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Pretreatment processes are essential for the preparation of biofuels from lignocellulosic feedstocks. Based on alkaline H2O2 pretreatment, photocatalytic alkaline H2O2 pretreatment (U-AHP) was investigated to examine the effects of reaction time, alkali concentration, and H2O2 concentration on the enzymatic digestion of corn stover. The optimum process conditions were determined by orthogonal tests: 1% NaOH, 2% H2O2, and reaction time of 8 h. Under these conditions, the lignin removal efficiency of UH-AHP was 90.2% and the saccharification yield was 94.7%. Furthermore, FT-IR, XRD, and SEM analyses showed that U-AHP pretreatment caused structural damage to the maize straw and increased the crystallinity of the cellulose, and it was speculated that the U-AHP pretreatment reaction was a complex mechanism, which might be a multiple synergistic reaction. This study shows that U-AHP pretreatment is a simple, green and effective method to promote lignin removal.

Exposure to ultraviolet B radiation (UV-B) stress can have serious effects on the growth and development of plants. Germin-like proteins (GLPs) may be involved in different abiotic and biotic stress responses in different plants, but little is known about the role of GLPs in UV-B stress response and acclimation in plants. In the present study, knockout of GLP 8–14 (OsGLP1) using the CRISPR/Cas9 system resulted in mutant rice (Oryza sativa L.) plants (herein called glp1) that exhibited UV-B-dependent formation of lesion mimic in leaves. Moreover, glp1 grown under solar radiation (including UV-B) showed decreased plant height and increased leaf angle, but we observed no significant differences in phenotypes between wild-type (WT) plants and glp1 grown under artificial light lacking UV-B. Fv/Fm, Y (II) and the expression of many genes, based on RNA-seq analysis, related to photosynthesis were also only reduced in glp1, but not in WT, after transfer from a growth cabinet illuminated with artificial white light lacking UV-B to growth under natural sunlight. The genes-associated with flavonoid metabolism as well as UV resistance locus 8 (OsUVR8), phytochrome interacting factor-like 15-like (OsPIF3), pyridoxal 5′-phosphate synthase subunit PDX1.2 (OsPDX1.2), deoxyribodipyrimidine photolyase (OsPHR), and deoxyribodipyrimidine photolyase family protein-like (OsPHRL) exhibited lower expression levels, while higher expression levels of mitogen-activated protein kinase 5-like (OsMPK3), mitogen-activated protein kinase 13-like (OsMPK13), and transcription factor MYB4-like (OsMYB4) were observed in glp1 than in WT after transfer from a growth cabinet illuminated with artificial white light to growth under natural sunlight. Therefore, mutations in OsGLP1 resulted in rice plants more sensitive to UV-B and reduced expression of some genes for UV-B protection, suggesting that OsGLP1 is involved in acclimation to UV-B radiation.

The folding and degradation of proteins in tumor cells are the key mechanisms maintaining their survival, and functions of the proteins involved are often related to the prevailing tumor resistance. With further scientific research, an increasing number of auxiliary proteins involved in protein folding and degradation have been reported in the literature. The chaperone heat shock protein 90 (HSP90) not only promotes protein folding and plays a role in maintaining protein conformation stability but also assists the proteasomal degradation of client proteins. Current research suggests that the function of HSP90 is regulated by post-translational modifications, such as acetylation. Histone deacetylase 6 (HDAC6) can inhibit the over-acetylation of HSP90 and maintain the chaperone function of HSP90 to ensure that the client protein of the chaperone HSP90 can be stably folded and maturely released, which creates conditions for tumor survival, proliferation, and metastasis. Furthermore, it can act as the client protein and autophagy receptor of HSP90. It recruits ubiquitinated proteins and deacetylates and modifies autophagy-related proteins, thus playing important roles in protein degradation and autophagy. Recently, studies revealed HDAC6, a client protein of HSP90, which plays an important role in protein degradation, cell autophagy, and maintenance of the activity of HSP90 by preventing its excessive acetylation. By inhibiting HDAC6 to promote HSP90 over-acetylation, it can effectively inhibit the binding between HSP90 and ATP, thereby affecting the folding and degradation of HSP90 on tumor proliferation and metastasis-related proteins. Simultaneously, HDAC inhibitors can help HSP90 bind more closely to its inhibitors. Therefore, HDAC6 and HSP90 inhibitors have also been widely used in related research on tumor treatment, and studies have shown that the combined application of HDAC6 and HSP90 inhibitors has a significant effect on inhibiting tumor proliferation and metastasis. Whether it is to inhibit HDAC6 alone or HSP90 alone, there are deficiencies in cancer treatment. The use of inhibitors alone may lead to the activation of other pathways related to tumor cell proliferation and survival. HDAC6-HSP90 dual-target inhibition can reduce the activation of compensatory pathways, such as autophagy, and reduce the possibility of off-target effects of HSP90 inhibitors. In this review, we focus on the crosstalk between HDAC6 and HSP90 to further explain how tumor cells initiate proliferation and metastasis signals by regulating protein folding and degradation mechanisms and discuss the research applications of HDAC6 and HSP90 inhibitors. The advantages and disadvantages are assessed to obtain novel strategies for cancer therapy by targeting the HSP90-HDAC6 pathway.

