[Effect and mechanism of MicroRNA-146a on TLR4 inflammatory signal pathway in the lung tissues of rats with mechanical ventilator-induced lung injury].

Objective: To investigate the effect and mechanism of microRNA-146a (miR-146a) on Toll-Like Receptor 4 (TLR4) inflammatory signal pathway in the lung tissues of rats with mechanical ventilator-induced lung injury. Methods: Thirty-two healthy male Sprague-Dawley rats were randomly divided into 4 groups (n=8 each): group A, normal control group, no mechanical ventilation, spontaneous breathing; group B, mechanical ventilation injury; group C, mechanical ventilation injury plus no-load virus transfection; group D, mechanical ventilation injury plus virus transfection; in group B, C, and D, mechanical ventilation were performed, respiratory rate was controlled at 80 beats/min, tidal volume was 40 ml/kg, inhaled oxygen concentration (FiO2) was 21%, inhalation/expiration ratio was 1∶2, positive end expiratory pressure ventilation (PEEP) was 0, each group were ventilated 4 hours daily, 7 days continuously to establish ventilator induced lung injury (VILI) rat model. Paraffin-embedded sections of lung tissue were stained with HE, the morphology and damage of lung tissue were observed under microscope. The lungs wet and dry ratio (W/D), the levels of inflammatory cytokines interleukin (IL)-1ß, IL-2 and tumor necrosis factor (TNF)-α were determined. Real-time PCR was used to detect the expression of TLR4 mRNA. The level of TLR4 protein was determined by Western blot. Results: The levels of lung tissue W/D and lung injury scores in group B (6.41±0.10, 11.38±0.92), group C (6.45±0.19, 11.75±1.04), group D (5.95±0.14, 7.53±4.78) were significantly increased than those in group A (4.33±0.08, 0.25±0.46), and in group D they were significantly decreased than group C (all P<0.01). The levels of IL-1ß, IL-2, TNF-α in group B[(36.07±4.28) pg/ml, (5.02±0.63) ng/ml, (382.57±35.41) ng/ml], group C[(35.82±5.47) pg/ml, (4.98±0.71) ng/ml, (375.13±36.95) ng/ml], group D[(27.01±3.18) pg/ml, (3.96±0.82) ng/ml, (297.56±39.08) ng/ml]were significantly increased than those in group A[(21.46±3.15) pg/ml, (2.45±0.17) ng/ml, (195.92±18.07) ng/ml], and in group D they were significantly decreased than group C (all P<0.01). The relative expression levels of TLR4 mRNA and TLR4 proteins in group B (29.57±5.10, 0.75±0.110), group C (27.27±4.72, 0.77±0.130), group D (12.89±2.58, 0.48±0.057) were significantly increased than those in group A (1.02±0.13, 0.18±0.025), and in group D they were significantly decreased than group C (all P<0.01). There was no significant difference of all the above indicators between group B and C (all P>0.05). Conclusions: MiR-146a can reduce acute lung inflammation and TLR4 expression in lungs of rats with mechanical ventilator-induced lung injury. MiR-146a may inhibit the inflammatory response through TLR4 signaling pathway.

Mechanical properties and energy absorption characteristics of tropical fruit durian (Durio zibethinus).

The paper presents for the first time the material properties and energy absorption capacity of durian shells with an attempt to use as an alternative sustainable material and mimic their structural characteristics to design a bio-inspired structure for protective packaging applications. A series of quasi-static compression tests were carried out to determine Young's modulus and bioyield stress of the durian shells as well as their energy absorption capacity. The mesocarp layers and thorns are interesting parts for investigating their energy absorption characteristics because they play an important role in protecting the flesh of durians during their drop impact onto the ground. The mesocarp layers of the shell were subjected to axial and lateral compression while the thorn specimens were compressed under axial loading with an increasing number of thorns. The results showed that the densification strain, plateau stress and specific energy absorption of the mesocarp layer under lateral loading is higher than that under axial loading. Furthermore, the compression tests on the thorns demonstrated that an increase in the number of thorns helped to absorb more energy and the specific energy absorption of the thorns was nearly two times higher than that of the mesocarp layer under the axial loading. In addition, the cyclic loading of the thorns showed that the extent of reversibility of deformation in the thorns decreases from 32% at the first cycle to around 10% at the 9th-cycle. Finally, the microstructure of the thorn and mesocarp layer was investigated to explain the experimental observation. The results indicated that the spherical shape associated with the thorns and mesocarp materials displayed an excellent energy absorption efficiency that can be mimicked to design an effective bio-inspired absorber for packing applications.

