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Ageing is an unavoidable process in humans and a major factor for the increasing risk of various diseases. In the United States, more than 50% of rheumatoid arthritis patients are middle-aged or elderly, but the risk factors and mechanisms by which ageing increases the incidence of rheumatoid arthritis are not known. It has been suggested that the accumulation of DNA fragments increases the risk of autoimmune diseases, such as systemic lupus erythematosus. DNA fragments are a common nucleic acid metabolite in ageing organisms as well as in the serum of humans and animals with rheumatoid arthritis; therefore, we hypothesize that DNA fragments are one of the factors contributing to the development of rheumatoid arthritis due to ageing. First, we analysed two in vitro DNA damage response models by using a gene silencing approach and determined that the DNA fragment clearance gene TREX1 can regulate inflammatory factor release in normal cells. Second, after TREX1 expression was knocked down locally or systemically in rats via the Cre-LoxP system and compared with that in AIA(adjuvant-induced arthritis) model rats treated with AAV-TREX1, it was determined that DNA fragments can result in manifestations of arthritis and abnormal activation of the immune system in rats. These results, including the low expression of the TREX1 gene in clinical patient and AIA model samples and the results of immunohistochemical, Western blot, and transcriptome analyses, revealed that the TREX1 gene can regulate cellular senescence-associated secretory phenotype (SASP)-related manifestations and showed that dysregulation of c-Jun and c-Fos, components of the TREX1 transcription factor AP-1, is associated with SASP induction. Finally, it was confirmed in vitro that different causes of decreased c-Fos expression can inhibit TREX1 expression. These DNA fragments are potent producers of inflammation-releasing mediators, and TREX1 is an effective degrader of DNA fragments; it is also a key gene that regulates cellular immunity and ageing. Therefore, effectively clearing excess DNA fragments from the body and ensuring the health of senescent cells may be a potential prevention strategy for RA.

Event-triggered consensus in leader-following multi-agent systems with actuator fault is considered in this paper, in which the fault investigated can be multiplicative fault and outage fault. An event-triggered mechanism is utilized to relieve the communication burden of the interconnected system. Then, control allocation is proposed to solve actuator fault in the multi-agent systems for the first time. Compared with the existing fault-tolerant methods, the proposed method can guarantee that the consensus errors converge to zero asymptotically without the traditional rank assumption. Meanwhile, the Zeno behavior of the event-triggered system is proved to be avoided. Simulation results are also provided to verify the effectiveness of the proposed method.

This study aimed to improve the conventional rat burn wound model and to validate its utility. In total, 60 Sprague-Dawley rats were divided equally into the control and experimental groups. Altogether, 60 burn wound models with zones of stasis were created in each group. Gross visual assessments of the burn wounds were performed at 0 h, 24 h, and 48 h after burn creation. The rates of necrosis in the zones of stasis were calculated, and the blood flow from the wounds was examined. Wound tissues were collected 48 h after the burn and subjected to hematoxylin and eosin staining to determine whether the models were successfully established. The model success rates were calculated. The success rate of the burn wound models was significantly different between the control group and the experimental group (93.33% [56/60] vs. 100%; P=0.042). The Cronbach's alpha values and the respective correlation coefficients indicated that the stability of the zones of stasis in the models on the 2 sides of the spine was higher in the experimental group than in the control group. The standard deviations of the rate of necrosis, blood flow, and density of necrotic cells and apoptosis cell density, and inflammatory factor content in the zones of stasis were smaller in the experimental group than in the control group at 48 h after model construction. This suggested that the stability of repeated procedures was higher in the experimental group than in the control group. The novel device for creating burns in animal models facilitated the effective creation of zones of stasis for rat burn wound models. Both the model success rate and stability were higher compared with the conventional model construction method. In addition, the use of the novel device can better align with the requirements of self-controlled studies. This article is protected by copyright. All rights reserved.

Consensus problem in a leader-following multi-agent system with actuator fault is investigated in this paper. By introducing the control allocation and optimal method, a novel distributed controller is proposed to deal with the partial loss of effectiveness and outage fault without reconfiguring the controller. Compared with the existing literatures, the proposed algorithm can guarantee the consensus errors converge to zero asymptotically without the traditional rank assumption. Finally, three simulations are provided to verify the effectiveness of the proposed method.

