OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment

Background:Colorectal cancer(CRC)represents a substantial risk to public health.Bevacizumab,thefirst US FDA-approved antiangiogenic drug(AAD)for human CRC treatment,faces resistance in patients.The role of lipid metabolism,particularly through OPA3-regulated lipid droplet production,in overcoming this resistance is under investigation.Methods:The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis.OPA3-overexpressed SW-480 and HCT-116 cell lines were established,and bevacizumab resistance and OPA3 effects on cell malignancy were examined.OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR.OPA3 subcellular localization was detected using immunofluorescence.Proliferation and apoptosis were assessed via colony formation andflow cytometry.Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells(HUVECs).Lipid analysis was used to measure the phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)levels in CRC cells.Results:Bioinformatics analysis revealed that OPA3 was downregulated in CRC.Overexpression of OPA3 inhibited CRC cell proliferation,stimulated apoptosis,and suppressed the angiogenic ability of HUVECs.OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells.Additionally,OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells,thereby increasing CRC cell sensitivity to bevacizumab treatment.Conclusion:This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells.Therefore,OPA3 may be a potential therapeutic target against the AAD resistance in CRC.

Coarse-to-Fine Video Instance Segmentation With Factorized Conditional Appearance Flows

We introduce a novel method using a new generative model that automatically learns effective representations of the target and background appearance to detect,segment and track each instance in a video sequence.Differently from current discriminative tracking-by-detection solutions,our proposed hierarchical structural embedding learning can predict more highquality masks with accurate boundary details over spatio-temporal space via the normalizing flows.We formulate the instance inference procedure as a hierarchical spatio-temporal embedded learning across time and space.Given the video clip,our method first coarsely locates pixels belonging to a particular instance with Gaussian distribution and then builds a novel mixing distribution to promote the instance boundary by fusing hierarchical appearance embedding information in a coarse-to-fine manner.For the mixing distribution,we utilize a factorization condition normalized flow fashion to estimate the distribution parameters to improve the segmentation performance.Comprehensive qualitative,quantitative,and ablation experiments are performed on three representative video instance segmentation benchmarks(i.e.,YouTube-VIS19,YouTube-VIS21,and OVIS)and the effectiveness of the proposed method is demonstrated.More impressively,the superior performance of our model on an unsupervised video object segmentation dataset(i.e.,DAVIS19)proves its generalizability.Our algorithm implementations are publicly available at https://github.com/zyqin19/HEVis.

Adsorption of Quaternary Ammonium Compounds onto Activated Sludge

The performance of activated sludge in the removal of tetradecyl benzyl dimethyl ammonium chloride (C14BDMA) by adsorption from aqueous solution was investigated with different PH, contact time, ionic strength and temperature. Equilibrium was achieved within 2 h of contact time. The adsorption capacity increased largely with increasing solution pH and remained constant above pH 9. The ionic strength had a negative effect on C14BDMA removal. The adsorption isotherms were analyzed by Langmuir and Freundlich isotherm models, and equilibrium partitioning data was described well by both models. Kinetics data was best described by the pseudo second-order model. Experimental results indicated that the adsorption was favorable at lower temperatures. Thermodynamic parameters, including the Gibbs free energy (ΔG0), enthalpy (ΔH0), and entropy (ΔS0), were also calculated. These parameters indicated that adsorption of C14BDMA onto activated sludge was feasible, spontaneous and exothermic in the temperature range of 15-35℃. The activated sludge was shown to be an effective adsorbent for C14BDMA.

A Triangulation-Based Visual Localization for Field Robots

Dear Editor,Visual localization relies on local features and searches a prestored GPS-tagged image database to retrieve the reference image with the highest similarity in feature spaces to predict the current location[1]-[3].For the conventional methods[4]-[6],local features are generally explored by multiple-stage feature extraction whichfirst detects and then describes key-point features[4],[7].

