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The retinoic acid receptor-related orphan receptor γt (RORγt) is a key regulator of Th17 cells, associated with autoimmune diseases, making it a significant drug target. Herein, we designed and synthesized 1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinoline derivatives, improving upon GSK2981278 to enhance bioavailability. Of which, D4 exhibited superior bioavailability (F = 48.1 and 32.9% in mice and rats, respectively) compared to GSK2981278 (F = 6.2 and 4.1%, respectively), and effectively treated psoriasis in mice at lower doses. Moreover, for the first time, we report the efficacies of a RORγt inverse agonist in mouse models of rheumatoid arthritis. ( R )-D4 , the eutomer of D4 , matched or exceeded GSK2981278's therapeutic effects at lower doses, with no adverse effects observed after 2 weeks of administration. These results position ( R )-D4 as a promising and orally bioavailable candidate for Th17-mediated autoimmune disease treatment.

The aim of this study was to reveal the effects of yeast culture replacing fish meal (FM) or chicken meal (CM) on the growth performance, serum biochemical indexes, intestinal digestive enzyme activities, hepatic antioxidant, and hepatic and intestinal histology of bullfrog ( Lithobates catesbeianus ). The basal diet contained 100 g/kg FM and 100 g/kg CM, and then yeast culture was used to decrease FM or CM level to 75 and 50 g/kg with yeast culture inclusion of 32 and 64 g/kg, respectively, resulting in five groups of isonitrogenous diets (control, FM75, FM50, CM75, and CM50). A total of 450 bullfrogs (45.5 ± 0.4 g initial weight) were fed the five diets for 50 days. (1) The FM50 group presented significantly lower weight gain, condition factor, hind leg index, and higher feed conversion ratio than the control group, while the other three groups of FM75, CM75, and CM50 showed no significant difference in growth performance when compared to the control group. (2) The serum triglyceride content of FM50 group was significantly lower, while the alkaline phosphatase activity was significantly higher than those of the control group. The serum total cholesterol levels were significantly lower in the CM50 group compared to the control group. (3) In intestinal digestive enzyme activities, the trypsin and α-amylase activities in the CM75 and CM50 groups, the trypsin activity in the FM75 group, and lipase activity in the CM50 group were all significantly higher than those in the other groups. (4) The replacement of 50% FM with yeast culture (FM50 and CM50 groups) promoted the total antioxidant capacity in the liver, but compared to the control group, the intestinal villi height and muscularis propria thickness in the FM50 group were significantly lower. There was no difference ( P > 0.05) in liver histology among all the groups. In conclusion, in a basal diet containing 100 g/kg FM and 100 g/kg CM, 32.0 and 64.0 g/kg yeast cultures could successfully replace 25% of dietary FM and 50% of dietary CM without negative effects on the growth performance, serum biochemical indexes, and hepatic and intestinal health of bullfrogs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Yun-Feng Chen et al.)

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123 . This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC 50 = 2.1 nM) and FLT3-ITD (IC 50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC 50 = 0.98 nM) and MV4-11 (IC 50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC 50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC 50 values of 3.3, 3.2 and 5.8 μM. Further cell assays showed IC 50 values of 0.2, 1.2 and 0.6 μM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible., (© 2024 Wiley-VCH GmbH.)

