Reactive oxygen species responsive chitooligosaccharides based nanoplatform for sonodynamic therapy in mammary cancer.

Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of ß-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (ß-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS). Moreover, the glucose oxidase (GOx) was loaded through electrostatic adsorption, which efficiently restricts the energy supply in tumor tissues, thus enhancing the therapeutic efficacy of SDT for tumors. Under optimal conditions, the entire system exhibited favorable water solubility, suitable particle size and viable biocompatibility. This facilitated the integration of the characteristics of starvation therapy and sonodynamic therapy, resulting in efficient inhibition of tumor growth with minimal side effects in vivo. This work may provide new insights into the application of natural oligosaccharides for construct multifunctional nanocarrier systems, which could optimize the design and development of sonodynamic therapy strategies and even combination therapy strategies.

NF-κB1 deficiency promotes macrophage-derived adrenal tumors but decreases neurofibromas in HTLV-I LTR-Tax transgenic mice.

Human T-cell leukemia virus type I (HTLV-I) is an oncogenic virus whose infection can cause diverse diseases, most notably adult T-cell leukemia/lymphoma (ATL or ATLL), an aggressive and fatal malignancy of CD4 T cells. The oncogenic ability of HTLV-I is mostly attributed to the viral transcriptional transactivator Tax. Tax alone is sufficient to induce specific tumors in mice depending on the promotor used to drive Tax expression, thereby being used to understand HTLV-I tumorigenesis and model the tumor types developed in Tax transgenic mice. Tax exerts its oncogenic role predominantly by activating the cellular transcription factor NF-κB. Here, we report that genetic deletion of NF-κB1, the prototypic member of the NF-κB family, promotes adrenal medullary tumors but suppresses neurofibromas in mice with transgenic Tax driven by the HTLV-I Long Terminal Repeat (LTR) promoter. The adrenal tumors are derived from macrophages. Neoplastic macrophages also infiltrate the spleen and lymph nodes, causing splenomegaly and lymphadenopathy in mice. Nevertheless, the findings could be human relevant, because macrophages are important target cells of HTLV-I infection and serve as a virus reservoir in vivo. Moreover, the spleen, lymph nodes and adrenal glands are the most common sites of tumor cell infiltration in HTLV-I-infected patients. These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.

The proliferation of antibiotic resistance genes (ARGs) and microbial communities in industrial wastewater treatment plant treating N,N-dimethylformamide (DMF) by AAO process.

The excessive use of antibiotics has resulted in the contamination of the environment with antibiotic resistance genes (ARGs), posing a significant threat to public health. Wastewater treatment plants (WWTPs) are known to be reservoirs of ARGs and considered to be hotspots for horizontal gene transfer (HGT) between bacterial communities. However, most studies focused on the distribution and dissemination of ARGs in hospital and urban WWTPs, and little is known about their fate in industrial WWTPs. In this study, collected the 15 wastewater samples containing N,N-dimethylformamide (DMF) from five stages of the anaerobic anoxic aerobic (AAO) process in an industrial WWTPs. The findings revealed a stepwise decrease in DMF and chemical oxygen demand (COD) content with the progression of treatment. However, the number and abundances of ARGs increase in the effluents of biological treatments. Furthermore, the residues of DMF and the treatment process altered the structure of the bacterial community. The correlation analysis indicated that the shift in bacterial community structures might be the main driver for the dynamics change of ARGs. Interestingly, observed that the AAO process may acted as a microbial source and increased the total abundance of ARGs instead of attenuating it. Additionally, found that non-pathogenic bacteria had higher ARGs abundance than pathogenic bacteria in effluents. The study provides insights into the microbial community structure and the mechanisms that drive the variation in ARGs abundance in industrial WWTPs.

Diverse functions of cytochrome c in cell death and disease.

