In the 2nd part of a series, the limits of delegated approval authority in China are discussed, the new procedures and requirements introduced by the Guidance Provisions and the SETC Notice regarding ...foreign investment are examined, and some of the consequences of having local and provincial authorities approve foreign investment enterprises (FIE) beyond the prescribed limits of their delegated approval authority are considered. Foreign investors should resist the temptation to have FIEs requiring central approval approved at local or provincial levels. They should be aware that not having an FIE approved by the appropriate approval authority involves potential risks that could affect the financing and operation of the FIE, including the following: 1. contractual issues, 2. expansion of operations, 3. exemptions from import duties and VAT, 4. financing, 5. foreign exchange, and 6. leverage.
The historical background for the recent promulgation of new regulations in the People's Republic of China (PRC) for approving foreign investment enterprises is introduced. The PRC approval hierarchy ...is discussed, and the approval procedures generally applicable to the establishment of foreign investment enterprises (FIE) are reviewed. The term "foreign investment enterprise" includes equity joint venture enterprises (EJV), cooperative joint venture enterprises (CJV), wholly foreign-owned enterprises (WFOE), foreign investment companies (holding companies), and foreign investment companies limited by shares (FIE joint stock companies). The approval procedures generally required for the establishment of FIEs are presented. EJVs and CJVs are the focus in the general discussion of approval procedures. The steps include: 1. project listing, 2. feasibility study, 3. asset appraisal, 4. joint venture contract and articles of association, and 5. business license.
Distant pointing using freehand is usually applied in interaction environments where the visual interface is out of a user's arm reach 1. One example is a user sitting on a couch who is controlling a ...smart television (TV) across the room. This kind of method is becoming more popular because of the rapid development of large-screen intelligent terminals in recent years. The visual freehand pointing technique is one kind of interaction method using gestures to control the computer.
A 3‐day workshop was held in Australia to discuss problems and issues facing coastal zones, including degradation of coastal ecosystems and the impacts of climate change such as sea level rise and ...changed weather patterns, and to formulate a collaborative research strategy to improve the coastal zone management (CZM) system to tackle these problems. The workshop, which brought together experts from University of New South Wales (UNSW) and Ocean University of China (OUC), highlighted the similarities in topics important to Australia and China. This workshop focused on science, policy, and the legal framework required to manage sustainable development of these coastal zones.
Many parallels exist between the difficult issues facing CZM in both countries. Significant research into changes in coastal areas and their causes has been undertaken, but this research effort has not been fully reflected in coastal zone planning and management activities. Workshop participants reviewed current progress in understanding scientific, engineering, and socioeconomic processes in the coastal zones, brainstormed challenges in developing a multidisciplinary research framework capable of integrating science into coastal zone management, and identified a cross‐institutional approach to addressing these issues.
Petrogeochemical data are reported for silicic volcanic rocks from the Tianshan Carboniferous rift, with the aim of discussing the petrogenesis of silicic magmas. Incompatible element vs. ...incompatible element diagrams display smooth positive trends for the Tianshan Carboniferous rift-related volcanic rocks; the isotope ratios of the silicic lavas ^87Sr/^86S（t）=0.699880.70532; eNd（t）=4.76-8.00; ^206pb/^204pb（t）=17.435-18.017; ^207Pb/^204Pb（t）=15.438-15.509; ^208Pb/^204Pb（t） = 37.075-37.723 encompass those of the basic lavas. These data suggest a genetic link between rhyolites and basalts, but are not definitive in establishing whether silicic rocks are related to basalts through fractional crystallization or partial melting. Geochemical modeling of incompatible vs. compatible elements excludes the possibility that silicic melts are generated by the melting of basaltic rocks, and indicates a derivation by fractional crystallization plus moderate assimilation of wall rocks （AFC） starting from intermediate rocks to silicic rocks. Continuous AFC from basalt to rhyolite, with small rates of crustal assimilation, best explains the geochemical data. The presence or absence of bimodal volcanism （the ＂Daly Gap＂） might be related to cooling rates of magma chambers. In central and eastern Tianshan, the crust was thinner and the cooling rates of the magma chamber within the crust were greater. These conditions resulted in a rapid fall in temperature within the magma reservoir and caused a narrow temperature interval over which intermediate melts formed, effectively reducing the volume of the intermediate melts.
Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer with limited treatment options. Cisplatin (DDP) is used as a mainstay of chemotherapeutic agents in combination with other drugs ...or radiotherapy for PDAC therapy. However, DDP exhibits severe side-effects that can lead to discontinuation of therapy, and the acquired drug resistance of tumor cells presents serious clinical obstacles. Therefore, it is imperative to develop a more effective and less toxic therapeutic strategy. We and others have previously discovered that dihydroartemisinin (DHA) represents a safe and promising therapeutic agent to preferentially induce cancer cell ferroptosis. In the present study, we find that DHA could intensively strengthen the cytotoxicity of DDP and significantly reduce its effective concentrations both in vitro and in vivo. Combination of DHA and DDP synergistically inhibits the proliferation and induces DNA damage of PDAC cells. Mechanically, the combinative treatment impairs mitochondrial homeostasis, characterized by destroyed mitochondrial morphology, decreased respiratory capacity, reduced ATP production, and accumulated mitochondria-derived ROS. Further studies show that ferroptosis contributes to the cytotoxic effects in PDAC cells under the challenge of DHA and DDP, together with catastrophic accumulation of free iron and unrestricted lipid peroxidation. Moreover, pharmacologic depleting of the free iron reservoir or reconstituted expression of FTH contributes to the tolerance of DHA/DDP-induced ferroptosis, while iron addition accelerates the ferroptotic cell death. In summary, these results provide experimental evidence that DHA acts synergistically with DDP and renders PDAC cells vulnerable to ferroptosis, which may act as a promising therapeutic strategy.
Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been revealed to be implicated in the ...carcinogenesis and progression of HCC. However, the expressions, clinical significances, and roles of most lncRNAs in HCC are still unknown.
The expression of lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in HCC tissues and cell lines was detected by qRT-PCR and fluorescence in situ hybridization. Immunoblotting, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MCM3AP-AS1 in HCC cell proliferation, cell cycle and apoptosis in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of HCC cells after MCM3AP-AS1 knockdown. The interactions among MCM3AP-AS1, miR-194-5p and FOXA1 were measured by RNA pull-down, RNA immunoprecipitation and luciferase reporter assay.
We revealed a novel oncogenic lncRNA MCM3AP-AS1, which is overexpressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage and poor prognosis of HCC patients. MCM3AP-AS1 knockdown suppressed HCC cell proliferation, colony formation and cell cycle progression, and induced apoptosis in vitro, and depletion of MCM3AP-AS1 inhibited tumor growth of HCC in vivo. Mechanistically, MCM3AP-AS1 directly bound to miR-194-5p and acted as competing endogenous RNA (ceRNA), and subsequently facilitated miR-194-5p's target gene forkhead box A1 (FOXA1) expression in HCC cells. Interestingly, FOXA1 restoration rescued MCM3AP-AS1 knockdown induced proliferation inhibition, G1 arrest and apoptosis of HCC cells.
Our results recognized MCM3AP-AS1 as a novel oncogenic lncRNA, which indicated poor clinical outcomes in patients with HCC. MCM3AP-AS1 exerted an oncogenic role in HCC via targeting miR-194-5p and subsequently promoted FOXA1 expression. Our findings suggested that MCM3AP-AS1 could be a potential prognostic biomarker and therapeutic target for HCC.
