Bottom-Up Construction of Metal-Organic Framework Loricae on Metal Nanoclusters with Consecutive Single Nonmetal Atom Tuning for Tailored Catalysis.

The introduction of single or multiple heterometal atoms into metal nanoparticles is a well-known strategy for altering their structures (compositions) and properties. However, surface single nonmetal atom doping is challenging and rarely reported. For the first time, we have developed synthetic methods, realizing "surgery"-like, successive surface single nonmetal atom doping, replacement, and addition for ultrasmall metal nanoparticles (metal nanoclusters, NCs), and successfully synthesized and characterized three novel bcc metal NCs Au38I(S-Adm)19, Au38S(S-Adm)20, and Au38IS(S-Adm)19 (S-Adm: 1-adamantanethiolate). The influences of single nonmetal atom replacement and addition on the NC structure and optical properties (including absorption and photoluminescence) were carefully investigated, providing insights into the structure (composition)-property correlation. Furthermore, a bottom-up method was employed to construct a metal-organic framework (MOF) on the NC surface, which did not essentially alter the metal NC structure but led to the partial release of surface ligands and stimulated metal NC activity for catalyzing p-nitrophenol reduction. Furthermore, surface MOF construction enhanced NC stability and water solubility, providing another dimension for tunning NC catalytic activity by modifying MOF functional groups.

Inhibition of JNK/c-Jun-ATF2 Overcomes Cisplatin Resistance in Liver Cancer through down-Regulating Galectin-1.

Due to drug resistance, the clinical response to cisplatin (CDDP) from patients with liver cancer is unsatisfactory. The alleviation or overcoming of CDDP resistance is an urgent problem to be solved in clinics. Tumor cells rapidly change signal pathways to mediate drug resistance under drug exposure. Here, multiple phosphor-kinase assays were performed and c-Jun N-terminal kinase (JNK) was activated in liver cancer cells treated with CDDP. The high activity of the JNK promotes poor progression and mediates cisplatin resistance in liver cancer, leading to a poor prognosis of liver cancer. Mechanistically, the highly activated JNK phosphorylated c-Jun and ATF2 formed a heterodimer to upregulate the expression of Galectin-1, leading to promoting cisplatin resistance in liver cancer. Importantly, we simulated the clinical evolution of drug resistance in liver cancer by continuous CDDP administration in vivo. In vivo bioluminescence imaging showed the activity of JNK gradually increased during this process. Moreover, the inhibition of JNK activity by small molecular or genetic inhibitors enhanced DNA damage and overcame CDDP resistance in vitro and in vivo. Collectively, our results underline that the high activity of JNK/c-Jun-ATF2/Galectin-1 mediates cisplatin resistance in liver cancer and provides an optional scheme for dynamic monitoring of molecular activity in vivo.

Overexpression of a Bcl-2-associated athanogene SlBAG9 negatively regulates high-temperature response in tomato.

The Bcl-2-associated athanogene (BAG) gene is a multi-functional family of co-chaperones regulator, modulating plant stress response. Our previous study revealed that the SlBAG9 of tomato (Solanum lycopersicum) had the higher expression level induced by high-temperature (HT) at the transcriptional and protein levels, but its biological function was still unclear. Here, we conducted an in-depth analysis of SlBAG9. SlBAG9 protein was not located in the mitochondria but in the cytoplasm and nucleus. Many cis-acting elements involved in plant stress and hormone responses were located in the promoter regions of SlBAG9 including heat-shock element (HSE1). The ß-glucuronidase (GUS) histochemical analysis showed that SlBAG9 promoter could drive GUS gene expression in transiently transformed Nicotiana tabacum leaves under non-inducing condition and HSE1 is critical for HT-induced GUS activity under HT. The transcription of SlBAG9 was expressed in different organs and was regulated by HT, cold, drought, and salt stresses as well as exogenous abscisic acid (ABA) and H2O2. To further elucidate SlBAG9 function in response to HT, the transgenic tomato plants overexpressing SlBAG9 were developed. Compared to the wild-type plants, SlBAG9-overexpressing plants exhibited more sensitivity to HT stress, reflected by the burning symptoms, the degradation of chlorophyll, and the reduction of photosynthetic rates. Additionally, SlBAG9-overexpressing lines showed higher accumulation of lipid peroxidation production (MDA) and H2O2, but lower activities of superoxide dismutase, catalase, and peroxidase. Therefore, it is speculated that SlBAG9 plays a negative role in thermotolerance probably by inhibition of antioxidant enzyme system leading to the oxidative damage, consequently aggravating the HT-caused injury phenotype.

