Search

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [14C]carboplatin or [14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376–87. ©2016 AACR.

Chemical structures, patient data, mouse survival curves, additional biomarker data

A hydrogen processing strategy is developed to enable bulk LaNi5 to attain high activity and long‐term stability toward the electrocatalytic oxygen evolution reaction (OER). By a combination of in situ Raman and quasi in situ X‐ray absorption (XAS) spectra, secondary‐electron‐excited scanning transmission electron microscopy (STEM) patterns as well as the Rietveld method and density functional theory (DFT) calculations, it is discovered that hydrogen‐induced lattice distortion, grain refinement, and particle cracks dictate the effective reconstruction of the LaNi5 surface into a porous hetero‐nanoarchitecture composed of uniformly confined active γ‐NiOOH nanocrystals by La(OH)3 layer in the alkaline OER process. This significantly optimizes the charge transfer, structural integrity, active‐site exposure, and adsorption energy toward the reaction intermediates. Benefiting from these merits, the overpotential (322 mV) at 100 mA cm−2 for the hydrogen‐processed OER catalyst deposited on nickel foam is reduced by 104 mV as compared to the original phase. Notably, it exhibits remarkable stability for 10 days at an industrial‐grade current density of more than 560 mA cm−2 in alkaline media.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis (NASH). The factors promoting the progression of steatosis to NASH are still unclear. Recent studies suggest that mitochondrial lipid composition is critical in NASH development. Here, we showed that CDP-DAG synthase 2 (Cds2) was downregulated in genetic or diet-induced NAFLD mouse models. Liver-specific deficiency of Cds2 provoked hepatic steatosis, inflammation and fibrosis in five-week-old mice. CDS2 is enriched in mitochondria-associated membranes (MAMs), and hepatic Cds2 deficiency impaired mitochondrial function and decreased mitochondrial PE levels. Overexpression of phosphatidylserine decarboxylase (PISD) alleviated the NASH-like phenotype in Cds2f/f;AlbCre mice and abnormal mitochondrial morphology and function caused by CDS2 deficiency in hepatocytes. Additionally, dietary supplementation with an agonist of peroxisome proliferator-activated receptor alpha (PPARα) attenuated mitochondrial defects and ameliorated the NASH-like phenotype in Cds2f/f;AlbCre mice. Finally, Cds2 overexpression protected against high-fat diet-induced hepatic steatosis and obesity. Thus, Cds2 modulates mitochondrial function and NASH development.

AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the glycerol-3-phosphate pathway for the synthesis of phospholipids and triacylglycerols. AGPAT2 is the only AGPAT isoform whose loss-of-function mutations cause a severe form of human congenital generalized lipodystrophy. Paradoxically, AGPAT2 deficiency is known to dramatically increase the level of its product, PA. Here, we find that AGPAT2 deficiency impairs the biogenesis and growth of lipid droplets. We show that AGPAT2 deficiency compromises the stability of CDP-diacylglycerol (DAG) synthases (CDSs) and decreases CDS activity in both cell lines and mouse liver. Moreover, AGPAT2 and CDS1/2 can directly interact and form functional complexes, which promote the metabolism of PA along the CDP-DAG pathway of phospholipid synthesis. Our results provide key insights into the regulation of metabolic flux during lipid synthesis and suggest substrate channelling at a major branch point of the glycerol-3-phosphate pathway., AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the synthesis of all glycerolipids. Here, the authors show that AGPAT2 and CDP-DAG synthases (CDS1 and CDS2) form functional complexes that promote further conversion of PA along the CDP-DAG pathway of phospholipid synthesis.

