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ABSTRACT Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension (PAH). The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt (PAH-CHD), the potential impact of the microbiome on the “gut-lung axis” remains underexplored. This study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the “gut-lung axis” microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.IMPORTANCEPrevious studies have primarily focused on the relationship between the gut microbiome and PAH. However, the impact of microbial homeostasis on the progression of PAH-CHD from the perspective of the gut-lung axis has not been adequately elucidated. Our study utilizes an integrated multi-omics approach to report on the differential characteristics of gut and lung microbiota between children with PAH-CHD and reference subjects. We found that microbiota influence the pathological changes and disease manifestations of PAH-CHD through their metabolic activity. Additionally, alterations in metabolites impact the microbial ecological structure. Our findings suggest that modulating the microbiome composition may have positive implications for maintaining and regulating the immune environment and pathological progression of PAH-CHD.

Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress-mediated autophagy and upregulates the expression of GABAA-receptor-associated protein like-1 (GABARAPL1). Intriguingly, overexpression of GABARAPL1 significantly induces autophagy, while its knockdown alleviates ACR-induced autophagic responses, underscoring its pivotal function. Furthermore, we demonstrate that transcription factors cAMP response element-binding protein 1 (CREB1) and POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) synergistically enhance Gabarapl1 gene transcription by interacting with its promoter region, contributing to ACR-induced autophagy in mouse Leydig cells. Notably, our findings suggest a reciprocal regulation between PATZ1 and CREB1. This study suggests the critical role of GABARAPL1 in ACR-induced autophagy of mouse Leydig cells, shedding light on the underlying mechanism of ACR-caused male reproductive impairment.

Introduction Lung-protective ventilation strategies (LPVS) for one-lung ventilation (OLV) in paediatric patients pose greater challenges than in adults. Optimising LPVS for paediatric OLV to mitigate postoperative pulmonary complications (PPCs) has emerged as a current research focal point. However, there remains a divergence of opinions concerning the individualised setting and application of positive end-expiratory pressure (PEEP). Lung dynamic compliance (Cdyn) can serve as a reflection of the lung’s physiological state in children during OLV and is a readily obtainable parameter. This study protocol is formulated to assess the effectiveness of Cdyn-guided PEEP titration on PPCs during paediatric OLV.Methods and analysis This study constitutes a single-centre, prospective, double-blind, randomised controlled trial. The trial aims to recruit 60 paediatric patients scheduled for video-assisted thoracoscopic surgery. These eligible patients will be randomly assigned to either the Cdyn-guided PEEP group or the conventional PEEP group during general anaesthesia for OLV. The primary outcome will involve assessing the incidence of PPCs at 7 days after surgery. Secondary outcomes will encompass the evaluation of the modified lung ultrasound score following surgery, as well as monitoring the oxygenation index, driving pressure and Cdyn during mechanical ventilation. Data collection will be performed by investigators who are kept blinded to the interventions.Ethics and dissemination The Clinical Trial Ethics Committee at Shenzhen Children’s Hospital has conferred ethical approvals for this trial (approval number: 2022076). Results from this trial will be disseminated in peer-reviewed journals and presented at professional symposiums.Trail registration number NCT05386901.

Artificial optoelectronic synaptic transistors have attracted extensive research interest as an essential component for neuromorphic computing systems and brain emulation applications. However, performance challenges still remain for synaptic devices, including low energy consumption, high integration density, and flexible modulation. Employing trapping and detrapping relaxation, a novel optically stimulated synaptic transistor enabled by the AlGaN/GaN hetero-structure metal-oxide semiconductor high-electron-mobility transistor has been successfully demonstrated in this study. Synaptic functions, including excitatory postsynaptic current (EPSC), paired-pulse facilitation index, and transition from short-term memory to long-term memory, are well mimicked and explicitly investigated. In a single EPSC event, the AlGaN/GaN synaptic transistor shows the characteristics of low energy consumption and a high signal-to-noise ratio. The EPSC of the synaptic transistor can be synergistically modulated by both optical stimulation and gate/drain bias. Moreover, utilizing a convolution neural network, hand-written digit images were used to verify the data preprocessing capability for neuromorphic computing applications.

