Chemical approaches for the stereocontrolled synthesis of 1,2-cis-ß-D-rhamnosides.

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-ß-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain ß-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of ß-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in ß-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.

Research progress on the therapeutic effects of polysaccharides on non-alcoholic fatty liver diseases.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is a leading cause of cirrhosis and hepatocellular carcinoma. Due to its complex pathophysiology, there is currently no approved therapy. Polysaccharide, a kind of natural product, possesses a wide range of pharmacological activities. Numerous preclinical studies have confirmed that polysaccharides could interfere with the occurrence and development of NAFLD at multiple interrelated levels, such as improvement of glucose and lipid metabolism, antioxidation, anti-inflammation, and regulation of gut-liver axis, thus showing great potential as novel anti-NAFLD drugs. In this paper, we reviewed the polysaccharides with anti-NAFLD effect in recent years, and also systematically analyzed their possible pharmacological mechanisms.

A Perovskite Photodetector Crossbar Array by Vapor Deposition for Dynamic Imaging.

With the development of perovskite photodetectors, integrating photodetectors into array image sensors is the next target to pursue. The major obstacle to integrating perovskite photodiodes for dynamic imaging is the optoelectrical crosstalk among the pixels. Herein, a perovskite photodiode-blocking diode (PIN-BD) crossbar array with pixel-wise rectifying property by the vapor deposition method is presented. The PIN-BD shows a large rectification ratio of 3.3 × 102 under illumination, suppressing electrical crosstalk to as small as 8.0% in the imaging array. The fast response time of 72.8 ns allows real-time image acquisition by over 25 frames per second. The imaging sensor exhibits excellent imaging capability with a large linear dynamic range of 112 dB with 4096 gray levels and weak light sensitivity under 1.2 lux.

Chemical Synthesis of the Highly Sterically Hindered Core Undecasaccharide of Helicobacter pylori Lipopolysaccharide for Antigenicity Evaluation with Human Serum.

Helicobacter pylori, listed as a human carcinogen by the Department of Health and Human Services, colonizes the gastric mucosa of more than half of the world's population. The individuals infected with H. pylori have a high risk to develop chronic gastritis, peptic ulcers, and even gastric cancer. The conserved core structure of H. pylori lipopolysaccharide (LPS) has been regarded as a promising candidate structure for development of a glycoconjugate vaccine targeting multiple serotypes. Here, we report a total synthesis of the core undecasaccharide of H. pylori LPS and its subunit antigens. The match and mismatch between the glycosyl donor and acceptor caused by the inert hydroxyl groups were addressed by a judicious choice of orthogonal protection strategies and glycosylation conditions. A combination of acyl remote participation and solvent effects has been applied for selective formation of the five 1,2-cis-glucosidic bonds. The high steric hindrance induced by the high carbon sugars and trinacriform architecture required that the core undecasaccharide was synthesized through a finely tuned linear assembly [2 + (1 + (3 + (1 + (1 + 3))))] rather than convergent strategies. An antigenicity evaluation using glycan microarrays showed that an α-(1 → 6)-glucan trisaccharide is recognized by IgG antibodies in sera of H. pylori-infected patients. The phosphate group of the inner core trisaccharide key epitope is very important for IgG recognition. These findings are an important step toward designing carbohydrate-based vaccines against H. pylori.

Anti-inflammatory Effect of a Novel Pectin Polysaccharide From Rubus chingii Hu on Colitis Mice.

Rubus chingii Hu has been used as a functional food for a long time. A novel pectin polysaccharide named RCHP-S from R. chingii Hu was structurally identified and explored its anti-inflammatory effect on colitis mice. RCHP-S was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. NMR spectroscopy and methylation analysis showed that RCHP-S was mainly composed of HG-type pectin domains but also contains a small amount of RG-I. The anti-inflammatory tests indicated that the mouse macrophage RAW 264.7 cells pretreated with RCHP-S could show a significant inhibitory effect on the mRNA level of iNOS, IL-1ß, IL-6, and TNF-α in vitro. Polysaccharide RCHP-S reduced the enteritis symptoms in dextran sulfate sodium (DSS)-induced colitis mice by inhibiting released inflammatory factors. These results indicated that the R. chingii Hu polysaccharide can be used as food additives for the treatment of intestinal inflammation.

Chemical Synthesis Elucidates the Key Antigenic Epitope of the Autism-Related Bacterium Clostridium bolteae Capsular Octadecasaccharide.

The gut pathogen Clostridium bolteae has been associated with the onset of autism spectrum disorder (ASD). To create vaccines against C. bolteae, it is important to identify exact protective epitopes of the immunologically active capsular polysaccharide (CPS). Here, a series of C. bolteae CPS glycans, up to an octadecasaccharide, was prepared. Key to achieving the total syntheses is a [2+2] coupling strategy based on a ß-d-Rhap-(1→3)-α-d-Manp repeating unit that in turn was accessed by a stereoselective ß-d-rhamnosylation. The 4,6-O-benzylidene-induced conformational locking is a powerful strategy for forming a ß-d-mannose-type glycoside. An indirect strategy based on C2 epimerization of ß-d-quinovoside was efficiently achieved by Swern oxidation and borohydride reduction. Sequential glycosylation, and regioselective and global deprotection produced the disaccharide and tetrasaccharide, up to the octadecasaccharide. Glycan microarray analysis of sera from rabbits immunized with inactivated C. bolteae bacteria revealed a humoral immune response to the di- and tetrasaccharide, but none of the longer sequences. The tetrasaccharide may be a key motif for designing glycoconjugate vaccines against C. bolteae.

Chemical Synthesis and Immunological Evaluation of Helicobacter pylori Serotype O6 Tridecasaccharide O-Antigen Containing a dd-Heptoglycan.

The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipo-polysaccharide (LPS) O-antigens that contain Lewis determinant oligosaccharides and unique dd-heptoglycans has not yet been identified. Reported here is the first total synthesis of H. pylori serotype O6 tridecasaccharide O-antigen containing a terminal Ley tetrasaccharide, a unique α-(1→3)-, α-(1→6)-, and α-(1→2)-linked heptoglycan, and a ß-d-galactose connector, by an [(2×1)+(3+8)] assembly sequence. Seven oligosaccharides covering different portions of the entire O-antigen were prepared for immunological investigations with a particular focus on elucidation of the roles of the dd-heptoglycan and Ley tetrasaccharide. Glycan microarray analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the α-(1→3)-linked heptoglycan, a key motif for designing glycoconjugate vaccines for H. pylori serotype O6.

Optimized volume models of earthquake-triggered landslides.

In this study, we proposed three optimized models for calculating the total volume of landslides triggered by the 2008 Wenchuan, China Mw 7.9 earthquake. First, we calculated the volume of each deposit of 1,415 landslides triggered by the quake based on pre- and post-quake DEMs in 20 m resolution. The samples were used to fit the conventional landslide "volume-area" power law relationship and the 3 optimized models we proposed, respectively. Two data fitting methods, i.e. log-transformed-based linear and original data-based nonlinear least square, were employed to the 4 models. Results show that original data-based nonlinear least square combining with an optimized model considering length, width, height, lithology, slope, peak ground acceleration, and slope aspect shows the best performance. This model was subsequently applied to the database of landslides triggered by the quake except for two largest ones with known volumes. It indicates that the total volume of the 196,007 landslides is about 1.2 × 10(10) m(3) in deposit materials and 1 × 10(10) m(3) in source areas, respectively. The result from the relationship of quake magnitude and entire landslide volume related to individual earthquake is much less than that from this study, which reminds us the necessity to update the power-law relationship.