Paclobutrazol induces the concurrent accumulation of chrysolaminarin and lipids in the diatom Phaeodactylum tricornutum

Paclobutrazol is a plant growth regulator and inhibitor of endogenous gibberellin synthesis.It is a powerful inhibitor of vegetative growth by changing the photosynthetic rate and plant hormone levels,thereby affecting plant growth and development.In this study,the effects of paclobutrazol on the model diatom Phaeodactylum tricornutum were investigated.Results show that 2.5-mg/L and 10-mg/L paclobutrazol significantly inhibited the algal growth by inhibiting chlorophyll synthesis,which affects photosynthesis.The antioxidant system,including catalase(CAT)and glutathione peroxidase(GPx)was severely damaged.Chrysolaminarin content was significantly elevated and doubled up to 127 mg/g dry cell weight(DCW)by 10-mg/L paclobutrazol treatment.In combination with transcriptomic analysis,paclobutrazol was demonstrated to play a regulatory role in the accumulation of chrysolaminarin and neutral lipids.

QoS-Aware Cloud Service Optimization Algorithm in Cloud Manufacturing Environment

In a cloud manufacturing environment with abundant functionally equivalent cloud services,users naturally desire the highest-quality service(s).Thus,a comprehensive measurement of quality of service(QoS)is needed.Opti-mizing the plethora of cloud services has thus become a top priority.Cloud ser-vice optimization is negatively affected by untrusted QoS data,which are inevitably provided by some users.To resolve these problems,this paper proposes a QoS-aware cloud service optimization model and establishes QoS-information awareness and quantification mechanisms.Untrusted data are assessed by an information correction method.The weights discovered by the variable precision Rough Set,which mined the evaluation indicators from historical data,providing a comprehensive performance ranking of service quality.The manufacturing cloud service optimization algorithm thus provides a quantitative reference for service selection.In experimental simulations,this method recommended the optimal services that met users’needs,and effectively reduced the impact of dis-honest users on the selection results.

Experimental study on magnetic drug targeting in treating cholangiocarcinoma based on internal magnetic fields

Objective: To evaluate the effect of magnetic nanoparticle containing 5-fluorouracil (5-FU) targeting in treating chol- angiocarcinoma based on internal magnetic fields built inside the tumor. Methods: 32 nude mice of BABL/C bearing ectopic tumor were built by subcutaneouly injecting cholangiocarcinoma cell line QBC 939. Three weeks after tumor inoculation, the animal models were divided equally into four groups at random including: (a) group A, consisting of internal magnetic field built by magnetic biliary stent wires inserted into tumor tissue and receiving magnetic nanoparticles containing 5-FU administered via tail vein injection at 250 mg/kg for consecutive five days; (b) group B, receiving placebo (sodium chloride); (c) group C, receiving pure magnetic biliary stent wires without the applying of magnetic nanoparticles; (d) group D, consisting of external magnetic fields and the same treatment of magnetic nanoparticles containing 5-FU as group A. The tumor volumes were measured every 3 days, totally six times from treatment started. Tumor tissues were observed by transmission electron microscope when the nude mice were killed after the observation period. Results: The experimental group (group A) showed significantly therapeutic efficacy. Moreover, apoptosis of tumor cells could be easily detected in this group. Conclusion: Magnetic particles containing 5-FU combined with internal magnetic field can effectively treat cholangiocarcinoma, and its therapeutic efficacy is better than that of the traditional method based on external magnetic fields.

Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance

Metabolic and epigenetic reprogramming play important roles in cancer therapeutic resistance.However,their interplays are poorly understood.We report here that elevated TIGAR(TP53-induced glycolysis and apoptosis regulator),an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2(nuclear receptor binding SET domain protein 2),is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 mark.Mechanistically,TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2,H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new(NSD2)and established(NQO1/2,PRDX1 and GSTM4)targets of NRF2,independent of its enzymatic activity.Nuclear TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy in vitro and in tumors through effective maintenance of redox homeostasis.In addition,nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor survival.These findings define a nuclear TIGAR-mediated epigenetic autoregulatory loop in redox rebalance for tumor therapeutic resistance.

Targeting castration-resistant prostate cancer with a novel RORγ antagonist elaiophylin

Prostate cancer(PCa)patients who progress to metastatic castration-resistant PCa(mCRPC)mostly have poor outcomes due to the lack of effective therapies.Our recent study established the orphan nuclear receptor RORγas a novel therapeutic target for CRPC.Here,we reveal that elaiophylin(Elai),an antibiotic from Actinomycete streptomyces,is a novel RORy antagonist and showed potent antitumor activity against CRPC in vitro and in vivo.We demonstrated that Elai selectively binded to RORy protein and potently blocked RORγtranscriptional regulation activities.Structure-activity relationship studies showed that Elai occupied the binding pocket with several key interactions.Furthermore,Elai markedly reduced the recruitment of RORγto its genomic DNA response element(RORE),suppressed the expression of RORγtarget genes AR and AR variants,and significantly inhibited PCa cell growth.Importantly,Elai strongly suppressed tumor growth in both cell line based and patient-derived PCa xenograft models.Taken together,these results suggest that Elai is novel therapeutic RORγinhibitor that can be used as a drug candidate for the treatment of human CRPC.