ROS signaling-induced mitochondrial Sgk1 expression regulates epithelial cell renewal.

Many types of differentiated cells can reenter the cell cycle upon injury or stress. The underlying mechanisms are still poorly understood. Here, we investigated how quiescent cells are reactivated using a zebrafish model, in which a population of differentiated epithelial cells are reactivated under a physiological context. A robust and sustained increase in mitochondrial membrane potential was observed in the reactivated cells. Genetic and pharmacological perturbations show that elevated mitochondrial metabolism and ATP synthesis are critical for cell reactivation. Further analyses showed that elevated mitochondrial metabolism increases mitochondrial ROS levels, which induces Sgk1 expression in the mitochondria. Genetic deletion and inhibition of Sgk1 in zebrafish abolished epithelial cell reactivation. Similarly, ROS-dependent mitochondrial expression of SGK1 promotes S phase entry in human breast cancer cells. Mechanistically, SGK1 coordinates mitochondrial activity with ATP synthesis by phosphorylating F1Fo-ATP synthase. These findings suggest a conserved intramitochondrial signaling loop regulating epithelial cell renewal.

Rational Design of 2D Metal Halide Perovskites with Low Congruent Melting Temperature and Large Melt-Processable Window.

Metal halide perovskites (MHPs) have garnered significant attention due to their distinctive optical and electronic properties, coupled with excellent processability. However, the thermal characteristics of these materials are often overlooked, which can be harnessed to cater to diverse application scenarios. We showcase the efficacy of lowering the congruent melting temperature (Tm) of layered 2D MHPs by employing a strategy that involves the modification of flexible alkylammonium through N-methylation and I-substitution. Structural-property analysis reveals that the N-methylation and I-substitution play pivotal roles in reducing hydrogen bond interactions between the organic components and inorganic parts, lowering the rotational symmetry number of the cation and restricting the residual motion of the cations. Additional I···I interactions enhance intermolecular interactions and lead to improved molten stability, as evidenced by a higher viscosity. The 2D MHPs discussed in this study exhibit low Tm and wide melt-processable windows, e.g., (DMIPA)2PbI4 showcasing a low Tm of 98 °C and large melt-processable window of 145 °C. The efficacy of the strategy was further validated when applied to bromine-substituted 2D MHPs. Lowering the Tm and enhancing the molten stability of the MHPs hold great promise for various applications, including glass formation, preparation of high-quality films for photodetection, and fabrication of flexible devices.

Room-Temperature Anisotropic Actuation Driven by a Synergistic Order-Disorder and Displacive Phase Transition in a Ferroelectric Crystal.

Actuating materials convert different forms of energy into mechanical responses. To satisfy various application scenarios, they are desired to have rich categories, novel functionalities, clear structure-property relationships, fast responses, and, in particular, giant and reversible shape changes. Herein, we report a phase transition-driven ferroelectric crystal, (rac-3-HOPD)PbI3 (3-HOPD = 3-hydroxypiperidine cation), showing intriguingly large and anisotropic room-temperature actuating behaviors. The crystal consists of rigid one-dimensional [PbI3] anionic chains running along the a-axis and discrete disk-like cations loosely wrapping around the chains, leaving room for anisotropic shape changes in both the b- and c-axes. The shape change is switched by a ferroelectric phase transition occurring at around room temperature (294 K), driven by the exceptionally synergistic order-disorder and displacive phase transition. The rotation of the cations exerts internal pressure on the stacking structure to trigger an exceptionally large displacement of the inorganic chains, corresponding to a crystal lattice transformation with length changes of +24.6% and -17.5% along the b- and c-axis, respectively. Single crystal-based prototype devices of circuit switches and elevators have been fabricated by exploiting the unconventional negative temperature-dependent actuating behaviors. This work provides a new model for the development of multifunctional mechanically responsive materials.

Halogen Substitution Regulates High Temperature Dielectric Switch in Lead-Free Chiral Hybrid Perovskites.

