Security Proofs for Key-Alternating Ciphers with Non-Independent Round Permutations

This work studies the key-alternating ciphers (KACs) whose round permutations are not necessarily independent. We revisit existing security proofs for key-alternating ciphers with a single permutation (KACSPs), and extend their method to an arbitrary number of rounds. In particular, we propose new techniques that can significantly simplify the proofs, and also remove two unnatural restrictions in the known security bound of 3-round KACSP (Wu et al., Asiacrypt 2020). With these techniques, we prove the first tight security bound for t-round KACSP, which was an open problem. We stress that our techniques apply to all variants of KACs with non-independent round permutations, as well as to the standard KACs

Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of H3K27 Deacetylation and Methylation

Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of brown adipocyte thermogenic program. HDAC1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing HDAC1 profoundly blocks, whereas deleting HDAC1 significantly enhances β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from, and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to UCP1 and PGC1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates brown adipocyte thermogenic program, and inhibiting HDAC1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching transcriptional repressive state to active state at the promoters of UCP1 and PGC1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis

Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of H3K27 Deacetylation and Methylation

Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of brown adipocyte thermogenic program. HDAC1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing HDAC1 profoundly blocks, whereas deleting HDAC1 significantly enhances β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from, and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to UCP1 and PGC1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates brown adipocyte thermogenic program, and inhibiting HDAC1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching transcriptional repressive state to active state at the promoters of UCP1 and PGC1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis

ADVANCED CONTROL OF GLYCOSYLATION AND TITER IN FED-BATCH MONOCLONAL ANTIBODY PRODUCTION

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Efficient wide-bandgap perovskite solar cells with open-circuit voltage deficit below 0.4 V via hole-selective interface engineering

Wide-bandgap mixed-halide perovskite solar cells (WBG-PSCs) are promising top cells for efficient tandem photovoltaics to achieve high power conversion efficiency (PCE) at low cost. However, the open-circuit voltage (VOC) of WBG-PSCs is still unsatisfactory as the VOC-deficit is generally larger than 0.45 V. Herein, we report a buried interface engineering strategy that substantially improves the VOC of WBG-PSCs by inserting amphophilic molecular hole-selective materials featuring with a cyanovinyl phosphonic acid (CPA) anchoring group between the perovskite and substrate. The assembly and redistribution of CPA-based amphiphilic molecules at the perovskite-substrate buried interface not only promotes the growth of a low-defect crystalline perovskite thin film, but also suppresses the photo-induced halide phase separation. The energy level alignment between wide-bandgap perovskite and the hole-selective layer is further improved by modulating the substituents on the triphenylamine donor moiety (methoxyls for MPA-CPA, methyls for MePA-CPA, and bare TPA-CPA). Using a 1.68 eV bandgap perovskite, the MePA-CPA-based devices achieved an unprecedentedly high VOC of 1.29 V and PCE of 22.3% under standard AM 1.5 sunlight. The VOC-deficit (&lt;0.40 V) is the lowest value reported for WBG-PSCs. This work not only provides an effective approach to decreasing the VOC-deficit of WBG-PSCs, but also confirms the importance of energy level alignment at the charge-selective layers in PSCs.</p

Intestinal Cgi-58 Deficiency Reduces Postprandial Lipid Absorption

Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes

Distinct interactions between fronto-parietal and default mode networks in impaired consciousness

Existing evidence suggests that the default-mode network (DMN) and fronto-pariatal network (FPN) play an important role in altered states of consciousness. However, the brain mechanisms underlying impaired consciousness and the specific network interactions involved are not well understood. We studied the topological properties of brain functional networks using resting-state functional MRI data acquired from 18 patients (11 vegetative state/unresponsive wakefulness syndrome, VS/UWS, and 7 minimally conscious state, MCS) and compared these properties with those of healthy controls. We identified that the topological properties in DMN and FPN are anti-correlated which comes, in part, from the contribution of interactions between dorsolateral prefrontal cortex of the FPN and precuneus of the DMN. Notably, altered nodal connectivity strength was distance-dependent, with most disruptions appearing in long-distance connections within the FPN but in short-distance connections within the DMN. A multivariate pattern-classification analysis revealed that combination of topological patterns between the FPN and DMN could predict conscious state more effectively than connectivity within either network. Taken together, our results imply distinct interactions between the FPN and DMN, which may mediate conscious state

Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition

How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of a/b-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in ApcMin/+ mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKa-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressin