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AbstractHelicobacter pylori, a gram‐negative bacterium, is known to be associated with various gastric pathologies including chronic gastritis, peptic ulcers and gastric carcinoma. Despite the emerging issue of bacterial resistance to antibiotic-based combination therapy, there is currently no vaccine available for H. pylori infection in the market. Here, we report the synthesis of α-(1,3)-D,D-heptoglycan with different chain length from the lipopolysaccharide of H. pylori serogroup O6. The [n + 1] iterative glycosylation strategy was used for heptoglycan chain elongation. The trifluoroacetimidate heptoside donor exhibited much higher efficiency than thioglycoside donor during glycosylation. An antigenicity evaluation using glycan microarrays indicated that α-(1,3)-D,D-hepto-disaccharide, pentasaccharide and hexasaccharide showed stronger binding affinity to IgG antibodies of H. pylori O6 LPS immunized rabbit serum or serum of H. pylori infected patients. These findings provide significant structure − activity relationship information for developing carbohydrate-based vaccines against H. pylori containing α-(1,3)-D,D-heptoglycan. [ABSTRACT FROM AUTHOR]

Nrf2 is a key regulator in the maintenance of cellular redox balance by regulating the expression of genes related to antioxidative responses and detoxification. Nrf2 protein levels are increased in response to oxidative stress. However, the regulation of the Nrf2 3′UTR on Nrf2 translation is unclear. Here, we report that the translational activity of the 3′UTR is required for Spodoptera litura Nrf2 protein expression. Experiments showed that the 3′UTR translation activity of S. litura Nrf2 was much higher than that of the 5′UTR. RNA interference (RNAi) of the expression of T cell internal antigen-related protein (TIAR), an RNA-binding protein that interacts with the 3′UTR of S. litura Nrf2 , resulted in Nrf2 mRNA movement out of translationally active polysomes and a decrease in cellular Nrf2 protein levels. TIAR interacted with poly(A)-binding protein (PABP) and translation initiation factors eIF2-2 and eIF2-3 to enhance Nrf2 translation, indicating that the 3′UTR regulates Nrf2 translation. Diethyl maleate (DEM) treatment increased reactive oxygen species (ROS) in cells and enhanced Nrf2 levels, which had been reduced by cycloheximide (CHX), an inhibitor of de novo protein synthesis; Tiar RNAi increased ROS levels in DEM-treated cells, suggesting TIAR-mediated 3′UTR involvement in Nrf2 translation in response to DEM treatment. Thus, we reveal a posttranscriptional regulation mechanism of Nrf2, in which TIAR binds with the Nrf2 mRNA 3′UTR to enhance Nrf2 translation, facilitating the increase in Nrf2 protein levels in response to oxidative stress. [Display omitted] • The Nrf2 3′UTR enhanced Nrf2 translation of Spodoptera litura. • TIAR bound to the 3′UTR to enhance Nrf2 translation. • TIAR enhanced the distribution of Nrf2 mRNA in polyribosomal components. • TIAR interacted with PABP, eIF2-2 and eIF2-3 to enhance Nrf2 translation. • TIAR was involved in antioxidative stress through regulating Nrf2 translation. [ABSTRACT FROM AUTHOR]

In this paper, the gasification reactivities of four types of Chinese coal were studied, each with different ash content and coal rank. Of the 4 coal types, 2 were HCl-washed and demineralized to investigate the effects of ash removal (for both dealkalization and demineralization) on coal gasification. The effects of ash on the evolution of physical and chemical structure were further studied using scanning electron microscopy equipped with energy dispersive X-ray analysis (SEM-EDX), N 2 absorption and FT-Raman techniques. The results show that the initial gasification rate of raw chars is twice as high as the HCl-washed and ash-free chars. The gasification rate of ash-free char significantly increases with the increase in carbon conversion and surpasses the gasification rate of raw char when carbon conversion is higher than 50%. Moreover, the specific surface area of ash-free char significantly increases with carbon conversion, resulting in the significant increase in the gasification rate. Whereas the specific surface areas of raw char and HCl-washed char both decrease during high-conversion stages. The FT-Raman analysis shows that the ash-free char band area ratios A D3 /A G and A D4 /A G are lower than those of raw char at the initial gasification stage; this results in the initial gasification rate decrease of ash-free chars. In addition, the ash-free char band area ratio A G /A all is smaller than that of raw char in the high conversion stages. [ABSTRACT FROM AUTHOR]