Hepatocellular carcinoma (HCC) is one of the paramount causes of cancer-related death worldwide. Despite recent advances have been made in clinical treatments of HCC, the general prognosis of ...patients remains poor. Therefore, it is imperative to develop a less toxic and more effective therapeutic strategy. Currently, series of cellular, molecular, and pharmacological experimental approaches were utilized to address the unrecognized characteristics of disulfiram (DSF), pursuing the goal of repurposing DSF for cancer therapy. We found that DSF/Cu selectively exerted an efficient cytotoxic effect on HCC cell lines, and potently inhibited migration, invasion, and angiogenesis of HCC cells. Importantly, we confirmed that DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, enhance lipid peroxidation, and eventually result in ferroptotic cell death. Of note, a compensatory elevation of NRF2 accompanies the process of ferroptosis, and contributes to the resistance to DSF/Cu. Mechanically, we found that DSF/Cu dramatically activated the phosphorylation of p62, which facilitates competitive binding of Keap1, thus prolonging the half-life of NRF2. Notably, inhibition of NRF2 expression via RNA interference or pharmacological inhibitors significantly facilitated the accumulation of lipid peroxidation, and rendered HCC cells more sensitive to DSF/Cu induced ferroptosis. Conversely, fostering NRF2 expression was capable of ameliorating the cell death activated by DSF/Cu. Additionally, DSF/Cu could strengthen the cytotoxicity of sorafenib, and arrest tumor growth both in vitro and in vivo, by simultaneously inhibiting the signal pathway of NRF2 and MAPK kinase. In summary, these results provide experimental evidence that inhibition of the compensatory NRF2 elevation strengthens HCC cells more vulnerable to DSF/Cu induced ferroptosis, which facilitates the synergistic cytotoxicity of DSF/Cu and sorafenib.
Ferroptosis, a new form of programmed cell death, not only promotes the pathological process of various human diseases, but also regulates cancer progression. Current perspectives on the underlying ...mechanisms remain largely unknown. Herein, we report a member of the NEET protein family, CISD3, exerts a regulatory role in cancer progression and ferroptosis both in vivo and in vitro. Pan-cancer analysis from TCGA reveals that expression of CISD3 is generally elevated in various human cancers which are consequently associated with a higher hazard ratio and poorer overall survival. Moreover, knockdown of CISD3 significantly accelerates lipid peroxidation and accentuates free iron accumulation triggered by Xc
inhibition or cystine-deprivation, thus causing ferroptotic cell death. Conversely, ectopic expression of the shRNA-resistant form of CISD3 (CISD3res) efficiently ameliorates the ferroptotic cell death. Mechanistically, CISD3 depletion presents a metabolic reprogramming toward glutaminolysis, which is required for the fuel of mitochondrial oxidative phosphorylation. Both the inhibitors of glutaminolysis and the ETC process were capable of blocking the lipid peroxidation and ferroptotic cell death in the shCISD3 cells. Besides, genetic and pharmacological activation of mitophagy can rescue the CISD3 knockdown-induced ferroptosis by eliminating the damaged mitochondria. Noteworthily, GPX4 acts downstream of CISD3 mediated ferroptosis, which fails to reverse the homeostasis of mitochondria. Collectively, the present work provides novel insights into the regulatory role of CISD3 in ferroptotic cell death and presents a potential target for advanced antitumor activity through ferroptosis.
•Degradation of bamboo mechanical properties with increasing moisture content is demonstrated.•Degradation is significant below fiber saturation point and less pronounced at higher moisture ...contents.•Location along the length of the culm also affects the observed degradation.•For scaffold applications, compression capacity is a conservative analogue for other mechanical properties.•In scaffold applications, the base of the culm and base of the scaffold will be most critical to performance.
Bamboo is widely used as scaffolding for which collapses, often associated with rain events, are not uncommon. The presented study quantifies the degradation of mechanical properties of bamboo samples following immersion in water for 1 and 7days to simulate the effects of significant rain events. Compression, longitudinal shear and splitting tests were conducted to obtain the respective strengths and moduli. The mechanical properties were observed to degrade significantly with increased moisture content (MC) up to about MC=30%, a value close to the expected fiber saturation point (FSP). Beyond MC=30%, further degradation, while apparent, was less significant. Immersion in water for one day was observed to be sufficient to achieve the FSP; under these conditions, compressive strength was observed to be 75% of that obtained from tests conducted at a standard ‘air-dry’ MC=12%. Accompanying the reduction in strength with increased MC, the bamboo was observed to transition from a relatively brittle behavior to a very ductile behavior. For scaffold applications, degradation of compression capacity is not only critical but also shown to be a conservative indicator for other mechanical properties.
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