The variations of single event transient (SET) pulse width of high-LET heavy ion irradiation in 16-nm-thick bulk silicon fin field-effect transistor (FinFET) inverter chains with different driven strengths are measured at different temperatures. Three-dimensional (3D) technology computer-aided design simulations are carried out to study the SET pulse width and saturation current varying with temperature. Experimental and simulation results indicate that the increase in temperature will enhance the parasitic bipolar effect of bulk FinFET technology, resulting in the increase of SET pulse width. On the other hand, the increase of inverter driven strength will change the layout topology, which has a complex influence on the SET temperature effects of FinFET inverter chains. The experimental and simulation results show that the device with the strongest driven strength has the least dependence on temperature.

Pyruvate dehydrogenase kinase 1 (PDK1) is a key factor in the connection between glycolysis and the tricarboxylic acid cycle. Restoring the mitochondrial OXPHOS function by inhibiting glycolysis through targeting PDK1 has become a hot spot for tumor therapy. However, the specific mechanism by which metabolic changes affect mitochondrial function remains unclear. Recent studies have found that mitochondrial quality control such as mitochondrial protein homeostasis plays an important role in maintaining mitochondrial function. Here, we focused on PDK1 and explored the specific mechanism by which metabolic changes affect mitochondrial OXPHOS function. We showed that glucose metabolism in HepG2 and HepG3B cells switched from anaerobic glycolysis to the mitochondrial tricarboxylic acid cycle under different concentrations of dichloroacetate (DCA) or short hairpin PDK1. After DCA treatment or knockdown of PDK1, the mitochondrial morphology was gradually condensed and exhibited shorter and more fragmented filaments. Additionally, expression of the mitochondrial autophagy proteins parkin and PTEN-induced kinase was down-regulated, and the biosynthetic protein peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and its regulated complex I, III, IV, and V protein were down-regulated. This indicated that PDK1 inhibition affected the level of mitochondrial quality control. Analysis of mitochondrial function revealed significantly increased mitochondrial reactive oxygen species and decreased membrane potential. Therefore, glucose metabolism reprogramming by PDK1 inhibition could induce mitochondrial quality control disorders to aggravate mitochondrial stress damage.

Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H: quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer.

Increasing evidence suggests that p62/SQSTM1 functions as a signalling centre in cancer. However, the role of p62 in tumour development depends on the interacting factors it recruits and its precise regulatory mechanism remains unclear. In this study, we investigated the pro‐death signalling recruitment of p62 with the goal of improving anti‐tumour drug effects in ovarian cancer treatment. We found that p62 with Caspase 8 high expression is correlated with longer survival time compared with cases of low Caspase 8 expression in ovarian cancer. In vivo experiments suggested that insoluble p62 and ubiquitinated protein accumulation induced by autophagy impairment promoted the activation of Caspase 8 and increased cell sensitivity to cisplatin. Furthermore, p62 functional domain UBA and LIR mutants regulated autophagic flux and attenuated Caspase 8 activation, which indicates that autophagic degradation is involved in p62‐mediated activation of Caspase 8 in ovarian cancer cells. Collectively, our study demonstrates that p62 promotes Caspase 8 activation through autophagy flux blockage with cisplatin treatment. We have provided evidence that autophagy induction followed by its blockade increases cell sensitivity to chemotherapy which is dependent on p62‐Caspase 8 mediated apoptosis signalling. p62 exhibits pro‐death functions through its interaction with Caspase 8. p62 and Caspase 8 may become novel prognostic biomarkers and oncotargets for ovarian cancer treatment.