Versatile fluorinated Pd@Au nanoplates doped with yttrium for tumor theranostics.

As one of the emerging modalities of magnetic resonance imaging (MRI), 19F MRI is highly conducive for the specific detection and imaging of deep-seated tumors, with negligible background. However, most 19F MRI probe designs are constructed with organic CF3, which contains rich fluorine atoms, and few of the fluorine-containing groups are equipped with therapeutic function. Herein, we designed a versatile 19F MRI-based theranostic nanoplatform, FY-Pd@Au nano-metallacages (FY-Pd@Au NCs), which not only serve as a 19F MRI/CT/PAI contrast agent, but also produce reactive oxygen species (ROS) by type I photodynamic therapy (PDT) pathway, as well as heat for photothermal therapy (PTT), under the single NIR laser irradiation. Overall, this work successfully built a theranostics nanoplatform based on 19F MRI.

A unique coordination-driven route for the precise nanoassembly of metal sulfides on metal-organic frameworks.

Incorporating different materials, such as metal sulfides, with metal-organic frameworks (MOFs) to develop MOF-based multifunctional composites with enhanced performance is an important area of research. However, the intrinsically high interfacial energy barrier significantly restricts the heterogeneous nucleation and nanoassembly of metal sulfides onto MOFs during the wet chemistry synthesis process. Herein, taking advantage of the natural tailorability of MOFs, the precise and controllable growth of metal sulfide nanoparticles (NPs) (CdS, ZnS, CuS and Ag2S) at the coordinatively unsaturated metal sites (CUSs) of MOFs to form MOF@metal sulfide composites under mild conditions is achieved via a cysteamine-assisted coordination-driven route. During the process, the molecular linker of cysteamine, possessing one amino group for chelating with the CUSs of the MOF and one thiol group as a docking site to anchor metal ions, plays a prominent role in enhancing interfacial interactions between the MOF and metal ions. The subsequent S2- anion exchange process leads to intimate surface-attached nucleation and epitaxial growth of metal sulfide NPs on the surface of the MOF. The as-formed composites exhibit enhanced charge separation and transfer capability, and thus boost photocatalytic performance. This general and simple approach provides a new avenue for the design of MOF-metal sulfide hybrids.

Regulating the Coordination Environment of MOF-Templated Single-Atom Nickel Electrocatalysts for Boosting CO2 Reduction.

The general synthesis and control of the coordination environment of single-atom catalysts (SACs) remains a great challenge. Herein, a general host-guest cooperative protection strategy has been developed to construct SACs by introducing polypyrrole (PPy) into a bimetallic metal-organic framework. As an example, the introduction of Mg2+ in MgNi-MOF-74 extends the distance between adjacent Ni atoms; the PPy guests serve as N source to stabilize the isolated Ni atoms during pyrolysis. As a result, a series of single-atom Ni catalysts (named NiSA -Nx -C) with different N coordination numbers have been fabricated by controlling the pyrolysis temperature. Significantly, the NiSA -N2 -C catalyst, with the lowest N coordination number, achieves high CO Faradaic efficiency (98 %) and turnover frequency (1622 h-1 ), far superior to those of NiSA -N3 -C and NiSA -N4 -C, in electrocatalytic CO2 reduction. Theoretical calculations reveal that the low N coordination number of single-atom Ni sites in NiSA -N2 -C is favorable to the formation of COOH* intermediate and thus accounts for its superior activity.

N-Acetyl-d-galactosamine prevents soya bean agglutinin-induced intestinal barrier dysfunction in intestinal porcine epithelial cells.

