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Introduction: Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenilemyelomonocytic leukemia (JMML) patients. Methods: This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DACmonotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival. Results: There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups (p=0.769). Clinical remission rates significantly improved following bridging treatment (p=0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p=0.002). Conclusion: Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments. [ABSTRACT FROM AUTHOR]

Biomass-derived carbon materials are being increasingly utilized in various fields. This paper reports a facile synthesis method for O/N co-doped hierarchical porous carbon, utilizing the inherent pore structure and high heteroatom content of sesame meal. The O/N co-doped hierarchical porous carbon (SC-120) exhibits a hierarchical pore structure and abundant surface functional groups, the specific surface area reached 1743 m2 g−1, and the O and N element contents were measured at 10.87% and 1.95% respectively. In the three-electrode system, the specific capacitance of SC-120 reached 358.6 F g−1 at a current density of 0.5 A g−1, and a specific capacitance of 262.5 F g−1 is maintained even at a high current density of 30 A g−1. Constructed using SC-120 as the electrode, the symmetrical supercapacitor exhibits a high energy density of 9.23 W h kg−1 at a power density of 100 W kg−1 and excellent cyclic stability of 93.58% capacitance retention rate after 7500 charge–discharge testing. Additionally, SC-120 demonstrates potential for electromagnetic interference shielding, attaining an efficiency of 33.18 dB and a shielding effectiveness of 99.59% within the X-band frequency range of 8.2–12.4 GHz. [ABSTRACT FROM AUTHOR]

Cerebral ischemic preconditioning (CIP) has been shown to improve brain ischemic tolerance against subsequent lethal ischemia. Reactive astrocytes play important roles in cerebral ischemia–reperfusion. Recent studies have shown that reactive astrocytes can be polarized into neurotoxic A1 phenotype (C3d) and neuroprotective A2 phenotype (S100A10). However, their role in CIP remains unclear. Here, we focused on the role of N-myc downstream-regulated gene 2 (NDRG2) in regulating the transformation of A1/A2 astrocytes and promoting to brain ischemic tolerance induced by CIP. A Sprague Dawley rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. Rats were divided into the following six groups: (1) sham group; (2) CIP group: left middle cerebral artery was blocked for 10 min; (3) MCAO/R group: left middle cerebral artery was blocked for 90 min; (4) CIP + MCAO/R group: CIP was performed 72 h before MCAO/R; (5) AAV-NDRG2 + CIP + MCAO/R group: adeno-associated virus (AAV) carrying NDRG2 was administered 14 days before CIP + MCAO/R; (6) AAV-Ctrl + CIP + MCAO/R group: empty control group. The rats were subjected to neurological evaluation 24 h after the above treatments, and then were sacrificed for 2, 3, 5-triphenyltetraolium chloride staining, thionin staining, immunofluorescence and western blot analysis. In CIP + MCAO/R group, the neurological deficit scores decreased, infarct volume reduced, and neuronal density increased compared with MCAO/R group. Notably, CIP significantly increased S100A10 expression and the number of S100A10+/GFAP+ cells, and also increased NDRG2 expression. MCAO/R significantly decreased S100A10 expression and the number of S100A10+/GFAP+ cells yet increased C3d expression and the number of C3d+/GFAP+ cells and NDRG2 expression, and these trends were reversed by CIP + MCAO/R. Furthermore, over-expression of NDRG2 before CIP + MCAO/R, the C3d expression and the number of C3d+/GFAP+ cells increased, while S100A10 expression and the number of S100A10+/GFAP+ cells decreased. Meanwhile, over-expression of NDRG2 blocked the CIP-induced brain ischemic tolerance. Taken together, these results suggest that CIP exerts neuroprotective effects against ischemic injury by suppressing A1 astrocyte polarization and promoting A2 astrocyte polarization via inhibiting NDRG2 expression. [ABSTRACT FROM AUTHOR]

Background The claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied. Methods We evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats. Results We found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test. Conclusion These data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions. [ABSTRACT FROM AUTHOR]