The clinical study on the treatment for acute cerebral infarction by intra-arterial thrombolysis combined with mild hypothermia.

OBJECTIVE: This study was purposed to evaluate the clinical efficacy of the treatment for acute cerebral infarction by intra-arterial thrombolysis combined with mild hypothermia. PATIENTS AND METHODS: Thirty patients, diagnosed with acute anterior circulation cerebral infarction and admitted to the Hospital between January 2013 and September 2015, were randomly divided into the control group and the mild hypothermia group, each group comprising 15 cases. The treatment of intra-arterial thrombolysis combined with mild hypothermia was administered to the mild hypothermia group, while only the treatment of intra-arterial thrombolysis was performed on the control group. The National Institutes of Health Stroke Scale (NIHSS) score, Modified RANKIN Scale (MRS) score, cerebral hemorrhage transformation, pulmonary infection, and the incidence of gastrointestinal bleeding of the two groups were compared on day 14, 30, and 90 following the onset of the disease. RESULTS: The prognosis (MRS score) of the group with mild hypothermia combined with intra-arterial thrombolysis was lower than that of the group treated only with intra-arterial thrombolysis (p < 0.05). The incidence of cerebral hemorrhage transformation of the group with mild hypothermia combined with intra-arterial thrombolysis was also lower than that of the control group (p < 0.05). There was no significant difference in the incidence of pulmonary infection and gastrointestinal bleeding between the two groups. CONCLUSIONS: Treatment of patients suffering from acute cerebral infarction by means of intra-arterial thrombolysis in combination with mild hypothermia can result in reduced risk of hemorrhagic transformation and improve clinical outcome.

Prolactin stimulation of tyrosyl phosphorylation of Shc proteins in Nb(2) lymphoma cells, but not mammary tissues.

Prolactin (PRL) stimulates lactogenesis in mammary cells and mitogenesis in a variety of cell types including Nb(2) cells. Studies indicate that a different composite of signaling pathways is involved in the PRL stimulation of mitogenesis as compared to lactogenesis. In the present studies, PRL is shown to stimulate the tyrosyl phosphorylation of all three isoforms of Shc proteins in Nb(2) cells (mitogenesis), but not in the mammary gland. Maximal phosphorylation of the Shc proteins is expressed between 10 and 15 min after a 50-ng/ml PRL treatment. In addition, there is an increased association between the Grb2 protein and Shc proteins upon PRL stimulation. However, no increased association between JAK2 and Shc proteins was observed in either the Nb(2) cells or mammary tissues.

The MEK inhibitor PD 098059 inhibits prolactin-induced Nb2 cell mitogenesis but not milk product synthesis in cultured mouse mammary tissues.

The MAP kinase pathway has been shown to be active in many growth factor signaling systems, including that of prolactin (PRL). In our studies, the main objective was to examine the possible involvement of MEK kinases (Map/Erk kinase kinases) in PRL-stimulated mitogenic and lactogenic processes. We used the MEK kinase inhibitor PD 098059 to block MEK kinase activation in the Nb2 cell line and mammary gland explants derived from 12- to 14-day pregnancy mice. PD 098059 attenuated PRL-induced Nb2 cell mitogenesis at 10 microM and a maximum inhibition was observed at 100 microM. In cultured mammary tissues, PD 098059 at 100 microM had no effect on the PRL stimulation of lipid, casein and lactose synthesis and iodide uptake. Further, the growth-inhibitory effect of PD 098059 on Nb2 cells was ameliorated when the drug was removed from the culture medium, indicating that PD 098059 acts in a reversible manner. When MEK1 was immunoprecipitated from PD 098059 and/or PRL treated Nb2 cells, PRL-stimulated MEK1 kinase activity was directly inhibited by PD 098059 at concentrations employed in the culture experiments. PRL has no effect on the tyrosyl phosphorylation of MAP kinases in cultured mammary tissues derived from pregnant mice, whereas earlier we found that PRL stimulates the tyrosyl phosphorylation of all four MAP kinases in Nb2 cells. The results suggest that the MAP kinase pathway plays an important role in the PRL stimulation of Nb2 cell mitogenesis but is not involved in the PRL stimulation of milk product synthesis.

