Mitochondrial outer membrane permeabilization and inner membrane permeabilization in regulating apoptosis and inflammation.

Recent studies delineate an intimate crosstalk between apoptosis and inflammation. However, the dynamic mechanism linking them by mitochondrial membrane permeabilization remains elusive. Here, we construct a mathematical model consisting of four functional modules. Bifurcation analysis reveals that bistability stems from Bcl-2 family member interaction and time series shows that the time difference between Cyt c and mtDNA release is around 30 min, which are consistent with previous works. The model predicts that Bax aggregation kinetic determines cells to undergo apoptosis or inflammation, and that modulating the inhibitory effect of caspase 3 on IFN-ß production allows the concurrent occurrence of apoptosis and inflammation. This work provides a theoretical framework for exploring the mechanism of mitochondrial membrane permeabilization in controlling cell fate.

Role of serotonin in regulation of pancreatic and mesenteric arterial function in diabetic mice.

The aim of this study was to investigate the reaction of pancreatic and mesenteric artery to 5-hydroxytryptamine (5-HT, serotonin) and the mechanism of nitric oxide in diabetes. Diabetic mice were induced by streptozotocin through intraperitoneal injection. The vascular tension of the pancreatic, mesenteric and brain basilar arteries in diabetic and control mice were measured by myograph in the applications of angiotensin II, 5-HT, 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), 5-HT1B/1D receptor agonist sumatriptan, 5-HT2B receptor agonist BW723C86, 5-HT1D receptor antagonist Palonosetron and 5-HT2 receptor antagonist Sarpogrelate. The effect of 5-HT on arteries pretreated with L-NAME and sodium nitroprusside (SNP) on arteries pretreated with norepinephrine were measured. The mRNA expressions of eNOS, 5-HT1B, 5-HT1D, 5-HT2A and 5-HT2B in pancreatic and mesenteric arteries were measured by Real-time PCR. The concentration of 5-HT in plasma and eNOS in pancreatic and mesenteric arteries were tested. Our results showed that the tension of pancreatic and mesenteric arteries in diabetic mice impaired to 5-HT, but not Ang II, and to DOI and sumatriptan, but normalized by incubation with L-NAME. Pancreatic and mesenteric arteries showed no differences to SNP after pretreated with NE between diabetic and control mice. The mRNA of eNOS and 5-HT receptors in pancreatic and mesenteric artery showed no difference between control and diabetic mice. We conclude that the effect of 5-HT on the tension of pancreatic and mesenteric arteries decrease in diabetic mice. It may due to the decreased activity of 5-HT receptors and the activation of eNOS, which causes nitric oxide to release more and makes the tension of vessels decreased.

Impact of full field digital mammography diagnosis for female patients with breast cancer.

BACKGROUND: Previous clinical studies have reported that full field digital mammography (FFDM) can be used for diagnosis on breast cancer (BC) with promising outcome results. However, no study systematically investigates its diagnostic impact on female patients with BC. Thus, this systematic review will assess the accurate of FFDM diagnosis on BC. METHODS: In this study, we will perform a comprehensive search strategy in the databases as follows: Cochrane Library, EMBASE, MEDILINE, PSYCINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data from inception to February 28, 2019. All case-controlled studies exploring the impacts of FFDM diagnosis for patients BC will be fully considered for inclusion in this study. Two authors will independently scan the title and abstracts for relevance, and assess full texts for inclusion. They will also independently extract data and will assess methodological qualify for each included study by using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RevMan V.5.3 software (London, UK) and Stata V.12.0 software (Texas, USA) will be used to pool the data and to conduct the meta-analysis. RESULTS: The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of FFDM will be used to determine the diagnostic accuracy of FFDM for the diagnosis of patients with BC. CONCLUSION: Its findings will provide latest evidence for the diagnostic accuracy of FFDM in female patients with BC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019125338.

Investigation on size tolerance of pore defect of girth weld pipe.