The morbidity rate of ischemic stroke is increasing annually with the growing aging population in China. Astrocytes are ubiquitous glial cells in the brain and play a crucial role in supporting neuronal function and metabolism. Increasing evidence shows that the impairment or loss of astrocytes contributes to neuronal dysfunction during cerebral ischemic injury. The mitochondrion is increasingly recognized as a key player in regulating astrocyte function. Changes in astrocytic mitochondrial function appear to be closely linked to the homeostasis imbalance defects in glutamate metabolism, Ca2+ regulation, fatty acid metabolism, reactive oxygen species, inflammation, and copper regulation. Here, we discuss the role of astrocytic mitochondria in the pathogenesis of brain ischemic injury and their potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Our previous study has proved that the Klotho up-regulation participated in cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance. However, the exact neuroprotective mechanism of Klotho in CIP remains unclear. We explored the hypothesis that STAT4-mediated Klotho up-regulation contributes to the CIP-induced brain ischemic tolerance via inhibiting neuronal pyroptosis. Firstly, the expressions of pyroptosis-associated proteins (i.e., NLRP3, GSDMD, pro-caspase-1, and cleaved caspase-1) in hippocampal CA1 region were determined during the process of brain ischemic tolerance. We found the expression of pyroptosis-associated proteins was significantly up-regulated in the ischemic insult (II) group, and showed no significant changes in the CIP group. The expression level of each pyroptosis-associated proteins was lower in the CIP + II group than that in the II group. Inhibition of Klotho expression increased the expression of pyroptosis-associated proteins in the CIP + II group and blocked the CIP-induced brain ischemic tolerance. Injection of Klotho protein decreased the expression of pyroptosis-associated proteins in the II group, and protected neurons from ischemic injury. Secondly, the transcription factor STAT4 of Klotho was identified by bioinformatic analysis. Double luciferase reporter gene assay and chromatin immunoprecipitation assay showed STAT4 can bind to the site between nt − 881 and – 868 on the Klotho promoter region and positively regulates Klotho expression. Moreover, we found CIP significantly enhanced the expression of STAT4. Knockdown STAT4 suppressed Klotho up-regulation after CIP and blocked the CIP-induced brain ischemic tolerance. Collectively, it can be concluded that STAT4-mediated the up-regulation of Klotho contributed to the brain ischemic tolerance induced by CIP via inhibiting pyroptosis. [ABSTRACT FROM AUTHOR]

C12H12N2O8Mn, orthorhombic, Pbca (no. 61), a = 11.5651(15) Å, b = 9.4169(12) Å, c = 25.634(3) Å, V = 2791.7(6) Å3, Z = 8, Rgt(F) = 0.0402, wRref(F2) = 0.1166, T = 296.15 K. [ABSTRACT FROM AUTHOR]

Conifers make up about one third of global forests but are threatened by seed parasitoid wasp species. Many of these wasps belong to the genus Megastigmus, yet little is known about their genomic background. In this study, we provide chromosome‐level genome assemblies for two oligophagous conifer parasitoid species of Megastigmus, which represent the first two chromosome‐level genomes of the genus. The assembled genomes of Megastigmus duclouxiana and M. sabinae are 878.48 Mb (scaffold N50 of 215.60 Mb) and 812.98 Mb (scaffold N50 of 139.16 Mb), respectively, which are larger than the genome size of most hymenopterans due to the expansion of transposable elements. Expanded gene families highlight the difference in sensory‐related genes between the two species, reflecting the difference in their hosts. We further found that these two species have fewer family members but more single‐gene duplications than polyphagous congeners in the gene families of ATP‐binding cassette transporter (ABC), cytochrome P450 (P450) and olfactory receptors (OR). These findings shed light on the pattern of adaptation to a narrow spectrum of hosts in oligophagous parasitoids. Our findings suggest potential drivers underlying genome evolution and parasitism adaptation, and provide valuable resources for understanding the ecology, genetics and evolution of Megastigmus, as well as for the research and biological control of global conifer forest pests. [ABSTRACT FROM AUTHOR]

Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP. [ABSTRACT FROM AUTHOR]

Background: As an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved noncoding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the Rorc gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether cis-acting elements regulate RORgt expression in ILC3s is unknown. Results: Here we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4+NKp46+ ILC3 population, though the overall numbers and frequencies of RORγt+ ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORgt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cellintrinsic generation of CD+NKp46+ ILC3 subset. Conclusion: Our study thus identifies CNS9 as an essential cis-regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORgt protein. [ABSTRACT FROM AUTHOR]

Seasonality is the common phenomena in ecological evolution. Firstly, we formulate and explore a simplified West Nile virus model, which describes the transmission of West Nile virus driven by seasonal fluctuations in a spatially variable habitat where the spatial movement of the infectious mosquitoes and infectious birds are described by Laplace diffusion. The range of the infected area is assumed to be a moving interval [0,h(t)] ⊂ ℝ, with its right end point representing the spreading fronts of the disease. We will mainly investigate the impact of spatial heterogeneity of environment and temporal periodicity on the persistence and extinction of West Nile virus. The basic reproduction number R0D in a fixed region and the spatial-temporal risk index R0F (t) for the free boundary problem, which depends on spatial heterogeneity, temporal periodicity and spatial diffusion, are defined by the associated linearized eigenvalue problems. Sufficient conditions for the spreading and vanishing of West Nile virus are presented for the spatial dynamics of the virus. At last, we explore the long time dynamical behavior of the solution to free boundary problem when the spreading occurs. [ABSTRACT FROM AUTHOR]