Metal-organic frameworks (MOFs) are regarded as one promising class of precatalysts for electrocatalytic oxygen evolution reaction (OER), yet most of them suffer from poor conductivity and lack of coordinatively unsaturated metal sites, which hinders the fast electrochemical reconstruction and thus a poor OER activity. To address this issue, a unique heterocomposite has been constructed by in situ inserting carbon dots (CDs) into cobalt-based zeolitic imidazolate framework (Co-ZIF) nanosheet arrays (Co-ZIF/CDs/CC) in the presence of carbon cloth (CC) via one-pot coprecipitation for alkaline OER. Benefiting from the synergism between CDs and Co-ZIF subunits such as superior conductivity, strong charge interaction as well as abundant metal sites exposure, the Co-ZIF/CDs/CC exhibits an enhanced promotion effect for OER and contributes to the deep phase transformation from CDs-coupled Co-ZIF to CDs-coupled active CoOOH. As expected, the achieved Co-ZIF/CDs/CC only requires an overpotential of 226 mV to deliver 10 mA cm

The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate whether PI(3)P is functionally linked to seipin and whether PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. Our results thus identify PI(3)P as a novel regulator of LD initiation and suggest that PI(3)P may impact the biogenesis of LDs through DFCP1.

—A rectangular array of seismic nodes is called a 3D seismic sensors array which is suitable for geographic routing. However, when certain seismic nodes have no location information, using detours or other methods to detect the path will increase latency and power consumption of geographic routing. It is challenging to maintain the high performance of geographic routing in practical 3D exploration networks. This letter proposes a greedy flee in the direction routing algorithm (GFDR). According to the feature that the intersection of the connection set of nodes is not empty, GFDR can drive the packet continuously forward in a specified direction without location information when the packet records the node ID of the path. Simulation results show that as the size of the area without location information (AWLI) increases, GFDR can keep the delivery ratio above 98%, while maintaining an approximately constant packet delay without increasing the number of packet-forwarding hops. A real seismic system experiment running GFDR algorithm confirms the simulation results and demonstrates the effectiveness of GFDR.

Cholesterol synthesis is both energy- and oxygen-intensive, yet relatively little is known of the regulatory effects of hypoxia on pathway enzymes. We previously showed that the rate-limiting and first oxygen-requiring enzyme of the committed cholesterol synthesis pathway, squalene monooxygenase (SM), can undergo partial proteasomal degradation that renders it constitutively active. Here, we show that hypoxia is the physiological trigger for this truncation, which occurs through a two-part mechanism: (1) increased targeting of SM to the proteasome via stabilization of the E3 ubiquitin ligase MARCHF6, and (2) accumulation of the SM substrate, squalene, which impedes the complete degradation of SM and liberates its truncated form. Truncation of SM is also increased in endometrial cancer tissues, where it correlates with levels of hypoxia-inducible factor−1α. These results uncover a feedforward mechanism that enables SM to accommodate fluctuations in substrate levels yet is also a likely contributor to its widely reported oncogenic properties.

Using two-dimensional electrophoresis along with mass spectroscopy, we have investigated how the cryopreservation process affected the protein profile of goat ejaculated sperm. In this study, five bucks were used for semen collection. After removal of seminal plasma, the Tris-based extender containing glycerol and egg yolk was used to freeze semen. The results indicated that the post-thaw sperm quality showed a significant reduction compared with fresh sperm. The numbers of protein spots acquired in fresh and post-thaw sperm were 2926 ± 57 and 3061 ± 81, respectively. Twenty-two different abundant proteins (DAPs) were identified between fresh sperm and frozen-thawed sperm (≥3.0-folds

As an emerging technique, unmanned aerial vehicle (UAV) aided multi-access edge computing (MEC) network has been improving the performance of the communication network. The novel architecture is beneficial for coverage, flexibility, and reliability. However, reducing network latency is a critical issue. In this paper, we design a UAV-aided network with a millimeter wave (mmWave) backhaul to achieve the multi-access edge computing. The routing problem is formulated and solved first to obtain the optimal routes through the ad hoc link for all users. Then, we formulate the joint trajectory design and resource allocation problem, which is a mixed-integer nonconvex programming, to minimize the network latency. Furthermore, we design a novel iterative algorithm framework to handle this challenging problem. In the outer loop, the proposed problem is separated into the primal problems and master problems by adopting generalized benders decomposition (GBD). In the inner loop, we design the algorithm to solve the continuous nonconvex primal problem by combining the alternating direction method of multipliers (ADMM), Dinkelbach algorithm, and successive convex approximation (SCA) algorithm. The simulation results demonstrate that our proposed algorithm framework is effective and feasible.

