Search

Recent studies suggested that the ejecta velocity of Type Ia supernova (SN Ia) is a promising indicator in distinguishing the progenitor systems and explosion mechanisms. By classifying the SNe Ia based on their ejecta velocities, studies found that SNe Ia with high |$\mathrm{Si}\, {\rm{\small II}}\, \lambda 6355$| velocities (HV SNe Ia; |$v \gtrsim 12\,000$|  km s−1) tend to be physically different from their normal-velocity counterparts (NV SNe Ia). In this work, we revisit the low- z sample studied in previous work and closely look into the spatially resolved environment local to the site of SN explosion. Our results reveal a possible trend (at 2.4σ significance) that HV SNe Ia are likely associated with older stellar populations than NV SNe Ia. While the trend is inconclusive, the local host-galaxy sample studied in this work is likely skewed towards massive galaxies, limiting the parameter space that we would like to investigate from the original parent sample. Nevertheless, our results do not rule out the possibility that parameters other than the host-galaxy age (such as metallicity) could be the underlying factors driving the differences between HV and NV SNe Ia due to the limitation of our data set. [ABSTRACT FROM AUTHOR]

Non-methane hydrocarbons (NMHCs) are a common type of volatile organic compounds (VOCs) pollutant in the petrochemical industry and have attracted widespread attention because of their adverse health effects and environmental impacts. In this paper, we report a new porous slurry formed with zeolitic imidazolate framework-8 (ZIF-8) and iso-hexadecane to capture the low-concentration and multi-component NMHCs (mainly ethane (C2H6), propane (C3H8), and n-butane (n-C4H10)) from the oil field exhaust. The sorption capacity of C2H6 in the slurry is significantly higher than that of nitrogen (N2) and methane (CH4). Moreover, the slurry demonstrated a clear advantage for C2H6 over N2 and CH4 in competitive adsorption through the pressure-drop curves. In the NMHCs capture experiments, the C3H8 and n-C4H10 concentrations after purification can be reduced to below 100 ppm, while the C2H6 concentration can reach approximately 180 ppm. More encouragingly, in the breakthrough tests, the slurry exhibits a perfect kinetic separation selectivity for multi-component NMHCs. Furthermore, to avoid structural collapse of ZIF-8 material during long-term use in acidic and wet environments, a certain amount of 2-methylimidazole was retained in the slurry as a protective agent in the material synthesis process. In this way, the ZIF-8 materials in the slurry can retain the stable characteristic structure in an aqueous and acidic environment and keep the capture capacity for NMHCs without degradation. We believe the porous ZIF-8/iso-hexadecane slurry is a promising capture agent for low-concentration and multi-component NMHCs with strong purification capacity and stability. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is one of the leading causes of death and disability. Complicated mechanisms are involved in the pathogenesis of IS. Immunomodulatory mechanisms are crucial to IS. Acupuncture is a traditional non-drug treatment that has been extensively used to treat IS. The exploration of neuroimmune modulation will broaden the understanding of the mechanisms underlying acupuncture treatment. This review summarizes the immune response of immune cells, immune cytokines, and immune organs after an IS. The immunomodulatory mechanisms of acupuncture treatment on the central nervous system and peripheral immunity, as well as the factors that influence the effects of acupuncture treatment, were summarized. We suggest prospects and future directions for research on immunomodulatory mechanisms of acupuncture treatment for IS based on current progress, and we hope that these will provide inspiration for researchers. Additionally, acupuncture has shown favorable outcomes in the treatment of immune-based nervous system diseases, generating new directions for research on possible targets and treatments for immune-based nervous system diseases. [ABSTRACT FROM AUTHOR]

Variation in leaf traits is critical for carbon gains and losses during leaf life and drives litter carbon and nutrient losses via decomposition. Accurately quantifying litter decomposition parameters is essential for assessing ecosystem carbon and nutrient dynamics. Leaf litterbags have commonly been employed to measure effects of environmental drivers, decomposers, and plant traits on decomposition rates. There has been much debate regarding the suitability of substituting senesced dead leaves with fresh (green) leaves in litterbags, which has been common practice for mimicking green leaf fall or for practical reasons. Therefore, we tested the null hypothesis that replacement of dead leaves with fresh leaves in litterbag experiments is justified, based on similarities in structural and chemical traits between fresh and dead leaves across plant species and growth forms.We conducted a paired litterbag decomposition experiment with both fresh and dead leaves of 26 common species in subtropical China, in each of five contrasting ecosystems.While fresh leaves generally decomposed faster than dead leaves, this deviation varied among species and growth forms, based on their traits. Overall, there was significant but rather weak correlation between dead leaf decomposition rate k and fresh leaf k, across species and ecosystem types; the deviation between fresh and dead leaf k was larger for fast‐decomposing, mostly herbaceous species. The different decomposition patterns for fresh versus dead leaves were underpinned by key underlying traits integrated in leaf resource economics spectra (LES) for fresh and dead leaves. The dead leaf LES exhibited a greater predictive capability for dead leaf k while the fresh leaf LES had higher explanatory value for the fresh leaf k values.Our findings partly reject the null hypothesis and ask for caution in inferring leaf litter decomposition rates based on green leaf litterbags or traits data. We suggest follow‐up research on substituting senesced roots and stems with fresh ones in decomposition experiments.Synthesis. Human activities and extreme weather events are leading to increasing pulse inputs of fresh plant parts and our study contributes to knowledge on how they contribute to overall decomposition rates besides senesced litter inputs. [ABSTRACT FROM AUTHOR]