Quercetin is a natural flavonoid with a higher antioxidant capacity and anti-inflammatory. Tall fescue [Schedonorus arundinaceus (Schreb.) Dumort; E+] is perennial cool-season grass for grazing livestock in North America. Fescue infected with the endophyte (Neotyphodium coenophialum) produces chemicals toxic to livestock. However, the impact of quercetin on alleviating fescue toxicosis has received only limited attention. The objective of this experiment was to investigate the mitigation effect of quercetin on fescue toxicosis-induced cardiotoxicity of lambs. A total number of 24 Dorper lambs were randomized to four groups (n = 6 per group) and grazed tall fescue seed for 42 days. The results indicated that quercetin treatment alleviated fescue toxicosis induced cardiovascular histopathology injury (Fig 1), inhibited the increased trend of creatine kinase activities, and serum prolactin concentrations (Fig 2). Meanwhile, quercetin mitigated fescue toxicosis-induced cardiovascular oxidative damage by decreasing MDA and H2O2 contents, increasing antioxidant enzymes (T-SOD, Cu-Zn SOD, CAT, and T-AOC) activities (Fig 3). Quercetin evidently enhanced fescue toxicosis-induced down-regulation of phase I, II, and II detoxification gene expression to relieve oxidative damage (Fig 4-6). Moreover, quercetin triggered the NF-kB signaling pathway to ameliorate fescue toxicosis-induced cardiovascular inflammation (Fig 7-9). Quercetin attenuated cardiac mitochondrial impaired via Parkin/PINK modulated mediated mitophagy and PGC1-α mediated biogenesis (Fig 10-13). Collectively, our findings demonstrated that quercetin explicated potential protection against fescue toxicosis-induced cardiovascular toxicity. [ABSTRACT FROM AUTHOR]

This study examined the roles of grandparent-child cohesion and friendship quality in left-behind children’s positive and negative affect compared with non-left-behind children. Data from 557 participants indicated that grandparent-child cohesion and friendship quality predicted children’s emotional adaptation. Friend trust and support and intimate exchange had a stronger predictive effect on positive affect among non-left-behind children. Moreover, the interaction effects between grandparent-child cohesion and friendship quality on children’s positive affect supported the reinforcement model, while the interaction effects on negative affect supported the reinforcement model among left-behind children but supported the compensation model among non-left-behind children. [ABSTRACT FROM AUTHOR]

Several studies indicated that autophagy activation participates in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP). However, the mechanism of autophagy activation during the process still remains unclear. The present study aimed to evaluate the role of p38 MAPK–peroxisome proliferator-activated receptor γ (PPARγ) signaling cascade in autophagy during the CIP-induced BIT. The results shown that, initially, autophagy activation was observed after CIP in the model of global cerebral ischemia in rats, as was indicated by the upregulation of Beclin 1 expression, an increase in LC3-II/LC3-I ratio, the enhanced LC3 immunofluorescence, and a rise in the number of autophagosomes in the neurons of the hippocampal CA1 area. Besides, the inhibitor of autophagy 3-methyladenine obliterated the neuroprotection induced by CIP. Furthermore, the upregulation of p-p38 MAPK and PPARγ expressions was earlier than autophagy activation after CIP. In addition, pretreatment with SB203580 (the inhibitor of p38 MAPK) reversed CIP-induced PPARγ upregulation, autophagy activation, and neuroprotection. Pretreatment with GW9662 (the inhibitor of PPARγ) reversed autophagy activation and neuroprotection, while it had no effect on p-p38 MAPK upregulation induced by CIP. These data suggested that the p38 MAPK–PPARγ signaling pathway participates in autophagy activation during the induction of BIT by CIP. [ABSTRACT FROM AUTHOR]

This paper analyses the online text comments in the online trading platform and identifies the abnormal and contradictory comments. Firstly, the abnormal contradiction detection and analysis model of online text reviews is constructed based on fuzzy ontology to identify the abnormal and contradictory online text reviews. Secondly, the fuzzy emotional ontology and emotional tendency analysis method identify abnormal and contradictory online text reviews. The online text review anomaly detection and analysis model constructed enriches the process and method of online review anomaly identification. [ABSTRACT FROM AUTHOR]

Two transition metal complexes {[Co2(bpda)4(H2O)2]·4H2O}n(Co-1) and {[Ni(bpda)2(H2O)2]·2H2O}(Ni-2) (H2bpda = 2,2′-bipyridine-4,4′-dicarboxylic acid) have been synthesized by a hydrothermal method and characterized. These two compounds can be explored as stable electrocatalysts in the hydrogen evolution reaction (HER) using two important parameters: the overpotential and Tafel slope (TS). Electrochemical studies suggest that the reaction kinetics of a Co-1 catalyst is more favorable than that of a Ni-2 catalyst. Co-1 exhibits better HER performance with an overpotential of 182 mV at a current density of 10 mA cm−2, a small TS of 87.21 mV dec−1 and superior long-term durability (of up to 3000 cycles). Structural analysis shows that its catalytic activity is improved due to the two mixed valence cobalt ions and the pore structure formed by hydrogen bonds in Co-1, which is different from that of Ni-2. In addition, the mechanism of the HER is also explained theoretically by DFT molecular orbital and free energy calculations in this article. [ABSTRACT FROM AUTHOR]

Automatic vectorization is an important technique for compilers to improve the parallelism of programs. With the widespread usage of SIMD (Single Instruction Multiple Data) extensions in modern processors, automatic vectorization has become a hot topic in the research of compiler techniques. Accurately evaluating the effectiveness of automatic vectorization in typical compilers is quite valuable for compiler optimization and design. This paper evaluates the effectiveness of automatic vectorization, analyzes the limitation of automatic vectorization and the main causes, and improves the automatic vectorization technology. This paper firstly classifies the programs by two main factors: program characteristics and transformation methods. Then, it evaluates the effectiveness of automatic vectorization in three well-known compilers (GCC, LLVM, and ICC, including their multiple versions in recent 5 years) through TSVC (Test Suite for Vectorizing Compilers) benchmark. Furthermore, this paper analyzes the limitation of automatic vectorization based on source code analysis, and introduces the differences between academic research and engineering practice in automatic vectorization and the main causes, Finally, it gives some suggestions as to how to improve automatic vectorization capability. [ABSTRACT FROM AUTHOR]

