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The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. The scRNA‐seq and bulk RNA‐seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single‐cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan‐cancer patients. The proportion of APOE+ macrophages is higher in ICI non‐responders of triple‐negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real‐world immunotherapy data accurately predicts the ICI response of pan‐cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells. [ABSTRACT FROM AUTHOR]

In the paper, the possibility of two complete conversions is investigated, one is from the two‐photon hyperentangled Knill–Laflamme–Milburn (KLM) state to hyperentangled Bell states, the other is from three‐photon KLM state to the hyperentangled Greenberger–Horne–Zeilinger states, for photonic systems hyper‐encoded in polarization and spatial degrees of freedom assisted by error‐heralded quantum units (EHQUs). The system inhomogeneity and/or the imperfect photon scattering often restrict the performance of effective conversions of two types of hyperentangled states, and result in the reductions of the fidelity and the efficiency in tangible quantum information technologies. The polarization EHQU and spatial EHQU are two critical tools for actualizing two hyperentangled conversions in a heralded way, as the errors stemming from the system inhomogeneity and practically imperfect scattering are converted into efficacious responses of the detectors in our protocols. Thus, the fidelities of these conversion cases keep unchanged and have close to unity fidelities, which deepen the understanding of the properties of hyperentanglement. [ABSTRACT FROM AUTHOR]

The efficient synthesis of N‐glycosides via direct N‐glycosylation of amides/azacycles has been reported. The glycosylation of amides/azacycles with glycosyl halides in the presence of a catalytic amount of urea proceeded smoothly to provide the corresponding N‐glycosylated amides or nucleosides in good to excellent yields with 1,2‐trans‐stereoselectivity. Moreover, by the addition of terpyridine, the 1,2‐cis‐stereoselectivity was achieved. [ABSTRACT FROM AUTHOR]

Radialenes and expanded radialenes are cross‐conjugated macrocycles displaying poor aromatic character. In this work, three 9‐fluorenylidene substituted expanded [n]radialenes (ER‐n, n=3–5) with a diacetylene spacer were synthesized and their structures were confirmed by X‐ray crystallographic analysis and NMR spectroscopy. They all can be easily reduced into relatively stable dianions. Detailed experimental measurements and theoretical calculations suggest that their dianions (ER‐n2−, n=3–5) are stabilized by both the aromatic fluorenyl anion substituents and the central aromatic rings with formally [4n+2] delocalized π electrons. In addition, the dianions of the extended radialenes (ER‐42− and ER‐52−) show unique open‐shell diradical character with a small singlet‐triplet energy gap. For comparison, their linear counterparts (L‐3 and L‐4) were also synthesized; their dianions exhibit very different redox and optical properties from their respective macrocycles. [ABSTRACT FROM AUTHOR]

The photoinitiated intramolecular hydroetherification of alkenols has been used to form C−O bonds, but the intermolecular hydroetherification of alkenes with alcohols remains an unsolved challenge. We herein report the visible‐light‐promoted 2‐deoxyglycosylation of alcohols with glycals. The glycosylation reaction was completed within 2 min in a high quantum yield (ϕ=28.6). This method was suitable for a wide array of substrates and displayed good reaction yields and excellent stereoselectivity. The value of this protocol was further demonstrated by the iterative synthesis of 2‐deoxyglycans with α‐2‐deoxyglycosidic linkages up to a 20‐mer in length and digoxin with β‐2‐deoxyglycosidic linkages. Mechanistic studies indicated that this reaction involved a glycosyl radical cation intermediate and a photoinitiated chain process. [ABSTRACT FROM AUTHOR]

Glycans have been hot topics in recent years due to their exhibition of numerous biological activities. However, the heterogeneity of their natural source and the complexity of their chemical synthesis impede the progress in their biological research. Thus, the development of glycan assembly strategies to acquire plenty of structurally well‐defined glycans is an important issue in carbohydrate chemistry. In this review, the latest advances in glycan assembly strategies from concepts to their applications in carbohydrate synthesis, including chemical and enzymatic/chemo‐enzymatic approaches, as well as solution‐phase and solid‐phase/tag‐assisted synthesis, are summarized. Furthermore, the automated glycan assembly techniques are also outlined. [ABSTRACT FROM AUTHOR]