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTβ1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dβ1 was replaced with BTβ1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dβ1 were replaced with the wildtype BTβ1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity. Author summary: The sweet potato whitefly, Bemisia tabaci, is an important target pest of neonicotinoid insecticides. Much is known about the neonicotinoid-resistance evolved in whitefly by over-expressed detoxifying enzymes. But the toxicological targets of neonicotinoids, the nAChR subunit genes in whitefly are less well understood. In this study, we characterized the nAChR subunit gene family of whitefly, and identified dual mutations in beta1 subunit that confer resistance to multiple neonicotinoid insecticides. These findings are significant as they demonstrate how resistance can arise as a result of mutations in insects that had a combined effect to repulse the insecticides thus overcoming the insect selectivity of an important class of insecticides. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is characterized by a gradual loss of kidney function and affects ~13.4% of the global population. Progressive tubulointerstitial fibrosis, driven in part by proximal tubule (PT) damage, is a hallmark of late stages of CKD and contributes to the development of kidney failure, for which there are limited treatment options. Normal kidney development requires signaling by vitamin A (retinol), which is metabolized to retinoic acid (RA), an endogenous agonist for the RA receptors (RARα, β, γ). RARα levels are decreased in a mouse model of diabetic nephropathy and restored with RA administration; additionally, RA treatment reduced fibrosis. We developed a mouse model in which a spatiotemporal (tamoxifen-inducible) deletion of RARα in kidney PT cells of adult mice causes mitochondrial dysfunction, massive PT injury, and apoptosis without the use of additional nephrotoxic substances. Long-term effects (3 to 4.5 mo) of RARα deletion include increased PT secretion of transforming growth factor β1, inflammation, interstitial fibrosis, and decreased kidney function, all of which are major features of human CKD. Therefore, RARα's actions in PTs are crucial for PT homeostasis, and loss of RARα causes injury and a key CKD phenotype. [ABSTRACT FROM AUTHOR]

Photocatalysis, a critical strategy for harvesting sunlight to address energy demand and environmental concerns, is underpinned by the discovery of high-performance photocatalysts, thereby how to design photocatalysts is now generating widespread interest in boosting the conversion efficiency of solar energy. In the past decade, computational technologies and theoretical simulations have led to a major leap in the development of high-throughput computational screening strategies for novel high-efficiency photocatalysts. In this viewpoint, we started with introducing the challenges of photocatalysis from the view of experimental practice, especially the inefficiency of the traditional "trial and error" method. Subsequently, a cross-sectional comparison between experimental and high-throughput computational screening for photocatalysis is presented and discussed in detail. On the basis of the current experimental progress in photocatalysis, we also exemplified the various challenges associated with high-throughput computational screening strategies. Finally, we offered a preferred high-throughput computational screening procedure for photocatalysts from an experimental practice perspective (model construction and screening, standardized experiments, assessment and revision), with the aim of a better correlation of high-throughput simulations and experimental practices, motivating to search for better descriptors. [ABSTRACT FROM AUTHOR]

Indium is considered a candidate low-temperature solder because of its low melting temperature and excellent mechanical properties. However, the solid-state microstructure evolution of In with different substrates has rarely been studied due to the softness of In. To overcome this difficulty, cryogenic broad Ar+ beam ion polishing was used to produce an artifact-free Cu/In interface for observation. In this study, we accomplished phase identification and microstructure investigation at the Cu/In interface after long-term thermal aging. CuIn2 was observed to grow at the Cu/In interface and proved to be a stable phase in the Cu–In binary system. The peritectoid temperature of the Cu11In9 + In → CuIn2 reaction was confirmed to be between 100 and 120 °C. In addition, the growth rate of CuIn2 was discovered to be dominated by the curvature of the reactant Cu11In9/In phase and the temperature difference with the peritectoid temperature. Finally, a comprehensive microstructural evolution mechanism of the Cu/In solid-state interfacial reaction was proposed. [ABSTRACT FROM AUTHOR]

The present study investigated the expression level of microRNA (miR)-137 in glioma tissues and cell lines and explored its potential diagnostic significance as well as its function effects on glioma cells. miR-137 expression level was detected in glioma tissues using in situ hybridization, and in glioma cell lines using reverse transcription-quantitative PCR (RT-qPCR). The diagnostic significance of miR-137 in glioma was assessed using receiver operating characteristic curve analyses. Quantibody® Human Inflammation Array 1 was used to evaluate the impact of ectopic miR-137 expression on release of cytokines in glioma cell lines. IL-13, TNF-a and IFN-? levels were detected using ELISA. To confirm that sphingosine kinase 2 (SPHK2) is a target of miR-137, RT-qPCR, western blot analysis and dual-luciferase assay were adopted. The results demonstrated that miR-137 expression was downregulated in both glioma tissues and cell lines. Downregulation of miR-137 was significantly associated with high grade gliomas. Additionally, it was found that overexpression of miR-137 reduced IL-13, but promoted TNFa and IFN-? production. SPHK2 knockdown inhibited IL-13 release, promoted TNF-a and IFN-? production. SPHK2 was a direct target of miR-137. Collectively, the results of the present study indicated that miR-137 expression plays a tumor-suppressive role in glioma. It is downregulated in glioma and may promote M1-type TAMs polarization, and may be a diagnostic biomarker and potential therapeutic strategy for glioma treatment in the future. [ABSTRACT FROM AUTHOR]

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 "FLASH" randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided. [ABSTRACT FROM AUTHOR]

