Development of Boronic Acid Flurescent Reporters, Boronic Acid-Modified Thymidine Triphosphates for Sensor Design and Antagonists of Bacterial Quorum Sensing in Vibrio Harveyi

Carbohydrates are known to play important roles in a large number of physiological and pathological processes. Conceivably, “binders” of carbohydrates of biological importance could be used as diagnostic and therapeutic agents. Currently, lectins are the major available tools in research for carbohydrate recognition. However, the available lectins often have cross-reactivity issues, along with the high costs and stability issues. Therefore, there is a critical need to develop alternatives (lectin mimics). In this regard, there have been very active efforts in developing different “binders”, such as small molecule lectinmimics and aptamers. Among all the small molecule lectinbmimics developments, boronic acid stands out as the most important building blocks of the sensors design for carbohydrates biomarkers due to its intrinsic binding affinities with diols. To address a fundamental question that whether boronic acid also binds to six-membered ring sugars, with very limited precedents, we provided a concrete experimental evidence of the binding. Specifically, a series of isoquinolinylboronic acids were found to have remarkably high binding affinities with fluorescence change upon binding to representative sugars. Most importantly, these isoquinolinylboronic aicds showed weak but very encouraging bindings with six-membered sugar model. All these promising results paves the way of using boronic acids, especially isoquinolinylboronic acid as building blocks for chemosensors design for biological carbohydrates biomarkers, which universally contain six-membered ring and liner diols. Aptamer provides another alternative way for sensors development for carbohydrates biomarkers as lectin mimics. Compared to lectins, they are normally cheaper and more stable. However, there is much less options. Another challenging area for aptamer-based lectin mimics development is the difficulty to differentiate changes in glycosylation patterns of a glycoprotein, which affect the function of a glycoprotein and thus recognized as biomarkers. To address this major challenge, our group first demonstrated that the incorporation of a boronic acid into DNA would allow for the aptamer selection process to gravitate towards the glycosylation site. To examine the generality of boronic acid incorporation, increase the structural diversity, and broaden the application of boronic acid-modified DNA, a series of B-TTP analogues with simplified structures were designed, synthesized, and successfully incorporated into DNA. A simple route was also developed using 1,7-octadiyne as a linker for both Sonogashira coupling with thymidine and CuAAC tethering of a boronic acid moiety. This paves the way for the preparation of a large number of B-TTPs with different structural features for aptamer selection or array analysis. Finally, bacterial quorum sensing has received much attention in recent years because of its relevance to pathological events such as biofilm formation. As one of the very first groups that developed a series of antagonists for AI-2 mediated quorum sensing, we herein designed and synthesized a series of analogues based on the structures of two lead inhibitors identified through virtual screening. Besides, we also examined their inhibitory activities, twelve of which showed equal or better inhibitory activities compared with the lead inhibitors. The best compound showed an IC50 of about 6 mM in a whole cell assay using Vibrio harveyi as the model organism. This encouraging results and SAR discuss also paves the way for the finding of more potent compound through further structure optimization

Biomechanical comparison of all-on-4 and all-on-5 implant-supported prostheses with alteration of anterior-posterior spread: a three-dimensional finite element analysis

Introduction: The all-on-4 concept is widely used in clinical practice. However, the biomechanical changes following the alteration of anterior-posterior (AP) spread in all-on-4 implant-supported prostheses have not been extensively studied.Methods: Three-dimensional finite element analysis was used to compare the biomechanical behavior of all-on-4 and all-on-5 implant-supported prostheses with a change in anterior-posterior (AP) spread. A three-dimensional finite element analysis was performed on a geometrical mandible model containing 4 or 5 implants. Four different implant configurations were modeled by varying the angle of inclination of the distal implants (0°and 30°), including all-on-4a, all-on-4b, all-on-5a, and all-on-5b, and a 100 N force was successively applied to the anterior and unilateral posterior teeth to observe and analyze the differences in the biomechanical behavior of each model under the static influence at different position.Results: Adding an anterior implant to the dental arch according to the all-on-4 concept with a distal 30° tilt angle implant exhibited the best biomechanical behavior. However, when the distal implant was implanted axially, there was no significant difference between the all-on-4 and all-on-5 groups.Discussion: In the all-on-5 group, increasing the AP spread with tilted terminal implants showed better biomechanical behavior. It can be concluded that placing an additional implant in the midline of the atrophic edentulous mandible and increasing the AP spread might be beneficial in improving the biomechanical behavior of tilted distal implants

The effects of short-term rainfall variability on leaf isotopic traits of desert plants in sand-binding ecosystems

Author's manuscript made available in accordance with the publisher's policy.Sand-binding vegetation is effective in stabilizing sand dunes and reducing soil erosion, thus helps minimize the detrimental effects of desertification. The aim of this study is to better understand the relationships between water and nutrient usage of sand-binding species, and the effects of succession and rainfall variability on plants’ water–nutrient interactions. We examined the effects of long-term succession (50 years), inter-annual rainfall variability (from 65% of the mean annual precipitation in 2004 to 42% in 2005) and seasonality on water–nutrient interactions of three major sand-binding species (Artemisia ordosica, Hedysarum scoparium and Caragana korshinskii) by measuring foliar δ13C, δ15N and [N]. Long-term succession in general did not significantly alter δ13C, δ15N and [N] of the three species. Short-term rainfall variability, however, significantly increased foliar δ13C levels of all three species by 1.0–1.8‰ during the severely dry year. No significant seasonal patterns were found in foliar δ13C and δ15N values of the three species, whereas foliar [N] varied by season. For the two leguminous shrubs, the correlations between δ13C and δ15N were positive in both sampling years, and the positive correlation between [N] and δ13C was only found in the severely dry year. The results indicate that these sand-binding plants have developed into a relatively stable stage and they are able to regulate their nitrogen and water use in responding to environmental conditions, which reinforces the effectiveness of plantation of native shrubs without irrigation in degraded areas. However, the results also indicate that short-term climate variability could have severe impact on the vegetation functions

Reconstruct the Mesoscale Information of Typhoon with BDA Method Combined with AMSU-A Data Assimilation Method

This paper conducts the assimilating experiments and simulating experiments on typhoon “Aere” (No. 0418), by use of bogus data assimilation (BDA) method combined with advanced microwave sounding unit-A (AMSU-A) data assimilation method in the fifth-generation National Center for Atmospheric Research (NCAR)/Penn State Mesoscale Model Version-3 (MM5V3), the Radiative Transfer for TIROS-N Operational Vertical Sounder Version-7 (RTTOV) model, and their adjoint models. The Bogus data constructed with BDA technique are mainly located at sea level, while the peak energy contribution levels of the sounder channels selected in AMSU-A data assimilation technique are mainly located at upper troposphere. The two types of data can reconstruct the meso-scale information and improve the typhoon initial fields under the model dynamic forcing effect, respectively from the low level and the upper level of atmosphere during the assimilating process. Numerical results show that with four-dimensional variational data assimilation (4DVAR) technique the circulation of initial fields is improved, the “warm core” of typhoon is enhanced, the “cloud water” phenomenon that occurs in the optimal initial fields and the numerical model is changed into “warm start” from “cold start”