Carbohydrates have gained a lot of appreciation in the past few decades due to their important roles in numerous biological events. Acquiring a structurally well‐defined carbohydrate compound is essential for the understanding of its functions. Although some innovative methods have been developed for the synthesis of complex oligosaccharides, glycan synthesis is in general still a time‐consuming and difficult work. Herein, we will introduce the preactivation‐based glycosylation strategy, which is an efficient protocol independent of the reactivity of glycosyl donor. This review will focus on summarizing the versatile applications of preactivation strategy in stereoselective glycosylation and one‐pot assembly of biologically important oligosaccharides and even polysaccharides. What is the most favorite and original chemistry developed in your research group? Preactivation‐based one‐pot glycosylation strategy and applications. How do you get into this specific field? Could you please share some experiences with our readers? I got into this field when I was a research associate in 1996. My supervisor, Prof. Chi‐Huey Wong, gave me a research topic for synthesis of oligosaccharide libraries. At that moment, as a beginner, I did not know too much carbohydrate chemistry, just to learn and to do it. The importance and challenge of carbohydrates attracted me. What is the most important personality for scientific research? Curiosity, passion, and creative thinking. How do you supervise your students? In my opinion, before the graduate students start a specific project, their experimental skills need to be well trained. During the period of graduate studies, the enhancement of abilities to analyze problems and to solve problems is very important. The graduate students should always keep an eye on the unusual experimental phenomena. What's your hobbies? Reading history books. What is your favorite journals? The journals publishing the latest research works in chemistry and medical science. [ABSTRACT FROM AUTHOR]

We report a novel and highly stereoselective electro‐2‐deoxyglycosylation from glycals. This method features excellent stereoselectivity, scope, and functional‐group tolerance. This process can also be applied to the modification of a wide range of natural products and drugs. Furthermore, a scalable synthesis of glycosylated podophyllotoxin and a one‐pot trisaccharide synthesis through iterative electroglycosylations were achieved. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: The N‐glycans attached to some chloroviruses comprise a hyperbranched core structure without precedent. We are interested in the chemical synthesis of the hexasaccharide attached to ATCV‐1 (Acanthocystis turfacea Chlorella virus 1) for its distinct structure. After exploring four routes, the target hexasaccharide 2 was successfully synthesized for the first time in overall 10% yield over 8 steps from thioglycoside building blocks. This synthetic protocol is characterized by the three‐component one‐pot glycosylation and the regioselective glycosylation reactions. The disclosed synthetic approach to this new type of N‐glycans will facilitate the in‐depth understanding of their biological functions. A highly branched hexasaccharide was successfully synthesized by the three‐component preactivation‐based one‐pot glycosylation and the regioselective glycosylation reactions for the first time. [ABSTRACT FROM AUTHOR]

The chirality of supramolecular polymeric materials is subtly affected by a delicate balance among various non‐covalent interactions, the details of which are inadequately understood. Now, a fine balance of intermolecular interactions, including closed‐shell metal–metal, dispersive and electrostatic interactions, is used to direct the delicate orientation of monomeric building blocks, thereby achieving the successful preparation of different nanostructures with distinct supramolecular chirality. Moreover, kinetically trapped and thermodynamically stable aggregates were monitored over time in the supramolecular polymerization of cationic PtII complexes. The dynamic self‐assembly process can be successfully controlled by modifying the counteranion and solvent composition. A chiral doping approach can also be used to induce the chirality of an achiral PtII complex at the supramolecular level. The chirality transfer process and the pathway complexity of a series of chiral pincer‐type PtII complexes are described. A chiral doping approach can be used to induce the chirality of an achiral PtII complex at the supramolecular level. [Pt]=PtII complex; counteranion X−. [ABSTRACT FROM AUTHOR]

Abstract: A large quantity of polysaccharide‐derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality‐controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate‐based vaccines, heparin‐related therapeutics and glycomimetics of polysaccharides are summarized. [ABSTRACT FROM AUTHOR]

Abstract: Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can differentiate the abnormal tissues from the healthy ones. Therefore, tumor‐associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance. Different approaches have been developed to address these problems. In this review, we want to summarize the latest advances in TACAs based anticancer vaccines. [ABSTRACT FROM AUTHOR]