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as β-secretase, is an aspartic protease. The sorting of this enzyme into Rab11-positive recycling endosomes regulates the BACE1-mediated cleavage of its substrates, however, the mechanisms underlying this targeting remain poorly understood. The neural cell adhesion molecule 2 (NCAM2) is a substrate of BACE1. We show that BACE1 cleaves NCAM2 in cultured hippocampal neurons and NCAM2-transfected CHO cells. The C-terminal fragment of NCAM2 that comprises the intracellular domain and a small portion of NCAM2’s extracellular domain, associates with BACE1. This association is not affected in cells with inhibited endocytosis, indicating that the interaction of NCAM2 and BACE1 precedes the targeting of BACE1 from the cell surface to endosomes. In neurons and CHO cells, this fragment and BACE1 co-localize in Rab11-positive endosomes. Overexpression of full-length NCAM2 or a recombinant NCAM2 fragment containing the transmembrane and intracellular domains but lacking the extracellular domain leads to an increase in BACE1 levels in these organelles. In NCAM2-deficient neurons, the levels of BACE1 are increased at the cell surface and reduced in intracellular organelles. These effects are correlated with increased levels of the soluble extracellular domain of BACE1 in the brains of NCAM2-deficient mice, suggesting increased shedding of BACE1 from the cell surface. Of note, shedding of the extracellular domain of Sez6, a protein cleaved exclusively by BACE1, is reduced in NCAM2-deficient animals. These results indicate that the BACE1-generated fragment of NCAM2 regulates BACE1 activity by promoting the targeting of BACE1 to Rab11-positive endosomes.

Based on the low cost and relatively high catalytic activity, considerable efforts have been devoted towards developing redox active transition metal TM oxygen electrocatalysts for the alkaline oxygen evolution reaction OER while the role of redox inactive alkaline earth metals has often been neglected in OER. Herein, for the first time, we developed a novel ternary intermetallic CaFe6Ge6 precatalyst, whose surface rapidly transforms into a porous ultrathin Ca amp; 8722;Fe amp; 8722;O heteroshell structure during alkaline OER through the oxidative leaching of surficial Ge. Benefiting from synergistic effects, this highly efficient OER active material with distinct Ca amp; 8722;Fe amp; 8722;O layers has a large electrochemical surface area and more exposed active Fe sites than a Ca free FeOx phase. Also, the presence of Ca in Ca amp; 8722;Fe amp; 8722;O is responsible for the enhanced transport and activation of hydroxyls and related OER reaction intermediate as unequivocally illustrated by a combination of quasi in situ Raman spectroscopy and various ex situ methods

To retrospectively analyze the pulmonary computed tomography (CT) characteristics and dynamic changes in the lungs of cured coronavirus disease 2019 (COVID-19) patients at discharge and reexamination.A total of 155 cured COVID-19 patients admitted to designated hospitals in Yunnan Province, China, from February 1, 2020, to March 20, 2020, were included. All patients underwent pulmonary CT at discharge and at 2 weeks after discharge (during reexamination at hospital). A retrospective analysis was performed using these two pulmonary CT scans of the cured patients to observe changes in the number, distribution, morphology, and density of lesions.At discharge, the lung CT images of 15 cured patients showed no obvious lesions, while those of the remaining 140 patients showed different degrees of residual lesions. Patients with moderate disease mostly had multiple pulmonary lesions, mainly in the lower lobes of both lungs. At reexamination, the lung lesions in the patients with moderate disease had significantly improved (P0.05), and the lung lesions in the patients with severe disease had partially improved, especially in patients with multi-lobe involvement (χ 2 =3.956, P0.05). At reexamination, the lung lesions of patients with severe disease did not show significant changes (P0.05).The pulmonary CT manifestations of cured COVID-19 patients had certain characteristics and variation patterns, providing a reference for the clinical evaluation of treatment efficacy and prognosis of patients.

