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Triglyceride (TAG) deposition in the liver is associated with metabolic disorders. In lower vertebrate, the propensity to accumulate hepatic TAG varies widely among fish species. Diacylglycerol acyltransferases (DGAT1 and DGAT2) are major enzymes for TAG synthesis. Here we show that large yellow croaker (Larimichthys crocea) has significantly higher hepatic TAG level than that in rainbow trout (Oncorhynchus mykiss) fed with same diet. Hepatic expression of DGATs genes in croaker is markedly higher compared with trout under physiological condition. Meanwhile, DGAT1 and DGAT2 in both croaker and trout are required for TAG synthesis and lipid droplet formation in vitro. Furthermore, oleic acid treatment increases DGAT1 expression in croaker hepatocytes rather than in trout and has no significant difference in DGAT2 expression in two fish species. Finally, effects of various transcription factors on croaker and trout DGAT1 promoter are studied. We find that DGAT1 is a target gene of the transcription factor CREBH in croaker rather than in trout. Overall, hepatic expression and transcriptional regulation of DGATs display significant species differences between croaker and trout with distinct hepatic triglyceride deposition, which bring new perspectives on the use of fish models for studying hepatic TAG deposition. Two diacylglycerol acyltransferases were shown to be differently regulated in large yellow croaker and rainbow trout. While DGAT1 is increased upon oleic acid treatment more in croaker than in trout, DGAT2 showed no significant expression difference. [ABSTRACT FROM AUTHOR]

We present a novel high-quality vectorized modeling pipeline for large-scale scenes. With a reconstructed dense point cloud and its corresponding multi-view source images and camera parameters as input, our system can efficiently reconstruct a geometrically complete and detail-preserved vectorized model. Unlike most existing planar shape assembling methods which cannot handle large-scale vectorized modeling well due to the limitation of memory and computation, we can achieve complete high-quality vectorized modeling for complicated large-scale scenes in a time and memory efficient way. Our pipeline first carries out a 3D semantic segmentation on the dense point cloud, by performing 2D semantic labeling on the source images with a semantic segmentation network and fusing the 2D semantic labels into the point cloud. According to the fused dense 3D semantic labels, we then divide the scene into main structure including the grounds, walls and ceilings, and isolated objects that do not belong to the main structure. After the scene division completes, vectorized modeling is performed successively on the main structure and isolated objects to extract their polygonal models respectively instead of vectorizing the whole scene, to improve both time and memory efficiencies. Additionally, the previously vectorized main polygonal structures are used as priors to refine the segmentation and guide the vectorization of the objects to ensure the geometrical completeness and topological consistency of the entire vectorized model. Especially, during the vectorization procedure, a well designed binary space partition tree is designed to better slice the space so that high-quality polygonal mesh with more geometric details can be reconstructed with both time and memory efficiencies. Experiments with quantitative and qualitative evaluations on large-scale scenes demonstrate the accuracy and efficiency of the proposed vectorization pipeline. We also compare our method with state-of-the-art planar shape reconstruction methods to show its effectiveness in reconstructing large-scale vectorized models. [ABSTRACT FROM AUTHOR]

Liposome‐mediated plasmid DNA (pDNA) transfection is a relatively efficient transfection method that depends highly on actively dividing cells. However, numerous fish cells are mitotically inactive under in vitro culture conditions, thus limiting the application of liposome‐mediated pDNA transfection. Liposome‐mediated mRNA transfection is an attractive alternative in post‐mitotic cells because it eliminates the transfer of genes into the nucleus and therefore is independent of cell proliferation. In this study, pDNA is compared with mRNA encoding biomarker proteins (enhanced green fluorescent protein [eGFP] and luciferase) mediated by cationic liposome in zebrafish embryo fibroblast cell line (ZF4), with or without proliferation restriction, and in mitotically inactive turbot liver primary cells. The results indicated that mRNA encoding eGFP exerted much higher transfection efficiency than pDNA in ZF4 cells. Moreover, mRNA encoding eGFP was detected and disappeared sooner than pDNA. Chemiluminescence of the biomarker protein luciferase showed that liposome‐mediated mRNA transfection translated about threefold more protein without proliferation restriction and about tenfold more protein with proliferation restriction than pDNA transfection. In turbot liver cells, mRNA induced higher transfection efficiency and greater luciferase protein expression than pDNA. Greater PPARα expression and expression of downstream target genes were induced by mRNA rather than by pDNA transfection. In conclusion, cationic liposome‐mediated mRNA is an alternative for fish cell transfection due to higher transfection efficiency and protein expression levels and faster translation onset. [ABSTRACT FROM AUTHOR]

In the present study, farnesoid X receptor (FXR) was cloned and characterized from liver of large yellow croaker ( L crocea ) and the effects of dietary chenodeoxycholic acid (CDCA), a nature ligand of FXR, on the inflammatory genes expression in the intestine and spleen of large yellow croaker were investigated. Multiple alignments showed that FXR of large yellow croaker contained highly conserved DNA-binding domain and ligand binding domain compared with other species. The subcellular localization analysis showed that FXR-GFP fusion protein could target to the nucleus in HEK 293 t. The tissue specific results demonstrated that FXR was highly expressed in liver, intestine and kidney of large yellow croaker. In addition, dietary soybean oil decreased the expression of FXR and IL-10 and significantly increased the expression of the pro-inflammatory genes in the intestine or spleen, such as TNFα, COX-2, IL-1β, IL-6, while the supplementation of CDCA could partly reverse these effects. These results suggested that the supplementation of CDCA may relieve the inflammation of intestine and spleen in large yellow croaker via the activation of FXR. [ABSTRACT FROM AUTHOR]

Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is an alternative therapeutic strategy for treating fatty liver in mammals. However, the effects of DGAT1 inhibition in fish remain unclear. Here, we found that inhibition of DGAT1 significantly reduced triglyceride (TAG) levels and lipid droplet formation in hepatocytes of large yellow croaker (Larimichthys crocea). Meanwhile, there were no significant effects of DGAT1 specific inhibitors on the cell viability. In addition, inactivation of DGAT1 significantly suppressed the mRNA expression of sterol regulatory element binding protein 1 (srebp1) and fatty acid synthase (fas), and promoted carnitine palmitoyltransferase 1 α (cpt1α) mRNA expression in croaker hepatocytes. After treated with DGAT1 specific inhibitor, expression of catalase (cat) was significantly decreased in hepatocytes under the condition of lipid overload, while glutathione peroxidase (gpx) was significantly increased. However, inhibition of DGAT1 had no significant effects on genes expression related to inflammatory response in croaker hepatocytes. Finally, injection of DGAT1 specific inhibitor into large yellow croaker juveniles showed statistically significant decrease in hepatic TAG contents induced by high fat diet. These results showed that DGAT1 inhibition could significantly alleviate the abnormal deposition of TAG in liver induced by lipid overload in large yellow croaker, which may provide novel therapeutic target for improving the quality control of fish. • DGAT1 inhibition significantly decreased lipid contents induced by lipid overload in hepatocytes of large yellow croaker. • DGAT1 inhibition had no significant effects on the cell viability and inflammatory response in croaker hepatocytes. • Inhibition of DGAT1 significantly reduced fatty acid synthesis and promoted β-oxidation under lipid overload. [ABSTRACT FROM AUTHOR]

Abstract: The hippocampus is involved in anxiety as well as spatial memory formation and is sexually dimorphic. Female rats typically show less anxiety in elevated plus maze procedure (EPM), a standard animal model of anxiety. Many intracellular proteins, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 and the cyclic AMP response element-binding protein (CREB), in hippocampus contribute to memory formation. However, less is known about the roles for hippocampal GluR1 and CREB in anxiety. We examined behavior in EPM in male and female rats and obtained hippocampal tissue samples to determine levels of GluR1 and CREB with western blots. EPM results showed that female rats exhibited less anxiety-like behaviors than male rats. Further, behaviors in EPM were significantly correlated with hippocampal GluR1 levels, but not with CREB. Yet, both proteins showed sex differences with lower levels in female rats. These data not only suggest some potential bases for sex differences in behaviors to which the hippocampus contributes but demonstrate that there is a strong association between hippocampal GluR1 levels and anxiety as assessed with EPM. [Copyright &y& Elsevier]

