Toward Quantifying the Increasing Accessibility of the Arctic Northeast Passage in the Past Four Decades

Sea ice,one of the most dominant barriers to Arctic shipping,has decreased dramatically over the past four decades.Arctic maritime transport is hereupon growing in recent years.To produce a long-term assessment of trans-Arctic accessibility,we systematically revisit the daily Arctic navigability with a view to the combined effects of sea ice thickness and concentration throughout the period 1979−2020.The general trends of Navigable Windows(NW)in the Northeast Passage show that the number of navigable days is steadily growing and reached 89±16 days for Open Water(OW)ships and 163±19 days for Polar Class 6(PC6)ships in the 2010s,despite high interannual and interdecadal variability in the NWs.More consecutive NWs have emerged annually for both OW ships and PC6 ships since 2005 because of the faster sea ice retreat.Since the 1980s,the number of simulated Arctic routes has continuously increased,and optimal navigability exists in these years of record-low sea ice extent(e.g.,2012 and 2020).Summertime navigability in the East Siberian and Laptev Seas,on the other hand,varies dramatically due to changing sea ice conditions.This systematic assessment of Arctic navigability provides a reference for better projecting the future trans-Arctic shipping routes.

Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair

The partitioning-defective 3 （Par3）, a key component in the conserved Par3/Par6/aPKC complex, plays fundamental roles in cell polarity. Herein we report the identification of Ku70 and Ku80 as novel Par3-interacting proteins through an in vitro binding assay followed by liquid chromatography-tandem mass spectrometry. Ku70/Ku80 proteins are two key regulatory subunits of the DNA-dependent protein kinase （DNA-PK）, which plays an essential role in repairing double-strand DNA breaks （DSBs）. We determined that the nuclear association of Par3 with Ku70/Ku80 was enhanced by γ-irradiation （IR）, a potent DSB inducer. Furthermore, DNA-PKcs, the catalytic subunit of DNA-PK, interacted with the Par3/Ku70/Ku80 complex in response to IR. Par3 over-expression or knockdown was capable of up- or downregulating DNA-PK activity, respectively. Moreover, the Par3 knockdown cells were found to be defective in random plasmid integration, defective in DSB repair following IR, and radiosensitive, phenotypes similar to that of Ku70 knockdown cells. These findings identify Par3 as a novel component of the DNA-PK complex and implicate an unexpected link of cell polarity to DSB repair.

Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair

The author affiliations were mixed up in the previous published version. The third fund number of National NaturalScience Foundation of China in the Acknowledgments was wrong, it should be "30270335". The Shanghai MunicipalCouncil for Science and Technology (No.06DZ22032) was missed in the Acknowledgments. There are some labelingand production errors in Figure 2A, Figure 3B and 3C, Figure 5C, Figure 6B and 6E, Figure 7B and 7D. In Figure 2A,left panel "A431" should be "Par3". In Figure 3B and 3C, "anti-Par3CT" should be "anti-Par3LCT", "GST-Par3CT"should be "GST-Par3LCT". In Figure 5C, the second arrow indicating "Lamin B" should be "[3-tubulin". In Figure 6Bright panel, the molecular weight for ?-actin should be "43" instead of"200". In Figure 6E, "Par3" should be "Par3i". Themolecular weight for the DNA-PKcs panel should be the same as the p-DNA-PKcs. In Figure 7B, the time point "240"in the left panel should be "120"; in the right panel of Figure 7B, the title for the y axis should be "DNA released (%)".In Figure 7D, the title for the y axis should be "Survival (%)", and the scale for the y axis should be "100, 10 and 1". These corrections do not affect the conclusions of the study. We apologize for any inconvenience this may havecaused.

MFSD12 affects glycosphingolipid metabolism by modulating lysosome homeostasis

Dear Editor,Glycosphingolipid(GSL)catabolism is strictly regulated in a sequential manner by lysosomal hydrolases with the help of lipid-binding proteins.Impairments of the catabolic pathway cause the onset of lysosomal storage diseases(LsDs),which are characterized by the aberrant accumulation of GSLs(Hannun and Obeid 2018;Breiden and Sandhoff 2019).The primary LSDs occur through the well-known mechanism of inherited defects in genes encoding the catabolic enzymes(or their related cofactors)which reside in the lumen of lysosomes(Hannun and Obeid 2018;Breiden and Sandhoff 2019).However,in some LSDs,the inherited mutations affect other proteins,such as those residing in the lysosomal membrane;these mutations are associated with defects in traffcking and fusion in the endocytic system(Platt et al.2012).However,the non-lumenal lysosomal membrane proteins involved in GSL metabolism remain to be identified.

Regulation of glucose and lipid metabolism in health and disease

Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.

PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation

A change in the metabolic flux of glucose from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis is regarded as one hallmark of cancer. However, the mechanisms underlying the metabolic switch between aerobic glycolysis and OXPHOS are unclear. Here we show that the M2 isoform of pyruvate kinase (PKM2), one of the rate-limiting enzymes in glycolysis, interacts with mitofusin 2 (MFN2), a key regulator of mitochondrial fusion, to promote mitochondrial fusion and OXPHOS, and attenuate glycolysis. mTOR increases the PKM2:MFN2 interaction by phosphorylating MFN2 and thereby modulates the effect of PKM2: MFN2 on glycolysis, mitochondrial fusion and OXPHOS. Thus, an mTOR-MFN2-PKM2 signaling axis couples glycolysis and OXPHOS to modulate cancer cell growth.

mTORC1 signaling in hepatic lipid metabolism

The mechanistic target of rapamycin （mTOR） signaling pathway regulates many metabolic and physiological processes in different organs or tissues. DysregulaUon of mTOR signaling has been implicated in many human diseases including obesity, diabetes, cancer, fatty liver diseases, and neuronal disorders. Here we review recent progress in understanding how mTORC1 （mTOR complex 1） signaling regulates lipid metabolism in the liver.

CRTC2 modulates hepatic SREBPlc cleavage by controlling Insig2a expression during fasting

Dear Editor, Dysregulation of hepatic lipid and glucose production results in obesity, diabetes and nonalcoholic fatty liver disease. De novo lipogenesis and gluconeogenesis in the liver con- tribute, at least in part, to the dynamic homeostasis of lipid and glucose levels （Rui, 2014; Han and Wang, 2017）. These processes are regulated at the transcriptional level by dif- ferent transcription factors Jn response to various environ- mental cues, including hormones, nutrition and stress. Regulators of lipogenesis include the sterol regulatory ele- ment-binding proteins （SREBPs）, which are members of the basic helix-loop-helix leucine zipper transcription factor family （Goldstein et al., 2006）. There are three closely rela- ted SREBPs, SREBPla, SREBPlc and SREBP2, among which SREBPlc and SREBP2 are the major isoforms expressed in the liver. SREBPlc mainly regulates fatty acid synthesis.

Evaluation indexes for symptom changes in Chinese medicine

OBJECTIVE: To screen and summarize evaluation indexes for symptom changes in Chinese medicine(CM).METHODS: A case database was established based on information from subsequent patient visits from the case records of famous doctors since 1866.Symptom change descriptions in the database were regarded as research materials. The evaluation indexes of the symptom changes were screened and summarized.RESULTS: In total, 243 evaluation indexes for 256symptoms were summarized. Among them, common symptoms were frequency, quantity, degree,mobility, color, and correlation with fatigue.CONCLUSION: There are many aspects to evaluating the changes in a symptom. Some symptoms occur with other simultaneous symptoms. The alleviation or aggravation of simultaneous symptoms could reflect the corresponding changes in a symptom. The changes of inducing factors are important to judging changes in symptoms.