Carbon-14 Labeling Synthesis of RORγt Inhibitor JNJ-61803534.

Carbon-14 labeling synthesis of RORγt inhibitor JNJ-61803534 (1) was accomplished in four steps with the C14 label located at the thiazole-2-carboxamide carbon. The synthesis featured a highly efficient conversion of nitrile [14C]-12 to ester [14C]-17 under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile 12 under either acidic or basic conditions. Since carbon-14 labeling via [14C]-nitrile installation and subsequent conversion to [14C]-carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses.

Melatonin reduces nanoplastic uptake, translocation, and toxicity in wheat.

With increasing plastic production and consumption, large amounts of polystyrene nanoplastics are accumulated in soil due to improper disposal causing pollution and deleterious effects to environment. However, little information is available about how to alleviate the adverse impacts of nanoplastics on crops. In this study, the involvement of melatonin in modulating nanoplastic uptake, translocation, and toxicity in wheat plant was investigated. The results demonstrated that exogenous melatonin application reduced the nanoplastic uptake by roots and their translocation to shoots via regulating the expression of genes associated with aquaporin, including the upregulation of the TIP2-9, PIP2, PIP3, and PIP1.2 in leaves and TIP2-9, PIP1-5, PIP2, and PIP1.2 in roots. Melatonin activated the ROS scavenging system to maintain a better redox homeostasis and ameliorated the negative effects of nanoplastics on carbohydrate metabolism, hence ameliorated the plant growth and enhanced the tolerance to nanoplastics toxicity. This process was closely related to the exogenous melatonin application induced melatonin accumulation in leave. These results suggest that melatonin could alleviate the adverse effects of nanoplastics on wheat, and exogenous melatonin application might be used as a promising management strategy to sustain crop production in the nanoplastic-polluted soils.

Status and Influential Factors of Intelligent Healthcare in Nursing Homes in China.

With the support of the Chinese government, nursing homes have increasingly adopted Internet and intelligent information technology to provide daily healthcare services to residents. However, no research has reported the status of intelligent healthcare in nursing homes. From September 2017 to May 2018, we conducted a survey of 197 nursing homes and collected information on their general characteristics, the intelligent healthcare services provided, the effectiveness of the application products used, and the attitudes of the staff and residents toward intelligent healthcare. Overall, 79.69% of the surveyed nursing homes have provided intelligent healthcare services, including medical care services (eg, chronic disease management and intelligent nursing) and daily life services (eg, fall monitoring and wireless positioning). Portable health monitoring devices and data management and service platforms are the most used healthcare products. The attitudes of staff probably affected the development of intelligent healthcare. Financial investment and the attitudes of staff and residents are factors that influence the effectiveness of the application of intelligent healthcare products in nursing homes. With the support of national policies, nursing homes have implemented primary intelligent healthcare. Stakeholders play pivotal roles in the provision of intelligent healthcare services.

Synthesis of carboxy-polyethylene glycol-amine (CA (PEG)n ) and [1-14 C]-CA (PEG)n via oxa-Michael addition of amino-polyethylene glycols to propiolates vs to acrylates.

Synthesis of carboxy-polyethylene glycol-amine (CA (PEG)n ) via oxa-Michael addition of amino-polyethylene glycols to either acrylates or propiolates was investigated. Compared with the oxa-Michael addition to acrylates, the corresponding addition to propiolates was found to proceed under mild reaction conditions and afford the adducts in high yields from a broad scope of substrates. A two-step efficient and convenient synthesis of benzyl [1-14 C]-propiolate from 14 CO2 was therefore developed and utilized as a common synthon to afford practical and high yielding access to [1-14 C]-CA (PEG)n .

Nano-ZnO-Induced Drought Tolerance Is Associated with Melatonin Synthesis and Metabolism in Maize.