Abstract: Helicobacter pylori, a widespread gastric bacterial pathogen that infects 90 % of the population in developing countries, causes chronic gastritis, peptic ulcers and gastric cancer. Battling H. pylori infection is a serious challenge due to the increased resistance to antibiotics and the lack of vaccines. The lipopolysaccharide covering the H. pylori cell‐surface outer membrane is an attractive target for the development of a glycoconjugate vaccine. Here, we report a [3+5] convergent synthesis of an outer core octasaccharide of H. pylori employing just three orthogonally protected building blocks. A synergistic glycosylation strategy enables the creation of five pivotal 1,2‐cis‐α‐glucosidic bonds consist of four types of linkages using just three monomers. This strategy can be expanded to many 1,2‐cis‐α‐gluoside‐containing oligosaccharides both in solution and solid phase. [ABSTRACT FROM AUTHOR]

Spodoptera litura is polyphagous pest insect and feeds on plants of more than 90 families. In this study the role of glutathione S -transferase epilson 1 ( slgste1 ) in S . litura in detoxification was examined. This gene was up-regulated in the midgut of S . litura at the transcriptional and protein levels when the insect fed on Brassica juncea or diet containing phytochemicals such as indole-3-carbinol and allyl-isothiocyanate that are metabolic products of sinigrin and glucobrassicin in B . juncea . The SlGSTE1 could catalyze the conjugation of reduced glutathione and indole-3-carbinol and allyl-isothiocyanate, as well as xanthotoxin, which is a furanocoumarin, under in vitro condition. When the expression of Slgste1 in the larvae was suppressed with RNAi, the larval growth and feeding rate were decreased. Furthermore, the up-regulated expression of the SlGSTE1 protein in the midgut of larvae that fed on different host plants was detected by 2-DE and ESI/MS analysis. The feeding adaptation from the most to the least of the larvae for the various host plants was Brassica alboglabra , Brassica linn . Pekinensis , Cucumis sativus , Ipomoea batatas , Arachis hypogaea and Capsicum frutescens . All the results together suggest that Slgste1 is a critical detoxifying enzyme that is induced by phytochmicals in the host plants and, inter alia , may be related to host plant adaptation of S . litura . [ABSTRACT FROM AUTHOR]

The fabrication of TiO 2 @MnO 2 nanotube arrays (NTAs) structure is accomplished via a pulsed electrodeposition technique. The successful preparation of this structure is owing to the high current pulse used, which creates a sufficient nucleation trend on the wall of the entire TiO 2 nanotube layer, that results in the continuous deposition of MnO 2 along the nanotube walls. The synthesized TiO 2 @MnO 2 NTAs sample is found to exhibit excellent electrochemical behavior with high specific capacitance of 425.0 F g −1 and areal capacitance of 150.9 mF cm −2 , ranking in the top level ever achieved by a MnO 2 -TiO 2 composite. Furthermore, a symmetric supercapacitor device is assembled using two strips of the TiO 2 @MnO 2 NTAs electrode that yielded energy density as high as 7.4 Wh kg −1 , a much higher value than most of the values reported for symmetric MnO 2 //MnO 2 supercapacitors. The remarkable electrochemical properties of the TiO 2 @MnO 2 NTAs sample make it an attractive candidate for the application of constructing high-performance supercapacitors. [ABSTRACT FROM AUTHOR]

The bacterium Vibrio vulnificus can cause severe infections internally and externally. The mortality rate of V. vulnificus -associated gangrene and septicemia has increased due to antibiotic resistance and the absence of human vaccine. Bacterial carbohydrates have been widely used in the development of bacterial vaccines. Here, a rare l -Gal p NAmA-containing disaccharide that exists in V. vulnificus biotype 2 serovar A O-antigen was synthesized from d -glucose and l -galactose. An investigation on the influence of different linkers on the disaccharide synthetic efficiency indicated that the amine linker has more practicality. Two α-glycosidic linkages were constructed with good stereoselectivity by using nonparticipating C2 azido group and solvent effect. An orthogonal protection strategy allowed introductions of carboxyl and acetamidino (Am) groups at the disaccharide stage. The synthesis of the amine-linked disaccharide will provide a basis for the preparation of the trisaccharide repeating unit and longer fragments of V. vulnificus biotype 2 serovar A O-antigen, as well as other complex glycans. [ABSTRACT FROM AUTHOR]