The redox-active protein cytochrome c is a highly positively charged hemoglobin that regulates cell fate decisions of life and death. Under normal physiological conditions, cytochrome c is localized in the mitochondrial intermembrane space, and its distribution can extend to the cytosol, nucleus, and extracellular space under specific pathological or stress-induced conditions. In the mitochondria, cytochrome c acts as an electron carrier in the electron transport chain, facilitating adenosine triphosphate synthesis, regulating cardiolipin peroxidation, and influencing reactive oxygen species dynamics. Upon cellular stress, it can be released into the cytosol, where it interacts with apoptotic peptidase activator 1 (APAF1) to form the apoptosome, initiating caspase-dependent apoptotic cell death. Additionally, following exposure to pro-apoptotic compounds, cytochrome c contributes to the survival of drug-tolerant persister cells. When translocated to the nucleus, it can induce chromatin condensation and disrupt nucleosome assembly. Upon its release into the extracellular space, cytochrome c may act as an immune mediator during cell death processes, highlighting its multifaceted role in cellular biology. In this review, we explore the diverse structural and functional aspects of cytochrome c in physiological and pathological responses. We summarize how posttranslational modifications of cytochrome c (e.g., phosphorylation, acetylation, tyrosine nitration, and oxidation), binding proteins (e.g., HIGD1A, CHCHD2, ITPR1, and nucleophosmin), and mutations (e.g., G41S, Y48H, and A51V) affect its function. Furthermore, we provide an overview of the latest advanced technologies utilized for detecting cytochrome c, along with potential therapeutic approaches related to this protein. These strategies hold tremendous promise in personalized health care, presenting opportunities for targeted interventions in a wide range of conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer.

Chlorogenic Acid from Burdock Roots Ameliorates Oleic Acid-Induced Steatosis in HepG2 Cells through AMPK/ACC/CPT-1 Pathway.

Hepatic steatosis can cause liver dysfunction and cell injury, on which natural functional factors are expected to be an effective approach for long-term intervention. However, the cellular molecular mechanisms are unclear. Chlorogenic acid is a phenolic compound, which can regulate lipid metabolism and is abundant in burdock root. The aim of this study was to investigate the potential molecular mechanism of the effect of chlorogenic acid from burdock root (ACQA) on steatosis in HepG2 cells. In this study, we found that ACQA reduced the number of lipid droplets and lipid levels in oleic acid-treated HepG2 cells. Molecular mechanistic results showed that ACQA enhanced CPT-1 expression by activating AMPK-related signaling pathways, and the concentrations of Ca2+ and cAMP were increased with the intervention of ACQA. In addition, ACQA enhanced the ß-oxidation of fatty acids, reduced alanine transaminase and aspartate transaminase, and inhibited apoptosis in oleic acid-treated HepG2 cells. Our studies elucidate a novel mechanism that ACQA enhances the ß-oxidation of fatty acids through the AMPK/ACC/CPT-1 pathway to protect against steatosis in HepG2 cells, which provides insight into its molecular mechanism as well as intervention strategies for chlorogenic acid against fatty liver diseases.

Dynamic Zn/Electrolyte Interphase and Enhanced Cation Transfer of Sol Electrolyte for All-Climate Aqueous Zinc Metal Batteries.

Zn metal as one of the promising anodes of aqueous batteries possesses notable advantages, but it faces severe challenges from severe side reactions and notorious dendrite growth. Here, ultrathin nanosheets of α-zirconium phosphate (ZrP) are explored as an electrolyte additive. The nanosheets not only create a dynamic and reversible interphase on Zn but also promote the Zn2+ transportation in the electrolyte, especially in the outer Helmholtz plane near ZrP. Benefited from the enhanced kinetics and dynamic interphase, the pouch cells of Zn||LiMn2 O4 using this electrolyte remarkably improve electrochemical performance under harsh conditions, i.e. Zn powders as the Zn anode, high mass loading, and wide temperatures. The results expand the materials available for this dynamic interphase, provide an insightful understanding of the enhanced charge transfer in the electrolyte, and realize the combination of dynamic interphase and enhanced kinetics for all-climate performance.

Synergistic Cooperation of Zn(002) Texture and Amorphous Zinc Phosphate for Dendrite-Free Zn Anodes.