The electrochemical oxygen reduction reaction ORR offers a most promising and efficient route to produce hydrogen peroxide H2O2 , yet the lack of cost effective and high performance electrocatalysts have restricted its practical application. Herein, an entropy enhancement strategy has been employed to enable the low cost perovskite oxide to effectively catalyze the electrosynthesis of H2O2. The optimized Pb NiWMnNbZrTi 1 6O3 ceramic is available on a kilogram scale and displays commendable ORR activity in alkaline media with high selectivity over 91 amp; 8201; across the wide potential range for H2O2 including an outstanding degradation property for organic dyes through the Fenton process. The exceptional performance of this perovskite oxide is attributed to the entropy stabilization induced polymorphic transformation assuring the robust structural stability, decreased charge mobility as well as synergistic catalytic effects which we confirm using advanced in situ Raman, transient photovoltage, Rietveld refinement as well as finite elemental analysis

Inducible degrader of low-density lipoprotein (LDL) receptor (Idol) is an E3 ubiquitin ligase coded by Idol, the target gene of liver X receptor (LXR), which primarily mediates the ubiquitination and lysosomal degradation of low-density lipoprotein receptor (LDLR). Previous studies from independent groups have shown that plasma cholesterol regulation by the LXR-Idol-LDLR axis is tissue- and species-specific, indicating that the precise molecular mechanism by which Idol modulates lipid metabolism has not been completely understood and needs to be further validated in other species. Hamster, a small rodent animal model expressing endogenous cholesterol ester transfer protein (CETP), possesses many metabolic characteristics that are different from mouse but similar to human. In this study, an Idol knockout (Idol-/-) hamster model was developed using CRISPR/Cas9 gene editing system to investigate the effect of Idol depletion on plasma lipid metabolism and atherosclerosis. Our results showed that there were no significant differences in hepatic LDLR protein and plasma cholesterol levels in Idol-/- hamsters compared with wild-type (WT) controls, which was consistent with the observation that LXR agonist treatment increased the expression of Idol mRNA in the small intestine but not in the liver of WT hamsters. However, we found that plasma triglyceride (TG) levels were significantly reduced in Idol-/- hamsters due to an enhancement of TG clearance. In addition, the morphological data demonstrated that inactivation of Idol significantly lowered plasma total cholesterol and TG levels and protected against spontaneous atherosclerotic lesions in aged LDLR knockout hamsters on a chow diet but had no effect on diet-induced atherosclerosis in hamsters lacking one copy of the Ldlr gene. In conclusion, our findings suggest that Idol can regulate plasma lipid metabolism and atherosclerosis independent of LDLR function.

Transition metals, in particular noble metals, are the most common species in metal-mediated water electrolysis because they serve as highly active catalytic sites. In many cases, the presence of nontransition metals, that is, s-, p-, and f-block metals with high natural abundance in the earth-crust in the catalytic material is indispensable to boost efficiency and durability in water electrolysis. This is why alkali metals, alkaline-earth metals, rare-earth metals, lean metals, and metalloids receive growing interest in this research area. In spite of the pivotal role of these nontransition metals in tuning efficiency of water electrolysis, there is far more room for developments toward a knowledge-based catalyst design. In this review, five classes of nontransition metals species which are successfully utilized in water electrolysis, with special emphasis on electronic structure-catalytic activity relationships and phase stability, are discussed. Moreover, specific fundamental aspects on electrocatalysts for water electrolysis as well as a perspective on this research field are also addressed in this account. It is anticipated that this review can trigger a broader interest in using s-, p-, and f-block metals species toward the discovery of advanced polymetal-containing electrocatalysts for practical water splitting.