Eutectic In-48Sn was considered a promising candidate for low-temperature solder due to its low melting point and excellent mechanical properties. Both Cu2(In,Sn) and Cu(In,Sn)2 formation were observed at the In-48Sn/Cu interface after 160 °C soldering. However, traditional mechanical polishing produces many defects at the In-48Sn/Cu interface, which may affect the accuracy of interfacial reaction investigations. In this study, cryogenic broad Ar+ beam ion milling was used to investigate the interfacial reaction between In-48Sn and Cu during soldering. The phase Cu6(Sn,In)5 was confirmed as the only intermetallic compound formed during 150 °C soldering, while Cu(In,Sn)2 formation was proven to be caused by room-temperature aging after soldering. Both the Cu6(Sn,In)5 and Cu(In,Sn)2 phases were confirmed by EPMA quantitative analysis and TEM selected area electron diffraction. The microstructure evolution and growth mechanism of Cu6(Sn,In)5 during soldering were proposed. In addition, the Young's modulus and hardness of Cu6(Sn,In)5 were determined to be 119.04 ± 3.94 GPa and 6.28 ± 0.13 GPa, respectively, suggesting that the doping of In in Cu6(Sn,In)5 has almost no effect on Young's modulus and hardness. [ABSTRACT FROM AUTHOR]

Background and Objectives: Periodontitis is an immunoinflammatory disease characterized by irreversible periodontal attachment loss and bone destruction. Ferroptosis is a kind of immunogenic cell death that depends on the participation of iron ions and is involved in various inflammatory and immune processes. However, information regarding the relationship between ferroptosis and immunomodulation processes in periodontitis is extremely limited. The purpose of this study was to investigate the correlation between ferroptosis and immune responses in periodontitis. Methods: Gene expression profiles of gingivae were collected from the Gene Expression Omnibus data portal. After detecting differentially expressed ferroptosis-related genes (FRGs), we used univariate logistic regression analysis followed by logistic least absolute shrinkage and selection operator (LASSO) regression to establish a ferroptosis-related classification model in an attempt to accurately distinguish periodontitis gingival tissues from healthy samples. The infiltration level of immunocytes in periodontitis was then assessed through single-sample gene-set enrichment analysis. Subsequently, we screened out immune-related genes by weighted correlation network analysis and protein–protein interaction (PPI) analysis and constructed an immune-related network based on FRGs and immune-related genes. Results: A total of 24 differentially expressed FRGs were detected, and an 8-FRG combined signature constituted the classification model. The established model showed outstanding discriminating ability according to the results of receiver operating characteristic (ROC) curve analysis. In addition, the periodontitis samples had a higher degree of immunocyte infiltration. Activated B cells had the strongest positive correlation while macrophages had a strong negative correlation with certain FRGs, and we found that XBP1, ALOX5 and their interacting genes might be crucial genes in the immune-related network. Conclusions: The FRG-based classification model had a satisfactory determination ability, which could bring new insights into the pathogenesis of periodontitis. Those genes in the immune-related network, especially hub genes along with XBP1 and ALOX5, would have the potential to serve as promising targets of immunomodulatory treatments for periodontitis. [ABSTRACT FROM AUTHOR]

Aims: The distribution of residual esophageal squamous cell carcinoma (ESCC) in the esophageal wall and resected lymph nodes was evaluated after neoadjuvant chemoimmunotherapy (nICT). Methods and results: Clinical data were collected from 137 ESCC patients who underwent anti-programmed death 1 therapy and esophagectomy. Ninety (65.7%) achieved an major pathological response (MPR) in the esophageal wall, and 27 (19.7%) achieved an MPR in the lymph nodes. Pathologically complete response (pCR, ypT0N0) was observed in 26 patients (19%). Residual tumors located in the mucosa and/or submucosa were found in 94.6% of nonpCR patients. In the minor responders, 97.8% had residual tumor >10% in the mucosa or submucosa. A preferential regression direction toward the lumen was found in 76.4% of prepT2 nonpCR patients, or 60.7% of prepT3-4a nonpCR patients. The correlation between pCR in the esophageal wall and in lymph nodes was not significant (P=0.143). Among 19 patients with pCR in resected recurrent laryngeal nerve (RLN) lymph nodes, 31.6% had residual tumor cells in other resected lymph nodes. A significant correlation was found between ypT/ypN downstaging and tumor regression grade (P<0.05). Conclusions: After nICT for ESCC, residual tumors were frequently found in the mucosa or submucosa, with relatively high responsiveness of the invasive front and a significant correlation with downstaging, which may help clinicians make appropriate decisions about postoperative treatment and surveillance. The differences in pCR status in primary tumors, resected lymph nodes, and RLN lymph nodes indicated the importance of assessing regression changes in all resected lymph nodes during clinical practice. [ABSTRACT FROM AUTHOR]

Camellia sinensis var. Assamica cv. Duntsa (C.duntsa), a valuable Theaceae from Hunan Province, has been looked at as a precious tea resource by local farmers because of its economic and ecological value. Genomics study on C.duntsa is essential for the domestication and enhancement of tea tree varieties. In the present study, we used a hybrid approach based on Illumina and PacBio data to sequence and assemble the mitochondrial genome of C.duntsa. The mitochondrial genome of C.duntsa was estimated to be 1,081,996 base pairs (bp) and eighty-one genes consisting of one pseudogene, three ribosomal RNA (rRNA) genes, thirty transfer RNA (tRNA) genes, and forty-seven protein-coding genes (PCGs). Tetramer repetitions made up 43.90% of simple sequence repeats (SSRs). The codon usage bias of the Theaceae mitochondrial gene atp9 was altered by mutation, but the codon usage of other genes was shaped by natural selection. Besides, there are eighteen gene-containing homologous regions between the chloroplast and mitochondrial genomes of C. duntsa. Some genomes including atp8, cox1, cox3, nad7, nad9, rpl16, rpl2, rps19, rps4, and sdh4 are absent in the mitochondrial genome of several Theaceae plant. However, C. duntsa maintains these genes integrity and functionality. Another gene, rps16, is either lacking from the mitochondrial genome of C. duntsa or is present as a pseudogene. C. duntsa and C. sinensis (OM809792) are very similar, as shown by a collinear match across four species of Theaceae; the most conservative genes are nad5, atp9, cox2, rps3, trnA-TGC, trnI-GAT, rrn18, trnV-GAC, and ccmFN. Similarly, the genome's phylogenetic trees revealed that C. duntsa was the sister species to C. sinensis. The results confirmed that the C. duntsa and C. sinensis (OM809792) mitochondrial genome underwent gene rearrangement. In general, our results shows that genomic information from organelles can help us understand plant phylogeny and can also be used to make molecular markers and study how genetic traits change over time. Our research will contribute to the population genetics and evolution of tea plant. [ABSTRACT FROM AUTHOR]

