Preparation and epitope analysis of monoclonal antibodies against African swine fever virus DP96R protein.

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.

Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

Discovery of novel 2,3,4,5-tetrahydrospiro[benzo[c]azepine-1,1'-cyclohexan]-5-ol derivatives as PARP-1 inhibitors.

As an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized. Among them, compound 11b exhibited better anti-proliferative effects against A549 cells (IC50 = 1.95 µM). The SI results showed that compound 11b had low toxicity. Moreover, compound 11b displayed excellent PARP-1 inhibitory activities with IC50 values of 19.24 nM. In addition, molecular docking studies provided the rational binding modes of compound 11b in complexes with PARP-1. The flow cytometry assays revealed that compound 11b could induce apoptosis of A549 cells (P < 0.001). Simultaneously, compound 11b could effectively reduce the formation of PAR (P < 0.001). The ADMET prediction results indicated compound 11b had similar properties to rucaparib. Collectively, compound 11b has potential research value for further investigation.

Effect of sling exercise therapy on surface electromyography and muscle thickness of superficial cervical muscle groups in female patients with chronic neck pain.

BACKGROUND: The persistence of symptoms in patients with chronic neck pain is considered to be associated with variation in the neck muscle structure and associated neuromuscular control. Sling exercise therapy (SET) has been demonstrated to relieve the symptoms of chronic neck pain, whereas it is controversial whether this benefit is correlated to altered neck muscle structure and associated neuromuscular control in the patients. OBJECTIVE: To investigate the effect of SET on cervical muscle structure (thickness) and associated neuromuscular control in patients with chronic neck pain. METHODS: Twenty-five patients with chronic neck pain were randomly assigned to the SET group (n= 12) or the control group (n= 13). The SET group received the SET intervention for 4 weeks, while the control group maintained normal activities of daily living. At baseline and after 4 weeks of intervention, Visual analogue scale and neck disability index were measured in both groups, and changes in the thickness of the superficial cervical muscles were assessed using musculoskeletal ultrasound. Surface electromyography (EMG) was adapted to assess the neuromuscular control of the neck while the participant was performing the cranio-cervical flexion test. RESULTS: At 4 weeks, the SET group had a significant reduction of RMS in both UT and SCM of EMG compared to the control group (p< 0.05). Regarding ultrasound, the SET group had significantly lower muscle thickness compared to the control group in both the rest position and the MVIC position (p< 0.05). There were no within-group differences in the control group (p> 0.05), while the SET group showed significant reductions in both RMS and muscle thickness (p< 0.05). CONCLUSION: 4-week SET was effective in reducing pain and dysfunction in patients with chronic neck pain, which may be related to improved neck muscle thickness and neuromuscular control of the neck.

Tai Chi for spatiotemporal gait features and dynamic balancing capacity in elderly female patients with non-specific low back pain: A six-week randomized controlled trial.

BACKGROUND: Non-specific low back pain (NS-LBP) is a serious public health problem. Tai Chi is promising in reducing the risk of falls and alleviating symptoms in this population. OBJECTIVE: To investigate the effect of Tai Chi on gait and dynamic balance in elderly women with NS-LBP. METHODS: 20 women (age > 65 yr.) with NS-LBP were randomly assigned to a Tai Chi group (n= 10) or a control group (n= 10). The Tai Chi group practiced Tai Chi exercise 3 times a week for 6 weeks. Each session lasted 60 minutes. Pain, spatiotemporal gait features and dynamic balancing capacity were assessed at 0 and 6 weeks. RESULTS: Compared to the control group at 6 weeks, the Tai Chi group had a significant decrease in VAS (p= 0.027) and stride width (p= 0.019), significant improvement in gait velocity, stride length (p< 0.001). Regarding dynamic balance capacity, the Tai Chi group had significant improvements in anterior (Left: p= 0.001; Right: p= 0.038), postero-lateral (Left: p< 0.001; Right: p= 0.038), and postero-medial (Left: p= 0.015; Right: p= 0.018). CONCLUSION: 6-week Tai Chi can relieve pain and improve gait and dynamic balance in elderly women with NS-LBP, which suggests Tai Chi could be a promising rehabilitation intervention to reduce the risk of falls in this population.

Comparison between Tai Chi and square dance on the antihypertensive effect and cardiovascular disease risk factors in patients with essential hypertension: a 12-week randomized controlled trial.

BACKGROUND: The prevalence of essential hypertension increases consistently among middle-aged and older adults in China. Aims of this study are to explore the impact of Tai Chi and square dance, which are popular in China, on antihypertensive effects and cardiovascular disease risk factors in patients with essential hypertension. METHODS: Patients with essential hypertension were randomly assigned to either a Tai Chi group, a square dance group or a control group. Blood pressure, cardiorespiratory fitness, and cardiovascular disease risk factors were measured at baseline and at the end of the 12-week intervention. The duration and frequency of both intervention exercises were 60 minutes per session, and 5 sessions per week. RESULTS: A total of 144 participants (59.89±6.85 years, 34.72% male) completed the study. The repeated-measures analysis of variance demonstrated a significant effect of time on BMI, systolic and diastolic blood pressure, and cardiorespiratory fitness in patients with essential hypertension (P<0.05), whereas no significant effect was observed on waist-to-hip ratio and body fat percentage (P>0.05). Post hoc analyses showed that only intervention groups had significant differences in blood pressure and cardiorespiratory fitness compared to the control group, while Tai Chi had greater effect sizes than square dance. CONCLUSIONS: Both Tai Chi and square dance can promote cardiorespiratory fitness and reduce BMI and blood pressure among patients with essential hypertension, whereas there was no significant difference between the two exercises. However, both Tai Chi and square dance were ineffective in reducing some of the cardiovascular disease risk factors.

