Glycopeptide Synthesis on an Ionic Liquid Support

An ionic liquid-supported synthetic method for the construction of glycopeptides in high yields is reported. This method avoids the use of large excesses of reagents and chromatographic purification and, therefore, represents a useful addition to existing approaches for the ionic liquid-supported synthesis of oligosaccharides and peptides

Carbohydrate-Functionalized Chitosan Fiber for Influenza Virus Capture

The high transmissibility and genetic variability of the influenza virus have made the design of effective approaches to control the infection particularly challenging. The virus surface hemagglutinin (HA) protein is responsible for the viral attachment to the host cell surface via the binding with its glycoligands, such as sialyllactose (SL), and thereby is an attractive target for antiviral designs. Herein we present the facile construction and development of two SL-incorporated chitosan-based materials, either as a water-soluble polymer or as a functional fiber, to demonstrate their abilities for viral adhesion inhibition and decontamination. The syntheses were accomplished by grafting a lactoside bearing an aldehyde-functionalized aglycone to the amino groups of chitosan or chitosan fiber followed by the enzymatic sialylation with sialyltransferase. The obtained water-soluble SL–chitosan conjugate bound HA with high affinity and inhibited effectively the viral attachment to host erythrocytes. Moreover, the SL-functionalized chitosan fiber efficiently removed the virus from an aqueous medium. The results collectively demonstrate that these potential new materials may function as the virus adsorbents for prevention and control of influenza. Importantly, these materials represent an appealing approach for presenting a protein ligand on a chitosan backbone, which is a versatile molecular platform for biofunctionalization and, thereby, can be used for not only antiviral designs, but also extensive medical development such as diagnosis and drug delivery

Synthesis and Assessment of Globotriose–Chitosan Conjugate, a Novel Inhibitor of Shiga Toxins Produced by <i>Escherichia coli</i>

Shiga toxin (Stx)-producing <i>Escherichia coli</i> (STEC) causes diarrhea and colitis in humans that can develop into a life-threatening hemolytic uremic syndrome (HUS). Developing efficient means of controlling STEC diseases, for which no drugs or vaccines are currently available, remains a high priority. We report here the construction and development of chitosan conjugates bearing the Stx ligand trisaccharide globotriose to demonstrate their potential as STEC disease treatment agents. The synthesis was accomplished by grafting a globotriose derivative containing an aldehyde-functionalized aglycone to chitosan amino groups. The obtained globotriose–chitosan conjugate bound with high affinity to Stx and efficiently neutralized its toxicity on Vero cells. Moreover, Stx levels in the gut of infected mice receiving oral doses of the conjugate were greatly diminished, enabling the mice to resist a fatal STEC challenge. The conjugate appears to function as a Stx adsorbent in the gut, preventing toxin entry into the bloodstream and consequent development of HUS. As such, the conjugate could act as a novel agent against STEC disease

Image_1_Anticipation of Uncertain Threat Modulates Subsequent Affective Responses and Covariation Bias.TIF

Uncertainty contributes to stress and anxiety-like behaviors by impairing the ability of participants to objectively estimate threat. Our study used the cue-picture paradigm in conjunction with the event-related potential (ERP) technique to explore the temporal dynamics of anticipation for and response to uncertain threat in healthy individuals. This task used two types of cue. While ‘certain’ cues precisely forecasted the valence of the subsequent pictures (negative or neutral), the valence of pictures following ‘uncertain’ cues was not predictable. ERP data showed that, during anticipation, uncertain cues elicited similar Stimulus-Preceding Negativity (SPN) to certain-negative cues, while both of them elicited larger SPN than certain-neutral cues. During affective processing, uncertainty enlarged the mean amplitude of late positive potential (LPP) for both negative and neutral pictures. Behavioral data showed that participants reported more negative mood ratings of uncertain-neutral pictures relative to certain-neutral pictures and overestimated the probability of negative pictures following uncertain cues. Importantly, the enlarged anticipatory activity evoked by uncertain cues relative to that evoked by certain-neutral cues positively modulated the more negative mood ratings of uncertain-neutral pictures relative to certain-neutral pictures. Further, this more negative mood ratings and the general arousal anticipation during anticipatory stage contributed to the covariation bias. These results can provide a novel insight into understanding the neural mechanism and pathological basis of anxiety.</p

Synthesis of Galabiose-chitosan Conjugate as Potent Inhibitor of Streptococcus suis Adhesion

The aim of this work is to construct a safe and effective drug candidate against Streptococcus suis infection. A panel of chitosan-based polymer conjugates with branched galabiose (Galα1−4Gal) side chains was synthesized as inhibitors of S. suis adhesion. The synthesis was achieved by using an aldehyde-functionalized galabiose derivative to graft it onto chitosan amino groups. Structural compositions of the conjugates were verified by 1H NMR spectroscopy and CHN elemental analyses. Potent inhibitory activities of the conjugates against S. suis adhesion to human erythrocytes were determined at low nanomolar concentration by HAI assay. An SPR study revealed a high affinity binding (Kd = 39.6 nM) of the conjugate with BSI-B4 lectin. By using biocompatible chitosan as the scaffold for presenting S. suis-specific galabiose units, as well as the concise route tailored for the conjugate syntheses, the present study provides a practical way for explorations of new anti-S. suis therapies

The ERP grand-average waveforms and the amplitudes of the FRN.

<p>(A) The grand-averaged ERP waveforms aligned at the onset of feedback stimuli for likable and unlikable players' performance (recorded for Fz and FCz sites). The left panel shows data from females, and the right panel shows data for males. (B) FRN response to win and loss outcomes of likable and unlikable players based on gender.</p

Forest plot of acute xerostomia in HNSCC patients treated with radiotherapy/concomitant chemoradiation.

<p>The squares and horizontal lines demonstrate the study-specific OR and 95% CI. The area of the squares reflects the study specific weight (inverse of the variance). The diamond represents the pooled OR and 95% CI.</p

Like or Dislike? Affective Preference Modulates Neural Response to Others' Gains and Losses - Figure 1

<p>(A) Schematic representation of the experimental procedure. The study included two independent experiments. One experiment was a social exchange game and the other one was an observation task. Each experiment consisted of two blocks which were alternated, and the study ended with a behavioral assessment. (B) Observation task: overview. (The vectogram for the human face used here is provided for illustration, photographs of human faces were used in the study.)</p

Forest plot of hematological toxicity in HNSCC patients treated with radiotherapy/concomitant chemoradiation.

<p>The squares and horizontal lines demonstrate the study-specific OR and 95% CI. The area of the squares reflects the study specific weight (inverse of the variance). The diamond represents the pooled OR and 95% CI.</p