Collapse Of Potential Research Articles

Influence of BRBs deformation capacity on the seismic performance of RC building frames

The deformation design requirements of buckling-restrained brace (BRB) are explicitly stipulated in design standards to ensure the safety of the building structures. However, BRBs still have the risk of failure when the building structures are subjected to an extremely rare earthquake event. This investigation gives an insight into the seismic and collapse performance of BRB braced reinforced concrete (RC) frame structures considering the ultimate deformation capacity of BRBs. Three case study buildings of 3-, 6-, and 9-story RC frames equipped with BRBs that possess various ultimate deformation capacities are designed in accordance with Chinese standards. First, the significance of considering BRB failure in seismic performance evaluation is illustrated through comparative analysis. Then, the static pushover analysis and incremental dynamic analysis are conducted on BRB frames to quantitatively evaluate the influence of BRB ultimate deformation capacity on the seismic and collapse performance. The results reveal that the BRB ultimate deformation capacity has a significant influence on seismic response and collapse mode, especially under extremely rare earthquake events, and shall be legitimately considered in numerical modeling for accurate seismic performance evaluation. The BRB with an ultimate deformation safety coefficient of 1.2 will provide sufficient redundancy to ensure the safety of the building structures from BRB failure and potential collapse risk.

Energy metabolism as a target for cyclobenzaprine: A drug candidate against Visceral Leishmaniasis

Leishmaniases have a broad spectrum of clinical manifestations, ranging from a cutaneous to a progressive and fatal visceral disease. Chemotherapy is nowadays the almost exclusive way to fight the disease but limited by its scarce therapeutic arsenal, on its own compromised by adverse side effects and clinical resistance. Cyclobenzaprine (CBP), an FDA-approved oral muscle relaxant drug has previously demonstrated in vitro and in vivo activity against Leishmania sp., but its targets were not fully unveiled. This study aimed to define the role of energy metabolism as a target for the leishmanicidal mechanisms of CBP. Methodology to assess CBP leishmanicidal mechanism variation of intracellular ATP levels using living Leishmania transfected with a cytoplasmic luciferase. Induction of plasma membrane permeability by assessing depolarization with DiSBAC(2)3 and entrance of the vital dye SYTOX® Green. Mitochondrial depolarization by rhodamine 123 accumulation. Mapping target site within the respiratory chain by oxygen consumption rate. Reactive oxygen species (ROS) production using MitoSOX. Morphological changes by transmission electron microscopy. CBP caused on L. infantum promastigotes a decrease of intracellular ATP levels, with irreversible depolarization of plasma membrane, the collapse of the mitochondrial electrochemical potential, mild uncoupling of the respiratory chain, and ROS production, with ensuing intracellular Ca2+ imbalance and DNA fragmentation. Electron microscopy supported autophagic features but not a massive plasma membrane disruption. The severe and irreversible mitochondrial damage induced by CBP endorsed the bioenergetics metabolism as a relevant target within the lethal programme induced by CBP in Leishmania. This, together with the mild-side effects of this oral drug, endorses CBP as an appealing novel candidate as a leishmanicidal drug under a drug repurposing strategy.

Traces of Our Interregnum: Selections from an Early Pandemic Archive

Interregnum is that moment of crisis in society wherein forces of dislocation and disruption cause, or at least open space for, the potential collapse or reorganization of hegemonic order, the space of the not-yet and, as such, epistemically opaque. It is this image which perhaps best captures those early and unsettling days of the pandemic: moments and spaces which I now attempt to represent herein through selected meditations on everyday life. These meditations—or traces as I see them now, were initially written in the spring and summer of 2020. I resurrect them in a world meaningfully distinct from that of those first weeks, a world all too similar still.

Iranian Mesobuthus Eupeus Crude Venom Induces Selective Toxicity in Chronic Lymphocytic Leukemia B-Lymphocytes Through Lysosomal/Mitochondrial Dysfunction and Reactive Oxygen Species Formation.