Tall fescue is a major cool-season grass for grazing livestock in North America. However, it is typically infected with endophyte fungus, and the intake of the infected tall fescue was toxic to ruminant animals. Quercetin is one of the natural flavonoids that could increase the anti-inflammatory and antioxidant capacity of an animal. This experiment aims to investigate the effects of infected tall fescue seeds on the carcass characteristics and meat quality of finishing lambs, and also to determine the mitigation effect of quercetin on the toxicity of tall fescue seeds. A total number of 24 lambs were randomly assigned to four groups: 1) Control group (C, n = 6), tall fescue seed group (E+Q-, n = 6, feed with tall fescue seed infected with alkaloid endophyte), tall fescue seed, and quer-cetin group (E+Q+, n = 6, feed with tall fescue seed infected with alkaloid endophyte), and quercetin group (E-Q+, n = 6, feed with quercetin). All the groups were fed ad libitum for 42 d. The longissimus dorsi muscle of each lamb was collected to analyze the meat quality parameters. The results show that the tall fescue seed decreased the final body weight and the hot carcass weight of finishing lambs (P < 0.05). Intake of tall fescue seed with quercetin increased the meat color parameters (L*, a*, b*, C, and h) significantly (P < 0.05). The tall fescue decreased the intramuscular fat content in the longissimus dorsi muscle and also modulated the fatty acids composition (P < 0.05). In conclusion, infected tall fescue negatively affected the carcass characteristics and intramuscular fat deposition of finishing lambs. However, the quercetin didn't mitigate the influence of tall fescue seeds on carcass characteristics but increased the meat color characteristics. [ABSTRACT FROM AUTHOR]

Augmented glycolysis due to metabolic reprogramming in lung myofibroblasts is critical to their profibrotic phenotype. The primary glycolysis byproduct, lactate, is also secreted into the extracellular milieu, together with which myofibroblasts and macrophages form a spatially restricted site usually described as fibrotic niche. Therefore, we hypothesized that myofibroblast glycolysis might have a non-cell autonomous effect through lactate regulating the pathogenic phenotype of alveolar macrophages. Here, we demonstrated that there was a markedly increased lactate in the conditioned media of TGF-β1 (transforming growth factor-β1)-induced lung myofibroblasts and in the BAL fluids (BALFs) from mice with TGF-β1- or bleomycin-induced lung fibrosis. Importantly, the media and BALFs promoted profibrotic mediator expression in macrophages.Mechanistically, lactate induced histone lactylation in the promoters of the profibrotic genes inmacrophages, consistent with the upregulation of this epigenetic modification in these cells in the fibrotic lungs. The lactate inductions of the histone lactylation and profibrotic gene expression were mediated by p300, as evidenced by their diminished concentrations in p300-knockdown macrophages. Collectively, our study establishes that in addition to protein, lipid, and nucleic acid molecules, a metabolite can also mediate intercellular regulations in the setting of lung fibrosis. Our findings shed new light on the mechanism underlying the key contribution of myofibroblast glycolysis to the pathogenesis of lung fibrosis. [ABSTRACT FROM AUTHOR]

Glial glutamate transporter 1 (GLT‐1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator‐activated receptor gamma (PPARγ) participates in regulating GLT‐1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT‐1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up‐regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT‐1 was studied in rat cortical astrocyte‐neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up‐regulation of GLT‐1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT‐1 up‐regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPARγ antagonist on GLT‐1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose‐dependently attenuated the up‐regulation of GLT‐1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT‐1 during the acquisition of BIT induced by IPC. Cover Image for this issue: doi: 10.1111/jnc.14532. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/ [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive and lethal cancers lacking valid prognostic biomarkers. As an essential component of a large ribonucleoprotein complex, U Three Protein 14a (UTP14a) might play important roles in human tumorigenesis. However, the clinical significance and functions of UTP14a in ESCC still remain unclear. Methods: From September 2009 to August 2015, 210 patients with ESCC of the thoracic esophagus underwent thoracoscopic esophagectomy in our institute. The corresponding 210 tissue samples and 30 cancer‐distant mucosa (CDM) samples were tested for UTP14a expression by immunohistochemical staining. The long‐term survival was analyzed by the Kaplan–Meier method and Cox proportional hazards regression analyses. CCK8, cell colony formation, cell cycle, apoptosis, cell invasion, and wound healing assays were carried out with ECA109 cells to evaluate the effects of UTP14a on ESCC in vitro. Results: UTP14a was positively expressed in 88.1% (185/210) of the ESCC samples. UTP14a expression in ESCC was significantly higher than in CDM, as further confirmed by Western blot analysis. High expression of UTP14a in ESCC correlated significantly with tumor invasive depth (pT stage), which predicts poor disease‐free survival and disease‐specific survival, as indicated by the log‐rank test and Cox proportional hazards regression analysis. Additionally, our in vitro experiments further demonstrated that knockdown of UTP14a inhibits cell proliferation and invasion in ECA109 cells. Conclusions: Our results suggest that UTP14a is aberrantly expressed in ESCC, plays a critical role in cancer progression and could be a potential prognosis predictor of ESCC. [ABSTRACT FROM AUTHOR]