Background: Although dietary DHA alleviates Toll-like receptor (TLR)-associated chronic inflammation in fish, the underlying mechanism is not well understood.Objectives: This study aimed to explore the role of Tlr22 in the innate immunity of large yellow croaker and investigate the anti-inflammatory effects of DHA on Tlr22-triggered inflammation.Methods: Head kidney-derived macrophages of croaker and HEK293T cells were or were not pretreated with 100 μM DHA for 10 h prior to polyinosinic-polycytidylic acid (poly I:C) stimulation. We executed qRT-PCR, immunoblotting, and lipidomic analysis to examine the impact of DHA on Tlr22-triggered inflammation and membrane lipid composition. In vivo, croakers (12.03 ± 0.05 g) were fed diets containing 0.2% [control (Ctrl)], 0.8%, and 1.6% DHA for 8 wk before injection with poly I:C. Inflammatory genes expression and rafts-related lipids and protein expression were measured in the head kidney. Data were analyzed by ANOVA or Student t test.Results: The activation of Tlr22 by poly I:C induced inflammation, and DHA diminished Tlr22-targeted inflammatory gene expression by 56-73% (P ≤ 0.05). DHA reduced membrane sphingomyelin (SM) and SFA-containing phosphatidylcholine (SFA-PC) contents, as well as lipid raft marker caveolin 1 amounts. Furthermore, lipid raft disruption suppressed Tlr22-induced Nf-κb and interferon h activation and p65 nuclear translocation. In vivo, expression of Tlr22 target inflammatory genes was 32-64% lower in the 1.6% DHA group than in the Ctrl group upon poly I:C injection (P ≤ 0.05). Also, the 1.6% DHA group showed a reduction in membrane SM and SFA-PC contents, accompanied by a decrease in caveolin 1 amounts, compared with the Ctrl group.Conclusions: The activation of Tlr22 signaling depends on lipid rafts, and DHA ameliorates the Tlr22-triggered inflammation in both head kidney and head kidney-derived macrophages of croaker partially by altering membrane SMs and SFA-PCs that are required for lipid raft organization. [ABSTRACT FROM AUTHOR]

The precise determination of atomic position of materials is critical for understanding the relationship between structure and properties, especially for compounds with light elements of boron and single or multiple transition metals. In this work, the single crystal X-ray diffraction is employed to analyze the atomic positions of Co2MoB4 and Fe2MoB4 with a Ta3B4-type structure, and it is found that the lengths of B-B bonds connecting the two zig-zag boron chains are 1.86 Å and 1.87 Å, but previously unreported 1.4 Å. Co and Fe atoms occupy the same crystallographic position in lattice for the doped samples and the valence is close to the metal itself, and Co/Fe K-edge X-ray Absorption Fine Structure(XAFS) spectra of borides with different ratios of Co to Fe are collected to detect the local environment and chemical valence of Co and Fe. Vickers hardness and nano indentation measurements are performed, together with the Density Functional Theory (DFT) calculations. Finally, Co2MoB4 possess better thermal stability than Fe2MoB4 evaluated by Thermogravimetric Differential Thermal Analysis (TG-DTA) results. [ABSTRACT FROM AUTHOR]

The long noncoding RNA growth arrest-specific 5 (lncRNA Gas5) is implicated in various kidney diseases. In this study, we investigated the lncRNA Gas5 expression profile and its critical role as a potential biomarker in the progression of chronic kidney disease. Subsequently, we assessed the effect of lncRNA Gas5 deletion on renal fibrosis induced by unilateral ureteral obstruction (UUO). The results indicated that loss of lncRNA Gas5 exacerbates UUO-induced renal injury and extracellular matrix deposition. Notably, the deletion of lncRNA Gas5 had a similar effect on control mice. The fibrogenic phenotype observed in mice lacking lncRNA Gas5 correlates with peroxisome proliferator-activated receptor (PPAR) signaling pathway activation and aberrant cytokine and chemokine reprogramming. Single-cell RNA sequencing analysis revealed key transcriptomic features of fibroblasts after Gas5 deletion, revealing heterogeneous cellular states suggestive of a propensity for renal fibrosis. Our findings indicate that lncRNA Gas5 regulates the differentiation and activation of immune cells and the transcription of key genes in the PPAR signaling pathway. These data offer novel insights into the involvement of lncRNA Gas5 in renal fibrosis, potentially paving the way for innovative diagnostic and therapeutic targets. • lncRNA Gas5 is a potential biomarker in chronic kidney disease. • Loss of lncRNA Gas5 exacerbates renal injury and extracellular matrix deposition in UUO-induced renal fibrosis. • We explain the role of lncRNA Gas5 in renal fibrosis based on the integration of scRNA-Seq and Bulk RNA-Seq analysis for the first time. • lncRNA Gas5 could regulate the differentiation and activation of immune cells and transcription of key genes in PPAR signal pathway. [ABSTRACT FROM AUTHOR]

Xiang, X. and Li, Q., 2020. Water resources vulnerability assessment and adaptive management based on projection pursuit model. In: Yang, Y.; Mi, C.; Zhao, L., and Lam, S. (eds.), Global Topics and New Trends in Coastal Research: Port, Coastal and Ocean Engineering. Journal of Coastal Research, Special Issue No. 103, pp. 431–435. Coconut Creek (Florida), ISSN 0749-0208. As the global climate continues to change, the demand for water resources in human society has been continuously expanding. Water shortages, frequent water pollution and natural disasters have become more and more serious. The issue of water resources security has aroused widespread concern in society. At present, the vulnerability of water resources is the main criterion for measuring the security status of water resources. The vulnerability assessment of water resources mainly studies the current vulnerability of water resources in the region and can reflect the degree of damage to water resources. The adaptive management is to improve the safety of water resources and optimize the future choice of water resources in the study area. Therefore, the assessment of water resources vulnerability combined with adaptive management is an important means to improve the safety of water resources. This article first defines the vulnerability and adaptive management of water resources in the basin based on the existing research results and the particularity of the water resources in the basin, and elaborate their connotations in detail. A water resources vulnerability assessment system based on DPSIR conceptual model is proposed. Secondly, by analyzing the influencing factors of water resources in the river basin, using the projection pursuit model and accelerated genetic algorithm (RAGA), a functional model of water vulnerability assessment based on RAGA projection pursuit was established. Finally, taking Hubei Province as an example, an empirical analysis was conducted to evaluate the vulnerability of water resources in Hubei Province, and a strategy for adaptive management of water resources was proposed. [ABSTRACT FROM AUTHOR]

Background: Overwhelming evidence suggests that increasing alcohol taxes is an effective strategy for curbing alcohol consumption. However, research on the effects of such strategies in low- and middle-income nations is limited. Objective: The aim is to explore the temporal effect of alcohol tax policy in China. Methods: We employ interrupted time series analysis to investigate the temporal effects of tax policy changes on alcohol consumption and related consequences in Mainland China from 1961 to 2019. The study population, the total population of mainland region of China, aged more than 15 years. Results: The results show that the volume tax policy, which was announced in 2000 and implemented in 2001, led to an immediate reduction in the alcohol consumption (coefficient = −0.429, p <.001). Following the implementation of higher alcohol taxes in 1998 and 2001, the prevalence of alcohol use disorders (AUDs) and related years lived with disability (YLDs) gradually decreased. The relaxation of tax policy in 2006 led to a significant increase in alcohol consumption, both immediately (coefficient = 0.406, p <.001) and in the middle term (coefficient = 0.495, p <.001), as well as contribute to an immediate or medium term significant increase in the prevalence of AUDs (coefficient = 0.038, p =.010; coefficient = 0.032, p <.001) and YLDs (coefficient = 4.363, p =.001; coefficient = 4.226, p <.001). Conclusion: This study demonstrates that changes in alcohol consumption and related consequences (increase or decrease) have followed corresponding changes in alcohol tax policies (easing or tightening), indicating that increasing alcohol taxes can be an effective strategy in China for controlling alcohol consumption and related harms. [ABSTRACT FROM AUTHOR]