In this study, the effects of trehalose and 1, 3-cyclohexanediol (1, 3-CHD) on the ultrastructure of frozen-thawed ram sperm were assessed and compared. In the control group, sperm were frozen without trehalose and 1, 3-CHD. In the trehalose group, 100 mM trehalose was used for sperm cryopreservation. In the cyclohexanediol group, the freezing extender contained 100 mM 1, 3-CHD. The transmission electron microscope (TEM) was used to observe the ultrastructural alterations of sperm. For verification of the TEM results, the plasma membrane and acrosome integrity of ram frozen sperm was assessed. Three fertility-proven rams were used in this study. Semen collection was repeated 6 times. The collected semen was pooled to preclude the individual difference each time. The sperm collected from a representative ram were used for ultrastructural observation. The TEM results indicated extensive and severe cryoinjuries on the main organelles of ram frozen sperm. Some alterations in plasma membrane, including detachment, rupture, dilation, or loss, appeared in post-thaw sperm. The bending shape and leakage of genetic materials were also observed in the nucleus. In addition, the outer acrosome membrane in some frozen sperm was broken or partly lost. Further, leakage of the inner contents of acrosomes also occurred. Sperm mitochondria was negatively influenced by cryopreservation. With 1, 3-CHD or trehalose, the percentage of sperm with normal acrosomes was 62% or 64%, and it was significantly higher than that of the control (41.51%

Developing advanced electrocatalysts with exceptional two electron 2e amp; 8722; selectivity, activity, and stability is crucial for driving the oxygen reduction reaction ORR to produce hydrogen peroxide H2O2 . Herein, a composition engineering strategy is proposed to flexibly regulate the intrinsic activity of amorphous nickel boride nanoarchitectures for efficient 2e amp; 8722; ORR by oriented reduction of Ni2 with different amounts of BH4 amp; 8722;. Among borides, the amorphous NiB2 delivers the 2e amp; 8722; selectivity close to 99 at 0.4 V and over 93 in a wide potential range, together with a negligible activity decay under prolonged time. Notably, an ultrahigh H2O2 production rate of 4.753 mol gcat amp; 8722;1 h amp; 8722;1 is achieved upon assembling NiB2 in the practical gas diffusion electrode. The combination of X ray absorption and in situ Raman spectroscopy, as well as transient photovoltage measurements with density functional theory, unequivocally reveal that the atomic ratio between Ni and B induces the local electronic structure diversity, allowing optimization of the adsorption energy of Ni toward OOH and reducing of the interfacial charge transfer kinetics to preserve the O amp; 63743;O bond

TMEM41B and VMP1, two endoplasmic reticulum (ER)-resident transmembrane proteins, play important roles in regulating the formation of lipid droplets (LDs), autophagy initiation, and viral infection. However, the biochemical functions of TMEM41B and VMP1 are unclear. A lipids distribution screen suggested TMEM41B and VMP1 are critical to the normal distribution of cholesterol and phosphatidylserine. Biochemical analyses unveiled that TMEM41B and VMP1 have scramblase activity. These findings shed light on the mechanism by which TMEM41B and VMP1 regulate LD formation, lipids distribution, macroautophagy, and viral infection.

Immunotherapy is a powerful treatment strategy being applied to cancer, autoimmune diseases, allergies, and transplantation. Although therapeutic monoclonal antibodies (mAbs) have demonstrated significant clinical efficacy, there is also the potential for severe adverse events, including cytokine release syndrome (CRS). CRS is characterized by the rapid production of inflammatory cytokines following delivery of therapy, with symptoms ranging from mild fever to life‐threating pathology and multi‐organ failure. Overall there is a paucity of models to reliably and accurately predict the induction of CRS by immune therapeutics. Here, we describe the development of a humanized mouse model based on the NOD‐scid IL2rgnull (NSG) mouse to study CRS in vivo. PBMC‐engrafted NSG, NSG‐MHC‐DKO, and NSG‐SGM3 mice were used to study cytokine release in response to treatment with mAb immunotherapies. Our data show that therapeutic‐stimulated cytokine release in these PBMC‐based NSG models captures the variation in cytokine release between individual donors, is drug dependent, occurs in the absence of acute xeno‐GVHD, highlighting the specificity of the assay, and shows a robust response following treatment with a TGN1412 analog, a CD28 superagonist. Overall our results demonstrate that PBMC‐engrafted NSG models are rapid, sensitive, and reproducible platforms to screen novel therapeutics for CRS.