It has been increasingly recognized lately that aberrant cellular metabolism plays an important role in the pathogenesis of pulmonary fibrosis. In our previous systemic studies, we found that human lung myofibroblasts undergo glutaminolytic reprogramming, which is mediated by an increased expression of glutaminase (Gls) 1. We showed that augmented glutaminolysis critically regulates collagen production by promoting its stabilization in human lung myofibroblasts. Our study indicates that lung fibroblast Gls1 is a promising therapeutic target for this disease. In this investigation, we primarily focused on delineating the in vivo role of fibroblast Gls1 in mouse models of pulmonary fibrosis and determining the efficacy of Gls1 inhibition in treating this pathology. We now show that fibroblast Gls1 is upregulated in fibrotic mouse lungs. We present evidence that mice with ablation of fibroblast Gls1 are protected from bleomycin-induced lung fibrosis. We show that the Gls1 inhibitor, CB-839, is therapeutically efficacious in treating both bleomycin- and transforming growth factor-b1-induced pulmonary fibrosis. Our study has thus established a solid rationale for advancing Gls1 inhibitors, particularly CB-839, to the next stage of testing in the treatment of this disease. [ABSTRACT FROM AUTHOR]

Tourism firms using visual social media marketing are struggling with its implementation, specifically in formulating engagement-based visual message strategies. Yet, creating such appealing posts can lead to positive brand and financial outcomes. Humour has been identified as a potent tool for social media communication, given its capability to develop social interactions. Yet, how humour works on social media is not well understood – specifically its visual form. Treating humour as a symbolic resource, this study adopted a compound content analysis-semiotic analysis to identify visual content and its symbolic meaning embedded in destination marketing organization (DMO)’s social media posts. 200 Sina Weibo posts containing humour images initiated by 5 Chinese provincial DMOs were collected. The results show 6 types of humour content and 6 types of symbolic meaning – none of which are product related. This study advances the tourism literature and humour theory, and offers tourism firms a holistic view of how to fully leverage social media-based visual humour to achieve consumer reach and engagement. [ABSTRACT FROM AUTHOR]

The Belle II experiment at SuperKEKB e + / e − collider, Japan, is aiming at exploring flavor physics in high intensity frontier. The target instantaneous luminosity of SuperKEKB is at 8 × 1 0 3 5 s − 1 cm − 2 , which is 40 times higher than that at KEKB. The renovated Belle II detectors around the interaction point are expected to collect 5 0 ab − 1 data within 7 years. This gives high data statistics for precision measurements and probing new physics in rare decay studies. The Belle II experiment has successfully recorded the first collision events at SuperKEKB in April 2018, and is ready for physics data taking. This paper will cover the current status of Belle II and highlight its prospects on flavor physics. [ABSTRACT FROM AUTHOR]

Previous studies have shown that intermittent hypobaric hypoxia (IH) preconditioning protected neurons survival from brain ischemia. However, the mechanism remains to be elucidated. The present study explored the role of nitric oxide (NO) in the process by measuring the expression of NO synthase (NOS) and NO levels. Male Wistar rats (100) were randomly assigned into four groups: sham group, IH + sham group, ischemia group and IH + ischemia group. Rats for IH preconditioning were exposed to hypobaric hypoxia mimicking 5000 m high-altitude (PB = 404 mmHg, PO2 = 84 mmHg) 6 h/day, once daily for 28 days. Global brain ischemia was established by four-vessel occlusion that has been created by Pulsinelli. Rats were sacrificed at 7th day after the ischemia for neuropathological evaluation by thionin stain. In addition, the expression of neuronal NOS (nNOS), inducible NOS (iNOS), and NO content in the hippocampal CA1 subfield were measured at 2nd day and 7th day after the ischemia. Results revealed that global brain ischemia engendered delayed neuronal death (DND), both nNOS and iNOS expression up-regulated, and NO content increased in the hippocampal CA1 subfield. IH preconditioning reduced neuronal injury induced by the ischemia, and prevented the up-regulation of NOS expression and NO production. In addition, L-NAME + ischemia group was designed to detect whether depressing NO production could alleviate the DND. Pre-administration of L-NAME alleviated DND induced by the ischemia. These results suggest that IH preconditioning plays a protective role by inhibiting the over expression of NOS and NO content after brain ischemia. [ABSTRACT FROM AUTHOR]