This paper aims to solve the problems of the low quality and shallow depth of the traditional straw return method. According to the requirements of the new furrow burial and return agronomic model, a corn straw ditch-buried returning machine was designed that could simultaneously complete the processes of picking, conveying, ditching, soil-covering and pressing. Key components were theoretically analyzed and designed, such as the pickup device, ditching device and straw-guiding soil-covering and pressing device. Based on a field experiment, the main factors influencing the effects of straw picking, soil ditching and straw return were studied. Both forward speed and pickup device speed significantly affected the straw picking rate. The ditching area, ditching width consistency factor and ditching depth stability factor gradually decreased with increasing forward speed and gradually increased with increasing trenching device speed. There was a significant interaction among the forward speed, pickup device speed and ditching device speed. At a forward speed of 1.68 m/s, the picking device speed was 330 r/min, the ditching device speed was 290 r/min, and the highest straw return rate was 93.65%. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD), which is the leading cause of blindness among the elderly in western societies, is majorly accompanied by retinal pigment epithelium (RPE) degeneration. Because of the irreversible RPE cell loss among oxidative stress, it is crucial to search for available drugs for atrophic (dry) AMD. RNA-Seq analysis revealed that genes related to aging and mitochondrial health were differentially expressed under Arbutin treatment, whereas compared to oxidative injury, our study demonstrated that Arbutin substantially abrogated oxidative stress-induced cell senescence and apoptosis linked to intracellular antioxidant enzyme system homeostasis maintenance, restored mitochondrial membrane potential (MMP), and reduced the SA-ß-GAL accumulation in RPE. Furthermore, Arbutin alleviated oxidative stress-mediated cell apoptosis and senescence via activation of SIRT1, as evidenced by the increase of the downstream FoxO3a and PGC-1a/ß that are related to mitochondrial biogenesis, and the suppression of NF-B p65 inflammasome, whereas rehabilitation of oxidative stress by SIRT1 inhibitor attenuated the protective effect of Arbutin. In conclusion, we validated the results in an in vivo model constructed by NAIO3-injured mice. OCT and HE staining showed that Arbutin sustained retinal integrity in the case of oxidative damage in vivo, and the disorder of RPE cytochrome was alleviated through fundus observation. In summary, our findings identified that oxidative stress-induced mitochondrial malfunction and the subsequent senescence acceleration in RPE cells, whereas Arbutin inhibited TBHP-induced RPE degeneration via regulating the SIRT1/Foxo3a/PGC-1a/ß signaling pathway. These findings suggested that Arbutin is a new agent with potential applications in the development of AMD diseases. [ABSTRACT FROM AUTHOR]

Secondary non-noble metals have frequently been introduced to metal nanocrystals to modify their physicochemical properties and decrease the amount of precious metal used. However, this usually causes deactivation. Here, we synthesized intermetallic PdCd nanocubes that not only preserved the catalytic activity but also exhibited an increase in catalytic activity upon illumination. The intermetallic PdCd nanocubes, which are typically identified as the face-centered tetragonal phase, were verified to have a body-centered tetragonal phase theoretically with all exposed facets bounded by Pd atoms and the maximum number of active Pd sites in the alloyed structure. Examination of the physicochemical properties of the intermetallic PdCd nanocubes compared with those of pure Pd nanocubes in a Suzuki coupling reaction as a proof of concept revealed that the intermetallic PdCd nanocubes preserved the catalytic activity, decreased the amount of Pd metal used, and increased catalytic activity by 27% upon illumination. This increase can be attributed to an increase in the number of s-band free electrons upon doping of Cd atoms. [ABSTRACT FROM AUTHOR]

Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H2S) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which H2S improves the progression of atrial fibrosis to AF remains unclear. A case-control study of patients with and without AF was designed to assess changes in H2S, the Warburg effect, and ERS in AF. The results showed that AF can significantly reduce cystathioninec-lyase (CSE) and 3-mercaptopyruvate thiotransferase (3-MST) expression and the H2S level, induce cystathionine-β-synthase (CBS) expression; increase the Warburg effect, ERS and atrial fibrosis; and promote left atrial dysfunction. In addition, AngII-treated SD rats had an increased Warburg effect and ERS levels and enhanced atrial fibrosis progression to AF compared to wild-type SD rats, and these conditions were reversed by sodium hydrosulfide (NaHS), dichloroacetic acid (DCA) or 4-phenylbutyric acid (4-PBA) supplementation. Finally, low CSE levels in AngII-induced HL-1 cells were concentration and time-dependent and associated with mitochondrial dysfunction, apoptosis, the Warburg effect and ERS, and these effects were reversed by NaHS, DCA or 4-PBA supplementation. Our research indicates that H2S can regulate the AngII-induced Warburg effect and ERS and might be a potential therapeutic drug to inhibit atrial fibrosis progression to AF. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited blistering skin disorders characterized by skin fragility following minor trauma, usually present since birth. EB can be categorized into four classical subtypes, EB simplex, junctional EB, dystrophic EB and Kindler EB, distinguished on clinical features, plane of blister formation in the skin, and molecular pathology. Treatment for EB is mostly supportive, focusing on wound care and patient symptoms such as itch or pain. However, therapeutic advances have also been made in targeting the primary genetic abnormalities as well as the secondary inflammatory footprint of EB. Pre-clinical or clinical testing of gene therapies (gene replacement, gene editing, RNA-based therapy, natural gene therapy), cell-based therapies (fibroblasts, bone marrow transplantation, mesenchymal stromal cells, induced pluripotential stem cells), recombinant protein therapies, and small molecule and drug repurposing approaches, have generated new hope for better patient care. In this article, we review advances in translational research that are impacting on the quality of life for people living with different forms of EB and which offer hope for improved clinical management. [ABSTRACT FROM AUTHOR]

