Curcumin alleviates zearalenone-induced liver injury in mice by scavenging reactive oxygen species and inhibiting mitochondrial apoptosis pathway.

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.

C-N Axially Chiral Heterobiaryl Isoquinolinone Skeletons Construction via Cobalt-Catalyzed Atroposelective C-H Activation/Annulation.

Herein, the atroposelective construction of isoquinolinones bearing a C-N chiral axis has been successfully developed via a Co-catalyzed C-H bond activation and annulation process. This conversion can be effectively carried out in an environmentally friendly oxygen atmosphere to generate the target C-N axially chiral frameworks with excellent reactivities and enantioselectivities (up to >99% ee) in the absence of any additives. Additionally, the current protocol has proved to be an alternative approach for the C-N axial architectures fabrication under electrochemical conditions for cobalt/Salox catalysis, and this strategy allowed the efficient and atom-economical synthesis of various axially chiral isoquinolinones under mild reaction conditions.

Cobalt-catalyzed atroposelective C-H activation/annulation to access N-N axially chiral frameworks.

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, and advanced material skeletons. The anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report an efficient method for the enantioselective synthesis of N-N axially chiral frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. The reaction proceeds under mild conditions by using Co(OAc)2·4H2O as the catalyst with a chiral salicyl-oxazoline (Salox) ligand and O2 as an oxidant, affording a variety of N-N axially chiral products with high yields and enantioselectivities. This protocol provides an efficient approach for the facile construction of N-N atropisomers and further expands the range of of N-N axially chiral derivatives. Additionally, under the conditions of electrocatalysis, the desired N-N axially chiral products were also successfully achieved with good to excellent efficiencies and enantioselectivities.

Cobalt-catalyzed enantioselective C-H/N-H annulation of aryl sulfonamides with allenes or alkynes: facile access to C-N axially chiral sultams.

Herein we report a cobalt-catalyzed enantioselective C-H/N-H annulation of aryl sulfonamides with allenes and alkynes, using either chemical or electrochemical oxidation. By using O2 as the oxidant, the annulation with allenes proceeds efficiently with a low catalyst/ligand loading of 5 mol% and tolerates a wide range of allenes, including 2,3-butadienoate, allenylphosphonate, and phenylallene, resulting in C-N axially chiral sultams with high enantio-, regio-, and position selectivities. The annulation with alkynes also exhibits excellent enantiocontrol (up to >99% ee) with a variety of functional aryl sulfonamides, and internal and terminal alkynes. Furthermore, electrochemical oxidative C-H/N-H annulation with alkynes is achieved in a simple undivided cell, demonstrating the versatility and robustness of the cobalt/Salox system. The gram-scale synthesis and asymmetric catalysis further highlight the practical utility of this method.

C-N Axially Chiral Heterobiaryl Skeletons Construction via Cobalt-Catalyzed Atroposelective Annulation.

Herein, the atroposelective construction of five-six heterobiaryl skeleton-based C-N chiral axis has been successfully accomplished via a Co-catalyzed C-H bond activation and annulation process, in which the isonitrile was employed as the C1 source and the 8-aminoquinoline moiety served as both directing group and integral part of C-N atropisomers, respectively. This conversion can be effectively carried out in an environmentally friendly oxygen atmosphere, generating the target axial heterobiaryls with excellent reactivities and enantioselectivities (up to >99% ee) in the absence of any additives, and the obtained 3-iminoisoindolinone products with a five membered N-heterocycle exhibit high atropostability. Additionally, the C-N axially chiral monophosphine backbones derived from this protocol possess the potential to become an alternative ligand platform.

Effects of Vitamin A on Immune Responses and Vitamin A Metabolism in Broiler Chickens Challenged with Necrotic Enteritis.