As an extensively employed plasticizer in industrial applications, di-2-ethylhexyl phthalate (DEHP) can induce apoptosis of mouse Leydig cells, yet the precise mechanism remains elusive. In the current study, we identified that DEHP could specially induced apoptosis in the Leydig cells of the testis tissue, accompanied with the upregulation of apoptosis-related protein in the TGF-β signaling pathway (ARTS) in the cells. Overexpression of ARTS significantly induced apoptosis of TM3 cells, while knockdown of ARTS inhibited apoptosis. Furthermore, DEHP-induced apoptosis of TM3 cells could be alleviated by knockdown of ARTS, which indicated that ARTS was involved in DEHP-induced apoptosis of mouse Leydig cells. Bioinformation assay predicts that there are four potential p53-responsive elements (p53-REs) located at − 6060, − 5726, − 5631 and − 5554 before the transcription start site of ARTS gene, implying that gene transcription of ARTS could be regulated by p53. Interestingly, DEHP was shown to specifically upregulate the expression of p53 in the Leydig cells of the testis tissue and TM3 cells. Consistently, p53 was proved to bind to the RE4 site of the ARTS gene promoter and transcriptionally activated the promoter-driven expression of the luciferase reporter gene. Overexpression of p53 could induce apoptosis of TM3 cells; while knockdown of p53 could not only rescue DEHP-induced apoptosis of the cells, but also inhibit DEHP-caused upregulation of ARTS. Meanwhile, we showed that oxidative stress could induce apoptosis of TM3 cells, accompanied with the increased protein levels of p53 and ARTS; while inhibition of oxidative stress dramatically alleviated DEHP-induced apoptosis and the up-regulation of p53 and ARTS. Taken together, these results indicated that DEHP-induced oxidative stress activates the p53-ARTS cascade to promote apoptosis of mouse Leydig cells.

As one of the most important phthalates, di-isononyl phthalate (DINP) has been widely used as a common plasticizer in the food and personal care products sectors. In our previous study, we found that DINP can induce autophagy of ovarian granulosa cells; while the underlying mechanism is unclear. In the study, we showed that DINP exposure could induce autophagy of ovarian granulosa cells and KGN cells, accompanied with the increase in the mRNA and protein level of DDIT4. Furthermore, overexpression of DDIT4 were shown to induce autophagy of KGN cells; while knockdown of DDIT4 inhibited DINP-induced autophagy, implying that DDIT4 played an important role in DINP-induced autophagy of ovarian granulosa cells. There were three putative binding sites of transcription factor ATF4 in the promoter region of DDIT4 gene, suggesting that DDIT4 might be regulated by ATF4. Herein, we found that overexpression of ATF4 could upregulate the expression of DDIT4 in KGN cells, while knockdown of ATF4 inhibited its expression. Subsequently, ATF4 was identified to bind to the promoter region of DDIT4 gene and promote its transcription. The expression of ATF4 was also increased in the DINP-exposed granulosa cells, and ATF4 overexpression promoted autophagy of KGN cells; whereas knockdown of ATF4 alleviated DINP-induced upregulation of DDIT4 and autophagy of the cells. Taken together, DINP triggered autophagy of ovarian granulosa cells through activating ATF4/DDIT4 signals.

Abstract A broadband circularly polarized (CP) printed monopole antenna which fed by coplanar waveguide (CPW) is proposed in the paper. The structure of the novel antenna includes a quarter circular disc radiating monopole, a coupled circular patch, and a bent L-shaped microstrip stub line. The L-shaped microstrip stub line is used to widen the impedance bandwidth and generate a horizontal component of the electromagnetic wave. The adoption of the asymmetric ground coplanar waveguide structure with the single-feed technology and the coupled circular patch, simultaneously achieve wide impedance bandwidth and wide axial ratio (AR) bandwidth. The structure parameters and the surface current of the designed antenna are analysed. The simulation and the measurement are conducted, showing good characterizations of the designed antenna. The 10-dB impedance bandwidth is 7.57 GHz, the fractional bandwidth from 6.05 to 13.62 GHz is 76.9%, the 3-dB axial ratio bandwidth is 3.01 GHz, and the fractional bandwidth from 6.05 to 9.06 GHz is 39.8%. The antenna can generate right/left hand circularly polarized waves in the direction of ± z axis. The designed antenna has wide applications in the fields of Internet of Things (IoT), broadband dual-CP communication systems and polarization diversity systems, wireless personal area network and other advanced communication systems.