Chimeric antigen receptor （CAR）-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV

Cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells contribute to the body＇s immune defenses. Current chimeric antigen receptor （CAR）-modified T cell immunotherapy shows strong promise for treating var- ious cancers and infectious diseases. Although CAR- modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cyto- toxic cell-mediated immunotherapies are urgently nee- ded. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the for- mation of the immunological synapse （IS） between CAR- modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat can- cer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus （HIV）, and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-medi- ated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.

Innovatively employing magnetic CuO nanosheet to activate peroxymonosulfate for the treatment of high-salinity organic wastewater

Magnetic CuO nanosheet(Mag-CuO), as a cheap, stable, efficient and easily separated peroxymonosulfate(PMS) activator, was prepared by a simple one-step precipitation method for the removal of organic compounds from salt-containing wastewater.The experiments showed that the removal efficiencies of various organic pollutants including Acid Orange 7, Methylene Blue, Rhodamine B and atrazine in a high-salinity system(0.2 mol/L Na2SO4) with the Mag-CuO/PMS process were 95.81%, 74.57%, 100% and 100%,respectively.Meanwhile, Mag-CuO still maintained excellent catalytic activity in other salt systems including one or more salt components(NaCl, NaNO3, Na2HPO4, NaHCO3).A radical-quenching study and electron paramagnetic resonance analysis confirmed that singlet oxygen(1O2) was the dominant reactive oxygen species for the oxidation of organic pollutants in high-salinity systems, which is less susceptible to hindrance by background constituents in wastewater than radicals(·OH or SO4·-).The surface hydroxylation of the catalyst and catalytic redox cycle including Cu and Fe are responsible for the generation of1O2.The developed Mag-CuO catalyst shows good application prospects for the removal of organic pollutants from saline wastewater.

Application of electrode materials and catalysts in electrocatalytic treatment of dye wastewater

The dye industry produces a large amount of hazardous wastewater every day worldwide,which brings potential threaten to the global environment.As an excellent method for removal of water chroma and chemical oxygen demand,electrocatalytic methods are currently widely used in the treatment of dye wastewater.The selection and preparation of electrode materials and electrocatalysts play an important role on the electrocatalytic treatment.The aim of this paper is to introduce the most excellent high-efficiency electrode materials and electrocatalysts in the field of dye wastewater treatment.Many electrode materials such as metal electrode materials,boron-doped diamond anode materials and three-dimensional electrode are introduced in detail.Besides,the mechanism of electrocatalytic oxidation is summarized.The composite treatment of active electrode and electrocatalyst are extensively examined.Finally,the progress of photo-assisted electrocatalytic methods of dye wastewater and the catalysts are described.

CILP-2 is a novel secreted protein and associated with insulin resistance

Genetic association studies have implicated that cartilage intermediate layer protein 2 (CILP-2) confers the risk susceptibility for type 2 diabetes (T2DM). However, it is still unknown whether CILP-2 is involved in the regulation of glucose homeostasis and insulin resistance (IR). In the current study, we initially observed that CILP-2 as a secreted protein was detected in both conditioned medium and lysates of cells transfected with an overexpressed vector. We then found that circulating CILP-2 levels had a progressive increase from normal to impaired glucose tolerance (a pre-diabetic status) and then to diabetes, which was correlated positively with waist-to-hip ratio, triglyceride, fasting blood glucose, 2-h blood glucose after glucose overload, HbA1c, fasting insulin, 2-h plasma insulin after glucose overload, and homeostasis model assessment of insulin resistance but negatively with HDL-C. CILP-2 expression was increased in the liver and muscle but decreased in adipose tissues of obese mice or T2DM patients. Furthermore, we demonstrated that CILP-2 circulating levels were affected by OGTT and Exenatide. CILP-2 overexpression resulted in impaired glucose tolerance and hepatic IR in vivo and increased PEPCK expression whereas suppressed phosphorylation of insulin receptor and Akt kinase in vitro. Based on these findings, we have identified a direct interaction between CILP-2 and PEPCK and suggested that CILP-2 plays an important role in the regulation of hepatic glucose production.