Spectrophotometric seawater pH measurement system is an urgent need of device due to its quick speed and high precision. Based on spectrophotometric method and flow injection analysis technique, an automated system for pH measurement of seawater was developed by integrating pump and valve flow path, LED light source, flow cell and spectrophotometer. This measurement system effectively avoided bubbles. The indicator of concentration gradient in the seawater sample was used to correct for the pH perturbation caused by the indicator, thus the operation of system was simple and convenient. with this system, only 1. 5 min was needed for a sample measurement with a precision of 0. 0013 pH units and an offset of 0. 0059 pH units. This system could be used for the rapid determination of pH of seawater collected by laboratory or research ship with high precision pH values.

Anaplastic lymphoma kinase (ALK) inhibitors are regarded as effective drugs for the treatment of ALK-positive NSCLC. However,the emergence of drug resistance has limited its further clinical application. This article briefly introduces the resistance mechanism of ALK inhibitors including acquired secondary mutations,gene amplification,bypass signaling pathway activation and reviews the recent advances on the reversal strategies such as drug combination,developing novel PROTACs to overcome drug resistance,so as to provide some reference for the development of ALK inhibitors.

AIM:To investigate the inhibitory effect of mogroside V(MV)on ferroptosis of human neuroblas-toma SH-SY5Y cells induced by RAS-selective lethal 3(RSL3),and to explore its possible mechanism.METHODS:To establish a model of ferroptosis,the SH-SY5Y cell was induced by RSL3.The cell viability and cellular morphology were determined by MTT assay and inverted microscopy,respectively.The intracellular ferrous ion content was measured by ferrous ion fluorescence probe FerrOrange.Mitochondrial membrane potential(MMP)was detected by mitochondrial red fluorescent probe MitoTracker Red CMXRos.The intracellular and mitochondrial reactive oxygen species(ROS)were de-tected by superoxide anion fluorescent probe dihydroethidium and mitochondrial superoxide red fluorescent probe MitoSOX Red,respectively.The cellular glutathione(GSH)and malondialdehyde(MDA)levels were tested by microplate assay.The protein levels of acyl-coenzyme A synthetase long-chain family member 4(ACSL4),cyclooxygenase-2(COX-2),glu-tathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.Molecu-lar docking techniques were employed to predict the targeting relations between MV and ACSL4/COX-2/GPX4/SLC7A11.RESULTS:Compared with control group,the SH-SY5Y cell viability,the MMP and the GSH level in RSL3 group were significantly reduced(P<0.01),while the intracellular ferrous ion level,the intracellular and mitochondrial ROS levels and the MDA level were significantly increased(P<0.05 or P<0.01).The protein levels of ACSL4 and COX-2 in RSL3 group were significantly increased,while the protein levels of GPX4 and SLC7A11 were significantly decreased(P<0.01),indicating the establishment of cell ferroptosis model.Compared with RSL3 group,the viability of SH-SY5Y cells,the MMP,the GSH level,and the GPX4 and SLC7A11 protein levels in RSL3+MV groups were significantly in-creased(P<0.05 or P<0.01),while the intracellular ferrous ion level,the intracellular and mitochondrial ROS levels,the MDA level,and the ACSL4 and COX-2 protein levels were significantly decreased(P<0.05 or P<0.01).The binding sites between MV and ferroptosis core proteins(ACSL4,COX-2,GPX4 and SLC7A11)were found by molecular docking.CONCLUSION:Treatment with MV alleviates RSL3-induced ferroptosis of SH-SY5Y cells,and the underlying mecha-nism may be associated with the activation of SLC7A11/GPX4 and the inhibition of ACSL4/COX-2.

Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first 2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, and the genetic causes of idiopathic seizures have been extensively investigated. In this study, we identified four missense mutations in the SETD1A gene (SET domain-containing 1A, histone lysine methyltransferase): three de novo mutations in three individuals and one inherited mutation in a four-generation family. Whole-exome sequencing indicated that all four of these mutations were responsible for the seizures. Mutations of SETD1A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations (R913C, Q269R, G1369R, and R1392H) in neural development. We found that their expression in mouse primary cortical neurons affected excitatory synapse development. Moreover, expression of the R913C mutation also affected the migration of cortical neurons in the mouse brain. We further identified two common genes (Neurl4 and Usp39) affected by mutations of SETD1A. These results suggested that the mutations of SETD1A play a fundamental role in abnormal synaptic function and the development of neurons, so they may be pathogenic factors for neurodevelopmental disorders.