Metabolic reprogramming is a central hallmark of cancer. Therefore, targeting metabolism may provide an effective strategy for identifying promising drug targets for cancer treatment. In prostate cancer, cells undergo metabolic transformation from zinc‐accumulating, citrate‐producing cells to citrate‐oxidizing malignant cells with lower zinc levels and higher mitochondrial aconitase (ACO2) activity. ACO2 is a Krebs cycle enzyme that converts citrate to isocitrate and is sensitive to reactive oxygen species (ROS)‐mediated damage. In this study, we found that the expression of ACO2 is positively correlated with the malignancy of prostate cancer. Both zinc and p53 can lead to an increase in ROS. ACO2 can be a target for remodeling metabolism by sensing changes in the ROS levels of prostate cancer. Our results indicate that targeting ACO2 through zinc and p53 can change prostate cancer metabolism, and thus provides a potential new therapeutic strategy for prostate cancer.

The study of cisplatin sensitivity is the key to the development of ovarian cancer treatment strategies. Mitochondria are one of the main targets of cisplatin, its self-clearing ability plays an important role in determining the fate of ovarian cancer cells. First, we proved that the sensitivity of ovarian cancer cells to cisplatin depends on mitophagy, and p62 acts as a broad autophagy receptor to regulate this process. However, p62′s regulation of mitophagy does not depend on its location on the mitochondria. Our research shows that the mutation of the UBA domain of p62 increases the localisation of HK2 on the mitochondria, thereby increasing the phosphorylated ubiquitin form of parkin, then stabilising the process of mitophagy and ultimately cell survival. Collectively, our results showed that a mutation in the UBA domain of p62 regulates the level of apoptosis stimulated by cisplatin in ovarian cancer.

The electrical characteristics and microstructures of β-Ga2O3 Schottky barrier diode (SBD) devices irradiated with swift heavy ions (2096 MeV Ta ions) have been studied. It was found that β-Ga2O3 SBD devices showed the reliability degradation after irradiation, including turn-on voltage V on, on-resistance R on, ideality factor n, and the reverse leakage current density J r. In addition, the carrier concentration of the drift layer was decreased significantly and the calculated carrier removal rates were 5 × 106–1.3 × 107 cm−1. Latent tracks induced by swift heavy ions were observed visually in the whole β-Ga2O3 matrix. Furthermore, crystal structure of tracks was amorphized completely. The latent tracks induced by Ta ions bombardments were found to be the reason for the decrease in carrier mobility and carrier concentration. Eventually, these defects caused the degradation of electrical characteristics of the devices. In terms of the carrier removal rates, the β-Ga2O3 SBD devices were more sensitive to swift heavy ions irradiation than SiC and GaN devices.

Invasiveness and metastatic potential are among the most essential characteristics of malignant tumors. Furthermore, it has been reported that autophagy and invasion are enhanced when tumor cells are grown in adverse conditions, such as nutritional deficiency and starvation. However, the association between autophagy and invasion remains largely unclear. In the present study, Earle's balanced salt solution (EBSS) was used to induce autophagy and an autophagy inhibitor was used to block autophagy. The results of Transwell assays revealed that autophagy inhibition limited the invasiveness of human ovarian cancer cells. Furthermore, the results of invadopodia formation assay indicated that autophagy stimulated invadopodia formation, and the selective autophagy receptor and signaling adaptor, sequestosome-1 (SQSTM1/p62 or simply p62), was closely associated with invadopodia formation in human ovarian cancer SKOV3 cells. The results of western blot analysis indicated that autophagy induced changes in p62 protein levels and p62 then functioned as a negative regulator of extracellular signal-regulated kinase 1/2 (ERK1/2) activity and invadopodia formation. The interaction between autophagy and invasion may thus be a self-protective mechanism for tumor cells in an unfavorable environment of nutritional deficiency, that maintains their survival and leads to increased invasiveness. An exploration of the intrinsic link between autophagy and invasion may provide a novel theoretical basis to reverse the resistance of tumor cells to a nutritional deficient environment.