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Over the past decades, the role of rearranged during transfection (RET) alterations in tumorigenesis has been firmly established. RET kinase inhibition is an essential therapeutic target in patients with RET-altered cancers. In clinical practice, initial efficacy can be achieved in patients through the utilization of multikinase inhibitors (MKIs) with RET inhibitory activity. However, the effectiveness of these MKIs is impeded by the adverse events associated with off-target effects. Recently, many RET-selective inhibitors, characterized by heightened specificity and potency, have been developed, representing a substantial breakthrough in the field of RET precision oncology. This Perspective focuses on the contemporary understanding of RET mutations, recent advancements in next-generation RET inhibitors, and the challenges associated with resistance to RET inhibitors. It provides valuable insights for the development of next-generation MKIs and selective RET inhibitors.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 μΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC 50 values of 0.75 μM and 0.64 μM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest. No disclosures were reported by all the authors., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Virus infection has been one of the main causes of human death since the ancient times. Even though more and more antiviral drugs have been approved in clinic, long-term use can easily lead to the emergence of drug resistance and side effects. Fortunately, there are many kinds of metabolites which were produced by plants, marine organisms and microorganisms in nature with rich structural skeletons, and they are natural treasure house for people to find antiviral active substances. Aiming at many types of viruses that had caused serious harm to human health in recent years, this review summarizes the natural products with antiviral activity that had been reported for the first time in the past ten years, we also sort out the source, chemical structure and safety indicators in order to provide potential lead compounds for the research and development of new antiviral drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Glioma is one of the most common types of brain tumors, and its high recurrence and mortality rates threaten human health. In 2008, the frequent isocitrate dehydrogenase 1 (IDH1) mutations in glioma were reported, which brought a new strategy in the treatment of this challenging disease. In this perspective, we first discuss the possible gliomagenesis after IDH1 mutations (mIDH1). Subsequently, we systematically investigate the reported mIDH1 inhibitors and present a comparative analysis of the ligand-binding pocket in mIDH1. Additionally, we also discuss the binding features and physicochemical properties of different mIDH1 inhibitors to facilitate the future development of mIDH1 inhibitors. Finally, we discuss the possible selectivity features of mIDH1 inhibitors against WT-IDH1 and IDH2 by combining protein-based and ligand-based information. We hope that this perspective can inspire the development of mIDH1 inhibitors and bring potent mIDH1 inhibitors for the treatment of glioma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

This study investigated the dietary effects of lipid and protein levels on growth performance, feed utilization, body composition, lipid metabolism, and antioxidant capacity of triploid rainbow trout, Oncorhynchus mykiss . A 3 × 2 two-factor design was conducted with three crude lipid levels of 4%, 9%, and 14% (L4, L9, and L14) and two crude protein levels of 44%, 49% (P44, P49). Therefore, a total of six diets were prepared as P44/L4, P44/L9, P44/L14, P49/L4, P49/L9, and P49/L14. Triploid rainbow trout (initial body weight 65.0 ± 0.1 g) were fed one of the six diets for 80 days. The results showed that weight gain (WG), protein retention (PR), and protein efficiency rate (PER) significantly increased with increasing the dietary lipid level at the same crude protein level, while feed conversion ratio (FCR) and hepatosomatic index significantly decreased ( P < 0.05). At the same lipid level, there was no difference in WG, FCR, PR, PER between 44% and 49% crude protein group ( P > 0.05). The P49/L14 group had the highest WG (374.6%) and lowest FCR (1.25), while P44/L14 group had the highest PER (1.80) and PR (25.06%) with similar WG and FCR to P49/L14 group. The crude lipid contents in whole fish were significantly higher in the L14 group than those in the L4 and L9 groups ( P < 0.05). Muscle n -3 PUFAs, n -6 PUFAs, and PUFAs levels were positively correlated with dietary lipid level, while n -6 PUFAs was negatively correlated with dietary protein level. Dietary protein, dietary lipid, and their interaction significantly affected hepatic malondialdehyde (MDA) content, aspartate aminotransferase, lipase (LPS), and fatty acid synthase (FAS) activities ( P < 0.05). In both P44 and P49 groups, LPS and FAS activities increased with increasing the dietary lipid level. MDA content significantly decreased in the P44 group and increased in the P49 group with increasing the dietary lipid level ( P < 0.05). As dietary protein level increased, serum total cholesterol level increased, while hepatic phosphoenolpyruvate carboxykinase activity decreased. With increasing the dietary lipid level, total superoxide dismutase, catalase, total nitric oxide synthase, and fructose-1,6-bisphosphatase activities showed an increasing trend, while the opposite was true for alanine aminotransferase activity. In conclusion, based on growth performance and feed utilization, dietary protein level of 44% and dietary lipid level of 14% (measured value, 43.71% and 13.62%) were suggested for young triploid rainbow trout., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Yun-Feng Chen et al.)