Probing Rotated Weyl Physics on Nonlinear Lithium Niobate-on-Insulator Chips.

Topological photonics, featured by stable topological edge states resistant to perturbations, has been utilized to design robust integrated devices. Here, we present a study exploring the intriguing topological rotated Weyl physics in a 3D parameter space based on quaternary waveguide arrays on lithium niobate-on-insulator (LNOI) chips. Unlike previous works that focus on the Fermi arc surface states of a single Weyl structure, we can experimentally construct arbitrary interfaces between two Weyl structures whose orientations can be freely rotated in the synthetic parameter space. This intriguing system was difficult to realize in usual 3D Weyl semimetals due to lattice mismatch. We found whether the interface can host gapless topological interface states or not is determined by the relative rotational directions of the two Weyl structures. In the experiment, we have probed the local characteristics of the TISs through linear optical transmission and nonlinear second harmonic generation. Our study introduces a novel path to explore topological photonics on LNOI chips and various applications in integrated nonlinear and quantum optics.

Synthesis, in vitro ADME profiling and in vivo pharmacological evaluation of novel glycogen phosphorylase inhibitors.

A small set of indole-2-carboxamide derivatives identified from a high-throughput screening campaign has been described as a novel, potent, and glucose-sensitive inhibitors of glycogen phosphorylase a (GPa). Among this series of compounds, compound 2 exhibited moderate GP inhibitory activity (IC50 = 0.29 µM), good cellular efficacy (IC50 = 3.24 µM for HepG2 cells and IC50 = 7.15 µM for isolated rat hepatocytes), together with good absorption, distribution, metabolism, and elimination (ADME) profiles. The in vivo animal study revealed that compound 2 significantly inhibited an increase of fasting blood glucose level in adrenaline-induced diabetic mice.

[Effect of rotation stimulation on the anesthetic sensitivity of sevoflurane in rats].

OBJECTIVE: To explore the effect of simulated navigation stimulation on the anesthetic sensitivity of sevoflurane in rats, so as to provide basis for rational using sevoflurane during navigation. METHODS: SD rats were stimulated by Crampton model and the conditioned taste aversion (CTA) was regarded as criterion of motion sickness. (1) 60 rats were randomly divided into control (n = 15) and rotation group (n = 45). The changes of behavior and autonomic activity, sevoflurane concentration achieved sleep and anesthesia states, and the revitalization time were observed in two group rats. (2) 32 rats were randomly divided into control (I), rotation (II), anesthesia (III) and rotation plus anesthesia (IV) group (n = 8). The acetylcholine (Ach), norepinephrine (NE), r-aminobutyric acid (GABA), glutamic acid (Glu) of brain cortex, thalamus and hippocampus were determined respectively in the four group rats. RESULTS: In control group, the sevoflurane concentration achieved sleep and anesthesia states were 1.74% +/- 0.05% and 3.54% +/- 0.05% respectively, but, those concentrations were 1.51% +/- 0.06% and 3.14% +/- 0.08% in rotation group. There were lower significantly in rotation group than those in control group (P < 0.01). It was a major characteristic that all of the neurotransmitters were reduced significantly in II group, this was even more in brain cortex and thalamus (P < 0.01). In II group, Ach was upward in brain cortex, NE and GABA were reduced in hippocampus obviously. The change tendency of neurotransmitters in IV group was more close to II group, that was, the effect of rotation stimulation was more obvious. CONCLUSION: The anesthetic sensitivity of sevoflurane could be obvious increased in rats simulated navigation stimulation.

Synthesis and antitumor activity of conjugates of 5-Fluorouracil and emodin.

A series of conjugates of 5-Fluorouracil (5-FU) and emodin were synthesized by coupling trimethyl emodin with N(1), N(3) dialkylated 5-FU. The 5-FU moiety contained various substituents at the N(3)-position were linked to the 2-position of trimethyl emodin via a methylene linkage. Their cytotoxicity against three cancer cell lines and one noncancerous cell were studied. The results revealed that some of conjugates exhibited better or comparable in vitro antitumor activity to 5-FU and emodin and low toxicity in the normal cell. The structure-activity relationship study showed N(3)-aromatic substituent was important for their cytotoxic activity.

[Discussion on medical malpractice in traumatic injury].

By reviewing five medical tangle cases after traumatic injury, the characters of these cases and the cause of medical malpractice had been discussed. After the analysis of the responsibility to the death caused by traumatic injury and medical malpractice, the assessment principle of cooperative competition of causes and degree of participation had been introduced. Meanwhile, it is believed that if comprehensive postmortem examination and pathologic examination were carried out to verify the death cause at first, they would play more important role in the appraisal of medical tangle cases after traumatic injury.