Hybrid metal halides (HMHs) based phase transition materials have received widespread attention due to their excellent performance and potential applications in energy harvesting, optoelectronics, ferroics, and actuators. Nevertheless, effectively regulating the properties of phase transitions is still a thorny problem. In this work, two chiral lead-free HMHs (R-3FP)2 SbCl5 (1; 3FP=3-fluoropyrrolidinium) and (R-3FP)2 SbBr5 (2) were synthesized. By replacing the halide ions in the inorganic skeleton, the phase transition temperature of 2 changes with an increase of about 20 K, compared with 1. Meanwhile, both compounds display reversible dielectric switching properties. Through crystal structure analysis and Hirshfeld surface analysis, their phase transitions are ascribed to the disorder of the cations and deformation of the inorganic chains.

Loss of Gcn2 exacerbates gossypol induced oxidative stress, apoptosis and inflammation in zebrafish.

Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2-/- zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2-/- zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2-/- zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.

EPA and DHA promote cell proliferation and enhance activity of the Akt-TOR-S6K anabolic signaling pathway in primary muscle cells of turbot (Scophthalmus maximus L.).

Fish growth and health are predominantly governed by dietary nutrient supply. Although the beneficial effects of omega-3 polyunsaturated fatty acids supplementation have been shown in a number of fish species, the underlying mechanisms are still mostly unknown. In this study, we conducted an investigation into the effects of EPA and DHA on cell proliferation, nutrient sensing signaling, and branched-chain amino acids (BCAA) transporting in primary turbot muscle cells. The findings revealed that EPA and DHA could stimulate cell proliferation, promote protein synthesis and inhibit protein degradation through activation of target of rapamycin (TOR) signaling pathway, a pivotal nutrient-sensing signaling cascade. While downregulating the expression of myogenin and myostatin, EPA and DHA increased the level of myogenic regulatory factors, such as myoD and follistatin. Furthermore, we observed a significant increase in the concentrations of intracellular BCAAs following treatment with EPA or DHA, accompanied by an upregulation of the associated amino acid transporters. Our study providing valuable insights into the mechanisms underlying the growth-promoting effects of omega-3 fatty acids in fish.

High-performance Pyroelectric Property Accompanied by Spin Crossover in a Single Crystal of Fe(II) Complex.

Pyroelectric materials hold significant potential for energy harvesting, sensing, and imaging applications. However, achieving high-performance pyroelectricity across a wide temperature range near room temperature remains a significant challenge. Herein, we demonstrate a single crystal of Fe(II) spin-crossover compound shows remarkable pyroelectric properties accompanied by a thermally controlled spin transition. In this material, the uniaxial alignment of polar molecules results in a polarization of the lattice. As the molecular geometry is modulated during a gradual spin transition, the polar axis experiences a colossal thermal expansion with a coefficient of 796×10-6 K-1. Consequently, the material's polarization undergoes significant modulation as a secondary pyroelectric effect. The considerable shift in polarization (pyroelectric coefficient, p=3.7-22 nC K-1cm-2), coupled with a low dielectric constant (ϵ'=4.4-5.4) over a remarkably wide temperature range of 298 to 400 K, suggests this material is a high-performance pyroelectric. The demonstration of pyroelectricity combined with magnetic switching in this study will inspire further investigations in the field of molecular electronics and magnetism.

Molecular Twist-Induced Single-Crystal Isomerization and Valence Tautomeric Transitions in a Cobalt-Dioxolene Complex.

A mononuclear valence tautomeric (VT) complex, [Co(pycz)2(Sq)(Cat)] (1-trans), where pycz = 9-(pyridin-4-yl)-9H-carbazole, Sq⋅- = 3,5-di-tert-butyl-semiquinonato, and Cat2- = 3,5-di-tert-butyl-catecholato, is synthesized in the trans configuration, which undergoes one-step valence tautomeric transition above room temperature. Remarkably, 1-trans can transform into its isomeric structure, [Co(pycz)2(Sq)(Sq)] (1-cis), at temperature above 350 K in a single-crystal-to-single-crystal way by in situ molecular twist, and the resulting 1-cis exhibits a pronounced two-step VT transition during magnetic measurements that is rare for mononuclear VT complexes. Such drastic solid-state structural transformation is reported in VT compounds for the first time, which is actuated by a crystal surface's melting-recrystallization induced phase transition process. DFT calculations offer an underlying mechanism suggesting a concerted bond rotation during the structural transformation. The results demonstrate an unconventional approach that realizes structural transformation of VT complexes and the control of VT performance.

Effects of dietary chloroquine on fish growth, hepatic intermediary metabolism, antioxidant and inflammatory responses in turbot.