Response of Woodpecker's Head during Pecking Process Simulated by Material Point Method.

Prevention of brain injury in woodpeckers under high deceleration during the pecking process has been an intriguing biomechanical problem for a long time. Several studies have provided different explanations, but the function of the hyoid bone, one of the more interesting skeletal features of a woodpecker, still has not been fully explored. This paper studies the relationship between a woodpecker head's response to impact and the hyoid bone. Based on micro-CT scanning images, the material point method (MPM) is employed to simulate woodpecker's pecking process. The maximum shear stress in the brainstem (SSS) is adopted as an indicator of brain injury. The motion and deformation of the first cervical vertebra is found to be the main reason of the shear stress of the brain. Our study found that the existence of the hyoid bone reduces the SSS level, enhances the rigidity of the head, and suppresses the oscillation of the endoskeleton after impact. The mechanism is explained by a brief mechanical analysis while the influence of the material properties of the muscle is also discussed.

Numerical simulation of effective phase velocity and attenuation of shear elastic wave propagation in unidirectional composite materials.

In this paper, a simple simulation approach is presented for calculating the effective phase velocity and attenuation coefficient of elastic shear waves propagating in composite materials with randomly distributed unidirectional inclusions. As an application of the developed numerical approach, the phase velocities and attenuation coefficients of the coherent waves in four different types of composite material are simulated for various incident frequencies up to π. Numerical results are compared with theoretical predictions obtained from three representative theoretical models. While all theoretical results agree very well with numerical values at low incident frequencies, the discrepancies increase with the increased incident frequency and volume fraction of inclusions. It has been found that within the frequency and volume fraction ranges considered in this work, the generalized self-consistent model by Kanaun and Levin [18] seems to provide the most accurate estimations.

Gene-dependent cell death in yeast.

Caspase-dependent apoptotic cell death has been extensively studied in cultured cells and during embryonic development, but the existence of analogous molecular pathways in single-cell species is uncertain. This has reduced enthusiasm for applying the advanced genetic tools available for yeast to study cell death regulation. However, partial characterization in mammals of additional genetically encoded cell death mechanisms, which lead to a range of dying cell morphologies and necrosis, suggests potential applications for yeast genetics. In this light, we revisited the topic of gene-dependent cell death in yeast to determine the prevalence of yeast genes with the capacity to contribute to cell-autonomous death. We developed a rigorous strategy by allowing sufficient time for gene-dependent events to occur, but insufficient time to evolve new populations, and applied this strategy to the Saccharomyces cerevisiae gene knockout collection. Unlike sudden heat shock, a ramped heat stimulus delivered over several minutes with a thermocycler, coupled with assessment of viability by automated counting of microscopic colonies revealed highly reproducible gene-specific survival phenotypes, which typically persist under alternative conditions. Unexpectedly, we identified over 800 yeast knockout strains that exhibit significantly increased survival following insult, implying that these genes can contribute to cell death. Although these death mechanisms are yet uncharacterized, this study facilitates further exploration.

Effect of prolactin on sodium iodide symporter expression in mouse mammary gland explants.

Iodide accumulates in milk at a concentration that is more than an order of magnitude higher than the iodide concentration in maternal plasma. In earlier studies from our laboratory, we have shown that prolactin (PRL) enhances iodide accumulation by two- to threefold in cultured mammary tissues taken from pregnant mice. In the present studies, we demonstrate via Western blotting techniques that prolactin elevates the quantity of the sodium iodide symporter (NIS) in cultured mouse mammary tissues. In time-course studies, the onset of the PRL effect of NIS accumulation was found to be between 4 and 16 h after addition of PRL to the explants. The lowest PRL concentration that elicited a significant response was 1 ng/ml, and a maximum effect was elicited with PRL concentrations >100 ng/ml. Actinomycin D, cycloheximide, and thiocyanate abolished the PRL effect on NIS accumulation, whereas perchlorate was without effect. These studies suggest that the PRL stimulation of iodide accumulation in milk is mediated, at least in part, by the PRL stimulation of NIS accumulation in mammary gland tissues. These studies further demonstrate that the PRL effect on NIS accumulation occurs via an RNA protein synthesis-dependent mechanism.