Breast cancer is the most common high-grade malignancy in women. The lack of therapeutic targets has limited the treatment of breast cancer. Recently, long noncoding RNAs (lncRNAs) have been demonstrated to be dysregulated in various types of cancer. However, the specific mechanisms by which lncRNAs influence breast cancer have remained largely unclear. To bridge this research gap, the present study focused on the lncRNA LINC00365, which is expressed at a low level in breast cancer. Secretoglobin family 2A member 1 (SCGB2A1) was identified as a potential target protein regulated by LINC00365. The results of the present study demonstrated that the overexpression of LINC00365 and SCGB2A1 inhibited cell viability and induced cell apoptosis through the inhibition of the NF-κB signaling pathway in breast cancer cells. These findings indicated that LINC00365 may serve a crucial role in breast cancer and may be considered as a novel target for the clinical treatment of breast cancer.

Purpose A lack of early diagnostic biomarkers and therapeutic targets has led to poor prognosis for gastric cancer patients. However, the analysis of cancer-associated genomic data has been shown to be effective in identifying potential markers. Recently, the long non-coding RNA LINC00365 and SCGB2A1 gene (as known as mammaglobin B) were predicted to be co-expressed in gastric cancer based on the Gene Expression Omnibus database. However, their precise role in gastric cancer tumors is still not clear. Methods The expressions of LINC00365 and SCGB2A1 in gastric cancer tissues were investigated using qPCR and their expressions were detected in a gastric cancer tissue microarray by in situ hybridization and immunohistochemical staining. The functions of LINC00365 in BGC-823 and MGC-803 gastric cancer cells were tested using the MTT assay, flow cytometry, colony formation assay, EDU staining, immunofluorescence and luciferase assay. Results We found that LINC00365 and SCGB2A1 mRNA were both expressed at low levels in 30 cases of gastric cancer. Gastric cancer tissue microarray analysis indicated that LINC00365 and SCGB2A1 were expressed at low levels in tumor tissue, and low expression of both factors correlated with shorter survival time. Functional studies showed that LINC00365 overexpression significantly inhibited gastric cancer cell viability through the impairment of proliferation rather than the promotion of apoptosis. Furthermore, overexpressed LINC00365 upregulated SCGB2A1 in gastric cancer cell lines. Immuno-fluorescence and luciferase assay analysis indicated that LINC00365 overexpression inhibited the NF-κB pro-survival signaling pathway. Consistent with the effects of LINC00365, SCGB2A1 upregulation also reduced cell survival and inactivated NF-κB. Conclusion Collectively, our findings revealed that SCGB2A1 may be the target coding protein regulated by LINC00365 in gastric cancer. LINC00365 and SCGB2A1 may function as tumor suppressors and may serve as potential prognostic and therapeutic markers in gastric cancer treatment.

The Bcl-2 antiapoptotic proteins are important cancer therapy targets; however, their role in cancer cell metabolism remains unclear. We found that the BH3-only protein mimetic S1, a novel pan Bcl-2 inhibitor, simultaneously interrupted glucose metabolism and induced apoptosis in human SKOV3 ovarian cancer cells, which was related to the activation of SIRT3, a stress-responsive deacetylase. S1 interrupted the cellular glucose metabolism mainly through causing damage to mitochondrial respiration and inhibiting glycolysis. Moreover, S1 upregulated the gene and protein expression of SIRT3, and induced the translocation of SIRT3 from the nucleus to mitochondria. SIRT3 silencing reversed the effects of S1 on glucose metabolism and apoptosis through increasing the level of HK-II localized to the mitochondria, while a combination of the glycolysis inhibitor 2-DG and S1 intensified the cytotoxicity through further upregulation of SIRT3 expression. This study underscores an essential role of SIRT3 in the antitumor effect of Bcl-2 inhibitors in human ovarian cancer through regulating both metabolism and apoptosis. The manipulation of Bcl-2 inhibitors combined with the use of classic glycolysis inhibitors may be rational strategies to improve ovarian cancer therapy.