Soya bean agglutinin (SBA) is a glycoprotein and the main anti-nutritional component in most soya bean feedstuffs. It is mainly a non-fibre carbohydrate-based protein and represents about 10% of soya bean-based anti-nutritional effects. In this study, we sought to determine the effects of N-Acetyl-D-galactosamine (GalNAc or D-GalNAc) on the damage induced by SBA on the membrane permeability and tight junction proteins of piglet intestinal epithelium (IPEC-J2) cells. The IPEC-J2 cells were pre-cultured with 0, 0.125 × 10-4 , 0.25 × 10-4 , 0.5 × 10-4 , 1.0 × 10-4 and 2.0 × 10-4  mmol/L GalNAc at different time period (1, 2, 4 and 8 hr) before being exposed to 0.5 mg/ml SBA for 24 hr. The results indicate that pre-incubation with GalNAc mitigates the mechanical barrier injury as reflected by a significant increase in trans-epithelial electric resistance (TEER) value and a decrease in alkaline phosphatase (ALP) activity in cell culture medium pre-treated with GalNAc before incubation with SBA as both indicate a reduction in cellular membrane permeability. In addition, mRNA levels of the tight junction proteins occludin and claudin-3 were lower in the SBA-treated groups without pre-treatment with GalNAc. The mRNA expression of occludin was reduced by 17.3% and claudin-3 by 42% (p < 0.01). Moreover, the corresponding protein expression levels were lowered by 17.8% and 43.5% (p < 0.05) respectively. However, in the GalNAc pre-treated groups, occludin and claudin-3 mRNAs were reduced by 1.6% (p > 0.05) and 2.7% (p < 0.01), respectively, while the corresponding proteins were reduced by 4.3% and 7.2% (p < 0.05). In conclusion, GalNAc may prevent the effect of SBA on membrane permeability and tight junction proteins on IPEC-J2s.

Eleutheroside B increase tight junction proteins and anti-inflammatory cytokines expression in intestinal porcine jejunum epithelial cells (IPEC-J2).

Eleutheroside B (EB) is a phenylpropanoid glycoside with anti-inflammatory properties, neuroprotective abilities, immunomodulatory effects, antinociceptive effects, and regulation of blood glucose. The aim of this study was to investigate the effects of EB on the barrier function in the intestinal porcine epithelial cells J2 (IPEC-J2). The IPEC-J2 cells were inoculated into 96-well plates at a density of 5 × 103 cells per well for 100% confluence. The cells were cultured in the presence of EB at concentrations of 0, 0.05, 0.10, and 0.20 mg/ml for 48 hr. Then, 0.10 mg/ml was selected as the suitable concentration for the estimation of transepithelial electric resistance (TEER) value, alkaline phosphatase activity, proinflammatory cytokines mRNA expression, tight junction mRNA and protein expression. The results of this study indicated that the supplementation of EB in IPEC-J2 cells decreased cellular membrane permeability and mRNA expression of proinflammatory cytokines, including interleukin-6 (IL-6), interferon-γ (INF-γ), and tumour necrosis factor-α (TNF-α). The supplementation of EB in IPEC-J2 cells increased tight junction protein expression and anti-inflammatory cytokines, interleukin 10 (IL-10) and transforming growth factor beta (TGF-ß). In addition, the western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) results indicated that EB significantly (p < 0.05) increased the mRNA and protein expression of intestinal tight junction proteins, Claudin-3, Occludin, and Zonula Occludins protein-1 (ZO-1). Therefore, dietary supplementation of EB may increase intestinal barrier function, tight junction protein expression, anti-inflammatory cytokines, and decrease proinflammatory cytokines synthesis in IPEC-J2 cells.

Application of coordination agent in high-speed counter-current chromatography for the preparative separation and isolation ginkgolic acids from the sarcotesta of Ginkgo biloba L.

