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Abstract Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1β production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

Abstract. Background:. Psoriasis is a common, chronic, immune-mediated inflammatory skin disease with increased epidermal proliferation. The objective of this review was to systematically identify the evidence and perform a network meta-analysis (NMA) to estimate the relative efficacy of secukinumab (SEC) against adalimumab (ADA) and infliximab (INF) for the treatment of moderate-to-severe plaque psoriasis. Methods:. A systematic literature review (SLR) was conducted according to a pre-specified protocol to identify relevant studies. Initially, the databases were searched from database inception till June 2013, and the SLR was updated in April 2020. The eligibility criteria included adult patients (≥18 years old) with moderate-to-severe plaque psoriasis, and the SLR included randomized controlled trials (RCTs). The comparators of interest were SEC, ADA, INF, and placebo (PLA), while outcomes of interest were Psoriasis Area and Severity Index (PASI) (50, 75, and 90) at weeks 12, 16, and 24. A Bayesian NMA for PASI was utilized with a framework that evaluated the probability of PASI responses in different categories of PASI thresholds within a single model. Results:. A total of 23 RCTs that assessed the efficacy of SEC, ADA, and INF in patients with moderate-to-severe plaque psoriasis were identified. At 12 weeks, SEC was associated with a significantly better response compared with PLA and ADA for PASI 75 and 90, while response results were comparable against INF. At 12 weeks, risk ratio (95% confidence interval) derived from NMA for SEC vs. ADA and INF for PASI 75 was 1.35 (1.19, 1.57) and 1.01 (0.90, 1.18), respectively. At the 16-week and 24-week time interval, SEC was significantly better than PLA, ADA, and INF for PASI 75 and 90. Conclusion:. Efficacy of SEC in the treatment of patient populations with moderate-to-severe plaque psoriasis is well demonstrated through NMA.

Aluminum matrix composites have been widely used in aerospace and automotive fields due to their excellent physical properties. Cryogenic treatment was successfully adopted to improve the performance of aluminum alloy components, while its effect and mechanism on the aluminum matrix composite remained unclear. In this work, the effects of cryogenic treatment on the microstructure evolution and mechanical properties of 15%SiCp/2009 aluminum matrix composites were systematically investigated by means of Thermoelectric Power (TEP), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The results showed that TEP measurement can be an effective method for evaluating the precipitation characteristics of 15%SiCp/2009 aluminum matrix composites during aging. The addition of cryogenic treatment after solution and before aging treatment promoted the precipitation from the beginning stage of aging. Furthermore, the aging time for the maximum precipitation of the θ″ phase was about 4 h advanced, as the conduction of cryogenic treatment accelerates the aging kinetics. This was attributed to the great difference in the linear expansion coefficient between the aluminum alloy matrix and SiC-reinforced particles, which could induce high internal stress in their boundaries for precipitation. Moreover, the lattice contraction of the aluminum alloy matrix during cryogenic treatment led to the increase in dislocation density and micro defects near the boundaries, thus providing more nucleation sites for precipitation during the aging treatment. After undergoing artificial aging treatment for 20 h, the increase in dispersive, distributed precipitates after cryogenic treatment improved the hardness and yield strength by 4% and 16 MPa, respectively.

The large volume and weak environmental adaptability of fiber optical frequency combs (OFCs) have become the main obstacles for their applications in various fields. To address these issues, in this study, we present a compact, low-cost f-to-2f interferometer and fiber actuator with a large tuning range and a high control bandwidth for a 200-MHz OFC that is based on a 1.5-μm all-polarization-maintaining fiber mode-locked laser. By employing customized fiber-coupled gradient index lenses, our f-to-2f interferometer is encapsulated in a miniature tube with a diameter of only 4 mm and a length of 40 mm, which substantially reduces the optical section size of the frequency comb as compared to conventional devices. The carrier envelope offset beat with a signal-to-noise ratio of 40 dB is detected in a resolution bandwidth of 360 kHz. In addition, a laboratory-made piezoelectric transducer-driven mechanical actuator for repetition rate regulation exhibited a large tuning range of 106 kHz (corresponding to an effective temperature drift of 53 °C) and a high control bandwidth of approximately 1 kHz. This resulted in a robust repetition rate locking with an Allan deviation of 330 μHz at a gate time of 1 s and a residual integrated timing jitter of 418 fs [3 Hz to 1 MHz] when referenced to a hydrogen maser. Along with reducing the size and improving the environmental adaptability of the OFC, our design can also decrease the power consumption of the system significantly. Our findings provide a new direction to the development of OFCs for various applications.