Autophagy is a conserved cellular self-digestion process and is essential for individual growth, cellular metabolism and inflammatory responses. It was responsive to starvation, pathogens infection and environmental stress. However, the information on the regulation of autophagy in fish hepatic intermediary metabolism, antioxidant system, and immune responses were limited. In the present study, turbot with inhibited autophagy flux was built by dietary chloroquine. The hepatic metabolic response, antioxidant enzymes and immune responses were explored. Results showed that dietary chloroquine induced the expression of Beclin 1, SQSTM and LC-3II, and effectively inhibited autophagy flux. Autophagy dysfunction depressed fish growth and feed utilization, while it induced clusters of liver lipid droplets. The genes involved in lipolysis and fatty acid ß-oxidation, as well as the lipogenesis-related genes in chloroquine group were depressed. The phosphorylation of AMPK was activated in chloroquine group, and the genes involved in glycolysis were induced. The hepatic content of malonyldialdehyde and the activities of SOD and CAT were induced when autophagy was inhibited. The content of Complement 3, Complement 4 and Immunoglobulin M, as well as the activity of lysozyme in plasma were depressed in chloroquine group. Dietary chloroquine induced the expression of toll-like receptors and stimulated the expression of myd88 and nf-κb p65, as well as the pro-inflammatory cytokines, such as tnf-α and il-1ß. The expression of anti-inflammatory cytokine tgf-ß was depressed in the chloroquine group. Our results would extend the knowledge on the role of autophagy in teleost and assist in improving fishery production.

Comprehensive study on the effect of dietary leucine supplementation on intestinal physiology, TOR signaling and microbiota in juvenile turbot (Scophthalmus maximus L.).

Intestinal damage and inflammation are major health and welfare issues in aquaculture. Considerable efforts have been devoted to enhancing intestinal health, with a specific emphasis on dietary additives. Branch chain amino acids, particularly leucine, have been reported to enhance growth performance in various studies. However, few studies have focused on the effect of leucine on the intestinal function and its underlying molecular mechanism is far from fully illuminated. In the present study, we comprehensively evaluated the effect of dietary leucine supplementation on intestinal physiology, signaling transduction and microbiota in fish. Juvenile turbot (Scophthalmus maximus L.) (10.13 ± 0.01g) were fed with control diet (Con diet) and leucine supplementation diet (Leu diet) for 10 weeks. The findings revealed significant improvements in intestinal morphology and function in the turbot fed with Leu diet. Leucine supplementation also resulted in a significant increase in mRNA expression levels of mucosal barrier genes, indicating enhanced intestinal integrity. The transcriptional levels of pro-inflammatory factors il-1ß, tnf-α and irf-1 was decreased in response to leucine supplementation. Conversely, the level of anti-inflammatory factors tgf-ß, il-10 and nf-κb were up-regulated by leucine supplementation. Dietary leucine supplementation led to an increase in intestinal complement (C3 and C4) and immunoglobulin M (IgM) levels, along with elevated antioxidant activity. Moreover, dietary leucine supplementation significantly enhanced the postprandial phosphorylation level of the target of rapamycin (TOR) signaling pathway in the intestine. Finally, intestinal bacterial richness and diversity were modified and intestinal bacterial composition was re-shaped by leucine supplementation. Overall, these results provide new insights into the beneficial role of leucine supplementation in promoting intestinal health in turbot, offering potential implications for the use of leucine as a nutritional supplement in aquaculture practices.

A Two-Dimensional Hybrid Lead Bromide Ferroelectric Semiconductor with an Out-of-Plane Polarization.

A two-dimensional (2D) organic-inorganic hybrid perovskite (OIHP) material with out-of-plane ferroelectricity is the key to the miniaturization of vertical-sandwich-type ferroelectric optoelectronic devices. However, 2D OIHP ferroelectrics with out-of-plane polarization are still scarce, and effective design strategies are lacking. Herein, we report a novel 2D Dion-Jacobson perovskite ferroelectric semiconductor synthesized by a rigid-to-flexible cationic tailoring strategy, achieving an out-of-plane polarization of 1.7 µC/cm2 and high photoresponse. Integrating out-of-plane ferroelectricity with excellent photoelectric properties affords a promising platform to investigate ferroelectricity-related effects in vertical optoelectronic devices.