Cobalt plays a crucial role in the systematic understanding of magnetic phenomena originating from 3d transition metals. Particularly, recent studies of Co systems doped with nitrogen (Co–N) have attracted a lot of attention for applications in spintronics and high-density magnetic data-storage devices. In this work, in order to understand the effect of interstitial incorporation of N atoms into a face-center cubic (fcc) Co lattice, we have studied the structure, elastic, and magnetic properties of spherical-like bulk CoNx (x = 0.06–0.07) samples. These samples were synthesized through a high-pressure solid-state metathesis reaction. We demonstrate that the use of a certain concentration of interstitial N atoms tends to stabilize the lattice of fcc Co at ambient conditions. Such a stabilizing effect is found to originate from the covalent bond between Co atoms and N atoms. High-pressure synchrotron x-ray diffraction indicates that the incorporation of N atoms into fcc Co has little effect on the elastic property up to 27.2 GPa with a bulk modulus (B0) of 200 GPa; the latter is found to be comparable to that of fcc and hcp Co. CoNx samples exhibited ferromagnetic behavior with saturation magnetization up to 153.55 emu/g and coercivity of 16.25 Oe. The introduction of small amounts of nitrogen in the cobalt matrix was found to induce a significant decrease in the coercive force parameter. [ABSTRACT FROM AUTHOR]

Abstract The shortage of fish oil (FO) leads to the extensive use of vegetable oil (VO) in marine fish diets. High replacement percentage of dietary FO by VO induced pro-inflammatory response of adipose tissue (AT) and liver tissue (LT) in large yellow croaker (Larimichthys crocea). Mammalian studies showed that the secretion of cytokines by AT affected the immune response of LT. To investigate whether or not the inflammation response of LT is related to AT in large yellow croaker, LT and AT cells from fish fed FO diet (FOL and FOA) and VO diet (VOL and VOA) were co-cultured in a trans -well system, which resulted in an assembly of the two cells types sharing the culture medium but being separated by the membrane of the insert. Co-culture of FOL and FOA was selected as the control group (FOL-FOA). Results indicated that, when compared with the control group, the expression of pro-inflammatory genes (toll like receptors [ TLRs ] , tumour necrosis factor α [ TNFα ], interleukin 1β [ IL1β ] , suppressor of cytokine signalling 3 [ SOCS3 ] and cyclooxygenase 2 [ COX2 ]) in FOL was significantly increased in the co-culture group of FOL and VOA (FOL-VOA), while the expression of anti-inflammatory genes (arginase I [ ArgI ] and transforming growth factor β1 [ TGFβ1 ]) in FOL was significantly depressed. On the contrary, a significantly depressed expression of pro-inflammatory genes (TLRs , TNFα , IL1β and COX2) and increased expression of anti-inflammatory genes (interleukin 10 [ IL10 ]) in VOL was observed in the co-culture group of VOL and FOA (VOL-FOA) when compared with the co-culture group of VOL and VOA (VOL-VOA). The change of immune-related gene expressions in LT cells was attributed to nuclear factor κB (NF-κB) signalling since the expression of the p65 protein was observed to show a similar trend to the expression of pro-inflammatory genes. It is speculated that dietary VO increased the secretion of cytokines, which induced pro-inflammatory response in LT cells. These ex vivo results indicate that AT plays a vital role in LT pro-inflammatory response in fish fed VO diet. Highlights • Adipose tissue cells from fish fed vegetable oil diets increased the expression of pro-inflammatory genes but decreased the expression of anti-inflammatory genes of liver tissue cells. • The change of immune-related gene expressions in liver tissue cells was attributed to NF-κB signalling. • Adipose tissue plays a vital role in liver tissue pro-inflammatory response of fish fed vegetable oil diet. [ABSTRACT FROM AUTHOR]

Although it has been nearly 70 years since iron-based catalysts were used to synthesize diamond from graphite at high pressure and high temperature (HPHT), the graphite to diamond transformation mechanism in this process is still a mystery. It is found that the formation of a eutectic melt between carbon and an iron-based catalyst plays a critical role in the graphite to diamond transformation at HPHT. In this work, the eutectic temperature of Fe–Ni–C (diamond and graphite) was determined using the in situ high-pressure temperature measurement (HPTM) and the high-pressure differential thermal analysis (HPDTA) method up to 8 GPa in a large-volume cubic press. The experimental results of XRD, Raman, SEM and XPS indicate that the transformation of graphite to diamond occurs in the Fe–Ni–C eutectic melt: the C–C bonds in graphite are broken in the eutectic melt, and the free carbon atoms in the melt form sp3 bond states in the thermodynamically stable region of diamond. In this process, the role of iron-based catalysts is to reduce the environmental conditions, in which the C–C bonds in graphite are destroyed, and to make the carbon atoms that are separated from the sp2 bond state form the sp3 bond state in the diamond P–T phase stable region. [ABSTRACT FROM AUTHOR]

Objective:To understand the attitudes among medical students in China toward different medical specialties and to find the factors that influenced their choice of career in psychiatry. Methods:A questionnaire was developed and administered to 287 medical students at the Xiangya Medical College, Central South University in Changsha, China. All the students were asked to rate the importance of five possible factors in choosing a specialty as a vocation: the ability to help patients, interesting and challenging work, lifestyle factors, financial reward, and prestige. Results:Students reported negative perceptions of psychiatry in regard to all five possible factors that were important in choosing a specialty as a vocation, especially in financial reward and prestige. Conclusions:Medical students in China have negative attitudes toward psychiatry as a career. Some negative beliefs about psychiatry seem to be due to erroneous or insufficient knowledge that could be corrected during the course of medical education. Some negative attitudes were unlikely to be completely changed until the mental health system in China improves. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cell fate and angiogenesis, with dysregulation of the signaling axis driving tumorigenesis. Therefore, many studies have targeted FGF/FGFR signaling for cancer therapy and several FGFR inhibitors have promising results in different tumors but treatment efficiency may still be improved. The clinical use of immune checkpoint blockade (ICB) has resulted in sustained remission for patients. Main: Although there is limited data linking FGFR inhibitors and immunotherapy, preclinical research suggest that FGF/FGFR signaling is involved in regulating the tumor microenvironment (TME) including immune cells, vasculogenesis, and epithelial-mesenchymal transition (EMT). This raises the possibility that ICB in combination with FGFR-tyrosine kinase inhibitors (FGFR-TKIs) may be feasible for treatment option for patients with dysregulated FGF/FGFR signaling. Conclusion: Here, we review the role of FGF/FGFR signaling in TME regulation and the potential mechanisms of FGFR-TKI in combination with ICB. In addition, we review clinical data surrounding ICB alone or in combination with FGFR-TKI for the treatment of FGFR-dysregulated tumors, highlighting that FGFR inhibitors may sensitize the response to ICB by impacting various stages of the "cancer-immune cycle". [ABSTRACT FROM AUTHOR]

Background: Large tumor suppressor kinase 1 (LATS1), one of the predominant components of the Hippo pathway, has been characterized as a key player controlling the proliferation and invasion of cancer cells, including gastric cancer (GC) cells. However, the mechanism by which the functional stability of LATS1 is modulated has yet to be elucidated. Methods: Online prediction tools, immunohistochemistry and western blotting assays were used to explore the expression of WW domain-containing E3 ubiquitin ligase 2 (WWP2) in GC cells and tissues. Gain- and loss-of-function assays, as well as rescue experiments were performed to determine the role of the WWP2-LATS1 axis in cell proliferation and invasion. Additionally, the mechanisms involving WWP2 and LATS1 were assessed by coimmunoprecipitation (Co-IP), immunofluorescence, cycloheximide and in vivo ubiquitination assays. Results: Our results demonstrate a specific interaction between LATS1 and WWP2. WWP2 was markedly upregulated and correlated with disease progression and a poor prognosis in GC patients. Moreover, ectopic WWP2 expression facilitated the proliferation, migration and invasion of GC cells. Mechanistically, WWP2 interacts with LATS1, resulting in its ubiquitination and subsequent degradation, leading to increased transcriptional activity of YAP1. Importantly, LATS1 depletion abolished the suppressive effects of WWP2 knockdown on GC cells. Furthermore, WWP2 silencing attenuated tumor growth by regulating the Hippo-YAP1 pathway in vivo. Conclusions: Our results define the WWP2-LATS1 axis as a critical regulatory mechanism of the Hippo-YAP1 pathway that promotes GC development and progression. 4DACTQjHnAfUrjtSe4YKAZ Video Abstract [ABSTRACT FROM AUTHOR]