Sulbactam is an atypical β-lactam medication and reported to be neuroprotective by up-regulating glial glutamate transporter-1 (GLT-1) in rats. The present study was undertaken to study the role of p38 MAPK signal pathway in sulbactam induced up-regulation of GLT-1 expression in astrocytes and anti-ischemic effect. Neuron-astrocyte co-cultures and astrocyte cultures from neonatal Wistar rats were used. Cerebral ischemia was mimicked by oxygen-glucose deprivation (OGD). Hoechst (HO)/propidium iodide (PI) double fluorescence staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay were used to evaluate neuronal death and cell viability, respectively. Immunocytochemistry and Western blot were used to detect protein expressions. Sulbactam pre-incubation significantly and dose-dependently prevented neuronal death and decline in cell viability induced by OGD in neuron-astrocyte co-cultures, and upregulated GLT-1 expression in astrocyte cultures endured OGD, which suggested that sulbactam might protect neurons against OGD by up-regulating astrocytic GLT-1 expression. It was further shown that the phosphorylated-p38 MAPK expression in astrocytes was up-regulated after the sulbactam pre-incubation and this up-regulation was moderate in amplitude. Especially, the time course of the up-regulation of phosphorylated-p38 MAPK was obviously earlier than that of GLT-1, which suggested possibility that p38 MAPK might be an upstream signal for GLT-1 up-regulation induced by sulbactam. We further found that SB203580, the specific inhibitor of p38 MAPK, dose-dependently inhibited the GLT-1 up-regulation induced by sulbactam either in non- or OGD-treated astrocytes and the protective effect of sulbactam on co-cultured neurons against OGD. Taken together, it might be concluded that sulbactam protects cerebral neurons against OGD by up-regulating astrocytic GLT-1 expression via p38 MAPK signal pathway. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming has been intrinsically linked to macrophage activation. Alveolar macrophages are known to play an important role in the pathogenesis of pulmonary fibrosis. However, systematic characterization of expression profile in these cells is still lacking. Furthermore, main metabolic programs and their regulation of cellular phenotype are completely unknown. In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis. We found that alveolar macrophages from both bleomycin and active TGF-β1-induced fi- brotic mouse lungs demonstrated a primarily profibrotic M2-like profile that was distinct from the well-defined M1 or any of the M2 subtypes. More importantly, we found that fibrotic lung alveolar macrophages assumed augmented glycolysis, which was likely attributed to enhanced expression of multiple key glycolytic mediators. We also found that fatty acid oxidation was upregulated in these cells. However, the profibrotic M2-like profile of fibrotic lung alveolar macrophages was not dependent on fatty acid oxidation and synthesis or lipolysis, but instead on glycolysis, in contrast to the typical IL-4-induced macrophages M(IL-4). Additionally, glutaminolysis, a key metabolic program that has been implicated in numerous pathologies, was not required for the profibrotic M2-like phenotype of these macrophages. In summary, our study identifies a unique expression and metabolic profile in alveolar macrophages from fibrotic lungs and suggests glycolytic inhibition as an effective antifibrotic strategy in treating lung fibrosis. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the short-term efficacy of concurrent chemoradiotherapy (CCRT) in primary fallopian tube carcinoma (PFTC) using magnetic resonance diffusion-weighted imaging (MR-DWI). Patients and Methods: Total abdominal irradiation was performed for 61 PFTC patients after surgery, and paclitaxel and carboplatin were used for CCRT. According to the response evaluation criteria in solid tumors (RECIST1.1), patients were divided into a sensitive (n = 36) and a resistant group (n = 25). Pearson correlation analysis was conducted to assess the correlations of tumor regression rate with apparent diffusion coefficient (ADC)pre, ADCpost, and ΔADCpost. The efficacy of CCRT in PFTC using MR-DWI was evaluated by ROC curve, logistic regression analysis, Kaplan-Meier survival curve, and Cox regression model. Results: The ADCpre in both the sensitive and the resistant group was negatively associated with the tumor regression rate (r = -0.508), while the ADCpost (r = 0.454) and ΔADCpost (r = 0.769) were positively associated with the tumor regression rate (all p < 0.05). Histopathological type, FIGO stage, lymphatic metastasis, tumor regression rate, ADCpre, ADCpost, and ΔADCpost were confirmed as key factors for CCRT in PFTC (all p < 0.05). Conclusion: Our retrospective study demonstrates the predictive value of MR-DWI in CCRT for PFTC patients. [ABSTRACT FROM AUTHOR]

