Synthesis and preliminary evaluation of novel 11C-labeled GluN2B-selective NMDA receptor negative allosteric modulators.

N-methyl-D-aspartate receptors (NMDARs) play critical roles in the physiological function of the mammalian central nervous system (CNS), including learning, memory, and synaptic plasticity, through modulating excitatory neurotransmission. Attributed to etiopathology of various CNS disorders and neurodegenerative diseases, GluN2B is one of the most well-studied subtypes in preclinical and clinical studies on NMDARs. Herein, we report the synthesis and preclinical evaluation of two 11C-labeled GluN2B-selective negative allosteric modulators (NAMs) containing N,N-dimethyl-2-(1H-pyrrolo[3,2-b]pyridin-1-yl)acetamides for positron emission tomography (PET) imaging. Two PET ligands, namely [11C]31 and [11C]37 (also called N2B-1810 and N2B-1903, respectively) were labeled with [11C]CH3I in good radiochemical yields (decay-corrected 28% and 32% relative to starting [11C]CO2, respectively), high radiochemical purity (>99%) and high molar activity (>74 GBq/µmol). In particular, PET ligand [11C]31 demonstrated moderate specific binding to GluN2B subtype by in vitro autoradiography studies. However, because in vivo PET imaging studies showed limited brain uptake of [11C]31 (up to 0.5 SUV), further medicinal chemistry and ADME optimization are necessary for this chemotype attributed to low binding specificity and rapid metabolism in vivo.

Bone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF-ß1 signaling.

BACKGROUND: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair. METHODS: BMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1ß, IL-6, angiopoietin, IL-4, IL-10 and TGF-ß1. The apoptotic rate of AR42J cells was quantitated by concurrent staining with Annexin-V-FITC and PI. RESULTS: BMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1ß and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-ß1 signaling. CONCLUSION: BMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-ß1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP.

[Prevention of poor incision healing after total knee arthroplasty].

OBJECTIVE: To investigate the causes of poor incision healing after total knee arthroplasty(TKA) and to propose active preventive and therapeutic measures. METHODS: Total 284 patients undergoing unilateral TKA from September 2016 to June 2018 were enrolled in the study and divided into control group and observation group. Firstly, 150 patients with unilateral TKA from September 2016 to June 2017 were retrospectively analyzed and included in the control group. There were 41 males and 109 females, with an average age of(63.5±7.2) years old. The causes of poor incision healing were discussed about patients themselves and surgical techniques. After analyzing, improvement measures were proposed. Total 134 patients with TKA from July 2017 to June 2018 were included in the observation group. There were 36 males and 98 females, with an average age of(62.4±8.9) years old. The patients in the observation group were treated with improved treatment strategies. RESULTS: Nine patients(6%) had poor incision healing in the control group and 1 patient (0.75%) had poor incision healing in the observation group. The incidence of poor incision healing was significantly different between the two groups (χ²=5.750, P<0.01). CONCLUSIONS: In order to prevent the poor incision healing after TKA, perioperative management and the operation techniques including stable, accurate, rapid and clean skills should be improved, leading to reduce the complications of incision and improve the recovery rate of patients.

Ni-catalyzed cross-electrophile coupling between vinyl/aryl and alkyl sulfonates: synthesis of cycloalkenes and modification of peptides.

We report here the coupling reactions between vinyl/aryl and alkyl C-O electrophiles that can be derived from chemical feedstocks and naturally occurring functional groups. This method provides an efficient approach to the synthesis of a wide range of functionalized, and/or secondary alkyl substituted cycloalkenes. These compounds are difficult to produce by conventional methods. The reaction proceeds with broad substrate scope, and tolerates various functional groups such as alcohol, aldehyde, ketone, ester, amide, alkene, alkyne, heterocycles, organotin and organosilicon compounds. The synthetic utility of this method has been demonstrated by providing facile access to important building blocks. We also demonstrated the possibility to apply this method for late-stage modification of peptides. A broad range of functionalized alkyl groups could be selectively introduced into tyrosine in peptides via C-C bond formation, which has been a challenge to the existing procedures.

Physiological and developmental traits associated with the grain yield of winter wheat as affected by phosphorus fertilizer management.

Although researchers have determined that attaining high grain yields of winter wheat depends on the spike number and the shoot biomass, a quantitative understanding of how phosphorus (P) nutrition affects spike formation, leaf expansion and photosynthesis is still lacking. A 3-year field experiment with wheat with six P application rates (0, 25, 50, 100, 200, and 400 kg P ha-1) was conducted to investigate this issue. Stem development and mortality, photosynthetic parameters, dry matter accumulation, and P concentration in whole shoots and in single tillers were studied at key growth stages for this purpose. The results indicated that spike number contributed the most to grain yield of all the yield components in a high-yielding (>8 t/ha) winter wheat system. The main stem (MS) contributed 79% to the spike number and tiller 1 (T1) contributed 21%. The 2.7 g kg-1 tiller P concentration associated with 15 mg kg-1 soil Olsen-P at anthesis stage led to the maximal rate of productive T1s (64%). The critical shoot P concentration that resulted in an adequate product of Pn and LAI was identified as 2.1 g kg-1. The thresholds of shoot P concentration that led to the maximum productive ability of T1 and optimal canopy photosynthetic capacity at anthesis were very similar. In conclusion, the thresholds of soil available P and shoot P concentration in whole plants and in single organs (individual tillers) were established for optimal spike formation, canopy photosynthetic capacity, and dry matter accumulation. These thresholds could be useful in achieving high grain yields while avoiding excessive P fertilization.

Highly Enantioselective Cross-Electrophile Aryl-Alkenylation of Unactivated Alkenes.

Enantioselective cross-electrophile reactions remain a challenging subject in metal catalysis, and with respect to data, studies have mainly focused on stereoconvergent reactions of racemic alkyl electrophiles. Here, we report an enantioselective cross-electrophile aryl-alkenylation reaction of unactivated alkenes. This method provides access to a number of biologically important chiral molecules such as dihydrobenzofurans, indolines, and indanes. The incorporated alkenyl group is suitable for further reactions that can lead to an increase in molecular diversity and complexity. The reaction proceeds under mild conditions at room temperature, and an easily accessible chiral pyrox ligand is used to afford products with high enantioselectivity. The synthetic utility of this method is demonstrated by enabling the modification of complex molecules such as peptides, indometacin, and steroids.

Carbon dioxide emissions from the electricity sector in major countries: a decomposition analysis.

The electric power sector is one of the primary sources of CO2 emissions. Analyzing the influential factors that result in CO2 emissions from the power sector would provide valuable information to reduce the world's CO2 emissions. Herein, we applied the Divisia decomposition method to analyze the influential factors for CO2 emissions from the power sector from 11 countries, which account for 67% of the world's emissions from 1990 to 2013. We decompose the influential factors for CO2 emissions into seven areas: the emission coefficient, energy intensity, the share of electricity generation, the share of thermal power generation, electricity intensity, economic activity, and population. The decomposition analysis results show that economic activity, population, and the emission coefficient have positive roles in increasing CO2 emissions, and their contribution rates are 119, 23.9, and 0.5%, respectively. Energy intensity, electricity intensity, the share of electricity generation, and the share of thermal power generation curb CO2 emissions and their contribution rates are 17.2, 15.7, 7.7, and 2.8%, respectively. Through decomposition analysis for each country, economic activity and population are the major factors responsible for increasing CO2 emissions from the power sector. However, the other factors from developed countries can offset the growth in CO2 emissions due to economic activities.