High-strain-induced microstructural refinement and dislocations are critical for the strengthening of metallic materials; however, this is difficult to achieve in ceramic materials due to their unique bonding characteristics and electronic structure. Here, a series of β -Mo 2 C bulk ceramics are consolidated by the high pressure and high temperature (HPHT) strategy. Our results demonstrate that high strain-induced grain plastic deformation at high pressure produces a lamellar sub-grain structure with high-density dislocations, and that the dislocations at the lath-like grain boundaries eventually evolve into low-angle grain boundaries. The mechanical properties, superconducting behavior, and onset of oxidation of the specimens are investigated. It is found that superconductivity and hardness arise from the high density of states at the Fermi level, while the high intrinsic hardness is attributed to the strong hybridization between Mo-4 d orbitals and C-2 p orbitals. Furthermore, strain-induced defect structure (dislocations and low-angle grain boundaries) mainly mainly enhances the intrinsic structure of β-Mo 2 C. [ABSTRACT FROM AUTHOR]

KN026 is a novel human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody that binds two distinct domains of HER2. We report the safety and efficacy results of the phase 2 trial in patients with advanced HER2-expressing gastric or gastroesophageal junction cancer who failed from at least one prior line of standard treatment. In this open-label, multicentre, phase 2 trial, eligible patients were enrolled in the high-level HER2 cohort or low-level HER2 cohort and assigned to receive KN026 10 mg/kg (once a week), 20 mg/kg (once every two weeks) or 30 mg/kg (once every three weeks) intravenously. The primary end-points were the objective response rate (ORR) and duration of response assessed according to Response Evaluation Criteria in Solid Tumours (version 1.1). Between 17th June 2019 and 23rd August 2021, 45 patients were enrolled and received at least one dose of KN026, including 27 patients in the high-level HER2 cohort, 14 patients in the low-level HER2 cohort and four patients who had no HER2 expression. The ORR in the high-level HER2 cohort was 56% (95% confidence interval [CI] 35%–76%), with a durable response duration of 9.7 months (95% CI 4.2–not evaluable); while for the patients with low-level HER2, the ORR was 14% (95% CI 2%–43%). The most frequent ≥ grade 3 treatment-emergent adverse events were gastrointestinal disorders (five patients, 11%). No drug-related deaths were reported. KN026 showed a favourable safety profile and promising anti-tumour activity. Our results support further studies evaluating KN026 and the combination treatment with other active drugs in patients with advanced gastric or gastroesophageal junction cancer having high-level HER2 expression. • KN026, a new anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody, binds HER2 domains II and IV. • KN026 improved the objective response rate as 2nd-line therapy in patients with HER2 high-level gastric/gastroesophageal junction cancer. • KN026 has a great potential to overcome Trastuzumab resistance. • KN026 demonstrated a favourable safety profile. [ABSTRACT FROM AUTHOR]

It was previously shown that lipid content of the whole larvae body fed the phospholipid (PL)-devoid diet was significantly lower than that of larvae fed PL-supplemented diets ( P < 0.05) (Feng et al., unpublished results). The mechanisms involved remain unclear and were explored from the perspective of fatty acids delivery, uptake, synthesis and oxidation in the present study. Besides, this study was also designed to investigate the effect of dietary PL on antioxidant capacity in large yellow croaker larvae ( Larimichthys crocea ). Triplicate groups of larvae (initial body weight: 3.86 ± 0.24 mg) were fed three isonitrogenous and isolipidic diets with increasing levels of PL (2.53%, 6.32% and 12.7%) eight times daily for 30 days. Results showed that the specific activities of superoxide dismutase and catalase were significantly higher in 12.7% PL group compared to those in 2.53% PL group ( P < 0.05), while an opposite trend was observed for MDA content ( P < 0.05). The specific activity of lipase and the mRNA abundance of fatty acids delivery and uptake-related genes, including lipoprotein lipase, hepatic lipase and fatty acids translocase (cluster of differentiation) were significantly higher in 12.7% PL group than those in 2.52% group ( P < 0.05). Compared to 2.53% PL group, the transcript levels of fatty acid synthase and stearoyl-CoA desaturase I were significantly lower in 6.32% PL group ( P < 0.05), while peroxisome proliferators-activated receptor α, carnitine palmitoyl transferase-I and acyl CoA oxidase mRNA expression levels were significantly higher in 12.7% PL group ( P < 0.05). These results indicated that dietary PL could enhance antioxidant capacity of larvae. Dietary PL might regulate lipid metabolism in large yellow croaker larvae by modulating fatty acids delivery, uptake, synthesis and oxidation at transcriptional level and improved fatty acids delivery and uptake might be responsible for higher body lipid content in 6.32% and 12.7% groups. [ABSTRACT FROM AUTHOR]

Background: Weak correlation between gamma passing rates and dose differences in target volumes and organs at risk (OARs) has been reported in several studies. Evaluation on the differences between planned dose–volume histogram (DVH) and reconstructed DVH from measurement was adopted and incorporated into patient‐specific quality assurance (PSQA). However, it is difficult to develop a methodology allowing the evaluation of errors on DVHs accurately and quickly. Purpose: To develop a DVH‐based pretreatment PSQA for volumetric modulated arc therapy (VMAT) with combined deep learning (DL) and machine learning models to overcome the limitation of conventional gamma index (GI) and improve the efficiency of DVH‐based PSQA. Methods: A DL model with a three‐dimensional squeeze‐and‐excitation residual blocks incorporated into a modified U‐net was developed to predict the measured PSQA DVHs of 208 head‐and‐neck (H&N) cancer patients underwent VMAT between 2018 and 2021 from two hospitals, in which 162 cases was randomly selected for training, 18 for validation, and 28 for testing. After evaluating the differences between treatment planning system (TPS) and PSQA DVHs predicted by DL model with multiple metrics, a pass or fail (PoF) classification model was developed using XGBoost algorithm. Evaluation of domain experts on dose errors between TPS and reconstructed PSQA DVHs was taken as ground truth for PoF classification model training. Results: The prediction model was able to achieve a good agreement between predicted, measured, and TPS doses. Quantitative evaluation demonstrated no significant difference between predicted PSQA dose and measured dose for target and OARs, except for Dmean of PTV6900 (p = 0.001), D50 of PTV6000 (p = 0.014), D2 of PTV5400 (p = 0.009), D50 of left parotid (p = 0.015), and Dmax of left inner ear (p = 0.007). The XGBoost model achieved an area under curves, accuracy, sensitivity, and specificity of 0.89 versus 0.88, 0.89 versus 0.86, 0. 71 versus 0.71, and 0.95 versus 0.91 with measured and predicted PSQA doses, respectively. The agreement between domain experts and the classification model was 86% for 28 test cases. Conclusions: The successful prediction of PSQA doses and classification of PoF for H&N VMAT PSQA indicating that this DVH‐based PSQA method is promising to overcome the limitations of GI and to improve the efficiency and accuracy of VMAT delivery. [ABSTRACT FROM AUTHOR]