The applications of ZnO nanoparticles in agriculture have largely contributed to crop growth regulation, quality enhancement, and induction of stress tolerance, while the underlying mechanisms remain elusive. Herein, the involvement of melatonin synthesis and metabolism in the process of nano-ZnO induced drought tolerance was investigated in maize. Drought stress resulted in the changes of subcellular ultrastructure, the accumulation of malondialdehyde and osmolytes in leaf. The nano-ZnO (100 mg L-1) application promoted the melatonin synthesis and activated the antioxidant enzyme system, which alleviated drought-induced damage to mitochondria and chloroplast. These changes were associated with upregulation of the relative transcript abundance of Fe/Mn SOD, Cu/Zn SOD, APX, CAT, TDC, SNAT, COMT, and ASMT induced by nano-ZnO application. It was suggested that modifications in endogenous melatonin synthesis were involved in the nano-ZnO induced drought tolerance in maize.

Discovery of potent and orally bioavailable indazole-based glucagon receptor antagonists for the treatment of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is characterized by chronically elevated plasma glucose levels. The inhibition of glucagon-induced hepatic glucose output via antagonism of the glucagon receptor (GCGR) using a small-molecule antagonist is a promising mechanism for improving glycemic control in the diabetic state. The present work discloses the discovery of indazole-based ß-alanine derivatives as potent GCGR antagonists through an efficient enantioselective synthesis and structure-activity relationship (SAR) exploration and optimization. Compounds within this class exhibited excellent pharmacokinetic properties in multiple preclinical species. In an acute dog glucagon challenge test, compound 13K significantly inhibited glucagon-mediated blood glucose increase when dosed orally at 10 mg/kg.

Design, synthesis and structure activity relationships of indazole and indole derivatives as potent glucagon receptor antagonists.

A novel series of indazole/indole derivatives were discovered as glucagon receptor (GCGR) antagonists through scaffold hopping based on two literature leads: MK-0893 and LY-2409021. Further structure-activity relationship (SAR) exploration and optimization led to the discovery of multiple potent GCGR antagonists with excellent pharmacokinetic properties in mice and rats, including low systemic clearance, long elimination half-life, and good oral bioavailability. These potent GCGR antagonists could be used for potential treatment of type II diabetes.

Salt Priming Protects Photosynthetic Electron Transport against Low-Temperature-Induced Damage in Wheat.

Low temperature limits the photochemical efficiency of photosystems in wheat plants. To test the effect of salt priming on the photosynthetic electron transport in wheat under low temperature, the germinating seeds of a winter wheat cv. Jimai44 were primed with varying concentrations of NaCl solutions (0, 10, 30, and 50 mM NaCl, indicated by S0, S10, S30, and S50, respectively) for 6 d, and after 11 d of recovery, the seedlings were subsequently exposed to 24-h low-temperature stress (2 °C). Under low temperature, the S30 plants possessed the highest absorption flux per reaction center and higher density of reaction center per cross-section among the treatments. In addition, S30 plants had higher trapped energy flux for reducing QA and fraction of QA-reducing reaction centers and non-QB reducing center than the non-primed plants under low temperature, indicating that S30 plants could maintain the energy balance of photosystems and a relatively higher maximum quantum efficiency of photosystem II under low temperature. In addition, the low temperature-induced MDA accumulation and cell death were alleviated by salt priming in S30 plants. It was suggested that salt priming with an optimal concentration of NaCl solution (30 mM) during seed germination enhanced the photochemical efficiency of photosystems in wheat seedlings, which could be a potential approach to improve cold tolerance in wheat at an early stage.

Melatonin alleviates low PS I-limited carbon assimilation under elevated CO2 and enhances the cold tolerance of offspring in chlorophyll b-deficient mutant wheat.

