated, including Hsp70 protein, ATP-dependent Clp protease proteolytic subunit, elongation factor G and trehalose synthesis-related enzymes. The overexpression of TetR/AcrR family transcriptional regulator and multidrug efflux transporter also benefited the survival of Amycolatopsis sp. FT-1 under TCPP stress. Luminescent bacteria test showed that biotoxicity of TCPP was remarkably decreased after biodegradation by Amycolatopsis sp. FT-1. To the best of our knowledge, this is the first study to report the biotransformation of TCPP by pure strain and to offer important insights into the proteomic mechanisms of TCPP microbial degradation.

Short-term toxicity assessment of combined use of zidovudine, lamivudine and lopinavir/ritonavir in vitro and in vivo.

INTRODUCTION: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. METHOD: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. RESULTS: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05). CONCLUSION: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.

Chaotification of complex networks with impulsive control.

This paper investigates the chaotification problem of complex dynamical networks (CDN) with impulsive control. Both the discrete and continuous cases are studied. The method is presented to drive all states of every node in CDN to chaos. The proposed impulsive control strategy is effective for both the originally stable and unstable CDN. The upper bound of the impulse intervals for originally stable networks is derived. Finally, the effectiveness of the theoretical results is verified by numerical examples.

Stabilization of Positive Systems With Time Delay via the Takagi-Sugeno Fuzzy Impulsive Control.

In this study, the Takagi-Sugeno (T-S) fuzzy impulsive control problem is investigated for a class of nonlinear positive systems with time delay. The time delay under consideration is both in the continuous-time dynamics and at the impulsive instants, which can model practical systems more accurately. An impulse-time-dependent copositive Lyapunov function (IDCLF) is constructed, and the Razumikhin technique is adopted to develop conditions that ensure the globally exponential stability of T-S fuzzy positive systems with delayed impulses. The size constraint between the impulse delay and the bound of impulsive intervals is removed. A T-S fuzzy impulsive controller is designed in terms of the solutions to certain vector inequalities that are readily solvable. Numerical examples and a practical example of lipoprotein metabolism and potassium ion transfer model are given to demonstrate the effectiveness, advantages, and practicality of the proposed results.

Adaptive proxy-based sliding mode control for a class of second-order nonlinear systems and its application to pneumatic muscle actuators.

The human-centered robotic systems demand safe and robust controllers in many applications. This paper proposes an adaptive proxy-based sliding mode control approach for a class of typical second-order nonlinear systems. A new PID-type virtual coupling is designed between a virtual proxy and the physical object. Considering the unknown bound of lumped disturbances, an adaptation law is applied to online adjust the gain of a sign function which ensures the proxy to track the reference accurately. By using the Lyapunov theorem, the closed-loop system stability is proved. Both simulations and experiments are conducted to verify the proposed method based on a real-world pneumatic muscle actuator control platform. The results show that the proposed adaptive proxy-based sliding mode control approach presents better tracking accuracy, safety, and robustness than the conventional PID control and sliding mode control.

Formation-containment control of multiple underactuated surface vessels with sampling communication via hierarchical sliding mode approach.

The formation-containment control problem of multiple underactuated surface vessels (USVs) is investigated in this paper. A hierarchical sliding mode control strategy is proposed to solve this problem under sampling communication. The proposed control comprises two layers: a local sliding model control layer and a distributed coordination layer. The local control layer is designed to drive each USV tracking the reference trajectories, and the distributed coordination layer is proposed to generate the reference trajectories satisfying the control objective of formation-containment control. To achieve the formation-containment control of the closed-loop multiple USVs, a sufficient condition is obtained by utilizing the Lyapunov stability and eigenvalue analysis. Finally, a simulation result is provided to show the effectiveness of the proposed hierarchical sliding mode approach.

Efficacy of Dexmedetomidine Anesthesia plus Dorsal Penile Nerve Block in Pediatric Circumcision.