Background: Dual inhibition of PD-1/PD-L1 and TGF-β pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701.Methods: This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR).Results: In total, 171 patients were enrolled (dose-escalation: n=17; dose-expansion, n=33; clinical-expansion, n=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4-36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5-73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR.Conclusions: SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration.Trial Registration: ClinicalTrials.gov , NCT03710265. [ABSTRACT FROM AUTHOR]

Some studies have highlighted the crucial role of aversion in addiction treatment. The pathway from the anterior paraventricular thalamus (PVT) to the shell of the nucleus accumbens (NAc) has been reported as an essential regulatory pathway for processing aversion and is also closely associated with substance addiction. However, its impact on alcohol addiction has been relatively underexplored. Therefore, this study focused on the role of the PVT-NAc pathway in the formation and relapse of alcohol addiction-like behaviour, offering a new perspective on the mechanisms of alcohol addiction. The chemogenetic inhibition of the PVT-NAc pathway in male mice resulted in a notable decrease in the establishment of ethanol-induced conditioned place aversion (CPA), and NAc-projecting PVT neurons were recruited due to aversive effects. Conversely, activation of the PVT-NAc pathway considerably impeded the formation of ethanol-induced conditioned place preference (CPP). Furthermore, during the memory reconsolidation phase, activation of this pathway effectively disrupted the animals' preference for alcohol-associated contexts. Whether it was administered urgently 24 h later or after a long-term withdrawal of 10 days, a low dose of alcohol could still not induce the reinstatement of ethanol-induced CPP. Our results demonstrated PVT-NAc circuit processing aversion, which may be one of the neurobiological mechanisms underlying aversive counterconditioning, and highlighted potential targets for inhibiting the development of alcohol addiction-like behaviour and relapse after long-term withdrawal. • Alcohol-induced aversive effects promote recruitment of the PVT-NAc pathway. • Activation of the PVT-NAc pathway inhibits the formation of alcohol reward memories. • Postretrieval activation of the PVT-NAc pathway prevents alcohol-primed relapse. [ABSTRACT FROM AUTHOR]

Fish are the main source of long-chain polyunsaturated fatty acids (LC-PUFA) for human consumption. In the process of evolution via natural selection, adaptation to distinct environments has likely driven changes in the endogenous capacity for LC-PUFA biosynthesis between marine and freshwater fishes. However, the molecular mechanisms underlying adaptive changes in this metabolic pathway are poorly understood. Here, we compared the transcriptional regulation of elongation of very long chain fatty acids protein 5 (Elovl5), which is one of the critical enzymes in LC-PUFA biosynthesis pathway, in marine large yellow croaker (Larimichthys crocea) and freshwater rainbow trout (Oncorhynchus mykiss). Comparative transcriptomic and absolute mRNA quantification analyses revealed that the expression of elovl5 in rainbow trout was markedly higher than that in large yellow croaker. Correspondingly, the number of chromatin accessible areas in the regulatory region of elovl5 in rainbow trout was higher than in large yellow croaker, which revealed that chromatin accessibility in the regulatory region of elovl5 in rainbow trout was higher. Furthermore, the differences in sequence and activity of the elovl5 promoter were observed between rainbow trout and large yellow croaker, and transcription factors including CCAAT/enhancer-binding protein β (CEBPβ), GATA binding protein 3 (GATA3) and upstream stimulatory factor 2 (USF2) displayed different regulatory roles on elovl5 expression between the two species. We propose that changes in the gene regulatory region driven by natural selection likely play a key role in differences in elovl5 expression and the activity of Elovl5, which may influence the LC-PUFA biosynthesis capacities of rainbow trout and large yellow croaker. These findings may also provide opportunities to improve the quality of aquatic products and, consequently, human health. [ABSTRACT FROM AUTHOR]

Background: Cervical adenosquamous carcinoma (ASC) was previously thought to be a subtype of cervical adenocarcinoma, but recent studies have found that the clinical features of the two diseases are different. Moreover, the pathological characteristics, survival, prognosis, and optimal ASC therapy remain unknown. This study aims to retrospectively analyze the postoperative survival of patients with early-stage ASC and to evaluate their condition after treatment with postoperative concurrent chemoradiotherapy (CCRT) and prophylactic irradiation of the para-aortic lymphatic drainage area.Methods: This study enrolled 131 patients with pathologically confirmed ASC screened from 3502 patients with confirmed stage I-II cervical cancer diagnosis who had completed surgical treatments in our hospital. Among the 131 enrolled patients, 75 patients received CCRT, 33 patients received chemotherapy (CT), and 23 patients did not receive adjuvant treatment (named surgery alone (S alone). Of the 75 patients CCRT, 43 patients received prophylactic irradiation of the para-aortic lymphatic drainage area. The efficacy of the postoperative treatments of patients among groups (CCRT, CT, and S alone) was compared.Results: The median follow-up time, age, and overall survival (OS) were 76 months, 43 years, and 74 months, respectively. The 3- and 5-year survival rates were 82% and 71.4%, respectively. The median disease-free survival (DFS) was 64 months. Cox regression analysis showed that postoperative adjuvant treatment modalities and positive lymph node metastases were associated with OS and DFS. Patients who received CCRT treatment had higher OS and DFS than those with CT and S alone. Prophylactic irradiation of the para-aortic lymphatic drainage area did not improve the OS and DFS of patients with CCRT treatment. However, further subgroup analysis suggested that it might improve survival rates in patients who had positive pelvic lymph nodes as confirmed by postoperative pathology.Conclusion: Postoperative CCRT improved the survival rates in patients with early-stage ASC. The value of prophylactic irradiation of the para-aortic lymphatic drainage area remains debatable, but it may benefit patients with pelvic lymph node involvement. [ABSTRACT FROM AUTHOR]

Background. Aberrant expression of tripartite motif 11 (TRIM11) and the Wnt/β-catenin pathway are essential for facilitating tumorigenesis and progression in multiple types of cancer. Aim. To investigate the molecular changes linking the dysregulation of TRIM11 and Wnt/β-catenin pathway activation in gastric cancer (GC) progression. Methods. The expression levels of TRIM11 were detected in GC tissues and cells by immunohistochemistry and western blotting. The role of TRIM11 in the growth, proliferation, and invasion of gastric cancer cells was observed by a series of cell functional experiments and further verified in vivo. Co-immunoprecipitation (Co-IP), immunofluorescence, cycloheximide, and western blotting assays and other experiments were conducted to explore the mechanisms of TRIM11 underlying the regulation of the Wnt/β-catenin pathway. For further verification, rescue experiments were performed by cotransfection of TRIM11 and Axin1 siRNA in GC cells. Results. Using Co-IP assays, we identified TRIM11 as a potent binding partner of Axin1 in GC cells. Elevated TRIM11 levels were significantly correlated with unfavorable clinical outcomes and poor survival in patients with GC. In addition, TRIM11 promoted the cell proliferation and invasion capacities of GC cells in vitro and tumor growth in vivo. Mechanistic investigations revealed that TRIM11 destabilized Axin1 protein by interacting with Axin1, thus inducing the activation of the Wnt/β-catenin pathway. Moreover, we found that the oncogenic effects of TRIM11 on GC cells were partly mediated by suppression of Axin1. Furthermore, the protein expression of TRIM11 and Axin1 was negatively correlated in GC tissues. Conclusion. Collectively, our findings not only establish a pivotal TRIM11-Axin1-β-catenin axis in driving GC progression but also indicate that TRIM11 serves as a valuable therapeutic target for the treatment of GC patients. [ABSTRACT FROM AUTHOR]

Porous diamonds have unique application prospects due to their flexible surface functionalities, high surface-area-to-volume ratio and high self-sharpening ability. Porous diamonds are usually prepared through microwave plasma chemical vapor deposition (MPCVD) techniques or through etching by transition metals, which are expensive and inefficient. Here, we report a simple and efficient method to grow large millimetre-scale porous single-crystal diamonds using high-pressure and high-temperature (HP-HT) techniques. The porous diamond crystal growth is driven by minimizing the surface energy through the attachment of small crystals to a large seed crystal surface in a metal solvent. Industrial-scale production of single-crystal porous diamonds is possible with this discovery. The porous single-crystal diamond is prepared by using high pressure and high temperature (HP-HT) technology. XRD, SEM, Raman spectroscopy and HRTEM observations illustrated the high quality of the porous diamond surface layer and confirmed the obtained diamonds as porous single crystals. [Display omitted] [ABSTRACT FROM AUTHOR]