From ancient times to the present-day animal venoms had been used as medicinal and therapeutic agents. Recently it has been reported that the scorpion venom is a potential source of active and therapeutic compounds to design potent drugs against variety of cancerous cells and other diseases. The current study aimed to evaluate the selective toxicity of Iranian Mesobuthus eupeus (IMe) crude venom as a potential source of anticancer compounds on cancerous CLL B-lymphocytes and normal lymphocytes. For this purpose, we isolated cancerous CLL B-lymphocytes and normal lymphocytes from chronic lymphocytic leukemia patients and healthy volunteers. Cancerous CLL B-lymphocytes and normal lymphocytes were treated with different concentration (0, 5, 10, 20, 40 and 80 µg/ml) of IMe crude venom for 12 hours and cytotoxicity, reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and lysosomal membrane integrity were determined. The data demonstrated the significant cytotoxic effect of IMe crude venom on cancerous CLL B-lymphocytes, with a concentration value (IC50) that inhibits 50% of the cell viability of 60 µg/ ml after 12 h of incubation. MTT assay proved that the IMe crude venom is selectively toxic to cancerous CLL B-lymphocytes, and IMe crude venom induced selective cell death via activation of ROS formation and mitochondrial/lysosomal dysfunction. These finding showed that IMe crude venom has a selective mitochondrial/lysosomal-mediated cell death effect on cancerous CLL B-lymphocytes. Therefore, the IMe crude venom and its fractions may be promising in the future anticancer drug development for treatment of CLL and variety of cancers.

Monitoring, modelling and managing beaver (Castor fiber) populations in the River Otter catchment, Great Britain

Abstract Eurasian beaver (Castor fiber) were nearly hunted to extinction but have recovered to occupy much of their former range. Beaver were extirpated from Great Britain c. 400 years ago but have recently been reintroduced. The River Otter catchment, Devon was the site of the first licensed wild release of beavers in England. With further releases being considered, there is a need to better understand population dynamics of this native, keystone species to inform conservation and management. Field signs were surveyed from 2015 to 2021. A semi‐automated territory detection method was adopted to estimate territory counts. A spatially explicit model was developed to estimate the ecological territory capacity of the catchment. Future territory expansion was modelled using logistic growth curves; initial growth rate was estimated from observed territory counts and the estimated territory capacity range was used to define the limiting value of the growth curve. Beaver territory removal was simulated, across a range of management intensities and start times, to determine potential impacts of translocation or lethal control upon population dynamics. Territory numbers increased from four to 18, inclusive of four additionally released individuals, during study period. In the absence of population management, the territory capacity of the catchment was estimated to range between 120 and 183; this may be reached between 2028 and 2057. Simulated territory removal, where territories were removed at a fixed rate from the sum of the estimated total population and the population increase for that year, demonstrated large uncertainties in predicted population responses. Simulations with territory removals >3/year all predicted potential population collapse. This finding emphasizes the need for caution when considering population management strategies; translocation of animals out of the catchment or culling should be considered only when populations are established and all alternatives have been considered. These results provide critical information for the expected rate and magnitude of beaver population change in the River Otter catchment. The methods provide a reproducible and generalizable approach for understanding beaver population change, which can inform policy on the reintroduction of beavers and the potential timing and intensity of future beaver population management.

New Mechanisms and Targets of Subarachnoid Hemorrhage: A Focus on Mitochondria.

Spontaneous subarachnoid hemorrhage (SAH) accounts for 5-10% of all strokes and is a subtype of hemorrhagic stroke that places a heavy burden on health care. Despite great progress in surgical clipping and endovascular treatment for ruptured aneurysms, cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) threaten the long-term outcomes of patients with SAH. Moreover, there are limited drugs available to reduce the risk of DCI and adverse outcomes in SAH patients. New insight suggests that early brain injury (EBI), which occurs within 72 h after the onset of SAH, may lay the foundation for further DCI development and poor outcomes. The mechanisms of EBI mainly include excitotoxicity, oxidative stress, neuroinflammation, blood-brain barrier (BBB) destruction, and cellular death. Mitochondria are a double-membrane organelle, and they play an important role in energy production, cell growth, differentiation, apoptosis, and survival. Mitochondrial dysfunction, which can lead to mitochondrial membrane potential (Δψm) collapse, overproduction of reactive oxygen species (ROS), release of apoptogenic proteins, disorders of mitochondrial dynamics, and activation of mitochondria-related inflammation, is considered a novel mechanism of EBI related to DCI as well as post-SAH outcomes. In addition, mitophagy is activated after SAH. In this review, we discuss the latest perspectives on the role of mitochondria in EBI and DCI after SAH. We emphasize the potential of mitochondria as therapeutic targets and summarize the promising therapeutic strategies targeting mitochondria for SAH.