Objective: To reduce the blood pressure and elevate intracranial pressure using nimodipine (Nimotop Intravenous (IV) infusion). Thus, intracerebral hemorrhage was controlled, and the purpose of hemostasis was achieved. Methods: Sixty-eight patients with intracerebral hemorrhage were divided into a treatment group (n = 51), and a control group (n = 35). Nimotop solution (10 mg) was administered as a fast-flowing IV infusion in the treatment group, and 250 ml 20% mannitol infusion was given to patients in the control group twice every day. Patients in both groups received treatment for seven days, and the blood pressure on the treatment day was measured. A brain Computed Tomography (CT) scan was performed as a reexamination within two weeks. Results: The blood pressure in the treatment group was decreased from 179/104 to 151/91 mmHg, averagely, and in the control group was decreased from 181/108 to 180/103 mmHg, averagely. The difference between these two groups was statistically significant (P P Conclusion: Nimodipine can dilate the arteries, reduce blood pressure, and elevate intracranial pressure, lowering pressure gradients across vessel wall which destroy the vessel wall. Also, nimodipine can prevent hemorrhage as well as recurrent hemorrhage, and can used as the first choice of rescue drug. What’s more, dehydration drugs such as mannitol should not be used in the early stage of intracerebral hemorrhage in order to prevent hematoma enlargement.

Fault tolerant consensus control in a linear leader-follower multi-agent system is investigated in this paper. The communication topology among followers is supposed to be undirected. An loss of effect fault is considered for the system. Firstly, a performance index function is proposed to analyze the consensus of the faulty system. Then, based on the Euler-Lagrange equation, a controller that guarantees the consensus of the faulty system without solving the difficult HJB equation is obtained in this paper. Finally, simulations are utilized to verify the effectiveness of the proposed method.

There exist such problems as high cost, difficult construction and low automation degree of existing landslide monitoring system. To treat these problems, a high-speed railway landslide monitoring system based on Zigbee wireless network technology is designed. In this system, high-speed railway landslide information is obtained by wireless sensor network location technology. Its monitoring data is transmitted by rail side room to remote monitoring center. According to the characteristics of the landslide, location coordinate system is improved. Plan of the system structure and program based on weighted Received Signal Strength Indicator (RSSI) location algorithm is introduced. The simulation experimental results show that the monitoring system can monitor effectively high-speed railway landslide.

Background Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed. Methods We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects. Results Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5. Conclusions Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

Recent studies have identified mutations in the dynein heavy chain gene (DYNC1H1), which lead to 2 closely related human motor neuropathies: a dominant spinal muscular atrophy with lower extremity predominance (SMALED) and axonal Charcot-Marie-Tooth (CMT) disease.(1,2) We describe the identification of a novel mutation (p.G807S) in DYNC1H1 as the cause of SMALED.

Most patients with amyotrophic lateral sclerosis (ALS) have mild cognitive impairment.1 A familial ALS (fALS) case carrying a SOD1 missense mutation with non-executive cognitive impairment was reported.2 However, cognitive impairment in fALS remains poorly understood. We report on a Chinese family with a novel SOD1 mutation, G41D, which causes slow progression of motor neuron function loss and cognitive impairment. The research was approved by the Ethics Committee of The People's Hospital of Jiangsu Province. A 62-year-old woman (the proband) was admitted to our department due to a 12-year history of progressive limb weakness and gait impairment. We obtained informed consent for the genetic study from the patient. The proband had muscle weakness in her left upper limb at 50 years of age and subsequently developed muscle weakness in both upper limbs as well as progressive upper motor neuron symptoms in her lower extremities. At 62 years of age, her muscle weakness worsened, with the appearance of atrophy in her upper limbs and diffuse cramps in her lower limbs, including gait abnormalities. She showed dysarthria and dysphonia, and no dysphagia. Neurological examination showed diffuse weakness in the distal arm muscles with less strength than antigravity, and moderate weakness in the proximal arm muscles with strength against resistance. Fasciculation was observed in these muscles. She also exhibited tongue hypotrophy with fasciculation. Additionally, there was pathological hyperreflexia. Cerebrospinal fluid analyses were normal and serum cryoglobulins were absent. MRI scans of the brain and cervical, thoracic and lumber spine were normal. The 18F-fluorodeoxyglucose cerebral positron emission tomography revealed reduced uptake in the left supermarginal gyrus and left frontopolar …

A decision-making problem is the process of finding the best option from all of the feasible alternatives. To some extent, the decision-makers usually are more confident making linguistic judgments than crisp value judgments. The aim of this paper is to extend the technique for order preference by similarity to ideal solution(TOPSIS) method to decision-making problems with the triangular fuzzy function. In this paper the triangular fuzzy function is introduced into the multi-objective decision making(MODM) problem under uncertainty and the fuzzy TOPSIS approach is proposed to solve the MODM problem with subjective linguistic variables. First the triangular fuzzy numbers are used to describe the degree of importance and the attribute value. Then it gives the general steps of solving the MODM problem through the fuzzy TOPSIS approach. Finally, a case study is used to illustrate the procedure of the proposed approach at the end of the paper. With this approach, we provide decision-makers more information to make more powerful decision.