Previous studies have shown that endoplasmic reticulum (ER) stress contributes to hepatic steatosis in several manners. However, how lipid droplet (LD) proteins participate in this process has rarely been reported. In the present study, ER stress was induced at both in vitro and in vivo levels with tunicamycin in large yellow croaker (Larimichthys crocea). Effects of LD protein perilipin2 (PLIN2) on hepatic lipid accumulation and lipoprotein transport under normal physiological condition and ER stress were then explored using dsRNA mediated knockdown. Subsequently, the transcriptional regulation of plin2 expression by transcription factors generated in the unfolded protein response (UPR) was determined by dual‐luciferase reporter assays, chromatin immunoprecipitation and electrophoretic mobility‐shift assay. We demonstrated that ER stress could promote LDs accumulation and inhibit lipoprotein transport by transcriptionally upregulating PLIN2 in liver. Among the transcription factors generated by UPR, spliced X‐box binding protein1 can directly upregulated the expression of plin2, whereas C/EBP homologous protein can upregulate the expression of plin2 through peroxisome proliferator activated‐receptor α. These results revealed that the LD protein PLIN2 played an important role in ER stress‐induced hepatic steatosis, which might be a novel mechanism explaining hepatic steatosis triggered by ER stress. [ABSTRACT FROM AUTHOR]

Abstract: Dopamine partial agonists have been suggested to be potential therapeutic candidates for pharmacological intervention in drug addiction. These drugs bind to dopamine receptors with high affinity and low intrinsic activity and are hypothesized to behave as functional antagonists in conditions of high dopaminergic tone. The aim of the present study was to characterize the effects of terguride, a partial dopamine agonist at the dopamine D2 receptor, on intravenous heroin self-administration on fixed- and progressive-ratio schedules of reinforcement. The effects of terguride on oral sweet solution (4% sucrose) self-administration on a fixed-ratio schedule were also tested. Terguride dose-dependently decreased heroin self-administration on the fixed-ratio schedule and decreased the maximum number of responses for heroin self-administration on a progressive-ratio schedule. In contrast, terguride did not significantly affect oral sucrose self-administration. These data suggest that terguride may represent a novel pharmacological strategy for the treatment of opiate addiction. [ABSTRACT FROM AUTHOR]

Not all experiences are memorized equally well. Especially, some types of stress are unavoidable in daily life and the stress experience can be memorized for life. Previous evidence has showed that synaptic plasticity, such as long-term potentiation (LTP) that may be the major cellular model of the mechanism underlying learning and memory, is influenced by behavioral stress. However, the effect of behavioral stress on age-related synaptic plasticity in vivo was primarily known. Here we found that the LTP induction in the hippocampal CA1 region of anesthetized rats obviously showed inverted-U shape related to ages (4, 10 and 74 weeks old rats), but low-frequency stimulation was unable to induce reliable long-term depression (LTD) in these animals. Furthermore, acute elevated platform (EP) stress enabled reliable LTD significantly and completely blocked LTP induction at these ages. Importantly, LTD after exposure to acute EP stress showed similar magnitude over these ages. The present results that stress enables LTD but impairs LTP induction at these three ages strengthen a view that stress experience-dependent LTD (SLTD) may underlie stress form of aberrant memories. [Copyright &y& Elsevier]

Acute kidney injury (AKI) is responsible for significant mortality among hospitalized patients that is especially troubling aged people. An effective self-made Chinese medicine formula, Xiaoyu Xiezhuo Drink (XXD), displayed therapeutic effects on AKI. However, the compositions and underlying mechanisms of XXD remain to be elucidated. In this study, we used the ultra-high-performance liquid chromatography method coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to investigate the chemical components in XXD. Then, the absorbable components of XXD were identified based on the five principles and inputted into the SwissTargetPrediction and STITCH databases to identify the drug targets. AKI-related targets were collected from the GenCLiP 3, GeneCards, and DisGeNET databases. The crossover genes of XXD and AKI were identified for functional enrichment analysis. The protein-protein interaction (PPI) network of crossover genes was constructed, followed by the identification of hub genes. Subsequently, the effects and potential mechanisms of XXD on AKI predicted by the network pharmacology and bioinformatics analyses were experimentally validated in ischemia-reperfusion (I/R) injury-induced AKI aged mouse models. A total of 122 components in XXD were obtained; among them, 58 components were found that could be absorbed in the blood. There were 800 potential drug targets predicted from the 58 absorbable components in AKI which shared 36 crossover genes with AKI-related targets. The results of functional enrichment analysis indicated that crossover genes mostly associated with the response to oxidative stress and the HIF1 signaling pathway. In the PPI network analysis, 12 hub genes were identified, including ALB, IL-6, TNF, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, and HMOX1. In AKI aged mice, XXD prominently alleviated I/R injury-induced renal dysfunction, abnormal renal pathological changes, and cellular senescence, inflammation, and oxidative damage with a reduction in the expression level of the inflammatory mediator, α-SMA, collagen-1, F4/80, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, ICAM-1, TGF-β1, Smad3, and p-Smad3 and an increase of nephridial tissue p-H3, Ki67, HMOX1, MMP-9, and Smad7 levels. In summary, our findings suggest that XXD has renoprotective effects against AKI in aged mice via inhibiting the TGF-β1/Smad3 and HIF1 signaling pathways. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is a potent stimulant and notoriously addictive. Individuals respond to MA effects differently and thus have a varying susceptible risk of developing MA use disorder. Cumulative evidence has indicated that gut dysbiosis contributes to behavioral response to drug effects. However, the role of gut microbiota in the susceptible risk of developing MA use disorder has remained elusive. Using an MA‐induced conditioned place preference (CPP) rat model, we administrated the same dose of MA to rats, which then showed distinct preferences in drug‐related place, indicating their different responses to MA. From all of the MA‐exposed rats, the eight with the highest CPP scores were labeled as group high CPP (H‐CPP), and the eight with the lowest were labeled as group low CPP (L‐CPP). By 16S ribosomal RNA (rRNA) sequencing, we found that the gut microbiota compositions differed between H‐CPP and L‐CPP. Specifically, Akkermansia was significantly higher in H‐CPP and positively correlated with the CPP scores. Notably, H‐CPP and L‐CPP differed in the gut microbiota composition prior to the CPP training; Ruminococcus was the dominant phylotype in H‐CPP at baseline. More importantly, rats pretreated by antibiotics showed a significantly stronger MA‐induced CPP than did the controls. Our study demonstrates that the gut dysbiosis was associated with the MA‐induced CPP, indicating that the gut microbiota might be important modulators for MA‐induced behavior and vulnerability to MA use disorder. [ABSTRACT FROM AUTHOR]

A 10‐week feed trial was conducted to investigate the effects of tributyrin (TB) supplementation on growth performance, body composition, serum biochemical indexes and lipid metabolism‐related genes expression of juvenile large yellow croaker (Larimichthys crocea) fed diets containing high level of soybean oil. In the negative control group, 80 g/kg fish oil was used as the only lipid source (FO group), while in the positive control group, 20 g/kg fish oil and 60 g/kg soybean oil were used as the lipid source (FS group). Based on the positive control diet, grade levels of 1, 2, 4 and 8 g/kg tributyrin were added, respectively. Results showed that compared with the negative control group, high level of dietary soybean oil significantly decreased the growth performance and increased the liver lipids deposition of juvenile large yellow croaker. Compared with the positive control group, supplementation of 2 g/kg tributyrin significantly increased the growth performance and reduced the liver triglycerides and serum cholesterol content of juvenile large yellow croaker. Supplementation of 4 g/kg tributyrin significantly decreased liver triglycerides and serum cholesterol and free fatty acids content of juvenile large yellow croaker. Moreover, supplementation of 2 and 4 g/kg tributyrin significantly decreased the expression of acc, srebp‐1, and pparγ and significantly increased the expression of cpt1. Results of the present study indicated that moderate tributyrin supplementation in diet containing high level of soybean oil could promote growth performance and reduce liver fat accumulation and hyperlipidemia of cultured juvenile large yellow croaker, which could be due to the decrease in lipogenesis‐related genes expression and the increase in lipid oxidation‐related genes expression. [ABSTRACT FROM AUTHOR]