Citrioside A, a new flavonoid glycoside, has been isolated from the n-butanol soluble fraction of Eucalyptus citriodora, along with five flavonoid glycosides, reported for the first time from Eucalyptus citriodora. Their structures were elucidated on the basis of spectroscopic methods and from literature values. [ABSTRACT FROM AUTHOR]

Phytochemicals are toxic to insects, but their insecticidal efficiencies are usually low compared to synthetic insecticides. Understanding the mechanism of insect adaptation to phytochemicals will provide guidance for increasing their efficacy. Reduced glutathione (GSH) is a scavenger of reactive oxygen species (ROS) induced by phytochemicals. However, in insects, the pathway of GSH biosynthesis in response to phytochemicals is unclear. We found that exposure to 0.5% indole-3-methanol (I3C), xanthotoxin, and rotenone (ROT) significantly retarded the growth of Spodoptera litura larvae. The oxidative stress in S. litura larvae exposed to phytochemicals was increased. The up-regulation of glutamate cysteine ligase but not glutathione reductase revealed that the de novo synthesis pathway is responsible for GSH synthesis in phytochemical-treated larvae. Treatment with the inhibitor (BSO) of γ-glutamylcysteine synthetase (gclc), a subunit of glutamate cysteine ligase, resulted in decreases of GSH levels and GST activities, increases of ROS levels in I3C-treated larvae, which finally caused midgut necrosis and larval death. Treatment with BSO or I3C alone did not cause larval death. The addition of GSH could partly reduce the influence of I3C and BSO on S. litura growth. Nilaparvata lugens gclc RNAi confirmed the result of BSO treatment in S. litura. N. lugens gclc RNAi significantly increased the mortality of ROT-sprayed N. lugens , in which ROS levels were significantly increased. All data indicate that gclc is involved in insect response to phytochemical treatment. Treatment with dsgclc will increase the insecticidal efficacy of plant-derived compounds. Unlabelled Image • Insect γ-glutamylcysteine synthetase (gclc) was responsive to phytochemical treatments. • The de novo biosynthesis pathway was responsible for GSH synthesis in Spodoptera litura. • The treatment of GCLC inhibitor with phytochemical resulted in pupation failure of S. litura. • Knockdown of gclc increased the mortality of phytochemical-treated Nilaparvata lugens. • Inhibition of GSH synthesis increased phytochemical toxicity by increasing ROS levels in pests. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Treponema is a Gram‐negative anaerobic bacterium, among which the pathogenic Treponema can cause various diseases, such as venereal syphilis (Treponema pallidum), yaws (Treponema carateum), and oral diseases (Treponema denticola and Treponema medium). Although different from conventional lipopolysaccharides, the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development. Hence, we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L‐ornithine (L‐Orn) and D‐aspartic acid (D‐Asp) derivatives. The efficiency of non‐reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors. Our [3+1] glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group, thereby improving the efficiency of synthesizing the target tetrasaccharide. The L‐Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. Therefore, the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional‐group modifications have provided valuable insights for synthesizing other complex bacterial glycans. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Helicobacter pylori (H. pylori) infection is a threat to human health. The lipopolysaccharide (LPS) O‐antigen holds promise for developing vaccines. It is meaningful to explore the immunological activity of oligosaccharides with different lengths and frameshifts for antigen development. Herein, a glycan library of H. pylori O2 O‐antigen containing eight fragments is constructed. After screening with anti‐H. pylori O2 LPS sera and patients' sera by glycan microarray, the disaccharide HPO2G‐2b and trisaccharide HPO2G‐3a show strong antigenicity and then are separately conjugated with carrier protein CRM197. Both glycoconjugates elicit a robust immunoglobulin G (IgG) immune response in rabbits. The anti‐HPO2G‐3a IgG antibodies possess a much stronger binding affinity with the LPS and bacteria of H. pylori O2 than the anti‐HPO2G‐2b IgG antibodies. There is no cross‐reaction between both sera IgG antibodies with LPS and bacteria of H. pylori O1, O6, and E. coli. The results demonstrate the trisaccharide HPO2G‐3a is a promising candidate for H. pylori vaccine development. [ABSTRACT FROM AUTHOR]

