Quantitative analysis of phosphoproteome in necroptosis reveals a role of TRIM28 phosphorylation in promoting necroptosis-induced cytokine production.

Necroptosis is a form of regulated necrotic cell death that promotes inflammation. In cells undergoing necroptosis, activated RIPK1 kinase mediates the formation of RIPK1/RIPK3/MLKL complex to promote MLKL oligomerization and execution of necroptosis. RIPK1 kinase activity also promotes cell-autonomous activation of proinflammatory cytokine production in necroptosis.

RIPK1 regulates starvation resistance by modulating aspartate catabolism.

RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth.

Stereoselective rhodium-catalyzed 2-C-H 1,3-dienylation of indoles: dual functions of the directing group.

A rhodium-catalyzed intermolecular highly stereoselective 1,3-dienylation at the 2-position of indoles with non-terminal allenyl carbonates has been developed by using 2-pyrimidinyl or pyridinyl as the directing group. The reaction tolerates many functional groups affording the products in decent yields under mild conditions. In addition to C-H bond activation, the directing group also played a vital role in the determination of -stereoselectivity for the C-H functionalization reaction with 4-aryl-2,3-allenyl carbonates, which is confirmed by the -selectivity observed with 4-alkyl-2,3-allenyl carbonates.

SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death.

Chirality memory of α-methylene-π-allyl iridium species.

Chirality is one of the most important types of steric information in nature. In addition to central chirality, axial chirality has been catching more and more attention from scientists. However, although much attention has recently been paid to the creation of axial chirality and the chirality transfer of allenes, no study has been disclosed as to the memory of such an axial chirality.

Construction of an isoquinolinone framework from carboxylic-ester-directed umpolung ring opening of methylenecyclopropanes.

An interesting type of reaction involving functionalized methylenecyclopropanes (MCPs) has been revealed. Here, a nucleophilic attack of an anionic species onto a partially polarity-reversed MCP was realized by treating a neighbouring carboxylic ester tethered to the MCP and amine with KHMDS to realize an umpolung ring opening of the MCP. This work established an operationally convenient protocol for the rapid construction of isoquinolinone frameworks.

Zwitterionic side chain-modified conjugated polymers with greatly enhanced ambipolar charge-transport mobilities.

A small amount of the 3-(hexyldimethylammonio)propane-1-sulfonate zwitterionic side chain was integrated into a diketopyrrolopyrrole ambipolar polymer to modulate its field-effect carrier-transport characteristics. It was found that such a modification can strengthen the interchain interaction, promote crystallization, and thus improve the hole and electron mobilities by 3.9- and 8.

CpM(iii)-catalyzed enantioselective C-H functionalization through migratory insertion of metal-carbenes/nitrenes.

CpM(iii)-catalyzed enantioselective C-H functionalization reactions have progressed rapidly using either chiral cyclopentadienyl ligands or appropriate chiral carboxylic acids. In this context, highly reactive carbene and nitrene precursors can serve as effective C-H coupling partners, providing a straightforward and efficient approach to access chiral molecules. In this review, we highlight the developments in CpM(iii)-catalyzed enantioselective C-H functionalization reactions through migratory insertion of metal-carbenes/nitrenes by employing chiral CpM(iii) complexes or achiral CpM(iii) complexes combined with chiral carboxylic acids.

Correction: NocU is a cytochrome P450 oxygenase catalyzing -hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins.

Correction for 'NocU is a cytochrome P450 oxygenase catalyzing -hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins' by Heng Guo , , 2021, DOI: 10.1039/d1ob01284c.

Dearomatization reaction of β-naphthols with disulfurating reagents.

-TsOH-catalyzed intermolecular dearomatization reactions of β-naphthols with disulfurating reagents were developed. Various β-naphthalenones bearing a quaternary carbon stereogenic center were obtained smoothly in good to excellent yields with high chemoselectivity in the presence of 5 mol% -TsOH. This reaction features mild reaction conditions and excellent functional group tolerance.

Palladium-catalyzed regio- and enantioselective migratory allylic C(sp)-H functionalization.

Transition metal-catalyzed asymmetric allylic substitution with a suitably pre-stored leaving group in the substrate is widely used in organic synthesis. In contrast, the enantioselective allylic C(sp)-H functionalization is more straightforward but far less explored. Here we report a catalytic protocol for the long-standing challenging enantioselective allylic C(sp)-H functionalization.

Rh-Catalyzed cyclization of 2,3-allenoic acids in the presence of 2,3-allenols.

Herein we report a [Cp*RhCl]-catalyzed coupling cyclization of two different classes of allenes with 2,3-allenoic acids affording 2(5)-furanone skeletons of products and 2,3-allenols forming a conjugated ()-enal or enone functionality to the β-position of the 2(5)-furanones. These products are important building blocks for the syntheses of potentially bioactive compounds. The reaction proceeded the nucleometalation, insertion, and stereodefined 1,4- delivery carried by rhodium.

Necroptosis activates UPR sensors without disrupting their binding with GRP78.

