Microglial repopulation induced by PLX3397 protects against ischemic brain injury by suppressing neuroinflammation in aged mice.

As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions in aged brains. Although studies have demonstrated the inflammatory profile of aged microglia in several neurological diseases, this issue is largely uncertain in stroke. Consequently, this study investigated the effects of primed and repopulated microglia on post-ischemic brain injury in aged mice.

Exercise blood pressure, cardiorespiratory fitness, fatness and cardiovascular risk in children and adolescents.

Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood pressure (BP) and obesity, face an elevated risk of experiencing organ-specific pathophysiological changes. This damage includes pathophysiological changes in the heart and peripheral vascular systems, such as ventricular hypertrophy, arterial stiffening, and vascular narrowing and stenosis.

BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis.

Background: The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy.

In Situ Sprayed Difunctional Gel Avoiding Microenvironments Limitations to Treat Pressure Ulcers.

How to avoid the microenvironment limitations in the therapeutic process of pressure ulcers is still challenging. The development of a functional gel can kill bacteria and scavenge reactive oxygen species (ROS), which is urgently required in the therapeutic process of pressure ulcers. Herein, an in situ sprayed gel is developed with silver nanoparticles (AgNPs) and polydopamine (PDA) NPs (APG) to obviate microenvironment restrictions in treating pressure ulcers.

Association between plasma selenium and risk of ischemic stroke: A community-based, nested, and case-control study.

Background: The prospective association between plasma Se and stroke risk remains inconclusive. The relationship between Se and ischemic stroke among a low circulating Se status population deserves more attention, especially for Chinese people who were a high-risk group for Se deficiency.

Objective: The relationship between plasma Se concentration and ischemic stroke risk in a large-scale Chinese community-based population and any potential effect modifiers were investigated.

Joint Modeling of Response Accuracy and Time in Between-Item Multidimensional Tests Based on Bi-Factor Model.

With the popularity of computer-based testing (CBT), it is easier to collect item response times (RTs) in psychological and educational assessments. RTs can provide an important source of information for respondents and tests. To make full use of RTs, the researchers have invested substantial effort in developing statistical models of RTs.

Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence.

Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort of adolescents.

The influence of fitness on exercise blood pressure and its association with cardiac structure in adolescence.

Purpose: Exaggerated exercise blood pressure (BP) is associated with altered cardiac structure and increased cardiovascular risk. Fitness modifies these associations, but the effect in healthy adolescents is unknown. We performed an observational study to determine the influence of fitness on post-exercise BP, and on its relationship with cardiac structure in adolescents.

Masked hypertension and submaximal exercise blood pressure among adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Purpose: Masked hypertension is associated with increased cardiovascular risk but is undetectable by clinic blood pressure (BP). Elevated systolic BP responses to submaximal exercise reveal the presence of masked hypertension in adults, but it is unknown whether this is the case during adolescence. We aimed to determine if exercise BP was raised in adolescents with masked hypertension, and its association with cardiovascular risk markers.

[Aerobic Denitrification and Microbial Community Shift in SBR Bioaugmented with Strains YH01 and YH02].

The enhanced aerobic denitrification capability of the mixed strains YH01+YH02 in utilizing potassium nitrate, and the dynamic changes in the microbial community component during the period of operation, were evaluated. The microbial community in different stages of the SBR was analyzed by using high-throughput sequencing technology after inoculation with YH01+YH02. The results showed that the NO-N, TN, and COD removal efficiencies increased by 12.

[Analysis of the Microbial Community Structure in Continuous Flow Reactor Enhanced by Heterotrophic Nitrification and Aerobic Denitrification Bacterium Burkholderia sp. YX02].

To reveal the dynamic succession of microbial community structure along with time in bio-denitrification reactor, a continuous flow reactor containing immobilized heterotrophic nitrification-aerobic denitrification bacterium Burkholderia sp. YX02 was taken as a model. The microbial community structure in the bioreactor was analyzed by PCR-DCGE, and its correlations with environmental factors such as pH, NH4+ -N, NO2- -N, NO3- -N and COD were simultaneously investigated.

Peptide Bond Formation in Water Mediated by Carbon Disulfide.

Demonstrating plausible nonenzymatic polymerization mechanisms for prebiotic monomers represents a fundamental goal in prebiotic chemistry. While a great deal is now known about the potentially prebiotic synthesis of amino acids, our understanding of abiogenic polymerization processes to form polypeptides is less well developed. Here, we show that carbon disulfide (CS2), a component of volcanic emission and sulfide mineral weathering, and a widely used synthetic reagent and solvent, promotes peptide bond formation in modest yields (up to ∼20%) from α-amino acids under mild aqueous conditions.

Chemically programmed antibodies targeting multiple alpha(v) integrins and their effects on tumor-related functions in vitro.

Integrins αvβ3 and αvβ6 are highly expressed on tumor cells and/or by the tumor vasculature of many human cancers, and represent promising targets for anticancer therapy. Novel chemically programmed antibodies (cpAbs) targeting these integrins were prepared using the catalytic aldolase Antibody (Ab) programming strategy. The effects of the cpAbs on cellular functions related to tumor progression were examined in vitro using tumor cell lines and their cognate integrin ligands, fibronectin and osteopontin.

Multiple catalytic aldolase antibodies suitable for chemical programming.