Rocky coastal cliffs reinforced by vegetation roots and potential collapse risk caused by sea-level rise

Evaluation of the effect of vegetation roots on the stability of rocky coastal cliffs is necessary to understand geomorphological, environmental and ecological changes in coastlines caused by sea-level rise (SLR). To better understand these topics, coastal cliffs with and without vegetation were investigated. Study cliffs were selected on Taketomi-jima Island and Kuro-shima Island, both in Okinawa, southwestern Japan, because their environmental settings are similar except for the vegetation cover: the islands are only 10 km away from each other and comprise uplifted coral limestone, with an elevation below 5 m. Pandanus odoratissimus (PO) covers the seaward edge of the top surface of the coastal cliffs in Taketomi-jima but is absent in Kuro-shima. Field investigations were conducted on both islands to map the distribution of blocks with the dimension of one side exceeding 1 m to obtain the parameters required for stability analysis. The results indicate that the actual coastal cliff elevation is higher in Taketomi-jima than that in Kuro-shima by approximately 1 m, which results in the presence of PO on the seaward edge of the coastal cliffs in Taketomi-jima and its absence in Kuro-shima. The PO root system likely reinforces the cliffs in Taketomi-jima because the stability analysis results revealed that these cliffs are unstable in terms of their dimensions. Therefore, the possible disappearance of PO in Taketomi-jima caused by an SLR of 1 m in the following several decades or hundred years can increase the apparent frequency of cliff collapses by approximately tenfold.

Evaluating the protective effects of Panax bipinnatifidus Seem. extracts on hypoxia/reoxygenation-subjected cardiomyocytes

The search for new products to treat ischemic heart diseases has interested scientists for years as it is the main cause of cardiovascular disease mortality. In this study, we evaluated the protective effects of Panaxbipinnatifidus Seem. extracts (PSE) on hypoxia/reoxygenation (HR)-treated rat H9C2 cardiomyocytes. Rat H9C2 cardiomyocytes were either grown under normal condition or subjected to HR conditions. NecroX-5 (10 μM) was used as positive control for cardiac protective effect. The PSE (5-500 μg/ml) was employed to culture media at the onset of reoxygenation. Cell viability and mitochondrial function were tested using a Cell Counting Kit-8 and suitable fluorescence kits. The obtained data shows that HR conditions dramatically induced H9C2 cell death (p<0.05). Treatment of PSE (5-62.5 μg/ml) effectively reduced HR injuries in a dose-dependent manner. Similar to the NecroX-5 group, ginseng extract-treated cells had higher viability levels compared to that of the HR-subjected cells (p<0.05). In addition, supplementing PSE at the onset of reoxygenation strongly prevented the collapse of mitochondrial membrane potential and reduced mitochondrial oxidative stress (p<0.05). This study suggested the total saponin extracts from Panax bipinnatifidus Seem. exerts cardioprotective properties against HR damage.

A rapid sustainability dynamic assessment of the USA and China 1995-2018.

The USA and China have the world's largest GDP and greenhouse gas emissions, as well as having a significant proportion of the world's total population. These form part of the triumvirate of influencing factors which potentially detrimentally impact upon sustainability. How the triumvirate factors have impacted upon the sustainability of the USA and China has not been adequately determined quantitatively or holistically. Understanding this can strongly indicate how significant levels of population, economic growth, and greenhouse gas emissions impacts and influences the indicated levels, nature, and dynamics of sustainability occurring. Therefore, to contribute towards developing understanding of the issues outlined, the Sustainability Dynamics Framework is applied to conduct a sustainability dynamic assessment for the USA and China 1995-2018. The results indicate both countries are consistently unsustainable due to significant levels of triumvirate-based factors, with differing dynamic trends, characteristics, and potential outcomes. The current static nature of the USA's environment-human system provides the opportunity for a managed co-evolutionary strategy. China's dynamic trends indicate a significant increasingly stressed environment-human system, which is at risk of a potential systemic crisis or collapse unless stringent corrective measures are implemented. In order for both countries to return to sustainability, there needs to be population mitigation to return them to optimum levels, and the use of contractionary policies and rapid decarbonation of their economies and societies. Unless this occurs, then their continued reticence to undertaking the urgent and necessary measures required not only risking their own future, but the world as well.