Nutrient sensing signaling and metabolic responses in shrimp Litopenaeus vannamei under acute ammonia stress.

Ammonia is the primary environmental factor affecting the growth and health of crustaceans. It would induce oxidative stress and metabolic disorders. Extra amount of energy was demanded to maintain the physiological functions under ammonia stress. However, limited information was available on its effects on the main nutrient metabolism, as well as the nutrient sensing signaling pathways. In the present study, shrimp Litopenaeus vannamei were exposed to acute ammonia stress and injected with amino acid solution. The results showed that acute ammonia exposure resulted in lower free amino acid levels in hemolymph, incomplete activation of the mechanistic target of rapamycin (mTOR) signaling and cascaded less protein synthesis in muscle. It induced autophagy and activated the AMP-activated protein kinase (AMPK) pathway. Meanwhile, ammonia exposure enhanced glycolysis and lipogenesis, but inhibited lipolysis. The results characterized the integrated metabolic responses and nutrient signaling to ammonia stress. It provides critical clues to understand the growth performance and physiological responses in shrimp under ammonia stress.

Transcervical inflatable mediastinoscopic esophagectomy versus thoracoscopic esophagectomy for local early- and intermediate-stage esophageal squamous cell carcinoma: A propensity score-matched analysis.

BACKGROUND AND OBJECTIVE: Transcervical inflatable mediastinoscopic esophagectomy (TIME) is a novel method of minimally invasive esophagectomy (MIE) for esophageal cancer. However, whether TIME is effective and feasible as conventional MIE remains unclear. This study aimed to evaluate the efficacy of TIME by comparing it with thoracoscopic esophagectomy (TE). METHODS: Surgical outcomes and relapse-free survival (RFS) rates of patients with local early- or intermediate-stage thoracic esophageal squamous cell carcinoma that underwent TIME or TE from January 2017 to December 2019 were analyzed in this retrospective study. Propensity score matching was used to control the confounding factors. RESULTS: The mean operation time in TIME was shorter than that in TE (p < 0.05). Patients in the TIME group achieved postoperative ambulation earlier than those in the TE group (p < 0.05). The rate of pulmonary complications was lower in TIME than in TE (p < 0.05). The number of lymph nodes harvested during surgery and the RFS rates of two groups did not have significant differences. CONCLUSION: TIME may be a feasible and safe method to treat local early- and intermediate-stage thoracic esophageal squamous cell carcinoma effectively and it could be a supplementary surgical method of TE for patients with poor pulmonary function or cannot undergo TE.

Slc38a9 Deficiency Induces Apoptosis and Metabolic Dysregulation and Leads to Premature Death in Zebrafish.

Eukaryotic cells control nutritional homeostasis and determine cell metabolic fate through a series of nutrient transporters and metabolic regulation pathways. Lysosomal localized amino acid transporter member 9 of the solute carrier family 38 (SLC38A9) regulates essential amino acids' efflux from lysosomes in an arginine-regulated fashion. To better understand the physiological role of SLC38A9, we first described the spatiotemporal expression pattern of the slc38a9 gene in zebrafish. A quarter of slc38a9-/- mutant embryos developed pericardial edema and died prematurely, while the remaining mutants were viable and grew normally. By profiling the transcriptome of the abnormally developed embryos using RNA-seq, we identified increased apoptosis, dysregulated amino acid metabolism, and glycolysis/gluconeogenesis disorders that occurred in slc38a9-/- mutant fish. slc38a9 deficiency increased whole-body free amino acid and lactate levels but reduced glucose and pyruvate levels. The change of glycolysis-related metabolites in viable slc38a9-/- mutant fish was ameliorated. Moreover, loss of slc38a9 resulted in a significant reduction in hypoxia-inducible gene expression and hypoxia-inducible factor 1-alpha (Hif1α) protein levels. These results improved our understanding of the physiological functions of SLC38A9 and revealed its indispensable role in embryonic development, metabolic regulation, and stress adaption.

Dietary lysine level affects digestive enzyme, amino acid transport and hepatic intermediary metabolism in turbot (Scophthalmus maximus).