Glioblastomas (GBM) are aggressive tumors that lack effective treatments. Here, we show that the Rho family guanine nucleotide exchange factor Syx promotes GBM cell growth both in vitro and in orthotopic xenografts derived from patients with GBM. Growth defects upon Syx depletion are attributed to prolonged mitosis, increased DNA damage, G2/M cell cycle arrest, and cell apoptosis, mediated by altered mRNA and protein expression of various cell cycle regulators. These effects are phenocopied by depletion of the Rho downstream effector Dia1 and are due, at least in part, to increased phosphorylation, cytoplasmic retention, and reduced activity of the YAP/TAZ transcriptional coactivators. Furthermore, targeting Syx signaling cooperates with radiation treatment and temozolomide (TMZ) to decrease viability in GBM cells, irrespective of their inherent response to TMZ. The data indicate that a Syx-RhoA-Dia1-YAP/TAZ signaling axis regulates cell cycle progression, DNA damage, and therapy resistance in GBM and argue for its targeting for cancer treatment.

Abstract Owing to their unique advantages, single‐electrode triboelectric nanogenerators (SETENGs) have gained wide attention and have been applied in myriad areas, especially in the burgeoning flexible/wearable electronics. However, there is still a lack of a clear understanding of SETENGs. For example, previous simulation models generally put the reference electrode perpendicularly below the working part, but in practice, the reference electrode is designed in various scenarios and noticeable differences in outputs often occur when the reference electrode changes. With SETENGs developing towards wearability and portability, its reference electrode is often required to be constructed inside the device. Consequently, to achieve optimum performance, it is essential to understand the reference electrode's influence on the outputs. Here, the influence of the reference electrode on the performance of SETENGs is systematically investigated and the targeted optimization strategies are thoroughly revealed. First, theoretical simulations are conducted to investigate the reference electrode's effect on the performance of SETENGs with different structures and in various working modes. Secondly, the theoretical results are certified through corresponding experiments. Based on the results, the targeted optimization strategies for SETENGs are comprehensively demonstrated. This work provides fundamental guidance for the development of TENGs and the design and fabrication of new electronic devices.

The eukaryotic ribosome is essential for cancer cell survival. Perturbation of ribosome biogenesis induces nucleolar stress or ribosomal stress, which restrains cancer growth, as rapidly proliferating cancer cells need more active ribosome biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and associated with poor prognoses. Interestingly, depletion of UTP11 inhibits cancer cell growth in vitro and in vivo through p53-depedednt and -independent mechanisms, whereas UTP11 overexpression promotes cancer cell growth and progression. On the one hand, the ablation of UTP11 impedes 18S rRNA biosynthesis to trigger nucleolar stress, thereby preventing MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins, RPL5 and RPL11. On the other hand, UTP11 deficiency represses the expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced levels of glutathione (GSH) and enhanced ferroptosis. Altogether, our study uncovers a critical role for UTP11 in maintaining cancer cell survival and growth, as depleting UTP11 leads to p53-dependent cancer cell growth arrest and p53-independent ferroptosis.

Gallium nitride (GaN) high-electron-mobility transistors (HEMTs) have been considered promising candidates for power devices due to their superior advantages of high current density, high breakdown voltage, high power density, and high-frequency operations. However, the development of GaN HEMTs has been constrained by stability and reliability issues related to traps. In this article, the locations and energy levels of traps in GaN HEMTs are summarized. Moreover, the characterization techniques for bulk traps and interface traps, whose characteristics and scopes are included as well, are reviewed and highlighted. Finally, the challenges in trap characterization techniques for GaN-based HEMTs are discussed to provide insights into the reliability assessment of GaN-based HEMTs.