In terms of the local bond-orientational order (LBOO) parameters, a cluster approach to analyze local structures of simple liquids was developed. In this approach, a cluster is defined as a combination of neighboring seeds having at least nb local-orientational bonds and their nearest neighbors, and a cluster ensemble is a collection of clusters with a specified nb and number of seeds ns. This cluster analysis was applied to investigate the microscopic structures of liquid Ga at ambient pressure (AP). The liquid structures studied were generated through ab initio molecular dynamics simulations. By scrutinizing the static structure factors (SSFs) of cluster ensembles with different combinations of nb and ns, we found that liquid Ga at AP contained two types of cluster structures, one characterized by sixfold orientational symmetry and the other showing fourfold orientational symmetry. The SSFs of cluster structures with sixfold orientational symmetry were akin to the SSF of a hard-sphere fluid. On the contrary, the SSFs of cluster structures showing fourfold orientational symmetry behaved similarly as the anomalous SSF of liquid Ga at AP, which is well known for exhibiting a high-q shoulder. The local structures of a highly LBOO cluster whose SSF displayed a high-q shoulder were found to be more similar to the structure of β-Ga than those of other solid phases of Ga. More generally, the cluster structures showing fourfold orientational symmetry have an inclination to resemble more to β-Ga. [ABSTRACT FROM AUTHOR]

To improve the quality of side deep fertilization in paddy fields and study the dynamic change in fertilizer particles in fertilizer boxes, a model connecting the mechanical components and fertilizer based on the discrete element method was established, and a numerical simulation analysis of the spiral fertilizer distributor was conducted with EDEM software. The primary factors affecting the uniformity and stability of the fertilizer were studied. Using an orthogonal experimental design and numerical simulation technology, the speed, lead and diameter of a steel wire were selected as experimental factors, the mean fertilization value and the fertilization coefficient of the variation were selected as evaluating indicators, a mathematical model between the factors and indicators was established by virtual orthogonal testing, and the numerical processing was optimized with Design-Expert 6.0.10 software. The results showed that the primary and secondary factors affecting the comprehensive performance occurred in the following sequence: steel wire speed > steel wire diameter > steel wire lead. When the speed, lead, and diameter of the steel wire were 15 r/min, 65 mm and 7 mm, respectively, the operation performance was superior. High-speed video camera analysis and bench tests showed that the results were consistent with the simulation optimization. The mean value and the coefficient of variation of fertilization were 9.39 g and 3.71%, respectively, which satisfy the agronomic requirements for paddy field side deep fertilization. [ABSTRACT FROM AUTHOR]

By simulating the rigid simple point charge extended model at temperature T = 300 K, the orientational relaxation of the OH-bond in water was investigated over short to intermediate timescales, within which molecules undergo inertial rotation and libration and then enter the rotational diffusion regime. According to the second-cumulant approximation, the orientational time correlation function (TCF) of each axis that is parallel or perpendicular to an OH-bond is related to an effective rotational density of states (DOS), which is determined using the power spectra of angular velocity autocorrelation functions (AVAFs) of the other two axes. In addition, the AVAF power spectrum of an axis was approximated as the rotational stable instantaneous normal mode (INM) spectrum of the axis. As described in a previous study [S. L. Chang, T. M. Wu, and C. Y. Mou, J. Chem. Phys. 121, 3605 (2004)], simulated molecules were classified into subensembles, according to either the local structures or the H-bond configurations of the molecules. For global molecules and the classified subensembles, the simulation results for the first- and second-rank orientational TCFs were compared with the second-cumulant predictions obtained using the effective rotational DOSs and the rotational stable- INM spectra. On short timescales, the OH-bond in water behaves similar to an inertial rotor and its anisotropy is lower than that of a water molecule. For molecules with three or more H-bonds, the OH-bond orientational TCFs are characterized by a recurrence, which is an indication for libration of the OH-bond. The recurrence can generally be described by the second-cumulant prediction obtained using the rotational stable-INM spectra; however, the orientational TCFs after the recurrence switch to a behavior similar to that predicted using the AVAF power spectra. By contrast, the OH-bond orientational TCFs of molecules initially connected with one or two H-bonds decay monotonically or exhibit a weak recurrence, indicating rapid relaxation into the rotational diffusion regime after the initial Gaussian decay. In addition to accurately describing the Gaussian decay, the second-cumulant predictions formulated using the rotational stable-INM spectra and the AVAF power spectra serve as the upper and lower limits, respectively, for the OH-bond orientational TCFs of these molecules after the Gaussian decay. [ABSTRACT FROM AUTHOR]

Background: The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data.Methods: A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups.Results: A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group.Conclusion: The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies. [ABSTRACT FROM AUTHOR]

Global warming, climate change, and ever-increasing energy demand are among the pressing challenges currently facing humanity. Particularly, indoor air conditioning, a major source of energy consumption, requires immediate improvement to prevent energy crises. In this study, various airfoil profiles were applied to create a window-type convection device that entrains air to improve convection between indoor and outdoor airflows and adjust the indoor temperature. How the geometric structure of the convection device affects its air entrainment performance was investigated on the basis of various airfoil profiles and outlet slit sizes of the airflow multiplier. The airfoil profiles were designed according to the 4-digit series developed by the National Advisory Committee for Aeronautics. The results revealed that airfoil thickness, airfoil camber, and air outlet slit size affected the mass flow rate of the convection device. Overall, the mass flow rate at the outlet of the convection device was more than 10 times greater than at the inlet, demonstrating the potential of the device to improve air convection. To validate these simulated results, the wind-deflector plate was processed using the NACA4424 airfoil with a 1.2 mm slit, and various operating voltages were applied to the convection device to measure the resulting wind speeds and calculate the corresponding mass flow rates. The experimental and simulated results were similar, with a mean error of <7%, indicating that the airfoil-shaped wind-deflector plate substantially improved air entrainment of the convection device to the goal of reduced energy consumption and carbon emissions. [ABSTRACT FROM AUTHOR]