Necrotic enteritis (NE) is an important enteric inflammatory disease of poultry, and the effects of vitamin A (VitA) on NE birds are largely unknown. The present study was conducted to investigate the effects of VitA on the immune responses and VitA metabolism of NE broilers as well as the underlying mechanisms. Using a 2 × 2 factorial arrangement, 336 1-day-old Ross 308 broiler chicks were randomly assigned to 4 groups with 7 replicates. Broilers in the control (Ctrl) group were fed a basal diet without extra VitA supplementation. Broilers in the VitA group were fed a basal diet supplemented with 12,000 IU/kg of VitA. Birds in NE and VitA + NE groups were fed corresponding diets and, in addition, co-infected with Eimeria spp. and Clostridium perfringens on days 14 to 20. Samples of the blood, jejunum, spleen and liver were obtained on day 28 for analysis, and meanwhile, lesion scores were also recorded. The results showed that NE challenge increased lesion score in the jejunum and decreased serum glucose, total glyceride, calcium, phosphorus and uric acid levels (p < 0.05). VitA supplementation reduced the levels of serum phosphorus, uric acid and alkaline phosphatase in NE-challenged birds and increased serum low-density lipoprotein content and the activity of aspartate aminotransferase and creatine kinase (p < 0.05). Compared with the Ctrl group, the VitA and NE groups had higher mRNA expression of interferon-γ in the jejunum (p < 0.05). NE challenge up-regulated mRNA expression of interleukin (IL)-13, transforming growth factor-ß4, aldehyde dehydrogenase (RALDH)-2 and RALDH-3 in the jejunum, while VitA supplementation increased jejunal IL-13 mRNA expression and hepatic VitA content, but down-regulated splenic IL-13 mRNA expression (p < 0.05). The VitA + NE group had higher serum prostaglandin E2 levels and the Ctrl group had higher splenic RALDH-3 mRNA expression than that of the other three groups (p < 0.05). NE challenge up-regulated jejunal retinoic acid receptor (RAR)-ß and retinoid X receptor (RXR)-α as well as splenic RAR-α and RAR-ß mRNA expression (p < 0.05). VitA supplementation up-regulated jejunal RAR-ß expression but down-regulated mRNA expression of RXR-α, RXR-γ, signal transducers and activators of transcription (STAT) 5 and STAT6 in the spleen (p < 0.05). Moreover, compared with the Ctrl group, the VitA and NE groups had down-regulated mRNA expression of jejunal and splenic Janus kinase (JAK) 1 (p < 0.05). In conclusion, NE challenge induced jejunal injury and expression of Th2 and Treg cell-related cytokines and enhanced RALDH and RAR/RXR mRNA expression, mainly in the jejunum of broilers. VitA supplementation did not alleviate jejunal injury or Th2 cell-related cytokine expression; however, it improved hepatic VitA deposition and inhibited the expression of RALDH-3, RXR and the JAK/STAT signaling pathway in the spleen of broilers. In short, the present study suggested the modulatory effects of vitamin A on the immune responses and vitamin A metabolism in broiler chickens challenged with necrotic enteritis.

Effects of Dietary Supplementation with Vitamin A on Antioxidant and Intestinal Barrier Function of Broilers Co-Infected with Coccidia and Clostridium perfringens.

Necrotic enteritis (NE) impairs poultry production and causes great economic loss. The nutritional regulation of diets has the potential to alleviate NE. The present study was conducted to investigate the effects of dietary supplementation with vitamin A (VA) on the antioxidant and intestinal barrier function of broilers co-infected with coccidia and C. perfringens (CCP). In a 2 × 2 factorial arrangement, 336 one-day-old Ross 308 broilers were divided into four treatments with two levels of VA (0 or 12,000 IU/kg) and challenged with or without CCP. The animal trial lasted for 42 days. The results showed that dietary supplemental VA improved body weight gain (BWG) and the feed intake (FI), and the FI was negatively affected by CCP. Additionally, the levels of catalase (CAT) in the serum, total superoxide dismutase (T-SOD), and CAT in the jejunum and glutathione peroxidase (GSH-Px) in the liver decreased with the CCP challenge (p < 0.05). The mRNA levels of SOD, CAT, GSH-Px1, and GSH-Px3 in the liver and jejunum were upregulated by the CCP challenge (p < 0.05). In addition, the level of serum diamine oxidase (DAO), and the mRNA level of ZO-1 were also upregulated with the CCP challenge. Dietary supplementation with VA contributed to the intestinal villi height and the mRNA level of Mucin-2 in the jejunum (p < 0.05). Additionally, dietary VA had the ability to alleviate the upregulation of SOD in the liver and SOD, CAT, GSH-Px1, GSH-Px3, ZO-1, and claudin-1 in the jejunum with the CCP challenge (p < 0.05). However, the mRNA level of GSH-Px3 and the levels of SOD in the liver and jejunum were downregulated with the VA supplementation in the diet. In conclusion, dietary VA improved the growth performance and the intestinal barrier function; nonetheless, it failed to alleviate the negative effects of CCP on the antioxidant function in broilers.