The effect of deep cryogenic treatment (DCT) on the artificial ageing kinetics of a SiC particles reinforced aluminum alloy composite (SiCp-Al) is experimentally studied in this paper. The evolutions of both macro-properties (i.e., yield strength and ultimate tensile strength) and microstructures (precipitates) have been investigated by a set of hardness tests, tensile tests, and microstructural observations (scanning electron microscope, SEM and transmission electron microscope, TEM) for a SiCp-Al composite material with conventional heat treatment (solution heat treatment + quenching + artificial ageing, CHT) or DCT (solution heat treatment + quenching + deep cryogenic + artificial ageing). The results show that SiCp could significantly accelerate the ageing kinetics of the composites. Meanwhile, compared with CHT conditions, DCT can further improve the yield strength (YS) and ultimate tensile strength (UTS) of the composite materials after artificial ageing. The microstructures show that DCT induces the generation of more thinner θ′ precipitates homogeneously distributed in the grains during artificial ageing compared with corresponding CHT conditions. A quantified analysis has been performed based on the microstructural data, and the calculated results further support the indication that the strengthening effect in DCT compared with CHT is mainly contributed by corresponding precipitation behavior.

ABSTRACT Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWI/SNF chromatin-remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological signals. The ATP-dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different metabolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.

A novel manufacturing process, enabling the production of high quality (i.e. with low and controllable residual stress (RS) distributions and good mechanical properties) T-section 7xxx panels, has been established. This process provides a solution to residual stress induced distortion problems, which greatly concerns a range of industries, especially the aircraft industry. This process consists of three sequential steps — water quenching (WQ), cold rolling (CR) and constrained ageing (CA). The effectiveness of this process was experimentally verified through applying this process to laboratory sized 7050 T-section panels. The RS was measured by neutron diffraction and X-ray techniques, in addition to deflections and hardness at each processing stage. An integrated Finite Element (FE) model, including all three steps, was developed to simulate this manufacturing process and predict both the RS and the final strength distributions. It has been concluded that this novel process can effectively reduce the residual stresses from ±300 MPa to within ±100 MPa and produce T-section panels with required mechanical properties (i.e. hardness: ~159 HV10). A cold rolling level of 1.5% was found most appropriate. The residual stress and yield strength distributions were accurately predicted by FE, providing a valuable prediction tool to process optimization for industrial applications. Keywords: Residual stress, Neutron and X-ray diffraction, Integrated FE model, New manufacturing process, 7050 T-section

A permutation $\tau$ in the symmetric group $S_j$ is minimally overlapping if any two consecutive occurrences of $\tau$ in a permutation $\sigma$ can share at most one element. B\'ona \cite{B} showed that the proportion of minimal overlapping patterns in $S_j$ is at least $3 -e$. Given a permutation $\sigma$, we let $\text{Des}(\sigma)$ denote the set of descents of $\sigma$. We study the class of permutations $\sigma \in S_{kn}$ whose descent set is contained in the set $\{k,2k, \ldots (n-1)k\}$. For example, up-down permutations in $S_{2n}$ are the set of permutations whose descent equal $\sigma$ such that $\text{Des}(\sigma) = \{2,4, \ldots, 2n-2\}$. There are natural analogues of the minimal overlapping permutations for such classes of permutations and we study the proportion of minimal overlapping patterns for each such class. We show that the proportion of minimal overlapping permutations in such classes approaches $1$ as $k$ goes to infinity. We also study the proportion of minimal overlapping patterns in standard Young tableaux of shape $(n^k)$.