Hypoxia, an important feature of the tumor microenvironment, is responsible for the chemo-resistance and metastasis of malignant solid tumors. Recent studies indicated that mitochondria undergo morphological transitions as an adaptive response to maintain self-stability and connectivity under hypoxic conditions. NAD+ may not only provide reducing equivalents for biosynthetic reactions and in determining energy production, but also functions as a signaling molecule in mitochondrial dynamics regulation. In this review, we describe the upregulated KDAC deacetylase expression in the mitochondria and cytoplasm of tumor cells that results from sensing the changes in NAD+ to control mitochondrial dynamics and distribution, which is responsible for survival and metastasis in hypoxia.

The mechanism of cisplatin resistance is complex. Previous studies have indicated that chloride voltage-gated channel 3 (CLCN3) is associated with drug resistance; however, the mechanisms are not fully understood. Therefore, the present study explored the involvement of CLCN3 in cisplatin resistance in human glioma U251 cells. The effects of combined cisplatin treatment and CLCN3 suppression on cultured U251 cells were investigated. The decreased viability of cisplatin-treated U251 cells indicated the cytotoxic effects of CLCN3 silencing. Expression of the apoptosis-related gene TP53 and caspase 3 activation were enhanced in cisplatin-treated U251 cells. Furthermore, the ratio of BCL2/BAX expression was decreased. Notably, CLCN3 suppression promoted cisplatin-induced cell damage in U251 cells. Thus, the combined use of cisplatin and CLCN3 antisense had additive effects in U251 cells. In addition, the present results indicated that CLCN3 suppression decreased lysosome stabilization in U251 cells treated with cisplatin. To conclude, the present results indicated that CLCN3 suppression can sensitize glioma cells to cisplatin through lysosomal dysfunction.

A novel amphiphilic copolymer consisting of tetraphenylethylene-oxazolidine (TPE-OX) as a pH-sensitive chromophore and poly(ethylene glycol) methyl ether methacrylate (PEGMA) as a water-soluble chain has been well designed and synthesized. A self-assembled polymeric micelle based on the copolymer exhibited clear dual-emission switching between cyan and red with a decrease of pH value in Tris-HCl buffer solution due to the extended conjugation and emerging intramolecular charge transfer effect when opening the spiro-ring of OX moiety. Fluorescence imaging of HepG2 cells stained by the polymeric micelle shows switched luminescence from cyan to red with high selectivity and contrast, indicating that the polymeric micelle was an effective probe for intracellular pH detection. Additionally, the red emission of the polymeric micelle in lysosomes can reversibly switch back to the original cyan emission in response to the two lysosomal activity inhibitors chloroquine and bafilomycin, which demonstrates that the polymeric micelle has potential applications in detecting the activity of lysosomal and further autophagy in cancer cells.

Sanguinarine (SAN), an alkaloid isolated from plants of the Papaveraceae family, is a compound with multiple biological activities. In the present study, we explored the anticancer properties of SAN in lung cancer using the human lung adenocarcinoma cell line SPC-A1. Our results revealed that SAN inhibited SPC-A1 cell growth and induced apoptosis in a dose-dependent manner. We found that SAN triggered reactive oxygen species (ROS) production, while elimination of ROS by N-acetylcysteine (NAC) reversed the growth inhibition and apoptosis induced by SAN. SAN-induced endoplasmic reticulum (ER) stress resulted in the upregulation of many genes and proteins involved in the unfolded protein response (UPR) pathway, including glucose-regulated protein 78 (GRP78), p-protein kinase R (PKR)-like ER kinase (PERK), p-eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homologous protein (CHOP). Blocking ER stress with tauroursodeoxycholic acid (TUDCA) markedly reduced SAN-induced inhibition of growth and apoptosis. Furthermore, TUDCA decreased SAN-induced ROS production, and NAC attenuated SAN-induced GRP78 and CHOP expression. Overall, our data indicate that the anticancer effects of SAN in lung cancer cells depend on ROS production and ER stress and that SAN may be a potential agent against lung cancer.