Zn anodes of aqueous Zn metal batteries face challenges from dendrite growth and side reactions. Building Zn(002) texture mitigates the issues but does not eradicate them. Zn(002) still faces severe challenges from corrosive electrolytes and dendrite growth, especially after hundreds of cycles. Therefore, it is necessary to have a passivation layer covering Zn(002). Here, Zn(002) texture and surface coating are achieved on Zn foils by an one-step annealing process, as demonstrated by ZnS, ZnSe, ZnF2, Zn3(PO4)2 (ZPO), etc. Using ZPO as a model, the coupling between surface coating and Zn(002) is illustrated in terms of dendrite-suppressing ability and diffusion energy barrier of Zn2+. The modified Zn foils (Zn(002)@ZPO) exhibit the excellent electrochemical performance, far superior to Zn(002) or ZPO alone. In the full cells, the performance is greatly improved even under harsh conditions, i.e., high areal capacity and limited Zn resource. This work achieves crystal engineering and surface coating on Zn anodes simultaneously and discloses the in-depth insights about the synergy of crystal orientation and passivation layers.

Tunable resonance Raman scattering of quantum dots in a nonlinear excitation regime.

Controllable tuning of electron-phonon coupling strength and excited state dynamics is important for the understanding of resonance Raman scattering in low-dimensional semiconductors. Here, we report a significant and reversible field-induced modulation in absolute resonance Raman intensity of quantum dots using ionic liquid gating. Meanwhile, a potential-dependent nonlinear relationship is present between Raman intensity and excitation power density. By exploring the parameter space within a time domain model, we find that the Raman intensity variation is mainly determined by the homogeneous linewidth. We further propose that the Fermi level positions and exciton species play key roles in the excited state decay rates.

1-Methylcyclopropene and UV-C Treatment Effect on Storage Quality and Antioxidant Activity of 'Xiaobai' Apricot Fruit.

The 'Xiaobai' apricot fruit is rich in nutrients and is harvested in summer, but the high temperature limits its storage period. To promote commercial quality and extend shelf life, we investigated the effectiveness of Ultraviolet C (UV-C) combined with 1-methylcyclopropene (1-MCP) treatment on 'Xiaobai' apricot fruit stored at 4 ± 0.5 °C for 35 days. The results revealed that the combination treatment of 1-MCP and UV-C performed better than either UV-C or 1-MCP alone in fruit quality preservation. The combination treatment could delay the increase in weight loss, ethylene production, and respiration rate; retain the level of soluble solid content, firmness, titratable acid, and ascorbic acid content; promote the total phenolics and flavonoids accumulation; improve antioxidant enzyme activity and relative gene expression, and DPPH scavenging ability; and reduce MDA, H2O2, O2.- production. The combined treatment improved the quality of apricot fruit by delaying ripening and increasing antioxidant capacity. Therefore, combining UV-C and 1-MCP treatment may be an effective way to improve the post-harvest quality and extend the storage period of the 'Xiaobai' apricot fruit, which may provide insights into the preservation of 'Xiaobai' apricot fruit.

ß-Glucan attenuates cognitive impairment of APP/PS1 mice via regulating intestinal flora and its metabolites.

BACKGROUND: The intestinal flora has been shown to be involved in the progression of Alzheimer's disease (AD) and can be improved by ß-glucan, a polysaccharide derived from Saccharomyces cerevisiae, which affects cognitive function through the intestinal flora. However, it is not known if this effect of ß-glucan is involved in AD. METHOD: This study used behavioral testing to measure cognitive function. After that, high-throughput 16 S rRNA gene sequencing and GC-MS were used to analyze the intestinal microbiota and metabolite SCFAs of AD model mice, and further explore the relationship between intestinal flora and neuroinflammation. Finally, the expressions of inflammatory factors in the mouse brain were detected by Western blot and Elisa methods. RESULTS: We found that appropriate supplementation of ß-glucan during the progression of AD can improve cognitive impairment and reduce A ß plaque deposition. In addition, supplementation of ß-glucan can also promote changes in the composition of the intestinal flora, thereby changing the flora metabolites in the intestinal content and reduce the activation of inflammatory factors and microglia in the cerebral cortex and hippocampus through the brain-gut axis. While reducing the expression of inflammatory factors in the hippocampus and cerebral cortex, thereby controlling neuroinflammation. CONCLUSION: The imbalance of the gut microbiota and metabolites plays a role in the progression of AD; ß-glucan blocks the development of AD by improving the gut microbiota and its metabolites and reducing neuroinflammation. ß-Glucan is a potential strategy for the treatment of AD by reshaping the gut microbiota and improving its metabolites.