[Relationship of hR24L gene expression, DNA damage repair and G2/M phase cell cycle arrest with ion radiation].

The hR24L gene ORF was cloned from the total RNA of HeLa cells by RT-PCR method. There is no mutation of the hR24L gene in HeLa cells. Ion radiation significantly increased the expression of hR24L gene, and the sense hR24L enhanced and accelerated the cell cycle arrest at G2/M phase in HeLa cells. Besides, it should seem that the overexpression of hR24L gene could enhance the repair ability of DNA damage induced by ion radiation, and vice versa.

Structure-activity relationship of tubeimosides in anti-inflammatory, antitumor, and antitumor-promoting effects.

AIM: To study structure-activity relationship of tubeimosides isolated from Bolbostemma paniculatum for their anti-inflammatory, antitumor, and antitumor-promoting effects. METHODS: Tubeimosides I, II, and III were isolated from tubers of Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), a Chinese folk medicine,"Tubeimu", and their anti-inflammatory, anti-tumor, anti-tumorigenic activities, and acute toxicity were studied in vivo. RESULTS: Tubeimosides I, II, and III are all natural analogues of oleanane type of triterpenoid saponins from the same medicinal plant, and all show anti-inflammatory, antitumor, and antitumor-promo ting effects. However, the anti-inflammatory, anti-tumor, and anti-tumorigenic activities of tubeimoside II are stronger than those of tubeimoside I, and the acute toxicity of tubeimoside II is lower than that of tubeimoside I; the anti-inflammatory, anti-tumor, and anti-tumorigenic activities of tubeimoside III are stronger than those of tubeimoside II, and the acute toxicity of tubeimoside III is also stronger than that of tubeimoside II. CONCLUSION: C-16 hydroxyl group of tubeimoside II plays an important role in enhancing biological activity of tubeimoside II and in decreasing its toxicity. The difference of chemical structure in B and/or C position between tubeimosides III and II plays an important role in enhancing biological activity and toxicity of tubeimoside III. Therefore tubeimosidre II may be the most promising agent for cancer chemoprevention and chemotherapy among tubeimosides I, II, and III.

A study of calcium ion-selective PVC membrane electrode based on neutral carrier N,n,n',n'-tetracyclo-3-oxapentanediamide (correction of oxapetanediamide).

A calcium ion-selective PVC membrane electrode based on neutral carrier n,n,n',n'-tetracyclohexyl-3-oxapetanediamide, using di-(2-ethylhexyl)phthalate as the plasticizer and potassium tetrakis (4-chlorophenyl) borate as the additive is reported in this paper. The ion selective membrane consists of 1 wt% of the Ca2+ selective ligand, 65 wt% of the plasticizer, 1 wt% of the additive and 33 wt% of poly (vinyl chloride) powder. The electrode has the linear response range of 2.0 x 10(-7)-10(-1) mol/L with the Nernstian slope of 28 mV/decade at 25 degrees C and the detection limit of 2.0 x 10(-8) mol/L. The response time of the calcium ion-selective electrode is as the concentration of calcium ion is rapidly shifted from 10(-5) to 10(-4) mol/L. The potential stability and reproducibility are good. The free calcium in blood serum was determined by the calcium ion-selective electrode with satisfactory results.

Formation of sp(3) bonding in nanoindented carbon nanotubes and graphite.

Nanoindentation-induced interlayer bond switching and phase transformation in carbon nanotubes (CNTs) and graphite are simulated by molecular dynamics. Both graphite and CNTs experience a soft-to-hard phase transformation at room temperature at compressive stresses of 12 and 16 GPa, respectively. Further penetration leads to the formation of interlayer sp(3) bonds, which are reversible upon unloading if the compressive stress is under about 70 GPa, beyond which permanent interlayer sp(3) bonds form. During nanoindentation, the maximum nanohardness of graphite can reach 109 GPa, and CNTs 120 GPa, which is comparable to that of diamond.