Lysine is one of the most important essential amino acids in fish, especially in the feed formulated with high levels of plant ingredients. Lysine restriction always led to growth inhibition and poor feed utilization. However, little information was available on its effects on digestion, absorption, and metabolism response in fish. In the present study, three experimental diets were formulated with three lysine levels, 1.69% (LL group), 3.32% (ML group), and 4.90% (HL group). A 10-week feeding trial was carried out to explore the effects of dietary lysine levels on the digestive enzymes, amino acid transporters, and hepatic intermediary metabolism in turbot (Scophthalmus maximus). As the results showed, the activities of lipase and trypsin in ML group were higher than in other groups. Lysine restriction inhibited the expression levels of peptides and amino acid transporters such as PpeT1, y+LAT2, b0,+AT, and rBAT but significantly induced the expression of CAT1. Meanwhile, lysine deficiency elevated the content of T-CHO and LDL-C in plasma, while a higher HDL-C/LDL-C ratio was observed in ML group. For hepatic intermediary metabolism, the increase of lysine level induced the mRNA expression of G6Pase1 and FBPase, but no differences were observed in the expression of the key regulators in glycolysis pathway, such as GK and PK. Furthermore, an appropriate increase in the level of lysine promoted the genes involved in lipolysis, including PPARα, ACOX1, CPT1A, and LPL. However, no differences were observed in the expression of PPARγ, FAS, SREBP1, and LXR, which were important genes related to lipid synthesis. These results provide clues on the metabolic responses on dietary lysine in teleost.

Fine-Tuning of Postprandial Responses via Feeding Frequency and Leucine Supplementation Affects Dietary Performance in Turbot (Scophthalmus maximus L.).

BACKGROUND: Feeding-induced cell signaling and metabolic responses affect utilization of dietary nutrients but are rarely taken advantage of to improve animal nutrition. OBJECTIVES: We hypothesized that by modulating postprandial kinetics and signaling, improved dietary utilization and growth performance could be achieved in animals. METHODS: Juvenile turbot (Scophthalmus maximus L.) with an initial mean ± SD weight of 10.1 ± 0.01 g were used. Two feeding frequencies (FFs), either 1 or 3 meals/d at a fixed 2.4% daily body weight ration, and 2 diets that were or were not supplemented with 1% crystalline leucine (Leu), were used in the 10-wk feeding trial. At the end of the trial, a 1-d force-feeding experiment was conducted using the aforementioned FF and experimental diets. Samples were collected for the analysis of postprandial kinetics of aminoacidemia, mechanistic target of rapamycin (mTOR) signaling activities, protein deposition, as well as the mRNA expression levels of key metabolic checkpoints at consecutive time points after feeding. RESULTS: Increased FF and leucine supplementation significantly enhanced fish growth by 7.68% ± 0.53% (means ±SD) and 7.89% ± 1.25%, respectively, and protein retention by 4.01% ± 0.59% and 4.44% ± 1.63%, respectively, in feeding trial experiments. The durations of postprandial aminoacidemia and mTOR activation were extended by increased FF, whereas leucine supplementation enhanced mTOR signaling without influencing the postprandial free amino acids kinetics. Increased FF and leucine supplementation enhanced muscle protein deposition 21.6% ± 6.85% and 22.3% ± 1.52%, respectively, in a 24-h postfeeding period. CONCLUSIONS: We provided comprehensive characterization of the postprandial kinetics of nutrient sensing and metabolic responses under different feeding regimens and leucine supplementation in turbot. Fine-tuning of postprandial kinetics could provide a new direction for better dietary utilization and animal performances in aquaculture.

Effects of dietary raw or Enterococcus faecium fermented soybean meal on growth, antioxidant status, intestinal microbiota, morphology, and inflammatory responses in turbot (Scophthalmus maximus L.).