In both civilian and military domains, the increasing use of highly toxic organophosphates (OPs) has created an urgent demand for developing an effective method that could protect the human body from OP poisoning. In this study, a novel dual-functional protecting material with both OP filtration and degradation functions was designed and fabricated. The filtration function was endowed by the electrospinning polyamide 66 (Nylon 66, PA-66) nanofibrous membrane, while the OP degradation function was based on the immobilization of organophosphorus hydrolase (OPH) on membrane through glutaraldehyde (GA) crosslinking. A systematic study of the relationship between the membrane structure, filtration ability and OP degradation activity revealed that PA-66 nanofibrous enzyme with 20 mu m thickness exhibited perfect uniform morphology, and the particle filtration efficiency was over 99%. The nanofibrous enzyme exhibited a specific activity of 41 U/g; the enzyme activity recovery was 53.3%, and the methyl parathion (MP) degradation efficiency was 40%. Moreover, the nanofibrous enzyme expressed excellent organic solvent stability; approximately 70% of its initial activity was retained after incubation in xylene solvent for 24 h at 25 degrees C. The residual activity was 40% after being stored for 30 d at 25 degrees C After 10 repeated uses, the residual activity of the nanofibrous membrane was 37%. This study demonstrated the application potential of dual-functional PA-66 nanofibrous enzyme in biochemical protection, aimed at various military and civilian applications. (C) 2015 Elsevier B.V. All rights reserved.

Poor prognosis and chemotherapy tolerance are the main obstacles encountered in the treatment of cholangiocarcinoma. Chloroquine (CQ), an antimalarial agent, is able to induce sustained endoplasmic reticulum (ER) stress by functioning as an autophagy inhibitor. The present study indicated that CQ had the ability to induce apoptosis in QBC939 cholangiocarcinoma cells. Furthermore, using western blotting, Hoechst staining and flow cytometry, it was demonstrated that CQ induced the apoptosis of QBC939 cholangiocarcinoma cells. Analysis by a polymerase chain reaction (PCR) array and confirmation via quantitative PCR technology indicated that the expression levels of growth arrest and DNA damage 153 [C/EBP homologous protein (CHOP)], a key molecule involved in ER stress-induced apoptosis, and its downstream death receptors were increased following CQ stimulation. It was considered that the upregulation of CHOP may mediate CQ-induced extrinsic pathways and autophagy-dependent apoptosis; therefore, the role of autophagy in cholangiocarcinoma treatment was elucidated based on the data demonstrating that CQ regulates the ER-autophagy network in tumor cells. Furthermore, it was considered that CQ may become a novel and effective strategy for the treatment of cholangiocarcinoma.

Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function. Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase. We demonstrated that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress and mitochondrial dysfunction. Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status. AMPK compensated for energy loss by increasing glycolysis. The impact of this was assessed by reducing glucose levels in the media or by using inhibitors (2-deoxyglucose, Compound C) of glycolysis and AMPK. The combination of these factors with metformin intensified cytotoxicity through further downregulation of ATP. Our study outlines an important role for SIRT3 in the antitumor effect of mitochondrial complex I inhibitors in human ovarian cancer cells. This effect appears to be mediated by induction of energy stress and apoptosis. Strategies that target the mitochondria could be enhanced by modulating glycolysis to further aggravate energy stress that may increase the antitumor effect.

Recovered blood supply after cerebral ischemia for a certain period of time fails to restore brain function, with more severe dysfunctional problems developing, called cerebral ischemia–reperfusion injury (CIR). CIR involves several extremely complex pathophysiological processes in which the interactions between key factors at various stages have not been fully elucidated. Mitochondrial dysfunction is one of the most important mechanisms of CIR. The mitochondrial deacetylase, sirtuin 3 (SIRT3), can inhibit mitochondrial oxidative stress by deacetylation, to maintain mitochondrial stability. Uncoupling protein 2 (UCP2) regulates ATP (Adenosine triphosphate) and reactive oxygen species production by affecting the mitochondrial respiratory chain, which may play a protective role in CIR. Finally, we propose that UCP2 regulates the activity of SIRT3 through sensing the energy level and, in turn, maintaining the mitochondrial steady state, which demonstrates a cytoprotective effect on CIR.