Simulated gastrointestinal digestion and colonic fermentation of blue honeysuckle: Phenolic profile and protectivity on ethyl carbamate-induced oxidative damage

Blue honeysuckle (Lonicera caerulea L.) is well-known fruit that belongs to the berries family, and is widely cultivated in China, Russia, and Japan. This study aimed to evaluate the impact of in vitro gastrointestinal digestion followed by gut microbiota fermentation on the phenolic profile of blue honeysuckle as well as the protective effect of digested-blue honeysuckle against ethyl carbamate (EC)-induced oxidative damage. Results of phenolic profile showed that cyanidin-3-O-glucoside was identified as the predominant anthocyanin in blue honeysuckle and was significantly decreased after in vitro digestion. The generation of some metabolites (gallic acid, ferulic acid, and 3,4-dihydroxybenzoic acid) could be attributed to the degradation of chlorogenic acid and anthocyanins. Cellular studies indicated that digested-blue honeysuckle (0.5 and 1 mg/mL) exhibited significant protection against EC-induced cytotoxicity. Digested-blue honeysuckle at a concentration 1.0 mg/mL exhibited significant (p < 0.05) protective effect against EC-induced cytotoxicity in Caco-2 cells via inhibiting ROS and superoxide anion accumulation, attenuating GSH depletion, and inhibiting mitochondrial membrane potential collapse compared to EC-treated group. Blue honeysuckle could be a promising resource for ameliorating EC-induced cellular oxidative damage, which could be an ingredient for functional foods. However, further in vivo studies are recommended to prove the functionality of blue honeysuckle.

Synthesis and characterization of polyimidazolium species on silica nanoparticles: Study on cytotoxicity and removal of nitrate from water

AbstractA nanocomposite containing imidazolium based on modified silica nanoparticles (polyimidazolium based on nano silica particles [PIZNS]) was prepared to remove nitrate from water. The prepared compounds were fully characterized by Fourier transform infrared, 1H‐NMR, field emission scanning electron microscopy, energy dispersive X‐ray (EDX) and thermogravimetric analyzes. The ability of PIZNS in nitrate ions adsorption was tested under different operating conditions. The maximum removal efficiency and adsorption capacity (Qmax) of the PIZNS were obtained 90.56% and 37.73 mg g−1, respectively (initial nitrate ion concentration of 50 mg/L, at pH = 7, 30 mg adsorbent, contact time of 30 min). To evaluate the selectivity coefficient, the removal of nitrate ion was determined in the presence of competitive sulfate, bicarbonate, chloride, and phosphate ions by adsorbent. Further, kinetic and isotherm investigation showed best fit by second order and Langmuir models, respectively. In addition, the anti‐cancer properties and subsequently the cytotoxicity effect of the PIZNS was assayed in vitro using cisplatin as a standard against three cancer cell lines including PC12, HL60, and βTC. The most potent inhibition effect was observed toward HL60 cells by PIZNS. Thus, the collapse of mitochondrial membrane potential was evaluated in these cells. In addition, the cytostatic effect of this polymer was depicted in the HL60 3D spheroid model.

Saprirearine protects H9c2 cardiomyocytes against hypoxia/reoxygenation-induced apoptosis by activating Nrf2.

Myocardial infarction is a major cause of mortality and disability worldwide. Ischemia/reperfusion injury is the key factor that results in the increase in infarct size in pathogenesis. To find a novel therapy for myocardial infarction, we have evaluated saprirearine, a natural diterpenoid, using H9c2 cardiomyocytes injured by hypoxia/reoxygenation and explored the possible mechanisms. The results showed that saprirearine improved cell survival by increasing cell viability and blocking the release of lactate dehydrogenase. Meanwhile, saprirearine was found to attenuate mitochondrial dysfunction by inhibiting calcium overload, collapse of the mitochondrial membrane potential, and opening of the mitochondrial permeability transition pore. And oxidative stress resulting from hypoxia/reoxygenation was ameliorated by saprirearine through the reduction of reactive oxygen species and malondialdehyde as well as activation of superoxide dismutase and catalase. Additionally, saprirearine inactivated cysteinyl aspartate-specific proteinase-3, the up-regulated B-cell lymphoma-2 and down-regulated Bcl-2-associated X protein, to inhibit hypoxia/reoxygenation-induced apoptosis. Further research revealed saprirearine-activated nuclear factor E2-related factor-2 in H9c2 cardiomyocytes, which is closely associated with its protective effects. These findings can provide evidence for the discovery of new therapies targeting myocardial infarction and the application of saprirearine in clinical practice.