Necroptosis is a form of regulated necrosis mediated by the formation of the necrosome, composed of the RIPK1/RIPK3/MLKL complex. Here, we developed a proximity ligation assay (PLA) that allows in situ visualization of necrosomes in necroptotic cells and in vivo. Using PLA assay, we show that necrosomes can be found in close proximity to the endoplasmic reticulum (ER).

Spatiotemporal dynamic regulation of membraneless organelles by chaperone networks.

Membraneless organelles (MLOs) present as a condensed metastable phase of different proteins and RNAs organized via liquid-liquid phase separation. Recent evidence suggests the extensive incorporation of molecular chaperones into the dynamic assembly of MLOs, where different chaperones coordinate to spatiotemporally maintain the protein homeostasis and avoid abnormal protein aggregation.

WaveICA 2.0: a novel batch effect removal method for untargeted metabolomics data without using batch information.

Introduction: Untargeted metabolomics based on liquid chromatography-mass spectrometry is inevitably affected by batch effects that are caused by non-biological systematic bias. Previously, we developed a novel method called WaveICA to remove batch effects for untargeted metabolomics data. To detect batch effect information, the method relies on a batch label.

NocU is a cytochrome P450 oxygenase catalyzing -hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins.

The ribosomally synthesized and post-translationally modified peptide (RiPP) natural products include the family of thiopeptide antibiotics, where nocathiacins (NOCs) and nosiheptide (NOS) are structurally related bicyclic members featuring an indolic moiety within the side ring system. Compared with NOS, NOCs bear additional functionalities that lead to the improvement of water solubility and bioavailability, a problem inherent to most of the thiopeptide antibiotics, and thus hold potential for clinical use in anti-infective agent development. The process through which post-translational modifications (PTMs) occur to afford these functionalities remains unclear.

Increased hemoglobin and heme in MALDI-TOF MS analysis induce ferroptosis and promote degeneration of herniated human nucleus pulposus.

Background: Neovasculogenesis is characteristic of herniated lumbar discs, in which extruded nucleus pulposus is prone to heme iron-induced cytotoxicity (increased oxidative stress causing ferroptosis). However, recent analyses of neovascularization are very complicated, and the mechanism of action is rarely reported.

Methods: Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) was performed to analyze human herniated and nonherniated nucleus pulposus.

A photoaffinity labeling strategy identified EF1A1 as a binding protein of cyclic dinucleotide 2'3'-cGAMP.

2'3'-cyclic GMP-AMP (2'3'-cGAMP), generated by cyclic GMP-AMP synthase (cGAS) under activation by cytosolic DNA, has a vital role in innate immune response via its receptor protein stimulator of interferon genes (STING) to fight viral infections and tumors. In order to have a complete understanding of biological functions of 2'3'-cGAMP, it is important to find out whether 2'3'-cGAMP has other unrevealed binding proteins present in mammalian cells and executes unknown functions. Here we report the 2'3'-cGAMP-based photoaffinity probes that capture and isolate 2'3'-cGAMP-binding proteins.

Diastereo- and enantioselective rhodium(III)-catalyzed reductive cyclization of cyclohexadienone-containing 1,6-dienes.

A diastereo- and enantioselective rhodium(III)-catalyzed reductive cyclization of cyclohexadienone-tethered terminal alkenes and ()-1,2-disubstituted alkenes (1,6-dienes) is reported, providing -bicyclic products bearing three contiguous stereocenters with good yields and high diastereo- and enantioselectivities. The kinetic resolution of the racemic precursor is also achieved with good efficiency. Moreover, a subgram-scale experiment, several transformations of the cyclization product, and one-pot preparation of bridged polycyclic frameworks are presented.

Heterologous characterization of mechercharmycin A biosynthesis reveals alternative insights into post-translational modifications for RiPPs.

Mechercharmycin A (MCM-A) is a marine natural product belonging to a family of polyazole cyclopeptides with remarkable bioactivities and unique structures. Identification, heterologous expression, and genetic characterizations of the MCM biosynthetic gene cluster in Bacillus subtilis revealed that it is a ribosomally synthesized and post-translationally modified peptide (RiPP) possessing complex with distinctive modifications. Based on this heterologous expression system, two MCM analogs with comparable antitumor activity are generated by engineering the biosynthetic pathway.

Targeted gene correction and functional recovery in achondroplasia patient-derived iPSCs.

Background: Achondroplasia (ACH) is the most common genetic form of dwarfism and belongs to dominant monogenic disorder caused by a gain-of-function point mutation in the transmembrane region of FGFR3. There are no effective treatments for ACH. Stem cells and gene-editing technology provide us with effective methods and ideas for ACH research and treatment.

Facile access to C-glycosyl amino acids and peptides via Ni-catalyzed reductive hydroglycosylation of alkynes.

C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins bearing O/N-glycosidic linkages, and are thus of great therapeutical potential. Herein, we disclose a protocol for the syntheses of vinyl C-glycosyl amino acids and peptides, employing a nickel-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with common glycosyl bromides. It accommodates a wide scope of the coupling partners, including complex oligosaccharide and peptide substrates.