Dramatic alterations in epigenetic landscapes are known to impact genome accessibility and transcription. Extensive evidence demonstrates that senescent cells undergo significant changes in chromatin structure; however, the mechanisms underlying the crosstalk between epigenetic parameters and gene expression profiles have not been fully elucidated. In the present study, we delineate the genome-wide redistribution of accessible chromatin regions that lead to broad transcriptome effects during senescence. We report that distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac-occupied enhancer regions, where they are responsible for elevated flanking senescence-associated secretory phenotype (SASP) expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, moves away from H3K27ac-labled SAAs to allow for prominent chromatin accessibility reconstruction during senescence. The enhanced SAAs signal driven by TEAD4 suppression subsequently induces a robust increase in the expression of adjacent SASP genes and the secretion of downstream factors, which contribute to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry, and further reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulates the overall transcriptional program of SASP genes. [ABSTRACT FROM AUTHOR]

Glycans on the surface of bacteria have diverse and essential biological functions and have widely been employed for treating various bacterial infectious diseases. Furthermore, these glycans comprise various functional groups, such as O-, N-, and carboxyl-modified, which significantly increase the diversity of glycan structures. These functional groups are not only crucial for glycans' structural identity but are also essential for their biological functions. Therefore, a clear understanding of the biological functions of these modified groups in corresponding bacterial glycans is crucial for their medical applications. Thus far, the activities of functional groups in some biomedical active carbohydrates have been elucidated. It has been shown that some functional groups are key constituents of biologically active bacterial glycans, while others are actually not essential and may even mask the functions of the glycans. This paper reviews the structures of naturally occurring side-chain functional groups in glycans located on the bacterial surface and their roles in immunological responses. [ABSTRACT FROM AUTHOR]

The highly stereoselective synthesis of complex carbohydrates containing 1,2-cis-quinovosamine is an on-going challenge. Here, we report a synergistic strategy of merging reagent modulation and acyl remote participation for highly stereoselective construction of 1,2-cis-D-quinovosamine linkages. The strategy is applied to the preparation of natural disaccharide present on the surface of Pseudomonas aeruginosa bacteria. The resulting disaccharide can be covalently bound to microarray surface or carrier via the aminopentyl linker at the reducing end, allowing for exploring its antigenic and immunogenic properties. [ABSTRACT FROM AUTHOR]

O-Antigens and core oligosaccharides from bacterial lipopolysaccharides (LPS) are often structurally unique and immunologically active, have become attractive targets in the development of antibacterial vaccines. Structurally well-defined and pure oligosaccharides can be used in identifying protective epitopes of the carbohydrate antigens, which is important for the design of an effective vaccine. Here, the recent progress on chemical synthesis and immunological evaluation of glycans related to O-antigens and core oligosaccharides from bacterial LPS are summarized. [ABSTRACT FROM AUTHOR]

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 β‐d‐Rhap‐(1→3)‐α‐d‐Manp repeating unit that in turn was accessed by a stereoselective β‐d‐rhamnosylation. The 4,6‐O‐benzylidene‐induced conformational locking is a powerful strategy for forming a β‐d‐mannose‐type glycoside. An indirect strategy based on C2 epimerization of β‐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. [ABSTRACT FROM AUTHOR]

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 β‐d‐Rhap‐(1→3)‐α‐d‐Manp repeating unit that in turn was accessed by a stereoselective β‐d‐rhamnosylation. The 4,6‐O‐benzylidene‐induced conformational locking is a powerful strategy for forming a β‐d‐mannose‐type glycoside. An indirect strategy based on C2 epimerization of β‐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. [ABSTRACT FROM AUTHOR]