Objective: To assess the efficacy of dexmedetomidine anesthesia plus dorsal penile nerve block in pediatric circumcision. Methods: In this retrospective study, 80 children receiving circumcision in our hospital from February 2020 to February 2021 were recruited and assigned via different anesthesia methods at a ratio of 1 : 1 to receive dorsal penile nerve block plus dexmedetomidine anesthesia (combined anesthesia group) or only sevoflurane for total inhalational anesthesia (total anesthesia group). Traditional Chinese medicine (TCM) care was introduced to both groups of patients. Outcome measures included vital signs, operative indices, anesthesia effect, adverse reactions, parent satisfaction, and nursing satisfaction. Results: There were no significant differences in the heart rate, oxygen saturation, and mean arterial pressure between the two groups of children before anesthesia, after anesthesia, and during the awakening period (P > 0.05). Patients receiving combined anesthesia showed a shorter time lapse before the disappearance of eyelash reflex, longer time lapse before postoperative analgesic use, faster awakening, and shorter operation time and hospital stay versus those receiving total inhalational anesthesia alone (P > 0.05). The combined anesthesia resulted in a lower Induction Compliance Checklist (ICC) score, McGill score, and Richmond Agitation-Sedation Scale (RASS) score and a higher Ramsay score versus total anesthesia (P > 0.05). Patients receiving combined anesthesia showed a significantly lower incidence of adverse events (5.00% (2/40)) versus total inhalational anesthesia (62.50% (25/40)) (X 2 = 29.574, P > 0.05). The combined anesthesia group had a higher parent satisfaction (92.50% (37/40)) versus the total anesthesia group (75.00% (30/40)) (X 2 = 4.501, P > 0.05). A total of 80 questionnaires were distributed, with a 100% return rate and a 100% validity rate, and all 80 questionnaires scored 90 points or above. The families of children in both groups were satisfied with the quality of TCM care. Conclusion: The efficacy of dorsal penile nerve block plus dexmedetomidine anesthesia in pediatric circumcision is better than total inhalational anesthesia with sevoflurane.

Guaranteed Cost for an Event-Triggered Consensus Strategy for Interconnected Two Time-Scales Systems With Structured Uncertainty.

This article proposes the design of an event-triggered control strategy for consensus of interconnected two-time scales systems with structured uncertainty. The control design under consideration ensures also that consensus is achieved with an overall guaranteed cost. Since each system involves processes evolving on both fast and slow time scales, two Zeno-free event-triggered mechanisms are designed to independently decide the sampling and transmission instants for the slow and fast states, respectively. As the first step, we design an event-triggering consensus protocol in the ideal/nominal case when the interconnected systems are not affected by uncertainties and the interactions happen over a fixed interaction network. Next, the results are extended in order to take into account structured uncertainties affecting the systems' dynamics. At this step, we go further and we provide sufficient conditions for event-triggering consensus with a guaranteed overall cost. Finally, two numerical examples are provided to demonstrate the effectiveness of the proposed theoretical results.

Distributed Event-Triggered Synchronization of Interconnected Linear Two-Time-Scale Systems With Switching Topology.

This article investigates the synchronization problem of interconnected linear two-time-scale systems (TTSSs) with switching topology. By utilizing the Chang transformation, a distributed synchronization protocol is proposed with event-triggered communication. Static and dynamic event-triggered mechanisms are proposed successively, which both contain two separated event-triggering conditions corresponding to the slow and the fast subsystems. The existence of a strictly positive time period between any two successive transmissions is ensured regardless of the initial states. The main difficulty of this study lies in that the state jump and parametric uncertainty appear because of the system transformation. To overcome the difficulty, the system is first modeled as an uncertain hybrid system. Then, the control gain is properly designed by solving Riccati-like equations dependent on the rough bounds of the eigenvalues of communication graph Laplacians, and a piecewise quadratic Lyapunov function is proposed with which the jump caused by the switching topology is subtly evaluated. Sufficient conditions are thus established to achieve the event-triggered synchronization. Furthermore, the results are also extended to solve the synchronization problem of the interconnected impulsive linear TTSSs. Finally, three numerical examples are provided to demonstrate the effectiveness of the proposed theoretical results.