The efficient delivery of nucleic acids as therapeutic agents is a major challenge in gene therapy. Peptides have recently emerged as a novel carrier for delivery of drugs and genes. C6M1 is a designed amphipathic peptide with the ability to form stable complexes with short interfering RNA (siRNA). The peptide showed a combination of random coil and helical structure in water but mainly adopted a helical conformation in the presence of anions or siRNA. Revealed by dynamic light scattering (DLS) and microscopy techniques, the interaction of C6M1 and siRNA in water and HEPES led to complexes of ∼70 and ∼155 nm in size, respectively, but showed aggregates as large as ∼500 nm in PBS. The time-dependent aggregation of the complex in PBS was studied by DLS and fluorescence spectroscopy. At molar ratio of 15∶1, C6M1 was able to completely encapsulate siRNA; however, higher molar ratios were required to obtain stable complexes. Naked siRNA was completely degraded in 4 h in the solution of 50% serum; however C6M1 protected siRNA against serum RNase over the period of 24 h. Western blotting experiment showed ∼72% decrease in GAPDH protein level of the cells treated with C6M1-siRNA complexes while no significant knockdown was observed for the cells treated with naked siRNA.

To overcome the bottleneck of low energy density in graphene-based supercapacitors and endow them with advanced properties such as ultralong life cycles, a key rational strategy is to couple graphene sheets with multielectron, redox-reversible, and structurally stable organic compounds. This work demonstrates the synthesis and characterization of hybridizing redox-active covalent organic frameworks (COFs) with nickel bis(dithiolene) units and graphene via covalent linkages to form heterostructures for high-performance supercapacitors. Efficient electron transfer between COFs and rGO is observed which results from the orderly assembled Ni-bis(dithiolene) units with unique electronic structure, as well as the unique design of COF/rGO morphology. The obtained Ni-TAP/rGO and Ni-TAPP/rGO heterojunctions display a gravimetric capacitance of 346.0 F g−1 and 367.5 F g−1 at a current loading of 0.5 A g−1, volumetric/gravimetric specific energy densities up to 48.1 W h kg−1 and 51.04 W h kg−1, and power densities up to 1.81 kW kg−1 and 1.78 kW kg−1, as well as exceptional rate capability and cycling stability (capacitance retention of 97.01% after 10 000 cycles). [ABSTRACT FROM AUTHOR]

Intracellular bacterial (ICB) infection is one of the most life‐threatening cases of drug resistance, and photodynamic therapy (PDT) is challenged by limited light penetration into tissues and unspecific toxicity to host cells. Herein, theranostic nanoparticles (NPs) are developed to facilitate on‐demand activation of photosensitizers inside ICBs and persistent PDT of deep‐tissue ICB infections. Mechanoluminescent SrAl2O4:Eu2+ and persistence luminescent CaS:Eu2+ are sequentially deposited on mesoporous silica to prepare mSC, followed by encapsulation by bacterial membranes with loaded nitroreductase (NTR)‐activatable methylene blue (nMB) to obtain mSC‐nMB@BM NPs. The fluorescence quenching of nMB with mSC offers few cytotoxicities even under ultrasonication, and bacterial membrane coatings mediate the specific NP internalization into ICB‐infected macrophages. Bacterial pore‐forming toxins trigger nMB release from NPs, and intrabacterial NTR rejuvenates methylene blue probes from nMB for real‐time imaging of ICB infections. Ultrasonication of NPs continuously excites the rejuvenated methylene blue to generate reactive oxidative species and reduce viable ICBs by 3.54 log magnitude folds. NP treatment on ICB‐infected mice exhibits full survival and restores viscera functions without any pathological abnormality. Therefore, this concise NP design demonstrates capabilities of bacterial membrane‐mediated specific internalization, bacterial toxin‐triggered release and intrabacterial NTR‐rejuvenation of fluorescent probes, and persistent internal light‐illumination for ICB theranostics. [ABSTRACT FROM AUTHOR]