• Enzymatic production of even-numbered o-HAs was quantitatively optimized. • A two-enzyme strategy for production of odd-numbered o-HAs was constructed. • Odd-numbered o-HAs (HA 2n+1 AA and HA 2n+1 NN, n = 1–3) were efficiently produced. • A library of even- and odd-numbered o-HAs was constructed. • The o-HAs provide building blocks for polysaccharide chemosynthesis. Hyaluronic acid (HA) and its oligosaccharides (o-HAs) have been receiving much attention as medical treatments. Even-numbered o-HAs with two different reducing ends (HA 2n AN and HA 2n NA, n = 1, 2, 3...) can be prepared using bovine testicular hyaluronidase (BTH) and leech hyaluronidase (LHase) respectively, while preparation of odd-numbered o-HAs (HA 2n+1 AA and HA 2n+1 NN, n = 1, 2, 3...) is relatively difficult. A new enzymatic method was developed to prepare odd-numbered o-HAs in this study, taking advantage of differences in the degradation of glycosidic linkages by BTH and LHase. Through quantitative analysis of the yield of even-numbered o-HAs, a dynamic model for LHase hydrolysis was established, providing optimal preparation conditions for HA 2n NA (n = 1–5). Then HA 2n NA (n = 2–5) was further degraded by BTH to produce odd-numbered o-HAs. The above o-HAs were separated and purified by combining high-performance Q-Sepharose ion-exchange (Q HP) and size exclusion column chromatography steps. [ABSTRACT FROM AUTHOR]

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 β‐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. [ABSTRACT FROM AUTHOR]

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 β‐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. [ABSTRACT FROM AUTHOR]

Exploiting synergistic remote participation effects of acyl groups at the O3 and O6 positions was key to the complete α-selectivity during the total synthesis of the unique (1 → 2)- and (1 → 3)-linked α-oligoglucosides from the Helicobacter pylori O2 O-antigen. Acyl remote participation and solvent effects were found to counteract during α-stereoselective glucosylations for the first time. The resulting antigen is a lead for the development of a carbohydrate-conjugate vaccine. [ABSTRACT FROM AUTHOR]

Plesiomonas shigelloides, a pathogen responsible for frequent outbreaks of severe travelers' diarrhea, causes grave extraintestinal infections. Sepsis and meningitis due to P. shigelloides are associated with a high mortality rate as antibiotic resistance increases and vaccines are not available. Carbohydrate antigens expressed by pathogens are often structurally unique and are targets for developing vaccines and diagnostics. Here, we report a total synthesis of the highly functionalized trisaccharide repeating unit 2 from P. shigelloides serotype 51 from three monosaccharides. A judicious choice of building blocks and reaction conditions allowed for the four amino groups adorning the sugar rings to be installed with two N-acetyl (Ac) groups, rare acetamidino (Am), and D-3-hydroxybutyryl (Hb) groups. The strategy for the differentiation of amino groups in trisaccharide 2 will serve well for the syntheses of other complex glycans. [ABSTRACT FROM AUTHOR]

Metamorphosis is an essential physiological process in insects. This process is triggered by 20-hydroxyecydsone (20E). Lebocin, an antimicrobial peptide of Lepidoptera insects, was significantly up-regulated in the midgut, but not in the fat body of Bombyx mori during metamorphosis. In this study, the expression regulation of lebocin in B. mori midgut was studied. The results showed that B. mori lebocin and its activator BmEts were not responsive to bacterial infection in the midgut, instead, the expression of both genes was up-regulated by 20E treatment. The transcription factor BR-C Z4 in the 20E signal pathway enhanced lebocin promoter activity by directly binding to an upstream cis -response element of the promoter. In the fat body, the mRNA level of B. mori lebocin was decreased when the insect transformed from larval to pupal stage and was increased by immune challenge. The expression profiles of lebocin in Lepidopteran Spodoptera litura was also analyzed and the similar results were observed, S. litura lebocin was significantly up-regulated during midgut regeneration and mainly present in the new-formed intestinal cells of the midgut. All results together suggest that during metamorphosis 20E may activate lebocin expression via BmBR-C Z4 and BmEts in the midgut, where the antimicrobial peptide was produced to protect the midgut from infection. [ABSTRACT FROM AUTHOR]