Welding quality control is an important parameter for safe operation of oil and gas pipes, especially for high-strength steel pipes. Size control of welding defect is a bottleneck problem for current pipe construction. As a key part of construction procedure for butt-welding of pipes, pore defects in girth weld is difficult to ignore. A three-dimensional non-linear finite element numerical model is established to study applicability of size control indices based on groove shape and softening phenomenon of material in heat-affected zone of practical pipe girth weld. Taking design criteria of pipe as the basis, basic tensile, extremely tensile and extremely compressive loading conditions are determined for pipe stress analysis, and failure criteria based on flow stress is employed to perform stress analysis for pipe girth weld with pore defect. Results show that pipe girth welding stresses of pores at various radial locations are similar. Whereas, stress for pores of different sharpness varied significantly. Besides, tolerance capability of API 5L X90 grade pipe to pore defect of girth weld is lower than that of API 5L X80 grade pipe, and size control index of 3 mm related to pore defect in current standards is applicable to API 5L X80 and X90 grade girth welded pipes with radially non-sharp pore defects.

Laparoscopic versus open appendectomy in adults and children: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to evaluate the differences of laparoscopic appendectomy (LA) versus open appendectomy (OA) in adults and children. METHODS: Randomized controlled trials (RCTs) comparing LA and OA in adults and children between January 1992-March 2016 were included in this study. A meta-analysis was performed to evaluate wound infection, intra-abdominal abscess, postoperative complications, reoperation rate, operation time, postoperative stay, and return to normal activity. RESULT: Thirty-three studies including 3642 patients (1810 LA, 1832 OA) were included. Compared with OA, LA in adults was associated with lower incidence of wound infection, fewer postoperative complications, shorter postoperative stay, and earlier return to normal activity, but a longer operation time. There was no difference in levels of intra-abdominal abscess and reoperation between the groups. Subgroup analysis in children did not reveal significant differences between the two techniques in wound infection, postoperative complications, postoperative stay, and return to normal activity. CONCLUSION: LA in adults is worth recommending as an effective and safe procedure for acute appendicitis, and further high-quality randomized trials comparing the two techniques in children are needed.

Vision and Relevant Risk Factor Interventions for Preventing Falls among Older People: A Network Meta-analysis.

Our study objective was to determine the effect of vision intervention and combinations of different intervention components on preventing falls and fall-related injuries among older people. Six electronic databases were searched to identify seven articles published before May, 2014. We conducted a systematic review of data from seven randomized controlled trails and identified eight regimens: vision intervention alone (V), vision plus exercise (referred to as physical exercise) interventions (V + E), vision plus home hazard interventions (V + HH), vision plus exercise plus home hazard interventions (V + E + HH), vision plus exercise plus sensation interventions (V + E + S), vision plus hearing interventions (V + H), vision plus various risk factor assessment and interventions (V + VRF), and the control group (C, no intervention group). The main outcome was the incidence of falls during the follow-up period. Seven papers included 2723 participants. Network meta-analysis of seven trials, using pairwise comparisons between each intervention, indicated there was no significant difference. However, there was a trend in which intervention incorporating V + VRF had more advantages than any other combination of interventions. In conclusion, V + VRF proves to be more effective than other V combination interventions in preventing falls in older people (≥65 years of age). V alone appears less effective in our network meta-analysis.

Assessing the effects of an educational program for the prevention of work-related musculoskeletal disorders among school teachers.

BACKGROUND: Musculoskeletal disorders represent one of the most common and most costly occupational health problems in both developed and developing countries. The aim of this study was to assess the effect of occupational health education and ergonomic training on awareness, attitude and behavior of work-related musculoskeletal disorders among teachers. METHODS: A self-controlled longitudinal study with pre/post design was used to evaluate the effects of intervention among school teachers from the 21st of June, 2010 to the 21st of August, 2011. Choosing a cluster random sampling method, 350 (70.0% response rate (350/500)) teachers from four schools were assigned to receive eight weeks of intervention (participatory ergonomic training and occupational health education). Evaluations focused on teachers who participated in both pre- and post-questionnaires. Two post-tests were then administered to the participants to identify changes at six and 12 months after intervention. RESULTS: The follow-up rate was 93.7% (328/350) at six months after intervention, and 90.9% (319/350) at 12 months after intervention. After the intervention, the awareness rate, attitude and health behavior improved. The self-reported prevalence of work-related musculoskeletal disorders for neck, shoulder, upper and lower back pain, or discomfort were lower than before intervention (P < 0.05). CONCLUSION: Interventions based on occupational health education lectures, on-site ergonomics training, publicity brochures and posters showed a positive effect on prevention and control of the occurrence of work-related musculoskeletal disorders in teachers. Improvement in awareness, behavior and attitude changes, and prevalence were found at both six and 12 months post-intervention, confirming that the effectiveness of the program can be sustained.