The Arctic climate system is rapidly transitioning into a new regime with a reduction in the extent of sea ice, enhanced mixing in the ocean and atmosphere, and thus enhanced coupling within the ocean-ice- atmosphere system; these physical changes are leading to ecosystem changes in the Arctic Ocean. In this review paper, we assess one of the critically important aspects of this new regime, the variability of Arctic freshwater, which plays a fundamental role in the Arctic climate system by impacting ocean stratification and sea ice formation. Liquid and solid freshwater exports also affect the global climate system, notably by impacting the global ocean overturning circulation. In this review paper we assess to what extent observations during the 2010-2019 period are sufficient to estimate the Arctic freshwater budget with greater certainty than previous assessments and how this budget has changed relative to the 2000-2010 period. We include discussions of processes not included in previous assessments, such as run off from the Greenland Ice Sheet, the role of snow on sea ice, and vertical redistribution. We show that the trend in Arctic freshwater in the 2010s has stabilized relative to the 2000s due to an increased compensation between a freshening of the Beaufort Gyre and a reduction in freshwater in the Amerasian and Eurasian basins. Notably, the sea ice cover has become more seasonal and more mobile, the mass loss of the Greenland ice sheet has shifted from the western to the eastern part, and the import of subpolar waters into the Arctic has increased. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of the application of role-play in endodontic study in improving the communication skills of Chinese dental undergraduates prior to their direct interactions with patients at the Fourth Military Medical University's School of Stomatology, China. Methods: Students were recruited from the 5-year bachelor's programme (n = 36) and randomly divided into six groups, and from the 8-year DDS programme (n = 10) and randomly divided into two groups to participate in the role-play training. Cases selected randomly from the case pool were distributed to the groups. The teacher gave an outline of the roles in the simulation. Each member of each group randomly selected their own role for the role-play. Four types of surveys were distributed to students and faculty members at different points after the role-plays had taken place, to evaluate their attitude towards the use of role-plays in endodontic study. Frequency analysis and a one sample t test were used to describe and analyse students' acceptance of role-play as a teaching technique. The level of statistical significance was set at P < 0.05. Results: Students' performance and satisfaction as well as the supporting faculty responses were very favourable towards role-playing. In total, 93.5% of students responded favourably to the role-play, answering 'strongly agree' or 'agree' to the positive statements about their role-play performance. A total of 95.1% of students stated that they had benefited psychologically and technically from the role-play ('strongly agree' or 'agree') after their 1-year rotating internship. Conclusion: The application of role-play in endodontic study is an effective way of educating Chinese dental undergraduates and can be beneficial for their transition from students to dentists. [ABSTRACT FROM AUTHOR]

The airway epithelium is seriously damaged upon pulmonary Pseudomonas aeruginosa infection, especially in cystic fibrosis (CF) sufferers. Therefore, the discovery of novel anti-infective agents accelerating healing of infected injured tissues is crucial. The antipseudomonal peptides esculentin-1a(1–21)NH2 and its diastereomer Esc(1–21)-1c (Esc peptides) hold promise in this respect. In fact, they stimulate airway epithelial wound repair, but no mechanistic insights are available. Here we demonstrated that this process occurs through promotion of cell migration by an indirect activation of epidermal growth factor receptor mediated by metalloproteinases. Furthermore, we showed an increased expression of metalloproteinase 9, at both gene and protein levels, in peptide-treated bronchial epithelial cells with a functional or mutated form of CF transmembrane conductance regulator. In addition, the two peptides counteracted the inhibitory effect of Pseudomonas lipopolysaccharide (mimicking an infection condition) on the wound healing activity of the airway epithelium, and they enhanced the production of interleukin-8 from both types of cells. Finally, no immunogenicity was discovered for Esc peptides, suggesting their potential safety for clinical usage. Besides representing a step forward in understanding the molecular mechanism underlying the peptide-induced wound healing activity, these studies have contributed to highlight Esc peptides as valuable therapeutics with multiple functions. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the prevalence of dental caries from 1980 to 2018 to provide evidence for caries prevention in mainland China. Methods: Four databases were selected with online search tools to offer maximum coverage of the published literature on the provincial or national level of caries prevalence: Medline, EMBASE, China National Knowledge Infrastructure (CNKI, in Chinese) and Wanfang databases (in Chinese). We supplemented the results with relevant publications from the government health sectors, textbooks and web-based databases. Studies published between 1 January 1980 and 26 March 2018 were included. The quality of literature was assessed, and a meta-analysis was conducted using Stata12.0. Results: A total of 82 studies were included in the final analysis. There were 1.49 million samples retrieved from 1980 to 2018, and the overall pooled prevalence of caries was 52.0% (95% CI: 49.4%-54.6%) in mainland China. The overall prevalence of caries increased from 36.4% (95% CI: 31.5%-41.5%) in the 1980s to 51.8% (95% CI: 34.9%-68.7%) in the 1990s, stabilised at 50.7% (95% CI: 43.8%-57.6%) in the 2000s and slightly increased to 53.1% (95% CI: 50.8%-55.5%) in the 2010s. The pooled caries prevalence was 64.8% (95% CI: 61.7%-67.8%), 47.3% (95% CI: 43.1%-51.5%), 42.4% (95% CI: 38.3%-46.5%), 66.7% (95% CI: 50.8%-82.6%) and 82.0% (95% CI: 72.5%-91.4%) for the ages/age groups 5, 12, 15, 35-44 and 65-74, respectively. The average dental caries pooled prevalence in urban areas was 51.4% (95% CI: 48.5%-54.2%), which was lower than 54.6% (95% CI: 47.9%-61.4%) in rural areas. Conclusion: The prevalence of dental caries in mainland China is generally high, and an increasing trend was observed over the past 38 years. The prevalence of dental caries in mainland China varied geographically, and its characteristics differed over time. Regional disparities between eastern/western China and rural/urban areas still exist. Comprehensive local prevalence data on caries are summarised here for the first time, which provide valuable evidence for the oral disease burden in China. [ABSTRACT FROM AUTHOR]