Chemical programming of nine murine antibodies with catalytic aldolase activity was examined using compounds, equipped with diketone or pro-vinyl ketone linkers that inhibit integrin adhesion receptor functions. The results showed that most Abs were programmed using the diketone compounds in a manner similar to previously reported catalytic antibody 38C2. On the other hand, only those antibodies, which catalyzed the retro aldol reaction of the pro-vinyl ketone linkers efficiently, were programmed.

Alteration of the bis-tetrahydrofuran core stereochemistries in asimicin can affect the cytotoxicity.

A systematic analysis using 10 synthetic asimicin stereoisomers revealed that the stereochemistry of the bis-tetrahydrofuran core, including the tetrahydrofuran rings and the adjacent hydroxy functions, had significant effect on its cytotoxicity. Our findings set to rest the highly controversial perception that the stereochemistry of the tetrahydrofuran core has little effect on the activity, which is not true for its cytotoxic effect, and also reinforces the previous conclusion that asimicin is a highly potent anticancer compound.

Biomimetic catalysis of diketopiperazine and dipeptide syntheses.

Modular, supramolecular catalysts based on the coiled coil peptide scaffold and designed to mimic nonribosomal peptide synthetases are demonstrated to catalyze the formation of diketopiperazine and linear dipeptides for several aminoacyl substrates. We further demonstrate that the nature of the active site residues in the peptide catalysts can be used to effect directed intermodular aminoacyl transfer processes and govern the relative yields of diketopiperazine, linear dipeptide, and hydrolyzed substrate.

Functional and mechanistic analyses of biomimetic aminoacyl transfer reactions in de novo designed coiled coil peptides via rational active site engineering.

Ribosomes and nonribosomal peptide synthetases (NRPSs) carry out instructed peptide synthesis through a series of directed intermodular aminoacyl transfer reactions. We recently reported the design of coiled-coil assemblies that could functionally mimic the elementary aminoacyl loading and intermodular aminoacyl transfer steps of NRPSs. These peptides were designed initially to accelerate aminoacyl transfer mainly through catalysis by approximation by closely juxtaposing four active site moieties, two each from adjacent noncovalently associated helical modules.

Biomimetic catalysis of intermodular aminoacyl transfer.

Intermodular aminoacyl transfer is the fundamental bond forming reaction in the biosynthesis of polypeptides by ribosomes and nonribosomal peptide synthetases (NRPS). Here we report the design and functional characterizations of short synthetic α-helical peptides that mimic the aminoacyl loading and intermodular aminoacyl transfer steps of NRPS with aminolysis rate enhancements in neutral aqueous solutions of up to 5400-fold (/). The catalysts operate as noncovalently associated peptide assemblies with composite active sites fashioned at the interface between helical subunits.

Diastereoselectivity-switchable and highly enantioselective 1,3-dipolar cycloaddition of nitrones to alkylidene malonates.

Trisoxazoline 1/Co(ClO(4))(2).6H(2)O catalyzed the 1,3-cycloaddition between nitrones 3 with alkylidene malonates 2 at 0 degrees C to give the isoxazolidines with both high enantioselectivity and high exo selectivity. However, when the temperature was lowered from 0 to -40 degrees C, the same cycloaddition afforded endo isomers as the major products with good to high enantioselectivity.

Controllable enantioselective Friedel-Crafts reaction between indoles and alkylidene malonates catalyzed by pseudo-C3-symmetric trisoxazoline copperII complexes.

Pseudo-C(3)-symmetric trisoxazoline copper(II) complexes prove to be excellent catalysts in the Friedel-Crafts alkylation of indoles with alkylidene malonates. The absolute stereochemistry of this reaction is shown to be dependent on the solvent. Reactions in isobutyl alcohol afford the Friedel-Crafts alkylation adducts in excellent yields and with up to +98% ee.

Chiral tris(oxazoline)/Cu(II) catalyzed coupling of terminal alkynes and nitrones.

Novel chiral iPr-tris(oxazoline)/Cu(ClO4)2 x 6H2O catalyzed coupling of terminal acetylenes and nitrones to afford cis-disubstituted beta-lactams is described; the choice of base proves essential to both the diastereoselectivity and the enantioselectivity.

Unexpected catalyst for Wittig-type and dehalogenation reactions.

A novel catalyst 2 for Wittig-type and dehalogenation reactions was developed. In the presence of triphenyl phosphite, a wide variety of aldehydes could react with alpha-bromoacetates to afford alpha,beta-unsaturated esters or ketones in high yields with excellent E-stereoselectivity when 1-2 mol % of compound 2 was used. Compound 2 was also an effective catalyst for reductive dehalogenation of alpha-bromocarbonyl compounds.

Wittig-type olefination catalyzed by PEG-telluride.

Soluble poly(ethylene glycol) (PEG)-supported telluride 2 was designed and synthesized for catalytic Wittig-type reactions. It was found that the catalytic loading could be reduced from 20 to 2 mol % by the introduction of PEG (even to 0.5 mol % when some telluride salts were used as the catalyst).

A novel chiral sulfonium yilde: highly enantioselective synthesis of vinylcyclopropanes.

A newly designed chiral sulfonium allylide, generated in situ from the corresponding sulfonium salt in the presence of KOBu(t), reacted with alpha,beta-unsaturated esters, ketones, amides, and nitriles to afford trans-2-silylvinyl-trans-3-substituted cyclopropyl esters, ketones, amides, and nitriles with outstanding diastereoselectivity and excellent enantioselectivity in good to high yields. A mechanistic rationale is proposed.