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4-(4-aminophenyl)-6-phenylisoxazolo[3,4-b]pyridine-3-amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC 50  = 123 nM) and FLT3-internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 μM. Besides, F15 exhibited potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell lines MOLM-13 (IC 50  = 253 nM) and MV4-11 (IC 50  = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML., (© 2023 Wiley Periodicals LLC.)

Aim: The clinical benefits of FLT3 inhibitors against acute myeloid leukemia (AML) have been limited by selectivity and resistance mutations. Thus, to identify FLT3 inhibitors possessing high selectivity and potency is of necessity. Methods & results: The authors used computational methods to systematically compare pocket similarity with 269 kinases. Subsequently, based on these investigations and beginning with in-house compound 10 , they synthesized a series of 6-methyl-isoxazol[3,4- b ]pyridine-3-amino derivatives and identified that compound 45 (IC 50 : 103 nM) displayed gratifying potency in human AML cell lines with FLT3-internal tandem duplications mutation as well as FLT3-internal tandem duplications-tyrosine kinase domain-transformed BaF3 cells. Conclusion: The integrated biological activity results indicated that compound 45 deserves further development for therapeutic remedies for AML.

Fms-like tyrosine kinase 3 (FLT3) mutation has been strongly associated with increased risk of relapse, and the irreversible covalent FLT3 inhibitors had the potential to overcome the drug-resistance. In this study, a series of simplified 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine derivatives containing two types of Michael acceptors (vinyl sulfonamide, acrylamide) were conveniently synthesized to target FLT3 and its internal tandem duplications (ITD) mutants irreversibly. The kinase inhibitory activities showed that compound C14 displayed potent inhibition activities against FLT3 (IC 50  = 256 nM) and FLT3-ITD by 73 % and 25.34 % respectively, at the concentration of 1 μM. The antitumor activities indicated that C14 had strong inhibitory activity against the human acute myeloid leukemia (AML) cell lines MOLM-13 (IC 50  = 507 nM) harboring FLT3-ITD mutant, as well as MV4-11 (IC 50  = 325 nM) bearing FLT3-ITD mutation. The biochemical analyses showed that these effects were related to the ability of C14 to inhibit FLT3 signal pathways, and C14 could induce apoptosis in MV4-11 cell as demonstrated by flow cytometry. Fortunately, C14 showed very weak potency against FLT3-independent human cervical cancer cell line HL-60 (IC 50  > 10 μM), indicating that it might have no off-target toxic effects. In light of these data, compound C14 represents a novel covalent FLT3 kinase inhibitor for targeted therapy of AML., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Connective tissue growth factor (ctgf) is involved in the proliferation, migration, adhesion of cell, and the constituent of extracellular matrix, which plays an important role in embryogenesis, angiogenesis, wound repair, and fibrosis diseases. In this study, the cDNA sequence of grass carp ctgf gene was cloned by rapid amplification of cDNA ends (RACE) method; then, the characteristics of this gene and the predicted protein sequence were analyzed by bioinformatics methods, and the tissue differential expression pattern was detected by the quantitative real-time PCR. The results showed that the grass carp ctgf gene has a full-length of 2223 bp, encoding 343 amino acids. The deduced CTGF protein is a hydrophilic and secretary protein with a molecular mass of 37,978.2 Da and an isoelectric point of 8.22. The signal peptide locates between residue positions 1 and 22 of the polypeptide chain. The protein contains α-helix, β-strand, and loops. The CTGF protein of grass carp shows a homology of 98%, 96%, 91%, and 91% with Wuchang bream (Megalobrama amblycephala), zebrafish (Danio rerio), common carp (Cyprinus carpio), and Mexican tetra (Astyanax mexicanus). The grass carp ctgf gene expressed significantly higher in blood and spleen than that in other tissues (P < 0.05). The low expression tissues included the heart, gill, skin, muscle, kidney, brain, and intestinal, and the lowest expression tissue was the liver. The results are consistent with the function of this gene.