Melatonin is involved in the regulation of carbohydrate metabolism and induction of cold tolerance in plants. The objective of this study was to investigate the roles of melatonin in modulation of carbon assimilation of wild-type wheat and the Chl b-deficient mutant ANK32B in response to elevated CO2 concentration ([CO2 ]) and the transgenerational effects of application of exogenous melatonin (hereafter identified as melatonin priming) on the cold tolerance in offspring. The results showed that the melatonin priming enhanced the carbon assimilation in ANK32B under elevated [CO2 ], via boosting the activities of ATPase and sucrose synthesis and maintaining a relatively higher level of total chlorophyll concentration in leaves. In addition, melatonin priming in maternal plants at grain filling promoted the seed germination in offspring by accelerating the starch degradation and improved the cold tolerance of seedlings through activating the antioxidant enzymes and enhancing the photosynthetic electron transport efficiency. These findings suggest the important roles of melatonin in plant response to future climate change, indicating that the melatonin priming at grain filling in maternal plants could be an effective approach to improve cold tolerance of wheat offspring at seedling stage.

Cold Priming Induced Tolerance to Subsequent Low Temperature Stress is Enhanced by Melatonin Application during Recovery in Wheat.

Cold priming can alleviate the effects of subsequent cold stress on wheat plant growth. Melatonin plays a key role in cold stress response in plants. In this study, the effects of foliar melatonin application during recovery on the cold tolerance of cold primed wheat plants were investigated. It was found that both melatonin and cold priming increased the photosynthetic rate and stomatal conductance, enhanced the activities of antioxidant enzymes, and altered the related gene expressions in wheat under cold stress. Melatonin application is helpful for the photosynthetic carbon assimilation and membrane stability of the cold primed plants under cold stress. These results suggested that foliar melatonin application during recovery enhanced the cold priming induced tolerance to subsequent low temperature stress in wheat.

Development of Decarboxylative Cyanation Reactions for C-13/C-14 Carboxylic Acid Labeling Using an Electrophilic Cyanating Reagent.

Degradation-reconstruction approaches for isotope labeling synthesis have been known for their remarkable efficiency, but applications are scarce due to some fundamental limitations of the chemistries developed to date. The decarboxylative cyanation reaction, as a degradation-reconstruction approach, is especially useful in rapid carboxylic acid carbon isotope labeling, however development toward its application as a widespread technique has stalled at the early stages due to numerous limitations which include somewhat narrow applicability. Employing the electrophilic cyanating reagent N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as the cyano source, efficient decarboxylative cyanation chemistry has been developed for aryl and alkyl carboxylic acids respectively with two rationally designed reaction pathways. The reactions provided good yields of nitrile products from carboxylic acids, with complete retention of isotopic purity from the [13CN]-NCTS used. The reaction conditions are relatively mild requiring no oxidant and no excess toxic heavy metal and the reagent [13/14CN]-NCTS is a stable, easy-to-handle crystalline solid that can be prepared quickly and effectively from the readily available [13/14C]-KCN. The following work describes this novel and efficient method for alkyl and aryl carboxylic acid isotopic labeling using a single reagent.

Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant Capacity in Wheat Exposed to Nano-ZnO Stress.

The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed plants. It was found that melatonin improved the photosynthetic C assimilation in nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy transport efficiency, higher chlorophyll concentration and higher activities of Rubisco and ATPases. In addition, melatonin enhanced the activities of antioxidant enzymes to protect the photosynthetic electron transport system in wheat leaves against the oxidative burst caused by nano-ZnO stress. These results suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO stress.

Arbuscular mycorrhiza improve growth, nitrogen uptake, and nitrogen use efficiency in wheat grown under elevated CO2.

Effects of the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis on plant growth, carbon (C) and nitrogen (N) accumulation, and partitioning was investigated in Triticum aestivum L. plants grown under elevated CO2 in a pot experiment. Wheat plants inoculated or not inoculated with the AM fungus were grown in two glasshouse cells with different CO2 concentrations (400 and 700 ppm) for 10 weeks. A (15)N isotope labeling technique was used to trace plant N uptake. Results showed that elevated CO2 increased AM fungal colonization. Under CO2 elevation, AM plants had higher C concentration and higher plant biomass than the non-AM plants. CO2 elevation did not affect C and N partitioning in plant organs, while AM symbiosis increased C and N allocation into the roots. In addition, plant C and N accumulation, (15)N recovery rate, and N use efficiency (NUE) were significantly higher in AM plants than in non-AM controls under CO2 enrichment. It is concluded that AM symbiosis favors C and N partitioning in roots, increases C accumulation and N uptake, and leads to greater NUE in wheat plants grown at elevated CO2.

