The dysfunctional Wnt pathway down-regulates MLH1/SET expression and promotes microsatellite instability and immunotherapy response in colorectal cancer

The tumor heterogeneity results in different clinical characteristics of tumor patients,so precise therapy is a popular treatment strategy clinically.Microsatellite instability(MSI)is found in 10%-15%of colorectal cancer(CRC)patients and exhibits different clinical outcomes than microsatellite stable(MSS)patients.Surprisingly,MSI patients have a better prognosis than patients with stable microsatellites.Msl patients exhibit clinical features that are not responsive to chemotherapy,however,Msl patients showed excellent responses to immunotherapy.'Although the subtype classification of MSI is beneficial to the clinical treatment of CRC patients,the mechanism of MSl remains unclear.

PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism

Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6)is highly expressed in lung cancer and is required for cell metabolism,tumorigenicity,and cisplatin response of lung cancer.PRMT6 regulated the oxidative pentose phosphate pathway(PPP)flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phosphogluconate dehydrogenase(6PGD)and a-enolase(ENO1).Furthermore,PRMT6 methylated R324 of 6PGD to enhancing its activity;while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate(2-PG)binding to ENO1,respectively.Lastly,targeting PRMT6 blocked the oxidative PPP flux,glycolysis pathway,and tumor growth,as well as enhanced the antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational modification(PTM)regulator of glucose metabolism,which leads to the pathogenesis of lung cancer.It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Improving the Stability of theMultiple-Relaxation-Time Lattice Boltzmann Method by a Viscosity Counteracting Approach

Numerical instability may occur when simulating high Reynolds number flows by the lattice Boltzmann method(LBM).The multiple-relaxation-time(MRT)model of the LBM can improve the accuracy and stability,but is still subject to numerical instability when simulating flows with large single-grid Reynolds number(Reynolds number/grid number).The viscosity counteracting approach proposed recently is a method of enhancing the stability of the LBM.However,its effectiveness was only verified in the single-relaxation-time model of the LBM(SRT-LBM).This paper aims to propose the viscosity counteracting approach for the multiple-relaxationtime model(MRT-LBM)and analyze its numerical characteristics.The verification is conducted by simulating some benchmark cases:the two-dimensional(2D)lid-driven cavity flow,Poiseuille flow,Taylor-Green vortex flow and Couette flow,and threedimensional(3D)rectangular jet.Qualitative and Quantitative comparisons show that the viscosity counteracting approach for the MRT-LBMhas better accuracy and stability than that for the SRT-LBM.

Numerical Study of Stability and Accuracy of the Immersed Boundary Method Coupled to the Lattice Boltzmann BGK Model

This paper aims to study the numerical features of a coupling scheme between the immersed boundary(IB)method and the lattice Boltzmann BGK(LBGK)model by four typical test problems:the relaxation of a circular membrane,the shearing flow induced by a moving fiber in the middle of a channel,the shearing flow near a non-slip rigid wall,and the circular Couette flow between two inversely rotating cylinders.The accuracy and robustness of the IB-LBGK coupling scheme,the performances of different discrete Dirac delta functions,the effect of iteration on the coupling scheme,the importance of the external forcing term treatment,the sensitivity of the coupling scheme to flow and boundary parameters,the velocity slip near non-slip rigid wall,and the origination of numerical instabilities are investigated in detail via the four test cases.It is found that the iteration in the coupling cycle can effectively improve stability,the introduction of a second-order forcing term in LBGK model is crucial,the discrete fiber segment length and the orientation of the fiber boundary obviously affect accuracy and stability,and the emergence of both temporal and spatial fluctuations of boundary parameters seems to be the indication of numerical instability.These elaborate results shed light on the nature of the coupling scheme and may benefit those who wish to use or improve the method.