Unconstrained coevolution of bacterial size and the latent period of plastic phage.

Viruses play critical roles in the dynamics of microbial communities. Lytic viruses, for example, kill significant fractions of autotrophic and heterotrophic microbes daily. The dynamic interplay between viruses and microbes results from an overlap of physiological, ecological, and evolutionary responses: environmental changes trigger host physiological changes, affecting the ecological interactions of host and virus and, ultimately, the evolutionary pressures influencing the two populations. Recent theoretical work studied how the dependence of viral traits on host physiology (viral plasticity) affects the evolutionarily stable host cell size and viral infection time emerging from coevolution. Here, we broaden the scope of the framework to consider any coevolutionary outcome, including potential evolutionary collapses of the system. We used the case study of Escherichia coli and T-like viruses under chemostat conditions, but the framework can be adapted to any microbe-virus system. Oligotrophic conditions led to smaller, lower-quality but more abundant hosts, and infections that were longer but produced a reduced viral offspring. Conversely, eutrophic conditions resulted in fewer but larger higher-quality hosts, and shorter but more productive infections. The virus influenced host evolution decreasing host size more noticeably for low than for high dilution rates, and for high than for low nutrient input concentration. For low dilution rates, the emergent infection time minimized host need/use, but higher dilution led to an opportunistic strategy that shortened the duration of infections. System collapses driven by evolution resulted from host failure to adapt quickly enough to the evolving virus. Our results contribute to understanding the eco-evolutionary dynamics of microbes and virus, and to improving the predictability of current models for host-virus interactions. The large quantitative and qualitative differences observed with respect to a classic description (in which viral traits are assumed to be constant) highlights the importance of including viral plasticity in theories describing short- and long-term host-virus dynamics.

Tri-ortho-cresyl phosphate induces axonal degeneration in chicken DRG neurons by the NAD+ pathway

Wallerian degeneration (WD) is a well-known process by which degenerating axons and myelin are cleared after nerve injury. Although organophosphate-induced delayed neuropathy (OPIDN) is characterized by Wallerian-like degeneration of long axons in human and sensitive animals, the precise pathological mechanism remains unclear. In this study, we cultured embryonic chicken dorsal root ganglia (DRG) neurons, the model of OPIDN in vitro, to investigate the underlying mechanism of axon degeneration induced by tri-ortho-cresyl phosphate (TOCP), an OPIDN inducer. The results showed that TOCP exposure time- and concentration-dependently induced a serious degeneration and fragmentation of the axons from the DRG neurons. A collapse of mitochondrial membrane potential and a dramatic depletion of ATP levels were found in the DRG neurons after TOCP treatment. In addition, nicotinamide nucleotide adenylyl transferase 2 (NMNAT2) expression and nicotinamide adenine dinucleotide (NAD+) level was also found to be decreased in the DRG neurons exposed to TOCP. However, the TOCP-induced Wallerian degeneration in the DRG neurons could be inhibited by ATP supplementation. And exogenous NAD+ or NAD+ processor nicotinamide riboside can rescue TOCP-induced ATP deficiency and prevent TOCP-induced axon degeneration of the DRG neurons. These findings may shed light on the pathophysiological mechanism of TOCP-induced axonal damages, and implicate the potential application of NAD+ to treat OPIDN.

Risperidone Toxicity on Human Blood Lymphocytes in Nano molar Concentrations.

Risperidone is an atypical antipsychotic drug used for the pharmacotherapy of psychiatric disorders. Some reports indicate that risperidone is toxic to various systems of the body, including the immune system. This study evaluated the toxicity effect of risperidone on human blood lymphocytes. To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12, 24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels. Finally, it could be concluded that oxidative stress is one of the mechanisms of risperidone-induced toxicity in human blood lymphocytes.