The construction industry is a high debt ratio, high operating risk and high financial leverage business. The financial instability causes a chain reaction among funds transferred among companies, therefore restricting competitiveness within the industry. The industry’s character and accounting principles of firm-years are different from that of other industries. Creating a hypothetical model of a financial crisis within the construction industry is therefore necessary. Application of this model to real scenarios involving relevant parties can help to forecast a financial crisis in the future. This study applied the market-based model, accounting-based model, hybrid models to predict a financial crisis. These models were then compared to find which can best predict a company that will default. Also, in this paper choosing variables for the Hybrid and Accounting-based models can promote their performance. Finally, the best can be selected for predicting stability. [ABSTRACT FROM AUTHOR]

Abstract: Background: Xenotransplantation is one of the promising strategies for overcoming the shortage of organs available for transplant. However, many immunological obstructions need to be overcome for practical use. Increasing evidence suggests that neutrophils contribute to xenogeneic cellular rejection. Neutrophils are regulated by activation and inhibitory signals to induce appropriate immune reactions and to avoid unnecessary immune reactivity. Therefore, we hypothesized that the development of neutrophil‐targeted therapies may have the potential for increased graft survival in xenotransplantation. Methods: A plasmid containing a cDNA insert encoding the human CD31 gene was transfected into swine endothelial cells (SEC). HL‐60 cells were differentiated into neutrophil‐like cells by culturing them in the presence of 1.3% dimethyl sulfoxide for 48 hours. The cytotoxicity of the differentiated HL‐60 cells (dHL‐60) and peripheral blood‐derived neutrophils was evaluated by WST‐8 assays. To investigate the mechanism responsible for hCD31‐induced immunosuppression, citrullinated histone 3 (cit‐H3) and phosphorylation of SHP‐1 were detected by a cit‐H3 enzyme‐linked immunosorbent assay (ELISA) and Western blotting, respectively. Results: A significant decrease in dHL‐60 and neutrophil‐mediated cytotoxicity in SEC/hCD31 compared with SEC was seen, as evidenced by a cytotoxicity assay. Furthermore, the suppression of NETosis and the induction of SHP‐1 phosphorylation in neutrophils that had been co‐cultured with SEC/CD31 were confirmed by cit‐H3 ELISA and Western blotting with an anti‐phosphorylated SHP‐1. Conclusion: These data suggest that human CD31 suppresses neutrophil‐mediated xenogenic cytotoxicity via the inhibition of NETosis. As CD31 is widely expressed in a variety of inflammatory cells, human CD31‐induced suppression may cover the entire xenogeneic cellular rejection, thus making the generation of human CD31 transgenic pigs very attractive for use in xenografts. [ABSTRACT FROM AUTHOR]

As the technology in automation and computation advances, traffic data can be easily collected from multiple sources, such as sensors and surveillance cameras. To extract value from the huge volumes of available data requires the capability to process and extract patterns in large datasets. In this paper, a machine learning method embedded within a big data analytics platform is constructed by using random forests method and Apache Hadoop to predict highway travel time based on data collected from highway electronic toll collection in Taiwan. Various prediction models are then developed for highway travel time based on historical and real-time data to provide drivers with estimated and adjusted travel time information. [ABSTRACT FROM AUTHOR]

Purpose: Various strategies, such as the generation of alpha-1,3-galactosyltransferase knocked-out pigs and CD55 transgenic pigs, have been investigated to inhibit pig to human xenogeneic rejection. Our aim is to develop strategies to overcome the hurdle of not only hyper acute rejection, but also that of cellular xenogeneic rejection (CXR). Although macrophages have been well known to play a critical role in CXR, monocyte/macrophage-mediated xenogeneic rejection has not been well studied. In this study, we evaluated the effect of CD200 in xenogeneic rejection by macrophages. Methods: Naïve swine endothelial cells (SEC) and SEC/CD200 were co-cultured with M0 macrophages and the cytotoxicity was measured by a WST-8 assay. The phagocytosis of SEC and SEC/CD200 by macrophages was analyzed by flow cytometry. Results: While CD200 failed to suppress a significant amount of cytotoxicity against SEC by monocytes, M0 macrophage-mediated cytotoxicity was significantly suppressed by human CD200. The phagocytosis by M0 macrophages was also tested. The phagocytosis assay revealed that human CD200 suppresses M0 macrophage-mediated phagocytosis. Conclusions: Our findings indicate that human CD200 suppresses the xenogeneic rejection by CD200R macrophages and that the generation of hCD200 transgenic pigs for use in xenografts is very attractive for preventing the macrophage-mediated rejection. [ABSTRACT FROM AUTHOR]