Mutations and clinical characteristics of dRTA caused by SLC4A1 mutations: Analysis based on published patients.

Background and Aims: The genetic and clinical characteristics of patients with distal renal tubular acidosis (dRTA) caused by SLC4A1 mutations have not been systematically recorded before. Here, we summarized the SLC4A1 mutations and clinical characteristics associated with dRTA. Methods: Database was searched, and the mutations and clinical manifestations of patients were summarized from the relevant articles. Results: Fifty-three eligible articles involving 169 patients were included and 41 mutations were identified totally. Fifteen mutations involving 100 patients were autosomal dominant inheritance, 21 mutations involving 61 patients were autosomal recessive inheritance. Nephrocalcinosis or kidney stones were found in 72.27%, impairment in renal function in 14.29%, developmental disorders in 61.16%, hematological abnormalities in 33.88%, and muscle weakness in 13.45% of patients. The age of onset was younger (P < 0.01), urine pH was higher (P < 0.01), and serum potassium was lower (P < 0.001) in recessive patients than patients with dominant SLC4A1 mutations. Autosomal recessive inheritance was more often found in Asian patients (P < 0.05). Conclusions: The children present with metabolic acidosis with high urinary pH, accompanying hypokalemia, hyperchloremia, nephrocalcinosis, growth retardation and hematological abnormalities should be suspected as dRTA and suggested a genetic testing. The patients with recessive dRTA are generally more severely affected than that with dominant SLC4A1 mutations. Autosomal recessive inheritance was more often found in Asian patients, and more attentions should be paid to the Asian patients.

Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity.

Despite the rapid utilization of immunotherapy, emerging challenges to the current immune checkpoint blockade need to be resolved. Here, we report that elevation of CD73 levels due to its aberrant turnover is correlated with poor prognosis in immune-cold triple-negative breast cancers (TNBCs). We have identified TRIM21 as an E3 ligase that governs CD73 destruction. Disruption of TRIM21 stabilizes CD73 that in turn enhances CD73-catalyzed production of adenosine, resulting in the suppression of CD8+ T cell function. Replacement of lysine 133, 208, 262, and 321 residues by arginine on CD73 attenuated CD73 ubiquitylation and degradation. Diminishing of CD73 ubiquitylation remarkably promotes tumor growth and impedes antitumor immunity. In addition, a TRIM21high/CD73low signature in a subgroup of human breast malignancies was associated with a favorable immune profile. Collectively, our findings uncover a mechanism that governs CD73 proteolysis and point to a new therapeutic strategy by modulating CD73 ubiquitylation.

Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis.