Salmonella typhi is responsible for typhoid fever, which is a serious health threat in developing countries. As a virulent factor of Salmonella typhi, the purified Vi polysaccharide (Vi PS) has become an effective vaccine to combat typhoid fever. The chemical synthesis can provide homogeneous and well-defined molecules for the development of Vi-based vaccines. However, the synthesis of Vi oligosaccharides in high yields and with exclusive α-stereoselectivities remains very challenging. In this paper, a series of Vi pseudooligosaccharides, including pseudo tetra-, hexa-, and octa-saccharides were efficiently synthesized. These oligosaccharide analogues were conjugated by carbon chain tether through olefin cross metathesis or by the 1,2,3-triazole moiety through copper (I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC). The binding affinities of these oligosaccharide mimics to anti-Vi antibodies were investigated. These results will be beneficial to the further development of Vi-based oligosaccharide vaccines. [ABSTRACT FROM AUTHOR]

Three new iminosugar-containing KRN7000 (also referred to as α- GalCer) analogues were designed and synthesized. In the design, the galactose moiety of KRN7000 was replaced by iminosugars and the iminosugar structures were connected with ceramide in different manners with a C-glycosidic bond instead of the O-glycosidic bond. To our knowledge, this is the first report in which iminosugars are incorporated in KRN7000 structure modifications. The synthetic compounds were evaluated for their ability to stimulate cytokine release. The results may benefit better understanding of structure-activity relationships and facilitate future design of more KRN7000 derivatives. [ABSTRACT FROM AUTHOR]

An analytical model has been developed in the present paper based on a square root transformation of white Gaussian noise. The mathematical expectation and variance of the new asymmetric distribution generated by white Gaussian noise after a square root transformation are analytically deduced from the preceding four terms of the Taylor expansion. The model was first evaluated against numerical experiments and a good agreement was obtained. The model was then used to predict time series of wind speeds and highway traffic flows. The simulation results from the new model indicate that the prediction accuracy could be improved by 0.1-1% by removing the mean errors. Further improvement could be obtained for non-stationary time series, which had large trends. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low a-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl) phosphine (TTMPP). [ABSTRACT FROM AUTHOR]

A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low a-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl) phosphine (TTMPP). [ABSTRACT FROM AUTHOR]

An efficient method for the construction of cyclopropane-fused dihydroquinolines was established by a novel Povarov-type three-component reaction of aromatic aldehydes, anilines and cyclopropenes in the presence of trifluoromethanesulfonic acid. The reaction proceeded in a regioselective and diastereoselective manner. Furthermore, the dihydroquinolines were smoothly converted to benzazepine derivatives via a ring opening/isomerization sequence, further expanding the synthetic scope. [ABSTRACT FROM AUTHOR]

Iminosugars are an extremely interesting and versatile class of compounds and have many potential therapeutic applications. However, the use of iminosugar derivatives as immunomodulating agents is an area that is less explored. This review describes recent advances in the field of iminosugars as immunomodulating agents with a particular emphasis on 1-deoxynojirimycin analogues and related compounds. Both chemical and biological aspects concerning their preparation and/or occurrence in nature, as well as their immunomodulatory properties, are discussed. [ABSTRACT FROM AUTHOR]

Keywords: 2-Deoxyglycosides; Bromine Radical; Intermolecular Hydroetherification; Photoreaction; Stereoselectivity EN 2-Deoxyglycosides Bromine Radical Intermolecular Hydroetherification Photoreaction Stereoselectivity 1 1 1 05/05/22 20220509 NES 220509 B Sichtbares Licht b vermittelt die iterative Synthese von 2-Desoxyoligosacchariden, über die De-Cai Xiong, Xin-Shan Ye und Mitarbeiter in ihrem Forschungsartikel berichten (e202114726). Innentitelbild: Iterative Synthesis of 2-Deoxyoligosaccharides Enabled by Stereoselective Visible-Light-Promoted Glycosylation (Angew. 2-Deoxyglycosides, Bromine Radical, Intermolecular Hydroetherification, Photoreaction, Stereoselectivity. [Extracted from the article]

2-Deoxyglycosides, Bromine Radical, Intermolecular Hydroetherification, Photoreaction, Stereoselectivity The rapid constructions of oligosaccharides, 20-mer deoxyglycan, and digoxin are facilitated by a bromide-based hydrogen species through an electron transfer process. Keywords: 2-Deoxyglycosides; Bromine Radical; Intermolecular Hydroetherification; Photoreaction; Stereoselectivity EN 2-Deoxyglycosides Bromine Radical Intermolecular Hydroetherification Photoreaction Stereoselectivity 1 1 1 05/05/22 20220509 NES 220509 B A visible-light-promoted b iterative synthesis of 2-deoxyoligosaccharides is reported by De-Cai Xiong, Xin-Shan Ye, and co-workers in their Research Article (e202114726). [Extracted from the article]