An efficient coordination high-speed counter-current chromatography method for the preparative separation of ginkgolic acids from the sarcotesta of Ginkgo biloba L was developed. The type, concentration, and mechanism of the coordination agent were investigated. Following the use of four types of metal salts including silver nitrate, copper chloride, ferric chloride, and aluminium nitrate, n-heptane/ethyl acetate/methanol/acetic acid 5:4:1:1, v/v with 0.20 mol/L silver nitrate as the coordination agent was chosen as the optimum two-phase solvent system. Five main ginkgolic acids including C13:0, C15:0, C15:1, C17:1, and C17:2 were successfully separated with purities greater than 98%. The sample loading was 500 mg, the flow-rate was 2.0 mL/min, rotation speed was 800 rpm and temperature was 20°C. The structures of the separated ginkgolic acids were identified by comparison with standard samples and electrospray ionization mass spectrometry. The introduction of coordination chemistry in high-speed counter-current chromatography is novel and effective for the preparative separation and isolation of ginkgolic acids from the sarcotesta of Ginkgo biloba L and could also be applied to separate compounds which form coordination bonds in other complex natural products.

Standardized Ginkgo biloba extract EGb 761® attenuates early brain injury following subarachnoid hemorrhage via suppressing neuronal apoptosis through the activation of Akt signaling.

BACKGROUND: Early brain injury (EBI) plays a critical role in determining the outcome of subarachnoid hemorrhage (SAH). The present study was designed to investigate the role of EGb 761, a standardized extract of Ginkgo biloba, in SAH-induced EBI and to explore its potential mechanism of action. METHOD: A rat SAH model was established by the endovascular perforation process. Doses of 10, 50 and 100 mg/kg EGb 761 were injected intraperitoneally 2 h after SAH was induced. Mortality, SAH grade, neurological score and brain water content were measured 24 h after SAH was induced. A Western blot assay was performed to assess the expression of the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, Akt and phosphorylated Akt (p-Akt). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and neuronal nuclei (NeuN) double immunofluorescence staining were used to detect apoptotic neurons. RESULTS: Animals suffered from serious neurological deficits and increased brain water content after induction of SAH. Rats treated with EGb 761 experienced dose-dependent attenuation of neurological dysfunction and decreased brain water content. In addition, EGb 761 significantly activated Akt signaling accompanied by increased Bcl-2 levels and decreased expression of Bax and cleaved caspase-3. Moreover, EGb 761 decreased the number of TUNEL/NeuN-positive cells in a dose-dependent manner. However, all the beneficial effects of EGb 761 for SAH were abolished by the Akt inhibitor MK2206. CONCLUSION: Our results indicated that EGb 761 could ameliorate SAH-induced EBI and that the neuroprotective effects of EGb 761 against SAH were exerted via suppression of neuronal apoptosis through activation of the Akt pathway.

SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer.

Tyrosine phosphatase SHP2, encoded by PTPN11, has been implicated in many physiologic and pathologic processes in neoplastic progression. However, controversies are emerging from many studies, indicating SHP2 has a dual role in different types of tumors. We aimed to explore the role of SHP2 in progression and prognosis of colorectal cancer (CRC). SHP2 inhibited CRC cell proliferation and migration, and the phosphorylation of STAT3 was negatively regulated by SHP2 in CRC. SHP2 and nuclear STAT3 were examined in 270 CRC tissues. SHP2 was significantly correlated with nuclear STAT3 (Spearman's rho = -0.408, P ≤ 0.001). Based on Cox regression analysis, patients with high levels of SHP2 and low levels of nuclear STAT3 had longer disease-specific survival (DSS) (HR, 0.362; 95% CI, 0.165-0.794) and disease-free survival (DFS) (HR, 0.447; 95% CI, 0.227-0.877). Further, low levels of SHP2 and high levels of nuclear STAT3 were independently associated with adverse outcomes in the whole cohort (DFS; HR, 2.353; 95% CI, 1.199-4.619). These results suggest that combination of SHP2 and nuclear STAT3 is a strong prognostic predictor in CRC.

Unprecedented Li+ Exchange in an Anionic Metal-Organic Framework: Significantly Enhanced Gas Uptake Capacity.

We herein report the first example of Li+ exchanged with both the guest H2N(Me)2+ cations located in the channels and the coordinated metal ions from an anionic metal-organic framework (MOF), leading to significant enhancement of the pore volume and gas sorption abilities of the exchanged MOF. Furthermore, both MOFs before and after Li+ exchange show good selective adsorption for CO2 over CH4.