As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma1. ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer’s disease and cancer2–7. Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family8. The structure of human ACAT1, which catalyses the transfer of an acyl group from acyl-coenzyme A to cholesterol to form cholesteryl ester, is resolved by cryo-electron microscopy.

The Ti-heteropolyacid H4[Ti(H2O)TiW11O39]·7H2O (TiW11Ti) loading TiO2 with different contents was prepared using dipping method. The TiW11Ti/TiO2 hybrid was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and diffuse reflectance spectra (DRS). The photocatalytic performance of TiW11Ti/TiO2 hybrid was investigated by rapid degradation of X-3B as simulated wastewater under xenon light irradiation. The different loading amount of TiW11Ti exhibited different activity. The order of different loading weights of TiW11Ti was as follows: 43 wt% TiW11Ti > 31 wt% TiW11Ti > 50 wt% TiW11Ti > 20 wt% TiW11Ti. The results revealed that the rapid degradation process followed the first-order kinetic reaction according to Langmuir equation. The TiW11Ti/TiO2 hybrid exhibited highly efficient photocatalytic activity, which was potential for environmental purification.

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms. Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays. Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice. Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

Recently, large-scale wireless seismometer array (WSA) have played an increasingly important role in oil/gas exploration industry and seismology research. However, due to limited wireless channel bandwidth, transmission latency and high power consumption caused by transmission conflicts in battery-powered seismometers, real-time large-scale WSA system remains unsolved. In this article, we introduce a LoRaWAN-based WSA system with high precise time slot deriving from a synchronization platform composed of GPS timing module and temperature compensated crystal oscillator (TCXO) clock counter. Using the global sharing time slot, we propose an Equal Air Time and CuckooHash (EAT&CH) algorithm for the WSA to resolve channel congestion and delays when multiple seismometers upload data simultaneously. In EAT&CH, an equal air-time spreading factor (SF) allocation method based on the coarse/fine-grained theory is employed to reduce the collision probability of data transmission. To improve the scalability of the WSA in terms of reducing both collision probability and data delay, a different carrier frequency (CF) channel with the same SF allocation plan depending on CuckooHash is designed to reduce the network latency. Simulation results show that the proposed algorithm achieves nearly 100% data extraction rate of the WSA with less than two times the delay, compared with the existing Adaptive Data Rate (ADR) mechanism.

Cholesterol plays essential structural and signaling roles in mammalian cells, but too much cholesterol can cause cytotoxicity. Acyl-CoA:cholesterol acyltransferases 1 and 2 (ACAT1/2) convert cholesterol into its storage form, cholesteryl esters, regulating a key step in cellular cholesterol homeostasis. Adipose tissue can store >50% of whole-body cholesterol. Interestingly, however, almost no ACAT activity is present in adipose tissue, and most adipose cholesterol is stored in its free form. We therefore hypothesized that increased cholesterol esterification may have detrimental effects on adipose tissue function. Here, using several approaches, including protein overexpression, quantitative RT-PCR, immunofluorescence, and various biochemical assays, we found that ACAT1 expression is significantly increased in the adipose tissue of the ob/ob mice. We further demonstrated that ACAT1/2 overexpression partially inhibited the differentiation of 3T3-L1 preadipocytes. In mature adipocytes, increased ACAT activity reduced the size of lipid droplets (LDs) and inhibited lipolysis and insulin signaling. Paradoxically, the amount of free cholesterol increased on the surface of LDs in ACAT1/2-overexpressing adipocytes, accompanied by increased LD localization of caveolin-1. Moreover, cholesterol depletion in adipocytes by treating the cells with cholesterol-deficient media or β-cyclodextrins induced changes in cholesterol distribution that were similar to those caused by ACAT1/2 overexpression. Our results suggest that ACAT1/2 overexpression increases the level of free cholesterol on the LD surface, thereby impeding adipocyte function. These findings provide detailed insights into the role of free cholesterol in LD and adipocyte function and suggest that ACAT inhibitors have potential utility for managing disorders associated with extreme obesity.