A short synthesis of d-[1-(14) C]-serine of high enantiomeric purity.

Herein, we report a short, three-step synthesis of d-[1-(14) C]-serine (4) in high enantiomeric purity. Starting from [(14) C]-KCN and 2-(benzyloxy)acetaldehyde, Strecker reaction using (R)-1-phenylethylamine as the chiral auxiliary gave two diastereomeric aminonitriles 1 and 2 in the ratio of 4:3, which were conveniently separated and purified chromatographically. Following hydrolysis and subsequent hydrogenolysis, the purified major diastereomer 1, was smoothly converted to d-[1-(14) C]-serine (4) in an enantiomeric excess of >99%, thus circumventing time intensive chiral HPLC enantiomeric resolution.

Silicon improves maize photosynthesis in saline-alkaline soils.

The research aimed to determine the effects of Si application on photosynthetic characteristics of maize on saline-alkaline soil, including photosynthetic rate (P n ), stomatal conductance (g s ), transpiration rate (E), and intercellular CO2 concentration (C i ) of maize in the field with five levels (0, 45, 90, 150, and 225 kg · ha(-1)) of Si supplying. Experimental results showed that the values of P n, g s, and C i of maize were significantly enhanced while the values of E of maize were dramatically decreased by certain doses of silicon fertilizers, which meant that Si application with proper doses significantly increased photosynthetic efficiency of maize in different growth stages under stressing environment of saline-alkaline soil. The optimal dose of Si application in this experiment was 150 kg · ha(-1) Si. It indicated that increase in maize photosynthesis under saline-alkaline stress took place by Si application with proper doses, which is helpful to improve growth and yield of maize.

Effects of silicon on photosynthetic characteristics of maize (Zea mays L.) on alluvial soil.

The objectives of the study were to determine the effects of silicon on photosynthetic characteristics of maize on alluvial soil, including total chlorophyll contents, photosynthetic rate (P n), stomatal conductance (g s), transpiration rate (E), and intercellular CO2 concentration (C i ) using the method of field experiment, in which there were five levels (0, 45, 90, 150, and 225 kg · ha(-1)) of silicon supplying. The results showed that certain doses of silicon fertilizers can be used successfully in increasing the values of total chlorophyll contents, P n, and g s and decreasing the values of E and C i of maize leaves, which meant that photosynthetic efficiency of maize was significantly increased in different growth stages by proper doses of Si application on alluvial soil, and the optimal dose of Si application was 150 kg · ha(-1). Our results indicated that silicon in proper amounts can be beneficial in increasing the photosynthetic ability of maize, which would be helpful for the grain yield and growth of maize.

Effect of different arbuscular mycorrhizal fungi on growth and physiology of maize at ambient and low temperature regimes.

The effect of four different arbuscular mycorrhizal fungi (AMF) on the growth and lipid peroxidation, soluble sugar, proline contents, and antioxidant enzymes activities of Zea mays L. was studied in pot culture subjected to two temperature regimes. Maize plants were grown in pots filled with a mixture of sandy and black soil for 5 weeks, and then half of the plants were exposed to low temperature for 1 week while the rest of the plants were grown under ambient temperature and severed as control. Different AMF resulted in different root colonization and low temperature significantly decreased AM colonization. Low temperature remarkably decreased plant height and total dry weight but increased root dry weight and root-shoot ratio. The AM plants had higher proline content compared with the non-AM plants. The maize plants inoculated with Glomus etunicatum and G. intraradices had higher malondialdehyde and soluble sugar contents under low temperature condition. The activities of catalase (CAT) and peroxidase of AM inoculated maize were higher than those of non-AM ones. Low temperature noticeably decreased the activities of CAT. The results suggest that low temperature adversely affects maize physiology and AM symbiosis can improve maize seedlings tolerance to low temperature stress.

Effectiveness of mHealth management with an implantable glucose sensor and a mobile application among Chinese adults with type 2 diabetes.