The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro

Remdesivir is a prodrug of a nucleoside analog and the first antiviral therapeutic approved for coronavirus disease. Recent cardiac safety concerns and reports on remdesivir-related acute kidney injury call for a better characterization of remdesivir toxicity and understanding of the underlying mechanisms. Here, we performed an in vitro toxicity assessment of remdesivir around clinically relevant concentrations (Cmax 9 µM) using H9c2 rat cardiomyoblasts, neonatal mouse cardiomyocytes (NMCM), rat NRK-52E and human RPTEC/TERT1 cells as cell models for the assessment of cardiotoxicity or nephrotoxicity, respectively. Due to the known potential of nucleoside analogs for the induction of mitochondrial toxicity, we assessed mitochondrial function in response to remdesivir treatment, early proteomic changes in NMCM and RPTEC/TERT1 cells and the contractile function of NMCM. Short-term treatments (24 h) of H9c2 and NRK-52E cells with remdesivir adversely affected cell viability by inhibition of proliferation as determined by significantly decreased 3H-thymidine uptake. Mitochondrial toxicity of remdesivir (1.6–3.1 µM) in cardiac cells was evident by a significant decrease in oxygen consumption, a collapse of mitochondrial membrane potential and an increase in lactate secretion after a 24–48-h treatment. This was supported by early proteomic changes of respiratory chain proteins and intermediate filaments that are typically involved in mitochondrial reorganization. Functionally, an impedance-based analysis showed that remdesivir (6.25 µM) affected the beat rate and contractility of NMCM. In conclusion, we identified adverse effects of remdesivir in cardiac and kidney cells at clinically relevant concentrations, suggesting a careful evaluation of therapeutic use in patients at risk for cardiovascular or kidney disease.

Protective Effect of Curcumin, Chrysin and Thymoquinone Injection on Trastuzumab-Induced Cardiotoxicity via Mitochondrial Protection.

Mitochondrial dysfunction may lead to cardiomyocyte death in trastuzumab (TZM)-induced cardiotoxicity. Accordingly, this study was designed to evaluate the mitochondrial protective effects of curcumin, chrysin and thymoquinone alone in TZM-induced cardiotoxicity in the rats. Forty-eight male adult Wistar rats were divided into eight groups: control group (normal saline), TZM group (2.5mg/kg I.P. injection, daily), TZM+ curcumin group (10mg/kg, I.P. injection, daily), TZM + chrysin (10mg/kg, I.P. injection, daily), TZM + thymoquinone (0.5mg/kg, I.P. injection, daily), curcumin group (10mg/kg, I.P. injection, daily), chrysin group (10mg/kg, I.P. injection, daily) and thymoquinone group (10mg/kg, I.P. injection, daily). Blood and tissue were collected on day 11 and used for assessment of creatine phosphokinase, lactate dehydrogenase (LDH), troponin, malondialdehyde (MDA) amount, glutathione levels and mitochondrial toxicity parameters. TZM increased mitochondrial impairments (reactive oxygen species formation, mitochondrial swelling, mitochondrial membrane potential collapse and decline in succinate dehydrogenase activity) and histopathological alterations (hypertrophy, enlarged cell, disarrangement, myocytes degeneration, infiltration of fat in some areas, hemorrhage and focal vascular thrombosis) in rat heart. As well as TZM produced a significant increase in the level of CK, LDH, troponin, MDA, glutathione disulfide. In most experiments, the co-injection of curcumin, chrysin and thymoquinone with TZM restored the level of CK, LDH, troponin, MDA, GSH, mitochondrial impairments and histopathological alterations. The study revealed the cardioprotective effects of curcumin, chrysin and thymoquinone against TZM-induced cardiotoxicity which could be attributed to their antioxidant and mitochondrial protection activities.

A modified Johnson-Cook constitutive model for structural steel after cooling from high temperature

High temperature has a significant impact on the mechanical properties of steel structural members, which can develop a potential collapse. Currently, various studies have been concentrating on the post-fire mechanical properties of different steels, while few of them considered the corresponding constitutive model. Therefore, in this paper, the classical Johnson-Cook constitutive equation is selected as a benchmark and is modified to fit the conditions in which the effects of heating and cooling on the mechanical properties of fire-affected steel are considered. To this end, three commonly used structural steels, namely Q345B, Q460 and Q690D, are selected in this paper. First, the specimens were heated to different target temperatures, and then naturally cooled down to the ambient temperature in the air. After cooling from the exposure temperatures, the subsequent tensile tests were performed on the fire-affected specimens to capture the failure modes and study the residual mechanical properties. To verify the proposed constitutive model, an Abaqus subroutine (UMAT) program was developed in this study. The experimental data of water-cooled specimens obtained in our previous studies were also selected to further test the feasibility of this new model. The results show that the exposure temperature and steel grade have significant effects on the residual mechanical properties of the structural steel specimens when the target temperature exceeds 700 °C. Meanwhile, the modified Johnson-Cook constitutive is able to predict the stress –strain behavior precisely, regardless of the cooling method. The results obtained in this study are helpful for both further research and engineering application when doing a numerical study of the fire-affected steel structures.

