Background and Aims
NAFLD, characterized by aberrant triglyceride accumulation in liver, affects the metabolic remodeling of hepatic and nonhepatic tissues by secreting altered hepatokines. Small ...ubiquitin‐related modifier (SUMO)–specific protease 2 (SENP2) is responsible for de‐SUMOylation of target protein, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic metabolism remains unclear.
Approach and Results
We found that SENP2 was the most dramatically increased SENP in the fatty liver and that its level was modulated by fed/fasted conditions. To define the role of hepatic SENP2 in metabolic regulation, we generated liver‐specific SENP2 knockout (Senp2‐LKO) mice. Senp2‐LKO mice exhibited resistance to high‐fat diet–induced hepatic steatosis and obesity. RNA‐sequencing analysis showed that Senp2 deficiency up‐regulated genes involved in fatty acid oxidation and down‐regulated genes in lipogenesis in the liver. Additionally, ablation of hepatic SENP2 activated thermogenesis of adipose tissues. Improved energy homeostasis of both the liver and adipose tissues by SENP2 disruption prompted us to detect the hepatokines, with FGF21 identified as a key factor markedly elevated in Senp2‐LKO mice that maintained metabolic homeostasis. Loss of FGF21 obviously reversed the positive effects of SENP2 deficiency on metabolism. Mechanistically, by screening transcriptional factors of FGF21, peroxisome proliferator–activated receptor alpha (PPARα) was defined as the mediator for SENP2 and FGF21. SENP2 interacted with PPARα and deSUMOylated it, thereby promoting ubiquitylation and subsequent degradation of PPARα, which in turn inhibited FGF21 expression and fatty acid oxidation. Consistently, SENP2 overexpression in liver facilitated development of metabolic disorders.
Conclusions
Our finding demonstrated a key role of hepatic SENP2 in governing metabolic balance by regulating liver–adipose tissue crosstalk, linking the SUMOylation process to metabolic regulation.
Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O‐heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with ...carbonyls has attracted increasing attention over the past decades. However, a catalyst‐controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper‐catalyzed asymmetric formal 2+1 and 4+1 annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom‐economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote‐stereocontrol strategy.
A copper‐catalyzed asymmetric formal 2+1 and 4+1 annulation of diynes with ketones via carbonyl ylides is disclosed. This protocol enables the divergent, practical and atom‐economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities.
Dilute alloying is an effective strategy to tune properties of solid catalysts but is rarely leveraged in complex reactions beyond small molecule conversion. In this work, dilute dopants are ...demonstrated to serve as activating centers to construct multiatom catalytic domains in metal nitride electrocatalysts for lithium–sulfur (Li–S) batteries, of which the sulfur cathode suffers from sluggish and complex conversion reactions. With titanium nitride (TiN) as a model system, the dilute cobalt alloying is shown to greatly improve the reaction kinetics while inducing negligible catalyst reconstruction. Compared to the pristine TiN, the dilute nitride alloy catalyst enables onefold increase in the high rate (2.0 C) capacities of Li–S batteries, as well as an impressively low cyclic decay rate of 0.17% at a sulfur loading of 4.0 mgS cm−2. This work opens up new opportunities toward the rational design of Li–S electrocatalysts by dilute alloying and also enlightens the understandings of complex domain‐catalyzed reactions in energy applications.
Dilute alloying implants “activating” centers in nitride alloy electrocatalysts to boost lithium–sulfur (Li–S) batteries. Dilute Co dopants activate the surrounding N and Ti atoms to construct multiatom active domains for efficient bidirectional catalysis of S redox reactions. The corresponding dilute nitride alloy improves the reaction kinetics and electrochemical performance of Li–S batteries.
The anode oxygen evolution reaction (OER) is known to largely limit the efficiency of electrolyzers owing to its sluggish kinetics. While crystalline metal oxides are promising as OER catalysts, ...their amorphous phases also show high activities. Efforts to produce amorphous metal oxides have progressed slowly, and how an amorphous structure benefits the catalytic performances remains elusive. Now the first scalable synthesis of amorphous NiFeMo oxide (up to 515 g in one batch) is presented with homogeneous elemental distribution via a facile supersaturated co‐precipitation method. In contrast to its crystalline counterpart, amorphous NiFeMo oxide undergoes a faster surface self‐reconstruction process during OER, forming a metal oxy(hydroxide) active layer with rich oxygen vacancies, leading to superior OER activity (280 mV overpotential at 10 mA cm−2 in 0.1 m KOH). This opens up the potential of fast, facile, and scale‐up production of amorphous metal oxides for high‐performance OER catalysts.
Amorphous NiFeMo oxide (up to 515 g one batch) with homogeneous elemental distribution was synthesized through a facile supersaturated co‐precipitation method. The amorphous NiFeMo oxide undergoes rapid surface self‐reconstruction during OER that forms a metal oxy(hydroxide) active layer with oxygen vacancies, enabling efficient OER catalysis.
Endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in mammalian cells. The physical connection between them is mitochondria associated ER membranes ...(MAM). In recent years, studies on endoplasmic reticulum and mitochondria have shifted from independent division to association and comparison, especially MAM has gradually become a research hotspot. MAM connects the two organelles, not only to maintain their independent structure and function, but also to promote metabolism and signal transduction between them. This paper reviews the morphological structure and protein localization of MAM, and briefly analyzes the functions of MAM in regulating Ca2+ transport, lipid synthesis, mitochondrial fusion and fission, endoplasmic reticulum stress and oxidative stress, autophagy and inflammation. Since ER stress and mitochondrial dysfunction are important pathological events in neurological diseases including ischemic stroke, MAM is likely to play an important role in cerebral ischemia by regulating the signaling of the two organelles and the crosstalk of the two pathological events.
•MAM is a multi-protein enrichment platform for multiple reactions.•MAM participates in Ca2+ and lipid exchange between the two organelles.•MAM regulates mitochondrial dynamics, ER stress, autophagy and inflammation.•MAM is expected to be a new therapeutic target for cerebral ischemia.
Summary
Despite continuous evolution and development of structural health monitoring (SHM) technology, interpreting a huge amount of sensed data from a sophisticated SHM system to extract useful ...information about structural health condition remains a challenge. Aiming to resolve this problem, a novel application of probabilistic data‐driven damage detection method was proposed in the context of Sparse Bayesian Learning (SBL) scheme. The framework involves constructing a new structural damage index and establishing SBL regression model as reference base only using the data acquired in health state. The construction of the structural damage index is based on damage‐sensitive frequency band, which is determined by NExT using vibration monitoring data. The structure will be classified to be damaged as the structural damage index based on new data deviates from the index predicted by SBL regression reference model, and further, the Bayes factor is adopted to quantify the damage degree. In addition, the relationship between the Bayes factors and the resonance frequency change rate is investigated in detail. The proposed methodology features the following merits: (i) It is probabilistic data‐driven method exempting from physical model of the structure, excitation/loading information, and (ii) it belongs to the unsupervised model in need for structural damage detection, which can be formulated using only monitoring data from health state in the absence of monitoring data from damaged state. Damage detection and discrimination capabilities of the proposed methodology are verified using field monitoring data acquired from a cable‐stayed bridge. Finally, a discussion of the SBL‐based approach is made and further challenges pertaining to damage detection processes in the context of SHM are identified.
Rheumatoid arthritis (RA) is an autoimmune disease that exhibits a high degree of heterogeneity, marked by unpredictable disease flares and significant variations in the response to available ...treatments. The lack of optimal stratification for RA patients may be a contributing factor to the poor efficacy of current treatment options. The objective of this study is to elucidate the molecular characteristics of RA through the utilization of mitochondrial genes and subsequently construct and authenticate a diagnostic framework for RA. Mitochondrial proteins were obtained from the MitoCarta database, and the R package limma was employed to filter for differentially expressed mitochondrial genes (MDEGs). Metascape was utilized to perform enrichment analysis, followed by an unsupervised clustering algorithm using the ConsensuClusterPlus package to identify distinct subtypes based on MDEGs. The immune microenvironment, biological pathways, and drug response were further explored in these subtypes. Finally, a multi-biomarker-based diagnostic model was constructed using machine learning algorithms. Utilizing 88 MDEGs present in transcript profiles, it was possible to classify RA patients into three distinct subtypes, each characterized by unique molecular and cellular signatures. Subtype A exhibited a marked activation of inflammatory cells and pathways, while subtype C was characterized by the presence of specific innate lymphocytes. Inflammatory and immune cells in subtype B displayed a more modest level of activation (Wilcoxon test P < 0.05). Notably, subtype C demonstrated a stronger correlation with a superior response to biologics such as infliximab, anti-TNF, rituximab, and methotrexate/abatacept (P = 0.001) using the fisher test. Furthermore, the mitochondrial diagnosis SVM model demonstrated a high degree of discriminatory ability in distinguishing RA in both training (AUC = 100%) and validation sets (AUC = 80.1%). This study presents a pioneering analysis of mitochondrial modifications in RA, offering a novel framework for patient stratification and potentially enhancing therapeutic decision-making.
High-quality and wafer-scale graphene on insulating gate dielectrics is a prerequisite for graphene electronic applications. For such applications, graphene is typically synthesized and then ...transferred to a desirable substrate for subsequent device processing. Direct production of graphene on substrates without transfer is highly desirable for simplified device processing. However, graphene synthesis directly on substrates suitable for device applications, though highly demanded, remains unattainable and challenging. Here, we report a simple, transfer-free method capable of synthesizing graphene directly on dielectric substrates at temperatures as low as 600 °C using polycyclic aromatic hydrocarbons as the carbon source. Significantly, N-doping and patterning of graphene can be readily and concurrently achieved by this growth method. Remarkably, the graphene films directly grown on glass attained a small sheet resistance of 550 Ω/sq and a high transmittance of 91.2%. Organic light-emitting diodes (OLEDs) fabricated on N-doped graphene on glass achieved a current density of 4.0 mA/cm2 at 8 V compared to 2.6 mA/cm2 for OLEDs similarly fabricated on indium tin oxide (ITO)-coated glass, demonstrating that the graphene thus prepared may have potential to serve as a transparent electrode to replace ITO.
Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate ...the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl‐2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP‐ribose) polymerase degradation. Treatment with resveratrol led to G1 phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin‐dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor‐2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer. (Cancer Sci 2009)
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