INTRODUCTION: This study aimed to evaluate the effectiveness of mHealth management with an implantable glucose sensor and a mobile application among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: A randomised controlled trial was carried out to compare the effectiveness of usual health management to mHealth management based on a model that consisted of the network platform, an implantable glucose sensor and a mobile app featuring guidance from general practitioners (GPs) over a four-week period. Patients (N=68) with T2DM were randomly divided into an intervention group and a control group. Before the intervention, there was no difference in body mass index (BMI), fasting blood glucose (FBG), postprandial two-hour blood glucose (2hPG) and glycosylated haemoglobin (HbA1c) between the intervention group and the control group (p>0.05). Patients in the control group received their usual health management, while patients in the intervention group received mHealth management. RESULTS: After health management, the mean BMI, FBG, 2hPG and HbA1c of the intervention group patients were all lower than those of the control group patients (p < 0.05), and the quality of life and self-management of the intervention group patients had significantly improved. DISCUSSION: mHealth management effectively showed significant reductions in BMI, FBG, 2hPG and HbA1c and improved quality of life and self-management among patients, which may be related to real-time feedback from an implantable glucose sensor and guidance from GPs through a mobile app. mHealth management is a very promising way to promote the health management of T2DM in China, and this study provides a point of reference for mHealth management abroad.

Relationship between endophytic microbial diversity and grain quality in wheat exposed to multi-generational CO2 elevation.

To explore the potential association between the diversity of endophytic microorganisms and modifications of grain quality in wheat exposed to multi-generational elevated CO2 concentration, the grain quality attributes and microbial diversity were tested after five generations successively grown in ambient CO2 concentration (F5_A, 400 µmol L-1) and elevated CO2 concentration (F5_E, 800 µmol L-1). Elevated CO2 concentration significantly increased the grain number and starch concentration, while decreased the grain protein concentration. Multi-generational exposure to elevated CO2 concentration also led to significant changes in grain amino acid concentration. In response to the elevated CO2 concentration, Pseudomonas, Rhodococcus, Ralstonia, and Klebsiella were the dominant bacterial genera, while Penicillium, Cutaneotrichosporon, Fusarium, Sarocladium, Acremonium and Aspergillus were the dominant fungal genera in wheat grain. A significantly positive correlation was found between Pseudomonas, Penicillium and ratio of starch to protein concentration, implying that the multi-generational CO2 elevation induced modifications in grain quality might be associated with the changes in grain microbial diversity. The results of this study suggest that the endophytic microbes may play an important role in modulating the grain nutritional quality in wheat under multi-generational e[CO2] exposure, through regulating starch and N metabolism and production of secondary metabolites.

Influence of arbuscular mycorrhiza on lipid peroxidation and antioxidant enzyme activity of maize plants under temperature stress.

The influence of the arbuscular mycorrhizal (AM) fungus, Glomus etunicatum, on characteristics of growth, membrane lipid peroxidation, osmotic adjustment, and activity of antioxidant enzymes in leaves and roots of maize (Zea mays L.) plants was studied in pot culture under temperature stress. The maize plants were placed in a sand and soil mixture under normal temperature for 6 weeks and then exposed to five different temperature treatments (5 degrees C, 15 degrees C, 25 degrees C, 35 degrees C, and 40 degrees C) for 1 week. AM symbiosis decreased membrane relative permeability and malondialdehyde content in leaves and roots. The contents of soluble sugar content and proline in roots were higher, but leaf proline content was lower in mycorrhizal than nonmycorrhizal plants. AM colonization increased the activities of superoxide dismutase, catalase, and peroxidase in leaves and roots. The results indicate that the AM fungus is capable of alleviating the damage caused by temperature stress on maize plants by reducing membrane lipid peroxidation and membrane permeability and increasing the accumulation of osmotic adjustment compounds and antioxidant enzyme activity. Consequently, arbuscular mycorrhiza formation highly enhanced the extreme temperature tolerance of maize plant, which increased host biomass and promoted plant growth.