Fermentation has been reported to improve the utilization of plant ingredients including soybean meal (SBM) by fish, but the detailed mechanism is still poorly understood. This study compared the effects of partial replacement of fish meal (FM) protein with SBM or Enterococcus faecium fermented SBM (EFSM) on the growth, antioxidant status, intestinal microbiota, morphology, and inflammatory responses in turbot (Scophthalmus maximus L.). The FM-based diet was used as the control (CONT). Two experimental diets were formulated in which 45% of the FM protein was replaced with SBM or EFSM. Each diet was fed to triplicate groups of fish (7.57 ± 0.01 g) twice daily for 79 d. Inferior growth performance was observed in SBM group, however, no significant depression was observed in EFSM group compared to the CONT group. The CONT group had the highest values of lysozyme, complement component 3, total antioxidant capacity, superoxide dismutase and catalase, followed by the EFSM group, and the lowest in SBM group. The malondialdehyde content was lowest in the CONT group, followed by the EFSM group, and was highest in the SBM group. Gut morphology showed that SBM diet induced alterations typical for intestinal inflammation including decreased villus and microvillus height, and increased width and inflammatory cell infiltration of the lamina propria. However, the EFSM group alleviated such SBM-induced intestinal pathological disruption. Paralleled with the morphological symptoms, the inflammatory gene expression levels of tumor necrosis factor alpha, interleukin-1 beta and interleukin-8 were highest in the SBM group, followed by the EFSM group, and were lowest in the CONT group. Furthermore, the intestinal microbiota analysis revealed that EFSM group had an overall more similar microbiota with CONT group than SBM group. Specifically, compared with the SBM group, EFSM group significantly enhanced the probiotics Lactobacillus and anti-inflammatory bacterium Faecalibaculum, and inhibited the Vibrio. Collectively, this study indicated that Enterococcus faecium fermentation effectively counteracted the negative effects of SBM by enhancing antioxidant capacity, suppressing inflammatory responses, and modulating gut microbiota in turbot.

Administration of commensal Shewanella sp. MR-7 ameliorates lipopolysaccharide-induced intestine dysfunction in turbot (Scophthalmus maximus L.).

This study was designed to evaluate whether the administration of commensal Shewanella sp. MR-7 (MR-7) could ameliorate lipopolysaccharide (LPS)-induced intestine dysfunction in turbot. Fish (body weight: 70.00 ± 2.00 g) were randomly divided into three groups including the control group treated with dough, the LPS group treated with dough plus LPS, and the LPS+MR-7 (LMR) group treated with dough plus LPS and MR-7. These three groups with 24 fish each were force-fed with 1 g dough daily for 7 continuous days. The results revealed that MR-7 administration ameliorated LPS-induced intestinal injury, showing higher intestinal villus and microvillus height. Further results showed that MR-7 could inhibit LPS-induced activation of TLR-NF-κB signaling thus maintaining the normal expression levels of cytokines and finally ameliorate the intestinal inflammatory response in turbot. Compared with the LPS group, LMR group had less goblet cells and lower mucin-2 expression level. Moreover, MR-7 restored LPS-induced down-regulation of tight junction protein-related gene expression (zonula occluden-1, occludin, tricellulin and claudin-3). Further investigations indicated that MR-7 partially counteracted LPS-induced changes in gut microbiota composition, enhanced the beneficial bacteria Lactobacillus and reduced the Pseudomonas, thus maintaining the overall microbiota balance. Taken together, the administration of MR-7 could effectively restore LPS-induced intestine function disorder in turbot by ameliorating inflammatory response, mucosal barrier dysfunction and microbiota dysbiosis.

Antimony-Assisted Assembly of Basic Supertetrahedral Clusters into Heterometallic Chalcogenide Supraclusters.

Reported here are two new heterometallic chalcogenide supraclusters ([Ga56Sb16S136] and [In36Sb6S75]), which present new self-assembly modes of basic supertetraheral clusters with the assistance of antimony ions. This work demonstrates the crucial role of the added metal ions with nontetrahedral coordination geometry in developing supertetrahedral-cluster-based supraclusters with a new level of complexity.

Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network.

The glucagon receptor (GCGR) is a G-protein-coupled receptor (GPCR) that mediates the activity of glucagon. Disruption of GCGR results in many metabolic alterations, including increased glucose tolerance, decreased adiposity, hypoglycemia, and pancreatic α-cell hyperplasia. To better understand the global transcriptomic changes resulting from GCGR deficiency, we performed whole-organism RNA sequencing analysis in wild type and gcgr-deficient zebrafish. We found that the expression of 1645 genes changes more than two-fold among mutants. Most of these genes are related to metabolism of carbohydrates, lipids, and amino acids. Genes related to fatty acid ß-oxidation, amino acid catabolism, and ureagenesis are often downregulated. Among gcrgr-deficient zebrafish, we experimentally confirmed increases in lipid accumulation in the liver and whole-body glucose uptake, as well as a modest decrease in total amino acid content. These results provide new information about the global metabolic network that GCGR signaling regulates in addition to a better understanding of the receptor's physiological functions.