To investigate the response of the bridge pounding, shaking table test was performed using 1/10 scaled reinforced concrete rigid frame bridge specimen. The influence of traveling effect on pounding and the anti-impact capability using dampers were discussed. The experimental results demonstrate that the acceleration responses of the girder and bridge piers, the frequency and the impact force are increased when the traveling wave excitation is considered. Moreover, relatively displacement of the adjacent bridge frames increased magnitudely. Dynamic responses, the frequency and the impact force are decrease when the dampers are installed.Therefore, installation of the dampers is a sustainable and effective way to improve the anti-impact capability.

Platinum-based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug-resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin. In this study, we demonstrate that the activity of the NF-κB signaling pathway and K63-linked ubiquitination of RIP1 was higher in cisplatin-resistant ovarian (SKOV3/DDP) cells compared with parental cells. In addition, cisplatin resistance could be reversed by inhibiting the expression of p62 using siRNA. Furthermore, deletion of the ZZ domain of p62 that interacts with RIP1 in SKOV3 cells markedly decreased K63-linked ubiquitination of RIP1 and inhibited the activation of the NF-κB signaling pathway. Moreover, loss of the ZZ domain from p62 led to poor proliferative capacity and high levels of apoptosis in SKOV3 cells and made them more sensitive to cisplatin treatment. Collectively, we provide evidence that p62 is implicated in the activation of NF-κB signaling that is partly dependent on RIP1. p62 promotes cell proliferation and inhibits apoptosis thus mediating drug resistance in ovarian cancer cells.

In order to investigate isolation effectiveness on seismic performance of the continuous rigid frame bridge, shaking table test with nine sub-tables on 1/10 scaled reinforced concrete rigid frame bridge specimen was performed. The experimental results demonstrate that isolation devices provide flexibility to transform natural period of the scaled model, and additional it can improve the ability of energy dissipation when lead is used. The initial first frequency is 8.17Hz for plate-type rubber bearing and 9.12Hz for leading rubber bearing. The plate rubber bearing and lead-rubber bearing are quite sensitive to seismic wave frequency. The use of various isolation devices affects response of the bridge model. The results show that the more difference in the isolation devices, the more difference in response. Moreover, isolation effect of lead-rubber bearing show obviously more advantage than the one of plate-type rubber bearing, especially in controlling responses of the bridge during major earthquakes.

To investigate the seismic response of long-span rigid frame bridges with high-pier, the shaking table test of a 1/10 scaled rigid frame bridge model is introduced in this paper. Details about test equipment, model design, test arrangement, input ground motion waves and test principle are provided. The response of bridge model under the seismic excitation included the uniform excitation and the multi-support excitation is observed. The influence of the soil-structure interaction on the bridge is considered through the real-time dynamic hybrid testing method. The impact effect for different ground motion input during the test is discussed. The influence of multi-support excitation, soil-structure interaction and impact effect on structural seismic responses are studied based on the test results. The isolation effectiveness and the damping effect are discussed as well.

A sensitive and efficient liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the simultaneous determination of geniposide, 6α-hydroxygeniposide, and genipin gentiobioside in rat plasma. After the addition of internal standard (I.S.) salidroside and acidification (formic acid, 0.1%), plasma samples were carried out by protein precipitation with acetonitrile and separated on a Kromasil C(18) column (200 mm × 4.6 mm, 5 μm) within a runtime of 15.0 min. The linear ranges were 2-250 ng/mL for both 6α-hydroxygeniposide and genipin gentiobioside and 2-2000 ng/mL for geniposide, respectively. The lower limit of quantification (LLOQ) was 2 ng/mL for all the analytes. The validated method was successfully applied to the pharmacokinetics study of geniposide, 6α-hydroxygeniposide, and genipin gentiobioside in rats after oral administration of Zhi-zi-chi decoction.