Inhibition of mitochondrial permeability transition pore and antioxidant effect of Delta-9-tetrahydrocannabinol reduces aluminium phosphide-induced cytotoxicity and dysfunction of cardiac mitochondria

Previous studies have demonstrated that phosphine gas (PH3) released from aluminium phosphide (AlP) can inhibit cytochrome oxidase in cardiac mitochondria and induce generation of free radicals, oxidative stress, alteration in antioxidant defense system and cardiotoxicity. Available evidence suggests that cannabinoids have protective effects in the reduction of oxidative stress, mitochondrial and cardiovascular damages. The objective of this study was to evaluate the effect of trans-Δ-9-tetrahydrocannabinol (THC) on AlP-induced toxicity in isolated cardiomyocytes and cardiac mitochondria. Rat heart isolated cardiomyocytes and mitochondria were cotreated with different concentrations of THC (10, 50 and 100 μM) and IC50 of AlP, then cellular and mitochondrial toxicity parameters were assayed. Treatment with AlP alone increased the cytotoxicity, depletion of cellular glutathione (GSH), mitochondrial reactive oxygen species (ROS) generation, lipid oxidation, mitochondria membrane potential (ΔΨm) collapse and mitochondrial swelling, when compared to control group. However, incubation with THC (10, 50 and 100 μM) attenuated the AlP-induced changes in all these parameters in a THC concentration-dependent manner. Interestingly, the obtained results showed remarkably significant protective effects of THC by attenuation the different parameters of cytotoxicity, mitochondrial toxicity and oxidative stress induced by ALP in isolated cardiomyocytes and cardiac mitochondria. It is the first report showing the protective effects of THC against AlP-induced toxicity, and these effects are related to antioxidant potential and inhibition of mitochondria permeability transition (MPT) pore. Based on these results, it was hypothesized that THC may be used as a potential therapeutic agent for the treatment of AlP-induced mitochondrial dysfunction and cardiotoxicity.

PI3K/AKT1 Signaling Pathway Mediates Sinomenine-Induced Hepatocellular Carcinoma Cells Apoptosis: An in Vitro and in Vivo Study.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers. Sinomenine (SIN) is a compound derived from Sinomenium acutum. Our previous investigations have found that SIN inhibited protein kinase B (AKT) signaling to induce autophagic death of tumor cells. However, whether inhibition of this pathway by SIN could impact the proliferation of HCC cells is unknown. Thus, we applied SIN to SK-Hep-1 cells and used cell counting kit 8 (CCK8), lactate dehydrogenase (LDH), colony formation and 5-ethynyl-20-deoxyuridine (EdU) incorporation experiments to detect cell viability. Then, staining with annexin V/propidium iodide (PI) coupled with terminal deoxynucleotidyl transferase-mediated biotinylated uridine 5'-triphosphate (UTP) nick end labeling (TUNEL) staining were utilized to monitor apoptosis. Changes in cell mitochondrial membrane capacity were explored via 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, whilst Western blot or immunohistochemistry was applied to evaluate the expression levels of key proteins, consisting of Cleaved Caspase 3, AKT1, B-cell leukemia/lymphoma 2 (BCL-2), phosphatidylinositol 3-kinase (PI3K) p85α, and Cleaved Caspase 9 etc. The Balb/c nude mice were utilized to establish HCC xenograft tumor model, administered by SIN. After treatments, the tumor volume along with weight were measured. The results illustrated that SIN suppressed SK-Hep-1 HCC cells' proliferation, enhanced the collapse of potential of the mitochondrial membrane, triggered cell apoptosis, down-regulated PI3K p85α, AKT1, BCL-2, Pro-Caspase 9, Pro-Caspase 3 expressions, and up-regulated Cleaved Caspase 9 and Cleaved Caspase 3 expressions in vitro and in vivo. Meanwhile, SIN reduced the tumor volume along with weight of mice. In addition, insulin-like growth factor-1 (IGF-1), a powerful activator of the PI3K/AKT pathway, could reverse the high apoptosis of SK-Hep-1 HCC cells induced by SIN. Overall, inhibition of PI3K/AKT1 signaling cascade by SIN induced HCC cells apoptosis.