Single-crystal boron phosphide (BP), a high-temperature semiconductor, is prepared by a eutectic melting method. Large BP single crystals (>1 mm) are synthesized at high pressure and high temperature (5.0 GPa and 3000 °C). Their growth mechanism is analyzed. Ultraviolet–visible spectroscopy and thermogravimetry/differential thermal analysis show that BP is an indirect semiconductor (2.01 eV) and has excellent thermal stability (>1200 °C). Success in the synthesis of good BP crystals offers a huge opportunity to determine their intrinsic properties and will also stimulate more research on their performance as semiconductors. • We demonstrate the melt crystallization method for synthesis of BP single crystals in a large volume cubic press • We save the process of long heat preservation and We increase the synthesis efficiency of BP single crystals. • The BP single crystal has a high thermal stability (>1200 °C) and is an indirect semiconductor (1.97 eV). [ABSTRACT FROM AUTHOR]

Background: Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated. Methods: The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real-time quantitative PCR (RT-qPCR) were used to analyze protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates were analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA), and LinkedOmics database. Results: The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC. Conclusions: The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks, and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC. [ABSTRACT FROM AUTHOR]

Adiponectin (APN), an adipose tissue-derived hormone, plays a key role in regulating energy metabolism in mammals. However, its physiological roles in teleosts remain poorly understood. In the present study, the apn gene was cloned from large yellow croaker, which was mainly expressed in the adipose, muscle and liver. Further studies showed that adaptor protein phosphotyrosine interaction PH domain and leucine zipper 1 (APPL1) was localized in the cytoplasm near the cell membrane and was directly bounded to adiponectin receptors (AdipoRs). Meanwhile, APN played a crucial role in lipid metabolism of primary muscle cells by promoting the synthesis, oxidation and transport of fatty acids, and the promoting effects were blocked by knockdown of appl1 and AdipoRs. Furthermore, the activation/inhibition of peroxisome proliferators activated receptor γ (PPARγ) enhanced/suppressed the APN-mediated lipid metabolism. Overall, results showed that APN mediated lipid metabolism through AdipoRs-APPL1 activated PPARγ and further regulated the synthesis, oxidation and transport of FA. This study will facilitate the investigation of APN functions in lipid metabolism and energy homeostasis and reveal the evolution of lipids utilization and energy homeostasis in vertebrates. • Adiponectin promotes the synthesis, oxidation and transport of fatty acids in large yellow croaker; • Adiponectin activates downstream PPARγ and AMPKα through AdipoRs-APPL1; • Differences in the metabolic action of APN reveal an adaptive strategy to utilize lipids between mammals and teleosts [ABSTRACT FROM AUTHOR]

Background: High linoleic acid (LA) intake leads to inflammation that adversely influences health in fish. However, whether the farnesoid X receptor (FXR) could be an effective target for regulating LA-induced inflammation remains unknown.Objective: The purpose of this study was to investigate the role of FXR in the regulation of LA-induced inflammation in large yellow croakers.Methods: Large yellow croakers (initial weight of 10.03 ± 0.02 g) were allocated to 4 groups and fed a fish oil diet (6% FO), a soybean oil diet (6% SO), or the SO diet supplemented with 300 or 900 mg chenodeoxycholic acid (CDCA)/kg for 10 wk. The cultured kidney cell line PCK and primary hepatocytes from large yellow croakers were stimulated by LA (50 μM) after pretreatment with an FXR ligand (GW4064 or CDCA) or transfection with fxr-small interfering RNA (siFXR). mRNA expression of proinflammatory genes in the head kidney and liver tissues, PCK cells, and primary hepatocytes was determined by qPCR. The luciferase reporter assay, electrophoretic mobility shift assay, and immunoprecipitation assay were conducted in HEK 293T cells to determine the transcriptional activity of P65 and protein interactions between P65 and FXR or the small heterodimer partner (SHP).Results: Proinflammatory genes were 93-1180% higher in the SO group compared with the FO group. CDCA supplementation decreased mRNA expression of proinflammatory genes by 17-87% while increasing fxr and shp expression by 120-460%. In PCK cells and primary hepatocytes, ligand-mediated activation of FXR decreased the LA-induced expression of proinflammatory genes by 18-67%, whereas siRNA-mediated knockdown of FXR increased the LA-induced expression of proinflammatory genes by 64-96%. FXR bound to the promoter of shp and regulated its mRNA expression. Both FXR and SHP could bind to P65 to suppress the transcriptional activity of P65.Conclusions: These results indicate that FXR has anti-inflammatory properties in large yellow croakers by directly and indirectly suppressing NFκB activity. [ABSTRACT FROM AUTHOR]

Anlotinib is an anti‐angiogenic drug that targets vascular endothelial growth factor receptor, platelet‐derived growth factor receptor, fibroblast growth factor receptor, c‐Kit, and other kinases and has been approved for the treatment of advanced non‐small cell lung cancer (NSCLC). As in other small‐molecule tyrosine kinase inhibitors, adverse effects such as hypertension and cardiotoxicity may be seen. However, the relationship between anlotinib and aortic dissection has not been previously reported. Here, we present a case of aortic dissection in a 58‐year‐old male patient with advanced NSCLC without history of hypertension who received anlotinib as third‐line treatment. After four courses of anlotinib treatment, he suffered a sudden onset of back pain, sweating, anxiety, and high blood pressure (180/120 mmHg) and heart rate (137 bpm). Emergency computed tomographic angiography revealed aortic dissection and thrombosis of the distal false lumen. Thereafter, the patient was administered nitroglycerin as antihypertensive treatment and he underwent stent‐graft intervention for aortic dissection. Anticoagulants and antihypertensive drugs were administered after the operation, and a moderate control of blood pressure was achieved. Thus, the adverse reactions of antolinib must be monitored and clinicians must be vigilant. [ABSTRACT FROM AUTHOR]

Elongation of very long chain fatty acids protein 6 (Elovl6) is a key enzyme in fatty acid synthesis, which participates in converting palmitate (C16:0) to stearate (C18:0). Although studies of Elovl6 have been carried out in mammals, the nutritional regulation of elovl6 in fish remains poorly understood. In the present study, the cloning and nutritional regulation of elovl6 were determined in large yellow croaker. Sequence and phylogenetic analysis revealed that the full-length cDNA of elovl6 was 1360 bp, including an open reading frame of 810 bp encoding a putative protein of 269 amino acid that possesses the characteristic features of Elovl proteins. The transcript level of elovl6 was significantly increased in the liver of croaker fed the diets with soybean oil (enriched with 18: 2n-6, LA) or linseed oil (enriched with 18: 3n-3, ALA) than that in croaker fed the diet with fish oil (enriched with 20: 5n-3 and 22: 6n-3). Correspondingly, the elovl6 expression in croaker's hepatocytes treated with ALA or LA was remarkably increased compared to the controls. Furthermore, the transcription factors including hepatocyte nuclear factor 1α (HNF1α), CCAAT-enhancer-binding protein β (CEBPβ), retinoid X receptor α (RXRα), and cAMP response element-binding protein 1 (CREB1) greatly enhanced promoter activity of elovl6 in large yellow croaker, and the expression of transcription factors is consistent with the changes of elovl6 expression in response to fatty acids in vivo and in vitro. In conclusion, this study revealed that elovl6 expression in large yellow croaker could be upregulated by dietary ALA or LA via the increased transcriptional expression of transcription factors including hnf1α, cebpβ, rxrα, and creb1. [ABSTRACT FROM AUTHOR]

Rationale: Although alcohol use disorder and anxiety disorders are highly comorbid in humans, controversy remains regarding whether anxiety predisposes individuals to alcohol reward, and the relationship with neurokinin-1 receptor (NK1R) is unclear.Objectives: The objectives of the study are to investigate the association between anxiety-like behavior and alcohol-induced conditioned place preference (CPP) and to examine the effect of NK1R antagonist L-703,606 on this preference and levels of NK1R protein in different brain regions in adolescent mice.Methods: The anxiety-like behavior of adolescent male C57BL/6 mice was assessed using the elevated plus maze (EPM) test, and the animals were then allocated into high-anxiety mouse (HAM) and low-anxiety mouse (LAM) groups based on the percent of open arm time (OT%). After the reinforcement of ethanol was established by alcohol-induced CPP (2 g/kg), NK1R expression was quantified in the hippocampus, prefrontal cortex, and amygdala. Finally, the effect of L-703,606 (10 mg/kg) on the alcohol-induced CPP was examined.Results: LAM showed a greater ethanol preference (P = 0.004) and a higher level of NK1R protein in the hippocampus (P = 0.026) than HAM group. Interestingly, the CPP score positively correlated with OT% (r = 0.520, P = 0.016) and the level of NK1R protein (r = 0.476, P = 0.029) in the hippocampus. Moreover, L-703,606 attenuated alcohol-induced CPP (P < 0.001) in both groups.Conclusions: The present results highlight the negative correlation between anxiety-like behavior and the propensity for alcohol and the critical role for NK1R in alcohol reward in adolescent mice. Importantly, the NK1R antagonist L-703,606 might be a promising therapeutic target for alcohol use disorder. [ABSTRACT FROM AUTHOR]

Abstract YAP1, a vital effector of Hippo pathway, promotes cancer development via transcriptionally regulating a batch of target genes involved in various signaling pathways, including proliferation, apoptosis, and cell drug sensitivity. Recently, circular RNAs (circRNAs) have been shown to control gene expression post-transcriptionally and become a new layer of gene regulation. However, whether circRNAs play roles in YAP1-induced tumorigenesis is still largely elusive. Here, we identify circRNA-000425 as a new inhibitory target of YAP1, and also find that it binds to miR-17/miR-106b, and thus suppresses cancer cell growth induced by these miRNAs. circRNA-000425 is revealed as a YAP1 target through circRNA microarray analysis of RNAs extracted from cells treated with or without YAP1 siRNAs, and further confirmed by RT-q-PCR and ChIP assays. Interestingly, bioinformatics analysis, luciferase assay, and RT-q-PCR results showed that circRNA-000425 binds to miR-17 and miR-106b, but not let-7a, and rescues the inhibitory effect of miR-17/miR-106 on the expressions of both p21 and BIM. In addition, colony formation and MTT assay showed that circRNA-000425 inhibits cancer cell growth induced by miR-17. These findings reveal a mechanism by which YAP1 promotes oncogenic activities of miR-17 and miR-106b through transcriptionally inhibiting circRNA-000425 expression. Highlights • Identification of circRNA-000425 as a potential YAP1 target. • YAP1 binds to promoter of HRNPH1, the host gene of circRNA-000425. • YAP1 activates miR-17 and miR-106 via circRNA-000425. [ABSTRACT FROM AUTHOR]

Abstract: The study was conducted to investigate the effects of dietary tea polyphenols (TP) on growth performance, biochemical and antioxidants responses, fatty acid composition, and lipid metabolism‐related gene expressions of large yellow croaker (Larimichthys crocea). Four diets were formulated with different levels of TP (0.00%, 0.01%, 0.02% and 0.05%). Results showed that growth performance of L. crocea were not different among dietary treatments. Compared with the control group, fish in 0.02% TP group had lower body and hepatic lipid content and lower total cholesterol content. The minimum content of triglycerides and low‐density lipoprotein‐cholesterol were found in 0.05% TP group. Hepatic n‐6 PUFA and n‐3 PUFA were significantly higher in TP supplementation groups. Malondialdehyde content was lower in TP supplementation groups, and superoxide dismutase activity was higher in 0.01% TP group than the control group. The mRNA expressions of carnitine palmitoyltransferase1, acyl‐CoA oxidase and peroxisome proliferators‐activated receptor α were up‐regulated in 0.01% and 0.02% TP groups, while lipoprotein lipase expression was down‐regulated in TP supplementation groups than the control group. Results suggested that 0.01%–0.02% TP supplementation could reduce the deposition of liver lipid of L. crocea caused by high‐lipid diet, which might be due to the increase in lipid oxidation related gene expressions. [ABSTRACT FROM AUTHOR]

The article reports on the several problems on the lithium isotope research in the study of salt lakes. Among the problems include the lithium isotopic fractionation mechanism and the variation in the lithium isotope's periodic trends. Futhermore, it also mentions the several places where liquid lithium exists such as in seawater, oil field water, and salt lake brine.

Disintegration in thalamocortical integration suggests its role in the mechanistic ‘switch’ from recreational to dysregulated drug seeking/addiction. In this study, we aimed to address whether thalamic nuclear groups show altered functional connectivity within the cerebral cortex in chronic ketamine users. One hundred and thirty subjects (41 ketamine users and 89 control subjects) underwent rsfMRI (resting-state functional Magnetic Resonance Imaging). Based on partial correlation functional connectivity analysis we partitioned the thalamus into six nuclear groups that correspond well with human histology. Then, in the area of each nuclear group, the functional connectivity differences between the chronic ketamine user group and normal control group were investigated. We found that the ketamine user group showed significantly less connectivity between the thalamic nuclear groups and the cortical regions-of-interest, including the prefrontal cortex, the motor cortex /supplementary motor area, and the posterior parietal cortex. However, no increased thalamic connectivity was observed for these regions as compared with controls. This study provides the first evidence of abnormal thalamocortical connectivity of resting state brain activity in chronic ketamine users. Further understanding of pathophysiological mechanisms of the thalamus in addiction (ketamine addiction) may facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of this complex disease. [ABSTRACT FROM AUTHOR]

The harmful use of alcohol is a severe public health issue globally. Chinese per-capita alcohol consumption has increased sharply in recent decades, which has contributed to a rise in alcohol-related problems. In this article we present an analysis of Chinese alcohol policy, beginning with a characterization of alcohol consumption in China followed by an examination of how the nation's alcohol control policy has evolved over the past 30 years, identifying shortcomings and obstacles to improvement. Finally, we present several recommendations informed by the Global Strategy to Reduce the Harmful Use of Alcohol and the SAFER Technical Package-Five Areas of Intervention at National and Subnational Levels (SAFER initiative), to the areas of taxation, alcohol availability, alcohol marketing regulation, and treatment. [ABSTRACT FROM AUTHOR]

Abstract: Ketamine is a non-competitive anatognist of the N-methyl-d-aspartate (NMDA) receptor commonly used as an anesthetic and analgesic. In sub-anesthetic doses, it can induce temporary psychotic symptoms and has served as a pharmacological model for schizophrenia. While its acute effects on brain and behavior have been studied, the effects of long-term exposure to ketamine on brain activity have been largely unexplored. In this study, we aimed to examine such effects on spontaneous brain dynamics measure using resting-state functional magnetic resonance imaging (fMRI). Forty-one patients with ketamine dependence and forty-four healthy control subjects were imaged with BOLD fMRI using a 3.0-Tesla Siemens scanner at the Magnetic Resonance Center of Hunan Provincial People''s Hospital, analyzed with the regional homogeneity (ReHo) method. Compared with healthy controls, decreased ReHo was found in ketamine users in the right anterior cingulate cortex and increased ReHo was found in left precentral frontal gyrus (p <0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption and ketamine craving levels. To our knowledge, this is the first study the long-term effects of ketamine exposure on brain functional activity. Our findings indicate that ketamine dependence is associated with alterations in the functional connectivity of medial and lateral prefrontal cortices. [Copyright &y& Elsevier]