Effects of Dietary Iron Modulation on Gut Microbial Composition and Function in Monogastrics: A Review.

Dietary iron is a crucial nutrient element for biological processes of both hosts and gut microbiota. Deficiency in dietary iron is a highly common disorder in the developing locations of the world and can be healed by oral iron administration or complementary iron diet. While the redundant iron that enters the gut lumen leads to negative effects, and modulates the gut microbial composition and function. Such modulation led to a significant effect on vital biological pathways of the host, including metabolic disease (obesity and type 2 diabetes), metabolites (SCFA, blood glucose and cholesterol), bile acid metabolism, endocrine, neural, and other well-being patterns. This review covers the multifaceted aspects of different nutritional iron stress on the composition and function of microbial gut in monogastrics and consequential health conditions as well as it reveals unclear points that need further studies.

Effects of Dietary Non-Fiber Carbohydrates on Composition and Function of Gut Microbiome in Monogastrics: A Review.

Non-fiber carbohydrates (NFC) have a crucial function on the gut health of monogastrics. This paper aims to review the relevant published materials on the influence of NFCs on the gut's microbial population and composition in monogastrics, and points out the areas of the required research. Total bacteria count and Lactobacillus sp. were decreased with an increase in composition of dietary NFC intake, as well as accompanied by a decrease in the short-chain fatty acids (SCFAs) levels. Consequently, some metabolites were affected by the accumulation of the bile acids, including molecules which control different gene expression levels, as regulators involved in glucose (FXR and TGR5) and fat metabolism (cholesterol). Cell proliferation rate of both gastrointestinal epithelium and microbiome cells was negatively correlated with the dietary NFC levels in many species of monogastric animals. Low levels of NFC diet are negatively associated with digestibility, total gut weight, and gastrointestinal secretions. High levels of dietary NFC have negative effects on the digestion and absorption of macronutrients, with an increase of the contact time of the carcinogens in the intestinal lumen. The data obtained from different animals' studies did not give the same results. In conclusion, dietary NFC should be adjusted to the optimal consumption levels as the human and the monogastric animals are anatomically and physiologically different. Digestion, metabolism, host wellbeing, and host behavior were negatively affected by the administration of high NFC levels. The relations between sulphate-reducing bacteria and some metabolic diseases such as diabetes mellitus and obesity need further exploration.

Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea.

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analyses, H-TL1 inhibited the interaction between TNF-α and TNF receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-α in L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF-α/TNFR1 downstream targets and suppressed the phosphorylation of well-characterized proteins of downstream signal transduction pathways in HEK-293 cells. In vivo data demonstrated that H-TL1 protects animals against dextran sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced acute shock. Given its significant anti-inflammatory activity in vitro and in vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF-α-associated inflammatory diseases.

Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis.

Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1-associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases.

Drug target identification using network analysis: Taking active components in Sini decoction as an example.

Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.

A Stretchable Electronic Fabric Artificial Skin with Pressure-, Lateral Strain-, and Flexion-Sensitive Properties.

A stretchable and multiple-force-sensitive electronic fabric based on stretchable coaxial sensor electrodes is fabricated for artificial-skin application. This electronic fabric, with only one kind of sensor unit, can simultaneously map and quantify the mechanical stresses induced by normal pressure, lateral strain, and flexion.

A new highly oxygenated daphnane diterpene esters from the flower buds of Daphne genkwa.

The phytochemical investigation of the flower buds of Daphne genkwa yielded eight highly oxygenated daphnane-type diterpene esters, including a new one, genkwanine N 20-palmitate (1) and seven known ones (2-8). The molecular structures of the isolated compounds were elucidated on the basis of extensive spectroscopic analysis, including UV, IR, NMR, and MS, and comparison with literature data. Furthermore, compound 1 showed potential cytotoxic activity in vitro, against A549 and Hep G2 tumour cell lines.

An amine-functionalized metal-organic framework as a sensing platform for DNA detection.

An amine-functionalized metal-organic framework (MOF) has been employed as an effective fluorescent sensing platform for DNA detection and is capable of distinguishing complementary and mismatched target sequences with high sensitivity and selectivity.