Sirtuins are NAD-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1-7. Four of them (Sirt4-7) have no detectable or very weak deacetylase activity. Here we found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg105) and tyrosine residue (Tyr102) in the acyl pocket of Sirt5. Several mammalian proteins were identified to have succinyl or malonyl lysine modifications by mass spectrometry. Deletion of Sirt5 in mice appeared to increases the level of succinylation on carbamoyl phosphate synthase 1, a known target of Sirt5. Thus protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo.

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SUMMARY Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting anti-tumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy.

A B S T R A C TBackgrounds: Up to February 16, 2020, 355 cases have been confirmed as having COVID-19 infection on the Diamond Princess cruise ship. It is of crucial importance to estimate the reproductive number (R0) of the novel virus in the early stage of outbreak and make a prediction of daily new cases on the ship. Method: We fitted the reported serial interval (mean and standard deviation) with a gamma distribution and applied "earlyR" package in R to estimate the R0 in the early stage of COVID-19 outbreak. We applied "projections" package in R to simulate the plausible cumulative epidemic trajectories and future daily incidence by fitting the data of existing daily incidence, a serial interval distribution, and the estimated R0 into a model based on the assumption that daily incidence obeys approximately Poisson distribution determined by daily infectiousness. Results: The Maximum-Likelihood (ML) value of R0 was 2.28 for COVID-19 outbreak at the early stage on the ship. The median with 95% confidence interval (CI) of R0 values was 2.28 (2.06-2.52) estimated by the bootstrap resampling method. The probable number of new cases for the next ten days would gradually increase, and the estimated cumulative cases would reach 1514 (1384-1656) at the tenth day in the future. However, if R0 value was reduced by 25% and 50%, the estimated total number of cumulative cases would be reduced to 1081 (981-1177) and 758 (697-817), respectively. Conclusion: The median with 95% CI of R0 of COVID-19 was about 2.28 (2.06-2.52) during the early stage experienced on the Diamond Princess cruise ship. The future daily incidence and probable outbreak size is largely dependent on the change of R0. Unless strict infection management and control are taken, our findings indicate the potential of COVID-19 to cause greater outbreak on the ship.

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To replace precious platinum (Pt)-based electrocatalysts for cathodic oxygen reduction reaction (ORR), edge-selectively sulfurized graphene nanoplatelets (SGnP) are synthesized as efficient metal-free electrocatalysts simply by ball-milling pristine graphite in the presence of sulfur (S8 ). The resultant SGnPs exhibit remarkable electrocatalytic activity toward ORR with better tolerance to methanol crossover/CO poisoning effects and longer-term stability than those of pristine graphite and commercial Pt/C electrocatalysts. Edge-Selectively Sulfurized Graphene Nanoplatelets as Efficient Metal-Free Electrocatalysts for Oxygen Reduction Reaction: The Electron Spin Effect.

Precuneus responds to a wide range of cognitive processes. Here, we examined how the patterns of resting state connectivity may define functional subregions in the precuneus. Using a K-means algorithm to cluster the whole-brain “correlograms” of the precuneus in 225 adult individuals, we corroborated the dorsal-anterior, dorsal-posterior, and ventral subregions, each involved in spatially guided behaviors, mental imagery, and episodic memory as well as self-related processing, with the ventral precuneus being part of the default mode network, as described extensively in earlier work. Furthermore, we showed that the lateral/medial volumes of dorsal anterior and dorsal posterior precuneus are each connected with areas of motor execution/attention and motor/visual imagery, respectively. Compared to the ventral precuneus, the dorsal precuneus showed greater connectivity with occipital and posterior parietal cortices, but less connectivity with the medial superior frontal and orbitofrontal gyri, anterior cingulate cortex as well as the parahippocampus. Compared to dorsal-posterior and ventral precuneus, the dorsal-anterior precuneus showed greater connectivity with the somatomotor cortex, as well as the insula, supramarginal, Heschl’s, and superior temporal gyri, but less connectivity with the angular gyrus. Compared to ventral and dorsal-anterior precuneus, dorsal-posterior precuneus showed greater connectivity with the middle frontal gyrus. Notably, the precuneus as a whole has negative connectivity with the amygdala and the lateral and inferior orbital frontal gyri. Finally, men and women differed in the connectivity of precuneus. Men and women each showed greater connectivity with the dorsal precuneus in the cuneus and medial thalamus, respectively. Women also showed greater connectivity with ventral precuneus in the hippocampus/parahippocampus, middle/anterior cingulate gyrus, and middle occipital gyrus, compared to men. Taken together, these new findings may provide a useful platform upon which to further investigate sex-specific functional neuroanatomy of the precuneus and to elucidate the pathology of many neurological illnesses.