The synergistic antioxidant mechanism of chlorogenic acids (CQAs) was studied in this paper through cyclic voltammograms (CV), oil-water partition coefficient (P), FT-IR, XRD and circular dichroism (CD). The antioxidant capability of CQAs isomers and their mixture was determined by using ABTS free radical quenching ability assay. The results showed that the bigger the antioxidant activity disparity between the CQAs molecules was, the higher the content of high antioxidant activity CQAs was, the better the synergistic effect of the CQAs combination mixture became; The oxidation potential (Epa) of CQAs combination mixture kept constant in the synergistic experiments, which indicted the oxidative coupling interaction don’t exist between the CQAs; The charge transferred (Q) and antioxidant activity exhibited high correlation (0.92); the practical Q was higher than the theoretical Q in the synergistic process and this confirmed that the CQAs (dicaffeoylquinic acids) regeneration of high antioxidant activity happened; the CQAs mixture with the absolute difference value of oil-water partition coefficient of 0.13 gave the good interface effect and high synergistic degree; the interaction and the regular arrangement between the CQAs combination were not discovered through FT-IR, XRD and CD. Therefore, the regeneration mechanism of CQAs molecules and the interface effect of reaction system were the main cause of the phenomenon of the synergistic antioxidant of CQAs.

Unc45 myosin chaperone b(unc45b)gene is a molecular chaperone that mediates the folding, assembly and accumulation of thick-filament myosin in the formation of sarcomere, which plays an important role in the development of striated muscle and the stability of sarcomere. In this study, the complete cDNA sequence of unc45b gene of grass carp was obtained by rapid amplification of cDNA ends (RACE), and the characteristics of the unc45b protein predicted from gene sequence was analyzed by bioinformatics methods. The differential expression pattern in tissues was also detected by quantitative real-time PCR. The results showed that the full-length of unc45b gene of grass carp is 3163 bp, which contains a 60 bp 5'UTR, a 298 bp 3'UTR, and a 2865 bp open reading frame (ORF) encoding a 934 amino acid peptide. The deduced unc45b protein exhibits a homology of 92, 86, 86 % with the protein of zebrafish (Danio rerio), channel catfish (Ietalurus punctatus) and tilapia (Oreochromis niloticus) respectively, and the protein contains UCS myosin head binding domain and TPR peptide repeat domain. The protein is a hydrophilic and non-secretory protein with a molecular mass and isoeletronic point of 103,699.8 and 7.39 Da. The structural elements of the protein includes α-helixes and loops, and the unc45b gene highly expresses in skeletal muscle and heart in grass carp. This study laid a foundation for further research in explaining the myofibril accumulation in crisped grass carp.

Scutellaria-coptis herb couple is widely used traditional Chinese medicine (TCM) in treating type 2 diabetes; however, the in vivo integrated metabolism of its main bioactive components in type 2 diabetic rats remains unknown. In this paper, ultra-performance liquid chromatography (UPLC) coupled to quadrupole time-of-flight (Q-TOF) and the MetaboLynx™ software combined with mass defect filtering (MDF) together provided unique high throughput capabilities for drug metabolism study with excellent MS mass accuracy and enhanced MS(E) data acquisition. This rapid automated analysis method was successfully applied for screening and identification of the absorbed and metabolized constituents after oral administration of scutellaria-coptis extract to rats. The results showed that a total of 14 metabolites of two parent compounds were detected and tentatively identified in vivo based on the characteristics of their protonated ions. Main parent components of scutellaria-coptis extract such as baicalin and berberine were absorbed into the blood circulation of the rats. Differences of metabolite classes were not observed between normal and type 2 diabetic rat plasma and urine samples. However, the concentrations of baicalin and methylated berberine in type 2 diabetic rat plasma were much higher than those in normal sample. While, the concentrations of these two compounds in type 2 diabetic rat urine were remarkably lower than those in normal sample. This helped maintain a high blood drug concentration which might be beneficial for the treatment of type 2 diabetes. Additionally, the developed method was simple and reliable, revealing that it could be used to rapid screen and propose the structures of active components responsible for pharmacological effects of scutellaria-coptis and to better clarify its action mechanism. This work suggests that the integrative metabolism approach makes a useful template for drug metabolism research of TCMs., (Copyright © 2014. Published by Elsevier B.V.)

