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 [C]-12 to ester [C]-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 [C]-nitrile installation and subsequent conversion to [C]-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.

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.

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

To explore the potential association between the diversity of endophytic microorganisms and modifications of grain quality in wheat exposed to multi-generational elevated CO concentration, the grain quality attributes and microbial diversity were tested after five generations successively grown in ambient CO concentration (F5_A, 400 μmol L) and elevated CO concentration (F5_E, 800 μmol L). Elevated CO concentration significantly increased the grain number and starch concentration, while decreased the grain protein concentration. Multi-generational exposure to elevated CO concentration also led to significant changes in grain amino acid concentration.

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.

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).

[Research advances in species diversity of arbuscular mycorrhizal fungi in terrestrial agro-ecosystem].

Arbuscular mycorrhizal fungi (AMF) are ancient and ubiquitous soil microorganisms, which can form mutually beneficial association with most terrestrial plants. Within the symbiotic relationship, AMF helps their host plants to absorb nutrients such as nitrogen and phosphorus while obtains carbon from the hosts. AMF plays an important role in agricultural ecosystem, including promoting plant growth, improving crop quality, increasing plant stress resistance, stabilizing soil structure, keeping ecological balance, and maintaining a sustainable agricultural development.

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

Synthesis of carboxy-polyethylene glycol-amine (CA (PEG) ) 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- C]-propiolate from CO was therefore developed and utilized as a common synthon to afford practical and high yielding access to [1- C]-CA (PEG) .

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 β-alanine derivatives as potent GCGR antagonists through an efficient enantioselective synthesis and structure-activity relationship (SAR) exploration and optimization.

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.

Discovery of N-(4-[F]Fluoro-5-methylpyridin-2-yl)isoquinolin-6-amine (JNJ-64326067), a New Promising Tau Positron Emission Tomography Imaging Tracer.

In Alzheimer's disease, the density and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure-activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic profile and no apparent off-target binding. This was confirmed in rat and monkey positron emission tomography studies using [F]9.

Response of Soil Fungal Community Structure to Long-Term Continuous Soybean Cropping.

Long-term continuous soybean cropping can lead to the aggravation of soil fungal disease. However, the manner in which the fungal community and functional groups of fungi are affected by continuous soybean cropping remains unclear. We investigated the fungal abundance, composition and diversity during soybean rotation (RS), 2-year (SS) and long-term (CS) continuous soybean cropping systems using quantitative real-time PCR and high-throughput sequencing.

Cold Tolerance of Photosynthetic Electron Transport System Is Enhanced in Wheat Plants Grown Under Elevated CO.

The effects of CO elevation on sensitivity of photosynthetic electron transport system of wheat in relation to low temperature stress are unclear. The performance of photosynthetic electron transport system and antioxidant system in chloroplasts was investigated in a temperature sensitive wheat cultivar Lianmai6 grown under the combination of low temperature (2 days at 2/-1°C in the day/night) and CO elevation (800 μmol l). It was found that CO elevation increased the efficiency of photosynthetic electron transport in wheat exposed to low temperature stress, which was related to the enhanced maximum quantum yield for electron transport beyond Q and the increased quantum yield for reduction of end electron acceptors at the PSI acceptor side in plants under elevated CO.

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.

Salicylic Acid Alleviates Aluminum Toxicity in Soybean Roots through Modulation of Reactive Oxygen Species Metabolism.

As an important signal molecule, salicylic acid (SA) improves plant tolerance to aluminum (Al) stress. The objective of this study was to investigate the effects of exogenous SA application on the dynamics of endogenous SA and reactive oxygen species in soybean ( L.) exposed to Al stress.

Melatonin alleviates low PS I-limited carbon assimilation under elevated CO 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 CO concentration ([CO ]) 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 [CO ], via boosting the activities of ATPase and sucrose synthesis and maintaining a relatively higher level of total chlorophyll concentration in leaves.

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.

Changes in soil bacterial community structure as a result of incorporation of Brassica plants compared with continuous planting eggplant and chemical disinfection in greenhouses.

Greenhouse eggplant monocropping in China has contributed to the aggravation of soil-borne diseases, reductions in crop quality and yield, and the degradation of physical and chemical soil properties. Crop rotation is one effective way of alleviating the problems of continuous cropping worldwide; however, few studies have reported changes in soil bacterial community structures and physical and chemical soil properties after Brassica vegetables had been rotated with eggplant in greenhouses. In this experiment, mustard-eggplant (BFN) and oilseed rape-eggplant (BFC) rotations were studied to identify changes in the physicochemical properties and bacterial community structure in soil that was previously subject to monocropping.

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.

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 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.

Changes in nitrogen metabolism and antioxidant enzyme activities of maize tassel in black soils region of northeast China.

Two varieties of maize (Zea mays L.) grown in fields in black soils of northeast China were tested to study the dynamic changes of nitrogen metabolism and antioxidant enzyme activity in tassels of maize. Results showed that antioxidant enzyme activity in tassels of maize increased first and then decreased with the growing of maize, and reached peak value at shedding period.