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.

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.

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.

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.

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.

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 .

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.

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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. We summarized the research advances of AMF in terrestrial agro-ecosystem in recent years, by focusing on AMF species diversity, spatial and temporal distribution, and influence factors of AMF biodiversity in terrestrial agro-ecosystem of China. Further research works were also prospected.

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.

Discovery of N-(4-[18F]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 [18F]9.

Cold Tolerance of Photosynthetic Electron Transport System Is Enhanced in Wheat Plants Grown Under Elevated CO2.

The effects of CO2 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 CO2 elevation (800 µmol l-1). It was found that CO2 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 QA and the increased quantum yield for reduction of end electron acceptors at the PSI acceptor side in plants under elevated CO2. Also, under low temperature, the activities of ATPases, ascorbate peroxidase, and catalase in chloroplasts were enhanced in wheat under elevated CO2. It suggested that the cold tolerance of photosynthetic electron transport system is enhanced by CO2 elevation.

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.

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.

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. The results showed that the fungal abundance was significantly higher in CS than in SS and RS. CS altered the fungal composition. Compared with RS, SS had an increase of 29 and a decrease of 12 genera in fungal relative abundance, and CS increased 38 and decreased 17 genera. The Shannon index was significantly higher in CS and SS than in RS. The result of principal coordinate analysis (PCoA) showed that CS and SS grouped together and were clearly separated from RS on the PCoA1. A total of 32 features accounted for the differences in fungal composition across RS, SS, and CS. The relative abundance of 10 potentially pathogenic and 10 potentially beneficial fungi changed, and most of their relative abundances dramatically increased in SS and CS compared with RS. Our study indicated that CS results in selective stress on pathogenic and beneficial fungi and causes the development of the fungal community structure that is antagonistic to plant health.

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 (Glycine max L.) exposed to Al stress. The roots of soybean seedlings were exposed to a combination of AlCl3 (30 µM) and SA (10 µM)/PAC (100 µM, paclobutrazol, SA biosynthesis inhibitor) for 3, 6, 9, and 12 h. Al stress induced an increase in endogenous SA concentration in a time-dependent manner, also verified by the up-regulated expression of GmNPR1, an SA-responsive gene. Al stress increased the activities of phenylalanine ammonia-lyase (PAL) and benzoic acid 2-hydroxylase (BA2H), and the contents of SA, [Formula: see text] and malondialdehyde (MDA) in the root apex. The application of exogenous SA increased PAL and BA2H, and reduced [Formula: see text] and MDA contents in soybean roots under Al stress. PAC inhibited the SA induced increase in BA2H activity. In addition, the SA application resulted in a rapid increase in hydrogen peroxide (H2O2) concentration under Al stress, followed by a sharp decrease. Compared with the plants exposed to Al alone, Al+SA plants possessed higher activities of superoxide dismutase, peroxidase, and ascorbate peroxidase, and lower catalase activity, indicating that SA alleviated Al-induced oxidative damage. These results suggested that PAL and BA2H were involved in Al-induced SA production and showed that SA alleviated the adverse effects of Al toxicity by modulating the cellular H2O2 level and the antioxidant enzyme activities in the soybean root apex.

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.

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. Samples were taken after two types of Brassica plants incorporated into soil for 15 days to compare with continually planted eggplant (control, CN) and chemical disinfection of soil (CF) in greenhouses. MiSeq pyrosequencing was used to analyze soil bacterial diversity and structure in the four different treatments. A total of 55,129 reads were identified, and rarefaction analysis showed that the soil treatments were equally sampled. The bacterial richness of the BFC treatment and the diversity of the BFN treatment were significantly higher than those of the other treatments. Further comparison showed that the bacterial community structures of BFC and BFN treatments were also different from CN and CF treatments. The relative abundance of several dominant bacterial genera in the BFC and BFN treatments (such as Flavobacteria, Stenotrophomonas, Massilia and Cellvibrio, which played different roles in improving soil fertility and advancing plant growth) was distinctly higher than the CN or CF treatments. Additionally, the total organic matter and Olsen-P content of the BFC and BFN treatments were significantly greater than the CN treatment. We conclude that Brassica vegetables-eggplant crop rotations could provide a more effective means of solving the problems of greenhouse eggplant monocultures.