Objective: To investigate the metabolic routes and metabolites of myricitrin, an important active ingredient of traditional herbal medicine, yielded by the isolated human intestinal bacteria, which have not been reported previously., Methods: Fresh human fecal samples were collected from a healthy female volunteer and about 100 different bacterial colonies were isolated. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry technique combined with Metabolynx™ software was used for analysis of the metabolic profile of myricitrin by the isolated human intestinal bacteria., Results: One hundred different bacterial colonies, which developed on plates, were picked up, and four of them were further identified by using the technique of 16S rRNA gene sequencing due to their relatively strong metabolic capacity toward myricitrin. Most of them belong to Escherichia. Parent compound and three metabolites (quercetin-3-O-rhamnoside, myricetin and quercetin) were detected in the isolated bacterial samples compared with blank samples. The metabolic pathways of myricitrin included deglycosylation and dehydroxylation., Conclusions: These metabolites suggested that myricitrin was first dehydroxylated to quercetin-3-O-rhamnoside and subsequently deglycosylated to quercetin. Additionally, myricitrin could also be deglycosylated to the aglycon myricetin. Moreover, those metabolites might influence the biological effect of myricitrin in vivo, which led to affect the clinical effects of the medicinal plants and traditional herb medicines.

Signal transducer and activator of transcription 3 (STAT₃) binds to Janus kinase 2 (JAK₂) to initiate the JAK₂/STAT₃ signal transduction pathway, which plays an important role in cancer cell proliferation, immune regulation, reproduction, lipid metabolism, and other physiological processes of the organism. In this study, the cDNA sequence of the STAT₃ gene from grass carp was cloned using RACE (rapid-amplification of cDNA ends). Twelve characteristics of the STAT₃ gene and its encoded protein sequence were predicted and analyzed using bioinformatics methods; these features included the general physical and chemical properties, the hydrophobicity, the secondary structure and the three-dimensional structure of the protein. Quantitative real-time PCR was employed to detect grass carp STAT₃ expression pattern in different tissues. The results showed that the full-length STAT₃ gene from grass carp is 2739-bp long and contains a 216-bp 5'UTR, a 300-bp 3'UTR, and a 2223-bp open reading frame (ORF) that encodes a 740-amino acid peptide. The deduced protein exhibited 99%∼94% homology to the STAT₃ protein of zebrafish (Danio rerio), medaka (Oryzias latipes), turbot (Scophthalmus maximus), white-spotted char (Salvelinus leucomaenis), mandarin fish (Siniperca chuatsi), rainbow trout (Oncorhynchus mykiss), and green pufferfish (Tetraodon fluviatilis). The deduced grass carp STAT₃ protein contains a protein interaction domain, an alpha domain, a DNA binding domain, and an SH2 domain. The STAT₃ protein of grass carp is a hydrophilic and non-secretory protein, and its molecular mass and isoeletronic point were found to be 98,5412.1 Da and 6.39, respectively. The structural elements of STAT₃ included α-helixes, β-sheets, and loops. The grass carp STAT₃ is expressed in all of the six tissues tested, which were the liver, spleen, gill, muscle, heart, and brain. The highest expression level was found in the liver (P < 0.05), whereas a significantly lower expression level was found in the spleen, gills, brain, and muscle (P < 0.05), and the lowest expression level was found in the heart (P < 0.05). This study provides a basis for further structural and functional exploration of the STAT₃ from grass carp, including its deduced protein and its signal transduction function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The objective of this study was to assess the effect of sage, at levels of 0.05%, 0.1% and 0.15% (w/w), on the oxidative stability of Chinese-style sausage stored at 4°C for 21 days. The results showed that inclusion of sage in sausages resulted in lower L* values (P<0.05) and higher a* values (P<0.05) compared to the control. During refrigerated storage, sausages containing sage showed significantly retarded increases in TBARS values, and in the formation of protein carbonyls (P<0.05), but showed accelerated losses of thiol groups (P<0.05). Addition of sage to the sausages at levels of 0.1% and 0.15% reduced textural deterioration during refrigerated storage (P<0.05). Sage used in this study had no negative effects on the sensory properties of sausages., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Bone morphogenetic protein (BMP15) is a member of the transforming growth factor β (TGF-β) superfamily with a key role in regulating follicle development in mammals and birds. However, potential ovarian roles of BMPs remain unexplored in teleosts. In this study, the full-length sequences of bmp15 were obtained using rapid-amplification of cDNA ends (RACE). The full-length cDNA sequence of bmp15 is 2217 bp which contained 214 bp 5'-UTR and 845 bp 3'-UTR. The open reading frame (ORF) sequence of bmp15 is 1158 bp, encoding a predicted protein of 385 amino acid residues. BMP15 has a specific RXXR protease cleavage site of TGF-β superfamily (is RIRR) and six conserved cysteine residues. Using real-time quantitative PCR revealed that bmp15 mRNA was largely expressed in the ovary and testis and mostly in oocytes within the follicle, slightly expressed in muscle, liver and pituitary. BMP15 is mainly present at stage I follicles by real-time quantitative PCR and immunohistochemistry. Phylogenetic analysis showed that gibel carp bmp15 was similar to bmp15 of zebrafish and other fish species. Treatment with human chorionic gonadotropin (hCG) in isolated follicles of gibel carp in vitro showed altered bmp15 mRNA expression: when treated with 10 ng/mL hCG for 10h, the expression level of bmp15 was significantly increased. However, with proceeding cultivation, the expression level of BMP15 mRNA decreased. The results of this study indicate that bmp15 may play a key role during development of follicles in gibel carp, especially in early stage follicles., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The interactions between three proteins (BSA, lysozyme and myoglobin) and three flavonoids (quercetin, kaempferol and rutin) were analyzed, using three-dimensional fluorescence spectrometry in combination with UV-Vis spectrometry and Fourier transform infrared (FTIR) spectroscopy. The stabilities of unbound flavonoids and protein-bound flavonoids were compared. The correlation between the interaction and stability was analyzed. The results showed that the hydrophobic interaction was the main binding code in all proteins and flavonoids systems. However, the hydrogen bond has been involved merely in the BSA system. The stability of all three flavonoids (quercetin, kaempferol and rutin) was improved by BSA. There was a great correlation between the hydrogen bonding and the stability of the flavonoids in the presence of BSA. It suggested that the protection of BSA on the flavonoids was due to the intermolecular hydrogen bonding between BSA and flavonoid, and the stronger hydrogen bonding resulted in more protection.