It is not yet clear whether there is any difference in using remote sensing data of different spatial resolutions and filtering methods to improve the above-ground biomass (AGB) estimation accuracy of alpine meadow grassland. In this study, field measurements of AGB and spectral data at Sangke Town, Gansu Province, China, in three years (2013-2015) are combined to construct AGB estimation models of alpine meadow grassland based on these different remotely-sensed NDVI data: MODIS, HJ-1B CCD of China and Landsat 8 OLI (denoted as NDVIMOD, NDVICCD and NDVIOLI, respectively). This study aims to investigate the estimation errors of AGB from the three satellite sensors, to examine the influence of different filtering methods on MODIS NDVI for the estimation accuracy of AGB and to evaluate the feasibility of large-scale models applied to a small area. The results showed that: (1) filtering the MODIS NDVI using the Savitzky-Golay (SG), logistic and Gaussian approaches can reduce the AGB estimation error; in particular, the SG method performs the best, with the smallest errors at both the sample plot scale (250 m × 250 m) and the entire study area (33.9% and 34.9%, respectively); (2) the optimum estimation model of grassland AGB in the study area is the exponential model based on NDVIOLI, with estimation errors of 29.1% and 30.7% at the sample plot and the study area scales, respectively; and (3) the estimation errors of grassland AGB models previously constructed at different spatial scales (the Tibetan Plateau, Gannan Prefecture and Xiahe County) are higher than those directly constructed based on the small area of this study by 11.9%-36.4% and 5.3%-29.6% at the sample plot and study area scales, respectively. This study presents an improved monitoring algorithm of alpine natural grassland AGB estimation and provides a clear direction for future improvement of the grassland AGB estimation and grassland productivity from remote sensing technology. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis is a well-known age-related disease. However, much less recognized has been the aging associated pathogenesis of this disorder. As we and others previously showed that dysregulation of micro-RNAs (miRNAs) was an important mechanism involved in pulmonary fibrosis, the role of these molecules in this pathology in the aged population has not been investigated (Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, Thannickal VJ, Cardoso WV, Lü J. Am J Respir Cell Mol Biol 45: 287–294, 2011; Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E. J Exp Med 207: 1589–1597, 2010; Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, Richards T, Selman M, Watkins SC, Pardo A, Ben-Yehudah A, Bouros D, Eickelberg O, Ray P, Benos PV, Kaminski N. Am J Respir Crit Care Med 182: 220–229, 2010). In this study, by using a lung fibrosis model established in old mice, we found that ablation of miR-34a protected aged animals from developing experimental lung fibrosis. miR-34a was upregulated in lung epithelial cells, but not in lung fibroblasts of aged mice, and miR-34a expression was further increased in epithelial cells of the fibrotic lungs of these old animals. We found that miR-34a induced dysfunctions in alveolar epithelial cells (AECs), as evidenced by increased cellular senescence and apoptosis and mitochondrial aberrations. More importantly, these abnormalities were attenuated in AECs of the fibrotic lungs of aged miR-34a−/− mice. We found that miR-34a targeted Sirt1, a master anti-aging regulator, and two key cell cycle modulators, E2F3 and cyclin E2, in lung epithelial cells, and the repression of these targets was relieved in miR-34a-deficient AECs. In summary, our data suggest that elevated AEC miR-34a plays a critical role in the pathogenesis of pulmonary fibrosis in the aged population. Our study also indicates miR-34a to be a more precise miRNA target for treating this disease that overwhelmingly affects people of advanced age. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are crucial regulatory molecules for adipogenesis. They contribute to the controlling of proliferation and differentiation of preadipocytes. Previous studies revealed an important role of miR-429 in cell invasion, migration, and apoptosis. Our previous work has shown that the expression of miR-429 in subcutaneous fat can be observed in newly born (3-day-old) Rongchang piglets rather than their adult counterparts (180-day-old). This expression pattern suggests that miR-429 might be functionally related to postnatal adipogenesis. However, we currently lack a mechanistic understanding of miR-429 within the context of preadipocyte differentiation. In this study, we investigated the function of miR-429 in porcine subcutaneous and intramuscular preadipocyte proliferation and differentiation. In our porcine preadipocyte differentiation model, miR-429 expression decreased remarkably upon adipogenic induction. Overexpression of miR-429 notably down-regulated the expression of adipogenic marker genes: PPARγ, aP2, FAS and impaired the triglyceride accumulation, while the expression of lipolytic gene ATGL was not affected. In addition, we observed that miR-429 significantly promoted the proliferation of porcine preadipocytes. We also found that miR-429 could directly bind to the 3'-UTRs of KLF9 and p27, which have been well documented to promote preadipocyte differentiation and repress cell cycle progression. Taken together, our data support a novel role of miR-429 in regulating porcine preadipocyte differentiation and proliferation, and KLF9 and p27 are potent targets of miR-429 during these processes. [ABSTRACT FROM AUTHOR]

Herpesviruses (HVs) can cause asymptomatic, benign, or fatal infections in a variety of animal species. However, the prevalence and phylogenetic characteristics of HVs in rodents and shrews in China are poorly understood. We thus performed a molecular detection and phylogenetic analysis of rat and shrew HVs in southern China between 2012 and 2014. Seventeen (6.7%) of 255 rectal swab specimens from rats and six (6.7%) of 90 rectal swab specimens from shrews tested positive for HVs. Phylogenetic analysis revealed that rodent and shrew HVs detected in this study were species specific, clustering in the Betaherpesvirinae and Gammaherpesvirinae clade. Novel Macavirus was detected in Rattus norvegicus (RN/13YX52/24 and RN/ 14HC50) and gammaherpesviruses in Suncus murinus (SM/14BY7/16/20/97/99/106).These findings have contributed to our understanding of the taxonomy, phylogeny, and biology of HVs. [ABSTRACT FROM AUTHOR]

To capture the impact of spatial heterogeneity of environment and available resource of the public health system on the persistence and extinction of the infectious disease, a simplified spatial SIS reaction-diffusion model with allocation and use efficiency of the medical resource is proposed. A nonlinear space dependent recovery rate is introduced to model impact of available public health resource on the transmission dynamics of the disease. The basic reproduction numbers associated with the diseases in the spatial setting are defined, and then the low, moderate and high risks of the environment are classified. Our results show that the complicated dynamical behaviors of the system are induced by the variation of the use efficiency of medical resources, which suggests that maintaining appropriate number of public health resources and well management are important to control and prevent the temporal-spatial spreading of the infectious disease. The numerical simulations are presented to illustrate the impact of the use efficiency of medical resources on the control of the spreading of infectious disease. [ABSTRACT FROM AUTHOR]

Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) catalyzes the conversion of free cholesterol (FC) to cholesterol ester. The human ACAT1 gene P1 promoter has been cloned. However, the activity and specificity of the ACAT1 gene P1 promoter in diverse cell types remains unclear. The P1 promoter fragment was digested with KpnI/XhoI from a P1 promoter cloning vector, and was subcloned into the multiple cloning site of the Firefly luciferase vector pGL3-Enhancer to obtain the construct P1E-1. According to the analysis of biological information, the P1E-1 plasmid was used to generate deletions of the ACAT1 gene P1 promoter with varying 5' ends and an identical 3' end at +65 by polymerase chain reaction (PCR). All the 5'-deletion constructs of the P1 promoter were identified by PCR, restriction enzyme digestion mapping and DNA sequencing. The transcriptional activity of each construct was detected after transient transfection into THP-1, HepG2, HEK293 and Hela cells using DEAE-dextran and Lipofectamine 2000 liposome transfection reagent. Results showed that the transcriptional activity of the ACAT1 gene P1 promoter and deletions of P1 promoter in THP-1 and HepG2 cells was higher than that in HEK293 and HeLa cells. Moreover, the transcriptional activity of P1E-9 was higher compared with those of other deletions in THP-1, HepG2, HEK293 and HeLa cells. These findings indicate that the transcriptional activity of the P1 promoter and the effects of deletions vary with different cell lines. Thus, the P1 promoter may drive ACAT1 gene expression with cell-type specificity. In addition, the core sequence of ACAT1 gene P1 promoter was suggested to be between -125 and +65 bp. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the apoptotic effect and molecular mechanisms of gecko peptides mixture (GPM) on the human liver carcinoma HepG2 cell line in vitro. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was performed to identify the dose- (0.10, 0.15, 0.20, 0.25 and 0.30 mg/ml) and time-dependent (24, 48 and 72 h) inhibitory effect of GPM on HepG2 cells and their proliferation. Hoechst 33258 staining was carried out to detect the nuclear change coupled with apoptosis induced by GPM. Western blotting was used to evaluate apoptosis-related protein expression changes induced by GPM, including caspase, cytochrome c (Cyt c) and apoptosis-inducing factor (AIF). MTT results showed that GPM significantly inhibited the proliferation of HepG2 cells in a dose- and time-dependent manner. Hoechst 33258 staining demonstrated that GPM induced typical apoptotic morphological changes, while western blotting analysis revealed that GPM increased caspase-3, caspase-9, Cyt c and AIF protein expression levels in HepG2 cells treated with 0.06 or 0.08 mg/ml for 24 h. In conclusion, GPM could induce apoptosis by activating the intrinsic mitochondrial apoptotic pathways. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is amajor risk factor for type 2 diabetes and metabolic syndrome. However, accurately differentiating nonalcoholic steatohepatitis (NASH) from hepatosteatosis remains a clinical challenge. We identified a critical transition stage (termed pre-NASH) during the progression from hepatosteatosis to NASH in a mouse model of high fat-induced NAFLD, using lipidomics and a mathematical model termed dynamic network biomarkers (DNB).Different from the conventional biomarker approach based on the abundance of molecular expressions, the DNB model exploits collective fluctuations and correlations of different metabolites at a network level. We found that the correlations between the blood and liver lipid species drastically decreased after the transition from steatosis to NASH, which may account for the current difficulty in differentiating NASH from steatosis based on blood lipids. Furthermore, most DNB members in the blood circulation, especially for triacylglycerol (TAG), are also identified in the liver during the disease progression, suggesting a potential clinical application of DNB to diagnose NASH based on blood lipids. We further identified metabolic pathways responsible for this transition. Our study suggests that the transition from steatosis to NASH is not smooth and the existence of pre-NASH may be partially responsible for the current clinical limitations to diagnose NASH. If validated in humans, our study will open a new avenue to reliably diagnose pre-NASH and achieve early intervention of NAFLD. [ABSTRACT FROM AUTHOR]

In this paper, centrifugal spinning technology and calcination were used to prepare SnO ultra-fine fibers. Several parameters such as the concentration of SnCl, rotational speed, and diameter of the spinneret were discussed to determine the optimum spinning conditions. The obtained as-spun fibers and SnO ultra-fine fibers were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), FT-IR spectra and X-ray photoelectron spectroscopy (XPS), and the low-temperature gas-sensing properties of the SnO sample were systematically investigated. The results proved that the SnO sample had good sensitivity for a variety of measured gases at low temperature. Among these, the SnO sensor showed the highest sensitivity for HCl gas, and the sensitivity for ethanol gas increased rapidly when its concentration exceeded 1200 ppm. Our results demonstrated that the centrifugal spinning could be a potential approach for preparing the SnO gas sensor. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]