Fuzzy fault tree assessment based on improved AHP for fire and explosion accidents for steel oil storage tanks.

Fire and explosion accidents of steel oil storage tanks (FEASOST) occur occasionally during the petroleum and chemical industry production and storage processes and often have devastating impact on lives, the environment and property. To contribute towards the development of a quantitative approach for assessing the occurrence probability of FEASOST, a fault tree of FEASOST is constructed that identifies various potential causes. Traditional fault tree analysis (FTA) can achieve quantitative evaluation if the failure data of all of the basic events (BEs) are available, which is almost impossible due to the lack of detailed data, as well as other uncertainties. This paper makes an attempt to perform FTA of FEASOST by a hybrid application between an expert elicitation based improved analysis hierarchy process (AHP) and fuzzy set theory, and the occurrence possibility of FEASOST is estimated for an oil depot in China. A comparison between statistical data and calculated data using fuzzy fault tree analysis (FFTA) based on traditional and improved AHP is also made. Sensitivity and importance analysis has been performed to identify the most crucial BEs leading to FEASOST that will provide insights into how managers should focus effective mitigation.

Isoprenaline: a potential contributor in sick sinus syndrome--insights from a mathematical model of the rabbit sinoatrial node.

The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca²âº transient, and i(Na) changes induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase in i(Na) and i(Ca,T) which were reduced by the mutation.

Induced dipoles incorporated into all-atom Zn protein simulations with multiscale modeling.

Zinc is found saturated in the deposited Amyloid-beta (Aß) peptide plaques in Alzheimer's disease (AD) patients' brains. Binding of zinc promotes aggregation of Aß, including the pathogenic aggregates. Up to now, only the region 1-16 of Aß complexed with zinc (Aß(1-16)-Zn) is defined structurally in experiment. In order to explore the induced polarization effect of zinc on the global fluctuations and the experimentally observed coordination mode of Aß(1-16)-Zn, we consider an all-atom molecular dynamics (MD) of Aß(1-16)-Zn solvated in implicit water. In our model, the zinc polarization affects the whole peptide. The induced dipoles are divided into three distinct scales according to their distances from zinc. Besides, the atomistic polarizability on the coordinating side chains is rescaled to describe the electron redistribution effect. We show that, associated with proper van der Waals (vdW) parameters, our model not only obtains the reasonable coordinating configuration of zinc binding site but also retains the global stabilization, especially the N-terminal region, of the Aß(1-16)-Zn. We suggest that it is the induced polarization effect that promotes reasonable solvent exposures of hydrophobic/hydrophilic residues regarding zinc-induced Aß aggregation.

Termination of Ca²+ release for clustered IP3R channels.

In many cell types, release of calcium ions is controlled by inositol 1,4,5-trisphosphate (IP3) receptor channels. Elevations in Ca²âº concentration after intracellular release through IP3 receptors (IP3R) can either propagate in the form of waves spreading through the entire cell or produce spatially localized puffs. The appearance of waves and puffs is thought to implicate random initial openings of one or a few channels and subsequent activation of neighboring channels because of an "autocatalytic" feedback. It is much less clear, however, what determines the further time course of release, particularly since the lifetime is very different for waves (several seconds) and puffs (around 100 ms). Here we study the lifetime of Ca²âº signals and their dependence on residual Ca²âº microdomains. Our general idea is that Ca²âº microdomains are dynamical and mediate the effect of other physiological processes. Specifically, we focus on the mechanism by which Ca²âº binding proteins (buffers) alter the lifetime of Ca²âº signals. We use stochastic simulations of channel gating coupled to a coarse-grained description for the Ca²âº concentration. To describe the Ca²âº concentration in a phenomenological way, we here introduce a differential equation, which reflects the buffer characteristics by a few effective parameters. This non-stationary model for microdomains gives deep insight into the dynamical differences between puffs and waves. It provides a novel explanation for the different lifetimes of puffs and waves and suggests that puffs are terminated by Ca²âº inhibition while IP3 unbinding is responsible for termination of waves. Thus our analysis hints at an additional role of IP3 and shows how cells can make use of the full complexity in IP3R gating behavior to achieve different signals.