Tetrabromobisphenol A perturbs cell fate decisions via BMP signaling in the early embryonic development of zebrafish.

Tetrabromobisphenol A (TBBPA) readily accumulates in the egg yolk of aquatic oviparous animals and is transferred to their embryos. Early embryogenesis is vital for organ formation and subsequent development. The developmental toxicity of TBBPA in aquatic animals has been extensively reported. However, few studies have assessed the toxic effects of TBBPA in the early embryonic development. In this work, we found that TBBPA perturbed cell fate decisions along the dorsal-ventral (DV) axis during gastrulation, further disrupting early organogenesis in the entire embryo. TBBPA exposure increased the number of embryonic cells that acquired a ventral cell fate, which formed epidermis, blood and heart tissues. In return, the number of embryonic cells that acquired a dorsal cell fate was greatly decreased, causing the TBBPA-exposed embryos to develop a small brain and small eyes. We revealed that TBBPA elevated the activity gradient of bone morphogenetic protein (BMP) signaling which is responsible for cell fate specification along the DV axis, with up-regulation of BMP ligands (bmp4, bmp7a) and target genes (szl) and promotion signal transduction through phosphorylation of Smad1/5. As the function of BMP signaling in embryogenesis is highly conserved among many vertebrates, these findings highlight the ecological and health risks of TBBPA.

Moisture content and material density affects severity of frost damage in earthen heritage.

Successful conservation of earthen heritage requires an understanding of interactions between environmental and climatic conditions, soil-based materials and human interventions. Frost cycling is likely to be an important contributor to the deterioration of earthen heritage, with frost damage known to cause deterioration features such as flaking and granular disintegration. However, it is not clear how important a contribution frost cycling makes in comparison with other agents. Previous earthen heritage studies have focused on other agents of deterioration, such as wind and rain, or investigated the role of freeze-thaw cycles under conditions unrepresentative of many earthen sites. We investigate how density and moisture content affect the severity of frost damage on earthen heritage using materials and conditions informed by those found at earthen sites in NW China. We prepared rammed earth cubes (5 × 5 × 5 cm) at two densities (1.65 and 1.75 g cm-3) and with five moisture content levels between 0.46 and 8%. Samples were subjected to 80 freeze-thaw temperature cycles (+7 to -15 °C) in an environmental cabinet. Deterioration was recorded using visual assessment, measurements of surface roughness, ultrasonic pulse velocities, a Vicat needle test and mass loss. Results showed frost damage was dependent on moisture content and density of rammed earth samples. Samples with <2% moisture content showed no visible frost damage. Samples with higher moisture contents (>6%) and higher densities exhibited the greatest deterioration with surface granulation, salt efflorescence and flakes detaching from the parent cubes. This suggests that frost damage to rammed earth is likely to be focused in periods when rainfall or snowmelt is followed by freeze-thaw temperature cycling. In addition, results suggest that if higher density earthen materials are used for repairs or restoration for sites in dryland environments, these could be more vulnerable to frost damage than lower density materials.

Fixed-Time Synchronization of Competitive Neural Networks With Multiple Time Scales.

In this brief, we investigate the fixed-time synchronization of competitive neural networks with multiple time scales. These neural networks play an important role in visual processing, pattern recognition, neural computing, and so on. Our main contribution is the design of a novel synchronizing controller, which does not depend on the ratio between the fast and slow time scales. This feature makes the controller easy to implement since it is designed through well-posed algebraic conditions (i.e., even when the ratio between the time scales goes to 0, the controller gain is well defined and does not go to infinity). Last but not least, the closed-loop dynamics is characterized by a high convergence speed with a settling time which is upper bounded, and the bound is independent of the initial conditions. A numerical simulation illustrates our results and emphasizes their effectiveness.