Nickel-Catalyzed anti-Markovnikov Hydrodifluoroalkylation of Unactivated Alkenes.

An efficient Ni-catalyzed hydrodifluoroalkylation of unactivated alkenes with bromodifluoroacetate by using PhSiH3 as hydride source was developed. The transformation affords aliphatic difluorides with anti-Markovnikov regioselectivity. A wide range of highly remote alkenes, simple alkenes, drug molecules, commercially available CF2 precursors, and even nonfluorinated substrates are competent in this reaction under mild conditions, demonstrating the practicability of the strategy. Moreover, mechanistic studies indicated that the difluoroalkyl radical might be a key intermediate to this transformation.

Reconstruction and optimization of the 3D geometric anatomy structure model for subject-specific human knee joint based on CT and MRI images.

BACKGROUND: Nowadays, the total knee arthroplasty (TKA) technique plays an important role in surgical treatment for patients with severe knee osteoarthritis (OA). However, there are still several key issues such as promotion of osteotomy accuracy and prosthesis matching degree that need to be addressed. OBJECTIVE: It is significant to construct an accurate three-dimensional (3D) geometric anatomy structure model of subject-specific human knee joint with major bone and soft tissue structures, which greatly contributes to obtaining personalized osteotomy guide plate and suitable size of prosthesis. METHODS: Considering different soft tissue structures, magnetic resonance imaging (MRI) scanning sequences involving two-dimensional (2D) spin echo (SE) sequence T1 weighted image (T1WI) and 3D SE sequence T2 weighted image (T2WI) fat suppression (FS) are selected. A 3D modeling methodology based on computed tomography (CT) and two sets of MRI images is proposed. RESULTS: According to the proposed methods of image segmentation and 3D model registration, a novel 3D knee joint model with high accuracy is finally constructed. Furthermore, remeshing is used to optimize the established model by adjusting the relevant parameters. CONCLUSIONS: The modeling results demonstrate that reconstruction and optimization model of 3D knee joint can clearly and accurately reflect the key characteristics, including anatomical structure and geometric morphology for each component.

Directed Cobalt-Catalyzed C-H Activation to Form C-C and C-O Bonds in One Pot via Three-Component Coupling.

Herein, we disclose an efficient cobalt-catalyzed three-component coupling of benzamides, diazo compounds, and tert-butyl hydroperoxide, which provides an efficient approach to construct C(sp2)-C(sp3) and C-O bonds in one-pot accompanied with C-H activation. This protocol features low catalyst loading (4 mol %), the avoidance of additives, and excellent functional group compatibility, providing three-component coupling adducts with high yields under mild conditions (up to 88%). Mechanism studies show that the reaction may involve a radical process.

Synthesis of 7-Amido Indolines by Cp*Co(III)-Catalyzed C-H Bond Amidation.

An efficient Cp*Co(III)-catalyzed C-H bond amidation of indolines at the C7-position using dioxazolone as amidating reagents was first reported. N-Methyl-N-(pyrimidin-2-yl)aniline was also found to be a competent coupling partner. This protocol exhibits several unique characteristics, including excellent isolated yields, good functional group tolerance, and operational convenience. Derivatization reactions revealed this method has great potential for applications in synthesis.