Thrombus therapy is challenged by potential bleeding risk of thrombolytic agents, and external irradiation is usually needed in thrombus imaging. Herein, highly efficient theranostic platforms are designed for piezoelectric‐Fenton‐photodynamic thrombolysis and endogenous thrombus imaging in response to the elevated shear stress at the thrombus site. Piezoelectric tetragonal barium titanate (tBT) nanoparticles (NPs) are coated with Fe3+‐coordinated metal‐organic frameworks (MOFs), followed by inoculation of chlorin e6‐luminol conjugates and heparin absorption to obtain theranostic tBT@MOFCL/Hep NPs. Shear stress‐induced piezopotential on NPs accelerates Fe3+/Fe2+ transformation to deplete MOF layers, activates Fenton reaction and produces reactive oxidative species (ROS) for non‐pharmacological thrombolysis. In the meantime, the site‐specific ROS generation oxidizes luminol and the chemiluminescent resonance energy transfer with chlorin e6 generates red fluorescence for thrombus imaging without using external light irradiation. After intravenous injection into a carotid artery thrombosis model, the heparin‐mediated thrombus targeting yields 6.5‐fold higher luminescent intensity at the thrombus site. Thrombi in the carotid arteries are almost completely dissolved with integration of piezoelectric dynamic therapy, piezopotential‐enhanced Fenton reaction, and chemiluminescence‐excited photodynamic therapy, while causing no haematologic and histopathologic abnormality. This study demonstrates a concise strategy to generate shear stress‐responsive built‐in piezoelectric potentials, site‐specific non‐pharmacological thrombolysis, self‐illuminating, and stenosis degree‐adaptable thrombus imaging. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Nomogram for Predicting Recurrence-Free Survival of Primary Localized Gastrointestinal Stromal Tumor." The correction states that there were mistakes in Table 2 and Figure 3 of the original publication. The corrected versions of Table 2 and Figure 3 are provided in the document. The authors of the article state that these corrections do not significantly impact the overall findings and conclusions of the paper. [Extracted from the article]

Background: Sepsis, a type of systemic disease, can impact nearly all organs, tissues and cells. Among them, endothelial cells are amongst the first to be affected and respond to the insult. In this study, we investigated the protective effects of microRNA-30a-5p (miR-30a-5p) on human pulmonary microvascular endothelial cells (HPMECs) treated with lipolysaccharide (LPS). Methods: An in vitro model of sepsis was established in HPMECs with the use of LPS. Transfecting with different tools (mimetic and inhibitor) to modify miR-30a-5p expression. Cell viability, proliferation and apoptosis were detected by the CCK-8 assay, the EdU kit and fluorescence staining, respectively. The autophagy-related protein and mRNA expression, the number of autophagosomes were separately examined through Western blot analysis, qPT-PCR and confocal microscopy. TargetScan and the luciferase reporter assays were used to probe target genes interacting with miR-30a-5p. Results: LPS caused a reduction in the viability and proliferation of HPMECs, as well as an elevation in the number of apoptotic cells. Subsequently, we observed that miR-30a-5p might play a role in preventing LPS-induced inhibition of cell damage and decreasing HPMEC apoptosis, suggesting the potential function of miR-30a-5p in this injury process. Finally, we confirmed that miR-30a-5p exerts its protective effect by regulating cell autophagy, possibly by targeting Beclin-1. Conclusion: Our study provided evidence that autophagy is a crucial aspect in the protective role of miR-30a-5p against LPS-induced HPMEC injury, identifying a promising target for sepsis-related endothelial cell injury. [ABSTRACT FROM AUTHOR]

Phthalimidine finds wide pharmaceutical applications and its deuterated derivative is supposed to exhibit enhanced stability towards metabolism. In this work, an electrochemically reductive deuteration strategy from phthalimide to phthalimidine‐d2 was achieved with D2O as a deuterium source at the reagent level in common solvents. This approach showed broad compatibility with a variety of functional groups. Mechanistic investigations assisted by electrochemical analysis revealed a 4‐electron reduction pathway, and the coupled anodic oxygen evolution collectively maintains a neutral to mild basic conditions for the ongoing electrochemical reaction. [ABSTRACT FROM AUTHOR]

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor (Vldlr) in retinal neovascularization and hypoxia-induced factor 1 alpha (Hif1a). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development. [ABSTRACT FROM AUTHOR]