Ensuring proper matching of the target wind characteristics of the inflow is vital for the accuracy of both experimental and numerical wind studies. In the current study, a calibrated turbulent inflow generation technique was developed to accurately simulate the inflow boundary condition for large eddy simulation (LES) of the lower region of the atmospheric boundary layer (ABL) based on a newly developed technique, namely consistent discrete random flow generator (CDRFG). The proposed technique, namely Calibrated-CDRFG (C-CDRFG), targets specific incoming turbulence at distances downstream to account for dissipation of the turbulent kinetic energy. The proposed technique generates accurate turbulent velocities with proper turbulence intensity, spectra, coherency, and correlation at the target distance downstream for a range of terrain conditions. The technique was validated by evaluating the wind-induced loads and responses for the Commonwealth Advisory Aeronautical Research Council (CAARC) and comparing that to the existing wind tunnel (WT) wind-induced response for the angle of attack (AOA) ranging between 0° and 90°. It was found that the resulting wind-induced response from the C-CDRFG technique resulted in an average matching of 91% of the wind tunnel results. The proposed technique is believed to be computationally efficient, flexible, and easy to be sustainable for parallel computing environments and thus provides significant value for Large Eddy Simulation (LES) wind engineering applications.

Abstract This study aimed to construct a widely accepted prognostic nomogram in Chinese high-grade osteosarcoma (HOS) patients aged ≤ 30 years to provide insight into predicting 5-year overall survival (OS). Data from 503 consecutive HOS patients at our centre between 12/2012 and 05/2019 were retrospectively collected. Eighty-four clinical features and routine laboratory haematological and biochemical testing indicators of each patient at the time of diagnosis were collected. A prognostic nomogram model for predicting OS was constructed based on the Cox proportional hazards model. The performance was assessed by the concordance index (C-index), receiver operating characteristic curve and calibration curve. The utility was evaluated by decision curve analysis. The 5-year OS was 52.1% and 2.6% for the nonmetastatic and metastatic patients, respectively. The nomogram included nine important variables based on a multivariate analysis: tumour stage, surgical type, metastasis, preoperative neoadjuvant chemotherapy cycle, postoperative metastasis time, mean corpuscular volume, tumour-specific growth factor, gamma-glutamyl transferase and creatinine. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.795 (range, 0.703–0.887). Moreover, the decision curve analysis curve also demonstrated the clinical benefit of this model. The nomogram provides an individualized risk estimate of the 5-year OS in patients with HOS aged ≤ 30 years in a Chinese population-based cohort.

Di-isononyl phthalate (DINP) has been widely utilized in industrial, commercial and medical applications for the past few years. Therefore, more attention should be paid to the toxicity of DINP. DINP can cause damage to female reproductive system; however, the potential mechanism remains to be further investigated. In this study, female mice were orally administered with 0, 2, 20 and 200 mg DINP/kg/day for 14 days. We found that DINP significantly affected the arrangement of granulosa cells in ovarian follicles. In addition, DINP could induce apoptosis, autophagy and oxidative stress of the ovary tissue. Meanwhile, the serum estradiol concentration distinctly decreased in the 20 and 200 mg/kg DINP-treated groups, suggesting that DINP might affect the function of ovarian granulosa cells. Primary mouse ovarian granulosa cells were utilized for further investigation after the cells were treated with 0, 100, 200, 400 μM DINP for 24 h. Similar to the in vivo experiment, DINP could also induce apoptosis and autophagy of ovarian granulosa cells, as well as oxidative stress; while inhibition of oxidative stress by NAC could alleviate DINP-induced apoptosis and autophagy. Furthermore, inhibition of autophagy by 3-MA could also rescue the induction of apoptosis by DINP. Taken together, these results indicated that DINP induced apoptosis and autophagy of mouse ovarian granulosa cells via oxidative stress, and autophagy played a cytotoxic role in DINP-induced apoptosis.

Abstract Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.

The poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) Olaparib is a widely used targeted therapy for a variety of solid tumors with homologous recombination deficiency (HRD) caused by mutation of BRCA1/2 or other DNA repair genes. The anti-tumor activity of Olaparib has been largely attributed to its ability to inhibit PARP enzymes and block DNA single-strand break (SSB) repair, which eventually leads to the most detrimental DNA damage, double-strand breaks (DSB), in HRD cells. Although PARPi was found to induce p53-dependent cell death, the underlying molecular mechanism remains incompletely understood. Here, we report that Olaparib treatment leads to p53 stabilization and activation of its downstream target genes in a dose- and time-dependent manner. Mechanistically, Olaparib triggers nucleolar stress by inhibiting biosynthesis of the precursor of ribosomal RNAs (pre-rRNA), resulting in enhanced interaction between ribosomal proteins (RPs), RPL5 and RPL11, and MDM2. Consistently, knockdown of RPL5 and RPL11 prevents Olaparib-induced p53 activation. More importantly, Olaparib efficiently suppresses breast and colorectal cancer cell survival and proliferation through activation of p53. Altogether, our study demonstrates that Olaparib activates the nucleolar stress-RPs-p53 pathway, suggesting rRNA biogenesis as a novel target for PARPi.