Directed Cobalt-Catalyzed anti-Markovnikov Hydroalkylation of Unactivated Alkenes Enabled by "Co-H" Catalysis.

The earth-abundant cobalt-catalyzed anti-Markovnikov hydroalkylation of unactivated alkenes with oxime esters was achieved by introducing an 8-aminoquinoline directing group on the alkenes. The catalytic system, consisting of commercially available Co(acac)3 and PhMeSiH2, enables the construction of unfunctionalized C(sp3)-C(sp3) bonds and features exclusive anti-Markovnikov selectivity, good functional group tolerance, and the avoidance of an extra ligand, oxidant, or base. Mechanistic insight into this new catalytic system indicates the involvement of both alkyl radical and cobalt hydride intermediates.

Achieved RGBY Four Colors Changeable Electrochromic Pixel by Coelectrodeposition of Iron Hexacyanoferrate and Molybdate Hexacyanoferrate.

Although multicolor electrochromic materials and devices have been studied by many researchers, there is still none an inorganic single-layer film that has red, blue, and green three typical color states, while red, green, and blue (RGB) are indispensably for multicolor display. Iron hexacyanoferrate (FeHCF) is a kind of well-studied inorganic electrochromic material with relatively colorful properties and a great family of analogues. In this Research Article, the RGBY film with red, green, blue and yellow four typical color states are obtained successfully by coelectrodeposition of FeHCF and molybdate hexacyanoferrate (MoOHCF). This film contains the electrochromic properties of both components. Moreover, benefiting from its high A+ (alkali cation ions that can insert/extract into/from the framework, such as Li+ and K+) content, the redox process of RGBY film can be fully completed to achieve rich color variation. The absorptivity adjustment range of RGBY film at 730 and 440 nm are 0.81 and 0.43, respectively. The response time of RGBY films varies from 3 to 30 s between states and maintains its optical properties without significant decay during 1000 cycles. Finally, a pixelated electrode and a facile electrochromic device based on RGBY film have been developed to exhibit its high application potential in nonemission display field.

Development of a Traceless Directing Group: Cp*-Free Cobalt-Catalyzed C-H Activation/Annulations to Access Isoquinolinones.

A new traceless directing group, 2-(hydroxymethyl)pyridine, has been reported for the Cp*-free cobalt-catalyzed C-H activation/annulation reaction to synthesize isoquinolinones. The reaction exhibits good functional group tolerance, affording products in good to excellent isolated yields under mild conditions. Notably, the directing group can be removed directly in situ along the catalytic process.

Manganese-catalyzed cascade annulations of alkyne-tethered N-alkoxyamides: synthesis of polycyclic isoquinolin-1(2H)-ones.

A strategy for the synthesis of isoxazolidine/1,2-oxazinane-fused isoquinolin-1(2H)-ones from alkyne-tethered N-alkoxyamides is described, in which cheap Mn(acac)2 is used as a catalyst to facilitate a radical cascade annulation. The method features mild conditions, additive-free reaction and broad substrate scope. It is the first example via manganese/air catalytic systems to construct isoquinolin-1(2H)-one heterocycles.

Cp*-Free Cobalt-Catalyzed C-H Activation/Annulations by Traceless N, O-Bidentate Directing Group: Access to Isoquinolines.

N, O-Bidentate directing-enabled, traceless heterocycle synthesis is described via Cp*-free cobalt-catalyzed C-H activation/annulation. The weakly coordinating nature of the carboxylic acid was employed for the preparation of isoquinolines. Meanwhile, the N-O bond of the α-imino-oxy acid can serve as an internal oxidant. Terminal as well as internal alkynes can be efficiently applied to the catalytic system. This operationally simple approach shows a broad substrate scope with the products obtained in good to excellent yields.

Synthesis, characterization, DNA binding, topoisomerase I inhibition and antiproliferation activities of three new functionalized terpyridine platinum(II) complexes.