Lipid droplets (LDs) are evolutionarily conserved organelles that play critical roles in mammalian lipid storage and metabolism. However, the molecular mechanisms governing the biogenesis and growth of LDs remain poorly understood. Phosphatidic acid (PA) is a precursor of phospholipids and triacylglycerols and substrate of CDP-diacylglycerol (CDP-DAG) synthase 1 (CDS1) and CDS2, which catalyze the formation of CDP-DAG. Here, using siRNA-based gene knockdowns and CRISPR/Cas9-mediated gene knockouts, along with immunological, molecular, and fluorescence microscopy approaches, we examined the role of CDS1 and CDS2 in LD biogenesis and growth. Knockdown of either CDS1 or CDS2 expression resulted in the formation of giant or supersized LDs in cultured mammalian cells. Interestingly, down-regulation of cell death-inducing DFF45-like effector C (CIDEC), encoding a prominent regulator of LD growth in adipocytes, restored LD size in CDS1- but not in CDS2-deficient cells. On the other hand, reducing expression of two enzymes responsible for triacylglycerol synthesis, diacylglycerol O-acyltransferase 2 (DGAT2) and glycerol-3-phosphate acyltransferase 4 (GPAT4), rescued the LD phenotype in CDS2-deficient, but not CDS1-deficient, cells. Moreover, CDS2 deficiency, but not CDS1 deficiency, promoted the LD association of DGAT2 and GPAT4 and impaired initial LD maturation. Finally, although both CDS1 and CDS2 appeared to regulate PA levels on the LD surface, CDS2 had a stronger effect. We conclude that CDS1 and CDS2 regulate LD dynamics through distinct mechanisms.

This paper proposes a distributed principal component analysis seismic data compression algorithm based on fidelity restriction for non-cable seismic exploration systems. The proposed method compresses data effectively according to a customized fidelity. It first determines the cumulative contribution rate, then calculates the global eigenvector matrix, generates a projection in the seismographs and finally transmits the projected data. The numerical simulation results show that when the total waveform fidelity reaches 92%, the compression ratio still stands at 77 times or more. Furthermore, the field experiment also verifies the performance of the algorithm.

Vacancy engineering is deemed as one of the powerful protocols to tune the catalytic activity of electrocatalysts. Herein, Se vacancy with charge polarization is created in the NiSe2 structure NiSe2 VSe via a sequential phase conversion strategy. By a combined analysis of the Rietveld method, transient photovoltage spectra TPV , in situ Raman and density functional theory DFT calculation, it is unequivocally discovered that the presence of charge polarized Se vacancy is beneficial for stabilizing the structure, decreasing the electron transfer kinetics, as well as optimizing the free adsorption energy of reaction intermediate during two electron oxygen reduction reaction 2e amp; 8722; ORR . Benefiting from these merits, the as prepared NiSe2 VSe delivered the highest selectivity of 96 toward H2O2 in alkaline media, together with a selectivity higher than 90 over the wide potential range from 0.25 to 0.55 V, ranking it in the top level among the previously reported transition metal based electrocatalysts. Most notably, it also displayed admirable stability with only a slight selectivity decay after 5000 cycles of accelerated degradation test ADT

The performance of seismic exploration instruments directly affects the quality of acquired seismic data as well as the efficiency of seismic survey operation. Consequently, they play a pivotal role in oil/gas and mineral resource exploration. Compared with traditional cabled seismic acquisition systems, nodal seismic acquisition systems have the advantages of light weight, small size, low capital and operational cost, reduced health safety and environment risk and strong adaptability to complex terrain environment. Therefore, they have been widely used in seismic exploration and have shown a trend of accelerated development. The major manufacturers have carried out research and development of nodal instruments, and various types of nodal seismographs have appeared. Based on the investigation of influential nodal seismographs, we summarize the research status of nodal seismographs. Based on different wireless monitoring capabilities and data harvesting modes, we classify the nodal seismographs into a shoot-blind system, semi-blind system, real-time system and enhanced real-time system. We discuss structural principles and key technologies of the four types of nodal seismographs, analyze their characteristics and predict their future development directions. Focusing on node data quality monitoring, we discuss the application of communication technologies, such as Bluetooth, Wi-Fi, ZigBee, Long Term Evolution, and satellites in nodal seismographs in detail. Furthermore, we analyze and evaluate three main networking architectures including planar multi-hop networks, hierarchical cluster networks and hybrid networks, and sum up the research progress of wireless routing algorithms and large-scale seismic data real-time harvesting methods. Finally, the latest applications of nodal seismographs in energy and mineral resource exploration, geological environment monitoring, urban subsurface space survey and novel seismic technologies are covered. As research on the application of micro-electro-mechanical systems technology, cloud computing, 5G, Internet of Things, edge computing, machine learning and robotics in nodal systems deepens, the performance of nodal seismographs will be greatly promoted.