BackgroundThe role of basal ganglia in the pathogenesis of obsessive–compulsive disorder (OCD) remains unclear. The studies on volume changes of basal ganglia in OCD commonly use the VBM method; however, the Atlas-based method used in such research has not been reported. Atlas-based method has a lower false positive rate compared with VBM method, thus having advantages partly.ObjectivesThe current study aimed to detect the volume changes of subregions within basal ganglia in OCD using Atlas-based method to further delineate the precise neural circuitry of OCD. What is more, we explored the influence of software used in Atlas-based method on the volumetric analysis of basal ganglia and compared the results of Atlas-based method and regularly used VBM method.MethodsWe analyzed the brain structure images of 37 patients with OCD and 41 healthy controls (HCs) using the VBM method, Atlas-based method based on SPM software, or Freesurfer software to find the areas with significant volumetric variation between the two groups, and calculated the effects size of these areas.ResultsVBM analysis revealed a significantly increased volume of bilateral lenticular nucleus in patients compared to HCs. In contrast, Atlas-based method based on Freesurfer revealed significantly increased volume of left globus pallidus in patients, and the largest effect size of volumetric variation was revealed by Freesurfer analysis.ConclusionsThis study showed that the volume of bilateral lenticular nucleus significantly increased in patients compared to HCs, especially left globus pallidus, which was in accordance with the previous findings. In addition, Freesurfer is better than SPM and a good choice for Atlas-based volumetric analysis of basal ganglia.

Abstract Gravity‐drainage‐assisted steam flooding is a new technology to improve the recovery factor after deep penetration in deep super‐heavy oil reservoirs. This study is based on a model of the 60‐H25 test well group in Block 59 in Liaohe Oilfield, China. The numerical model uses the C programming language to analyze the influence of change in the bottom water height on the drainage effect and provides a theoretical basis for physical model experiments and field production. The physical model experiment uses similar principles to describe the production characteristics at different stages in a short cycle. We combine the numerical model and the physical model experiment to analyze the production rule of the Wa59 block over a long time period. The results show that the physical model experiment and the actual production of the block reflect the productivity change law of the well group, the degree of production, and the productivity relationship of the well group over short cycles and long periods, respectively. The comparison showed that the actual production was consistent with the production model of the physical model test, and the drainage effect was verified. The study of gravity‐drainage‐assisted steam flooding provides a reliable basis for the next stage of oilfield production.

Hyperstimulation of the cholecystokinin 1 receptor (CCK1R), a G protein–coupled receptor (GPCR), in pancreatic acinar cells is commonly used to induce pancreatitis in rodents. Human pancreatic acinar cells lack CCK1R but express cholinergic receptor muscarinic 3 (M3R), another GPCR. To test whether M3R activation is involved in pancreatitis, a mutant M3R was conditionally expressed in pancreatic acinar cells in mice. This mutant receptor loses responsiveness to its native ligand, acetylcholine, but can be activated by an inert small molecule, clozapine-N-oxide (CNO). Intracellular calcium and amylase were elicited by CNO in pancreatic acinar cells isolated from mutant M3R mice but not WT mice. Similarly, acute pancreatitis (AP) could be induced by a single injection of CNO in the transgenic mice but not WT mice. Compared with the cerulein-induced AP, CNO caused more widespread acinar cell death and inflammation. Furthermore, chronic pancreatitis developed at 4 weeks after 3 episodes of CNO-induced AP. In contrast, in mice with 3 recurrent episodes of cerulein-included AP, pancreas histology was restored in 4 weeks. Furthermore, the M3R antagonist ameliorated the severity of cerulein-induced AP in WT mice. We conclude that M3R activation can cause the pathogenesis of pancreatitis. This model may provide an alternative approach for pancreatitis research.