Expression, purification, and characterization of a 2,3-dihydroxybiphenyl-1,2-dioxygenase from Bacillus sp. JF8 in Escherichia coli.

2,3-Dihydroxybiphenyl-1,2-dioxygenase plays an important role in the degradation of polychlorinated biphenyls. The gene (BsbphCI) encoding a 2,3-DHBP dioxygenase from Bacillus sp. JF8 is 960 bp. We synthesized a 960 bp BsbphCI gene encoding a 2,3-DHBP dioxygenase derived from Bacillus sp. JF8 and expressed it in Escherichiacoli. The recombinant protein was about 36 kDa, confirmed by SDS-PAGE. The concentration of the purified protein was about 1.8 mg/mL. With 2,3-DHBP as a substrate, the optimal temperature for enzyme activity at pH 8.5 was 50 °C. The optimal pH for the 2,3-DHBP dioxygenase was 8.5. The enzyme retained 33% activity after heating at 60 °C for 60 min. We found that Cu(2+), K(+), Zn(2+), Mg(2+), Ni(2+), Co(2+), and Cd(2+) activated the enzyme. However, Ca(2+), Fe(2+), Li(+), and Cr(3+) inhibited it. Enzyme activity was reduced by exposure to H(2)O(2), SDS, and KI. The results of HPLC indicated that the transgenic E. coli strain with the BsbphCI gene degraded 2,3-DHBP more quickly than the wild type strain.

Neuronal modeling with intracellular calcium signaling.

Cytosolic Ca(2+) ions play an important role in the regulation of numerous aspects of cellular activity in virtually all cell types. There is a complex interaction between the neuronal electrical signals on plasma membrane and the chemical signals of intracellular calcium. Each neuron can be considered as a binary membrane system with plasma membrane and endoplasmic reticulum membrane, and the neuronal endoplasmic reticulum can be regarded as a neuron-within-a-neuron. This review explores the simulation modeling of neuronal dynamics mutually coupled with the intracellular calcium signaling released from endoplasmic reticulum through the inositol 1,4,5-trisphosphate receptor calcium channels. We show that a current trend is to include the intracellular calcium dynamics into the neuronal models, and the frontier of this research is now shifting to spatial neuronal models with diffusing intracellular calcium. It is expected that more important results will be obtained with the neuronal models incorporating the intracellular calcium dynamics, especially the spatial models considering the calcium diffusion both in soma and dendritic branches.

[Advance in bioremediation of polychlorinated biphenyls].

As one of the persistent organic pollutants, polychlorinated biphenyls are harmful to the environment and humans. Biodegradation is the most potential way to remove PCBs. Biodegradation can mainly be divided into microbial degradation, phytoremediation, plant and microbial combined remediation. Here, we introduced isolation of the PCBs-degrading strains, cloning and modification of the related degradation genes. Additionally, on the other hand, the natural remediation of plant, plant and microbial combined remediation, plant transgenic remediation were described.

Expression, purification and functional characterization of a recombinant 2,3-dihydroxybiphenyl-1,2-dioxygenase from Rhodococcus rhodochrous.

