Enantioselective construction of ortho-sulfur- or nitrogen-substituted axially chiral biaryls and asymmetric synthesis of isoplagiochin D.

Axially chiral biaryl motifs possessing ortho-heteroatom-substituted functionalities exist widely in the structures of natural products and have served as foundation for constructing prominent chiral organocatalysts, ligands, functional materials, and even bioactive molecules. However, a general and enantioselective synthesis of such chiral structures with high synthetic value is rare. Taking advantage of the BaryPhos-facilitated asymmetric Suzuki-Miyaura cross-coupling, we have established a general, efficient and enantioselective construction of the ortho sulfur- or nitrogen-substituted axially chiral biaryls.

Quantitative Acetylomics Reveals Dynamics of Protein Lysine Acetylation in Mouse Livers During Aging and Upon the Treatment of Nicotinamide Mononucleotide.

Lysine acetylation is a reversible and dynamic post-translational modification that plays vital roles in regulating multiple cellular processes including aging. However, acetylome-wide analysis in the aging process remains poorly studied in mammalian tissues. Nicotinamide adenine dinucleotide (NAD), a hub metabolite, benefits health span at least in part due to the activation of Sirtuins, a family of NAD-consuming deacetylases, indicating changes in acetylome.

Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology.

α-Synuclein (α-syn), as a primary pathogenic protein in Parkinson's disease (PD) and other synucleinopathies, exhibits a high potential to form polymorphic fibrils. Chemical ligands have been found to involve in the assembly of α-syn fibrils in patients' brains. However, how ligands influence the fibril polymorphism remains vague.

Hyperosmotic-stress-induced liquid-liquid phase separation of ALS-related proteins in the nucleus.

Hyperosmotic stress as physiologic dysfunction can reduce the cell volume and then redistribute both protein concentration and ionic strength, but its effect on liquid-liquid phase separation (LLPS) is not well understood. Here, we map the hyperosmotic-stress-induced nuclear LLPS of amyotrophic lateral sclerosis (ALS)-related proteins (fused in sarcoma [FUS], TAR DNA-binding protein 43 [TDP-43]). The dynamic and reversibility of FUS granules are continuable with the increase of hypertonic stimulation time, but those of TDP-43 granules decrease significantly.

Discovery of glycosylated naphthacemycins and elucidation of the glycosylation.

Two glycosylated naphthacemycins (naphthacemycins D and D) were identified in Streptomyces sp. N12W1565. These two compounds not only showed antimicrobial potential against bacteria but also exhibited more aqueous solubility than naphthacemycins.

Rh(i)-catalyzed dimerization of ene-vinylidenecyclopropanes for the construction of spiro[4,5]decanes and mechanistic studies.

Rh(i) complex catalyzed dimerization of ene-vinylidenecyclopropanes took place smoothly to construct a series of products containing spiro[4,5]decane skeletons featuring a simple operation procedure, mild reaction conditions, and good functional group tolerance. In this paper, the combination of experimental and computational studies reveals a counterion-assisted Rh(i)-Rh(iii)-Rh(v)-Rh(iii)-Rh(i) catalytic cycle involving tandem oxidative cyclometallation/reductive elimination/selective oxidative addition/selective reductive elimination/reductive elimination steps; in addition, a pentavalent spiro-rhodium intermediate is identified as the key intermediate in this dimerization reaction upon DFT calculation.

Nickel-catalyzed decarboxylative cross-coupling of indole-3-acetic acids with aryl bromides by convergent paired electrolysis.

Herein, nickel-catalyzed decarboxylative cross-coupling of indole-3-acetic acids with aryl bromides by convergent paired electrolysis was developed in an undivided cell. This protocol features good functional group tolerance, and is chemical redox agent- and sacrificial electrode-free. Mechanistic studies indicated that the base was crucial for the decarboxylation step and a Ni/Ni catalytic cycle was involved in this transformation.

Enhancing room-temperature phosphorescence intermolecular charge transfer in dopant-matrix systems.

Some specific organic dopants have been found to form intermolecular charge transfer complexes with phosphorescence-inactive organic matrices to mediate intersystem crossing of the organic matrices and thus activate room-temperature phosphorescence of the organic matrices. This method of boosting intersystem crossing paves the way for high-performance organic room-temperature phosphorescent materials.

Profiling protein interactions by purification with capillary monolithic affinity column in combination with label-free quantitative proteomics.

An approach for profiling protein-protein interactions by using affinity purification with capillary monolithic immobilized metal affinity chromatography column (cm-IMAC) in combination with label free quantitative proteomics was described in the present work. The cm-IMAC columns were prepared in a single step by copolymerization of the function monomer, namely (S)-2,2'-((1-carboxy-5-(pent‑4-enamido)pentyl)azanediyl)diacetic acid which provide a nitrilotriacetate (NTA) moiety to form chelated complexation with Ni (II) ions, inside the fused silica capillaries. The His-tagged bait protein can be easily immobilized on the cm-IMAC columns through the formation of chelating complexation with the NTA-Ni (II) functional groups of the matrix.

Global stable-isotope tracing metabolomics reveals system-wide metabolic alternations in aging Drosophila.

System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Delineating system-wide metabolic homeostasis at the whole-organism level remains challenging.

Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions.

Photo and copper dual catalysis for allene syntheses from propargylic derivatives via one-electron process.

Different from the traditional two-electron oxidative addition-transmetalation-reductive elimination coupling strategy, visible light has been successfully integrated into transition metal-catalyzed coupling reaction of propargylic alcohol derivatives highly selectively forming allenenitriles: specifically speaking, visible light-mediated Cu-catalyzed cyanation of propargylic oxalates has been realized for the general, efficient, and exclusive syntheses of di-, tri, and tetra-substituted allenenitriles bearing various synthetically versatile functional groups. A set of mechanistic studies, including fluorescence quenching experiments, cyclic voltammetric measurements, radical trapping experiments, control experiments with different photocatalyst, and DFT calculation studies have proven that the current reaction proceeds via visible light-induced redox-neutral reductive quenching radical mechanism, which is a completely different approach as compared to the traditional transition metal-catalyzed two-electron oxidative addition processes.

