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.

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.

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.

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.

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.

α-Ketoglutarate-Mediated DNA Demethylation Sustains T-Acute Lymphoblastic Leukemia upon TCA Cycle Targeting.

Despite the development of metabolism-based therapy for a variety of malignancies, resistance to single-agent treatment is common due to the metabolic plasticity of cancer cells. Improved understanding of how malignant cells rewire metabolic pathways can guide the rational selection of combination therapy to circumvent drug resistance. Here, we show that human T-ALL cells shift their metabolism from oxidative decarboxylation to reductive carboxylation when the TCA cycle is disrupted. The α-ketoglutarate dehydrogenase complex (KGDHC) in the TCA cycle regulates oxidative decarboxylation by converting α-ketoglutarate (α-KG) to succinyl-CoA, while isocitrate dehydrogenase (IDH) 1 and 2 govern reductive carboxylation. Metabolomics flux analysis of T-ALL reveals enhanced reductive carboxylation upon genetic depletion of the E2 subunit of KGDHC, dihydrolipoamide-succinyl transferase (DLST), mimicking pharmacological inhibition of the complex. Mechanistically, KGDHC dysfunction causes increased demethylation of nuclear DNA by α-KG-dependent dioxygenases (e.g., TET demethylases), leading to increased production of both IDH1 and 2. Consequently, dual pharmacologic inhibition of the TCA cycle and TET demethylases demonstrates additive efficacy in reducing the tumor burden in zebrafish xenografts. These findings provide mechanistic insights into how T-ALL develops resistance to drugs targeting the TCA cycle and therapeutic strategies to overcome this resistance.

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.

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.

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.

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.

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.

Lag-Bipartite Formation Tracking of Networked Robotic Systems Over Directed Matrix-Weighted Signed Graphs.

This article studies the lag-bipartite formation tracking (LBFT) problem of the networked robotic systems (NRSs) with directed matrix-weighted signed graphs. Unlike the traditional formation tracking problems with only cooperative interactions, solving the LBFT problem implies that: 1) the robots of the NRS are divided into two complementary subgroups according to the signed graph, describing the coexistence of cooperative and antagonistic interactions; 2) the states of each subgroup form a desired geometric pattern asymptotically in the local coordinate; and 3) the geometric center of each subgroup is forced to track the same leader trajectory with different plus-minus signs and a time lag. A new hierarchical control algorithm is designed to address this challenging problem. Based on the Lyapunov stability argument and the property of the matrix-weighted Laplacian, some sufficient criteria are derived for solving the LBFT problem. Finally, simulation examples are proposed to validate the effectiveness of the main 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.

Output Multiformation Tracking of Networked Heterogeneous Robotic Systems via Finite-Time Hierarchical Control.

This article investigates the finite-time output multiformation tracking (OMFT) problem of networked heterogeneous robotic systems (NHRSs), where each robot model involves external disturbances, parametric uncertainties, and possible kinematic redundancy. Besides, the interactions among robotic systems are described as a directed graph with an acyclic partition. Then, several novel practical finite-time hierarchical control (FTHC) algorithms are designed. The convergence analysis of the closed-loop dynamics is extremely difficult due to the lack of effective analysis methods. Based on the mathematics induction and reductio ad absurdum, a new nonsmooth Lyapunov function is proposed to derive the sufficient conditions and settling time functions. Finally, numerical simulations are performed on the NHRS to verify the main results.

Safety Assessment of Water-Extract Sericin from Silkworm (Bombyx mori) Cocoons Using Different Model Approaches.

Sericin is a natural protein component of silks of silkworm and has potential utility in multiple areas such as pharmacological, cosmetics, and biotechnological industries. However, the understanding of its toxicological safety is still limited. This study evaluated the safety of water-extract sericin from silkworm (Bombyx mori) cocoons using different model approaches, including three genotoxicity studies (the bacterial reverse mutation test, the mammalian erythrocyte micronucleus test, and the mouse spermatogonia chromosomal aberration test) and a 90-day subchronic toxicity study in Sprague-Dawley (SD) rats. The results of this study showed that water-extract sericin was nonmutagenic and nongenotoxic both in vitro and in vivo. Sericin did not induce significant changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine index, and histopathology in rats. The NOAEL of sericin was determined to be 1 g/kg/day for male and female rats. These results indicated that water-extract sericin was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.

Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis.

Deregulation of MYC plays an essential role in T cell acute lymphoblastic leukemia (T-ALL), yet the mechanisms underlying its deregulation remain elusive. Herein, we identify a molecular mechanism responsible for reciprocal activation between Aurora B kinase (AURKB) and MYC. AURKB directly phosphorylates MYC at serine 67, counteracting GSK3ß-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomal degradation. Stabilized MYC, in concert with T cell acute lymphoblastic leukemia 1 (TAL1), directly activates AURKB transcription, constituting a positive feedforward loop that reinforces MYC-regulated oncogenic programs. Therefore, inhibitors of AURKB induce prominent MYC degradation concomitant with robust leukemia cell death. These findings reveal an AURKB-MYC regulatory circuit that underlies T cell leukemogenesis, and provide a rationale for therapeutic targeting of oncogenic MYC via AURKB inhibition.

Distributed Control of Nonlinear Multiagent Systems With Unknown and Nonidentical Control Directions via Event-Triggered Communication.

In this paper, the leader-following output consensus problem for a class of uncertain nonlinear multiagent systems with unknown control directions is investigated. Each agent system has nonidentical dynamics and is subject to external disturbances and uncertain parameters. The agents are connected through a directed and jointly connected switching network. A novel two-layer distributed hierarchical control scheme is proposed. In the upper layer, to save the communication resources and to handle the switching networks, an event-triggered communication scheme is proposed, and a Zeno-free event-triggered mechanism is designed for each agent to generate the asynchronous triggering time instants. Furthermore, to avoid the continuous monitoring of the system states, a Zeno-free self-triggering algorithm is proposed. In the lower layer, to handle the unknown control directions problem and to achieve the output tracking of the local references generated in the upper layer, the Nussbaum-type function-based technique is combined with internal model principle. With the proposed two-layer distributed hierarchical controller, the leader-following output consensus is achieved. The obtained result is further extended to the formation control problem. Finally, three numerical examples are provided to demonstrate the effectiveness of the proposed theoretical results.

Subchronic Study of a White Kidney Bean (Phaseolus vulgaris) Extract with α-Amylase Inhibitory Activity.

Common bean extract as a dietary supplement has received increased attention globally owing to its α-amylase inhibitory activity. The objective of this study was to evaluate the toxicity of a white kidney bean (Phaseolus vulgaris) extract by a repeated-dose 90-day subchronic oral toxicity study in Sprague-Dawley rats. In the subchronic toxicity study, 80 rats were orally administrated with white kidney bean extract at doses of 4, 2, and 1 g/kg body weight daily for 90 days. The results showed that the white kidney bean extract at doses up to 4 g/kg/day did not induce significant changes in body weight, organ weight, food consumption, hematology, serum biochemistry, and histopathology in rats, as compared to the control. The no-observed-adverse-effect level (NOAEL) of white kidney bean extract was determined to be >4 g/kg/day for both male and female rats, under the experimental conditions of this study.

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.