With the rapid development of bionic robot technology, material technology and rapid prototyping technology, compared with the traditional rigid robot, soft robot has high flexibility, good adaptability and natural safe interaction, and has a huge application potential in various fields. This paper designs a soft actuator with multiple degrees of freedom that can achieve multiple spatial deformation motions. It can realize torsion in two directions, swing, elongation and other functions. The main structure of the pneumatic soft actuator studied in this paper is composed of a cylindrical matrix and six air chambers. Two sides of the three datum planes of the equidistant cylinder circle are symmetrically distributed with "groove" air chambers. The air chamber is divided into a semi-cylindrical connected chamber and a circular ridge. We use principle of virtual work and elastic strain energy to establish the kinematic relationship of torsion angle and pressure. The software ABAQUS is used to simulate the soft actuator by Finite Element Analysis.

In order to simultaneously inhibit the Ni sintering and coke formation as well as investigate the effects of WO3 promoter on catalytic performance, the ordered mesoporous Ni–WO3/Al2O3 catalysts were synthesized by a facile one-pot evaporation-induced self-assembly method for CO methanation reaction to produce synthetic natural gas. Addition of WO3 species could significantly promote the catalytic activity due to the enhancement of the Ni reducibility and the increase of active centers, and the optimal N10W5/OMA catalyst with NiO of 10 wt% and WO3 of 5 wt% achieved the maximum CH4 yield 80% at 425 °C, 0.1 MPa and a weight hourly space velocity of 60000 mL g−1 h−1. Besides, the reference catalyst N10W5/OMA-Im prepared by the conventional co-impregnation method was also evaluated. Compared with N10W5/OMA, N10W5/OMA-Im showed lower catalytic activity due to the partial block of channels by Ni and WO3 nanoparticles, which reduced active centers and restrict the mass transfer during the reaction. In addition, the N10W5/OMA catalyst showed superior anti-sintering and anti-coking properties in a 425oC-100 h-lifetime test, mainly because of confinement effect of ordered mesoporous structure to anchor the Ni particle in the alumina matrix.

The development of nonprecious, highly active and robust bifunctional electrocatalysts for both hydrogen and oxygen evolution reactions via water splitting is of primary significance, but still remains challenging. Herein, we develop a three-dimension (3D) heterostructured catalyst (Ni0.82Co0.18O@C/NF) by coupling of ultrathin Co-doped NiO (Ni0.82Co0.18O) nanosheets and carbon on nickel foam (NF) with synergism of geometric engineering and electronic modulation. Benefiting from the unique 3D configuration, highly exposed active sites and the synergistic effect of the active Ni0.82Co0.18O and the carbon, the catalyst exhibits exceptional hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performance with low overpotentials and Tafel slopes and excellent stability in alkaline media. Specifically, the Ni0.82Co0.18O@C/NF employed as catalyst for both anode and cathode enables an alkaline electrolyzer to achieve a current density of 10 mA cm−2 by a cell voltage of only 1.42 V, which is not only much lower than that of the integrated performance of the commercial noble Pt/C and IrO2/C catalyst couple (∼1.61 V), but also superior to most reported results to date. Our finding may provide a new opportunity to design advanced bifunctional catalysts toward practical overall water splitting.