Selective macroautophagy/autophagy maintains cellular homeostasis through the lysosomal degradation of specific cellular proteins or organelles. The pro-survival effect of selective autophagy has been well-characterized, but the mechanism by which it drives cell death is still poorly understood. Here, we use a quantitative proteomic approach to identify HPCAL1 (hippocalcin like 1) as a novel autophagy receptor for the selective degradation of CDH2 (cadherin 2) during ferroptosis. HPCAL1-dependent CDH2 depletion increases susceptibility to ferroptotic death by reducing membrane tension and favoring lipid peroxidation. Site-directed mutagenesis aided by bioinformatic analyses revealed that the autophagic degradation of CDH2 requires PRKCQ (protein kinase C theta)-mediated HPCAL1 phosphorylation on Thr149, as well as a non-classical LC3-interacting region motif located between amino acids 46-51. An unbiased drug screening campaign involving 4208 small molecule compounds led to the identification of a ferroptosis inhibitor that suppressed HPCAL1 expression. The genetic or pharmacological inhibition of HPCAL1 prevented ferroptosis-induced tumor suppression and pancreatitis in suitable mouse models. These findings provide a framework for understanding how selective autophagy promotes ferroptotic cell death.Abbreviations: ANXA7: annexin A7; ARNTL: aryl hydrocarbon receptor nuclear translocator like; CCK8: cell counting kit-8; CDH2: cadherin 2; CETSAs: cellular thermal shift assays; CPT2: carnitine palmitoyltransferase 2; DAMP, danger/damage-associated molecular pattern; DPPH: 2,2-diphenyl-1-picrylhydrazyl; DFO: deferoxamine; EBNA1BP2: EBNA1 binding protein 2; EIF4G1: eukaryotic translation initiation factor 4 gamma 1; FBL: fibrillarin; FKBP1A: FKBP prolyl isomerase 1A; FTH1: ferritin heavy chain 1; GPX4: glutathione peroxidase 4; GSDMs: gasdermins; HBSS: Hanks' buffered salt solution; HMGB1: high mobility group box 1; HNRNPUL1: heterogeneous nuclear ribonucleoprotein U like 1; HPCAL1: hippocalcin like 1; H1-3/HIST1H1D: H1.3 linker histone, cluster member; IKE: imidazole ketone erastin; KD: knockdown; LDH: lactate dehydrogenase; LIR: LC3-interacting region; MAGOH: mago homolog, exon junction complex subunit; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MDA: malondialdehyde; MLKL: mixed lineage kinase domain like pseudokinase; MPO: myeloperoxidase; MTOR: mechanistic target of rapamycin kinase; OE: overexpressing; OSTM1: osteoclastogenesis associated transmembrane protein 1; PRKC/PKC: protein kinase C; PRKAR1A: protein kinase cAMP-dependent type I regulatory subunit alpha; PRDX3: peroxiredoxin 3; PTGS2: prostaglandin-endoperoxide synthase 2; ROS: reactive oxygen species; SLC7A11: solute carrier family 7 member 11; SLC40A1: solute carrier family 40 member 1; SPTAN1: spectrin alpha, non-erythrocytic 1; STS: staurosporine; UBE2M: ubiquitin conjugating enzyme E2 M; ZYX: zyxin.

The Emerging Role of Deubiquitinases in Cell Death.

Regulated cell death (RCD) is a signal-controlled process that not only eliminates infected, damaged, or aged cells but is also implicated in a variety of pathological conditions. The process of RCD is regulated by intracellular proteins that undergo varying levels of post-translational modifications, including mono- or polyubiquitination. Functionally, ubiquitination can affect protein abundance, localization, and activity. Like other post-translational modifications, ubiquitination is a dynamic and reversible process mediated by deubiquitinases, a large class of proteases that cleave ubiquitin from proteins and other substrates. The balance between ubiquitination and deubiquitination machinery determines cell fate under stressful conditions. Here, we review the latest advances in our understanding of the role of deubiquitinases in regulating the main types of RCD, including apoptosis, necroptosis, pyroptosis, and ferroptosis. This knowledge may contribute to identifying new protein degradation-related prognostic markers and therapeutic targets for human disease.

Bispecific T cell engagers kill resistant cells during KRAS-G12C blockade therapy.

The covalent KRAS-G12C inhibitors (G12Ci) are rapidly changing the treatment landscape for advanced non-small cell lung cancer, but drug resistance remains a clinical challenge. Two recent studies have developed bispecific T cell engagers that form a link between T cells and tumor cells to selectively eliminate G12Ci-resistant cells.

A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis.

Ferroptosis is a type of lipid peroxidation-dependent cell death that is emerging as a therapeutic target for cancer. However, the mechanisms of ferroptosis during the generation and detoxification of lipid peroxidation products remain rather poorly defined. Here, we report an unexpected role for the eukaryotic translation initiation factor EIF4E as a determinant of ferroptotic sensitivity by controlling lipid peroxidation. A drug screening identified 4EGI-1 and 4E1RCat (previously known as EIF4E-EIF4G1 interaction inhibitors) as powerful inhibitors of ferroptosis. Genetic and functional studies showed that EIF4E (but not EIF4G1) promotes ferroptosis in a translation-independent manner. Using mass spectrometry and subsequent protein-protein interaction analysis, we identified EIF4E as an endogenous repressor of ALDH1B1 in mitochondria. ALDH1B1 belongs to the family of aldehyde dehydrogenases and may metabolize the aldehyde substrate 4-hydroxynonenal (4HNE) at high concentrations. Supraphysiological levels of 4HNE triggered ferroptosis, while low concentrations of 4HNE increased the cell susceptibility to classical ferroptosis inducers by activating the NOX1 pathway. Accordingly, EIF4E-dependent ALDH1B1 inhibition enhanced the anticancer activity of ferroptosis inducers in vitro and in vivo. Our results support a key function of EIF4E in orchestrating lipid peroxidation to ignite ferroptosis.