We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of ′hit′ compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21 h, 21 k, 21 n, 21 t, and 21 x with improved activities (IC50=12-30 μ M) and low Jurkat cytotoxicities (IC50>100 μ M). These new compounds also inhibited the secretion of IFN-γ and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity. [ABSTRACT FROM AUTHOR]

By employing lithium and nitrogen codoping method, p-type zinc oxide (ZnO) films have been prepared, and the p-type conduction can maintain for 207 days. ZnO p-n junctions have been constructed based on the p-type ZnO. Under the drive of continuous current, obvious emission has been observed from the p-n junctions, and the ZnO p-n junction light-emitting devices (LEDs) can still work after placing in air ambient for 180 days. Room temperature electroluminescence spectra of the p-ZnO:(Li,N)/n-ZnO structured LEDs under continuous current recorded intermittently for 180 days. [ABSTRACT FROM AUTHOR]

The bright side of triple double bonds: Two series of stable tridentate cyclometalated PtII and AuIII allenylidene complexes were found to exhibit many functionalities, such as long‐lived excited states, self‐assembly into supramolecular nanostructures, DNA and nucleus binding and cellular imaging capabilities (see figure). [ABSTRACT FROM AUTHOR]

The increased awareness of the central role of RNA has led to realization that RNA, as structural and functional information accumulation, is also drug target to small molecular therapy. Aminoglycosides are a group of well-known antibiotics, which function through binding to specific sites in prokaryotic ribosomal RNA (rRNA) and affecting the fidelity of protein synthesis. Unfortunately, their clinical practice has been curtailed by toxicity and rapid increasing number of resistant strains. Therefore, it is highly desirable to design new modified aminoglycosides that will overcome the undesirable properties of natural occurring aminoglycosides. On the other hand, aminoglycosides as potential antiviral (HIV) agents were also reported. Herein, we survey the current efforts to develop new aminoglycoside derivatives with modification and reconstruction on each sugar ring and review the latest advances in structure-activity relationships (SAR). © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 279-316, 2007 [ABSTRACT FROM AUTHOR]

T-DNA integration is a key step in the process of plant transformation, which is proven to be important for analyzing T-DNA integration mechanism. The structures of T-DNA right borders inserted into the rice (Oryza sativaL.) genome and their flanking sequences were analyzed. It was found that the integrated ends of the T-DNA right border occurred mainly on five nucleotides“TGACA” in inverse repeat (IR) sequence of 25 bp, especially on the third base“A”. However, the integrated ends would sometimes lie inward of the IR sequence, which caused the IR sequence to be lost completely. Sometimes the right integrated ends appeared on the vector sequences rightward of the T-DNA right border, which made the T-DNA, carrying vector sequences, integrated into the rice genome. These results seemingly suggest that the IR sequence of the right border plays an important role in the process of T-DNA integration into the rice genome, but is not an essential element. The appearance of vector sequences neighboring the T-DNA right border suggested that before being transferred into the plant cell fromAgrobacterium, the entire T-DNA possibly began from the left border in synthesis and then read through at the right border. Several nucleotides in the T-DNA right border homologous with plant DNA and filler DNAs were frequently discovered in the integrated position of T-DNA. Some small regions in the right border could match with the plant sequence, or form better matches, accompanied by the occurrence of filler DNA, through mutual twisting, and then the T-DNA was integrated into plant chromosome through a partially homologous recombination mechanism. The appearance of filler DNA would facilitate T-DNA integration. The fragments flanking the T-DNA right border in transformed rice plants could derive from different parts of the inner T-DNA region; that is, disruption and recombination could occur at arbitrary positions in the entire T-DNA, in which the homologous area was comparatively easier to be disrupted. The structure of flanking sequences of T-DNA integrated in the rice chromosome presented various complexities. These complexities were probably a result of different patterns of recombination in the integrating process. Some types of possible integrating mechanism are detailed.(Managing editor: Li-Hui ZHAO) [ABSTRACT FROM AUTHOR]