Nuclear RIPK1 promotes chromatin remodeling to mediate inflammatory response.

RIPK1 is a master regulator of multiple cell death pathways, including apoptosis and necroptosis, and inflammation. Importantly, activation of RIPK1 has also been shown to promote the transcriptional induction of proinflammatory cytokines in cells undergoing necroptosis, in animal models of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and in human ALS and AD. Rare human genetic carriers of non-cleavable RIPK1 variants (D324V and D324H) exhibit distinct symptoms of recurrent fevers and increased transcription of proinflammatory cytokines.

Conformational strains of pathogenic amyloid proteins in neurodegenerative diseases.

Amyloid proteins, which are considered 'villains' in many neurodegenerative diseases, form enigmatic pathological strains that underlie disease pathogenesis and progression. Recent technical advances in cryogenic electron microscopy and solid-state NMR spectroscopy have enabled the high-resolution structures of full-length amyloid fibrils to be determined, initiating an era in which we have the opportunity to gain atomic-level structural understanding of pathogenic protein aggregation in neurodegenerative diseases. In this Review, we aim to explain the clinicopathological heterogeneity of neurodegenerative diseases by considering the polymorphic structures of amyloid fibrils.

Plasma and serum exosome markers analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry coupled with electron multiplier.

Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a simple, rapid, and high-throughput assay, its microchannel plate (MCP) detector is limited by the low sensitivity and ion saturation effect when analyzing macromolecules. Herein, we introduced a strategy that combined MALDI-TOF MS with electron multiplier (EM) for the direct analysis of exosomal proteins isolated from human plasma and serum. The results demonstrated that EM yielded a higher sensitivity than MCP detector in high-mass range (m/z 5000-100000).

Trapped ion mobility spectrometry-mass spectrometry improves the coverage and accuracy of four-dimensional untargeted lipidomics.

Lipids play vital roles in many physiological and pathological processes in living organisms. Due to the high structural diversity and the numerous isomers and isobars of lipids, high-coverage and high-accuracy lipidomic analysis of complex biological samples remain the bottleneck to investigate lipid metabolism. Here, we developed the trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) based four-dimensional untargeted lipidomics to support accurate lipid identification and quantification in biological samples.

Ultrasound-assisted enzymatic hydrolysis of yeast β-glucan catalyzed by β-glucanase: Chemical and microstructural analysis.

The purpose of this study was to investigate the effect of ultrasound-assisted enzymolysis on modified solubilization of yeast β-glucan and its related mechanism. The depolymerization effects of this system on the physicochemical properties and structural features of the degraded fragments were studied systematically. The structure and physicochemical properties of the samples showed that the solubility of yeast β-glucan achieved 75.

SulfoxFluor-enabled deoxyazidation of alcohols with NaN.

Direct deoxyazidation of alcohols with NaN is a straightforward method for the synthesis of widely used alkyl azides in organic chemistry. However, known methods have some limitations such as high reaction temperatures and narrow substrate scope. Herein, a general and practical method for the preparation of alkyl azides from alcohols using NaN has been developed.

Ultrasimple air-annealed pure graphene oxide film for high-performance supercapacitors.

Realizing both high gravimetric and volumetric specific capacitances (noted as C and C, respectively) is an essential prerequisite for the next-generation, high performance supercapacitors. However, the need of electronic/ionic transport for electrochemical reactions causes a "trade-off" between compacted density and capacitance of electrode, thereby impairing gravimetric or volumetric specific capacitances. Herein, we report a high-performance, film-based supercapacitor via a thermal reduction of graphene oxide (GO) in air.

Chemical synthesis of polysaccharides.

Here we summarize the chemical syntheses of glycans containing over 20 monosaccharide units, with the recent syntheses of ultra-long glycans, including a 92mer arabinogalactan, a 100mer and a 151mer mannan, and a 128mer rhamnomannan, being highlighted. The assembly strategies, glycosylation methods, and protecting group manipulations, which are crucial to the successful synthesis, are discussed to give guidance for the future synthesis of various polysaccharides.

Hydroxyl ions: flexible tailoring of CuO crystal morphology.

The precise control architectures of CuO crystals are very crucial, which have a significant influence on their various performances. Herein, CuO crystals with diverse architectures were achieved finely adjusting the concentration of NaOH. The intriguing results showed that the addition of specific amounts of OH to the solution was crucial to tailor the morphology and size of the resulting microcrystals.

Rational design of a potent macrocyclic peptide inhibitor targeting the PD-1/PD-L1 protein-protein interaction.

We report optimization by rational design of JMPDP-027, a potent cyclic peptide that interferes with the PD-1/PD-L1 protein-protein interaction. JMPDP-027 shows a potent restoring ability towards T-cells with an EC of 5.9 nM that is comparable to that of the anti-PD-1 monoclonal antibody pembrolizumab.

Toward azo-linked covalent organic frameworks by developing linkage chemistry via linker exchange.

Exploring new linkage chemistry for covalent organic frameworks (COFs) provides a strong driving force to promote the development of this emerging class of crystalline porous organic materials. Herein we report a strategy to synthesize COFs with azo linkage, one of the most important functional unit in materials science but having not yet been exploited as a linkage of COFs. This strategy is developed on the basis of in situ linker exchange, by which imine-linked COFs are completely transformed into azo-linked COFs (Azo-COFs).