A 2,3-dihydroxybiphenyl (2,3-DHBP) dioxygenase gene from a Rhodococcus sp. strain, named RrbphCI and involved in the degradation of polychlorinated biphenyls (PCBs), was synthesized. RrbphCI was expressed in Escherichia coli and its encoded enzyme was purified. SDS-PAGE analysis indicated that the size of the protein encoded by RrbphCI was about 32 kDa. The activity of the 2,3-DHBP dioxygenase was 82.8 U/mg when the substrate was 2,3-DHBP, with optimum pH 8.0 at 30°C, and optimum temperature was 40°C at pH 8.0. The RrbphCI gene was transformed into Pseudomonas putida strain EG11, to determine the ability of the enzyme to degrade 2,3-DHBP. The wild type EG11 degraded 61.86% of supplied 2,3-DHBP and the transformed EG11 (hosting the RrbphCI gene) utilized 52.68% after 2 min of treatment at 30°C. The overexpressed and purified enzyme was able to degrade 2,3-DHBP. The 2,3-DHBP dioxygenase is a key enzyme in the PCB degradation pathway. RrbphCI and its encoded 2,3-DHBP dioxygenase may have transgenic applications in bioremediation of PCBs.

Identification and analysis of polychlorinated biphenyls (PCBs)-biodegrading bacterial strains in Shanghai.

As one of China's great metropolises, Shanghai is vulnerable to various forms of industrial and agricultural contamination associated with its development. Polychlorinated biphenyls (PCBs) are man-made chemicals that never existed in nature until the 1900s when they started to be released into the environment. PCBs are hazardous environmental contaminants that bind strongly to soil. In this study, four soil samples were screened for the presence of PCB-degrading bacteria. The 16 S rDNAs were amplified from those genomes and the products (~1.5 kb) were purified and sequenced for the isolation and identification of bacterial species. Four Pseudomonas strains (strain 1-212 from sample 1; strain 2-241 from sample 2; strain 3-318 from sample 3; and strain 4-150 from sample 4) were selected for analysis by HPLC. Setting the content of the biphenyl in CK as 100%, the biphenyl contents was 2.32% in 1-212, 73.11% in 2-241, 69.83% in 3-318, and 86.16% in 4-150. The results of this study suggest directions for future research, including genetic screening, cloning and restructuring, and provide guidance for the cultivation of PCBs-degrading bacteria.

Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth.

We investigated the effects of metformin on the growth of lewis lung LLC1 carcinoma in C57BL/6J mice provided with either a control diet or a high-energy diet, previously reported to lead to weight gain and systemic insulin resistance with hyperinsulinemia. Forty-eight male mice were randomized into four groups: control diet, control diet+metformin, high-energy diet, or high-energy diet+metformin. Following 8 weeks on the experimental diets, selected groups received metformin in their drinking water. Three weeks following the start of metformin treatment, mice were injected with 0.5x10(6) LLC1 cells and tumor growth was measured for 17 days. By day 17, tumors of mice on the high-energy diet were nearly twice the volume of those of mice on the control diet. This effect of diet on tumor growth was significantly attenuated by metformin, but metformin had no effect on tumor growth of the mice on the control diet. Metformin attenuated the increased insulin receptor activation associated with the high-energy diet and also led to increased phosphorylation of AMP kinase, two actions that would be expected to decrease neoplastic proliferation. These experimental results are consistent with prior hypothesis-generating epidemiological studies that suggest that metformin may reduce cancer risk and improve cancer prognosis. Finally, these results contribute to the rationale for evaluation of the anti-neoplastic activity of metformin in hyperinsulinemic cancer patients.

Stochastic properties of Ca(2+) release of inositol 1,4,5-trisphosphate receptor clusters.

Intracellular Ca(2+) release is controlled by inositol 1,4,5-trisphosphate (IP(3)) receptors or ryanodine receptors. These receptors are typically distributed in clusters with several or tens of channels. The random opening and closing of these channels introduces stochasticity into the elementary calcium release mechanism. Stochastic release events have been experimentally observed in a variety of cell types and have been termed sparks and puffs. We put forward a stochastic version of the Li-Rinzel model (the deactivation binding process is described by a Markovian scheme) and a computationally more efficient Langevin approach to model the stochastic Ca(2+) oscillation of single clusters. Statistical properties such as Ca(2+) puff amplitudes, lifetimes, and interpuff intervals are studied with both models and compared with experimental observations. For clusters with tens of channels, a simply decaying amplitude distribution is typically observed at low IP(3) concentration, while a single peak distribution appears at high IP(3) concentration.