Rapid population growth and urbanization have led to the development of high-density and high-rise structures around the world. Tall structures in proximity can negatively affect pedestrian comfort by directing strong winds to the ground near the structure. Pedestrian level wind (PLW) may affect local businesses/services, pedestrian comfort and in extreme cases jeopardizes pedestrian safety. The downtown portion of the City of Toronto (∼10 km2) was chosen as the study region due to the recent development of many high-rise structures. The region was split into 10 zones and Computational Fluid Dynamics (CFD) was utilized to study the wind effects of the local building geometry and arrangements. Wind velocities were extracted from Computational Fluid Dynamics and coupled with historical meteorological data from Billy Bishop Airport. The coupled velocities from CFD were found to be within 20 and 5% RMSE, respectively, of the recorded data at the wind station for 85% of the sampled data. Wind velocities were then extracted at various elevations and coupled with meteorological weather data to generate real-time, historical, and statistical visualization of local wind fields. This study enables the prediction of real-time, historical, and statistical wind speeds, bearings at various elevations. Visualization of the flow field provides important insights for pedestrians, architects, engineers, and city planners regarding local wind speeds and identify problematic areas.

Bulk materials Ba8Ga16InxGe30-x (x = 0.5, 1.0, 1.5) were prepared by High-Pressure and High-Temperature (HPHT) method and the crystal structure has been confirmed by X-ray diffraction and cell refinement. The actual In composition was much lower than the starting composition, and lattice constants increased with the increase of substitution. As the temperature increased, the Seebeck coefficient and electrical resistivity increased first and then decreased, while the thermal conductivity was the opposite, which leads to significant enhancement on thermoelectric properties of the clathrates. The substitution of indium elements decreased the seebeck coefficient and electrical resistivity, and also changed the microstructure of the compounds. A minimum thermal conductivity of 0.84 Wm−1K−1 was obtained, and a good ZT value of 0.52 was achieved. The grain boundaries and lattice defects generated by high pressure can effectively scatter phonons of different frequencies, which reduce the lattice thermal conductivity.

Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

Abstract TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.

Left ventricular hypertrophy is a maladaptive response to pressure overload and an important risk factor for heart failure. Intermedin (IMD), a multi-functional peptide, plays important roles in cardiovascular protection. In this study, we revealed an autophagy-dependent mechanism involved in IMD's protection against cardiac remodeling and cardiomyocyte death in heart hypertrophy. We observed that transverse aortic contraction (TAC) induction, Ang II or ISO exposure induced remarkable increase in the expression of endogenous IMD and its receptor components, CRLR, RAMP1 and RAMP3, in mouse hearts and H9c2 cell cultures, respectively. Furthermore, the heart size, heart weight/body weight ratios, cardiomyocyte size and apoptosis, interstitial collagen, hypertrophic markers including ANP and BNP expression were also significantly increased, which were effectively suppressed by IMD supplementation. In addition, IMD induced capillary angiogenesis and improved functions in hypertrophic hearts. We further observed that IMD induced strong autophagy in hypertrophic hearts and cultured cells, which was paralleling with the decrease in cardiomyocyte size and apoptosis. Furthermore, an autophagy inhibitor, 3-MA, was used to block the IMD-augmented autophagy level, and then the protection of IMD on cardiomyocyte hypertrophy and apoptosis was almost abrogated. We also observed that IMD supplementation stirred intracellular cAMP production, and augmented the ERK1/2 phosphorylation induced by Ang II/ISO exposure in H9c2 cells. In addition, we inhibited PI3K, PKA and MAPK/ERK1/2 signaling pathways by using wortamannin, H89 and PD98059, respectively, in H9c2 cells co-incubating with both IMD and Ang II or ISO, and observed that these inhibitors effectively reduced IMD-augmented autophagy level, but only H89 and PD98059 pre-incubation abrogated the anti-apoptotic action of IMD. These results indicate that the endogenous IMD and its receptor complexes are induced in hypertrophic cardiomyocytes and proposed to play an important role in the pathogenesis of cardiac hypertrophy, and the autophagy stirred by IMD supplementation is involved in its protection against cardiomyocyte hypertrophy and apoptosis through the activation of both cAMP/PKA and MAPK/ERK1/2 pathways.