Ten-eleven translocation-2 (TET2) protein is a DNA demethylase that regulates gene expression through DNA demethylation and also plays important roles in various diseases including atherosclerosis. Endothelial dysfunction represents an early key event in atherosclerotic disease. The cystathionine-g-lyase (CSE)/hydrogen sulfide (H2S) is a key endogenous system with protective effects on endothelial functions. In this study, we examined how TET2 regulates oxidized low-density lipoprotein (oxLDL)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and determined the role of the CSE/H2S system. Treatment with oxLDL resulted in downregulation of both TET2 expression and CSE/H2S system in HUVECs. TET2 was found to have protective effects on oxLDL-induced HUVEC dysfunction, which was confirmed with TET2 overexpression plasmid or TET2 shRNA plasmid. Moreover, TET2 was found to upregulate the CSE/H2S system and inhibit NF-κB activation, leading to decreased expression of ICAM-1 and VCAM-1 and attenuated adhesion of THP-1 cells to oxLDL-activated HUVECs. The protective effect of TET2 was reduced by treatment with CSE siRNA. Further studies revealed that CSE promoter region contains a well-defined CpG island. We also showed that TET2 enhanced 5-hydroxymethylcytosine (5hmC) level and promoted DNA demethylation of CSE gene promoter, leading to an increase in CSE expression. In conclusion, TET2 has protective effects on oxLDL-induced HUVEC dysfunction, likely through upregulating the CSE/H2S system by DNA demethylation of CSE gene promoter. TET2 may become a novel therapeutic target for endothelial dysfunction-associated vascular diseases. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadjuvant chemoradiation with minimally invasive esophagectomy (MIE) may reduce postoperative mortality, which can revive preoperative chemoradiation. No randomized controlled studies comparing neoadjuvant chemoradiation plus MIE with neoadjuvant chemotherapy plus MIE have been performed so far. The present trial is initiated to obtain valid information whether neoadjuvant chemoradiation plus MIE yields better survival without worse postoperative morbidity and mortality in the treatment of locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0).Methods/design: CMISG1701 is a multicenter, prospective, randomized, phase III clinical trial, investigating the safety and efficacy of neoadjuvant chemoradiation plus MIE compared with neoadjuvant chemotherapy plus MIE. Patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) are eligible for the study. A total of 264 patients are randomly assigned to neoadjuvant chemoradiation (arm A) or neoadjuvant chemotherapy (arm B) with a 1:1 allocation ratio. The primary outcome is overall survival assessed with a minimum follow-up of 36 months. Secondary outcomes are progression-free survival, recurrence-free survival, postoperative pathologic stage, treatment-related complications, postoperative mortality as well as quality of life.Discussion: The objective of this trial is to identify the superior protocol with regard to patient survival, treatment morbidity/mortality and quality of life between neoadjuvant chemoradiation plus MIE and neoadjuvant chemotherapy plus MIE.Trial Registration: NCT03001596 (December 17, 2016). [ABSTRACT FROM AUTHOR]

Background: Hyperlipidemia is a risk factor for neurodegenerative diseases. Proprotein convertase subtilisin / Kexin type 9 (PCSK9) degrades hepatic low-density lipoprotein receptor (LDLR) to regulate lipid metabolism. It is unclear if PCSK9 plays a role in neurodegenerative diseases.Objective: This study was designed to determine whether PCSK9 is crucial between hyperlipidemia and Alzheimer's disease. The interrelationship between PCSK9 and neuronal apoptosis was explored in PC12 cells in response to treatment with oxidized low-density lipoprotein (oxLDL).Methods: Cultured PC12 cells were serum-starved and incubated with different concentrations of oxLDL for 24 h. Intracytoplasmic lipid droplets were observed by oil red O staining. Morphological assessment of apoptotic cells was performed using Hoechst 33258 staining and flow cytometry analysis. The expression of mRNA and protein was detected by reverse-transcription polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Transfection of small interfering RNA (siRNA) into PC12 cells was conducted using HiperFect Transfection Reagent. Concentrations of Aβ40 and Aβ42 were detected by enzyme-linked immunosorbent assay (ELISA) kit.Results: Intracellular lipid content, the number of apoptotic cells, and PCSK9 expression were increased in PC12 cells after oxLDL treatment. Transfection with PCSK9 siRNA reduced the oxLDL-induced apoptosis of PC12 cells. We further confirmed the involvement of Bcl-2/Bax-Caspase (9, 3) signaling pathway in the regulation of PC12 cells apoptosis.β-Secretase 1, another target gene of PCSK9, was downregulated in PC12 cells in response to oxLDL treatment. Aβ40 and Aβ42 contents were also decreased.Conclusion: PCSK9 promotes oxLDL-induced PC12 cell apoptosis through the Bcl-2/Bax-Caspase 9/3 signaling pathway. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a lipid regulatory gene involved in cell apoptosis. However, the function and mechanism of PCSK9 in neuronal apoptosis following hyperlipidemia remains to be elucidated. The present study established a hyperlipidemic mouse model by feeding a high-fat diet (HFD) to 6-week-old apoE(-/-) mice. Plasma lipid levels, hippocampal lipid accumulation, hippocampal histology, and hippocampal neuronal apoptosis were all monitored for changes. The expression levels of PCSK9, β-secretase 1 (BACE1), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase-3 in hippocampal CA3 and CA1 neurons were also measured. Results demonstrated that a HFD increased the lipid accumulation in the CA3 hippocampus and the levels of plasma lipids, including triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein. In addition, CA3 neurons in the HFD group indicated apparent injuries and increased neuronal apoptosis, which are associated with the expression of Bcl-2, Bax, and caspase-3. A HFD also increased the expression levels of PCSK9 and BACE1. BACE1 promotes cleavage of amyloid precursor proteins to generate β-amyloid peptide (Aβ), which induces neuronal apoptosis. Protein levels of Aβ are associated with the observation of amyloid plaques in the hippocampus of the HFD group. The results suggest that hyperlipidemia regulates neuronal apoptosis by increasing PCSK9 and BACE1 expression. Overall, the current study may elucidate the role of lipid metabolism disorder in AD pathogenesis. [ABSTRACT FROM AUTHOR]