Factors influencing intention to apply spatial approaches to on-farm experimentation: insights from the Australian winegrape sector.

Grape growers are often constrained by available time and labor to conduct trials that deliver informative results. Spatially distributed trial designs coupled with data collection using sensing technologies can introduce efficiencies and also account for the impact of land variability on trial results. Various spatial approaches have been proposed, yet how farmers perceive them is largely unknown. We collaborated with four wine businesses in Australia to explore how grape growers and viticultural consultants perceive a simplified spatial approach to experimentation involving one or more vineyard rows or "strips." In each case, the simplified strip approach was applied alongside growers' or consultants' own methods to compare the perceived value of different methods. The Theory of Planned Behavior was used as an analytical framework to identify factors influencing participants' intentions towards adopting the strip approach. Our findings show that growers and consultants perceived several advantages of the strip approach over their own methods. Key factors impeding uptake were resource constraints for collecting trial data and lack of skills and knowledge to use and analyze spatial data to position the trial and interpret results. These constraints highlight the need to support growers and consultants who see value in this approach by developing automated and affordable measurements for viticultural variables beyond yield, and by providing training on how to analyze and interpret spatial and response data. This study provides novel insights for private and public sectors on where to focus efforts to facilitate adoption of spatial approaches to On-Farm Experimentation by specific target audiences.

The evolving views of the simplest pectic polysaccharides: homogalacturonan.

Pectin is an important component of cell wall polysaccharides and is important for normal plant growth and development. As a major component of pectin in the primary cell wall, homogalacturonan (HG) is a long-chain macromolecular polysaccharide composed of repeated α-1,4-D-GalA sugar units. At the same time, HG is synthesized in the Golgi apparatus in the form of methyl esterification and acetylation. It is then secreted into the plasmodesmata, where it is usually demethylated by pectin methyl esterase (PME) and deacetylated by pectin acetylase (PAE). The synthesis and modification of HG are involved in polysaccharide metabolism in the cell wall, which affects the structure and function of the cell wall and plays an important role in plant growth and development. This paper mainly summarizes the recent research on the biosynthesis, modification and the roles of HG in plant cell wall.

A bibliometrics analysis and visualization of autism spectrum disorder.

Background: The prevalence of autism spectrum disorder (ASD) increased rapidly in the last 20 years. Although related research has developed rapidly, little is known about its etiology, diagnostic marker, or drug treatment, which forces researchers to review and summarize its development process and look for the future development direction. Methods: We used bibliometrics to analyze papers of ASD in the Web of Science from 1998 to 2021, to draw the network of authors, institutions, countries, and keywords in the ASD field, and visualize the results. Results: A total of 40,597 papers were included with a continually increasing trend. It turns out that the research on ASD is mainly concentrated in universities. The United States has the largest number of ASD studies, followed by England and Canada. The quality of papers related to ASD is generally high, which shows that ASD research has become a hot spot of scientific research. The keywords of ASD etiology and diagnostic markers can be classified into at least 7 aspects. The detection of keywords shows that ASD research is mostly based on its subtypes, takes children as the study population, focuses on neurodevelopmental imaging or genetics, and pays attention to individual differences. And ASD research has changed greatly under the impact of Corona Virus Disease 2019 in the past 2 years. Conclusion: We consider the future development direction should be based on the improvement of case identification, accurate clinical phenotype, large-scale cohort study, the discovery of ASD etiology and diagnostic markers, drug randomized controlled trials, and telehealth.

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.