Three new platinum(II) complexes with pendent morpholine were synthesized, namely complex 1 ([Pt(L)Cl]CF3SO3), complex 2 ([Pt(L)(NH3)](CF3SO3)2) and complex 3 ([Pt(L)(PPh3)](CF3SO3)2), where L = 4'-[4-(4-morpholinobutyloxy)phenyl]-2,2':6',2″-terpyridine and PPh3 = triphenylphosphine. The detailed molecular structures of complex 3, L and its precursor L' (1,4'-[4-(4-bromobutyloxy)phenyl]-2,2':6',2″-terpyridine) were determined by single crystal X-ray diffraction. An evaluation of in vitro cytotoxicity for both ligand and complexes was performed by methyl thiazolyl tetrazolium (MTT) assay in three cancer cell lines and normal cells as the control, respectively. IC50 values of complexes 1-3 were lower than those exhibited for the reference drug cisplatin, and selectivity of these complexes were greater than cisplatin. Among them, complex 3 with a leaving group PPh3 was found to be the most efficacious complex against certain cell lines, especially for cisplatin-resistant A549cisR cells. These complexes were found to bind DNA, induce efficient DNA unwinding. Meanwhile, topoisomerase (Topo) I inhibitory activities by three complexes were detected, and a minimum inhibitory concentration of 15 µM of complex 3 was found totally inhibit Topo I activity.

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives.

A cobalt-catalyzed C(sp2)-H alkoxylation of 1-naphthylamine derivatives has been disclosed, which represents an efficient approach to synthesize aryl ethers with broad functional group tolerance. It is noteworthy that secondary alcohols, such as hexafluoroisopropanol, isopropanol, isobutanol, and isopentanol, were well tolerated under the current catalytic system. Moreover, a series of biologically relevant fluorine-aryl ethers were easily obtained under mild reaction conditions after the removal of the directing group.

Mechanical Energy Expenditure-based Comfort Evaluation Model for Gesture Interaction.

As an advanced interaction mode, the gesture has been widely used for the human-computer interaction (HCI). The paper proposes a comfort evaluation model based on the mechanical energy expenditure (MEE) and the mechanical efficiency (ME) to predict the comfort of gestures. The proposed comfort evaluation model takes nineteen muscles and seven degrees of freedom into consideration based on the data of muscles and joints and is capable of simulating the MEE and the ME of both static and dynamic gestures. The comfort scores (CSs) can be therefore calculated by normalizing and assigning different decision weights to the MEE and the ME. Compared with the traditional comfort prediction methods based on measurement, on the one hand, the proposed comfort evaluation model makes it possible for providing a quantitative value for the comfort of gestures without using electromyography (EMG) or other measuring devices; on the other hand, from the ergonomic perspective, the results provide an intuitive indicator to predict which act has the higher risk of fatigue or injury for joints and muscles. Experiments are conducted to validate the effectiveness of the proposed model. According to the comparison result among the proposed comfort evaluation model, the model based on the range of motion (ROM) and the model based on the method for movement and gesture assessment (MMGA), a slight difference can be found due to the ignorance of dynamic gestures and the relative kinematic characteristics during the movements of dynamic gestures. Therefore, considering the feedback of perceived effects and gesture recognition rate in HCI, designers can achieve a better optimization for the gesture design by making use of the proposed comfort evaluation model.

Cobalt(II)-Catalyzed Oxidative C-H Arylation of Indoles and Boronic Acids.

Co(II)-catalyzed C-H C2 selective arylation of indoles with boronic acids through monodentate chelation assistance has been achieved for the first time. The unique features of this methodology include mild reaction conditions, highly C2 regioselectivity, and employment of a Grignard reagent-free catalytic system. A wide range of substrates, including unreactive arenes, are well tolerated, which enables the construction of the coupling products efficiently. This new strategy provides an alternative and versatile approach to construct biaryls using inexpensive cobalt catalyst.