The microstructure of the pectin/whey protein isolate mixtures under incompatible conditions was investigated using dynamic light scattering spectroscopy, transmission electron microscopy and shear-viscosity model. Under the condition of 90 degrees C and pH 7.4, the presence of negatively charged pectin could induce depletion aggregation in a 5% protein solution, and promote phase separation; precisely, when the mass ratio of pectin/whey protein isolate was lower than 0.08, the hydrodynamic size of the aggregates was less than 300 nm, and the system showed Newtonian properties; when the mass ratio was higher than 0.08, the viscosity of the solution increased rapidly, the shear thinning properties became obvious and the size of the aggregates was close to 700 nm.

The particles conformation of the sericin protein extracted from silkworm Bombyx mori was studied under the conditions of different pH and salt concentrations by infrared spectroscopy (IR), dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. The IR spectrum of sericin protein arises predominantly from C=O stretching vibration around the amide I region of 1 700-1 600 cm(-1). A strong trend of aggregation of the protein could be observed under specified experimental conditions. The apparent isoelectric point of the sericin protein was about 3.7. The DLS method was used to investigate the effects of pH and NaCl on the size distribution, where a large polydispersity of the system could be observed. Compared to pH 4 or high NaCl concentration, at pH 3, 8 or low NaCl concentration the sericin aggregation shows a relatively smaller size but larger polydispersity. TEM was used to investigate the microstructure of the aggregated sericin protein, where a loose and pine-like branched form could be observed at pH 3 or 8; however, a relatively compact structure was observed near pH 4 or at high salt concentration At pH 4 the spherical monomer size can be calculated at around (60 +/- 6) nm (n = 10) by TEM measurement. These phenomena could be explained by the effects of the electrostatic repulsion, hydrogen bonding and Van der Waals attractive force, which provide a basic theory for the application of sericin as biomaterial.